Oxford University Press (OUP)Acta Medica Okayama1470-162617122026Rho kinase and RND3 regulate the direct effect of estradiol-17β on oviductal tonusxaag004ENSayakaKubotaLaboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRisaOkawaraSchool of Agriculture, Okayama UniversityKoheiKawanoLaboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKojiKimuraLaboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEnsuring the timely transport of gametes and embryos within the oviduct is essential for the successful establishment of pregnancy. This study investigated the direct effect of estradiol-17β (E2) on bovine oviductal contractility and the differences in responsiveness to E2 during the estrous cycle. Bovine isthmic tissues from four estrous stages were analyzed using the Magnus method to assess contractile responses to E2 and related reagents. Protein expression of G-protein-coupled estrogen receptor 1 (GPER1) and components of the RhoA/Rho kinase (ROCK) signaling pathway were also evaluated. E2 and a GPER1 agonist significantly increased oviductal tonus at 1–4 days after ovulation. This effect was significantly suppressed by treatment with a GPER1 antagonist and a ROCK inhibitor. At 1–4 days after ovulation, both ROCK II expression and ROCK activity were elevated. E2 also enhanced phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and myosin light chain (MLC), key downstream targets of ROCK. Before ovulation, when endogenous E2 levels peak, the expression of RND3―a ROCK inhibitor―was upregulated. The application of an RND inhibitor restored E2 responsiveness in oviductal tonus, ROCK activity, and the phosphorylation of MYPT1 and MLC in oviductal tissues before ovulation. These findings suggest that E2 directly increases oviductal tonus via GPER1 and ROCK/MYPT1/MLC activation at 1–4 days after ovulation. Differences in oviductal responsiveness to E2 during the estrous cycle appear to be mediated by the expression of ROCK and RND3. This mechanism can enable sperm transport within the oviduct at an appropriate time.No potential conflict of interest relevant to this article was reported.岡山大学農学部附属山陽圏フィールド科学センターActa Medica Okayama0910-8742462024目次iiiiENNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1046-13104562026Adolescent screen use in the pre-internet era and subsequent health and well-being: an outcome-wide longitudinal study657ENPedro Antoniode la Rosa Fernández-PachecoYouth in Transition, Institute for Culture and Society, Universidad de NavarraRenaeWilkinsonHuman Flourishing Program, Institute for Quantitative Social Science, Harvard UniversityRichard G.CowdenHuman Flourishing Program, Institute for Quantitative Social Science, Harvard UniversityYingChenHuman Flourishing Program, Institute for Quantitative Social Science, Harvard UniversityBrendanCaseHuman Flourishing Program, Institute for Quantitative Social Science, Harvard UniversityEtsujiSuzukiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTyler J.VanderWeeleDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThis study used data from the National Longitudinal Study of Adolescent to Adult Health (Add Health, N = 11,054) to assess whether increases in screen-based leisure during adolescence (Wave II, from 1996) predicted adult well-being (Wave IV, from 2008-09), adjusting for a wide range of covariates (Wave I, from 1995). Using an outcome-wide analytic approach, we examined associations between screen time and 38 adult outcomes, adjusting for prior screen time, values of most outcomes, and confounders. Most associations were null. Modest evidence was found for links between screen time (continuous) and reduced sense of control, illicit drug use, and allostatic load. High screen time (14 h/week) or more also showed weak associations with lower depression and preventive care use. Because the data predate widespread internet use, the findings help establish a baseline for the long-term effects of non-internet screen activities, which appeared to behave had limited impact on adult health and well-being.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1462-891027102025D3 lymph node dissection in colon cancer patients aged 90 years and over: Is it justified? A multi‐institutional retrospective studye70269ENFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University HospitalSatoeTakanagaDepartment of Gastroenterological Surgery, Okayama University HospitalRyoInadaDepartment of Surgery, Kochi Health Sciences CenterToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Medical Development Field, Okayama UniversityToshiakiToshimaDepartment of Surgery, Kagawa Rosai HospitalTsuyoshiOhtaniDepartment of Surgery, Saiseikai Okayama HospitalRyosukeYoshidaDepartment of Surgery, Okayama Rosai HospitalRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University HospitalSetouchi Colorectal Neoplasm Registration study group collaboratorsAim: The oncological benefit of D3 lymph node dissection (D3 LND) for colon cancer in patients aged ≥90 years remains unclear. This study aimed to evaluate the impact of D3 LND on outcomes in this specific, vulnerable population.<br>
Method: This retrospective cohort study evaluated 166 patients aged ≥90 years with pathological Stages II–III colon cancer undergoing non-D3 or D3 LND from a multicentre database (2011–2022). Postoperative complications, overall survival and cancer-specific survival were compared between LND groups using propensity score-weighted analyses.<br>
Results: D3 LND group had significantly more females and laparoscopic procedures. Operation time was longer, and blood loss was lower in the D3 LND group. Postoperative complications and severe complications were significantly fewer, and postoperative hospital stay was shorter in the D3 LND group. The number of harvested lymph nodes and distal margin was significantly higher in the D3 group. While unadjusted analysis showed better overall survival with D3 LND (p < 0.001), adjusted cancer-specific survival showed no significant difference (p = 0.10). Adjusted mortality risk was significantly higher in the non-D3 group (p = 0.001).<br>
Conclusion: In nonagenarian colon cancer patients, D3 LND is safe and feasible without increasing complications, but lacks survival benefit. Careful consideration is warranted, and high-quality D2 LND must be consistently ensured when limited surgery is chosen.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1435-245141112025Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches21ENRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoeTakanagaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalRyoInadaDepartment of Surgery, Kochi Health Sciences CenterToshiakiToshimaDepartment of Surgery, Kagawa Rosai HospitalTsuyoshiOhtaniDepartment of Surgery, Saiseikai Okayama HospitalRyosukeYoshidaDepartment of Surgery, Okayama Rosai HospitalNaotoHoriDepartment of Surgery, Tottori Municipal HospitalKaoruShigemitsuDepartment of Surgery, Tsuyama Chuo HospitalSumiharuYamamotoDepartment of Surgery, Okayama City HospitalTetsushiKubotaDepartment of Surgery, Kobe Red Cross HospitalYukaOkanoDepartment of Surgery, Onomichi City HospitalTetsujiNobuhisaDepartment of Surgery, Himeji Red Cross HospitalFumitakaTaniguchiDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterWataruIshikawaDepartment of Surgery, Fukuyama City HospitalTatsuoMatsudaDepartment of Surgery, Matsuda HospitalTatsuoUmeokaDepartment of Surgery, Matsuyama City HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSetouchi Colorectal Neoplasm Registration study group collaboratorsPurpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged ≥ 90 years with resectable colon cancer.<br>
Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS).<br>
Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p = 0.038) and lower ASA scores (p = 0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p = 0.046) but less intraoperative blood loss (10 vs. 78 mL, p < 0.01). Postoperative complication rates were comparable (Lap: 31.8%, Open: 33.8%), while the Lap group had a significantly shorter hospital stay (13 vs. 17 days, p < 0.01). D3 lymph node dissection was more frequently performed in the Lap group (p < 0.01). After sIPTW, overall survival did not differ significantly between groups (p = 0.61).<br>
Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach.No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231912026「創造性が社会と出会う美術教育」による教員の学びに関する基礎研究U ― 市井の他者との対話がもたらす教員の意味変容に関する考察 ―157167ENAiMATSUURAFaculty of Education, Okayama UniversityYusukeSENOOOkayama Prefectural Tamashima High SchoolHitoshiKIMURAShiga University Faculty of Education Elementary SchoolSoichiroTAKEDAOkayama University Junior High SchoolChandeSONOsaka Kyoiku University Tennoji Junior High SchoolTetsuoKIYOTA,Faculty of Education, Okayama University10.18926/bgeou/70204 本研究は，清田哲男の理論枠組を基盤として，教員が日常生活で出会う市井の他者との対話を通じて創造性や授業観を変容させるプロセスを明確化したものである。市井プロジェクトの質的分析により，教員は他者の生き方や姿勢から新たな価値を受け取り（市井からの享受過程），その経験を契機に教育観を再編し（教育観変容過程），さらに授業構想に具体的変化を生じさせること（授業内容関与過程）が確認された。とりわけ，制度的研修では得にくい偶発的対話や生活知の受容が，教員の創造性を喚起し，日常に根ざした学びとして機能する点が成果である。本研究は，教員自身が学ぶ創造性という新たな研究領域の基盤を形成し，美術教育における創造性育成の新たな可能性を提示した。No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1123-63372912025Safety and feasibility of D3 lymph node dissection in oldest-old patients undergoing colorectal cancer surgery: a multi-institutional, retrospective analysis146ENR.InadaDepartment of Surgery, Kochi Health Sciences CenterF.TeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesT.MitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalS.TakanagaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesT.ToshimaDepartment of Surgery, Kagawa Rosai HospitalT.OhtaniDepartment of Surgery, Saiseikai Okayama HospitalR.YoshidaDepartment of Surgery, Okayama Rosai HospitalN.HoriDepartment of Surgery, Tottori Municipal HospitalK.ShigemitsuDepartment of Surgery, Tsuyama Chuo HospitalS.YamamotoDepartment of Surgery, Okayama City HospitalT.KubotaDepartment of Surgery, Kobe Red Cross HospitalY.OkanoDepartment of Surgery, Onomichi City HospitalT.NobuhisaDepartment of Surgery, Himeji Red Cross HospitalF.TaniguchiDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterW.IshikawaDepartment of Surgery, Fukuyama City HospitalR.ShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesT.MatsudaDepartment of Surgery, Matsuda HospitalT.UmeokaDepartment of Surgery, Matsuyama City HospitalT.FujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSetouchi Colorectal Neoplasm Registration Study Group CollaboratorsBackground Colorectal cancer (CRC) is a significant health burden, with lymph node dissection (LND) playing a critical role in staging and guiding treatment. However, the optimal extent of LND for the oldest-old population (aged ≥ 90 years) remains undefined because of insufficient targeted clinical data. This study aimed to compare the short-term outcomes of D3 versus non-D3 LND in Stage II–III CRC in oldest-old patients.<br>
Methods This retrospective cohort study utilized data from the Setouchi Colorectal Neoplasm Registration database, including 282 oldest-old patients with CRC treated between 2011 and 2022. Patients were stratified into D3 and non-D3 LND groups, with inverse-probability-weighted regression adjustment implemented to address potential confounding factors. Postoperative complications and hospital stays were analyzed using regression models and descriptive statistics.<br>
Results D3 LND resulted in significantly higher lymph node harvests in both Stage II and Stage III patients (p < 0.01). There were no significant differences in overall or major postoperative complications between D3 and non-D3 groups. Hospital stays were comparable for Stage II patients but shorter for Stage III patients in the D3 group (p < 0.01). Complication rates ranged from 28% to 47.7%, with surgical site infections and pneumonia being the most common.<br>
Conclusions D3 LND can be safely performed in oldest-old patients with CRC without increasing postoperative complications or extending hospital stays. These findings support the feasibility of extensive LND in this age grNo potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1664-462X162025Structural analysis of PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte alga Rhodomonas sp. NIES-23321716939ENWenyueZhangAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNozomiYoneharaAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMizukiIshiiAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHaoweiJiangAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRomainLa RoccaAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPi-ChengTsaiAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHongjieLiAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKojiKatoAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityFusamichiAkitaAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityJian-RenShenAdvanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityLight energy is converted to chemical energy by two photosystems (PSI and PSII) in complex with their light-harvesting complex proteins (LHCI and LHCII) in photosynthesis. Rhodomonas is a member of cryptophyte alga whose LHCs contain unique chlorophyll a/c proteins (ACPs) and phycobiliproteins. We purified PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte Rhodomonas sp. NIES-2332 and analyzed their structures at high resolutions of 2.08 Å and 2.17 Å, respectively, using cryo-electron microscopy. These structures are largely similar to those reported previously from two other species of cryptophytes, but exhibited some differences in both the pigment locations and subunit structures. A part of the antenna subunits of both photosystems is shifted compared with the previously reported structures from other species of cryptophytes, suggesting some differences in the energy transfer rates from the antenna to the PSI and PSII cores. Newly identified lipids are found to occupy the interfaces between the antennae and cores, which may be important for assembly and stabilization of the supercomplexes. Water molecules surrounding three iron-sulfur clusters of the PSI core are found in our high-resolution structure, some of which are conserved from cyanobacteria to higher plants but some are different. In addition, our structure of PSII-ACPII lacks the subunits of oxygen-evolving complex as well as the Mn4CaO5 cluster, suggesting that the cells are in the S-growth phase, yet the PSI-ACPI structure showed the binding of PsaQ, suggesting that it is in an L-phase. These results suggest that the S-phase and L-phase can co-exist in the cryptophytic cells. The high-resolution structures of both PSI-ACPIs and PSII-ACPIIs solved in this study provide a more solid structural basis for elucidating the energy transfer and quenching mechanisms in this group of the organisms.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1068-926532122025Mesenteric Route Superior Mesenteric Artery First Approach in Robot-Assisted Pancreatoduodenectomy89038905ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAteneItoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTsubasaYanagiharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground. The superior mesenteric artery (SMA) approach is crucial for the successful implementation of robot-assisted pancreatoduodenectomy (RPD). Herein, we present a novel technique, the mesenteric route SMA-first approach, for RPD.<br>
Patients and Methods. A 20-year-old woman with a 50 mm intraductal papillary mucinous neoplasm underwent RPD. As the tumor was large and located close to the mesenteric vessels, we developed the mesenteric route SMA-first approach.<br>
Results. Following the mesenteric Kocher maneuver, the mesenteric route SMA-first approach was applied. With appropriate retraction of the pancreatic head, dissection around the mesenteric vessels was performed and their branches were divided. The uncinate process dissection (PL, ph II) was performed via the mesenteric route. This approach facilitated dorsal dissection, particularly around the large tumor. After dissection of the hepatoduodenal ligament, the remaining pancreatic nerve plexus (PL ph I) was dissected. Finally, the pancreas was divided on the superior mesenteric vein, and the specimen was resected. Operative time was 390 min with minimal blood loss.<br>
Conclusions. The mesenteric route SMA-first approach enables uncinate process dissection via the mesenteric route. This technique may be a safe and feasible option for selected patients, such as nonobese individuals with a large pancreatic head tumor near major vessels.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841762025Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Studye86575ENShoSaekiDepartment of Respiratory Medicine, Kumamoto University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalShinyaSakataDepartment of Respiratory Medicine, Kumamoto University HospitalNaohiroOdaDepartment of Respiratory Medicine, Okayama University HospitalKojiInoueDepartment of Respiratory Medicine, Kitakyushu Municipal Medical CenterTomokiTamuraDepartment of Respiratory Medicine, Okayama University HospitalRyoToyozawaDepartment of Thoracic Oncology, National Hospital Organization Kyushu Cancer CenterDaijiroHaradaDepartment of Thoracic Oncology, National Hospital Organization Shikoku Cancer CenterKentaroTanakaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityKojiInoueDepartment of Respiratory Medicine, Ehime Prefectural Central HospitalYoshiyukiShioyamaRadiation Oncology, Ion Beam Therapy Center, SAGA HIMAT FoundationKenichiGembaDepartment of Respiratory Medicine, Chugoku Central HospitalTomonariSasakiDepartment of Radiation Oncology, Iizuka HospitalAkihiroBesshoDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalJunjiKishimotoCenter for Clinical and Translational Research, Kyushu University HospitalKuniakiKatsuiDepartment of Radiology, Division of Radiation Oncology, Kawasaki Medical SchoolKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalKenjiSugioThoracic and Breast Surgery, Oita UniversityBackground and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression.<br>
Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients.<br>
Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported.<br>
Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417112025Association of Carboxyhemoglobin With Severity and Outcomes in Hypothermic Patients: A Retrospective Cohort Studye97962ENYuyaMiyoshiDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityIntroduction<br>
Carboxyhemoglobin (COHb), an endogenous marker of carbon monoxide production mediated by heme oxygenase-1, may reflect physiological stress responses in critically ill patients. However, its clinical relevance in accidental hypothermia remains unclear.<br>
<br>
Methods<br>
We conducted a single-center retrospective cohort study of adult patients admitted to the emergency ICU with accidental hypothermia between January 1, 2019, and March 31, 2025. Patients were categorized into low- and high-COHb groups based on median COHb levels upon emergency department arrival. Associations between COHb levels, disease severity (Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores), and 28-day mortality were analyzed using regression models adjusted for clinical confounders.<br>
<br>
Results<br>
Among the 88 patients, who had a median admission temperature of 28.7°C, 45 were classified into the low-COHb group and 43 into the high-COHb group, based on a median COHb level of 0.3%. Lower COHb levels on admission were significantly associated with higher APACHE II scores (β = −4.20; 95% CI, −7.56 to −0.85), but not with SOFA scores. Admission and minimum COHb levels were not associated with 28-day mortality. However, higher maximum COHb levels within the first 24 hours were independently associated with lower 28-day mortality (adjusted OR, 0.17; 95% CI, 0.023 to 0.93).<br>
<br>
Conclusions<br>
Lower COHb levels were associated with greater disease severity, and higher maximum COHb levels were associated with lower 28-day mortality. COHb may reflect systemic stress in accidental hypothermia, but its prognostic value appears limited.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841812026Saliva as a Reliable and Non-invasive Sample for Detecting Influenza A in Severe Acute Respiratory Infection Casese100872ENJunko STakeuchiDepartment of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health SecurityNobuakiMatsunagaAntimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health SecurityAiTsukadaAntimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health SecurityNorikoIwamotoDisease Control and Prevention Center, Japan Institute for Health SecurityNorikoFuwaDisease Control and Prevention Center, Japan Institute for Health SecurityTakahiroIchikawaDepartment of Infectious Diseases, Sapporo City General HospitalYasuyukiKatoDepartment of Infectious Diseases, International University of Health and Welfare (IUHW) Narita HospitalYukaTomitaDepartment of Infectious Diseases, Japanese Red Cross Aichi Medical Center Nagoya Daini HospitalHirokiKitagawaDepartment of Infectious Diseases, Hiroshima University HospitalMasayaYamatoDepartment of General Internal Medicine and Infectious Diseases, Rinku General Medical CenterTetsujiAoyagiDepartment of Clinical Infectious Diseases, Tohoku University Graduate School of MedicineHideharuHagiyaDepartment of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaHaseDepartment of Infectious Diseases, Japanese Red Cross Narita HospitalShujiHatakeyamaDivision of Infectious Diseases, Jichi Medical University HospitalTohruInabaDepartment of Infection Control and Laboratory Medicine, Kyoto Prefectural University of MedicineKoichiIzumikawaYoshioTakesueDepartment of Infectious Diseases, Nagasaki University Graduate School of Biomedical SciencesMotoKimuraDepartment of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health SecurityNorioOhmagariDisease Control and Prevention Center, Japan Institute for Health SecurityBackground<br>
Nasopharyngeal swab sampling remains the gold standard for influenza diagnosis; however, it has several limitations, including dependence on medical staff, invasiveness, potential for nosocomial transmission, and occupational exposure risk. Non-invasive alternatives, such as saliva and nasal vestibular swabs, may improve patient comfort and participation in clinical studies. In addition, diagnosis with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Although rapid diagnostic devices such as the GenPad® offer potential alternatives to RT-qPCR, their performance with non-invasive samples remains insufficiently explored. This study addresses the two key questions for influenza detection in severe acute respiratory infection (SARI) cases: (i) whether saliva or nasal vestibular swab samples serve as suitable alternatives to nasopharyngeal swab samples, and (ii) whether the GenPad® provides a reliable option for detecting influenza using saliva samples.<br>
Methodology<br>
A prospective observational study was conducted with 16 inpatients classified as having SARIs and diagnosed with influenza between December 2024 and March 2025 in Japan. Paired saliva and nasal vestibular swab samples were collected 1-9 (median = 3.5) days after symptom onset. RT-qPCR testing was performed according to the National Institute of Infectious Diseases protocol. Saliva samples were also tested using the GenPad® system. Comparisons between sample types and diagnostic methods were analyzed using the exact McNemar's test.<br>
Results<br>
Among the 16 influenza-positive patients, saliva samples demonstrated higher sensitivity (87.5%) than nasal vestibular swabs (31.3%) in RT-qPCR when compared with the diagnostic results obtained from nasopharyngeal swabs. A comparison of RT-qPCR results between saliva and nasal vestibular swabs revealed a total agreement of 43.8%, with exact McNemar's test showing a significant difference (p = 0.0039). While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within seven days of symptom onset (100% positive agreement). The GenPad®, a rapid diagnostic device, showed promising performance (92.9%) using saliva samples compared to RT-qPCR.<br>
Conclusions<br>
Saliva is a reliable non-invasive alternative to nasopharyngeal swabs for influenza detection in SARI cases, particularly within seven days of symptom onset, whereas nasal vestibular swabs show lower sensitivity. Additionally, the GenPad® provides comparable performance to RT-qPCR using saliva samples, offering a rapid, portable diagnostic option. These approaches may mitigate discomfort, minimize infection risk for healthcare workers, and improve testing capacity. However, the absence of influenza-negative controls and the small sample size (n = 16) substantially limit the assessment of diagnostic accuracy and specificity. As a result, the broader applicability of our findings should be interpreted with caution, and further studies are required to validate these observations.No potential conflict of interest relevant to this article was reported.Ovid Technologies (Wolters Kluwer Health)Acta Medica Okayama1743-915911222025Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis23012310ENTatsuyaHayashiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiharuMitsuhashiCenter of Innovative Clinical Medicine, Okayama University HospitalHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohiroHabuOkayama University Thoracic Surgery Study Group (OUTSSG)KazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromasaYamamotoOkayama University Thoracic Surgery Study Group (OUTSSG)TomoakiOtsukaOkayama University Thoracic Surgery Study Group (OUTSSG)MototsuguWatanabeOkayama University Thoracic Surgery Study Group (OUTSSG)TakeshiKurosakiOkayama University Thoracic Surgery Study Group (OUTSSG)EijiYamadaOkayama University Thoracic Surgery Study Group (OUTSSG)EisukeMatsudaOkayama University Thoracic Surgery Study Group (OUTSSG)TatsurouHayashiOkayama University Thoracic Surgery Study Group (OUTSSG)ToshiyaFujiwaraOkayama University Thoracic Surgery Study Group (OUTSSG)MakioHayamaOkayama University Thoracic Surgery Study Group (OUTSSG)HiroyukiTaoOkayama University Thoracic Surgery Study Group (OUTSSG)MasaomiYamaneOkayama University Thoracic Surgery Study Group (OUTSSG)HidetoshiInokawaOkayama University Thoracic Surgery Study Group (OUTSSG)YujiHiramiOkayama University Thoracic Surgery Study Group (OUTSSG)KazuhiroWashioOkayama University Thoracic Surgery Study Group (OUTSSG)TakahikoMisaoOkayama University Thoracic Surgery Study Group (OUTSSG)MotohiroYamashitaOkayama University Thoracic Surgery Study Group (OUTSSG)YoshifumiSanoOkayama University Thoracic Surgery Study Group (OUTSSG)MasaoNakataOkayama University Thoracic Surgery Study Group (OUTSSG)OsamuKawamataOkayama University Thoracic Surgery Study Group (OUTSSG)ShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear.<br>
Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors.<br>
Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group.<br>
Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8012026A Novel Nomogram that Predicts Chronic Hemodialysis Patients’ Survival Based on Their Sedentary Behavior916ENKentaroSugaharaDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityTakashiKondoInnoshima General HospitalNobuyukiMiyatakeDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityHiroyukiNishiInnoshima General HospitalKazuhiroUjikeInnoshima General HospitalKiichiKoumotoInnoshima General HospitalKeiichiNamioDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityShuheiHishiiDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityAkihikoKatayamaFaculty of Social Studies, Shikokugakuin UniversityHiromiSuzukiDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityYorimasaYamamotoInnoshima General HospitalOriginal Article10.18926/AMO/70068Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patients’ survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patients’ sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7±11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patients’ sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patients’ 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8012026Usefulness of D-dimer Assay to Confirm the Course of Overt Venous Thromboembolism (VTE) in Cancer Patients17ENHidenaruYamaokaDepartment of Cardiovascular Medicine, IMS Tokyo Katsushika General HospitalMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshihiroSarashinaSeisukai Kuroda ClinicSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMitsuruMunemasaDepartment of Cardiovascular Medicine, Okayama Rosai HospitalKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of General Internal Medicine 3, Kawasaki Medical School General Medical CenterShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/70067Venous thromboembolism (VTE) is a serious complication in patients with cancer. In this population, the presence of thrombi is often assessed at cancer diagnosis by measuring D-dimer levels, which have high sensitivity but low specificity for identifying VTE at this clinical time point. However, the usefulness of D-dimer measurement during anticoagulation therapy has not been fully established, despite its widespread use. In this retrospective observational study, we investigated whether D-dimer measurement during anticoagulation therapy in cancer patients could predict overt VTE at follow-up. The study included patients who underwent D-dimer testing and contrast-enhanced computed tomography between 30 and 100 days after initiation of anticoagulation therapy. Eighty-two patients were included: 60 with cancer and 22 without. The diagnostic performance of D-dimer for overt VTE was as follows: sensitivity, 85.7%; specificity, 87.2%; positive predictive value, 78.3%; and negative predictive value, 89.2%. These findings suggest that D-dimer measurement at follow-up has high sensitivity and specificity for overt VTE in cancer patients and may aid in assessing thrombotic status. Clinically, if anticoagulation therapy is continued until D-dimer levels become negative, the absence of overt VTE could be inferred without additional invasive testing.No potential conflict of interest relevant to this article was reported.American Association for the Advancement of Science (AAAS)Acta Medica Okayama2375-254811442025Structural insights into the divergent evolution of a photosystem I supercomplex in Euglena graciliseaea6241ENKojiKatoResearch Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshikiNakajimaResearch Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRunaSakamotoResearch Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMinoruKumazawaInstitute of Low Temperature Science, Hokkaido UniversityKentaroIfukuGraduate School of Agriculture, Kyoto UniversityTakahiroIshikawaInstitute of Agricultural and Life Sciences, Academic Assembly, Shimane UniversityJian-RenShenResearch Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAtsushiTakabayashiInstitute of Low Temperature Science, Hokkaido UniversityRyoNagaoFaculty of Agriculture, Shizuoka UniversityPhotosystem I (PSI) forms supercomplexes with light-harvesting complexes (LHCs) to perform oxygenic photosynthesis. Here, we report a 2.82-angstrom cryo–electron microscopy structure of the PSI-LHCI supercomplex from Euglena gracilis, a eukaryotic alga with secondary green alga-derived plastids. The structure reveals a PSI monomer core with eight subunits and 13 asymmetrically arranged LHCI proteins. Euglena LHCIs bind diadinoxanthin, which is one of the carotenoids typically associated with red-lineage LHCs and is not present in the canonical LHCI belt found in green-lineage PSI-LHCI structures. Phylogenetic analysis shows that the Euglena LHCIs originated from LHCII-related clades rather than from the green-lineage LHCI group and that the nuclear-encoded PSI subunit PsaD likely originated from cyanobacteria via horizontal gene transfer. These observations indicate a mosaic origin of the Euglena PSI-LHCI. Our findings uncover a noncanonical light-harvesting architecture and highlight the structural and evolutionary plasticity of photosynthetic systems, illustrating how endosymbiotic acquisition and lineage-specific adaptation shape divergent light-harvesting strategies.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama2694-2445562025Electronic Structure of the S1 State Manganese Cluster in Photosystem II Investigated Using Q-Band Selective Hole-Burning660671ENShinyaKosakiDepartment of Physics, Graduate School of Science, Nagoya UniversityNaohikoNakamuraDepartment of Physics, Graduate School of Science, Nagoya UniversityYoshikiNakajimaResearch Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroyukiMinoDepartment of Physics, Graduate School of Science, Nagoya UniversityThe electronic structure of the S1 state of photosystem II (PSII) was investigated using selective hole burning of Q-band pulsed electron paramagnetic resonance. The free induction decay and spin–echo signals of the tyrosine radical YD• in the plant PSII oscillated because of the magnetic dipole–dipole interaction with the S1 state Mn cluster. The initial period was 410 ns (2.44 MHz) and was assigned to the S = 1 spin state. Based on the oscillation analysis, both Mn1 and Mn4 and both Mn2 and Mn3 were assigned as Mn(III) and Mn(IV), respectively, which is consistent with the quantum chemical calculations. The 410 ns period was accounted for in the simplified model using the isotropic spin density distribution ratio [1.6:–1.1:–1.1:1.6] for Mn1–4 ions. This oscillation was identical with that observed in the presence of methanol. The oscillation decreased in PsbP/Q- and PsbO/P/Q-depleted PSII. In Thermosynechococcus vulcanus, two periods, 390 ns (2.56 MHz) and 630 ns (1.59 MHz), were detected, indicating that the cyanobacterial S1 state includes two isomers, S = 1 and S ≥ 2 spins. The S ≥ 2 spin was not detected in PsbO/U/V-depleted PSII without polyethylene glycol. The S ≥ 2 state was consistent with the reported quantum chemical calculation using S = 3. A simplified model accounted for the S = 1 state as the spin density distribution [1.8:–1.3:–1.3:1.8] and for the S ≥ 2 state as the isotropic spin density distribution [−0.5:0.5:0.5:0.5] for Mn1–4 ions. In combination with quantum chemical calculations, the most probable protonated structure is W1 = H2O, W2 = H2O, O4 = O2–, and O5 = O2– for the S1 state. These results demonstrate that the selective hole burning method is a powerful tool to complement X-ray studies to determine the valence and protonation structure of manganese clusters, not only in the S1 state but also in higher S-states and general metal clusters, which would provide important insights into the water oxidation mechanism.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0925-571012252025Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial733743ENNorikoDokiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalShinichiKakoDivision of Hematology, Jichi Medical University Saitama Medical CenterEmikoSakaidaDepartment of Hematology, Chiba University HospitalYoshinobuKandaDivision of Hematology, Department of Medicine, Jichi Medical UniversityIdiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT. Seven male patients (all male; mean age: 43.3 years) received HLC-001 and three completed the trial. The survival rate at day 56 (primary endpoint) was 71.4% (5/7 patients; 95% confidence interval: 29.0%–96.3%) and was sustained at day 100, suggesting that HLC-001 was more effective than previously reported treatment. Three of the five patients with ≥ 100 days of follow-up died. Five patients experienced at least one adverse drug reaction, none of which were serious. These findings indicate that HLC-001 was potentially effective and generally well tolerated in Japanese patients with steroid-dependent or refractory IPS after HSCT. Given there is no effective cure for steroid-dependent or refractory IPS, HLC-001 may be a promising treatment option and further clinical evaluation is warranted.<br>
Trial registration: Japan Registry of Clinical Trials identifier: jRCT2063220014.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1873-96011942025Interaction between nuclear‐translocated cellular communication network factor 2 and purine‐rich box 1 regulates the expression of fibrosis‐related genese70051ENXuan ThiNguyenDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaharuTakigawaAdvanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama JapanTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCellular communication network factor 2 (CCN2) with a nuclear localization signal-like peptide is known to promote fibrosis. However, translocation of CCN2 into the nucleus and its role in fibrosis remain unclear. We hypothesized that nuclear-translocated CCN2 is associated with purine-rich box 1 (PU.1), which is a transcription factor regulating the differentiation of myofibroblasts. Western blot analysis of the cytoplasmic and nuclear fractions of cell lysate and immunofluorescence analysis revealed that CCN2 was detectable in both the cytoplasm and nuclei of murine fibroblastic NIH3T3 cells. Additionally, chromatin immunoprecipitation (IP)-PCR and an electrophoretic mobility shift assay revealed that recombinant CCN2 protein bound to the regulatory region of Spi1, which encodes PU.1. Furthermore, IP-Western blot analysis showed that CCN2 interacted with PU.1. Finally, the forced expression of both Ccn2 and Spi1 significantly promoted the production of angiotensin II, and increased fibrosis-related molecules, such as Col1a1 and Acta2, at the gene and protein levels. These findings indicate that CCN2 translocated to the nucleus interacts with PU.1 and that the complex promotes the markers of myofibroblast differentiation, suggesting that CCN2 plays an important role in fibrosis via cooperation with PU.1, as a transcription co-factor.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006726182025Interaction Between Thyroid Hormones and Bone Morphogenetic Proteins in the Regulation of Steroidogenesis by Granulosa Cells9127ENKanonMotohashiDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshiakiSoejimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiroYamamotoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNahokoIwataDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsuhitoSuyamaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThyroid hormones are fundamental regulators of cellular differentiation, development, and metabolism. Their receptors are expressed in reproductive tissues, including the ovary, and dysregulation of thyroid hormone homeostasis has been associated with menstrual disturbances, infertility, and adverse pregnancy outcomes. Bone morphogenetic protein (BMP) ligands and their receptors are functionally involved in gonadotropin-induced ovarian steroidogenesis in an autocrine or paracrine manner. In this study, we examined the effects of thyroid hormones on steroidogenesis and their interplay with BMP signaling by using human granulosa-like KGN cells and primary rat granulosa cells (GCs). In KGN cells, triiodothyronine (T3) enhanced forskolin-induced expression of key steroidogenic enzymes involved in both estradiol biosynthesis and progesterone synthesis/metabolism, whereas thyroxine (T4) exerted minimal effects. In rat GCs, T3 treatment increased follicle-stimulating hormone (FSH)-stimulated estradiol production without altering progesterone output. T3 pretreatment attenuated BMP-6-induced phosphorylation of Smad1/5/9 in KGN cells, accompanied by upregulation of inhibitory Smad6 and downregulation of the BMP type II receptor. Conversely, BMP-6 stimulation elevated thyroid hormone receptor β expression, indicating reciprocal regulatory interactions between thyroid hormone and BMP pathways. Collectively, these findings suggest that thyroid hormones modulate steroidogenesis, at least in part, through suppression of endogenous BMP-6 signaling in granulosa cells.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama2155-543515142025Mesoporous Oxyhalide Aggregates Exhibiting Improved Photocatalytic Activity for Visible-Light H2 Evolution and CO2 Reduction1255112562ENHirotoUekiDepartment of Chemistry, School of Science, Institute of Science TokyoToshiyaTanakaDepartment of Chemistry, School of Science, Institute of Science TokyoShujiAnabukiGraduate School of Natural Science and Technology, Okayama UniversityRyuichiNakadaDepartment of Chemistry, School of Science, Institute of Science TokyoMegumiOkazakiDepartment of Chemistry, School of Science, Institute of Science TokyoKentaAiharaDepartment of Chemistry, School of Science, Institute of Science TokyoMasashiHattoriMaterials and Structures Laboratory, Institute of Integrated Research, Institute of Science TokyoFumitakaIshiwariDepartment of Applied Chemistry, Graduate School of Engineering, Osaka UniversityRieHarukiInstitute of Materials Structure Science, High Energy Accelerator Research OrganizationShunsukeNozawaInstitute of Materials Structure Science, High Energy Accelerator Research OrganizationToshiyukiYokoiNanospace Catalysis Unit, Institute of Integrated Research, Institute of Science TokyoMichikazuHaraMaterials and Structures Laboratory, Institute of Integrated Research, Institute of Science TokyoOsamuIshitaniDepartment of Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima UniversityAkinoriSaekiDepartment of Applied Chemistry, Graduate School of Engineering, Osaka UniversityAkiraYamakataGraduate School of Natural Science and Technology, Okayama UniversityKazuhikoMaedaDepartment of Chemistry, School of Science, Institute of Science TokyoOxyhalides are promising visible-light photocatalysts for water splitting and CO2 conversion; however, those exhibiting high activity for these reactions have rarely been reported. Here, we show that using water-soluble Ti complexes as precursors in the microwave-assisted hydrothermal synthesis of the oxyhalide photocatalyst Pb2Ti2O5.4F1.2 (PTOF) resulted in the production of nanoparticulate PTOF. The primary particle size of the synthesized PTOF ranged from several tens of nanometers to several hundreds of nanometers. Using Ti-citric acid or Ti-tartaric acid complexes as precursors, the PTOF was formed as mesoporous aggregates, compared with a bulky analogue (0.5–1 μm) prepared using a TiCl4 precursor. The PTOF prepared from Ti-citric acid complex had a particle size of 50–100 nm and showed a one-order-of-magnitude greater activity for H2 evolution from an aqueous ethylenediaminetetraacetic acid solution with the aid of a Rh cocatalyst. An apparent quantum yield (AQY) of 15.4 ± 1.0% at 420 nm, which is the highest among the reported oxyhalide photocatalysts, was achieved under optimal conditions. Although excess particle size reduction of PTOF lowered the H2 evolution activity, the PTOF with the smallest possible primary particle size of 15–30 nm, prepared from Ti-tartaric acid complex, showed the highest activity toward the selective reduction of CO2 into formate in a nonaqueous environment when combined with a binuclear Ru(II) complex. The CO2 reduction AQY was 10.4 ± 1.8% at 420 nm, a record-high value among metal-complex/semiconductor binary hybrid photocatalysts. This study highlights the importance of morphological control of oxyhalides for realizing their full potential as photocatalysts for artificial photosynthesis.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2073-43441522025Palladium-Catalyzed Decarbonylative Nucleophilic Halogenation of Acid Anhydrides191ENTianTianGraduate School of Natural Science and Technology, Okayama UniversityShuheiUeiDepartment of Chemistry, Faculty of Science, Okayama UniversityWeidanYanGraduate School of Natural Science and Technology, Okayama UniversityYasushiNishiharaResearch Institute for Interdisciplinary Science (RIIS), Okayama UniversityIn this study, we developed a palladium-catalyzed decarbonylative nucleophilic halogenation reaction using inexpensive and readily available acid anhydrides as substrates. This approach effectively circumvents the instability of acyl chlorides and the low reactivity of acyl fluorides. The Pd/Xantphos catalyst system exhibited excellent compatibility with the thermodynamically and kinetically challenging reductive elimination of C–X bonds (X = I, Br, and Cl) from Pd(II) intermediates. Notably, for electron-donating substrates, adopting an open system significantly improved the reaction efficiency. The positive effect of the open system may be due to the reversible nature of CO insertion and deinsertion, which helps direct the reaction toward the desired pathway by allowing the generated CO to exit the reaction system. Mechanistic studies suggest that the reaction proceeds through a highly reactive acyl halide intermediate, followed by a unimolecular fragment coupling (UFC) pathway via decarbonylation or an alternative pathway involving the formation of an activated anionic palladate complex in the presence of lithium halide.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1648-91446162025Accuracy Verification of a Computed Tomography-Based Navigation System for Total Hip Arthroplasty in Severe Hip Dysplasia: A Simulation Study Using 3D-Printed Bone Models of Crowe Types II, III, and IV973ENRyuichiroOkudaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomonoriTetsunagaDepartment of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazukiYamadaDepartment of Orthopaedic Surgery, Okayama University HospitalTomokoTetsunagaDepartment of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiKouraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohiroInoueDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasutakaMasadaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground and Objective: The use of computed tomography (CT)-based navigation systems has been shown to improve surgical accuracy in total hip arthroplasty. However, there is limited literature available about the application of CT-based navigation systems in severe hip dysplasia. This study aimed to evaluate the accuracy of a CT-based navigation system in patients with severe hip dysplasia using three-dimensional (3D)-printed bone models. Methods: 3D-printed bone models were generated from CT data of patients with severe hip dysplasia (Crowe type II, 10 hips; type III, 10 hips; and type IV, 10 hips). The accuracy of automatic segmentation, success rate, point-matching accuracy across different registration methods, and deviation values at reference points after registration were assessed. Results: For the combined cohort of Crowe II, III, and IV cases (n = 30), the Dice Similarity Coefficient and Jaccard Index were 0.99 ± 0.01 and 0.98 ± 0.02, respectively. These values indicate a high level of segmentation accuracy. The “Matching with true and false acetabulum + iliac crest” method achieved a 100% success rate across all groups, with mean deviations of 0.08 ± 0.28 mm in the Crowe II group, 0.12 ± 0.33 mm in the Crowe III group, and 0.14 ± 0.50 mm in the Crowe IV group (p = 0.572). In the Crowe IV group, the anterior superior iliac spine deviation was significantly lower using the “Matching with true and false acetabulum + iliac crest” method compared to the “Matching with true and false acetabulum” method (0.28 ± 0.49 mm vs. 3.29 ± 2.56 mm, p < 0.05). Conclusions: This study demonstrated the high accuracy of automatic AI-based segmentation, with a Dice Similarity Coefficient of 0.99 ± 0.01 and a Jaccard Index of 0.98 ± 0.02 in the combined cohort of Crowe type II, III, and IV cases (n = 30). The matching success rate was 100%, with additional points on the iliac crest, which improved matching accuracy and reduced deviations, depending on the case.No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231902025創造性・STEAM 教育を基にした Creative Educator 育成プログラムに関する基礎研究U ― CE コンピテンシーの整理を通した教育実践ロールモデル構築に向けて ―127137ENAiMATSUURAFaculty of Education, Okayama UniversityYoshiakiTUTUMIKushiro Compulsory Education School, Hokkaido University of Education Late CourseChandeSONOsaka Kyoiku University Tennoji Junior High SchoolHitoshiKIMURAShiga University Faculty of Education Elementary SchoolTetsuoKIYOTAFaculty of Education, Okayama UniversityYoshihikoINADAFaculty of Education, Okayama University10.18926/bgeou/69616 創造性とSTEAM 教育を基盤としたCreative Educator（ CE）育成プログラムに関する研究では，CE を「身体的な感受や経験を通して創造性教育を担う教員」と定義し，その育成に必要なコンピテンシーを「身体的思考」「空間的思考」「批判的対話」「創造的な態度」とした。そこで本論では，授業における創造性育成の要素として四つ挙げ，創造性に関する先行研究を整理した。その結果，創造性の研究において四つの要素を以下の通り捉えられることを確認した。@身体を通した予期せぬ刺激「想定外」は，身体化された認知や素材との相互作用から生じる新しい思考を促す。A他者との関係性を意識した「場づくり」は，対話や協働を通して創造性を育む。B空間的思考に基づく「可視化」は，視覚情報の統合や変換により創造的イメージを支える。C「チャレンジ」は，自律的意思決定や創造的自信を高め，潜在的創造力の発揮を促す。No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1664-3224162025A pilot transcriptomic study of a novel multitargeted BRT regimen for anti–MDA5 antibody-positive dermatomyositis: improving survival over conventional therapy1568338ENMoeTokunagaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuNakaiDivision of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama HospitalYoshiharuSatoDNA Chip Research Inc., Medical LaboratoryMitoriHiratsukaDNA Chip Research Inc., Medical LaboratoryYoshinoriMatsumotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakeshiNakatsueDivision of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross HospitalTakakoSaekiDivision of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross HospitalTakatsuneUmayaharaDivision of Dermatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama HospitalJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinobuKoyamaDivision of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama HospitalBackground: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5-DM) is associated with severe outcomes, primarily due to rapidly progressive interstitial lung disease (RP-ILD), which is often refractory to standard therapies such as calcineurin inhibitors (e.g., tacrolimus) combined with cyclophosphamide (TC-Tx). This study evaluated the efficacy of a novel multitargeted regimen combining baricitinib, rituximab, and tacrolimus (BRT-Tx) in improving survival outcomes for MDA5-DM patients with poor prognostic factors.<br>
Methods: Fourteen MDA5-DM patients with multiple adverse prognostic factors were studied. Seven received the BRT-Tx regimen, and the remaining seven, previously treated with TC-Tx, served as historical controls. Twelve-month survival was assessed. Transcriptome analysis was performed for six patients (BRT=3, TC=3), beginning with cluster analysis to evaluate whether changes in peripheral blood gene expression varied according to treatment or prognosis. Gene ontology analysis characterized expression profiles in survivors and distinguished treatment effects. Alterations in the type I, II, and III interferon signatures were also assessed.<br>
Results: In the TC-Tx group, four of seven patients succumbed to RP-ILD, whereas all seven BRT-Tx patients survived the 12-month observation period. Only one BRT-Tx patient required combined rescue therapies, including plasma exchange, and one case of unexplained limbic encephalitis (LE) occurred. Cytomegalovirus reactivation was observed in both groups (BRT: 5/7; TC: 6/7). Transcriptomic analysis revealed no treatment-specific clustering of differentially expressed genes (DEGs) before and after therapy. However, survivors and nonsurvivors formed distinct clusters, with survivors showing significant posttreatment suppression of B-cell-related gene expression. Moreover, interferon signature scores were significantly lower after treatment in survivors than in nonsurvivors. BRT-Tx effectively suppressed B-cell-mediated immune responses and maintained a low interferon signature, while TC-Tx resulted in nonspecific gene suppression, and in nonsurvivors, an elevated interferon signature was observed.<br>
Conclusion: BRT-Tx has the potential to improve survival in MDA5-DM patients by effectively targeting hyperactive immune pathways. The combination of rituximab and tacrolimus is expected to disrupt B-cell–T-cell interactions and reduce autoantibody production, whereas baricitinib may suppress both IFN and GM-CSF signaling, regulating excessive autoimmunity mediated by cells such as macrophages. Unlike TC-Tx, BRT-Tx avoids cyclophosphamide-associated risks such as infertility and secondary malignancies. Future randomized controlled trials are warranted to validate its efficacy and safety.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0007-10482025Impact of methotrexate-dosing regimens for GVHD prophylaxis on clinical outcomes of HLA-matched allogeneic HSCTENTomotakaSuzukiDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical SciencesTomoyasuJoDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityKotaYoshifujiDepartment of Hematology, Institute of Science TokyoTadakazuKondoDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityNorikoDokiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome HospitalYoshinobuKandaDivision of Hematology, Jichi Medical University Saitama Medical CentreTetsuyaNishidaDepartment of Hematology, Japanese Red Cross Aichi Medical Centre Nagoya Daiichi HospitalYasushiOnishiDepartment of Hematology, Tohoku University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalTakahiroFukudaDepartment of Haematopoietic Stem Cell Transplantation, National Cancer Centre HospitalMasashiSawaDepartment of Hematology and Oncology, Anjo Kosei HospitalYutaHasegawaDepartment of Hematology, Hokkaido University HospitalKentaroSerizawaDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineShuichiOtaDepartment of Hematology, Sapporo Hokuyu HospitalMasatsuguTanakaDepartment of Hematology, Kanagawa Cancer CentreMakotoYoshimitsuDepartment of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima UniversityYoshikoAtsutaJapanese Data Centre for Haematopoietic Cell TransplantationJunyaKandaDepartment of Hematology, Graduate School of Medicine, Kyoto UniversitySevere graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7 mg/m2 on day 11) and an original-dose 3-day regimen (Od3: 15 mg/m2 on day 1, 10 mg/m2 on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II–IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III–IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0007-10482025Efficacy of ciclosporin monotherapy in non-severe aplastic anaemia not requiring transfusions: Results from a multicentre phase II studyENKenIshiyamaDepartment of Hematology, Kanazawa University HospitalMasahideYamazakiDepartment of Internal Medicine, Keiju Medical CenterHiroyukiMaruyamaDepartment of Hematology, Kanazawa University HospitalNaokoHosonoDepartment of Hematology and Oncology, University of Fukui HospitalHirokiYamaguchiDepartment of Hematology, Nippon Medical SchoolNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalKazukiTanimotoDepartment of Hematology and Oncology, Japanese Red Cross Fukuoka HospitalHiroyukiSugiuraDepartment of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School TeachersKensukeUsukiDepartment of Hematology, NTT Medical Center TokyoKenichiYoshimuraDepartment of Biostatistics and Health Data Science, Graduate School of Medical Science, Nagoya City UniversitySeishiOgawaDepartment of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto UniversityYuzuruKanakuraSumitomo HospitalItaruMatsumuraDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineKoichiAkashiDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical SciencesShinjiNakaoDepartment of Hematology, Kanazawa University HospitalThe efficacy of ciclosporin (CsA) to treat transfusion-independent non-severe aplastic anaemia (TI-NSAA) has not yet been systematically evaluated. We conducted a prospective trial in patients with TI-NSAA treated with CsA monotherapy. CsA (3.5 mg/kg/day) was administered to patients with TI-NSAA aged ≥16. The CsA dose was adjusted to maintain a blood CsA level of ≥600 ng/mL at 2 h post-administration. Blood cell counts were assessed after 8, 16 and 52 weeks of therapy. Thirty-two evaluable patients from 21 institutions were enrolled. The median age was 63.5 (range: 16–83) years. At 8 weeks, haematological improvement, with increases in haemoglobin (Hb) ≥1.5 g/dL (haematological improvement in erythrocytes [HI-E]) and platelet count ≥30 × 109/L (haematological improvement in platelets [HI-P]), was observed in 0/25 (0%) and 6/32 (19%) evaluable cases respectively. HI-E and HI-P occurred in 1/25 (4%) and 10/32 (31%) patients at 16 weeks, respectively, and at 52 weeks in 5/25 (20%) and 16/32 (50%) patients respectively. Nine grade 3 adverse events (AEs) occurred in six patients, but there were no grade ≥4 AEs. Ten of the 32 patients experienced grade 2 renal toxicity. Low-dose CsA is effective in TI-NSAA patients and demonstrates minimal renal toxicity. However, at least 16 weeks are necessary to adequately evaluate its efficacy.No potential conflict of interest relevant to this article was reported.BMJActa Medica Okayama2044-60551562025Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemiae098532ENNorikoFukuharaHematology, Tohoku University Graduate School of MedicineMakotoOnizukaDepartment of Hematology and Oncology, Tokai University School of Medicine Graduate School of MedicineJunyaKandaDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalKojiKatoDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu UniversityKiyoshiAndoDepartment of Hematology, Hiroshima UniversityIntroduction Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy. This study aimed to evaluate the tolerability, safety, efficacy, and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with ANKL.<br>
Methods and analysis This multicentre, open-label, dose-escalation phase I/II study will be conducted at nine hospitals in Japan. Patients diagnosed with ANKL (whether as a primary or recurrent disease) and exhibiting abnormal liver function or hepatomegaly due to the primary disease will be included. The primary endpoint is the tolerability and safety of repeated continuous intravenous administration of PPMX-T003 in the first course, based on adverse events and dose-limiting toxicities. PPMX-T003 will be administered as a continuous intravenous infusion every 24 hours for five consecutive days, followed by a 2-day break. Pretreatment will be provided to minimise the risk of infusion-related reactions. Initial doses of PPMX-T003 will be 0.5, 1.0 or 2.0 mg/kg, with subsequent dose increases determined by the Data and Safety Monitoring Committee. The sample size is set at seven participants, with enrolment increased to up to 12 participants if dose-limiting toxicities occur, based on feasibility due to the rarity of ANKL. Descriptive statistics will summarise data according to initial dose, and pharmacokinetic analysis will be conducted based on administered dose.<br>
Ethics and dissemination This study was approved by the institutional review boards at participating hospitals. The results will be disseminated in peer-reviewed journals.<br>
Trial registration number jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov).No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-230X2512025Neoadjuvant chemotherapy strategies for optimizing safety and efficacy in elderly patients with locally advanced gastric cancer670ENYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShinjiKurodaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShunyaHanzawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNobuhikoKanayaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHajimeKashimaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSatoruKikuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShunsukeKagawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineBackground The completion rate of adjuvant chemotherapy for gastric cancer (GC) is suboptimal, particularly in elderly patients. While neoadjuvant chemotherapy (NAC) for locally advanced GC has shown promise, data on elderly patients remain limited. Given the considerable physical burden of NAC, optimizing its administration is crucial. This study evaluates the safety and efficacy of a modified approach for elderly patients.<br>
Methods A retrospective analysis was conducted on 38 patients with cStage II/III GC who received NAC between November 2015 and December 2023. Additionally, 25 patients aged ≥ 75 years with cStage III who underwent upfront surgery during the same period were analyzed.<br>
Results The NAC group was divided into non-elderly (< 75 years, n = 27) and elderly (≥ 75 years, n = 11) groups. The elderly group had poorer ECOG-PS (p = 0.016). While all non-elderly patients completed ≤ 3 cycles, more elderly patients underwent 4 cycles (p = 0.0047). However, per-cycles of S-1 (p = 0.0003) and oxaliplatin (p = 0.0018) were lower in the elderly group. Importantly, adverse events and treatment efficacy were comparable between groups. Among patients aged ≥ 75 years, the upfront surgery group had poorer ECOG-PS (p = 0.017) and underwent more frequent distal gastrectomy (p = 0.014).<br>
Conclusions NAC can be safely administered to elderly patients by increasing cycles while reducing per-cycle dosage. It may also serve as a viable alternative to upfront surgery.No potential conflict of interest relevant to this article was reported.Ovid Technologies (Wolters Kluwer Health)Acta Medica Okayama0194-911X82102025Redefining AT1 Receptor PET Imaging: Introducing the Radiotracer [18F]DR2916261637ENXinyuChenNuclear Medicine, Faculty of Medicine, University of AugsburgHiroyukiKimuraAgency for Health, Safety and Environment, Kyoto UniversityTakanoriSasakiFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKonradKlimekGoethe University Frankfurt, University Hospital, Clinic for Radiology and Nuclear Medicine, Department of Nuclear MedicineSaskiaMühligDepartment of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital WürzburgAnahi PaulaArias-LozaDepartment of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital WürzburgNaokoNoseFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeYagiFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySteven PRoweMolecular Imaging and Therapeutics, Department of Radiology, School of Medicine, University of North Carolina, Chapel HillConstantinLapaNuclear Medicine, Faculty of Medicine, University of AugsburgRudolf A.WernerDepartment of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of MunichTakahiroHiguchiFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBACKGROUND: AT1R (angiotensin II type 1 receptors) are central to the renin-angiotensin system and are involved in regulating blood pressure and renal physiology. This study introduces [18F]DR29, a fluorine-18-labeled radiotracer for positron emission tomography imaging, to enable noninvasive visualization of AT1R expression. Its potential applications in understanding AT1R-associated renal processes are explored in healthy and hypertensive rat models.<br>
METHODS: Radiolabeling was established, and biodistribution studies were conducted on healthy Wistar rats with and without the AT1R antagonist candesartan and transporter inhibitors. Dynamic positron emission tomography imaging assessed tracer specificity, and feasibility for renal AT1R quantification was explored using a hypertensive rat model.<br>
RESULTS: [18F]DR29 was radiolabeled with a yield of 36±6%. High kidney uptake was observed, significantly reduced by candesartan (kidney-to-blood ratio, 0.43±0.01 versus 4.54±1.59 in vehicle, where vehicle refers to saline without any treatment). Transporter inhibition protocols targeting organic anion transporting polypeptides (liver) and organic anion transporters (kidneys) successfully reduced radiotracer clearance, increasing the specific accumulation of [18F]DR29 in the kidneys and improving renal imaging contrast. Positron emission tomography imaging revealed rapid kidney uptake and stable retention over 2 hours. In hypertensive rats, kidney uptake was higher, aligning with AT1R expression levels.<br>
CONCLUSIONS: These results support [18F]DR29 as a promising tool for the noninvasive evaluation of renal AT1R expression in healthy and diseased states. The findings lay the groundwork for clinical translation, offering potential applications in diagnosing and managing kidney-related diseases, including hypertension and other conditions involving AT1R dysregulation.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0250-832X2025Radiological assessment of dissected cervical lymph nodes in level III affected by the area of supraomohyoid neck dissectionENYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshioOhyamaClinical Anatomy Research Association in Oral and Maxillofacial SurgerySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiMatsushitaClinical Anatomy Research Association in Oral and Maxillofacial SurgeryR ShaneTubbsClinical Anatomy Research Association in Oral and Maxillofacial SurgeryNorioKitagawaClinical Anatomy Research Association in Oral and Maxillofacial SurgeryToshiyukiKawazuDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMikiHisatomiDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalShunsukeOkadaDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalMamikoFujikuraDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalYoshinobuYanagiDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJoeIwanagaClinical Anatomy Research Association in Oral and Maxillofacial SurgeryObjectives: To compare the number of dissected cervical lymph nodes in the anatomical level III with that in supraomohyoid neck dissection (SOHND) level III affected by the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND.<br>
Methods: CE-CT images of the patients who suffered from malignant tumours in the oral and maxillofacial regions were reviewed. The number of cervical lymph nodes both in the anatomical level III (area between the centre of the inferior border of the hyoid bone [HB] and the inferior border of the cricoid cartilage [CC]) and SOHND level III (area between HB and the intersection of the omohyoid muscle and internal jugular vein [OM-IJ]) were recorded, respectively.<br>
Results: The rate of patients whose number of lymph nodes in level III was affected by the positional relationship between the OM-IJ and CC was almost equal in males and females. As for the patients with OM-IJ below the CC, the number of lymph nodes in SOHND level III increased from that of anatomical level III. Females showed significantly higher values than males (P < .05). Meanwhile, for patients with OM-IJ at or above the CC, the number of lymph nodes in SOHND level III decreased from that of anatomical level III.<br>
Conclusions: The number of dissected cervical lymph nodes differed between the SOHND dissection area and levels I, II, and III. In most cases, SOHND dissects more cervical lymph nodes, especially in female patients.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0952-19761502025Surrogate-assisted motion planning and layout design of robotic cellular manufacturing systems110530ENTomoyaKawabeGraduate School of Environmental, Life and Natural Science and Technology, Okayama UniversityTatsushiNishiGraduate School of Environmental, Life and Natural Science and Technology, Okayama UniversityZiangLiuGraduate School of Environmental, Life and Natural Science and Technology, Okayama UniversityTomofumiFujiwaraGraduate School of Environmental, Life and Natural Science and Technology, Okayama UniversityA surrogate-assisted multi-objective evolutionary algorithm is proposed for simultaneous optimization of robot motion planning and layout design in robotic cellular manufacturing systems. A sequence-pair is used to represent the layout of components in a robotic cell to avoid overlapping in the evolutionary computation. The robot motion planning with Rapidly exploring Random Trees Star (RRT*) is applied to compute the total operation time of a robot arm for each layout. Non-dominated Sorting Genetic Algorithm II (NSGA-II) is used to minimize the total required layout area and the operation time for a robot arm. The proposed surrogate model can estimate the robot’s operation time with 98% of accuracy without explicit computations of the motion planning algorithm. The experimental results with a physical 6 Degree of Freedom (DOF) manipulator show that the total computation time is approximately 1/400, significantly shorter than the conventional methods.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1876-20181082025Introduction to the “Japanese and Western approaches to psychotrauma” symposium104508ENMasanoriNagamineDivision of Behavioral Science, National Defense Medical College Research InstituteTomoyoNakaoGraduate School of Humanities and Social Sciences, Okayama UniversityLeovan BergenFreelance Medical HistorianJunShigemuraFaculty of Health Sciences, Mejiro UniversityTakuSaitoDivision of Behavioral Science, National Defense Medical College Research InstituteFlorentine H.S.van der DoesDepartment of Psychiatry, Leiden University Medical Center (LUMC)MasatoKitanoDivision of Behavioral Science, National Defense Medical College Research InstituteErik J.GiltayDepartment of Psychiatry, Leiden University Medical Center (LUMC)Nic J.van der WeeDepartment of Psychiatry, Leiden University Medical Center (LUMC)EricVermettenDepartment of Psychiatry, Leiden University Medical Center (LUMC)Understandings of psychotrauma have changed throughout medical history, shaped by cultural and social factors. Reviewing transcultural perspectives of psychotrauma helps understand its complexities and contextual impacts. This paper summarizes the Japan–Netherlands symposium on psychotrauma held on March 1, 2024. Despite experiencing psychological trauma from World War II and numerous natural disasters, Japan did not actively research post-traumatic stress disorder (PTSD) for nearly 50 years after the war. The Great Hanshin-Awaji Earthquake and the Tokyo subway Sarin gas attack (1995) popularized the term PTSD in Japan and triggered related research. The absence of psychotrauma research in Japan may reflect a form of state-level PTSD, characterized by avoidance. Japan’s collectivist culture, stigma against seeking psychological help, view of patience as a virtue, survivor guilt, and moral injury were potential related factors. Additionally, sociocultural factors (e.g., insufficient collective grieving and focusing on post-war reconstruction) were discussed as potential hinderances to discussing war experiences. From a European perspective, we examined how “Konzentrationslager” (KZ) syndrome, a trauma-related disorder, evolved independently into diverse conceptual frameworks, ultimately contributing to the acceptance of PTSD following its introduction in 1980. Beyond state compensation for concentration camp survivors, advocacy by feminist movements and veterans' groups increased awareness of psychotrauma across Europe, fostering scholarly research and public discourse. Both PTSD and KZ syndromes are diagnostic categories shaped by specific historical and cultural contexts and should not be regarded as simple, universally applicable medical conditions. They reflect how trauma is interpreted and responded to differently depending on cultural, political, and historical factors.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1752-19471912025The safety and efficacy of finasteride for transgender men with androgenetic alopecia: a case series468ENYusukeTominagaDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTomokoKobayashiDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYukoMatsumotoDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTomokoSakoDepartment of Urology, Hiroshima City Hiroshima Citizens HospitalTakatoshiMoriwakeDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSatoshiHoriiDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakuyaSadahiraDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSatoshiKatayamaDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakehiroIwataDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShingoNishimuraDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKensukeBekkuDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKoheiEdamuraDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasamiWatanabeCenter for Innovative Clinical Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMotooArakiDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineBackground Testosterone replacement therapy is commonly used in transgender men for masculinization. One of the most common adverse effects of testosterone replacement therapy is androgenetic alopecia. In Japan, finasteride is approved exclusively for cisgender men and is not indicated for transgender men. The aim of this clinical trial was to evaluate the safety and efficacy of finasteride in transgender men with androgenetic alopecia.<br>
Case presentation This study included three transgender men (assigned female at birth, identifying as male), aged 44, 43, and 29 years. All participants were of Asian ethnicity. A clinical trial was conducted from October 2021 to December 2023. Transgender men aged 20–60 years who had not undergone hysterectomy, were undergoing testosterone replacement therapy, and who had been diagnosed with stage ≥ II androgenetic alopecia on the basis of the Norwood–Hamilton scale were recruited. The participants initiated treatment with 0.2 mg of finasteride per day for 3 months (phase 1). If no adverse events above grade 2 occurred, the dose was increased to 1.0 mg per day for an additional 3 months (phase 2). The primary endpoints were the incidence of treatment-related adverse events at 1 week, 1 month, and 3 months, as well as the rate of participants continuing treatment at 3 months. None of the patients experienced serious adverse events at 3 months, and all the patients extended their treatment to a total of 6 months. Improvements of at least one stage on the N–H scale were observed, but two participants experienced resumption of menstruation.<br>
Conclusion Finasteride appears to be a safe and effective treatment for androgenetic alopecia in transgender men undergoing testosterone replacement therapy. However, its potential for reducing some of the effects of testosterone replacement therapy warrants further investigation. Trial registration: jRCT, jRCTs061210040, registered 7 October 2021, https://jrct.mhlw.go.jp/latest-detail/jRCTs061210040.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7952025Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation329337ENKeiMatsubaraDepartment of Thoracic Surgery, Hiroshima City Hiroshima Citizens HospitalKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesReview10.18926/AMO/69433Primary graft dysfunction (PGD) is one of the major risk factors affecting patients’ short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patient’s need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0960-741212352025RNA processing/modifying enzymes play key roles in the response to thermospermine in Arabidopsis thalianae70476ENMitsuruSaraumiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakahiroTanakaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityDaikiKoyamaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshitakaNishiGraduate School of Engineering, Kyushu Sangyo UniversityYoshihiroTakahashiDepartment of Life Science, Faculty of Life Science, Kyushu Sangyo UniversityHiroyasuMotoseGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakuTakahashiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThermospermine is involved in negative regulation of xylem differentiation by enhancing the translation of mRNAs of the SAC51 gene family in Arabidopsis (Arabidopsis thaliana). These mRNAs contain conserved upstream open reading frames (uORFs) that interfere with the translation of the main ORF. To investigate the mechanism by which thermospermine acts in this process, we isolated mutants insensitive to thermospermine, named ‘its’. We show that the four genes responsible for these mutants, its1 to its4, encode: (i) a homolog of SPOUT RNA methyltransferase, (ii) an rRNA pseudouridine synthase CBF5/NAP57, (iii) a putative spliceosome disassembly factor STIPL1/NTR1, and (iv) a plant-specific RNA-binding protein PHIP1. These four mutants were found to have much higher levels of thermospermine than the wild-type. While all these mutants except its1 appear almost normal, they enhance the dwarf phenotype of a mutant of ACL5, which encodes thermospermine synthase, resulting in tiny plants resembling a double knockout of ACL5 and SACL3, a member of the SAC51 family. Reporter assays revealed that GUS activity from the CaMV 35S promoter-SAC51 5′-GUS fusion construct was significantly reduced in its1 and its4 or not affected in its2 and its3, while it was slightly increased in its1, its3, and its4, or not changed in its2 by thermospermine. These findings underscore the critical role of RNA processing and modification in the thermospermine-dependent translational regulation of uORF-containing transcripts.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0014-48001422025Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu104967ENDarabGhadimiDepartment of Microbiology and Biotechnology, Max Rubner-InstitutReginaFölster-HolstClinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-HolsteinSophiaBlömerClinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-HolsteinMichaelEbsenStädtisches MVZ Kiel GmbH (Kiel City Hospital), Department of PathologyChristophRöckenInstitute of Pathology, Kiel University, University Hospital, Schleswig-HolsteinJumpeiUchiyamaDepartment of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityShigenobuMatsuzakiDepartment of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen UniversityWilhelmBockelmannDepartment of Microbiology and Biotechnology, Max Rubner-InstitutUnder an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria.No potential conflict of interest relevant to this article was reported.Ceramic Society of JapanActa Medica Okayama1348-653513392025Preparation and structural characterization of nanoporous silica/magnesium(II)-whitlockite composite particles555561ENTakuyaKataokaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityDaikiHirotaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityEijiFujiiIndustrial Technology Center of Okayama PrefectureTomohikoYoshiokaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySatoshiHayakawaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThe preparation of particles composed of nanoporous silica (NS) and Mg2+-whitlockite (Mg-WH) would provide valuable insights for designing particles for biomedical applications. In this study, NS and Mg-WH composite particles were successfully synthesized. The addition of chitosan during synthesis possibly promoted the crystallization of calcium phosphate phases in the composite particles. Pore size distribution analysis of the particles showed a maximum at 3.2 nm. Investigating the adsorption of methylene blue onto the particles in a phosphate buffer (pH 7.4) showed that the saturated adsorption amount of methylene blue on the particles was significantly higher than that on commercial hydroxyapatite. The composite particles provided important results for potential applications as drug carriers for bone regeneration and repair.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1751-73621812024Cyanorhodopsin-II represents a yellow-absorbing proton-pumping rhodopsin clade within cyanobacteriawrae175ENMasumiHasegawa-TakanoAtmosphere and Ocean Research Institute, The University of TokyoToshiakiHosakaLaboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics ResearchKeiichiKojimaFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYosukeNishimuraAtmosphere and Ocean Research Institute, The University of TokyoMarieKuriharaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuNakajimaAtmosphere and Ocean Research Institute, The University of TokyoYoshikoIshizuka-KatsuraLaboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics ResearchTomomiKimura-SomeyaLaboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics ResearchMikakoShirouzuLaboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics ResearchYukiSudoFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySusumuYoshizawaAtmosphere and Ocean Research Institute, The University of TokyoMicrobial rhodopsins are prevalent in many cyanobacterial groups as a light-energy-harvesting system in addition to the photosynthetic system. It has been suggested that this dual system allows efficient capture of sunlight energy using complementary ranges of absorption wavelengths. However, the diversity of cyanobacterial rhodopsins, particularly in accumulated metagenomic data, remains underexplored. Here, we used a metagenomic mining approach, which led to the identification of a novel rhodopsin clade unique to cyanobacteria, cyanorhodopsin-II (CyR-II). CyR-IIs function as light-driven outward H+ pumps. CyR-IIs, together with previously identified cyanorhodopsins (CyRs) and cyanobacterial halorhodopsins (CyHRs), constitute cyanobacterial ion-pumping rhodopsins (CyipRs), a phylogenetically distinct family of rhodopsins. The CyR-II clade is further divided into two subclades, YCyR-II and GCyR-II, based on their specific absorption wavelength. YCyR-II absorbed yellow light (λmax = 570 nm), whereas GCyR-II absorbed green light (λmax = 550 nm). X-ray crystallography and mutational analysis revealed that the difference in absorption wavelengths is attributable to slight changes in the side chain structure near the retinal chromophore. The evolutionary trajectory of cyanobacterial rhodopsins suggests that the function and light-absorbing range of these rhodopsins have been adapted to a wide range of habitats with variable light and environmental conditions. Collectively, these findings shed light on the importance of rhodopsins in the evolution and environmental adaptation of cyanobacteria.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72572025A case of retrograde colonic intussusception by tubulovillous adenomaENMichikoIkiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshitakaKondoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction Retrograde colonic intussusception is a rare condition in adults, often caused by organic lesions such as tumors. Autonomic dysfunction in disorders like multiple system atrophy (MSA) might contribute to its occurrence.<br>
Case presentation An 81-year-old bedridden woman with a history of MSA presented with severe abdominal pain and abdominal distension lasting 4 days. She had chronic severe constipation managed with laxatives and manual disimpaction. CT imaging revealed retrograde intussusception of the rectum into the sigmoid colon. Endoscopic reduction was attempted but was unsuccessful due to scope impassability. Emergency laparotomy identified a 4–5 cm tumor at the lead point, and manual reduction resulted in bowel perforation. Hartmann’s procedure with D2 lymphadenectomy was performed. The tumor was histopathologically diagnosed as a tubulovillous adenoma with no malignant features. The patient’s postoperative recovery was uneventful except for a urinary tract infection (Clavien–Dindo Grade II), and she was transferred to a rehabilitation facility on postoperative day 24.<br>
Conclusion Failure of reduction by air enema should raise suspicion for retrograde intussusception, warranting prompt surgery if an organic lead point is suspected.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0915-56352025Vendor‐Agnostic Vision Transformer‐Based Artificial Intelligence for Peroral Cholangioscopy: Diagnostic Performance in Biliary Strictures Compared With Convolutional Neural Networks and EndoscopistsENRyosukeSatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalMasahiroTomiyaHealthcare Solutions Division, Ryobi Systems Co., LtdTakayoshiTanimotoHealthcare Solutions Division, Ryobi Systems Co., LtdAkimitsuOhtoHealthcare Solutions Division, Ryobi Systems Co., LtdKentaroOkiDepartment of Gastroenterology and Hepatology, Okayama University HospitalSatoshiKajitaniDepartment of Gastroenterology and Hepatology, Okayama University HospitalTatsuyaKikuchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalDaisukeUchidaDepartment of Gastroenterology and Hepatology, Okayama University HospitalKoichiroTsutsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalYoshiroKawaharaDepartment of Gastroenterology and Hepatology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalObjectives: Accurate diagnosis of biliary strictures remains challenging. This study aimed to develop an artificial intelligence (AI) system for peroral cholangioscopy (POCS) using a Vision Transformer (ViT) architecture and to evaluate its performance compared to different vendor devices, conventional convolutional neural networks (CNNs), and endoscopists.<br>
Methods: We retrospectively analyzed 125 patients with indeterminate biliary strictures who underwent POCS between 2012 and 2024. AI models including the ViT architecture and two established CNN architectures were developed using images from CHF-B260 or B290 (CHF group; Olympus Medical) and SpyScope DS or DS II (Spy group; Boston Scientific) systems via a patient-level, 3-fold cross-validation. For a direct comparison against endoscopists, a balanced 440-image test set, containing an equal number of images from each vendor, was used for a blinded evaluation.<br>
Results: The 3-fold cross-validation on the entire 2062-image dataset yielded a robust accuracy of 83.9% (95% confidence interval (CI), 80.9–86.7) for the ViT model. The model's accuracy was consistent between CHF (82.7%) and Spy (86.8%, p = 0.198) groups, and its performance was comparable to the evaluated conventional CNNs. On the 440-image test set, the ViT's accuracy of 78.4% (95% CI, 72.5–83.8) was comparable to that of expert endoscopists (82.0%, p = 0.148) and non-experts (73.0%, p = 0.066), with no statistically significant differences observed.<br>
Conclusions: The novel ViT-based AI model demonstrated high vendor-agnostic diagnostic accuracy across multiple POCS systems, achieving performance comparable to conventional CNNs and endoscopists evaluated in this study.No potential conflict of interest relevant to this article was reported.JMIR Publications Inc.Acta Medica Okayama1929-0748142025Optimization of Preemptive Therapy for Cytomegalovirus Infections With Valganciclovir Based on Therapeutic Drug Monitoring: Protocol for a Phase II, Single-Center, Single-Arm Triale72549ENNaokiTamuraDepartment of Pharmacy, Kobe University HospitalKotaroItoharaDepartment of Pharmacy, Kobe University HospitalYoUedaDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of MedicineYumiKitahiroDepartment of Pharmacy, Kobe University HospitalKazuhiroYamamotoDepartment of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroOmuraDepartment of Pharmacy, Kobe University HospitalToshiyasuSakaneDepartment of Pharmaceutical Technology, Kobe Pharmaceutical UniversityJunSaegusaDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of MedicineIkukoYanoDepartment of Pharmacy, Kobe University HospitalBackground: Valganciclovir (VGCV) is the first-line drug for preemptive therapy of cytomegalovirus (CMV) infections. However, even when administered at the dose specified in the package insert, there is significant interindividual variability in the plasma concentrations of ganciclovir (GCV). In addition, correlations have been reported between the area under the concentration–time curve and therapeutic efficacy or adverse events. Therefore, therapeutic drug monitoring (TDM) can be used to improve the efficacy and safety of preemptive VGCV therapy.<br>
Objective: This study aims to evaluate whether the dosage adjustment of VGCV based on TDM in patients undergoing preemptive therapy for CMV infections is associated with the successful completion rate of treatment without severe hematological adverse effects.<br>
Methods: This phase II, single-center, single-arm trial aims to enroll 40 patients admitted at the Department of Rheumatology and Clinical Immunology, Kobe University Hospital, who will receive oral VGCV as preemptive therapy for CMV infections. Participants will begin treatment with VGCV at the dose recommended in the package insert, with subsequent dose adjustments based on weekly TDM results. The primary end point will be the proportion of patients who achieve CMV antigenemia negativity within 3 weeks without severe hematological adverse events. The secondary end points will include weekly changes in CMV antigen levels, total VGCV dose, and duration of preemptive therapy. For safety evaluation, the occurrence, type, and severity of VGCV-related adverse events will be analyzed. Additionally, this study will explore the correlations between the efficacy and safety of preemptive therapy and the pharmacokinetic parameters of GCV, CMV-polymerase chain reaction values, and nudix hydrolase 15 (NUDT15) genetic polymorphisms. The correlation between GCV plasma concentrations obtained from regular venous blood and blood concentrations will be examined using dried blood spots.<br>
Results: This study began with patient recruitment in September 2024, with 5 participants enrolled as of June 16, 2025. The target enrollment is 40 participants, and the anticipated study completion is set for July 2027.<br>
Conclusions: This is the first study to investigate the impact of TDM intervention in patients receiving VGCV as preemptive therapy. The findings are postulated to provide valuable evidence regarding the utility of TDM in patients receiving VGCV as preemptive therapy.<br>
Trial Registration: Japan Registry of Clinical Trials jRCTs051240080; https://jrct.mhlw.go.jp/latest-detail/jRCTs051240080<br>
International Registered Report Identifier (IRRID): DERR1-10.2196/72549No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1867-10714322024Evaluation of a novel central venous access port for direct catheter insertion without a peel-away sheath282289ENToshihiroIguchiDepartment of Radiology, Okayama University HospitalTakahiroKawabataDepartment of Radiology, Okayama University HospitalYusukeMatsuiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKojiTomitaDepartment of Radiology, Okayama University HospitalMayuUkaDepartment of Radiology, Okayama University HospitalNoriyukiUmakoshiDepartment of Radiology, Okayama University HospitalSoichiroOkamotoDepartment of Radiology, Okayama University HospitalKazuakiMunetomoDepartment of Radiology, Okayama University HospitalTakaoHirakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose This study retrospectively evaluated the feasibility and safety of implanting a newly developed central venous access port (CV-port) that allows catheter insertion into a vein without the use of a peel-away sheath, with a focus on its potential to minimize risks associated with conventional implantation methods.<br>
Materials and methods All procedures were performed using a new device (P-U CelSite Port™ MS; Toray Medical, Tokyo, Japan) under ultrasound guidance. The primary endpoint was the implantation success rate. The secondary endpoints were the safety and risk factors for infection in the early postprocedural period (< 30 days).<br>
Results We assessed 523 CV-port implantations performed in a cumulative total of 523 patients (240 men and 283 women; mean age, 61.6 ± 13.1 years; range, 18–85 years). All implantations were successfully performed using an inner guide tube and over-the-wire technique through 522 internal jugular veins and one subclavian vein. The mean procedural time was 33.2 ± 10.9 min (range 15–112 min). Air embolism, rupture/perforation of the superior vena cava, or hemothorax did not occur during catheter insertion. Eleven (2.1%) intraprocedural complications occurred, including Grade I arrhythmia (n = 8) and subcutaneous bleeding (n = 1), Grade II arrhythmia (n = 1), and Grade IIIa pneumothorax (n = 1). Furthermore, 496 patients were followed up for ≥ 30 days. Six early postprocedural complications were encountered (1.1%), including Grade IIIa infection (n = 4), catheter occlusion (n = 1), and skin necrosis due to subcutaneous leakage of trabectedin (n = 1). These six CV-ports were withdrawn, and no significant risk factors for infection in the early postprocedural period were identified.<br>
Conclusion The implantation of this CV-port device demonstrated comparable success and complication rates to conventional devices, with the added potential benefit of eliminating complications associated with the use of a peel-away sheath.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2227-90591322025The Asia-Pacific Body Mass Index Classification and New-Onset Chronic Kidney Disease in Non-Diabetic Japanese Adults: A Community-Based Longitudinal Study from 1998 to 2023373ENYukariOkawaDepartment of Public Health and Welfare, Zentsuji City HallToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalToshihideTsudaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground/Objectives: Obesity is a risk factor for chronic kidney disease (CKD) in Asians. The Asia-Pacific body mass index (BMI) classification sets lower obesity cutoffs than the conventional BMI classification for all races, generally reflecting the lower BMIs in Asians. This longitudinal study evaluated the association between BMI, as classified by the Asia-Pacific BMI system, and CKD development in non-diabetic Asian adults. Methods: A population-based longitudinal study (1998–2023) was conducted in non-diabetic Japanese adults (hemoglobin A1c < 6.5%) in Zentsuji City (Kagawa Prefecture, Japan). The generalized gamma model was used to assess the relationship between time-varying BMI categories and CKD development, stratified by sex. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2. BMI was calculated as weight (kg) divided by the square of height (m2) and categorized per the Asia-Pacific classification as overweight (23.0–24.9 kg/m2), obesity class I (25.0–29.9 kg/m2), and obesity class II (≥30.0 kg/m2). Results: CKD developed in 34.2% of 3098 men and 34.8% of 4391 women. The mean follow-up times were 7.41 years for men and 8.25 years for women. During follow-up, the BMI distributions for men were 5.0% underweight, 43.3% normal weight, 25.6% overweight, 24.1% obesity class I, and 2.0% obesity class II; those for women were 7.7%, 50.5%, 20.5%, 18.3%, and 2.9%, respectively. Compared with normal weight, obesity class I was associated with a 6% (95% confidence interval [CI]: 2–10%) shorter time to CKD onset in men and 5% (95% CI: 2–7%) in women. In both sexes, obesity class II showed shorter survival times than normal weight by point estimates, although all 95% CIs crossed the null value. Conclusions: Obesity, as classified by the Asia-Pacific BMI system, shortened the time to CKD onset in non-diabetic Asians. The conventional BMI cutoff for obesity (≥30.0 kg/m2) may be too high to identify CKD risk in this population. The findings of this study may be useful for public health professionals in designing interventions to prevent CKD.No potential conflict of interest relevant to this article was reported.Japanese Physical Therapy AssociationActa Medica Okayama2189-84482732024Association Between Early Mobilization and Postoperative Pneumonia Following Robot-assisted Minimally Invasive Esophagectomy in Patients with Thoracic Esophageal Squamous Cell Carcinoma121127ENYasuakiNOZAWADivision of Physical Medicine and Rehabilitation, Okayama University HospitalKazuhiroHARADAGraduate School of Health Science Studies, Kibi International UniversityKazuhiroNOMADepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshimiKATAYAMADivision of Physical Medicine and Rehabilitation, Okayama University HospitalMasanoriHAMADADivision of Physical Medicine and Rehabilitation, Okayama University HospitalToshifumiOZAKIDivision of Physical Medicine and Rehabilitation, Okayama University HospitalObjective: The objective of this study was to confirm that early mobilization (EM) could reduce pneumonia in patients undergoing robot-assisted minimally invasive esophagectomy (RAMIE) for thoracic esophageal squamous cell carcinoma (TESCC). Methods: Postoperative pneumonia was defined as physician-diagnosed pneumonia using the Esophagectomy Complications Consensus Group definition of pneumonia with a Clavien–Dindo classification grade II–V on postoperative day (POD) 3–5. EM was defined as achieving an ICU Mobility Scale (IMS) ≥7 by POD 2. Patients were divided into EM (n = 36) and non-EM (n = 35) groups. Barriers to EM included pain, orthostatic intolerance (OI), and orthostatic hypotension. Results: The overall incidence of postoperative pneumonia was 12.7%, with a significant difference between the EM (2.8%) and non-EM (22.9%) groups (P = 0.014). The odds ratio was 0.098 in the EM group compared to the non-EM group. A significant difference was found between the two groups in terms of the barriers to EM at POD 2 only for OI, with a higher incidence in the non-EM group. Multivariate logistic regression analysis showed that patients with OI were more likely to be unable to achieve EM than those without OI (odds ratio, 7.030; P = 0.006). Conclusion: EM within POD 2 may reduce the incidence of postoperative pneumonia in patients undergoing RAMIE for TESCC. Furthermore, it was suggested that OI can have a negative impact on the EM after RAMIE.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025Bloodstream Infections Caused by Gram-Negative Bacteria in Geriatric Patients: Epidemiology, Antimicrobial Resistance and The Factors Affecting Mortality231242ENM Enes KardanDepartment of Infectious Diseases, Faculty of Medicine, Namik Kemal UniversityIlknurErdemDepartment of Infectious Diseases, Faculty of Medicine, Namik Kemal UniversityEmreYildizDepartment of Infectious Diseases, Faculty of Medicine, Namik Kemal UniversityNuriKirazDepartment of Medical Microbiology, Faculty of Medicine, Namik Kemal UniversityAliyeÇelikkolDepartment of Biochemistry, Faculty of Medicine, Namik Kemal UniversityOriginal Article10.18926/AMO/69148Bloodstream infections (BSIs) are an important cause of morbidity and mortality in geriatric patients. We retrospectively analyzed the cases of geriatric patients who developed BSIs due to gram-negative bacteria in order to evaluate the epidemiology, antimicrobial resistance, and the factors affecting mortality. The cases of 110 patients aged ≥ 65 years admitted to our hospital between January 1, 2017, and December 31, 2022 were assessed; 70 (63.6%) of the BSIs were healthcare-associated BSIs. The urinary system was the most common detectable source of infection at 43.6%. The most frequently isolated bacteria were Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, in that order. Carbapenem resistance was detected in 17 patients (15.5%), and extended-spectrum beta-lactamase (ESBL) production from Enterobacterales family members was detected in 37 (51.4%) patients. Multivariate analysis revealed that (i) the probability of mortality in the patients with total bilirubin was increased by approx. sixfold and (ii) the likelihood of mortality for those with a Pitt bacteremia score (PBS) ≥ 4 points was approx. 17 times higher. PBS and simplified qPitt scores can help predict mortality and manage geriatric patients. There is a significant increase in mortality among patients with procalcitonin (PCT) levels at ≥ 2 nm/ml.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025Organ Donation after Extracorporeal Cardiopulmonary Resuscitation: Clinical and Ethical Perspectives221229ENTetsuyaYumotoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakafumiObaraDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinoriKosakiDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoheiAgetaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTsuyoshiNojimaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoheiTsukaharaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityReview10.18926/AMO/69147Extracorporeal cardiopulmonary resuscitation (ECPR) has evolved into a life-saving therapy for select cardiac arrest patients, yet a growing body of evidence suggests it also holds promise as a bridge to organ donation in non-survivors. This review explores the clinical outcomes, ethical complexities, and evolving policies surrounding organ donation after ECPR. We summarize recent international and Japanese data demonstrating favorable graft function from ECPR donors, with the exception of lung transplantation. The ethical challenges ― particularly those involving brain death determination on extracorporeal membrane oxygenation and adherence to the dead donor rule ― are discussed in the context of Japan’s recent regulatory reforms. Additionally, we highlight the importance of structured end-of-life communication through multidisciplinary team meetings in facilitating ethically sound transitions from rescue efforts to donation pathways. Moving forward, improvements in donor management, standardized legal frameworks, and public and professional education are essential to optimizing the life-saving and life-giving potential of ECPR.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2197-11531142024Quadriceps muscle strength of the affected limb in medial meniscus posterior root tears is negatively correlated with the progression of postoperative medial joint space narrowinge70057ENKokiKawadaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMikaoFukubaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYukiOkazakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasanoriTamuraDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYusukeYokoyamaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityToshifumiOzakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakayukiFurumatsuDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityPurpose: The effect of quadriceps muscle strength on medial joint space (MJS) narrowing after repair for medial meniscus (MM) posterior root tears (MMPRTs) has not yet been determined. This study aimed to evaluate the effect of preoperative and postoperative quadriceps muscle strength on the change in MJS (ΔMJS) in MMPRTs.<br>
Methods: Thirty patients who underwent pullout repair for MMPRTs were retrospectively evaluated. The MJS width using fixed-flexion view radiographs, MM extrusion (MME) using magnetic resonance imaging, quadriceps muscle strength using the Locomo Scan-II and clinical scores were measured and compared preoperatively and 1 year postoperatively. Correlations between the ΔMJS, change in MME (ΔMME), and preoperative and postoperative quadriceps muscle strength were evaluated using Spearman's rank correlation coefficient.<br>
Results: MJS narrowing and MME progressed significantly at 1 year postoperatively (p < 0.001). Quadriceps muscle strength in MMPRT knees and all clinical scores significantly improved at 1 year postoperatively (p < 0.001). ΔMJS and ΔMME showed a significant positive correlation (0.50 ± 0.70 and 1.22 ± 0.92 mm, respectively; r = 0.516, p = 0.004). Both preoperative and postoperative quadriceps muscle strength in MMPRT knees showed significant negative correlations with ΔMJS (preoperative: r = −0.529, p = 0.003; postoperative: r = −0.477, p = 0.008) and ΔMME (preoperative: r = −0.431, p = 0.018; postoperative: r = −0.443, p = 0.014).<br>
Conclusions: In pullout repair for MMPRTs, preoperative and postoperative quadriceps muscle strength in MMPRT knees was negatively correlated with the progression of MJS narrowing and MME. Rehabilitation with a focus on quadriceps muscle strengthening, including preoperative rehabilitation, may delay knee-osteoarthritis progression after pullout repair for MMPRTs.<br>
Level of Evidence: Level IV.No potential conflict of interest relevant to this article was reported.Spandidos PublicationsActa Medica Okayama2049-94502332025Association of the expression of 5‑FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S‑1 adjuvant chemotherapy: Follow‑up results of the Setouchi Lung Cancer Group Study 120179ENJunichiSohDepartment of Thoracic Surgery, Okayama University HospitalHiromasaYamamotoDepartment of Thoracic Surgery, Okayama University HospitalNorihitoOkumuraDepartment of Thoracic Surgery, Kurashiki Central HospitalHiroyukiSuzukiDepartment of Chest Surgery, Fukushima Medical University HospitalMasaoNakataDepartment of General Thoracic Surgery, Kawasaki Medical School HospitalToshiyaFujiwaraDepartment of Thoracic Surgery, Hiroshima City Hiroshima Citizens HospitalKenicehiGembaDepartment of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720‑0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku HospitalIsaoSanoDepartment of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku HospitalTakujiFujinagaDepartment of General Thoracic Surgery, National Hospital Organization Nagara Medical CenterMasafumiKataokaDepartment of Surgery and Respiratory Center, Okayama Saiseikai General HospitalYasuhiroTerasakiDepartment of Respiratory Surgery, Saga Medical Center KoseikanNobukazuFujimotoDepartment of Medical Oncology and Respiratory Medicine, Okayama Rosai HospitalKazuhikoKataokaDepartment of Thoracic Surgery, National Hospital Organization Iwakuni Clinical CenterShinjiKosakaDepartment of Thoracic Surgery, Shimane Prefectural Central HospitalMotohiroYamashitaDepartment of Thoracic Surgery, National Hospital Organization Shikoku Cancer CenterHidetoshiInokawaDepartment of Thoracic Surgery, National Hospital Organization Yamaguchi‑Ube Medical CenterMasaakiInoueDepartment of Thoracic Surgery, Shimonoseki City HospitalHiroshigeNakamuraDivision of General Thoracic Surgery, Tottori University HospitalYoshinoriYamashitaDepartment of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer CenterYutaTakahashiDepartment of Thoracic Surgery, Okayama University HospitalHidejiroTorigoeDepartment of Thoracic Surgery, Okayama University HospitalHirokiSatoDepartment of Thoracic Surgery, Okayama University HospitalShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical University HospitalSatoshiMoritaDepartment of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of MedicineKeitaroMatsuoDivision of Cancer Epidemiology and Prevention, Aichi Cancer Center Research InstituteJunichiSakamotoTokai Central HospitalHiroshiDateDepartment of Thoracic Surgery, Kyoto University HospitalShinichiToyookaDepartment of Thoracic Surgery, Okayama University HospitalManaging elderly patients presents several challenges because of age‑related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non‑small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5‑fluorouracil (5‑FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5‑FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S‑1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5‑FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross‑complementation group 1 (ERCC1), were assessed via quantitative reverse‑transcription PCR assays in 89 elderly patients (≥75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S‑1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ≥75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence‑free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S‑1 adjuvant chemotherapy. The age‑related decrease in TS expression supports the potential benefit of 5‑FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2197-11531222025Clinical outcomes following medial meniscus posterior root repairs: A minimum of 5‐year follow‐up studye70262ENYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhisaSugiuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYusukeKamatsukiDepartment of Orthopaedic Surgery, Okayama Saiseikai General HospitalMasanoriTamuraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKokiKawadaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTsubasaHasegawaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesPurpose: This study assessed the clinical outcomes of the FasT-Fix dependent modified Mason-Allen suture (F-MMA) and two simple stitches (TSS) on mid-term postoperative outcomes following medial meniscus (MM) posterior root repair.<br>
Methods: Forty-three patients who underwent transtibial pullout repair for MM posterior root tear (PRT) between November 2016 and September 2018 were initially enrolled. Patients with a femorotibial angle ≤ 180°, Kellgren–Lawrence grade of 0–2, and modified Outerbridge grade I or II cartilage lesions were included. The Lysholm, Tegner activity, International Knee Documentation Committee score, pain visual analogue scale and Knee injury and Osteoarthritis Outcome scores were assessed as clinical outcomes. Conversion surgery to knee arthroplasty was considered as the endpoint. Surgeries other than second-look arthroscopy and plate or screw removal were also recorded.<br>
Results: The mean follow-up period was 5.9 years. All evaluated 5-year postoperative clinical outcomes were significantly improved compared to the preoperative outcomes (p < 0.001). Both the F-MMA and TSS significantly improved all clinical scores at 5 years postoperatively in patients with MMPRT, whereas the F-MMA and TSS groups showed no significant differences in the pre- and postoperative clinical scores. None of the patients required ipsilateral knee arthroplasty during the follow-up, and the survival rate after pullout repair was 100%. However, the progression of osteoarthritis could not be completely suppressed, although there were no Kellgren–Lawrence grade 4 cases. The rate of subsequent knee-related surgical treatment was 11.6% in pullout-repaired knees, including arthroscopic debridement for arthrofibrosis with a limited range of motion, an additional all-inside suture repair and partial meniscectomy.<br>
Conclusion: Both F-MMA and TSS pullout repairs yielded satisfactory clinical outcomes in patients with MMPRT with a mean follow-up of 5.9 years, and no conversion to knee arthroplasty was required. Further follow-up is warranted to assess long-term survival rates.<br>
Level of Evidence: Level III.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Autoantibody spark response predicts treatment outcome in patients receiving chemoradiation followed by durvalumab therapy27502ENTakeruMoriGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMioKitagawaDepartment of Radiology, Sapporo Medical University School of MedicineTomokazuHasegawaDepartment of Radiology, Sapporo Medical University School of MedicineMasanoriSomeyaDepartment of Radiology, Sapporo Medical University School of MedicineTakaakiTsuchiyaDepartment of Radiology, Sapporo Medical University School of MedicineToshioGochoDepartment of Radiology, Sapporo Medical University School of MedicineTomokoHonjoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMireiDateGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMarikoMoriiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAiMiyamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJunichiroFutamiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThe PACIFIC regimen, comprising chemoradiotherapy (CRT) followed by maintenance with the immune checkpoint inhibitor (ICI) durvalumab, has become the standard of care for patients with unresectable non-small cell lung cancer (NSCLC). Although ICI is used to prevent recurrence by targeting residual microtumors, biomarkers capable of monitoring immune activity during this phase remain lacking. Here, we evaluated whether temporal changes in serum autoantibody levels can predict treatment efficacy. This retrospective study included 20 patients with unresectable stage II or III NSCLC who received the PACIFIC regimen. Serum autoantibodies against 130 antigens were quantified before CRT, after CRT, and two weeks after the first ICI dose. The primary outcome was progression-free survival (PFS), and its association with autoantibody dynamics was examined. We observed an immediate and strong autoantibody response (spark response [SR]) after ICI initiation in patients with favorable treatment outcomes. Patients with SR and programmed death ligand 1 (PD-L1) expression ≥ 50% showed better PFS (two-year PFS; 72.9% vs. 18.2%, p = 0.0021). These findings suggest that serial monitoring of serum autoantibodies can provide a noninvasive approach to assess immune activity and predict treatment outcomes in patients receiving CRT or ICI therapy.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0006-291X77920251,2-naphthoquinone enhances IFN-γ-induced MHC-I expression in dendritic cells, thereby inducing CD8 T cell activation152453ENKazuyukiFurutaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKanonMiyazatoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKaiKobataGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKazuyaIshikawaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityChikaraKaitoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityDendritic cells play a crucial role in immune responses by capturing pathogens and presenting antigens to T cells via major histocompatibility complex (MHC) molecules, thus triggering adaptive immune responses. 1,2-naphthoquinone (1,2-NQ), a quinone found in diesel exhaust and cigarette smoke, has various physiological functions. In this study, we investigated the effect of 1,2-NQ on the expression of antigen presentation-related molecules in the dendritic cell line DC2.4. The results revealed that 1,2-NQ enhanced the IFN-γ-induced upregulation of MHC-I expression at the transcriptional level. Moreover, it upregulated the expression of NLRC5, a transcriptional activator of MHC-I. 1,2-NQ is a reactive oxygen species (ROS) producing reagent. The 1,2-NQ-induced upregulation of MHC-I expression and downregulation of MHC-II expression were abolished by the ROS scavenger N-acetylcysteine. Similar effects on MHC expression were also observed with ROS-inducing reagents, such as paraquat and diethyl maleate. In addition, dendritic cells stimulated with 1,2-NQ exhibited enhanced efficacy in CD8 T cell activation, which was accompanied by increased IFN-γ production by T cells. These findings demonstrate that 1,2-NQ enhances the IFN-γ-induced activation of dendritic cells and promotes the activation of CD8 T cells.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2772-963X422025Simplified Outcome Prediction in Patients Undergoing Transcatheter Tricuspid Valve Intervention by Survival Tree-Based Modelling101575ENVeraFortmeierDepartment of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University BochumMarkLachmannFirst Department of Medicine, Klinikum rechts der Isar, Technical University of MunichLukasStolzDZHK (German Center for Cardiovascular Research), Partner Site Munich Heart AllianceJennifervon SteinDepartment of Cardiology, Heart Center, University of CologneKarl-PhilippRommelDepartment of Cardiology, Heart Center Leipzig, University of LeipzigMohammadKassarDepartment of Cardiology, Inselspital Bern, Bern University HospitalMuhammedGerçekDepartment of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University BochumAnne R.SchöberDepartment of Cardiology, Heart Center Leipzig, University of LeipzigThomas J.StockerDZHK (German Center for Cardiovascular Research), Partner Site Munich Heart AllianceHazemOmranDepartment of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University BochumMichelleFettDepartment of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University BochumJuleTervoorenDepartment of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University BochumMaria I.KörberDepartment of Cardiology, Heart Center, University of CologneAmelieHesseFirst Department of Medicine, Klinikum rechts der Isar, Technical University of MunichGerhardHarmsenDepartment of Physics, University of JohannesburgKai PeterFriedrichsDepartment of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University BochumShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama UniversityTanja K.RudolphDepartment of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University BochumMichaelJonerDZHK (German Center for Cardiovascular Research), Partner Site Munich Heart AllianceRomanPfisterDepartment of Cardiology, Heart Center, University of CologneStephanBaldusDepartment of Cardiology, Heart Center, University of CologneKarl-LudwigLaugwitzFirst Department of Medicine, Klinikum rechts der Isar, Technical University of MunichStephanWindeckerDepartment of Cardiology, Inselspital Bern, Bern University HospitalFabienPrazDepartment of Cardiology, Inselspital Bern, Bern University HospitalPhilippLurzDepartment of Cardiology, Heart Center Leipzig, University of LeipzigJörgHausleiterDZHK (German Center for Cardiovascular Research), Partner Site Munich Heart AllianceVolkerRudolphDepartment of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University BochumBackground Patients with severe tricuspid regurgitation (TR) typically present with heterogeneity in the extent of cardiac dysfunction and extra-cardiac comorbidities, which play a decisive role for survival after transcatheter tricuspid valve intervention (TTVI).<br>
Objectives This aim of this study was to create a survival tree-based model to determine the cardiac and extra-cardiac features associated with 2-year survival after TTVI.<br>
Methods The study included 918 patients (derivation set, n = 631; validation set, n = 287) undergoing TTVI for severe TR. Supervised machine learning-derived survival tree-based modelling was applied to preprocedural clinical, laboratory, echocardiographic, and hemodynamic data.<br>
Results Following univariate regression analysis to pre-select candidate variables for 2-year mortality prediction, a survival tree-based model was constructed using 4 key parameters. Three distinct cluster-related risk categories were identified, which differed significantly in survival after TTVI. Patients from the low-risk category (n = 261) were defined by mean pulmonary artery pressure ≤28 mm Hg and N-terminal pro–B-type natriuretic peptide ≤2,728 pg/mL, and they exhibited a 2-year survival rate of 85.5%. Patients from the high-risk category (n = 190) were defined by mean pulmonary artery pressure >28 mm Hg, right atrial area >32.5 cm2, and estimated glomerular filtration rate ≤51 mL/min, and they showed a significantly worse 2-year survival of only 52.6% (HR for 2-year mortality: 4.3, P < 0.001). Net re-classification improvement analysis demonstrated that this model was comparable to the TRI-Score and outperformed the EuroScore II in identifying high-risk patients. The prognostic value of risk phenotypes was confirmed by external validation.<br>
Conclusions This simple survival tree-based model effectively stratifies patients with severe TR into distinct risk categories, demonstrating significant differences in 2-year survival after TTVI.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama2041-652016262025Collective motions in the primary coordination sphere: a critical functional framework for catalytic activity of the oxygen-evolving complex of photosystem II12024ENHiroshiIsobeTakayoshiSuzukiResearch Institute for Interdisciplinary Science, Okayama UniversityMichihiroSugaResearch Institute for Interdisciplinary Science, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science, Okayama UniversityKizashiYamaguchiCenter for Quantum Information and Quantum Biology, Osaka UniversityPhotosynthetic water oxidation, vital for dioxygen production and light energy conversion, is catalyzed by the oxygen-evolving complex of photosystem II, where the inorganic Mn4CaO5 cluster acts as the catalytic core. In this study, we investigate the functional significance of collective motions of amino acid side chains within the primary coordination sphere of the Mn cluster, focusing on their role in modulating the energetic demands for catalytic transformations in the S3 state. We applied regularized canonical correlation analysis to quantitatively correlate the three-dimensional arrangement of coordinating atoms with catalytic driving forces computed via density functional theory. Our analysis reveals that distinct collective side chain motions profoundly influence the energetic requirements for structural reconfigurations of the Mn cluster, achieved through expansion and contraction of the ligand cavity while fine-tuning its geometry to stabilize key intermediates. Complementary predictions from a neural network-based machine learning model indicate that the coordination sphere exerts a variable energetic impact on the catalytic transformations of the Mn cluster, depending on the S-state environment. Integrated computational analyses suggest that the extended lifetime of the S3YZ˙ state, consistently observed after three flash illuminations, may result from slow, progressive protein dynamics that continuously reshape the energy landscape, thereby shifting the equilibrium positions of rapid, reversible chemical processes over time. Overall, our findings demonstrate that collective motions in the primary coordination sphere constitute an active, dynamic framework essential for the efficient execution of multi-electron catalysis under ambient conditions, while simultaneously achieving a high selectivity with irreversible nature required for effective 3O2 evolution.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0039-91402972026Microfluidic paper-based analytical devices for antioxidant vitamins C and E in foods128540ENManaKawaharaDepartment of Chemistry, Okayama UniversityKaewtaDanchanaDepartment of Chemistry, Okayama UniversityTakashiKanetaDepartment of Chemistry, Okayama UniversityIn this study, we developed microfluidic paper-based analytical devices (μPADs) for the determination of antioxidant vitamins. The proposed μPADs utilize the reduction of metal ions by hydrophilic and hydrophobic antioxidant vitamins, which is followed by colorimetric reactions with chelating reagents. Hydrophilic vitamin C reduces Fe(III) to Fe(II) and forms a stable Fe(II)-bathophenanthroline complex in an aqueous solution. By contrast, this complex is unstable in organic solvents, and hydrophobic vitamin E requires Fe(III) and bathophenanthroline to be replaced with Cu(II) and bathocuproine. In these results, the relationship between the logarithm of a vitamin's concentration and its color intensity was linear and ranged from 4.4 to 35 mg L−1 for ascorbic acid and 50–200 mg L−1 for α-tocopherol. The limits of detection, estimated from the standard deviation of blank samples, were 3.1 mg L−1 for ascorbic acid and either 27 mg L−1 (in hexane) or 48 mg L−1 (in ethanol) for α-tocopherol. The proposed method was used to quantify vitamin C in bell peppers, mandarin oranges, kiwifruit, and lemons, as well as vitamin E in almonds, almond milk, and dietary supplements. The results demonstrate the effectiveness of these μPADs for the practical analysis of antioxidant vitamins in food samples.No potential conflict of interest relevant to this article was reported.Japanese Circulation SocietyActa Medica Okayama1346-98438972025Hemodynamic Changes After Wire Frame Occluders vs. Metal Mesh Devices for Atrial Septal Defect930938ENMitsutakaNakashimaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTeijiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Transcatheter atrial septal defect (ASD) closure is the first treatment option for secundum ASD, but parameters for optimal device selection have not been established. We compared outcomes between occluders with a wire frame and metal mesh devices.<br>
Methods and Results: This study included secundum ASD patients implanted with a wire frame occluder (GORE®CARDIOFORM ASD occluder [GCA]; W.L. Gore & Associates) or metal mesh devices (Amplatzer septal occluder device [Abbott] and Occlutech Figulla Flex II device [Occlutech]). The presence of residual shunt and B-type natriuretic peptide (BNP) levels after implantation were compared. Of the 970 patients with either GCA (n=48) or a metal mesh device (n=922; control), 42 patients from each group were analyzed after propensity score matching. The prevalence of residual shunt was significantly lower in the GCA group 1 day and 1 month after implantation (P<0.001 and P=0.017, respectively), whereas there was no significant difference between the 2 groups 6 months later (P=0.088). BNP levels at 1 month were significantly higher in the GCA group (ratio of change 1.36; 95% confidence interval [CI] 1.01–1.83), but did not differ significantly between the 2 groups at 6 months (ratio of change 1.04; 95% CI 0.65–1.65).<br>
Conclusions: Patients implanted with a wire frame occluder had a lower prevalence of residual shunt and a greater increase in BNP levels in the early period after implantation.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2041-17231612025Structure of a photosystem II-FCPII supercomplex from a haptophyte reveals a distinct antenna organization4175ENRomainLa RoccaResearch Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKojiKatoResearch Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPi-ChengTsaiResearch Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshikiNakajimaResearch Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityFusamichiAkitaResearch Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHaptophytes are unicellular algae that produce 30 to 50% of biomass in oceans. Among haptophytes, a subset named coccolithophores is characterized by calcified scales. Despite the importance of coccolithophores in global carbon fixation and CaCO3 production, their energy conversion system is still poorly known. Here we report a cryo-electron microscopic structure of photosystem II (PSII)-fucoxanthin chlorophyll c-binding protein (FCPII) supercomplex from Chyrostila roscoffensis, a representative of coccolithophores. This complex has two sets of six dimeric and monomeric FCPIIs, with distinct orientations. Interfaces of both FCPII/FCPII and FCPII/core differ from previously reported. We also determine the sequence of Psb36, a subunit previously found in diatoms and red algae. The principal excitation energy transfer (EET) pathways involve mainly 5 FCPIIs, where one FCPII monomer mediates EET to CP47. Our findings provide a solid structural basis for EET and energy dissipation pathways occurring in coccolithophores.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7932025Emotional Changes among Young Patients with Breast Cancer to Foster Relationship-Building with Their Partners: A Qualitative Study185195ENAyumiYoshikawaFaculty of Nursing, Osaka Dental UniversityNarutoTairaKawasaki Medical School, Department of Breast and Thyroid SurgeryMayumiOkanagaGifu College of Nursing, Nursing of Children and Child-Rearing FamiliesShinyaSaitoGraduate School of Health Sciences, Okayama UniversityOriginal Article10.18926/AMO/68726We investigated the emotional changes that young patients with breast cancer need to undergo in order to foster relationship-building with their partners by conducting a qualitative descriptive study (March 1 to Nov. 26, 2021) and semi-structured interviews with eight postoperative patients (age 20-40 years) with breast cancer. The data were analyzed using the modified grounded theory approach (M-GTA), yielding five categories: (i) Awareness of being a breast cancer patient, (ii) Being at a loss, (iii) Support from significant others, (iv) The struggle to transition from being a patient with cancer to becoming “the person I want to be”, and (v) Reaching the “me” I want to be who can face building a relationship with a partner. These findings suggest that young breast cancer patients must feel that they can lead a normal life through activities such as work or acquiring qualifications before building relationships with their partners, and that getting closer to their desired selves is important. Nurses can provide information to young patients with breast cancer to assist them in building a solid relationship with their partners. We believe that this support may enhance the patients’ quality of life and help them achieve stronger relationships with their partners.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7932025Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells157166ENOmer FarukHatipogluDepartment of Pharmacology, Faculty of Medicine, Kindai UniversityTakashiNishinakaDepartment of Pharmacology, Faculty of Medicine, Kindai UniversityKursat OguzYaykasliDepartment of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenShujiMoriDepartment of Pharmacology, School of Pharmacy, Shujitsu UniversityMasahiroWatanabeDepartment of Pharmacology, School of Pharmacy, Shujitsu UniversityTakaoToyomuraDepartment of Pharmacology, School of Pharmacy, Shujitsu UniversityMasahiroNishiboriDepartment of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiHirohataDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityHideoTakahashiDepartment of Pharmacology, Faculty of Medicine, Kindai UniversityHidenoriWakeDepartment of Pharmacology, Faculty of Medicine, Kindai UniversityOriginal Article10.18926/AMO/68723Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 μg/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama1435-02117112025Quantitative assessment of adhesive effects on partial and full compressive strength of LVL in the edge-wise direction19ENRyutaroSudoOkayama University, Graduate School of Environmental, Life, Natural Science and TechnologyKohtaMiyamotoForestry and Forest Products Research InstituteHirofumiIdoForestry and Forest Products Research InstituteLaminated wood-based materials have been widely developed, and the laminating process and adhesive itself have been reported to enhance performance beyond the sum of the individual layers' performance. This phenomenon is particularly notable under loads applied in the "edge-wise direction", where each layer bears stress collectively. These combined effects are referred to as the "adhesive effect". Strength under partial compressive loads is critical in timber engineering, as partial compressive stress generates complex stress distributions influenced by boundary conditions. The adhesive effect may also be impacted by these conditions. The aim of this study was to quantitatively and directly evaluate the adhesive effect under partial and full compressive loads using various parameters. The strength of laminated veneer lumber (LVL) with adhesive was compared to that of simply layered veneers without adhesive to assess the adhesive effect. Three mechanisms contributing to the adhesive effect were proposed: Mechanism I, caused by the deformation of the adhesive layer independently from the veneers; Mechanism II, resulting from the adhesive impregnating the veneers; and Mechanism III, arising from the reinforcement provided by adjacent veneers. The results suggested the following: (i) Mechanism I had minimal impact, as the fiber direction and the presence of additional length showed strong and slight effects on the adhesive effect, respectively; (ii) Mechanism II contributed to preventing crack propagation and altering the relationships among mechanical properties, with its effectiveness increasing as the adhesive weight increased; and (iii) Mechanism III functioned as a crossband effect, reinforcing weaknesses caused by the slope of the grain and the angle of the annual rings.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7922025Safe Resection of Esophageal Cancer with a Non-Recurrent Inferior Laryngeal Nerve Associated with an Aberrant Right Subclavian Artery Using Intraoperative Nerve Monitoring139144ENYasushigeTakedaDepartment of Gastroenterological Surgery, Okayama University HospitalKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University HospitalNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University HospitalYoheiMizusawaDepartment of Gastroenterological Surgery, Okayama University HospitalHijiriMatsumotoDepartment of Gastroenterological Surgery, Okayama University HospitalYuheiKondoDepartment of Gastroenterological Surgery, Okayama University HospitalTomoyoshiKunitomoDepartment of Gastroenterological Surgery, Okayama University HospitalYukinoriTanoueDepartment of Gastroenterological Surgery, Okayama University HospitalMasashiHashimotoDepartment of Gastroenterological Surgery, Okayama University HospitalShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University HospitalCase Report10.18926/AMO/68654In thoracic esophageal cancer, lymph node dissection around the recurrent laryngeal nerve is crucial but poses a risk of nerve palsy, affecting postoperative quality of life. In cases with an aberrant right subclavian artery (ARSA), the right recurrent laryngeal nerve is absent, and the non-recurrent inferior laryngeal nerve (NRILN) enters the larynx directly from the vagus nerve in the cervical region. Identifying the course of the NRILN is vital to avoid injury. A case of esophageal cancer with an ARSA, in which the course of the NRILN was preserved using the Nerve Integrity Monitoring (NIM) system during surgery, is described.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7922025Effectiveness of Postoperative Irradiation in Patients with cN0 Early Breast Cancer Treated with Sentinel Lymph Node Surgery101107ENHiroshiIsozakiDepartment of Surgery, Oomoto HospitalSasauMatsumotoDepartment of Surgery, Oomoto HospitalTakehiroTakamaDepartment of Surgery, Oomoto HospitalYukaIsozakiDepartment of Surgery, Oomoto HospitalOriginal Article10.18926/AMO/68648To evaluate the effectiveness of postoperative irradiation (POI) for patients with cN0 early breast cancer, we retrospectively analyzed the cases of 650 consecutive breast cancer patients who underwent sentinel lymph node (SLN)-guided surgery (2005-2022) at our hospital. In this cohort, 53% (278/521) of the patients who underwent breast conservative surgery (BCS) and 96% (124/129) of those treated with mastectomy did not receive POI. The patients who underwent BCS were treated with POI using opposing tangential field irradiation. A false negative (FN) SLN was retrospectively defined as a negative metastasis in SLN plus positive recurrence in the axillary lymph nodes. Recurrence was detected in 83 patients. A logistic regression analysis revealed that the nuclear grade (odds ratio [OR] 1.69), POI (OR 0.41), and postoperative hormone therapy (OR 0.40) were each significantly related to recurrence. The 26.1% (12/46) FN rate of the non-POI patients decreased to 5.8% (1/17) compared to those treated with POI. The rate of axillary recurrence was significantly lower in the POI group (0.4%) versus the non-POI group (2.7%) (p=0.0355). The rate of locoregional recurrence was also significantly lower in the POI group (2.0%) versus the non-POI group (13.4%) (p<0.0001). No significant difference was observed in the rate of distant recurrence between the POI (4.0%) and non-POI (3.3%) (p=0.831) groups. These results indicated that the postoperative opposing tangential field irradiation of conserved breast tissue inhibited recurrence in the axillary lymph nodes.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7922025Lower Work Engagement Is Associated with Insomnia, Psychological Distress, and Neck Pain among Junior and Senior High School Teachers in Japan93100ENRinaTsuchieDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMariFukudaDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidekiTsumuraDepartment of Psychology, Graduate School of Technology, Industrial and Social Sciences, Tokushima UniversityMinakoKinutaDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiHisamatsuDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideyukiKandaDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/68647School teachers are subject to both physical and mental health problems. We examined cross-sectional relationships between work engagement and major health outcomes among junior and senior high school teachers in Japan via a nationwide survey in 2019-2020. A total of 3,160 respondents were included in the analyses (19.9% response rate). Work engagement was assessed with the Utrecht Work Engagement Scale-9 (UWES-9), and we thus divided the teachers into quartiles according to their UWES-9 scores. Based on validated questionnaires, we assessed insomnia, psychological distress, and neck pain as health outcomes. A binomial logistic regression adjusted for age, gender, school type, teacher’s roles, involvement in club activities, division of duties, employment status, and whether they lived with family demonstrated that the teachers with lower UWES-9 scores had higher burdens of insomnia, psychological distress, and neck pain (odds ratios [95% confidence intervals] in 4th vs. 1st quartile, 2.92 (2.34-3.65), 3.70 (2.81-4.88), and 2.12 (1.68-2.68), respectively; all trend p<0.001). There were no significant differences in these associations between full-time and part-time teachers. Our findings indicate that low work engagement may contribute to physical and mental health issues among junior and senior high school teachers, thus providing insights for preventing health problems in this profession.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7922025Clinical Outcomes of Neoadjuvant Paclitaxel/Cisplatin/Gemcitabine Compared with Gemcitabine/Cisplatin for Muscle-Invasive Bladder Cancer8192ENTatsushiKawadaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuyukiKobayashiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakujiTsugawaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazumaTsuboiDepartment of Urology, Hiroshima City Hiroshima Citizens HospitalSatoshiKatayamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakehiroIwataDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKensukeBekkuDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoKobayashiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiEdamuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinEbaraDepartment of Urology, Hiroshima City Hiroshima Citizens HospitalMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/68646We retrospectively evaluated the oncologic outcomes of paclitaxel, cisplatin, and gemcitabine (PCG) with those of gemcitabine and cisplatin (GC) as neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients. The primary outcome was efficacy: pathological complete response (pCR), ypT0N0; and pathological objective response (pOR), ypT0N0, ≤ ypT1N0, or ypT0N1. Secondary outcomes included overall survival (OS), recurrence-free survival (RFS), predictive factors for pOR, OS, and RFS, and hematologic adverse events (AEs). Among 113 patients treated (PCG, n=28; GC, n=85), similar pOR and pCR rates were achieved by the groups (pOR: PCG, 57.1% vs. GC, 49. 4%; p=0.52; pCR: PCG, 39.3% vs. GC, 29.4%; p=0.36). No significant differences were observed in OS (p=1.0) or RFS (p=0.20). Multivariate logistic regression analysis showed that hydronephrosis (odds ratio [OR] 0.32, 95%CI: 0.11-0.92) and clinical node-positive status (cN+) (OR 0.22, 95%CI: 0.050-0.99) were significantly associated with a decreased probability of pOR. On multivariate Cox regression analyses, pOR achievement was associated with improved OS (hazard ratio [HR] 0.23, 95%CI: 0.10-0.56) and RFS (HR 0.30, 95%CI: 0.13-0.67). There were no significant between-group differences in the incidence of grade ≥ 3 hematologic AEs or dose-reduction required, but the PCG group had a higher incidence of grade 4 neutropenia.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7922025Potential for Radiation Dose Reduction in Temporal Bone CT Imaging Using Photon-Counting Detector CT7580ENFumiyoHigakiDepartment of Radiology, Okayama University HospitalYusukeMorimitsuDepartment of Radiological Technology, Okayama University HospitalToshihiroIguchiDepartment of Radiological Technology, Faculty of Health Sciences, Okayama UniversitySung IlHwangDepartment of Radiology, Seoul National University Bundang HospitalTakahiroKitayamaDepartment of Radiology, Okayama University HospitalYukaTakahashiDepartment of Radiology, Okayama University HospitalMayuUkaDepartment of Radiology, Okayama University HospitalNoriakiAkagiDepartment of Radiological Technology, Okayama University HospitalAkikoSugayaDepartment of Otolaryngology-Head and Neck Surgery, Okayama University HospitalToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalYusukeMatsuiDepartment of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakaoHirakiDepartment of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/68645Temporal bone computed tomography (CT) is frequently performed for pediatric patients with ear diseases. Advances in CT technology have improved diagnostic imaging quality, but reduction of radiation exposure remains a goal. We evaluated the potential for radiation dose reduction in temporal bone CT examinations using porcine ear ossicles and a photon-counting detector CT system. Three scans of the bilateral temporal bone were performed on each of three pig cadaver heads. In each of seven successive imaging sessions, the radiation dose was reduced by an additional one-seventh of the recommended dose (RD). Two board-certified radiologists independently scored the resulting images on a scale of 1 to 5 points, where 5 represented the image quality at the RD. Images scoring ≥4.5 points were considered acceptable. Noise was assessed in a 2-cm-diameter region near the ear ossicles, and standard deviation was measured for each of the seven decrements from the RD. As the radiation dose decreased, the noise progressively increased, and visual assessment scores progressively decreased. Acceptable image scores were obtained at six-sevenths (4.9), five-sevenths (4.8), four-sevenths (4.7), and three-sevenths (4.6) of the RD. Thus, acceptable porcine temporal bone CT images were obtained with a radiation dose reduction of approximately 50%.No potential conflict of interest relevant to this article was reported.Department of Mathematics, Faculty of Science, Okayama UniversityActa Medica Okayama0030-15666712025Tsetlin library on p-colored permutations and q-analogue133147ENYutoNakagawaMathematical Institute, Tohoku UniversityFumihikoNakanoMathematical Institute, Tohoku UniversityK. Brown [1] studied the random to top shuffle (the Tsetlin libary) by semigroup method. In this paper, (i) we extend his results to the colored permutation groups, and (ii) we consider a q-analogue of Tsetlin library which is different from what is studied in [1]. In (i), the results also extends those results for the top to random shuffle [4],[5], [6] to arbitrary distribution of choosing cards, but we still have derangement numbers in the multiplicity of each eigenvalues. In (ii), a version of q-analogue of derangement numbers by Chen-Rota [3] appears in the multiplicity of eigenvalues.No potential conflict of interest relevant to this article was reported.岡山大学教育学部Acta Medica Okayama0471-4008841990キャンベラにおける開発の諸段階（U）165177ENMASAONOBE10.18926/bgeou/68589No potential conflict of interest relevant to this article was reported.岡山大学教育学部Acta Medica Okayama0471-4008901992「混住化農村調査」第１次報告書（U）915ENMASAONOBE10.18926/bgeou/68585No potential conflict of interest relevant to this article was reported.岡山大学教育学部Acta Medica Okayama0471-4008931993キャンベラの概説(2)219236ENMASAONOBE10.18926/bgeou/68582No potential conflict of interest relevant to this article was reported.岡山大学教育推進機構Acta Medica Okayama1881-595222025日本への留学を促進する要因に関する研究 −東南アジアからの留学生を事例として−1332ENTakaoINAMORIInstitute of Global Human Resource Development, Okayama University10.18926/68451 本研究では、東南アジアから留学している留学生15人を対象として「なぜ日本に留学したのか？」、半構造化インタビューにより情報を収集した。その結果、(i) 留学生の日本に対するイメージ、(ii) 保護者の日本に対するイメージ、(iii) 奨学金の機会、(iv) 私費留学が可能な学費・生活費レベル、(v) 出身国コミュニティーの有無、が重要であることが分かった。これらの情報やイメージの一部は、(1) 留学先での満足度、(2) 日本人との交流機会、(3) 生活のしやすさ、(4) 留学生の日本語レベル、(5) 日本文化に対する理解等によって形成され、ロコミやインターネットを通じて強化されることが推測された。よって、上記の項目に着目し、留学生の満足度等を向上させるための環境づくりを支援していくことが、日本留学に対するプラスのイメージを作り、東南アジアからの留学生増につながっていくと考えられた。No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-17291522025Distinct Infection Mechanisms of Rhizoctonia solani AG-1 IA and AG-4 HG-I+II in Brachypodium distachyon and Barley235ENNiranjanMahadevanGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRoziFernandaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYusukeKouzaiCrop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO)NatsukaKohnoFaculty of Agriculture, Okayama UniversityReikoNagaoFaculty of Agriculture, Okayama UniversityKhin ThidaNyeinGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMegumiWatanabeGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNanamiSakataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidenoriMatsuiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKazuhiroToyodaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukiIchinoseGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKeiichiMochidaRIKEN Center for Sustainable Resource ScienceHiroshiHisanoInstitute of Plant Science and Resources, Okayama UniversityYoshiteruNoutoshiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRhizoctonia solani is a basidiomycete phytopathogenic fungus that causes rapid necrosis in a wide range of crop species, leading to substantial agricultural losses worldwide. The species complex is divided into 13 anastomosis groups (AGs) based on hyphal fusion compatibility and further subdivided by culture morphology. While R. solani classifications were shown to be independent of host specificity, it remains unclear whether different R. solani isolates share similar virulence mechanisms. Here, we investigated the infectivity of Japanese R. solani isolates on Brachypodium distachyon and barley. Two isolates, AG-1 IA (from rice) and AG-4 HG-I+II (from cauliflower), infected leaves of both plants, but only AG-4 HG-I+II infected roots. B. distachyon accessions Bd3-1 and Gaz-4 and barley cultivar 'Morex' exhibited enhanced resistance to both isolates compared to B. distachyon Bd21 and barley cultivars 'Haruna Nijo' and 'Golden Promise'. During AG-1 IA infection, but not AG-4 HG-I+II infection, resistant Bd3-1 and Morex induced genes for salicylic acid (SA) and N-hydroxypipecolic acid (NHP) biosynthesis. Pretreatment with SA or NHP conferred resistance to AG-1 IA, but not AG-4 HG-I+II, in susceptible B. distachyon Bd21 and barley Haruna Nijo. On the leaves of susceptible Bd21 and Haruna Nijo, AG-1 IA developed extensive mycelial networks with numerous infection cushions, which are specialized infection structures well-characterized in rice sheath blight. In contrast, AG-4 HG-I+II formed dispersed mycelial masses associated with underlying necrosis. We propose that the R. solani species complex encompasses at least two distinct infection strategies: AG-1 IA exhibits a hemibiotrophic lifestyle, while AG-4 HG-I+II follows a predominantly necrotrophic strategy.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7912025Retrospective Analysis of the Safety of High-Volume Dental Articaine Preparations for Japanese Patients3137ENShigeruMaedaDepartment of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoAtiphanPimkhaokhamDepartment of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn UniversityMichihiroYoshidaData Science Division, Center for Innovative Clinical Medicine, Okayama University HospitalHirokiHosoiData Science Division, Center for Innovative Clinical Medicine, Okayama University HospitalAyakoOhshimaData Science Division, Center for Innovative Clinical Medicine, Okayama University HospitalRyokoKurisuDepartment of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoNozomiUtsumiDepartment of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoHitoshiHiguchiDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University HospitalTakuyaMiyawakiDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/68356We retrospectively analyzed the safety of the use of articaine, an amide-type local anesthetic, in Japanese dental patients (n=300) treated in Thailand in 2015-2017. The dosage, adverse events (AEs) caused by local anesthesia, and treatment efficacy were examined. Articaine, which is safe for patients with liver impairments due to its unique metabolism, has not been thoroughly tested in Japan for doses above 5.1 mL. Eighty of the present patients had undergone root canal treatment (RCT), 71 underwent tooth extraction, and 149 underwent implant-related surgery. More than three articaine cartridges were used in 41 patients, and no AEs occurred in these cases. The only AE occurred in a 52-year-old woman who was treated with three cartridges and presented with what appeared to be hyperventilation syndrome; she later recovered and received her dental treatment as scheduled. Most treatments were completed with three or fewer cartridges, suggesting that this number is generally sufficient. Our findings, particularly the low AE risk even with doses exceeding three cartridges, support the potential applicability of the overseas recommended maximum dose of articaine (7 mg/kg) in Japanese patients. This conclusion is significant for advancing dental anesthetic practices and ensuring patient safety and treatment efficacy in Japan.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7912025Endothelial Cell Polarity in Health and Disease17ENMoeThihaDepartment of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoHikitaDepartment of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasanoriNakayamaDepartment of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesReview10.18926/AMO/68353Endothelial cell polarity is fundamental to the organization and function of blood vessels, influencing processes such as angiogenesis, vascular stability, and response to shear stress. This review elaborates on the molecular mechanisms that regulate endothelial cell polarity, focusing on key players like the PAR polarity complex and Rho family GTPases. These pathways coordinate the front–rear, apical–basal and planar polarity of endothelial cells, which are essential for the proper formation and maintenance of vascular structures. In health, endothelial polarity ensures not only the orderly development of blood vessels, with tip cells adopting distinct polarities during angiogenesis, but also ensures proper vascular integrity and function. In disease states, however, disruptions in polarity contribute to pathologies such as coronary artery disease, where altered planar polarity exacerbates atherosclerosis, and cancer, where disrupted polarity in tumor vasculature leads to abnormal vessel growth and function. Understanding cell polarity and its disruption is fundamental not only to comprehending how cells interact with their microenvironment and organize themselves into complex, organ-specific tissues but also to developing novel, targeted, and therapeutic strategies for a range of diseases, from cardiovascular disorders to malignancies, ultimately improving patient outcomes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0167-594X17222025Identification of factors related to functional prognoses in craniopharyngiomas471479ENTsuyoshiUmedaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroFujiiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJojiIshidaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuichiroHiranoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasukiSurugaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoyaKemmotsuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyojiImotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhitoKegoyaRyoMizutaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoheiInoueDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMadokaHokamaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroMakiharaDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalKenichiInagakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoYasuharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose Craniopharyngiomas are histologically benign tumors, but their proximity to vital neurovascular structures can significantly deteriorate functional prognoses and severely restrict patients’ social interaction and activity. We retrospectively identified risk factors related to the functional prognoses in patients with craniopharyngioma treated at our center.<br>
Methods A retrospective analysis was conducted on 40 patients who underwent surgery for craniopharyngioma and follow-up at our institution between 2003 and 2022. Functional prognoses were evaluated in terms of obesity (body mass index [BMI] ≥ 25 for adults, BMI-Z ≥ 1.65 for children), visual function, endocrine function, and social participation. We investigated whether patient characteristics, tumor size, tumor location, hypothalamic involvement, surgical hypothalamic damage, extent of resection, and recurrence rate correlated with these functional prognostic factors.<br>
Results The median age at diagnosis was 28.0 years, with a median follow-up of 80.5 months. Postoperative obesity was present in 22 patients, and those with postoperative obesity had a significantly higher preoperative BMI or BMI-Z (preoperative BMI for adults: p = 0.074; preoperative BMI-Z for children: p = 0.020) and were significantly correlated with preoperative hypothalamic involvement grade 2 (p = 0.012) and surgical hypothalamic damage grade II (p = 0.0001). Deterioration in social participation was significantly associated with a larger tumor size (p = 0.023) and tumor recurrence (p = 0.0047).<br>
Conclusions Patients with higher preoperative BMI or BMI-Z and hypothalamic involvement have a greater risk of postoperative obesity, and larger tumor size and recurrence can significantly deteriorate the rate of patients’ social participation.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1756-46461252025Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways106672ENSakiOkamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySayaKakimaruGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMayukoKoreishiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMikaSakamotoNational Institute of Genetics, ROISYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityHideyaAndoDepartment of Applied Chemistry and Biotechnology, Okayama University of ScienceYoshioTsujinoGraduate School of Science, Technology, and Innovation, Kobe UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityResveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25-50 mu M, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation.No potential conflict of interest relevant to this article was reported.Informa UK LimitedActa Medica Okayama1323-58184512024A new species of Ovassiminea Thiele, 1927 (Gastropoda: Truncatelloidea: Assimineidae) from the Yaeyama Islands, Okinawa, southern Japan ― the northernmost record among recent species of the genus5873ENHiroshiFukudaConservation of Aquatic Biodiversity, Faculty of Agriculture, Okayama UniversityHirofumiKuboOkinawa Prefectural Institute of Health and EnvironmentOvassiminea hayasei n. sp. is described from mangrove swamps in Iriomote and Ishigaki Islands, of the Yaeyama Islands at the southwestern part of the Ryūkyū Archipelago, Okinawa, Japan. This is the northernmost record among recent species of the genus Ovassiminea Thiele, 1927, which is distributed in the tropical and subtropical regions of the Western Pacific. The new species is known to be restricted to extremely narrow ranges and is evaluated as vulnerable in red lists by the governments of Japan and Okinawa Prefecture. A list of all available (five recent and five fossil) species names of Ovassiminea hitherto described, with synonymies, is also given as an Appendix.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama2059-13811012024Case series showing the safety and changes in lipid profiles of hemodialysis patients with hypertriglyceridemia after pemafibrate administration74ENRinoOkadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesNaoyaKobayashiOkayama Saidaiji HospitalHiroyukiIshiharaOkayama Saidaiji HospitalTomohisaYokoyamaOkayama Saidaiji HospitalTomoyoMifuneOkayama Saidaiji HospitalYoshimasaSakurabuDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesIchiroNojimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorinagaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesBackground Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic kidney disease and end-stage renal disease (ESRD). Dyslipidemia is a key focus of cardiovascular therapy and is characterized by hypertriglyceridemia mainly caused by lipoprotein lipase-mediated metabolism of ApoC-III in patients with ESRD. Pemafbrate, a selective peroxisome proliferator-activated receptor alpha modulator, can be used regardless of renal function and inhibit ApoC-III expression in the liver.<br>
Case presentation We reported the cases of four patients on hemodialysis who met at least 175 mg/dL of triglycerides on the consecutive three tests between September 2022 and November 2022 and took 0.1 mg pemafbrate twice a day from November 2022 to May 2023. They experienced no adverse events after pemafbrate treatment. Pemafbrate signifcantly reduced triglyceride (TG) (302±72 to 140±50 mg/dL, p=0.048), total cholesterol (187±34 to 156±48 mg/dL, p=0.025), and Apo C-III (15.9±8.2 to 12.6±7.1, p=0.030) levels. Apo A-II levels signifcantly increased after treatment (27.0±6.1 to 37.1±5.8, p=0.041).<br>
Conclusions Pemafbrate decreased TG, total cholesterol, and Apo-CIII and increased Apo A-II without adverse events. Further study is needed to examine the favorable efects of pemafbrate on the risk of CVD.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0022-304216912024Exploring the Role of Ccn3 in Type III Cell of Mice Taste Budse16291ENKuanyuWangDepartment of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihiroMitohDepartment of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKengoHorieDepartment of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyusukeYoshidaDepartment of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDifferent taste cells express unique cell-type markers, enabling researchers to distinguish them and study their functional differentiation. Using single-cell RNA-Seq of taste cells in mouse fungiform papillae, we found that Cellular Communication Network Factor 3 (Ccn3) was highly expressed in Type III taste cells but not in Type II taste cells. Ccn3 is a protein-coding gene involved in various biological processes, such as cell proliferation, angiogenesis, tumorigenesis, and wound healing. Therefore, in this study, we aimed to explore the expression and function of Ccn3 in mouse taste bud cells. Using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry (IHC), we confirmed that Ccn3 was predominantly expressed in Type III taste cells. Through IHC, quantitative real-time RT-PCR, gustatory nerve recordings, and short-term lick tests, we observed that Ccn3 knockout (Ccn3-KO) mice did not exhibit any significant differences in the expression of taste cell markers and taste responses compared to wild-type controls. To explore the function of Ccn3 in taste cells, bioinformatics analyses were conducted and predicted possible roles of Ccn3 in tissue regeneration, perception of pain, protein secretion, and immune response. Among them, an immune function is the most plausible based on our experimental results. In summary, our study indicates that although Ccn3 is strongly expressed in Type III taste cells, its knockout did not influence the basic taste response, but bioinformatics provided valuable insights into the possible role of Ccn3 in taste buds and shed light on future research directions.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0093-691X2282024Exogenous expression of PGC-1α during in vitro maturation impairs the developmental competence of porcine oocytes3036ENSon QuangDoDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityHai ThanhNguyenDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityTakuyaWakaiDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityHiroakiFunahashiDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityObjectives of the current study were to examine the effects of exogenous expression of PGC-1α, which is a transcription factor responsive for controlling mitochondrial DNA (mtDNA) replication, mitochondria quantity control, mitochondrial biogenesis, and reactive oxygen species (ROS) maintenance, in porcine oocytes during in-vitro maturation (IVM) on the developmental competence, as well as mitochondrial quantity and function. Exogenous over-expression of PGC-1α by injection of the mRNA construct into oocytes 20 h after the start of IVM culture significantly increased the copy number of mtDNA in the oocytes, but reduced the incidences of oocytes matured to the metaphase-II stage after the IVM culture for totally 44 h and completely suppressed the early development in vitro to the blastocyst stage following parthenogenetic activation. The exogenous expression of PGC-1α also significantly induced spindle defects and chromosome misalignments. Furthermore, markedly higher ROS levels were observed in the PGC-1α-overexpressed mature oocytes, whereas mRNA level of SOD1, encoded for a ROS scavenging enzyme, was decreased. These results conclude that forced expression of PGC-1α successfully increase mtDNA copy number but led to increased ROS production, evidently by downregulation of SOD1 gene expression, inducement of spindle aberration/chromosomal misalignment, and consequently reduction in the meiotic and developmental competences of porcine oocytes.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7862024Treatment of Tenosynovial Giant Cell Tumor of the Cervical Spine with Postoperative Anti-RANKL Antibody (Denosumab) Administration469474ENYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayukiNagaseDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuSasadaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshiyukiAyadaDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHayatoMiyakeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChiakiSugaharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinaoOdaDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu UniversityTakaoYasuharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/67877Tenosynovial giant cell tumor (TGCT) is a fibrous histiocytic tumor originating in the synovial membrane. While cervical TGCT may not be considered a common diagnosis preoperatively because it is relatively rare, it has a high recurrence rate and should be considered. Total resection is preferable, but it can be challenging due to the risk of damaging the vertebral artery. Denosumab has shown effectiveness as a postoperative treatment for osteolytic bone lesion. Denosumab administration coupled with close follow-up might offer an effective postoperative treatment option for unresectable TGCT with bone invasion.No potential conflict of interest relevant to this article was reported.American Chemical SocietyActa Medica Okayama2470-13439502024Conformational Flexibility of D1-Glu189: A Crucial Determinant in Substrate Water Selection, Positioning, and Stabilization within the Oxygen-Evolving Complex of Photosystem II5004150048ENHiroshiIsobeResearch Institute for Interdisciplinary Science, Okayama UniversityTakayoshiSuzukiResearch Institute for Interdisciplinary Science, Okayama UniversityMichihiroSugaResearch Institute for Interdisciplinary Science, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science, Okayama UniversityKizashiYamaguchiCenter for Quantum Information and Quantum Biology, Osaka UniversityPhotosynthetic water oxidation is a vital process responsible for producing dioxygen and supplying the energy necessary to sustain life on Earth. This fundamental reaction is catalyzed by the oxygen-evolving complex (OEC) of photosystem II, which houses the Mn4CaO5 cluster as its catalytic core. In this study, we specifically focus on the D1-Glu189 amino acid residue, which serves as a direct ligand to the Mn4CaO5 cluster. Our primary goal is to explore, using density functional theory (DFT), how the conformational flexibility of the D1-Glu189 side chain influences crucial catalytic processes, particularly the selection, positioning, and stabilization of a substrate water molecule within the OEC. Our investigation is based on a hypothesis put forth by Li et al. (Nature, 2024, 626, 670), which suggests that during the transition from the S2 to S3 state, a specific water molecule temporarily coordinating with the Ca ion, referred to as O6*, may exist as a hydroxide ion (OH-). Our results demonstrate a key mechanism by which the detachment of the D1-Glu189 carboxylate group from its coordination with the Ca ion allows the creation of a specialized microenvironment within the OEC that enables the selective attraction of O6* in its deprotonated form (OH-) and stabilizes it at the catalytic metal (MnD) site. Our findings indicate that D1-Glu189 is not only a structural ligand for the Ca ion but may also play an active and dynamic role in the catalytic process, positioning O6* optimally for its subsequent participation in the oxidation sequence during the water-splitting cycle.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0378-37743062024Regional-scale evaluation of tertiary irrigation system in Muda Irrigation Scheme from space109175ENAliya MhdZahirGraduate School of Environmental and Life Science, Okayama UniversityHiroakiSomuraGraduate School of Environmental and Life Science, Okayama UniversityToshitsuguMoroizumiGraduate School of Environmental and Life Science, Okayama UniversityA tertiary irrigation system is essential for efficient water management in large-scale irrigation scheme and requires regular evaluation to understand their effectiveness. The current water balance method for tertiary irrigation system evaluation requires extensive data, making continuous monitoring over vast areas unfeasible. A better approach using geospatial data from the Google Earth Engine (GEE) is introduces to evaluate the efficiency of tertiary irrigation systems on a regional scale, aiding water management strategies. This study aims to (1) define the rice cultivation boundary for accurate data collection and (2) quantitatively evaluate irrigation system performance using specific indicators. Remote sensing evapotranspiration (RS-ET) and yield derived from Normalized Difference Vegetation Index (NDVI) were collected within rice cultivation boundary across 60 irrigation blocks, including 14 blocks equipped with tertiary irrigation system in Region II of the Muda Irrigation Scheme. Three irrigation system performance indicators (equity, adequacy, and water productivity) were used as a key metric in over four rice-growing seasons to evaluate tertiary irrigation system. Results reveal that tertiary irrigation system performance varies with the current three-phase water management strategy. Equity performance was highest during the off-season, particularly in phase 1 (2–8 %). Adequacy was moderate across all phases and seasons (median: 0.6–0.67), while water productivity showed consistent strength in phases 1 and 3, with fluctuations in phase 2, across seasons. This study underscores the cost-effectiveness and efficiency of using geospatial data from space for continuous regional-scale monitoring, highlighting areas for improvement in the current water management strategy.No potential conflict of interest relevant to this article was reported.American Physical Society (APS)Acta Medica Okayama2469-995011092024Ferrimagnetic structure in the high-pressure phase of 𝛼−Mn094420ENShingoArakiDepartment of Physics, Okayama UniversityKaiseiIwamotoGraduate School of Natural Science and Technology, Okayama UniversityKazutoAkibaDepartment of Physics, Okayama UniversityTatsuo C.KobayashiDepartment of Physics, Okayama UniversityKojiMunakataNeutron Science and Technology Center, Comprehensive Research Organization for Science and SocietyKojiKanekoMaterials Sciences Research Center, Japan Atomic Energy AgencyToyotakaOsakabeMaterials Sciences Research Center, Japan Atomic Energy AgencyThe 𝛼−Mn phase exhibits a large anomalous Hall effect (AHE) in its pressure-induced weak ferromagnetic (WFM) state, despite its relatively small spontaneous magnetization of ∼0.02𝜇B/Mn. To understand the underlying mechanism behind this AHE, we performed single crystal neutron diffraction measurements at 2.0 GPa to determine the magnetic structure of the WFM phase. Our investigation reveals a ferrimagnetic structure characterized by nearly collinear magnetic moments aligned along the [001] direction at sites I, II, III-1, and IV-1. In contrast, the small moments at sites III-2 and IV-2 lie within the (001) plane. The calculated net magnetization of this magnetic structure, (−0.08±0.10)𝜇B/Mn atom, is in agreement with the experimentally determined spontaneous magnetization. The observation of a magnetic reflection at 𝒒=(0,0,0) satisfies a key condition for the emergence of the AHE.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1661-659625222024Efficient Production of Chondrocyte Particles from Human iPSC-Derived Chondroprogenitors Using a Plate-Based Cell Self-Aggregation Technique12063ENShojiroHanakiDepartment of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineDaisukeYamadaDepartment of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTomokaTakaoDepartment of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineRyosukeIwaiInstitute of Frontier Science and Technology, Okayama University of ScienceTakeshiTakaradaDepartment of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineThe limited capacity of articular cartilage for self-repair is a critical challenge in orthopedic medicine. Here, we aimed to develop a simplified method of generating chondrocyte particles from human-induced pluripotent stem cell-derived expandable limb-bud mesenchymal cells (ExpLBM) using a cell self-aggregation technique (CAT). ExpLBM cells were induced to form chondrocyte particles through a stepwise differentiation protocol performed on a CAT plate (prevelex-CAT (R)), which enables efficient and consistent production of an arbitrary number of uniformly sized particles. Histological and immunohistochemical analyses confirmed that the generated chondrocyte particles expressed key cartilage markers, such as type II collagen and aggrecan, but not hypertrophic markers, such as type X collagen. Additionally, when these particles were transplanted into osteochondral defects in rats with X-linked severe combined immunodeficiency, they demonstrated successful engraftment and extracellular matrix production, as evidenced by Safranin O and Toluidine Blue staining. These data suggest that the plate-based CAT system offers a robust and scalable approach to produce a large number of chondrocyte particles in a simplified and efficient manner, with potential application to cartilage regeneration. Future studies will focus on refining the system and exploring its clinical applications to the treatment of cartilage defects.No potential conflict of interest relevant to this article was reported.Taylor and FrancisActa Medica Okayama0883-95143812024Surrogate-Assisted Multi-Objective Optimization for Simultaneous Three-Dimensional Packing and Motion Planning Problems Using the Sequence-Triple Representation2398895ENZiangLiuFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityTomoyaKawabeFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityTatsushiNishiFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityShunItoFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityTomofumiFujiwaraFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityPacking problems are classical optimization problems with wide-ranging applications. With the advancement of robotic manipulation, there are growing demands for the automation of packing tasks. However, the simultaneous optimization of packing and the robot's motion planning is challenging because these two decisions are interconnected, and no previous study has addressed this optimization problem. This paper presents a framework to simultaneously determine the robot's motion planning and packing decision to minimize the robot's processing time and the container's volume. This framework comprises three key components: solution encoding, surrogate modeling, and evolutionary computation. The sequence-triple representation encodes complex packing solutions by a sequence of integers. A surrogate model is trained to predict the processing time for a given packing solution to reduce the computational burden. Training data is generated by solving the motion planning problem for a set of packing solutions using the rapidly exploring random tree algorithm. The Non-Dominated Sorting Genetic Algorithm II searches for the Pareto solutions. Experimental evaluations are conducted using a 6-DOF robot manipulator. The experimental results suggest that implementing the surrogate model can reduce the computational time by 91.1%. The proposed surrogate-assisted optimization method can obtain significantly better solutions than the joint angular velocity-based estimation method.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2073-436016162024Long-Term Bonding Performance of One-Bottle vs. Two-Bottle Bonding Agents to Lithium Disilicate Ceramics2266ENMasaoIrieDepartment of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroOkadaDepartment of Dental Biomaterials, Tohoku University Graduate School of DentistryYukinoriMaruoDepartment of Prosthodontics, Okayama University HospitalGoroNishigawaDepartment of Prosthodontics, Okayama University HospitalTakuyaMatsumotoDepartment of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe aim of this study was to compare the long-term bonding performance to lithium disilicate (LDS) ceramic between one-bottle and two-bottle bonding agents. Bonding performance was investigated under these LDS pretreatment conditions: with hydrofluoric acid (HF) only, without HF, with a two-bottle bonding agent (Tokuyama Universal Bond II) only. Shear bond strengths between LDS and nine resin cements (both self-adhesive and conventional adhesive types) were measured at three time periods: after one-day water storage (Base), and after 5000 and 20,000 thermocycles (TC 5k and TC 20k respectively). Difference in degradation between one- and two-bottle bonding agents containing the silane coupling agent was compared by high-performance liquid chromatography. With HF pretreatment, bond strengths were not significantly different among the three time periods for each resin cement. Without HF, ESTECEM II and Super-Bond Universal showed significantly higher values than others at TC 5k and TC 20k when treated with the recommended bonding agents, especially at TC 20k. Difference in degradation between one- and two-bottle bonding agents containing the silane coupling agent was compared by high-performance liquid chromatography (HPLC). For both cements, these values at TC 20k were also not significantly different from pretreatment with only Tokuyama Universal Bond II. For LDS, long-term bond durability could be maintained by pretreatment with Tokuyama Universal Bond II instead of the hazardous HF.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2212-53456252024A randomized, open-label phase II study on the preventive effect of goshajinkigan against peripheral neuropathy induced by paclitaxel-containing chemotherapy: The OLCSG2101 study protocol897900ENNaokiNakamuraDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesGoMakimotoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalTakaakiTanakaDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukaKatoCenter of Innovative Clinical Medicine, Okayama University HospitalIsaoOzeDivision of Cancer Epidemiology and Prevention, Aichi Cancer Center Research InstituteToshiyukiKozukiDepartment of Respiratory Medicine, Shikoku Cancer CenterToshihideYokoyamaDepartment of Respiratory Medicine, Kurashiki Central HospitalHirohisaIchikawaDepartment of Respiratory Medicine, KKR Takamatsu HospitalShoichiKuyamaDepartment of Respiratory Medicine, Iwakuni Clinical CenterNaofumiHaraDepartment of Respiratory Medicine, Okayama Rosai HospitalYoshinobuMaedaDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiHottaCenter of Innovative Clinical Medicine, Okayama University HospitalBackground: Paclitaxel (PTX) is an essential cytotoxic anticancer agent and a standard treatment regimen component for various malignant tumors, including advanced unresectable non-small cell lung cancer, thymic cancer, and primary unknown cancers. However, chemotherapy-induced peripheral neuropathy (CIPN) caused by PTX is a significant adverse event that may lead to chemotherapy discontinuation and deterioration of the quality of life (QOL). Although treatment modalities such as goshajinkigan (GJG), pregabalin, and duloxetine are empirically utilized for CIPN, there is no established evidence for an agent as a preventive measure. We designed a randomized phase II trial (OLCSG2101) to investigate whether prophylactic GJG administration can prevent the onset of CIPN induced by PTX.<br>
Methods: This study was designed as a two-arm, prospective, randomized, multicenter phase II trial. The patients will be randomly assigned to either the GJG prophylaxis arm (Arm A) or the GJG non-prophylaxis arm (Arm B), using cancer type (lung cancer or not) and age (<70 years or not) as adjustment factors. A total of 66 patients (33 in each arm) will be enrolled.<br>
Discussion: The results of this study may contribute to better management of CIPN, which can enable the continuation of chemotherapy and maintenance of the patient's QOL.<br>
Ethics and dissemination: Ethical approval was obtained from the certified review board of Okayama University (approval no. CRB21-005) on September 28, 2021. Results will be published in peer-reviewed journals and presented at national and international conferences.<br>
Trial registration: Japan Registry of Clinical Trials (registration number jRCTs061210047).No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813622024令和５年度岡山医学会賞 総合研究奨励賞（結城賞）4850ENHiromichiNaitoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231862024子どもの創造性が社会に与える影響についての基礎研究U― 子どもの作品に関する文献調査による課題整理 ―4350ENAiMATSUURAFaculty of Education, Okayama University10.18926/bgeou/67573 本研究の目的は，子どもの創造性と社会とを関連付ける活動を通して，大人が子どもの表現活動に対する新たな価値を獲得するよう促すことである。第一次研究の二つ目にあたる本論では，子どもの作品に関する先行研究から，美術教育における子どもの作品への捉え方について整理する。本調査では，先行研究の調査期間を2008 年から2023 年の16 年間と設定し，美術教育に関する学会誌の三誌に掲載されている研究論文を対象とした。その結果，本調査においては，小学生や未就学児の作品を取り上げる研究が多く，写実表現に向かう中学生や高校生の作品への言及がなされていないことと，子どもの作品自体の「価値を生産」する研究は散見されるものの，「価値を普及」する視点が不足していることがわかった。No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7842024Middle-Ear Salivary Gland Choristoma with Congenital, Single-Sided Hearing Loss349355ENYuichiroTominagaDepartment of Otolaryngology, Head and Neck Surgery, Hiroshima City, Hiroshima Citizens HospitalAkikoSugayaDepartment of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinKariyaDepartment of Otolaryngology, Head and Neck Surgery, Kawasaki Medical School HospitalAikoShimizuDepartment of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoKataokaDepartment of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMizuoAndoDepartment of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/67554Middle-ear salivary gland choristoma (SGCh) is a rare, benign tumor that causes conductive hearing loss owing to middle-ear morphological abnormalities. Early diagnosis is challenging, and surgical resection is indispensable for a definitive diagnosis. We report the case of a 3-year-old boy diagnosed with middle-ear SGCh during the follow-up period for left-sided hearing loss discovered at newborn hearing screening (NHS). Long-term follow-up after the NHS result, subsequent computed tomography/magnetic resonance imaging, and surgical resection led to its relatively early diagnosis and treatment.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2077-038313152024Evolution and Effects of Ad Hoc Multidisciplinary Team Meetings in the Emergency Intensive Care Unit: A Five-Year Analysis4324ENTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKoheiAgetaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityToshiyukiAokageDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKoheiTsukaharaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBackground: Multidisciplinary team meetings (MDTMs) are crucial in the ICU. However, daily rounds may not address all sensitive issues due to time constraints and the complexity of cases. This study aimed to describe detailed information and characteristics of ad hoc MDTMs in the ICU. Methods: This single-center, retrospective study analyzed adult emergency ICU admissions at Okayama University Hospital from 1 January 2019 to 31 December 2023. During this period, weekly regular multidisciplinary team ICU rounds were introduced in June 2020, and regular weekday morning MDTMs began in April 2022. A multiple logistic regression analysis was applied to determine the impact of these changes on the frequency of ad hoc MDTMs, adjusting for variables including annual changes. Results: The study analyzed 2487 adult EICU patients, with a median age of 66, and 63.3% of them male. MDTMs were held for 168 patients (6.8%), typically those with severe conditions, including higher COVID-19 prevalence and APACHE II scores, and longer ICU stays. Despite a constant total number of MDTMs, the likelihood of conducting ad hoc MDTMs increased annually (adjusted OR 1.19; 95% CI, 1.04-1.35). Of the 329 MDTMs conducted for these patients, 59.0% addressed end-of-life care, involving an average of 11 participants, mainly nurses and emergency and critical-care physicians. Conclusions: Changes in ICU round and meeting structures might be associated with a higher frequency of conducting ad hoc MDTMs, highlighting their evolving role and importance in patient care management.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2223-774713152024Light-Driven H2 Production in Chlamydomonas reinhardtii: Lessons from Engineering of Photosynthesis2114ENMichaelHipplerInstitute of Plant Science and Resources, Okayama UniversityFatemehKhosravitabarDepartment of Biological and Environmental Sciences, University of GothenburgIn the green alga Chlamydomonas reinhardtii, hydrogen production is catalyzed via the [FeFe]-hydrogenases HydA1 and HydA2. The electrons required for the catalysis are transferred from ferredoxin (FDX) towards the hydrogenases. In the light, ferredoxin receives its electrons from photosystem I (PSI) so that H-2 production becomes a fully light-driven process. HydA1 and HydA2 are highly O-2 sensitive; consequently, the formation of H-2 occurs mainly under anoxic conditions. Yet, photo-H-2 production is tightly coupled to the efficiency of photosynthetic electron transport and linked to the photosynthetic control via the Cyt b(6)f complex, the control of electron transfer at the level of photosystem II (PSII) and the structural remodeling of photosystem I (PSI). These processes also determine the efficiency of linear (LEF) and cyclic electron flow (CEF). The latter is competitive with H-2 photoproduction. Additionally, the CBB cycle competes with H-2 photoproduction. Consequently, an in-depth understanding of light-driven H-2 production via photosynthetic electron transfer and its competition with CO2 fixation is essential for improving photo-H-2 production. At the same time, the smart design of photo-H-2 production schemes and photo-H-2 bioreactors are challenges for efficient up-scaling of light-driven photo-H-2 production.No potential conflict of interest relevant to this article was reported.American Association for the Advancement of ScienceActa Medica Okayama2375-25489432023Structure of a diatom photosystem II supercomplex containing a member of Lhcx family and dimeric FCPIIeadi8446ENYueFengPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesZhenhuaLiPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesXiaoyiLiPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesLiliShenPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesXueyangLiuPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesCuicuiZhouPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesJinyangZhangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesMinSangChina National Botanical GardenGuangyeHanPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesWenqiangYangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesTingyunKuangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesWendaWangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesJian-RenShenResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityDiatoms rely on fucoxanthin chlorophyll a/c-binding proteins (FCPs) for their great success in oceans, which have a great diversity in their pigment, protein compositions, and subunit organizations. We report a unique structure of photosystem II (PSII)-FCPII supercomplex from Thalassiosira pseudonana at 2.68-angstrom resolution by cryo-electron microscopy. FCPIIs within this PSII-FCPII supercomplex exist in dimers and monomers, and a homodimer and a heterodimer were found to bind to a PSII core. The FCPII homodimer is formed by Lhcf7 and associates with PSII through an Lhcx family antenna Lhcx6_1, whereas the heterodimer is formed by Lhcf6 and Lhcf11 and connects to the core together with an Lhcf5 monomer through Lhca2 monomer. An extended pigment network consisting of diatoxanthins, diadinoxanthins, fucoxanthins, and chlorophylls a/c is revealed, which functions in efficient light harvesting, energy transfer, and dissipation. These results provide a structural basis for revealing the energy transfer and dissipation mechanisms and also for the structural diversity of FCP antennas in diatoms.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0167-68062082024Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306145-154ENTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalHitoshiTsudaDepartment of Basic Pathology, National Defense Medical CollegeKeitaSasakiJCOG Data Center/Operations Office, National Cancer Center HospitalJunkiMizusawaJCOG Data Center/Operations Office, National Cancer Center HospitalFutoshiAkiyamaDepartment of Pathology, Cancer Institute HospitalMasafumiKurosumiDepartment of Diagnostic Pathology, Kameda Kyobashi ClinicMasatakaSawakiDepartment of Breast Oncology, Aichi Cancer Center HospitalNobukoTamuraDepartment of Breast Surgery, Toranomon HospitalKiyoTanakaDepartment of Breast Surgery, Toranomon HospitalTakahiroKogawaDepartment of Breast Medical Oncology, Cancer Institute HospitalMinaTakahashiDepartment of Breast Oncology, National Hospital Organization Shikoku Cancer CenterNaokiHayashiDepartment of Breast Surgery Oncology, St Lukes International HospitalHirofumiMukaiDepartment of Breast and Medical Oncology, National Cancer Center Hospital EastNorikazuMasudaDepartment of Surgery, Breast Oncology, National Hospital Organization Osaka National HospitalFumikataHaraDepartment of Breast Medical Oncology, Cancer Institute HospitalHirojiIwataDepartment of Breast Oncology, Aichi Cancer Center HospitalBackground In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis.<br>
Methods We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined.<br>
Results ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175–0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073–0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is.<br>
Conclusions RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1661-659625112024SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes6269ENTianyiWangDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTongGaoDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasakiyoSakaguchiDepartment of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySprouty-related enabled/vasodilator-stimulated phosphoprotein homology 1 domain containing 2 (SPRED2) is an inhibitor of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and has been shown to promote autophagy in several cancers. Here, we aimed to determine whether SPRED2 plays a role in autophagy in hepatocellular carcinoma (HCC) cells. The Cancer Genome Atlas (TCGA) Liver Cancer Database showed a negative association between the level of SPRED2 and p62, a ubiquitin-binding scaffold protein that accumulates when autophagy is inhibited. Immunohistochemically, accumulation of p62 was detected in human HCC tissues with low SPRED2 expression. Overexpression of SPRED2 in HCC cells increased the number of autophagosomes and autophagic vacuoles containing damaged mitochondria, decreased p62 levels, and increased levels of light-chain-3 (LC3)-II, an autophagy marker. In contrast, SPRED2 deficiency increased p62 levels and decreased LC3-II levels. SPRED2 expression levels were negatively correlated with translocase of outer mitochondrial membrane 20 (TOM20) expression levels, suggesting its role in mitophagy. Mechanistically, SPRED2 overexpression reduced ERK activation followed by the mechanistic or mammalian target of rapamycin complex 1 (mTORC1)-mediated signaling pathway, and SPRED2 deficiency showed the opposite pattern. Finally, hepatic autophagy was impaired in the liver of SPRED2-deficient mice with hepatic lipid droplet accumulation in response to starvation. These results indicate that SPRED2 is a critical regulator of autophagy not only in HCC cells, but also in hepatocytes, and thus the manipulation of this process may provide new insights into liver pathology.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7832024Effect of Humidified High-Flow Nasal Cannula Oxygen Therapy with a Pulmonary Infection Control Window as a Ventilation Switching Indication in Combination with Atomizing Inhalation of Terbutaline on the Lung Function of Patients with Acute Exacerbation of COPD271279ENMengjiaoYeDepartment of Respiratory and Critical Care Medicine, Tiantai Hospital of Traditional Chinese MedicineRenweiZhangDepartment of Respiratory and Critical Care Medicine, Tiantai Hospital of Traditional Chinese MedicineOriginal Article10.18926/AMO/67202We investigated how humidified high-flow nasal cannula oxygen therapy (HFNC) with a pulmonary infection control (PIC) window as a ventilation switching indication in combination with atomizing inhalation of terbutaline affects the lung function of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We examined 140 hospitalized AECOPD patients randomized to control and observation groups. Conventional supportive therapy and invasive mechanical ventilation with tracheal intubation were conducted in both groups, with a PIC window as the indication for ventilation switching. Noninvasive positive pressure ventilation (NIPPV) plus atomizing inhalation of terbutaline was used in the control group. In the observation group, HFNC combined with atomizing inhalation of terbutaline was used. Compared to the control group, after 48-hr treatment and treatment completion, the observation group had significantly increased levels of lung function indicators (maximal voluntary ventilation [MVV] plus forced vital capacity [FVC], p<0.05) and oxygen metabolism indicators (arterial oxygen partial pressure [PaO2], arterial oxygen content [CaO2], and oxygenation index, p<0.05). The comparison of the groups revealed that the levels of airway remodeling indicators (matrix metalloproteinase-2 [MMP-2], tissue inhibitor of metalloproteinase 2 [TIMP-2] plus MMP-9) and inflammatory indicators (interferon gamma [IFN-γ] together with interleukin-17 [IL-17], IL-10 and IL-4) were significantly lower after 48 h of treatment as well as after treatment completion (both p<0.05). These results demonstrate that HFNC with a PIC window as the indication for ventilation switching combined with atomizing inhalation of terbutaline can relieve the disorder of oxygen metabolism and correct airway hyper-reactivity.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7832024Thoughts on and Proposal for the Education, Training, and Recruitment of Infectious Disease Specialists205213ENHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalReview10.18926/AMO/67195The global pandemic of COVID-19 has underscored the significance of establishing and sustaining a practical and efficient infection control system for the benefit and welfare of society. Infectious disease (ID) specialists are expected to take on leadership roles in enhancing organizational infrastructures for infection prevention and control (IPC) at the hospital, community, and national levels. However, due to an absolute shortage and an uneven distribution, many core hospitals currently lack the ID specialists. Given the escalating global risk of emerging and re-emerging infectious diseases as well as antimicrobial resistance pathogens, the education and training of ID specialists constitutes an imperative concern. As demonstrated by historical changes in the healthcare reimbursement system, the establishment and enhancement of IPC measures is pivotal to ensuring medical safety. The existing structure of academic society-driven certification and training initiatives for ID specialists, contingent upon the discretionary decisions of individual physicians, possesses both quantitative and qualitative shortcomings. In this article, I first address the present situations and challenges related to ID specialists and then introduce my idea of securing ID specialists based on the new concepts and platforms; (i) ID Specialists as National Credentials, (ii) Establishment of the Department of Infectious Diseases in Medical and Graduate Schools, (iii) Endowed ID Educative Courses Funded by Local Government and Pharmaceutical Companies, and (iv) Recruitment of Young Physicians Engaged in Healthcare Services in Remote Areas. As clarified by the COVID-19 pandemic, ID specialists play a crucial role in safeguarding public health. Hopefully, this article will advance the discussion and organizational reform for the education and training of ID specialists.No potential conflict of interest relevant to this article was reported.BMJ Publishing GroupActa Medica Okayama2052-48971232024Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3)e004237ENAsamiUenoOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesYasuhiroOnishiOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKokiMiseOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesSatoshiYamaguchiOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesAyakaKannoOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesIchiroNojimaOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesChigusaHiguchiOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHaruhito A.UchidaOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKenichiShikataOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesSatoshiMiyamotoOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesAtsukoNakatsukaOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesJunEguchiOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKazuyukiHidaDepartment of Diabetology and Metabolism, National Hospital Organization Okayama Medical CenterAkihiroKatayamaDepartment of Diabetology and Metabolism, National Hospital Organization Okayama Medical CenterMayuWatanabeDepartment of Diabetology and Metabolism, National Hospital Organization Okayama Medical CenterTatsuakiNakatoDepartment of Internal Medicine, Okayama Saiseikai General HospitalAtsuhitoToneDepartment of Internal Medicine, Okayama Saiseikai General HospitalSanaeTeshigawaraOkayama Saiseikai General HospitalTakashiMatsuokaDepartment of Diabetic Medicine, Kurashiki Central HospitalShinjiKameiDepartment of Diabetic Medicine, Kurashiki Central HospitalKazutoshiMurakamiDepartment of Diabetic Medicine, Kurashiki Central HospitalIkkiShimizuSakakibara Heart Institute of OkayamaKatsuhitoMiyashitaJapanese Red Cross Okayama HospitalShinichiroAndoOkayama City General Medical CenterTomokazuNunoueNunoue ClinicJunWadaOkayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesIntroduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.<br>
Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.<br>
Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.<br>
Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2041-17231512024Structure and distinct supramolecular organization of a PSII-ACPII dimer from a cryptophyte alga Chroomonas placoidea4535ENZhiyuanMaoPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesXingyueLiPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesZhenhuaLiPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesLiangliangShenPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesXiaoyiLiPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesYanyanYangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesWendaWangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesTingyunKuangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesJian-RenShenInstitute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama UniversityGuangyeHanPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesCryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C. placoidea), and analyze its structure at a resolution of 2.47 & Aring; using cryo-electron microscopy. This structure reveals a dimeric organization of PSII-ACPII containing two PSII core monomers flanked by six symmetrically arranged ACPII subunits. The PSII core is conserved whereas the organization of ACPII subunits exhibits a distinct pattern, different from those observed so far in PSII of other algae and higher plants. Furthermore, we find a Chl a-binding antenna subunit, CCPII-S, which mediates interaction of ACPII with the PSII core. These results provide a structural basis for the assembly of antennas within the supercomplex and possible excitation energy transfer pathways in cryptophyte algal PSII, shedding light on the diversity of supramolecular organization of photosynthetic machinery.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024Studies on Selective Synthesis and Coordination Abilities of Unsymmetrical Azines with Pyridyl, Imidazolyl, and Oxazolyl Substituents and Structures and Properties of Their Iron(II) and Nickel(II) ComplexesENKENNEDY MAWUNYA HAYIBORGraduate School of Natural Science and Technology, Okayama universityNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0946-271610142023Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells431447ENYumaGoharaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNahokoTomonobuDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineRieKinoshitaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineJunichiroFutamiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityLénaAudebertDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYouyiChenDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNi Luh Gede YoniKomalasariDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineFanJiangDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineChikakoYoshizawaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHitoshiMurataDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKen-ichiYamamotoDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasamiWatanabeDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHiromiKumonInnovation Center Okayama for Nanobio-Targeted Therapy, Okayama UniversityMasakiyoSakaguchiDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineThe adenovirus-REIC/Dkk-3 expression vector (Ad-REIC) has been the focus of numerous clinical studies due to its potential for the quenching of cancers. The cancer-suppressing mechanisms of the REIC/DKK-3 gene depend on multiple pathways that exert both direct and indirect effects on cancers. The direct effect is triggered by REIC/Dkk-3-mediated ER stress that causes cancer-selective apoptosis, and the indirect effect can be classified in two ways: (i) induction, by Ad-REIC-mis-infected cancer-associated fibroblasts, of the production of IL-7, an important activator of T cells and NK cells, and (ii) promotion, by the secretory REIC/Dkk-3 protein, of dendritic cell polarization from monocytes. These unique features allow Ad-REIC to exert effective and selective cancer-preventative effects in the manner of an anticancer vaccine. However, the question of how the REIC/Dkk-3 protein leverages anticancer immunity has remained to be answered. We herein report a novel function of the extracellular REIC/Dkk-3―namely, regulation of an immune checkpoint via modulation of PD-L1 on the cancer-cell surface. First, we identified novel interactions of REIC/Dkk-3 with the membrane proteins C5aR, CXCR2, CXCR6, and CMTM6. These proteins all functioned to stabilize PD-L1 on the cell surface. Due to the dominant expression of CMTM6 among the proteins in cancer cells, we next focused on CMTM6 and observed that REIC/Dkk-3 competed with CMTM6 for PD-L1, thereby liberating PD-L1 from its complexation with CMTM6. The released PD-L1 immediately underwent endocytosis-mediated degradation. These results will enhance our understanding of not only the physiological nature of the extracellular REIC/Dkk-3 protein but also the Ad-REIC-mediated anticancer effects.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1867-10714242023Time course of complications after small renal mass biopsy: evaluation of initial follow-up images398405ENSoichiroKajitaDepartment of Radiology, Okayama University HospitalToshihiroIguchiDepartment of Radiology, Okayama University HospitalYusukeMatsuiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKojiTomitaDepartment of Radiology, Okayama University HospitalMayuUkaDepartment of Radiology, Okayama University HospitalNoriyukiUmakoshiDepartment of Radiology, Okayama University HospitalTakahiroKawabataDepartment of Radiology, Okayama University HospitalKazuakiMunetomoDepartment of Radiology, Okayama University HospitalTakaoHirakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose To retrospectively assess the time course of complications after image-guided small renal mass biopsy using initial follow-up imaging.<br>
Materials and methods A total of 190 masses (mean, 2.1 ± 0.70 cm; range, 0.6–3.8 cm) were assessed using initial computed tomography (43 non-enhanced and 141 enhanced) or magnetic resonance imaging (five non-enhanced and one enhanced) after biopsy. Initial follow-up imaging was classified into two groups (i.e., with or without hematoma) and various factors were compared.<br>
Results The masses were histologically diagnosed in all patients except one. Post-procedural complications included 129 Grade I hematomas, 1 Grade I hemothorax, 9 Grade II hematomas, and 1 Grade IIIa pneumothorax. Residual 28 Grade I and 6 Grade II hematomas and 8 new complications (6 small hematomas, 1 pseudoaneurysm, and 1 arteriovenous fistula) were observed on the initial follow-up imaging obtained at a median of 21 days (3–90 days) after the biopsy. On the initial follow-up imaging, the groups with and without hematoma differed significantly in the following factors: age (P = 0.04), size (P = 0.02), guided images (P < 0.01), hematoma at the end of the procedure (P < 0.01), and days after biopsy (P < 0.01). Although three masses exhibited > 25% shrinkage, no significant change was observed in mass diameter on initial follow-up imaging (mean, 2.1 ± 0.71 cm; P = 0.90).<br>
Conclusion Initial follow-up imaging after a biopsy revealed improvements in most of the complications, a few new complications, and an unchanged mass diameter.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7822024The Relationships among Internalized Stigma, Sense of Coherence, and Personal Recovery of Persons with Schizophrenia Living in the Community171184ENAyaKuramotoGraduate School of Health Sciences, Okayama UniversityShinyaSaitoGraduate School of Health Sciences, Okayama UniversityKumiWatanabeSchool of Nursing, Faculty of Medicine, Kagawa UniversityOriginal Article10.18926/AMO/66926We investigated (i) the relationships among internalized stigma (IS), sense of coherence (SOC), and the personal recovery (PR) of persons with schizophrenia living in the community, and (ii) how to improve the support for these individuals. A questionnaire survey on IS, SOC, and PR was sent by mail to 270 persons with schizophrenia living in the community who were using psychiatric daycare services, of whom 149 responded and 140 were included in the analysis. We established a hypothetical model in which IS influences PR, and SOC influences IS and PR, and we used structural equation modeling to examine the relationships among these concepts. The goodness of fit was acceptable. Our findings suggest that rather than directly promoting PR, SOC promotes PR by mitigating the impact of IS. It is important for nurses/supporters to support individuals with schizophrenia living in the community so that they have opportunities to reflect on their own experiences through their activities and to share their experiences with peers. Nurses/supporters themselves should also reflect on their own support needs. Our findings suggest that this will lead to a reduction of IS and the improvement of SOC, which will in turn promote personal recovery.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2072-66941672024Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation1298ENKumikoOhsawaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesShujiMomoseDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityAsamiNishikoriDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMidori FilizNishimuraDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYukaGionDepartment of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health SciencesKeisukeSawadaDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityMorihiroHigashiDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityMichihideTokuhiraDepartment of Hematology, Japan Community Health Care Organization Saitama Medical CenterJun-IchiTamaruDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesA subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7822024The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response95106ENJunkoItanoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Allergy and Respiratory Medicine, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalReview10.18926/AMO/66912The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0028-083662679992024Oxygen-evolving photosystem II structures during S1–S2–S3 transitions670677ENHongjieLiResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityYoshikiNakajimaResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityErikoNangoInstitute of Multidisciplinary Research for Advanced Materials, Tohoku UniversityShigekiOwadaJapan Synchrotron Radiation Research InstituteDaichiYamadaDepartment of Picobiology, Graduate School of Life Science, University of HyogoKanaHashimotoResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityFangjiaLuoJapan Synchrotron Radiation Research InstituteRieTanakaRIKEN SPring-8 CenterFusamichiAkitaResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityKojiKatoResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityJungminKangRIKEN SPring-8 CenterYasunoriSaitohResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityShunpeiKishiResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityHuaxinYuResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityNaokiMatsubaraResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityHajimeFujiiResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityMichihiroSugaharaJapan Synchrotron Radiation Research InstituteMamoruSuzukiInstitute for Protein Research, Osaka UniversityTetsuyaMasudaDivision of Food and Nutrition, Faculty of Agriculture, Ryukoku UniversityTetsunariKimuraDepartment of Chemistry, Graduate School of Science, Kobe UniversityTran NguyenThaoResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityShinichiroYonekuraResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityLong-JiangYuResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityTakehikoToshaRIKEN SPring-8 CenterKensukeTonoJapan Synchrotron Radiation Research InstituteYasumasaJotiJapan Synchrotron Radiation Research InstituteTakakiHatsuiJapan Synchrotron Radiation Research InstituteMakinaYabashiJapan Synchrotron Radiation Research InstituteMinoruKuboDepartment of Picobiology, Graduate School of Life Science, University of HyogoSoIwataRIKEN SPring-8 CenterHiroshiIsobeResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityKizashiYamaguchiCenter for Quantum Information and Quantum Biology, Osaka UniversityMichihiroSugaResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityPhotosystem II (PSII) catalyses the oxidation of water through a four-step cycle of Si states (i = 0–4) at the Mn4CaO5 cluster1,2,3, during which an extra oxygen (O6) is incorporated at the S3 state to form a possible dioxygen4,5,6,7. Structural changes of the metal cluster and its environment during the S-state transitions have been studied on the microsecond timescale. Here we use pump-probe serial femtosecond crystallography to reveal the structural dynamics of PSII from nanoseconds to milliseconds after illumination with one flash (1F) or two flashes (2F). YZ, a tyrosine residue that connects the reaction centre P680 and the Mn4CaO5 cluster, showed structural changes on a nanosecond timescale, as did its surrounding amino acid residues and water molecules, reflecting the fast transfer of electrons and protons after flash illumination. Notably, one water molecule emerged in the vicinity of Glu189 of the D1 subunit of PSII (D1-E189), and was bound to the Ca2+ ion on a sub-microsecond timescale after 2F illumination. This water molecule disappeared later with the concomitant increase of O6, suggesting that it is the origin of O6. We also observed concerted movements of water molecules in the O1, O4 and Cl-1 channels and their surrounding amino acid residues to complete the sequence of electron transfer, proton release and substrate water delivery. These results provide crucial insights into the structural dynamics of PSII during S-state transitions as well as O–O bond formation.No potential conflict of interest relevant to this article was reported.Oxford University PressActa Medica Okayama2056-3418102022Fabrication of initial trabecular bone-inspired three-dimensional structure with cell membrane nano fragmentsrbac088ENKoichiKadoyaDepartment of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEmilio SatoshiHaraDepartment of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroOkadaDepartment of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYu YangJiaoDepartment of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayoshiNakanoDivision of Materials & Manufacturing Science, Osaka UniversityAkiraSasakiDepartment of Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaMatsumotoDepartment of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe extracellular matrix of trabecular bone has a large surface exposed to the bone marrow and plays important roles such as hematopoietic stem cell niche formation and maintenance. In vitro reproduction of trabecular bone microenvironment would be valuable not only for developing a functional scaffold for bone marrow tissue engineering but also for understanding its biological functions. Herein, we analyzed and reproduced the initial stages of trabecular bone formation in mouse femur epiphysis. We identified that the trabecular bone formation progressed through the following steps: (i) partial rupture of hypertrophic chondrocytes; (ii) calcospherite formation on cell membrane nano fragments (CNFs) derived from the ruptured cells; and (iii) calcospherite growth and fusion to form the initial three-dimensional (3D) structure of trabecular bones. For reproducing the initial trabecular bone formation in vitro, we collected CNFs from cultured cells and used as nucleation sites for biomimetic calcospherite formation. Strikingly, almost the same 3D structure of the initial trabecular bone could be obtained in vitro by using additional CNFs as a binder to fuse biomimetic calcospherites.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1347-694787112023The effect of exogenous dihydroxyacetone and methylglyoxal on growth, anthocyanin accumulation, and the glyoxalase system in Arabidopsis13231331ENMaoxiangZhaoGraduate School of Environmental and Life Science, Okayama UniversityToshiyukiNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityShintaroMunemasaGraduate School of Environmental and Life Science, Okayama UniversityIzumi CMoriInstitute of Plant Science and Resources, Okayama UniversityYoshiyukiMurataGraduate School of Environmental and Life Science, Okayama UniversityDihydroxyacetone (DHA) occurs in wide-ranging organisms, including plants, and can undergo spontaneous conversion to methylglyoxal (MG). While the toxicity of MG to plants is well-known, the toxicity of DHA to plants remains to be elucidated. We investigated the effects of DHA and MG on Arabidopsis. Exogenous DHA at up to 10 mM did not affect the radicle emergence, the expansion of green cotyledons, the seedling growth, or the activity of glyoxalase II, while DHA at 10 mM inhibited the root elongation and increased the activity of glyoxalase I. Exogenous MG at 1.0 mM inhibited these physiological responses and increased both activities. Dihydroxyacetone at 10 mM increased the MG content in the roots. These results indicate that DHA is not so toxic as MG in Arabidopsis seeds and seedlings and suggest that the toxic effect of DHA at high concentrations is attributed to MG accumulation by the conversion to MG.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0020-16935642024Synthesis and characterization of iron(II) complex with unsymmetrical heterocyclic (2-pyridyl)(4-imidazolyl)azine121937ENKennedy MawunyaHayiborYukinariSunatsukiTakayoshiSuzukiA new iron(II) complex bearing unsymmetrical azine, [Fe(HLH)2](PF6)2·H2O·MeCN (HLH = 2-pyridylmethylidenehydrazono(4-imidazolyl)methane), was synthesized exclusively by a reaction of 2-pyridine carboxaldehyde, 1H-imidazole-4-carboxaldehyde, hydrazine monohydrate and FeCl2·4H2O (in a molar ratio of 2:2:2:1) in methanol, followed by the addition of an aqueous NH4PF6 solution. It was characterized using spectroscopic techniques, elemental analysis, magnetic measurement, and cyclic voltammetry. The molecular and crystal structure of the compound was revealed by X-ray analysis, where an iron(II) ion was surrounded by two HLH azines with a planar E(py),Z(im) conformation, and tridentate κ3N,N’,N” coordination mode, forming a monomeric six-coordinated and diamagnetic complex. The complex cations were linked by water molecules via intermolecular hydrogen-bonding interactions between the imidazole N−H and the neighboring uncoordinated azine-N atom, forming a 1D chain structure. The selective formation of this unsymmetrical azine (HLH) from a stoichiometric mixture of the components would result from the steric preference of the five- and six-membered chelate rings by the 2-pyridyl and 4-imidazolyl azine moieties, respectively, with the E(py),Z(im) configuration.No potential conflict of interest relevant to this article was reported.岡山大学教師教育開発センターActa Medica Okayama2186-1323142024大学教養教育に適した創造性を重視した探究型授業の提案 岡山大学教養教育科目「生活の中の創造性」の実践結果の分析U191205ENYoshihikoINADAFaculty of Education, Okayama UniversityYokoSHINOHARAFaculty of Education, Okayama University10.18926/CTED/66781新学習指導要領で探究的な学びを経験した高校生が大学で学び始める2025年度を控え，大学の教養教育科目として，「色」を主題にして物理学と被服学の知見を組み合わせ，プロジェクト型の活動も組み入れた新たな授業を開発し実践した。昨年度の実践と同様に，様々なつながりを意識してものごとを捉えたり，学生自身の思考や感覚の特徴を自覚させることを促す仕掛けを組み込むことで，学生の主体性を促して創造的な思考を刺激する授業になっている。受講生のシャトルカードの記述，考察過程で作成したウェビング，物理や物理学習に対する学生の思考や態度を測定するCLASS調査紙などの分析の結果，「主体的，対話的に考え，感じ，判断する自分自身の存在を意識すること」を促す効果が大きいことが明らかになった。これは，探究的な学びの土台として重要な創造性の涵養に欠かせない要素になる。No potential conflict of interest relevant to this article was reported.岡山大学経済学会Acta Medica Okayama2433-41465532024Adam Smith’s Support for Big Government: Evolution of his Views on Government from Lectures on Jurisprudence to The Wealth of Nations2531ENSatoshiNiimura10.18926/OER/66734Adam Smith has advocated laissez-faire: however, many of Smith’s interpreters have pointed out that Smith discusses several exceptions to laissez-faire. Most of the important exceptions are not in Lectures on Jurisprudence (LJ); rather, they first appear in The Wealth of Nations (WN). These references seem to reflect a conscious shift in Smith’s policy principle from laissez-faire with small government to state intervention under big government. To compare small government with big, i.e. laissez-faire with government intervention, we must historically distinguish between two types of government intervention. The older type predated laissez-faire and included feudal governments, absolute governments and mercantilism, whereas the newer type includes various primitive forms of modern social or welfare states.<br>
Smith’s primary purpose in LJ is to criticise the older type of big government. In WN, he criticises the older big government in Books I, III and IV and promotes a newer type of government intervention in Books II and V, particularly regarding three important fields. First, he proposes regulating banking and financial markets in Book II of WN. Second, in contrast to LJ, where he gave little attention to public works and institutions, he considers them among the government’s three major duties in Book V of WN. Third, Smith drastically changes his views on taxation. He argues that they should be as light as possible in LJ, but in Book V of WN, he insists on increasing land taxes and abolishing taxes on necessaries; he also recommends introducing progressive taxes and abolishing regressive ones to achieve income redistribution.<br>
This paper considers the shifts in Smith’s position from endorsing the laissez-faire role of government in LJ to promoting government intervention in WN, particularly regarding financial regulation, public works and institutions and taxation.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2041-17231412023Structural insights into photosystem II supercomplex and trimeric FCP antennae of a centric diatom Cyclotella meneghiniana8164ENSonghaoZhaoPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesLiliShenPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesXiaoyiLiPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesQiushuangTaoPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesZhenhuaLiPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesCaizheXuPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesCuicuiZhouPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesYanyanYangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesMinSangChina National Botanical GardenGuangyeHanPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesLong-JiangYuPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesTingyunKuangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesJian-RenShenResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityWendaWangPhotosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of SciencesDiatoms are dominant marine algae and contribute around a quarter of global primary productivity, the success of which is largely attributed to their photosynthetic capacity aided by specific fucoxanthin chlorophyll-binding proteins (FCPs) to enhance the blue-green light absorption under water. We purified a photosystem II (PSII)-FCPII supercomplex and a trimeric FCP from Cyclotella meneghiniana (Cm) and solved their structures by cryo-electron microscopy (cryo-EM). The structures reveal detailed organizations of monomeric, dimeric and trimeric FCP antennae, as well as distinct assemblies of Lhcx6_1 and dimeric FCPII-H in PSII core. Each Cm-PSII-FCPII monomer contains an Lhcx6_1, an FCP heterodimer and other three FCP monomers, which form an efficient pigment network for harvesting energy. More diadinoxanthins and diatoxanthins are found in FCPs, which may function to quench excess energy. The trimeric FCP contains more chlorophylls c and fucoxanthins. These diversified FCPs and PSII-FCPII provide a structural basis for efficient light energy harvesting, transfer, and dissipation in C. meneghiniana.No potential conflict of interest relevant to this article was reported. ElsevierActa Medica Okayama1083-351X29972023Structural insights into the action mechanisms of artificial electron acceptors in photosystem II104839ENShinjiKamadaFaculty of Science, Okayama UniversityYoshikiNakajimaResearch Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama UniversityPhotosystem II (PSII) utilizes light energy to split water, and the electrons extracted from water are transferred to QB, a plastoquinone molecule bound to the D1 subunit of PSII. Many artificial electron acceptors (AEAs) with molecular structures similar to that of plastoquinone can accept electrons from PSII. However, the molecular mechanism by which AEAs act on PSII is unclear. Here, we solved the crystal structure of PSII treated with three different AEAs, 2,5-dibromo-1,4-benzoquinone, 2,6dichloro-1,4-benzoquinone, and 2-phenyl-1,4-benzoquinone, at 1.95 to 2.10 angstrom resolution. Our results show that all AEAs substitute for QB and are bound to the QB-binding site (QB site) to receive electrons, but their binding strengths are different, resulting in differences in their efficiencies to accept electrons. The acceptor 2-phenyl-1,4-benzoquinone binds most weakly to the QB site and showed the highest oxygen-evolving activity, implying a reverse relationship between the binding strength and oxygen-evolving activity. In addition, a novel quinonebinding site, designated the QD site, was discovered, which is located in the vicinity of QB site and close to QC site, a binding site reported previously. This QD site is expected to play a role as a channel or a storage site for quinones to be transported to the QB site. These results provide the structural basis for elucidating the actions of AEAs and exchange mechanism of QB in PSII and also provide information for the design of more efficient electron acceptors.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2211-12474322024Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment113797ENWenhaoZhouDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShusukeKawashimaDepartment of Dermatology, Chiba University Graduate School of MedicineTakamasaIshinoDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsushigeKawaseChiba Cancer Center, Research InstituteYoukiUedaDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuoYamashitaKOTAI Biotechnologies, Inc. TomofumiWatanabeDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahitoKawazuChiba Cancer Center, Research Institute, Division of Cell TherapyHiromichiDansakoDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutakaSuzukiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoHiroyoshiNishikawaDepartment of Immunology, Nagoya University Graduate School of MedicineTakashiInozumeDepartment of Dermatology, Chiba University Graduate School of MedicineJojiNagasakiDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeTogashiDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesImmune checkpoint inhibitors exert clinical efficacy against various types of cancer through reinvigoration of exhausted CD8+ T cells that attack cancer cells directly in the tumor microenvironment (TME). Using single-cell sequencing and mouse models, we show that CXCL13, highly expressed in tumor-infiltrating exhausted CD8+ T cells, induces CD4+ follicular helper T (TFH) cell infiltration, contributing to anti-tumor immunity. Furthermore, a part of the TFH cells in the TME exhibits cytotoxicity and directly attacks major histocompatibility complex-II-expressing tumors. TFH-like cytotoxic CD4+ T cells have high LAG-3/BLIMP1 and low TCF1 expression without self-renewal ability, whereas non-cytotoxic TFH cells express low LAG-3/BLIMP1 and high TCF1 with self-renewal ability, closely resembling the relationship between terminally differentiated and stem-like progenitor exhaustion in CD8+ T cells, respectively. Our findings provide deep insights into TFH-like CD4+ T cell exhaustion with helper progenitor and cytotoxic differentiated functions, mediating anti-tumor immunity orchestrally with CD8+ T cells.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1661-65962532024Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes1443ENYoshifumiHottaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiroNishidaLocomotive Pain Center, Okayama University HospitalAkiYoshidaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaNasuDepartment of Orthopaedic Surgery, Okayama University HospitalRyuichiNakaharaDepartment of Orthopaedic Surgery, Okayama University HospitalShuichiNaniwaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNoriyukiShimizuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChinatsuIchikawaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDetingLinDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohiroFujiwaraDepartment of Orthopaedic Surgery, Okayama University HospitalToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesWe investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and β-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1β in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1β, as well as the nuclear translocation of NF-κB and β-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of β-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7812024Significance of Continuous Low-Dose Lenvatinib for the Treating of the Patients with Unresectable Thyroid Carcinoma6370ENDaizoMurakamiDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of MedicineKoheiNishimotoDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of MedicineSoshiTakaoDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruMiyamaruDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of MedicineTomokaKadowakiDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHarukiSaitoDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of MedicineHirokiTakedaDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of MedicineMomokoIseDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of MedicineKoichiSuyamaDepartment of Medical Oncology, Toranomon HospitalYorihisaOritaDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of MedicineOriginal Article10.18926/AMO/66672The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7812024Long-Term Follow-up Data of a Multi-Institutional Phase-2 Study of S-1/oxaliplatin and Bevacizumab Therapy in Patients with Advanced Colorectal Cancer: The HiSCO-02 Study4752ENManabuShimomuraDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityKatsunoriShinozakiDivision of Clinical Oncology, Hiroshima Prefectural HospitalTakuyaYanoDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityShintaroAkabaneDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityHidekiOhdanDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityHiroshima Surgical study group of Clinical Oncology (HiSCO)Original Article10.18926/AMO/66670Oral fluoropyrimidines (FUs) have certain advantages over intravenous FUs, such as longer intervals between outpatient visits, no requirement for central venous port (CVP) implantation, and lower incidence of neutropenia. We previously reported the efficacy of S-1/oxaliplatin (SOX) with bevacizumab therapy as a first-line treatment for advanced colorectal cancer (CRC) in a prospective phase-II multi-institutional clinical trial (HiSCO-02 study). However, our prognostic data at the time lacked a sufficient observation period. Herein, we analyze the longer-term follow-up data, focusing on the status of eventual CVP implantation via an open-label, non-randomized, multicenter study. This study enrolled 55 patients (mean age, 64 years), of whom 43 died (41 of primary cancer). The median overall survival was 22.7 months (95% CI: 20.1-34.7 months). Post-treatment regimens after failure of first-line treatment were initiated in 43 patients; CPT11-based regimens were selected in most cases, and other oral FU combinations in nine. CVP was implanted in 35 patients prior to first-line treatment; eleven of the remaining 20 patients did not require CVP implantation. In conclusion, we report here the final prognostic update of the Phase II clinical trial examining the efficacy of SOX plus bevacizumab therapy, the results of which confirm the clinical efficacy of this regimen.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7812024Is Proximal Triangular Fixation Better than the Conventional Method in Adult Spinal Deformity Surgery?3746ENMasatoTanakaDepartment of Orthopaedic Surgery, Okayama Rosai HospitalUmeshMeenaDepartment of Orthopaedic Surgery, Okayama Rosai HospitalTakuyaTaokaDepartment of Orthopaedic Surgery, Okayama Rosai HospitalYoshihiroFujiwaraDepartment of Orthopaedic Surgery, Okayama Rosai HospitalDaiichiroYokomizoDepartment of Orthopaedic Surgery, Okayama Rosai HospitalSantosh KumarBashyalDepartment of Orthopaedic Surgery, Okayama Rosai HospitalNaveenSakeDepartment of Orthopaedic Surgery, Okayama Rosai HospitalShinyaAratakiDepartment of Orthopaedic Surgery, Okayama Rosai HospitalOriginal Article10.18926/AMO/66669In adult spinal deformity (ASD) surgery, one of the key factors working to prevent proximal junctional kyphosis is the proximal anchor. The aim of this study was to compare clinical and radiographic outcomes of triangular fixation with conventional fixation as proximal anchoring techniques in ASD surgery. We retrospectively evaluated 54 patients who underwent corrective spinal fusion for ASD. Fourteen patients underwent proximal triangular fixation (Group T; average 74.6 years), and 40 patients underwent the conventional method (Group C; average 70.5 years). Clinical and radiographic outcomes were assessed using visual analogue scale (VAS) values for back pain and the Oswestry disability index (ODI). Radiographic evaluation was also collected preoperatively and postoperatively. Surgical times and intraoperative blood loss of the two groups were not significantly different (493 vs 490 min, 1,260 vs 1,173 mL). Clinical outcomes such as VAS and ODI were comparable in the two groups. Proximal junctional kyphosis in group T was slightly lower than that of group C (28.5% vs 47.5%, p=0.491). However, based on radiology, proximal screw pullout occurred significantly less frequently in the triangular fixation group than the conventional group (0.0% vs 22.5%, p=0.049). Clinical outcomes in the two groups were not significantly different.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1661-65962532024Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells1585ENYoshiakiSoejimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNahokoIwataDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiroYamamotoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsuhitoSuyamaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOrexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine beta-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells.No potential conflict of interest relevant to this article was reported.岡山大学農学部附属山陽圏フィールド科学センターActa Medica Okayama0910-8742422020目次iiiiENNo potential conflict of interest relevant to this article was reported.eLife Sciences PublicationsActa Medica Okayama2050-084X122023Characterization of tryptophan oxidation affecting D1 degradation by FtsH in the photosystem II quality control of chloroplastsRP88822ENYusukeKatoInstitute of Plant Science and Resources (IPSR), Okayama UniversityHiroshiKurodaResearch Institute for Interdisciplinary Science, Okayama UniversityShin-IchiroOzawaInstitute of Plant Science and Resources (IPSR), Okayama UniversityKeisukeSaitoResearch Center for Advanced Science and Technology, The University of TokyoVivekDograShanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of SciencesMartinScholzInstitute of Plant Biology and Biotechnology, University of MünsterGuoxianZhangInstitute of Plant Science and Resources (IPSR), Okayama UniversityCatherinede VitryInstitut de Biologie Physico-Chimique, Unité Mixte de Recherche 7141, Centre National de la Recherche Scientifique and Sorbonne Université Pierre et Marie CurieHiroshiIshikitaResearch Center for Advanced Science and Technology, The University of TokyoChanhongKimShanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of SciencesMichaelHipplerInstitute of Plant Science and Resources (IPSR), Okayama UniversityYuichiroTakahashiResearch Institute for Interdisciplinary Science, Okayama UniversityWataruSakamotoInstitute of Plant Science and Resources (IPSR), Okayama UniversityPhotosynthesis is one of the most important reactions for sustaining our environment. Photosystem II (PSII) is the initial site of photosynthetic electron transfer by water oxidation. Light in excess, however, causes the simultaneous production of reactive oxygen species (ROS), leading to photo-oxidative damage in PSII. To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. In PSII subunits, photo-oxidative modifications of several amino acids such as Trp have been indeed documented, whereas the linkage between such modifications and D1 degradation remains elusive. Here, we show that an oxidative post-translational modification of Trp residue at the N-terminal tail of D1 is correlated with D1 degradation by FtsH during high-light stress. We revealed that Arabidopsis mutant lacking FtsH2 had increased levels of oxidative Trp residues in D1, among which an N-terminal Trp-14 was distinctively localized in the stromal side. Further characterization of Trp-14 using chloroplast transformation in Chlamydomonas indicated that substitution of D1 Trp-14 to Phe, mimicking Trp oxidation enhanced FtsH-mediated D1 degradation under high light, although the substitution did not affect protein stability and PSII activity. Molecular dynamics simulation of PSII implies that both Trp-14 oxidation and Phe substitution cause fluctuation of D1 N-terminal tail. Furthermore, Trp-14 to Phe modification appeared to have an additive effect in the interaction between FtsH and PSII core in vivo. Together, our results suggest that the Trp oxidation at its N-terminus of D1 may be one of the key oxidations in the PSII repair, leading to processive degradation by FtsH.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-36434102023Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors100573ENHidekiIkedaChiba Cancer Center, Research InstituteJojiNagasakiChiba Cancer Center, Research InstituteDaikiShimizuDivision of Thoracic Surgery, Chiba Cancer CenterYukiKatsuyaDepartment of Experimental Therapeutics, National Cancer Center HospitalHidehitoHorinouchiDepartment of Thoracic Oncology, National Cancer Center HospitalYukioHosomiDepartment of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalEtsukoTanjiChiba Cancer Center, Research InstituteTakekazuIwataDivision of Thoracic Surgery, Chiba Cancer CenterMakikoItamiDepartment of Surgical Pathology, Chiba Cancer CenterMasahitoKawazuChiba Cancer Center, Research InstituteYuichiroOheDepartment of Thoracic Oncology, National Cancer Center HospitalTakujiSuzukiDepartment of Respirology, Graduate School of Medicine, Chiba UniversityYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs).<br>
Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II–expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo.<br>
Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti–programmed cell death protein 1 monoclonal antibody.<br>
Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1661-659624242023Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors17294ENLoc DinhHoangAdvanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesErikoAoyamaAdvanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikiHiasaLaboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiOmoteLaboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuoKubokiDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaharuTakigawaAdvanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesS-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.No potential conflict of interest relevant to this article was reported.Public Library of ScienceActa Medica Okayama1932-620318102023Shortage and unequal distribution of infectious disease specialists in Japan: How can we refine the current situation?e0291677ENHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalBackground<br>
This study aimed to assess the distribution of board-certified infectious disease (ID) specialists at medical schools and Designated Medical Institutions (DMIs) in Japan. <br>
Methods<br>
Data on the number of board-certified ID specialists was extracted by gender, prefecture, and hospital from the Japanese Association for Infectious Diseases database. The numbers and types of Japanese university hospitals that have a Faculty of Medicine, as well as the DMIs legally determined by the Infectious Diseases Control Law, were collected from the database of the Ministry of Health, Labour, and Welfare of Japan. <br>
Results<br>
As of November 2022, there were 1,688 board-certified ID specialists in Japan, with 510 employed at 82 university hospitals. Two medical schools had no ID specialists, and six had only one ID specialist. There was no ID specialists in 14.3% of Class I DMIs and 66.7% of Class II DMIs. Additionally, 14.9% of prefectures had no ID specialists at all in their Class II DMIs. The percentage of female doctors among ID specialists was 12.7%, approximately half of the overall male-to-female ratio of medical doctors in Japan. <br>
Conclusion<br>
The allocation of Japanese ID specialists to medical schools and legally designated healthcare institutes is inadequate and skewed. Female physicians are expected to play a more active role in this increasing demand.No potential conflict of interest relevant to this article was reported.SAGE PublicationsActa Medica Okayama0963-6897322023Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical TrialENToruYamashitaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumikoNakanoDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoSasakiDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKohTadokoroDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshioOmoteDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTaijunYunokiDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoKawaharaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNamikoMatsumotoDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiTairaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChikaMatsuokaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyutaMoriharaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiAbeDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAmyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients’ serum IL-6 and TNF-α levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7762023Effects of Nutritional Support Combined with Neuromuscular Electrical Stimulation on Muscle Strength and Thickness: A Randomized Controlled Trial in Healthy Young Adult Males635645ENTomohiroIkedaDepartment of Rehabilitation Medicine, Okayama University HospitalKazunoriOkamuraDepartment of Physical Therapy, Faculty of Health and Welfare, Prefectural University of HiroshimaMasakiHasegawaDepartment of Physical Therapy, Faculty of Health and Welfare, Prefectural University of HiroshimaSatoshiTanakaDepartment of Physical Therapy, Faculty of Health and Welfare, Prefectural University of HiroshimaShusakuKanaiDepartment of Physical Therapy, Faculty of Health and Welfare, Prefectural University of HiroshimaOriginal Article10.18926/AMO/66156In the management of post-injury patients with activity limitations, methods to prevent musculoskeletal disorders and hasten recovery are important. This randomized controlled, single-blinded study was a preliminary investigation of the combined effect of nutritional support with neuromuscular electrical stimulation (NMES) on muscle strength and thickness. Healthy young adult males (median age, 21 years) were enrolled; each of their hands was randomly assigned to one of the following four groups: Placebo, Nutrition, NMES, and Nutrition + NMES. All participants received whey protein or placebo (3x/week for 6 weeks) and NMES training (3x/week for 6 weeks) on the abductor digiti minimi (ADM) muscle of either the left or right hand. ADM muscle strength and thickness were analyzed at baseline and at week 7. We analyzed 38 hands (9 Placebo, 10 Nutrition, 9 NMES, 10 Nutrition + NMES). There was significantly greater muscle strengthening in the Nutrition + NMES group compared to the Placebo group or the NMES group, but no significant difference in gain of muscle thickness. The combined intervention may be effective in improving muscle strength. Future clinical trials targeting various muscles after sports-related injuries are warranted.No potential conflict of interest relevant to this article was reported.Department of Mathematics, Faculty of Science, Okayama UniversityActa Medica Okayama0030-15666612024Several homotopy fixed point spectral sequences in telescopically localized algebraic K-theory135157ENDaniel G.DavisDepartment of Mathematics, University of Louisiana at LafayetteLet n ≥ 1, p a prime, and T(n) any representative of the Bousfield class of the telescope v−1n F(n) of a finite type n complex. Also, let En be the Lubin-Tate spectrum, K(En) its algebraic K-theory spectrum, and Gn the extended Morava stabilizer group, a profinite group. Motivated by an Ausoni-Rognes conjecture, we show that there are two spectral sequences<br>
IEs,t2 ⇒ πt−s((LT(n+1)K(En))hGn) ⇐ IIEs,t2<br>
with common abutment π∗(−) of the continuous homotopy fixed points of LT(n+1)K(En), where IEs,t2 is continuous cohomology with coefficients in a certain tower of discrete Gn-modules. If the tower satisfies the Mittag-Leffler condition, then there are isomorphisms with continuous cochain cohomology groups:<br>
IE∗,∗2 ≅ H∗cts(Gn, π∗(LT(n+1)K(En))) ≅ IIE∗,∗2.<br>
We isolate two hypotheses, the first of which is true when (n, p) = (1, 2), that imply (LT(n+1)K(En))hGn ≃ LT(n+1)K(LK(n)S0). Also, we show that there is a spectral sequence<br>
Hscts(Gn, πt(K(En) ⊗ T(n + 1))) ⇒ πt−s((K(En) ⊗ T(n + 1))hGn).No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1867-107140102022Evidence on percutaneous radiofrequency and microwave ablation for liver metastases over the last decade10351045ENKojiTomitaDepartment of Radiology, Okayama University HospitalYusukeMatsuiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMayuUkaDepartment of Radiology, Okayama University HospitalNoriyukiUmakoshiDepartment of Radiology, Okayama University HospitalTakahiroKawabataDepartment of Radiology, Okayama University HospitalKazuakiMunetomoDepartment of Radiology, Okayama University HospitalShomaNagataDepartment of Radiology, Okayama University HospitalToshihiroIguchiDepartment of Radiological Technology, Faculty of Health Sciences, Okayama UniversityTakaoHirakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose This review aimed to summarize the treatment outcomes of percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA) for metastatic liver tumors based on the findings of published studies over the last decade.<br>
Materials and methods Literature describing the survival outcomes of ablation therapy for liver metastases was explored using the PubMed database on April 26, 2022, and articles published in 2012 or later were selected. The included studies met the following criteria: (i) English literature, (ii) original clinical studies, and (iii) literature describing overall survival (OS) of thermal ablation for metastatic liver tumors. All case reports and cohort studies with fewer than 20 patients and those that evaluated ablation for palliative purposes were excluded.<br>
Results RFA was the most commonly used method for ablation, while MWA was used in several recent studies. RFA and MWA for liver metastases from various primary tumors have been reported; however, majority of the studies focused on colorectal cancer. The local control rate by RFA and MWA varied widely among the studies, ranging approximately 50–90%. Five-year survival rates of 20–60% have been reported following ablation for colorectal liver metastases by a number of studies, and several reports of 10-year survival rates were also noted.<br>
Conclusion Comparative studies of local therapies for colorectal liver metastases demonstrated that RFA provides comparable survival outcomes to surgical metastasectomy and stereotactic body radiation therapy.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1471-24742412023Increased quadriceps muscle strength after medial meniscus posterior root repair is associated with decreased medial meniscus extrusion progression727ENKokiKawadaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMikaoFukubaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasanoriTamuraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNaohiroHigashiharaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYusukeYokoyamaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshimiKatayamaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasanoriHamadaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground This study aimed to assess quadriceps muscle strength after medial meniscus (MM) posterior root repair and determine its relationship with clinical scores and MM extrusion (MME). <br>
Methods Thirty patients who underwent pullout repair for MM posterior root tear and were evaluated for quadriceps muscle strength preoperatively and at 1 year postoperatively were included in this study. Quadriceps muscle strength was measured using the Locomo Scan-II instrument (ALCARE, Tokyo, Japan). MME and clinical scores (i.e., Knee Injury and Osteoarthritis Outcome Score [KOOS], International Knee Documentation Committee score, Lysholm score, Tegner score, and visual analog scale pain score) were evaluated preoperatively and at 1 year postoperatively, and second-look arthroscopy was performed at 1 year postoperatively. Wilcoxon ' s signed-rank test was used to compare each measure pre-and postoperatively. Pearson ' s correlation coefficient was used to assess the correlation with quadriceps muscle strength values. Multiple regression analysis was performed to identify factors associated with the change in MME (.MME). <br>
Results Second-look arthroscopy confirmed continuity of the posterior root in all patients. The quadriceps muscle strength measured at 1 year postoperatively (355.1 +/- 116.2 N) indicated significant improvement relative to the quadriceps muscle strength measured preoperatively (271.9 +/- 97.4 N, p < 0.001). The MME at 1 year postoperatively (4.59 +/- 1.24 mm) had progressed significantly relative to the MME preoperatively (3.63 +/- 1.01 mm, p < 0.001). The clinical scores at 1 year postoperatively were improved significantly relative to the scores preoperatively (p < 0.001). The postoperative quadriceps muscle strength was correlated with.MME (correlation coefficient = -0.398, p = 0.030), and the change in quadriceps muscle strength was correlated with the KOOS-Quality of Life (correlation coefficient = 0.430, p = 0.018). Multiple regression analysis showed that the postoperative quadriceps muscle strength had a significant effect on.MME even when the body mass index and time from injury to surgery were included. <br>
Conclusions After MM posterior root repair, patients with greater quadriceps muscle strength showed less MME progression. In addition, patients with greater improvement in quadriceps muscle strength had better clinical scores; therefore, continued rehabilitation aimed at improving quadriceps muscle strength after MM posterior root repair is recommended.No potential conflict of interest relevant to this article was reported.Spandidos PublicationsActa Medica Okayama1792-10742452022Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line‑derived xenograft model382ENQiushengShanDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHarukaOmoriDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHotakaKawaiDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMay WathoneOoDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShintaroSukegawaDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaeFujiiDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasunoriInadaDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShoSanoDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeisukeNakanoDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe cancer stroma regulates bone invasion in oral squamous cell carcinoma (OSCC). However, data on normal stroma are limited. In the present study, the effects of gingival and periodontal ligament tissue‑derived stromal cells (G‑SCs and P‑SCs, respectively) and human dermal fibroblasts (HDFs) on bone resorption and osteoclast activation were assessed using hematoxylin and eosin and tartrate‑resistant acid phosphatase staining in a cell line‑derived xenograft model. The results demonstrated that G‑SCs promoted bone invasion and osteoclast activation and inhibited osteoclast proliferation following crosstalk with the human OSCC HSC‑3 cell line, whereas P‑SCs inhibited bone resorption and promoted osteoclast proliferation in vitro but had a minimal effect on osteoclast activation both in vitro and in vivo following crosstalk with HSC‑3 cells. Furthermore, the effects of G‑SCs, P‑SCs and HDFs on protein expression levels of matrix metalloproteinase (MMP)‑9, membrane type 1 MMP (MT1‑MMP), Snail, parathyroid hormone‑related peptide (PTHrP) and receptor activator of NF‑κB ligand (RANKL) in HSC‑3 cells in OSCC bone invasion regions were assessed using immunohistochemistry. The results demonstrated that G‑SCs had a more prominent effect on the expression of MMP‑9, MT1‑MMP, Snail, PTHrP, and RANKL, whereas P‑SCs only promoted RANKL and PTHrP expression and exerted a minimal effect on MMP‑9, MT1‑MMP and Snail expression. The potential genes underlying the differential effects of G‑SCs and P‑SCs on bone invasion in OSCC were evaluated using a microarray, which indicated that cyclin‑dependent kinase 1, insulin, aurora kinase A, cyclin B1 and DNA topoisomerase II alpha underlaid these differential effects. Therefore, these results demonstrated that G‑SCs promoted bone invasion in OSCC by activating osteoclasts on the bone surface, whereas P‑SCs exerted an inhibitory effect. These findings could indicate a potential regulatory mechanism for bone invasion in OSCC.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7752023Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer517525ENShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKosakuMorimotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalTatsuhiroYamazakiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKoichiroTsutsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHironariKatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalOriginal Article10.18926/AMO/65974We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7752023Childcare and Child Development in Japan479490ENAkikoMurataDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaomiMatsumotoFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChikaraMiyajiDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoshiTakaoFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiYorifujiFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityOriginal Article10.18926/AMO/65970For decades, the notion has persisted in developed countries that exclusive care by the mothers is best for the development of children up to 3 years of age. To examine the veracity of this “myth of the first three years” in Japan, we examined the effects of childcare facility use for children younger than 3 years on their development using the cohorts of the Longitudinal Survey of Newborns in the 21st Century conducted in Japan. Of the 47,015 respondents to the survey, we studied the children of 5,508 mothers with university/professional education to evaluate the relationships between primary early (< 2.5 years) childcare providers during weekday daytime hours and specific development indices for the ages of 2.5, 5.5, and 8 years. At the age of 2.5 and 5.5 years, children attending childcare facilities were judged as having more advanced developmental behaviors by their parents, such as being able to compose a two-word sentence (adjusted odds ratio [aOR]: 0.22) or to express emotions (aOR: 0.81), compared with those cared for by mothers. However, at the age of 8 years, children who attended childcare facilities as infants < 2.5 years showed more aggressive behavior in interrupting people (aOR: 1.20) and causing disturbances in public (aOR: 1.26) than those cared for by mothers (after adjustment for numerous child and parental factors). Although these results are generally consistent with previous studies, issues potentially involved with problem behavior such as quality of childcare require further investigation, as does the case of children of mothers with more modest educational attainment.No potential conflict of interest relevant to this article was reported.Pharmaceutical Society of JapanActa Medica Okayama0009-23637122023Identification of a Functionally Efficient and Thermally Stable Outward Sodium-Pumping Rhodopsin (BeNaR) from a Thermophilic Bacterium154164ENMarieKuriharaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityVeraThielDepartment of Biological Sciences, Tokyo Metropolitan UniversityHironaTakahashiDepartment of Chemistry, Graduate School of Science, Okayama University of ScienceKeiichiKojimaFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDavid M.WardDepartment of Land Resources and Environmental Sciences, Montana State UniversityDonald A.BryantDepartment of Biochemistry and Molecular Biology, The Pennsylvania State UniversityMakotoSakaiDepartment of Chemistry, Graduate School of Science, Okayama University of ScienceSusumuYoshizawaAtmosphere and Ocean Research Institute, The University of TokyoYukiSudoFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRhodopsins are transmembrane proteins with retinal chromophores that are involved in photo-energy conversion and photo-signal transduction in diverse organisms. In this study, we newly identified and characterized a rhodopsin from a thermophilic bacterium, Bellilinea sp. Recombinant Escherichia coli cells expressing the rhodopsin showed light-induced alkalization of the medium only in the presence of sodium ions (Na+), and the alkalization signal was enhanced by addition of a protonophore, indicating an outward Na+ pump function across the cellular membrane. Thus, we named the protein Bellilinea Na+-pumping rhodopsin, BeNaR. Of note, its Na+-pumping activity is significantly greater than that of the known Na+-pumping rhodopsin, KR2. We further characterized its photochemical properties as follows: (i) Visible spectroscopy and HPLC revealed that BeNaR has an absorption maximum at 524 nm with predominantly (>96%) the all-trans retinal conformer. (ii) Time-dependent thermal denaturation experiments revealed that BeNaR showed high thermal stability. (iii) The time-resolved flash-photolysis in the nanosecond to millisecond time domains revealed the presence of four kinetically distinctive photointermediates, K, L, M and O. (iv) Mutational analysis revealed that Asp101, which acts as a counterion, and Asp230 around the retinal were essential for the Na+-pumping activity. From the results, we propose a model for the outward Na+-pumping mechanism of BeNaR. The efficient Na+-pumping activity of BeNaR and its high stability make it a useful model both for ion transporters and optogenetics tools.No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231832023中学校の「職場体験」を生かした複数教科横断的な キャリア教育の開発（U） ― 現在から未来を見つめるキャリアプランニング能力の育成 ―6172ENTazukoAOKIGraduate School of Education, Okayama UniversityKeiHAYASHIDABenesse Style Care Co.KeisukeITOHirose Elementary School in Yasugi City, Shimane.SeonTAKEUCHIa public employeeDaichiHAYASHIMinato Elementary School in Arita City, Wakayama.10.18926/bgeou/65926 職場体験はほぼすべての中学校で実施されているキャリア教育である。本稿は，青木・杉田・山崎（2021）で報告した実践について，「キャリアプランニング能力」の育成にかかわる部分について紹介する。具体的には，中学校２年生の職場体験の「事前指導（１時間目）」として，インタビュー内容を考える活動を取り入れ，生徒たち一人ひとりが職場体験の目的や意義を見出せるようにした。「事後指導U（４，５時間目）」では，独自に開発した「ジブン×イマ×ミライシート」を使用し，未来と今の自分と職場体験で生徒が学習した仕事のつながりを意識する活動を行った。これらの活動の成果は，生徒が記入したワークシートの記述や実践後のアンケートを分析することで確認した。その結果，本実践によって，生徒たちが現在と未来のつながりを考えるようになったとの記述が多く見られた。No potential conflict of interest relevant to this article was reported.Public Library of ScienceActa Medica Okayama1932-62031852023Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201e0285273ENHiromasaYamamotoDepartment of Thoracic Surgery, Okayama University HospitalJunichiSohDepartment of Surgery, Division of Thoracic Surgery, Kindai University Faculty of MedicineNorihitoOkumuraDepartment of Thoracic Surgery, Kurashiki Central HospitalHiroyukiSuzukiDepartment of Chest Surgery, Fukushima Medical University HospitalMasaoNakataDepartment of General Thoracic Surgery, Kawasaki Medical School HospitalToshiyaFujiwaraDepartment of Thoracic Surgery, Hiroshima City Hiroshima Citizens HospitalKenichiGembaDepartment of Respiratory Medicine, Chugoku Central HospitalIsaoSanoDepartment of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku HospitalTakujiFujinagaDepartment of General Thoracic Surgery, National Hospital Organization Nagara Medical CenterMasafumiKataokaDepartment of Surgery and Respiratory Center, Okayama Saiseikai General HospitalYasuhiroTerazakiDepartment of Respiratory S0urgery, Saga-Ken Medical Centre KoseikanNobukazuFujimotoDepartment of Medical Oncology and Respiratory Medicine, Okayama Rosai HospitalKazuhikoKataokaDepartment of Thoracic Surgery, National Hospital Organization Iwakuni Clinical CenterShinjiKosakaDepartment of Thoracic Surgery, Shimane Prefectural Central HospitalMotohiroYamashitaDepartment of Thoracic Surgery, National Hospital Organization Shikoku Cancer CenterHidetoshiInokawaDepartment of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical CenterMasaakiInoueDepartment of Chest Surgery, Shimonoseki City HospitalHiroshigeNakamuraDivision of General Thoracic Surgery, Tottori University HospitalYoshinoriYamashitaDepartment of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer CenterKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical University HospitalSatoshiMoritaDepartment of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of MedicineKeitaroMatsuoDivision of Cancer Epidemiology and Prevention, Aichi Cancer Center Research InstituteJunichiSakamotoTokai Central HospitalHiroshiDateDepartment of Thoracic Surgery, Kyoto University HospitalShinichiToyookaDepartment of Thoracic Surgery, Okayama University HospitalBackground<br>
It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC.<br>
<br>
Methods<br>
Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more.<br>
<br>
Results<br>
We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11).<br>
<br>
Conclusion<br>
Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1661-659624162023Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells12559ENYoshiakiSoejimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNahokoIwataDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRanNishiokaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMakoHondaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiroYamamotoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsuhitoSuyamaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOrexins are neuropeptides that play important roles in sleep-wake regulation and food intake in the central nervous system, but their receptors are also expressed in peripheral tissues, including the endocrine system. In the present study, we investigated the functions of orexin in adrenal steroidogenesis using human adrenocortical H295R cells by focusing on its interaction with adrenocortical bone morphogenetic proteins (BMPs) that induce adrenocortical steroidogenesis. Treatment with orexin A increased the mRNA levels of steroidogenic enzymes including StAR, CYP11B2, CYP17, and HSD3B1, and these effects of orexin A were further enhanced in the presence of forskolin. Interestingly, orexin A treatment suppressed the BMP-receptor signaling detected by Smad1/5/9 phosphorylation and Id-1 expression through upregulation of inhibitory Smad7. Orexin A also suppressed endogenous BMP-6 expression but increased the expression of the type-II receptor of ActRII in H295R cells. Moreover, treatment with BMP-6 downregulated the mRNA level of OX1R, but not that of OX2R, expressed in H295R cells. In conclusion, the results indicate that both orexin and BMP-6 accelerate adrenocortical steroidogenesis in human adrenocortical cells; both pathways mutually inhibit each other, thereby leading to a fine-tuning of adrenocortical steroidogenesis.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2005新規な酸性バイオアイソスターを有するアンジオテンシンII受容体拮抗薬に関する研究ENNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2005Infusion of angiotensin II reduces loss of glomerular capillary area in the early phase of anti-Thy-1.1 nephritis possibly via regulating angiogenesis-associated factorsENYukiTakazawaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2005Novel transdermal photodynamic therapy using ATX-S10・Na(II) induces apoptosis of synovial fibroblasts and ameliorates collagen antibody-induced arthritis in miceENSMiyazawaNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7742023Acute Coronary Spasm Following Pelvic Fracture, Bleeding, and Shock in a Trauma Patient423427ENYasuakiYamakawaEmergency and Critical Care Center, Kochi Health Sciences CenterKoheiMiyashitaEmergency and Critical Care Center, Kochi Health Sciences CenterAtsushiMorizaneEmergency and Critical Care Center, Kochi Health Sciences CenterMasatoTakeuchiDepartment of Cardiology, Kochi Health Sciences CenterYutaKawashimaDepartment of Radiology, Kochi Health Sciences CenterTomokoSugimuraEmergency and Critical Care Center, Kochi Health Sciences CenterYuichiSaisakaEmergency and Critical Care Center, Kochi Health Sciences CenterCase Report10.18926/AMO/65753We report a case of a patient with severe pelvic fracture who showed concurrent ST elevation on electrocardiogram. A 70-year-old man incurred an unstable pelvic fracture from a motorcycle accident. On admission, he was hemodynamically unstable, and massive transfusion and noradrenaline were administered immediately. Although ST elevation was present in leads II, III, aVF, V5, and V6, cardiac function was preserved; thus, trans-arterial embolization and external fixation for pelvic fracture were given priority. Four days after the injury, he suffered a cardiac arrest, and coronary angiography revealed that the cause of ST elevation and cardiac arrest was coronary vasospasm. Physicians should be aware that pain-related stress and platelet activation as well as use of noradrenaline in severe trauma cases can induce coronary vasospasm.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7742023Usefulness of Force-Controlled Pelvic Stress Radiograph in the Evaluation and Treatment of Fragility Fractures of the Pelvis in Geriatric Patients: A Pilot Study407414ENKensukeHottaDepartment of Orthopaedic Surgery, Amagi Chuo HospitalTakaomiKobayashiDepartment of Orthopaedic Surgery, Karatsu Red Cross HospitalOriginal Article10.18926/AMO/65751This study aimed to investigate the usefulness of force-controlled pelvic stress radiographs in the evaluation and treatment of fragility fractures of the pelvis (FFP) using a functional treatment strategy. We conducted a retrospective study of 55 geriatric patients with FFP who underwent pelvic stress radiographs on admission. The differences in the sacral width, pelvic ring width, and medial femoral head width between the radiographs with and without the Sam Sling II M size were defined as Δ sacral width, Δ pelvic ring width, and Δ medial femoral head width, respectively. We used Pearson’s correlation test to assess the relationship between the degree of radiographic instability and the Johns Hopkins highest level of mobility scale (JH-HLM) at 10-days postadmission. Conventional receiver-operating-characteristic curve analysis was used to identify cases requiring surgery using the best cutoff value for radiographic instability. The JH-HLM was significantly correlated with Δ sacral width (r=−0.401, p=0.017), but not with Δ pelvic ring width (r=−0.298, p=0.080) nor with Δ medial femoral head width (r= −0.261, p=0.128). The best cutoff value of Δ sacral width in identifying surgical cases was 10.7 mm (sensitivity 75.0%, specificity 98.0%). Force-controlled pelvic stress radiographs could be helpful in assessing the need for surgery on admission.No potential conflict of interest relevant to this article was reported.Cell PressActa Medica Okayama2405-8440972023Expression and clinicopathological characteristics of PDX1, PTF1A, and SALL4 in large and small ducts of ectopic pancreas located in gastro-duodenum and jejunume18241ENMengxiChenDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuroIgawaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYanyanHanDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFangliPengDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesZaishunJinDepartment of Pathology, Mudanjiang Medical UniversityTadashiYoshinoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAn ectopic pancreas is defined as pancreatic tissue outside its normal location, anatomically separated from the pancreas.<br>
The transcription factor pancreas/duodenum homeobox protein 1 (PDX1) is involved in maintaining the pancreas and functions in early pancreatic development, beta cell differentiation, and endocrine non beta cells. Pancreatic transcription factor 1 subunit alpha (PTF1A) affects exocrine cell formation and regulation of acinar cell identity, and is expressed in exocrine cells as a transcription factor. The depletion of SALL4 disrupts self-renewal and induces differentiation.<br>
To clarify which of PDX1, PTF1A, or SALL4 determines the difference in Heinrich's classification, we examined the localization and number of positive cells. We analyzed the differential expression of PDX1, PTF1A, and SALL4 in large and small ducts in ectopic pancreas by immunohistochemistry. Results showed that the number of PTF1A-positive cells in large ducts was more widespread in type I than in type II in the gastro-duodenum, and more SALL4-positive cells were noticed in large ducts than in small ducts in the gastro-duodenum of type II. Our results revealed that PTF1A might promote exocrine differentiation in developing the pancreatic tissues, and that those with widespread expression differentiate into exocrine cells.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7742023Biological Roles of Hepatitis B Viral X Protein in the Viral Replication and Hepatocarcinogenesis341345ENMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Academic Field of Medicine, Density and Pharmaceutical Sciences, Okayama UniversityReview10.18926/AMO/65739Hepatitis B virus is a pathogenic virus that infects 300 million people worldwide and causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Hepatitis B virus encodes four proteins. Among them, the HBx protein plays a central role in the HBV pathogenesis. Because the HBx protein is considered to play a central role in the induction of viral replication and hepatocarcinogenesis, the regulation of its function could be a key factor in the development of new interventions against hepatitis B. In this review, HBx protein-related viral replication and hepatocarcinogenesis mechanisms are described, with a focus on the recently reported viral replication mechanisms related to degradation of the Smc5/6 protein complex. We also discuss our recent discovery of a compound that inhibits HBx protein-induced degradation of the Smc5/6 protein complex, and that exerts inhibitory effects on both viral replication and hepatocarcinogenesis. Finally, prospects for future research on the HBx protein are described.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0925-98647132023Analysis of genetic diversity and population structure in Cambodian melon landraces using molecular markers10671083ENPervin MstNazninGraduate School of Environmental and Life Science, Okayama UniversityOdirichi NnennayaImohGraduate School of Environmental and Life Science, Okayama UniversityKatsunoriTanakaFaculty of Agriculture and Life Science, Hirosaki UniversityOuchSreynechCambodian Agricultural Research and Development InstituteGentaroShigitaDepartment of Life Science Systems, Technical University of MunichYonSopheaCambodian Agricultural Research and Development InstituteSakhanSophanyCambodian Agricultural Research and Development InstituteOukMakaraPlant Breeder, Retired Director of the Cambodian Agricultural Research and Development InstituteNorihikoTomookaResearch Center of Genetic Resources, National Agriculture and Food Research Organization (NARO)YukiMondenGraduate School of Environmental and Life Science, Okayama UniversityHidetakaNishidaGraduate School of Environmental and Life Science, Okayama UniversityKenjiKatoGraduate School of Environmental and Life Science, Okayama UniversityGenetic diversity of Cambodian melons was evaluated by the analysis of 12 random amplified polymorphic DNA (RAPD) and 7 simple sequence repeat (SSR) markers using 62 accessions of melon landraces and compared with 231 accessions from other areas for genetic characterization of Cambodian melons. Among 62 accessions, 56 accessions were morphologically classified as small-seed type with seed lengths shorter than 9 mm, as in the horticultural groups Conomon and Makuwa. Gene diversity of Cambodian melons was 0.228, which was equivalent to those of the groups Conomon and Makuwa and smaller than those of Vietnamese and Central Asian landraces. A phylogenetic tree constructed from a genetic distance matrix classified 293 accessions into three major clusters. Small-seed type accessions from East and Southeast Asia formed clusters I and II, which were distantly related with cluster III consisting of large-seed type melon from other areas. All Cambodian melons belonged to cluster I (except three accessions) along with those from Thailand, Myanmar, Yunnan (China), and Vietnam (“Dua thom” in the northwest), thus indicating genetic similarity in these areas. In addition, the Cambodian melons were not differentiated among geographical populations. Conomon and Makuwa were classified into cluster II, together with melon groups from the plains of Vietnam. The presence of two groups of melons in Southeast Asia was also indicated by population structure and principal coordinate analysis. These results indicated a close genetic relationship between Cambodia and the neighboring countries, thus suggesting that Cambodian melons are not directly related to the establishment of Conomon and Makuwa.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1364-85352712023Prevalence, reasons, and timing of decisions to withhold/withdraw life-sustaining therapy for out-of-hospital cardiac arrest patients with extracorporeal cardiopulmonary resuscitation252ENHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasaakiSakurayaDepartment of Emergency and Intensive Care Medicine, JA Hiroshima General HospitalTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroakiTakadaDepartment of Critical Care Medicine and Trauma, National Hospital Organization Disaster Medical CenterTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakashiYorifujiDepartment of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceToruHifumiDepartment of Emergency and Critical Care Medicine, St. Luke’s International HospitalAkihikoInoueDepartment of Emergency and Critical Care Medicine, Hyogo Emergency Medical CenterTetsuyaSakamotoDepartment of Emergency Medicine, Teikyo University School of MedicineYasuhiroKurodaDepartment of Emergency, Disaster, and Critical Care Medicine, Faculty of Medicine, Kagawa UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSAVE-J II Study GroupBackground Extracorporeal cardiopulmonary resuscitation (ECPR) is rapidly becoming a common treatment strategy for patients with refractory cardiac arrest. Despite its benefits, ECPR raises a variety of ethical concerns when the treatment is discontinued. There is little information about the decision to withhold/withdraw life-sustaining therapy (WLST) for out-of-hospital cardiac arrest (OHCA) patients after ECPR.<br>
Methods We conducted a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter study of ECPR in Japan. Adult patients who underwent ECPR for OHCA with medical causes were included. The prevalence, reasons, and timing of WLST decisions were recorded. Outcomes of patients with or without WLST decisions were compared. Further, factors associated with WLST decisions were examined.<br>
Results We included 1660 patients in the analysis; 510 (30.7%) had WLST decisions. The number of WLST decisions was the highest on the first day and WSLT decisions were made a median of two days after ICU admission. Reasons for WLST were perceived unfavorable neurological prognosis (300/510 [58.8%]), perceived unfavorable cardiac/pulmonary prognosis (105/510 [20.5%]), inability to maintain extracorporeal cardiopulmonary support (71/510 [13.9%]), complications (10/510 [1.9%]), exacerbation of comorbidity before cardiac arrest (7/510 [1.3%]), and others. Patients with WLST had lower 30-day survival (WLST vs. no-WLST: 36/506 [7.1%] vs. 386/1140 [33.8%], p < 0.001). Primary cerebral disorders as cause of cardiac arrest and higher severity of illness at intensive care unit admission were associated with WLST decisions.<br>
ConclusionFor approximately one-third of ECPR/OHCA patients, WLST was decided during admission, mainly because of perceived unfavorable neurological prognoses. Decisions and neurological assessments for ECPR/OHCA patients need further analysis.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221312023Social aspects of collision avoidance: a detailed analysis of two-person groups and individual pedestrians5756ENAdrienGregorjOkayama UniversityZeynepYucelOkayama UniversityFrancescoZanlungoOkayama UniversityClaudioFelicianiThe University of TokyoTakayukiKandaATR InternationalPedestrian groups are commonly found in crowds but research on their social aspects is comparatively lacking. To fill that void in literature, we study the dynamics of collision avoidance between pedestrian groups (in particular dyads) and individual pedestrians in an ecological environment, focusing in particular on (i) how such avoidance depends on the group's social relation (e.g. colleagues, couples, friends or families) and (ii) its intensity of social interaction (indicated by conversation, gaze exchange, gestures etc). By analyzing relative collision avoidance in the "center of mass" frame, we were able to quantify how much groups and individuals avoid each other with respect to the aforementioned properties of the group. A mathematical representation using a potential energy function is proposed to model avoidance and it is shown to provide a fair approximation to the empirical observations. We also studied the probability that the individuals disrupt the group by "passing through it" (termed as intrusion). We analyzed the dependence of the parameters of the avoidance model and of the probability of intrusion on groups' social relation and intensity of interaction. We confirmed that the stronger social bonding or interaction intensity is, the more prominent collision avoidance turns out. We also confirmed that the probability of intrusion is a decreasing function of interaction intensity and strength of social bonding. Our results suggest that such variability should be accounted for in models and crowd management in general. Namely, public spaces with strongly bonded groups (e.g. a family-oriented amusement park) may require a different approach compared to public spaces with loosely bonded groups (e.g. a business-oriented trade fair).No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2040-111614102023Role of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes11481156ENNaokoKurookaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunEguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIn diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 [GPIHBP1], apolipoprotein C-II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel-1 suppressor of lin-12-like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin-like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators, GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low-density lipoprotein to low-density lipoprotein in the endogenous pathway. The null mutation of GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications.No potential conflict of interest relevant to this article was reported.American Physical Society (APS)Acta Medica Okayama2469-9950107242023Phonon-mediated superconductivity in the Sb square-net compound LaCuSb2245117ENKazutoAkibaGraduate School of Natural Science and Technology, Okayama UniversityTatsuo C.KobayashiGraduate School of Natural Science and Technology, Okayama UniversityWe investigated the electronic structure and superconducting properties of single-crystalline LaCuSb2. The resistivity, magnetization, and specific heat measurements showed that LaCuSb2 is a bulk superconductor. The observed Shubnikov–de Haas oscillation and magnetic field dependence of the Hall resistivity can be reasonably understood assuming a slightly hole-doped Fermi surface. An electron-phonon coupling calculation clarified the difference from the isostructural compound LaAgSb2, indicating that (i) low-frequency vibration modes related to the interstitial layer sandwiched between the Sb square nets significantly contribute to the superconductivity and (ii) carriers with sizable electron-phonon coupling distribute isotropically on the Fermi surface. These are assumed to be the origin of the higher superconducting transition temperature compared with LaAgSb2. We conclude that the superconducting properties of LaCuSb2 can be understood within the framework of the conventional phonon-mediated mechanism.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0944-11745892023Endoscopic evaluation by the Kyoto classification of gastritis combined with serum anti-Helicobacter pylori antibody testing reliably risk-stratifies subjects in a population-based gastric cancer screening program848855ENRyosukeHiraiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMamiHiraiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalYuichiShimodateDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalHirokazuMouriDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalKazuhiroMatsuedaDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalHiroshiYamamotoDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalMotowoMizunoDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalBackground We previously demonstrated that the Kyoto classification of gastritis was useful for judging the status of Helicobacter pylori infection in a population-based screening program, and that adding H. pylori antibody test improved its accuracy (UMIN000028629). Here, we tested whether our endoscopic diagnosis of H. pylori infection status reliably estimated gastric cancer risk in the program.<br>
Methods Data were collected from1345 subjects who underwent endoscopic follow-up 4 years after the end of the registration. We analyzed the association of three diagnostic methods of H. pylori infection with gastric cancer detection: (1) endoscopic diagnosis based on the Kyoto classification of gastritis; (2) serum diagnosis according to the ABC method (H. pylori antibody and pepsinogen I and II); and (3) endoscopic diagnosis together with H. pylori antibody test.<br>
Results During the follow-up, 19 cases of gastric cancer were detected. By Kaplan–Meier analysis, the detection rates of cancer were significantly higher in the past or current H. pylori infection groups than in the never-infected group with all 3 methods. By the Cox proportional hazards model, the hazard ratio for cancer detection was highest in evaluation with the combined endoscopic diagnosis and the antibody test (method 3; hazard ratio 22.6, 95% confidence interval 2.99–171) among the three methods (the endoscopic diagnosis (method 1); 11.3, 2.58–49.8, and the ABC method (method 2); 7.52, 2.49–22.7).<br>
Conclusions Endoscopic evaluation of H. pylori status with the Kyoto classification of gastritis, especially combined with serum anti-Helicobacter pylori antibody testing, reliably risk-stratified subjects in a population-based gastric cancer screening program.No potential conflict of interest relevant to this article was reported. ElsevierActa Medica Okayama1083-351X29942023ATP and its metabolite adenosine cooperatively upregulate the antigen-presenting molecules on dendritic cells leading to IFN-gamma production by T cells104587ENKazuyukiFurutaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHirokaOnishiGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYukiIkadaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKentoMasakiGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversitySatoshiTanakaDepartment of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityChikaraKaitoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityDendritic cells (DCs) present foreign antigens to T cells via the major histocompatibility complex (MHC), thereby inducing acquired immune responses. ATP accumulates at sites of inflammation or in tumor tissues, which triggers local inflammatory responses. However, it remains to be clarified how ATP modulates the functions of DCs. In this study, we investigated the effects of extracellular ATP on mouse bone marrow- derived dendritic cells (BMDCs) as well as the potential for subsequent T cell activation. We found that high concentrations of ATP (1 mM) upregulated the cell surface expression levels of MHC-I, MHC-II, and co-stimulatory molecules CD80 and CD86 but not those of co-inhibitory molecules PD-L1 and PD-L2 in BMDCs. Increased surface expression of MHC-I, MHC-II, CD80, and CD86 was inhibited by a pan-P2 receptor antagonist. In addition, the upregulation of MHC-I and MHC-II expression was inhibited by an adenosine P1 receptor antagonist and by inhibitors of CD39 and CD73, which metabolize ATP to adenosine. These results suggest that adenosine is required for the ATP-induced upregulation of MHC-I and MHC-II. In the mixed leukocyte reaction assay, ATP-stimulated BMDCs activated CD4 and CD8T cells and induced interferon-gamma (IFN-gamma) production by these T cells. Collectively, these results suggest that high concentrations of extracellular ATP upregulate the expression of antigenpresenting and co-stimulatory molecules but not that of coinhibitory molecules in BMDCs. Cooperative stimulation of ATP and its metabolite adenosine was required for the upregulation of MHC-I and MHC-II. These ATP-stimulated BMDCs induced the activation of IFN-gamma-producing T cells upon antigen presentation.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7732023A Case of High-Grade Glioma in an Eloquent Area Treated with Awake Craniotomy in an 85-year-old Patient335340ENKentaroFujiiDepartment of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShuichiroHiranoDepartment of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoKurozumiDepartment of Neurological Surgery, Hamamatsu University School of Medicine, University HospitalIsaoDateDepartment of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/65504An 85-year-old woman presented with aphasia due to an occupying lesion in the left frontal lobe near the language area. Complete resection of the contrast-enhancing lesion was performed under awake conditions. The pathological diagnosis was anaplastic astrocytoma, and postoperative radiochemotherapy was administered. Awake surgery is a useful technique to reduce postoperative neurological sequelae and to maximize surgical resection. Although the patient was elderly, which is generally considered high risk, she did not have any severe neurological deficits and had a good outcome. Even in the extreme elderly, awake surgery can be useful for gliomas in language cortices.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7732023Early Fluid Balance Is Associated with 90-Day Mortality in Patients Receiving Continuous Renal Replacement Therapy263272ENYushengGuoDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunkoKosakaDepartment of Anesthesiology and Resuscitology, Okayama University HospitalHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/65491Continuous renal replacement therapy (CRRT) is widely used to control fluid balance, but the optimal fluid balance to improve the prognosis of patients remains debated. Appropriate fluid management may depend on hemodynamic status. We investigated the association between 90-day mortality and fluid balance/mean arterial pressure (MAP) in patients receiving CRRT. This single-center retrospective study was conducted between May 2018 and March 2021. Based on the cumulative fluid balance at 72 h after initiation of CRRT, the cases were divided into negative (< 0 mL) and positive (> 0 mL) fluid balance groups. Ninety-day mortality was higher in the positive fluid balance group (p=0.009). At 4 h before and after CRRT initiation, the mean MAP was lower in the positive fluid balance group (p<0.05). After multivariate cox adjustment, 72-h positive fluid balance was independently associated with 90-day mortality (p=0.004). In addition, the cumulative fluid balance was associated with 90-day mortality (p<0.05) in cases without shock, high APACHE II score, sepsis, dialysis dependence, or vasopressor use. A 72-h positive fluid balance was associated with 90-day mortality in patients receiving CRRT.No potential conflict of interest relevant to this article was reported.Institute of Electrical and Electronics EngineersActa Medica Okayama2169-3536112023Artificial Neural Network Based Audio Reinforcement for Computer Assisted Rote Learning3946639483ENParisaSupitayakulGraduate School of Natural Science and Technology, Okayama UniversityZeynep YücelGraduate School of Natural Science and Technology, Okayama UniversityAkitoMondenGraduate School of Natural Science and Technology, Okayama UniversityThe dual-channel assumption of the cognitive theory of multimedia learning suggests that importing a large amount of information through a single (visual or audio) channel overloads that channel, causing partial loss of information, while importing it simultaneously through multiple channels relieves the burden on them and leads to the registration of a larger amount of information. In light of such knowledge, this study investigates the possibility of reinforcing visual stimuli with audio for supporting e-learners in memorization tasks. Specifically, we consider three kinds of learning material and two kinds of audio stimuli and partially reinforce each kind of material with each kind of stimuli in an arbitrary way. In a series of experiments, we determine the particular type of audio, which offers the highest improvement for each kind of material. Our work stands out as being the first study investigating the differences in memory performance in relation to different combinations of learning content and stimulus. Our key findings from the experiments are: (i) E-learning is more effective in refreshing memory rather than studying from scratch, (ii) Non-informative audio is more suited to verbal content, whereas informative audio is better for numerical content, (iii) Constant audio triggering degrades learning performance and thus audio triggering should be handled with care. Based on these findings, we develop an ANN-based estimator to determine the proper moment for triggering audio (i.e. when memory performance is estimated to be declining) and carry out follow-up experiments for testing the integrated framework. Our contributions involve (i) determination of the most effective audio for each content type, (ii) estimation of memory deterioration based on learners' interaction logs, and (iii) the proposal of improvement of memory registration through auditory reinforcement. We believe that such findings constitute encouraging evidence the memory registration of e-learners can be enhanced with content-aware audio incorporation.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2688-1152422023Association between prehospital advanced life support by emergency medical services personnel and neurological outcomes among adult out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation: A secondary analysis of the SAVE-J II studye12948ENTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityToruHifumiDepartment of Emergency and Critical Care Medicine, St. Luke’s International HospitalAkihikoInoueDepartment of Emergency, Disaster and Critical Care Medicine, Hyogo Emergency Medical CenterTetsuyaSakamotoDepartment of Emergency Medicine, Teikyo University School of MedicineYasuhiroKurodaDepartment of Emergency, Disaster, and Critical Care Medicine, Kagawa University HospitalTakashiYorifujiDepartment of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversitySAVE-J II study groupStudy Objective: Early deployment of extracorporeal cardiopulmonary resuscitation (ECPR) is critical in treating refractory out-of-hospital cardiac arrest (OHCA) patients who are potential candidates for ECPR. The effect of prehospital advanced life support (ALS), including epinephrine administration or advanced airway, compared with no ALS in this setting remains unclear. This study's objective was to determine the association between any prehospital ALS care and outcomes of patients who received ECPR with emergency medical services-treated OHCA.<br>
Methods: This was a secondary analysis of data from the Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE-J) II study. Patients were separated into 2 groups-those who received prehospital ALS (ALS group) and those did not receive prehospital ALS (no ALS group). Multiple logistic regression analysis was used to investigate the association between prehospital ALS and favorable neurological outcomes (defined as Cerebral Performance Category scores 1-2) at hospital discharge.<br>
Results: A total of 1289 patients were included, with 644 patients in the ALS group and 645 patients in the no ALS group. There were fewer favorable neurological outcomes at hospital discharge in the ALS group compared with the no ALS group (10.4 vs 19.8%, p <0.001). A multiple logistic regression analysis revealed that any prehospital ALS care (adjusted odds ratios 0.47; 95% confidence interval 0.34-0.66; p <0.001) was associated with unfavorable neurological outcomes at hospital discharge.<br>
Conclusion: Prehospital ALS was associated with worse neurological outcomes at hospital discharge in patients treated with ECPR for OHCA. Further prospective studies are required to determine the clinical implications of these findings.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7722023Locally Advanced Rectal Cancer Invading the Gluteus Maximus Muscle Completely Responded to Total Neoadjuvant Therapy209213ENMasakiSakamotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/65152A 70-year-old male with anal pain and fever was diagnosed with rectal cancer perforation and abscess in the right gluteus maximus (GM) muscle. He underwent a transverse colon colostomy followed by preoperative capecitabine+oxaliplatin. Some local control was achieved but a residual abscess was observed in the right GM muscle. To secure circumferential resection margin by tumor reduction, he received chemoradiotherapy as total neoadjuvant therapy (TNT) and underwent laparoscopic abdominoperineal resection, D3 lymph node dissection, combined coccyx resection, and partial resection of the right GM muscle. The skin defect and pelvic dead space were filled with a right lateral vastus lateral great muscle flap. Histopathologically, the resected specimen showed no tumor cells in the primary tumor or lymph nodes, indicating a pathological complete response (pCR). This case suggests that TNT might improve the R0 resection and pCR rates and overall survival.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7722023Complications of Percutaneous Cryoablation for Renal Tumors and Methods for Avoiding Them121129ENToshihiroIguchiDepartment of Radiology, Okayama University HospitalYusukeMatsuiDepartment of Radiology, Okayama University HospitalKojiTomitaDepartment of Radiology, Okayama University HospitalMayuUkaDepartment of Radiology, Okayama University HospitalNoriyukiUmakoshiDepartment of Radiology, Okayama University HospitalTakahiroKawabataDepartment of Radiology, Okayama University HospitalKazuakiMunetomoDepartment of Radiology, Okayama University HospitalShomaNagataDepartment of Radiology, Okayama University HospitalMotooArakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakaoHirakiDepartment of Radiology, Okayama University HospitalReview10.18926/AMO/65141Percutaneous cryoablation of renal tumors is widely used because of its high efficacy and safety. This high safety can be attributed, at least in part, to the visibility of the ablated area as an “ice ball”. This therapy has fewer complications (incidence, 0-7.2%) and is less invasive than surgery. Minor bleeding is inevitable in most kidney-related procedures, and indeed the most common complication of this therapy is bleeding (hematoma and hematuria). However, patients require treatment such as transfusion or transarterial embolization in only 0-4% of bleeding cases. Various other complications such as ureteral or collecting system injury, bowel injury, nerve injury, skin injury, infection, pneumothorax, and tract seeding also occur, but they are usually minor and asymptomatic. However, operators should know and avoid the various complications associated with this therapy. This study aimed to summarize the complications of percutaneous cryoablation for renal tumors and provide some techniques for achieving safe procedures.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0032-38962023Preparation of crystalline polyimide nanofibers via solution crystallizationENShotaKumanoGraduate School of Natural Science and Technology, Okayama UniversityTomoyasuTakakiGraduate School of Natural Science and Technology, Okayama UniversityTetsuyaUchidaGraduate School of Natural Science and Technology, Okayama UniversityTwo crystalline polyimide nanofibers (PINFs) with different morphologies were prepared. The crystalline unit cells of the aromatic PI crystals and the crystal morphologies of the fabricated PINFs were examined. PINF-I (lengths = 305 ± 152 nm and diameters = 12 ± 2 nm) was crystallized from crystalline PI dissolved in a concentrated sulfuric acid solution. The resulting PINF-I was isolated from this solution, and it did not aggregate in water. PINF-II with diameters of 105 ± 99 nm was prepared by dispersing PINF-I in a mixed water and t-butanol (TBA) solution (water:TBA = 4:1), followed by freeze-drying. Then, the PINF-II was heated to enhance its crystallinity. X-ray diffraction and transmission electron microscopy studies of the heat-treated PINF-II revealed a PI crystalline unit cell [orthorhombic, a = 1.21 nm, b = 0.88 nm, and c = 2.23 nm (molecular chain axis direction)]. The crystal structure of the heat-treated PINF-II suggested that highly crystalline PINFs were fabricated in which the PI molecular chains were oriented along the direction of the fiber lengths.No potential conflict of interest relevant to this article was reported.WILEYActa Medica Okayama2473-40392023Enzyme-Cleaved Bone Marrow Transplantation Improves the Engraftment of Bone Marrow Mesenchymal Stem CellsENHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMay WathoneOoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIkueTosaDepartment of Regenerative Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYaminSoeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHtoo ShweEainDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShoSanouDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShigekoFushimiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShintaroSukegawaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakaradaTakeshiDepartment of Regenerative Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMesenchymal stem cell (MSC) therapy is a promising approach to curing bone diseases and disorders. In treating genetic bone dis-orders, MSC therapy is local or systemic transplantation of isolated and in vitro proliferated MSC rather than bone marrow transplan-tation. Recent evidence showed that bone marrow MSC engraftment to bone regeneration has been controversial in animal and human studies. Here, our modified bone marrow transplantation (BMT) method solved this problem. Like routine BMT, our modified method involves three steps: (i) isolation of bone marrow cells from the donor, (ii) whole-body lethal irradiation to the recipient, and (iii) injection of isolated bone marrow cells into irradiated recipient mice via the tail vein. The significant modification is imported at the bone marrow isolation step. While the bone marrow cells are flushed out from the bone marrow with the medium in routine BMT, we applied the enzymes' (collagenase type 4 and dispase) integrated medium to wash out the bone marrow cells. Then, cells were incubated in enzyme integrated solution at 37 degrees C for 10 minutes. This modification designated BMT as collagenase-integrated BMT (c-BMT). Notably, successful engraftment of bone marrow MSC to the new bone formation, such as osteoblasts and chondrocytes, occurs in c-BMT mice, whereas routine BMT mice do not recruit bone marrow MSC. Indeed, flow cytometry data showed that c-BMT includes a higher proportion of LepR(+), CD51(+), or RUNX2(+) non-hematopoietic cells than BMT. These findings suggested that c-BMT is a time-efficient and more reliable technique that ensures the disaggregation and collection of bone marrow stem cells and engraftment of bone marrow MSC to the recipient. Hence, we proposed that c-BMT might be a promising approach to curing genetic bone disorders. (c) 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.No potential conflict of interest relevant to this article was reported.Cureus Inc.Acta Medica Okayama2168-818414112022Increased CCR4+ and Decreased Central Memory CD4+ T Lymphocytes in the Background Gastric Mucosa of Patients Developing Gastric Cancer After Helicobacter pylori Eradication: An Exploratory Studye31713ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University HospitalTakahideTakahashiDivision of Medical Support, Okayama University HospitalArakiHirabataDivision of Medical Support, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHoroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesThe composition of lymphocytes in the gastric mucosa following the eradication of Helicobacter pylori (H. pylori) in patients with and without gastric cancer has not been compared. This study performed a single spot analysis of gastric mucosal lymphocytes after H. pylori eradication in patients with (n = 13) and without (n = 20) gastric cancer. Our comprehensive analysis of lymphocyte composition in the gastric mucosa revealed that: i) the proportion of CD8+/CD3+ cells was relatively higher in the peri-tumor mucosa than in the background mucosa; ii) the proportion of CCR4+/CD3+ cells was higher, and the ratio of CD62L+/CD3+CD4+ cells was relatively lower in the gastric mucosa of cancer patients than in non-cancer patients; and iii) the proportion of CD45RA-CD62L+/CD3+CD4+ cells, namely, the central memory CD4+ T -cell fraction, was lower in the gastric mucosa of cancer patients than in non-cancer patients. Although the exact mechanism of the altered proportions of CCR4+/CD3+ and central memory CD4+ cells in the gastric mucosa of patients with cancer is unknown, focusing on lymphocytes in the gastric mucosa might help improve our understanding of gastric cancer development after H. pylori eradication.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7712023Osteonecrosis of the Jaw in Two Rheumatoid Arthritis Patients Not Treated with a Bisphosphonate111116ENKatsuhikoAmanoDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkinariSugauchiThe first department of Oral and Maxillofacial Surgery, Osaka University Graduate School of DentistryChiakiYamadaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikihikoKogoThe first department of Oral and Maxillofacial Surgery, Osaka University Graduate School of DentistrySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/64371Medication-related osteonecrosis of the jaw (MRONJ) is a side effect in patients taking bone-modifying agents (BMAs), which are highly beneficial for treating osteoporosis and cancer. Bisphosphonates are prescribed to treat secondary osteoporosis in patients with rheumatoid arthritis (RA). We recently encountered two unusual cases of intraoral ONJ in RA patients who had not been treated with a BMA and did not have features of methotrexate- associated lymphoproliferative disorder. Their ONJ stage II bone exposures were treated by conservative therapy, providing good prognoses. These cases indicate that ONJ can occur in RA patients not treated with bisphosphonates. Several risk factors are discussed.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7712023Treatment of Severe Open Bite Malocclusion with Four-Piece Segmental Horseshoe Le Fort I Osteotomy97104ENMitsuhiroHoshijimaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaokiOkaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsushiMatsumuraDepartment of Oral and Maxillofacial Surgery, Wakayama Medical UniversitySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiKamiokaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/64369Appropriate operations in severe anterior open bite (AOB) cases are extremely complicated to perform because of the multiple surgical procedures involved, the difficulty of predicting posttreatment aesthetics, and the high relapse rate. We herein report a 16-year-old girl with skeletal Class II, severe AOB malocclusion, and crowding with short roots, and aesthetic and functional problems. Four-piece segmental Le Fort I osteotomy with horseshoe osteotomy was performed for maxillary intrusion, and bilateral sagittal split ramus osteotomy (SSRO) and genioplasty were performed for mandibular advancement. The malocclusion and skeletal deformity were significantly improved by the surgical orthodontic treatment. Functional and aesthetic occlusion with an improved facial profile was established, and no further root shortening was observed. Acceptable occlusion and dentition were maintained after a two-year retention period. This strategy of surgical orthodontic treatment with a complicated operative procedure might be effective for correcting certain severe AOB malocclusion cases.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7712023Effect of a Cyclooxygenase-2 Inhibitor in Combination with (−)-Epigallocatechin Gallate or Polyphenon E on Cisplatin-Induced Lung Tumorigenesis in A/J Mice6570ENKenSatoDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNagioTakigawaDepartment of General Internal Medicine 4, Kawasaki Medical SchoolToshioKuboDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidekiKatayamaDepartment of Medicine, Yamaguchi-Ube Medical CenterDaizoKishinoDepartment of Medicine, Yamaguchi-Ube Medical CenterToshiakiOkadaDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkikoHisamotoDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunkoMimotoDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiOchiDepartment of General Internal Medicine 4, Kawasaki Medical SchoolTadashiYoshinoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiUeokaDepartment of Medicine, Yamaguchi-Ube Medical CenterMitsuneTanimotoDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshionobuMaedaDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/64363We investigated the effects of celecoxib combined with (−)-epigallocatechin-3-gallate (EGCG) or polyphenon E in a cisplatin-induced lung tumorigenesis model. Four-week-old female A/J mice were divided into seven groups: (i) Control, (ii) 150 mg/kg celecoxib (150Cel), (iii) 1,500 mg/kg celecoxib (1500Cel), (iv) EGCG+150 mg/kg celecoxib (EGCG+150Cel), (v) EGCG+1,500 mg/kg celecoxib (EGCG+1500Cel), (vi) polyphenon E+150 mg/kg celecoxib (PolyE+150Cel), and (vii) polyphenon E+1,500 mg/kg celecoxib (PolyE+1500Cel). All mice were administered cisplatin (1.62 mg/kg of body weight, i.p.) 1×/week for 10 weeks and sacrificed at week 30; the numbers of tumors on the lung surface were then determined. The tumor incidence and multiplicity (no. of tumors/mouse, mean±SD) were respectively 95% and 2.15±1.50 in Control, 95% and 2.10±1.29 in 150Cel, 86% and 1.67±1.20 in 1500Cel, 71% and 1.38±1.24 in EGCG+150Cel, 67% and 1.29±1.38 in EGCG+1500Cel, 80% and 1.95±1.36 in PolyE+150Cel, and 65% and 1.05±0.10 in PolyE+1500Cel. The combination of high-dose celecoxib with EGCG or polyphenon E significantly reduced multiplicity in cisplatin-induced lung tumors.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7712023Development, Disappearance, and Clinical Course of Melanosis Coli: Sex Differences in the Progression of Severity5764ENRyoKatsumataDepartment of General Internal Medicine 2, Kawasaki Medical School General Medical CenterNoriakiManabeDivision of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical CenterYasumasaMonobePathology, Kawasaki Medical School General Medical CenterMakiAyakiDivision of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical CenterMitsuhikoSuehiroDepartment of General Internal Medicine 2, Kawasaki Medical School General Medical CenterMinoruFujitaDivision of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical CenterTomoariKamadaHealth Care Medicine, Kawasaki Medical School General Medical CenterHirofumiKawamotoDepartment of General Internal Medicine 2, Kawasaki Medical School General Medical CenterKenHarumaDepartment of General Internal Medicine 2, Kawasaki Medical School General Medical CenterOriginal Article10.18926/AMO/64362Melanosis coli (MC) is an acquired colorectal disorder visualized as colonic mucosa pigmentation. Disease severity is confirmed based on MC depth, shape, and coloration, although the clinical course is not fully understood. This study sought to clarify characteristics of MC development and disappearance and to investigate its clinical course and severity. Contributors to MC grade progression were explored. This study reviewed MC cases discovered via colonoscopy at a single institution over a 10-year period. Of all 216 MC cases, 17 developing and 10 disappearing cases were detected. Anthranoid laxative use was a key factor: 29.4% of the developing cases had used such agents before the initial MC diagnosis, whereas 40% of disappearing cases had discontinued anthranoids prior to detection of MC disappearance. Among 70 grade I cases, progression to grade II occurred in 16 cases during a mean follow-up of 3.67±2.1 years (rate of progression=22.8%). Males more commonly showed progressive than stable grade I cases, and the probability of progression was higher for male than for female cases. An association between anthranoid administration and MC presence was presumed, and grade I MC was found to progress in severity over 5 years.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7712023The Efficacy of Inflammatory and Immune Markers for Predicting the Prognosis of Patients with Stage IV Breast Cancer3743ENKoshoYamanouchiDepartment of Surgery, National Hospital Organization, Nagasaki Medical CenterShigetoMaedaDepartment of Surgery, National Hospital Organization, Nagasaki Medical CenterOriginal Article10.18926/AMO/64360Systemic therapy for stage IV breast cancer is usually an initial treatment and is based on findings regarding biomarkers (e.g., hormone receptors and human epidermal growth factor receptor-2 [HER2]). However, the response to therapy and outcomes sometime differ among patients with similar prognostic factors including grade, hormone receptor, HER2, and more. We conducted retrospective analyses to evaluate the correlations between the overall survival (OS) of 46 stage IV breast cancer patients and (i) the peripheral absolute lymphocyte count (ALC) and (ii) composite blood cell markers. The peripheral blood cell markers included the neutrophil- to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI), and the most recently introduced indicator, the pan-immune-inflammatory value (PIV). The SIRI and PIV showed prognostic impacts on the patients: those with a low SIRI or a low PIV showed significantly better OS than those with a high SIRI (5-year, 66.0% vs. 35.0%, p<0.05) or high PIV (5-year, 68.1% vs. 38.5%, p<0.05), respectively. This is the first report indicating the possible prognostic value of the PIV for OS in patients with stage IV breast cancer. Further studies with larger numbers of patients are necessary for further clarification.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1083-351X298122022Crystal structures of photosystem II from a cyanobacterium expressing psbA2 in comparison to psbA3 reveal differences in the D1 subunit102668ENYoshikiNakajimaResearch Institute for Interdisciplinary Science, Okayama UniversityNatsumiUgai-AmoGraduate School of Natural Science and Technology, Okayama UniversityNaokiToneGraduate School of Natural Science and Technology, Okayama UniversityAkikoNakagawaProteo-Science Research Center, Ehime UniversityMasakoIwaiGraduate School and College of Arts and Sciences, The University of TokyoMasahikoIkeuchiGraduate School and College of Arts and Sciences, The University of TokyoMiwaSugiuraProteo-Science Research Center, Ehime UniversityMichihiroSugaResearch Institute for Interdisciplinary Science, Okayama UniversityShenJian-RenResearch Institute for Interdisciplinary Science, Okayama UniversityThree psbA genes (psbA1, psbA2, and psbA3) encoding the D1 subunit of photosystem II (PSII) are present in the ther-mophilic cyanobacterium Thermosynechococcus elongatus and are expressed differently in response to changes in the growth environment. To clarify the functional differences of the D1 protein expressed from these psbA genes, PSII dimers from two strains, each expressing only one psbA gene (psbA2 or psbA3), were crystallized, and we analyzed their structures at resolu-tions comparable to previously studied PsbA1-PSII. Our results showed that the hydrogen bond between pheophytin/D1 (PheoD1) and D1-130 became stronger in PsbA2-and PsbA3-PSII due to change of Gln to Glu, which partially explains the increase in the redox potential of PheoD1 observed in PsbA3. In PsbA2, one hydrogen bond was lost in PheoD1 due to the change of D1-Y147F, which may explain the decrease in stability of PheoD1 in PsbA2. Two water molecules in the Cl-1 channel were lost in PsbA2 due to the change of D1-P173M, leading to the narrowing of the channel, which may explain the lower efficiency of the S-state transition beyond S2 in PsbA2-PSII. In PsbA3-PSII, a hydrogen bond between D1-Ser270 and a sulfoquinovosyl-diacylglycerol molecule near QB dis-appeared due to the change of D1-Ser270 in PsbA1 and PsbA2 to D1-Ala270. This may result in an easier exchange of bound QB with free plastoquinone, hence an enhancement of oxygen evolution in PsbA3-PSII due to its high QB exchange efficiency. These results provide a structural basis for further functional examination of the three PsbA variants.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0010-85454712022Geometric, electronic and spin structures of the CaMn4O5 catalyst for water oxidation in oxygen-evolving photosystem II. Interplay between experiments and theoretical computations214742ENKizashiYamaguchiCenter for Quantum Information and Quantum Biology, Osaka UniversityMitsuoShojiCenter of Computational Sciences, Tsukuba UniversityHiroshiIsobeResearch Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama UniversityTakashiKawakamiRIKEN Center for Computational ScienceKoichiMiyagawaCenter of Computational Sciences, Tsukuba UniversityMichihiroSugaResearch Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama UniversityFusamichiAkitaResearch Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama UniversityThe aim of this review is to elucidate geometric structures of the catalytic CaMn4Ox (x = 5, 6) cluster in the Kok cycle for water oxidation in the oxygen evolving complex (OEC) of photosystem II (PSII) based on the high-resolution (HR) X-ray diffraction (XRD) and serial femtosecond crystallography (SFX) experiments using the X-ray free-electron laser (XFEL). Quantum mechanics (QM) and QM/molecular mechanics (MM) computations are performed to elucidate the electronic and spin structures of the CaMn4Ox (x = 5, 6) cluster in five states S-i (i = 0 similar to 4) on the basis of the X-ray spectroscopy, electron paramagnetic resonance (EPR) and related experiments. Interplay between the experiments and theoretical computations has been effective to elucidate the coordination structures of the CaMn4Ox (x = 5, 6) cluster ligated by amino acid residues of the protein matrix of PSII, valence states of the four Mn ions and total spin states by their exchange-couplings, and proton-shifted isomers of the CaMn4Ox (x = 5, 6) cluster. The HR XRD and SFX XFEL experiments have also elucidated the biomolecular systems structure of OEC of PSII and the hydrogen bonding networks consisting of water molecules, chloride anions, etc., for water inlet and proton release pathways in PSII. Large-scale QM/MM computations have been performed for elucidation of the hydrogen bonding distances and angles by adding invisible hydrogen atoms to the HR XRD structure. Full geometry optimizations by the QM and QM/MM methods have been effective for elucidation of the molecular systems structure around the CaMn4Ox (x = 5, 6) cluster in OEC. DLPNO-CCSD(T-0) method has been applied to elucidate relative energies of possible intermediates in each state of the Kok cycle for water oxidation. Implications of these results are discussed in relation to the blueprint for developments of artificial catalysts for water oxidation.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama1520-6106126382022Roles of the Flexible Primary Coordination Sphere of the Mn4CaOx Cluster: What Are the Immediate Decay Products of the S-3 State?72127228ENHiroshiIsobeResearch Institute for Interdisciplinary Science, Okayama UniversityMitsuoShojiCenter for Computational Science, University of Tsukuba,TakayoshiSuzukiResearch Institute for Interdisciplinary Science, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science, Okayama UniversityKizashiYamaguchiInstitute for NanoScience Design, Osaka UniversityThe primary coordination sphere of the multinuclear cofactor (Mn4CaOx) in the oxygen-evolving complex (OEC) of photosystem II is absolutely conserved to maintain its structure and function. Recent time-resolved serial femtosecond crystallography identified large reorganization of the primary coordination sphere in the S-2 to S-3 transition, which elicits a cascade of events involving Mn oxidation and water molecule binding to a putative catalytic Mn site. We examined how the crystallographic fields, created by transient conformational states of the OEC at various time points, affect the thermodynamics of various isomers of the Mn cluster using DFT calculations, with an aim of comprehending the functional roles of the flexible primary coordination sphere in the S-2 to S-3 transition and in the recovery of the S-2 state. The results show that the relative movements of surrounding residues change the size and shape of the cavity of the cluster and thereby affect the thermodynamics of various catalytic intermediates as well as the ability to capture a new water molecule at a coordinatively unsaturated site. The implication of these findings is that the protein dynamics may serve to gate the catalytic reaction efficiently by controlling the sequence of Mn oxidation/reduction and water binding/release. This interpretation is consistent with EPR experiments; g similar to 5 and g similar to 3 signals obtained after near-infrared (NIR) excitation of the S-3 state at 4 K and a g similar to 5 only signal produced after prolonged incubation of the S-3 state at 77 K can be best explained as originating from water-bound S-2 clusters (S-total = 7/2) under a S-3 ligand field, i.e., the immediate one-electron reduction products of the oxyl-oxo (S-total = 6) and hydroxo-oxo (S-total = 3) species in the S-3 state.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7662022A Case of Paraplegia Treated with Cerebrospinal Fluid Drainage and Permissive Hypertension after Graft Replacement of the Ascending Aorta and the Total Aortic Arch for Acute Aortic Dissection Stanford Type A737742ENMasakazuYamaokaDepartment of Anesthesiology, Japanese Red Cross Society Himeji HospitalYumiYamamotoDepartment of Anesthesiology and Critical Care Medicine, Hiroshima Citizens HospitalErikoMinamiDepartment of Anesthesiology, Japanese Red Cross Society Himeji HospitalCase Report10.18926/AMO/64125Paraplegia after an operation for acute aortic dissection Stanford type A (AADA) is fairly uncommon, and there is no consensus about optimal treatment. We present a case in which cerebrospinal fluid drainage (CSFD) and permissive hypertension were used for treatment of paraplegia. When the patient showed complete bilateral paraplegia after operation for AADA, we immediately began CSFD and maintained mean arterial blood pressure at over 90 mmHg. His neurological deficit gradually recovered, and he was eventually able to walk without support. The combination of CSFD and permissive hypertension could be a first-line emergent treatment for postoperative paraplegia after AADA surgery.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7662022History of Transcatheter Arterial Chemoembolization Predicts the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients695703ENHidekiOnishiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNousoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkinobuTakakiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsushiOyamaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaAdachiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNozomuWadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasutoTakeuchiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidenoriShirahaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/64120This study sought to identify factors that are predictive of a therapeutic response to hepatic arterial infusion chemotherapy (HAIC) by focusing on the number of prior transcatheter arterial chemoembolization (TACE) sessions. To determine the parameters predicting a good response to HAIC, we retrospectively analyzed 170 patients with hepatocellular carcinoma (HCC) who received HAIC regimens comprising low-dose cisplatin combined with 5-fluorouracil (LFP) or cisplatin (CDDP) for the first time. In both the LFP and CDDP regimens, the response rates were significantly lower in patients with three or more prior TACE sessions than in those with two or fewer prior TACE sessions (LFP 57% versus 28%; p=0.01, CDDP 27% versus 6%; p=0.01). Multivariable logistic regression analysis revealed that the number of prior TACE sessions (≥ 3) was significantly associated with non-responder status (odds ratio 4.17, 95% Confidence Interval (CI) 1.76-9.86) in addition to the HAIC regimen. Multivariable analysis using the Cox proportional hazards model revealed that a larger number of prior TACE sessions (≥ 3) was a significant risk factor for survival (hazard ratio 1.60, 95% CI 1.12-2.29) in addition to Child-Pugh class, serum alpha-fetoprotein concentration, and maximum diameter of HCC. HCC patients who receive fewer prior TACE sessions (≤ 2) were found to be better responders to HAIC.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7662022An Evaluation of the Efficacy of Compression Therapy Using Sleeves and Stockings to Prevent Docetaxel-induced Peripheral Neuropathy in Breast Cancer Patients689694ENKoshoYamanouchiDepartment of Surgery, Nagasaki University Graduate School of Biomedical ScienceSayakaKubaDepartment of Surgery, Nagasaki University Graduate School of Biomedical ScienceMegumiMatsumotoDepartment of Surgical Oncology, Nagasaki University Graduate School of Biomedical ScienceHiroshiYanoDepartment of Surgical Oncology, Nagasaki University Graduate School of Biomedical ScienceMichiMoritaDepartment of Surgery, Nagasaki University Graduate School of Biomedical ScienceChikaSakimuraDepartment of Surgery, Nagasaki University Graduate School of Biomedical ScienceRyotaOtsuboDepartment of Surgical Oncology, Nagasaki University Graduate School of Biomedical ScienceMasaakiHidakaDepartment of Surgery, Nagasaki University Graduate School of Biomedical ScienceTakeshiNagayasuDepartment of Surgical Oncology, Nagasaki University Graduate School of Biomedical ScienceSusumuEguchiDepartment of Surgery, Nagasaki University Graduate School of Biomedical ScienceOriginal Article10.18926/AMO/64119Taxanes are key drugs for patients with breast cancer. A major adverse effect of taxanes is peripheral neuropathy (PN). To investigate the ability of compression therapy using sleeves and stockings to prevent PN due to the taxane docetaxel, we conducted a single-center historical control trial. Patients receiving docetaxel at 75 mg/m2 every 3 weeks for 4 cycles as first-line chemotherapy for breast cancer were eligible. PN was evaluated using the common terminology criteria for adverse events version 4.0. The primary endpoint was the incidence of allgrade PN until 3 weeks after the fourth docetaxel administration. We evaluated 26 patients in the intervention group and compared their data to those collected retrospectively from 52 patients treated with docetaxel without compression. Neither the incidence of all-grade PN until 3 weeks after the fourth docetaxel administration (63.5% in the control group vs. 76.9% in the intervention group, p=0.31) nor that of PN grade ≥ 2 (13.5% vs. 15.4%, p=0.99) differed between the groups. In this study, the efficacy of compression therapy using sleeves and stockings to prevent PN induced by docetaxel was not demonstrated. Further clinical studies including medications or intervention are needed to reduce the incidence and severity of PN induced by chemotherapy.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7662022Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients661671ENYukoAbeDepartment of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNarutoTairaDepartment of Breast and Endocrine surgery, Kawasaki Medical School HospitalKosukeKashiwabaraClinical Research Promotion Center, University of Tokyo HospitalJunjiTsurutaniAdvanced Cancer Translational Research Institute, Showa UniversityMasahiroKitadaBreast Disease Center, Asahikawa Medical University HospitalMasatoTakahashiDepartment of Breast Surgery, National Hospital Organization Hokkaido Cancer CenterHiroakiKatoDepartment of Breast Surgery, Teine Keijinkai HospitalYuichiroKikawaDepartment of Breast Surgery, Kansai Medical University HospitalEikoSakataDepartment of Breast Surgery, Niigata City General HospitalYoichiNaitoDepartment of Medical Oncology, National Cancer Center Hospital EastYoshieHasegawaDepartment of Breast Surgery, Hachinohe City HospitalTsuyoshiSaitoDepartment of Breast Surgery, Japanese Red Cross Saitama HospitalTsutomuIwasaDepartment of Medical Oncology, Kindai University Faculty of MedicineTsutomuTakashimaDepartment of Breast and Endocrine Surgery, Osaka City University Graduate School of MedicineTomohikoAiharaBreast Center, Aihara HospitalHirofumiMukaiDepartment of Medical Oncology, National Cancer Center Hospital EastFumikataHaraBreast Oncology Center, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTadahikoShienDepartment of Breast and Endocrine surgery, Okayama University HospitalHiroyoshiDoiharaDepartment of Breast surgery, Kawasaki Medical School General Medical CenterShinichiToyookaDepartment of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/64116Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01).No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7662022Artificial Intelligence-based Detection of Epileptic Discharges from Pediatric Scalp Electroencephalograms: A Pilot Study617624ENKatsuhiroKobayashiDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiShibataDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokiTsuchiyaDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyukiAkiyamaDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/64111We developed an artificial intelligence (AI) technique to identify epileptic discharges (spikes) in pediatric scalp electroencephalograms (EEGs). We built a convolutional neural network (CNN) model to automatically classify steep potential images into spikes and background activity. For the CNN model’ training and validation, we examined 100 children with spikes in EEGs and another 100 without spikes. A different group of 20 children with spikes and 20 without spikes were the actual test subjects. All subjects were ≥ 3 to < 18 years old. The accuracy, sensitivity, and specificity of the analysis were >0.97 when referential and combination EEG montages were used, and < 0.97 with a bipolar montage. The correct classification of background activity in individual patients was significantly better with a referential montage than with a bipolar montage (p=0.0107). Receiver operating characteristic curves yielded an area under the curve > 0.99, indicating high performance of the classification method. EEG patterns that interfered with correct classification included vertex sharp transients, sleep spindles, alpha rhythm, and low-amplitude ill-formed spikes in a run. Our results demonstrate that AI is a promising tool for automatically interpreting pediatric EEGs. Some avenues for improving the technique were also indicated by our findings.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2022Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: a Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer PatientsENYukoABEGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1420-304927202022Selective Formation of Unsymmetric Multidentate Azine-Based Ligands in Nickel(II) Complexes6788ENKennedy MawunyaHayiborGraduate School of Natural Science and Technology, Okayama UniversityYukinariSunatsukiAdvanced Science Research Center, Okayama UniversityTakayoshiSuzukiGraduate School of Natural Science and Technology, Okayama UniversityA mixture of 2-pyridine carboxaldehyde, 4-formylimidazole (or 2-methyl-4-formylimidazole), and NiCl2 center dot 6H(2)O in a molar ratio of 2:2:1 was reacted with two equivalents of hydrazine monohydrate in methanol, followed by the addition of aqueous NH4PF6 solution, afforded a Ni-II complex with two unsymmetric azine-based ligands, [Ni(HLH)(2)](PF6)(2) (1) or [Ni(HLMe)(2)](PF6)(2) (2), in a high yield, where HLH denotes 2-pyridylmethylidenehydrazono-(4-imidazolyl)methane and HLMe is its 2-methyl-4-imidazolyl derivative. The spectroscopic measurements and elemental analysis confirmed the phase purity of the bulk products, and the single-crystal X-ray analysis revealed the molecular and crystal structures of the Ni-II complexes bearing an unsymmetric HLH or HLMe azines in a tridentate kappa(3) N, N', N" coordination mode. The HLH complex with a methanol solvent, 1 center dot MeOH, crystallizes in the orthorhombic non-centrosymmetric space group P2(1)2(1)2(1) with Z = 4, affording conglomerate crystals, while the HLMe complex, 2 center dot H2O center dot Et2O, crystallizes in the monoclinic and centrosymmetric space group P2(1)/n with Z = 4. In the crystal of 2 center dot H2O center dot Et2O, there is intermolecular hydrogen-bonding interaction between the imidazole N-H and the neighboring uncoordinated azine-N atom, forming a one-dimensional polymeric structure, but there is no obvious magnetic interaction among the intra- and interchain paramagnetic Ni-II ions.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X76420225-Nitro-2-(3-phenylpropylamino) Benzoic Acid Inhibits the Proliferation and Migration of Lens Epithelial Cells by Blocking CaMKII Signaling415421ENHaijunKangDepartment of Ophthalmology, Suining Central HospitalDongmeiHuangDepartment of Cardiovascular, Suining Central HospitalGangjinKangDepartment of Ophthalmology, The Affiliated Hospital of Southwest Medical UniversityXuYangDepartment of Ophthalmology, Suining Central HospitalHengLiDepartment of Ophthalmology, Suining Central HospitalSiyuanLiuDepartment of Ophthalmology, Suining Central HospitalWenjunGouDepartment of Ophthalmology, Suining Central HospitalLinglinLiuDepartment of Ophthalmology, Suining Central HospitalYuyanQiuDepartment of Ophthalmology, Suining Central HospitalOriginal Article10.18926/AMO/63896Posterior capsule opacification (PCO) is a post-surgery complication of cataract surgery, and lens epithelial cells (LECs) are involved in its development. A suppressive effect on LECs is exerted by the non specific chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) exerts. Herein, the growth and migration inhibitory effects of NPPB on LECs were assessed, and the mechanism underlying the effects were investigated by focusing on Ca2+/CaMKII signaling. LECs were treated with different concentrations of NPPB, and the changes in cell viability, cell-cycle distribution, anchorage-dependent growth, migration, Ca2+ level, and CaMKII expression were evaluated. NPPB inhibited LECs’ proliferation and induced G1 cell-cycle arrest in the cells. Regarding LECs’ mobility, NPPB suppressed the cells’ anchorage-dependent growth ability and inhibited their migration. Changes in cell phenotypes were associated with an increased intracellular Ca2+ level and down-regulation of CaMKII. Together these results confirmed the inhibitory effect of NPPB on the proliferation and migration of LECs, and the effect was shown to be associated with the induced level of Ca2+ and the inhibition of CaMKII signaling transduction.No potential conflict of interest relevant to this article was reported.SAGE PublicationsActa Medica Okayama1757-17742352022Gap between self-evaluation and actual hand hygiene compliance among health-care workers239242ENHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanRyosukeTakaseDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanYosukeSazumiDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanYoshitoNishimuraDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanHiroyukiHondaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanHand hygiene (HH) compliance among health-care workers has not satisfactorily improved despite multiple educative approaches. Between October 2019 and February 2020, we performed a self-evaluation test and a direct observation for the compliance of the 5 Moments for Hand Hygiene program advocated by the World Health Organization at two Japanese hospitals. Average percentages of self-evaluated HH compliance were as follows: (i) 76.9% for “Before touching a patient,” (ii) 85.8% for “Before clean/aseptic procedures,” (iii) 95.9% for “After body fluid exposure/risk,” (iv) 84.0% for “After touching a patient,” and (v) 69.2% for “After touching patient surroundings.” On the other hand, actual HH compliance was 11.7% for “Before touching a patient” and 18.0% for “After touching a patient or patient surroundings.” The present study demonstrated a big gap between self-evaluation and actual HH compliance among nurses working at hospitals, indicating the need of further providing the education in infection prevention.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2218-273X1282022Edaravone Attenuated Angiotensin II-Induced Atherosclerosis and Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice1117ENHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTetsuharuTakatsukaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYoshikoHadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKenichiShikataCenter for Innovative Clinical Medicine, Okayama University HospitalVenkateswaranSubramanianSaha Cardiovascular Research Center, University of KentuckyAlanDaughertySaha Cardiovascular Research Center, University of KentuckyJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesBackground: The aim of the study was to define whether edaravone, a free-radical scavenger, influenced angiotensin II (AngII)-induced atherosclerosis and abdominal aortic aneurysms (AAAs) formation. Methods: Male apolipoprotein E-deficient mice (8-12 weeks old) were fed with a normal diet for 5 weeks. Either edaravone (10 mg/kg/day) or vehicle was injected intraperitoneally for 5 weeks. After 1 week of injections, mice were infused subcutaneously with either AngII (1000 ng/kg/min, n = 16-17 per group) or saline (n = 5 per group) by osmotic minipumps for 4 weeks. Results: AngII increased systolic blood pressure equivalently in mice administered with either edaravone or saline. Edaravone had no effect on plasma total cholesterol concentrations and body weights. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas and en face atherosclerosis but was significantly attenuated by edaravone administration. Edaravone also reduced the incidence of AngII-induced AAAs. In addition, edaravone diminished AngII-induced aortic MMP-2 activation. Quantitative RT-PCR revealed that edaravone ameliorated mRNA abundance of aortic MCP-1 and IL-1 beta. Immunostaining demonstrated that edaravone attenuated oxidative stress and macrophage accumulation in the aorta. Furthermore, edaravone administration suppressed thioglycolate-induced mice peritoneal macrophages (MPMs) accumulation and mRNA abundance of MCP-1 in MPMs in male apolipoprotein E-deficient mice. In vitro, edaravone reduced LPS-induced mRNA abundance of MCP-1 in MPMs. Conclusions: Edaravone attenuated AngII-induced AAAs and atherosclerosis in male apolipoprotein E-deficient mice via anti-oxidative action and anti-inflammatory effect.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-006723162022Cilostazol Attenuates AngII-Induced Cardiac Fibrosis in apoE Deficient Mice9065ENYoshikoHadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesCardiac fibrosis is characterized by the net accumulation of extracellular matrix in the myocardium and is an integral component of most pathological cardiac conditions. Cilostazol, a selective inhibitor of phosphodiesterase type III with anti-platelet, anti-mitogenic, and vasodilating properties, is widely used to treat the ischemic symptoms of peripheral vascular disease. Here, we investigated whether cilostazol has a protective effect against Angiotensin II (AngII)-induced cardiac fibrosis. Male apolipoprotein E-deficient mice were fed either a normal diet or a diet containing cilostazol (0.1% wt/wt). After 1 week of diet consumption, the mice were infused with saline or AngII (1000 ng kg(-1) min(-1)) for 28 days. AngII infusion increased heart/body weight ratio (p < 0.05), perivascular fibrosis (p < 0.05), and interstitial cardiac fibrosis (p < 0.0001), but were significantly attenuated by cilostazol treatment (p < 0.05, respectively). Cilostazol also reduced AngII-induced increases in fibrotic and inflammatory gene expression (p < 0.05, respectively). Furthermore, cilostazol attenuated both protein and mRNA abundance of osteopontin induced by AngII in vivo. In cultured human cardiac myocytes, cilostazol reduced mRNA expression of AngII-induced osteopontin in dose-dependent manner. This reduction was mimicked by forskolin treatment but was cancelled by co-treatment of H-89. Cilostazol attenuates AngII-induced cardiac fibrosis in mice through activation of the cAMP-PKA pathway.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-441811112021Cholera Rapid Diagnostic Tests for the Detection of Vibrio cholerae O1: An Updated Meta-Analysis2095ENBasilua AndreMuzemboGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiKitaharaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAyumuOhnoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAnusuyaDebnathGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeinosukeOkamotoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShin-IchiMiyoshiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe rapid diagnosis of cholera contributes to adequate outbreak management. This meta-analysis assesses the diagnostic accuracy of cholera rapid tests (RDTs) to detect Vibrio cholerae O1. Methods: Systematic review and meta-analysis. We searched four databases (Medline, EMBASE, Google Scholar, and Web of Science up to 8 September 2021) for studies that evaluated cholera RDTs for the detection of V. cholerae O1 compared with either stool culture or polymerase chain reaction (PCR). We assessed the studies' quality using the QUADAS-2 criteria. In addition, in this update, GRADE approach was used to rate the overall certainty of the evidence. We performed a bivariate random-effects meta-analysis to calculate the pooled sensitivity and specificity of cholera RDTs. Results: Overall, 20 studies were included in this meta-analysis. Studies were from Africa (n = 11), Asia (n = 7), and America (Haiti; n = 2). They evaluated eight RDTs (Crystal VC-O1, Crystal VC, Cholkit, Institut Pasteur cholera dipstick, SD Bioline, Artron, Cholera Smart O1, and Smart II Cholera O1). Using direct specimen testing, sensitivity and specificity of RDTs were 90% (95% CI, 86 to 93) and 86% (95% CI, 81 to 90), respectively. Cholera Sensitivity was higher in studies conducted in Africa [92% (95% CI, 89 to 94)] compared with Asia [82% (95% CI, 77 to 87)]. However, specificity [83% (95% CI, 71 to 91)] was lower in Africa compared with Asia [90% (95% CI, 84 to 94)]. GRADE quality of evidence was estimated as moderate. Conclusions: Against culture or PCR, current cholera RDTs have moderate sensitivity and specificity for detecting Vibrio cholerae O1.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1664-462X132022Examining the Role of Low Temperature in Satsuma Mandarin Fruit Peel Degreening via Comparative Physiological and Transcriptomic Analysis918226ENOscar W.MitaloGraduate School of Environmental and Life Science, Okayama UniversityWilliam O.AsicheDepartment of Research and Development, Del Monte Kenya LtdSeung W.KangGraduate School of Life and Environmental Sciences, University of TsukubaHiroshiEzuraGraduate School of Life and Environmental Sciences, University of TsukubaTakashiAkagiGraduate School of Environmental and Life Science, Okayama UniversityYasutakaKuboGraduate School of Environmental and Life Science, Okayama UniversityKoichiroUshijimaGraduate School of Environmental and Life Science, Okayama UniversityPeel degreening is the most conspicuous aspect of fruit ripening in many citrus fruits because of its importance for marketability. In this study, peel degreening in response to propylene (an ethylene analog) and at varying storage temperatures was characterized in Satsuma mandarin (Citrus unshiu Marc.) fruit. Propylene treatment triggered rapid peel degreening (within 4-6 days), indicated by an increase in the citrus color index (CCI) and chlorophyll loss. Peel degreening was also observed in fruit at 10 degrees C and 15 degrees C after 28-42 days, with gradual CCI increase and chlorophyll reduction. However, fruit at 5 degrees C, 20 degrees C, and 25 degrees C remained green, and no substantial changes in peel CCI and chlorophyll content were recorded during the 42-day storage duration. The transcriptomes of peels of fruit treated with propylene for 4 days and those stored at varying temperatures for 28 days were then analyzed by RNA-Seq. We identified three categories of differentially expressed genes that were regulated by (i) propylene (and by analogy, ethylene) alone, (ii) low temperature (5 degrees C, 10 degrees C, or 15 degrees C vs. 25 degrees C) alone, and (iii) either propylene or low temperature. Gene-encoding proteins associated with chlorophyll degradation (such as CuSGR1, CuNOL, CuACD2, CuCAB2, and CuLHCB2) and a transcription factor (CuERF114) were differentially expressed by propylene or low temperature. To further examine temperature-induced pathways, we also monitored gene expression during on-tree fruit maturation vs. postharvest. The onset of on-tree peel degreening coincided with autumnal drops in field temperatures, and it was accompanied by differential expression of low temperature-regulated genes. On the contrary, genes that were exclusively regulated by propylene (such as CuCOPT1 and CuPOX-A2) displayed insignificant expression changes during on-tree peel degreening. These findings indicate that low temperatures could be involved in the fruit ripening-related peel degreening independently of ethylene.No potential conflict of interest relevant to this article was reported.ELSEVIERActa Medica Okayama2059-7029742022Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study (vol 6, 100191, 2021)ENK.HottaCenter for Innovative Clinical Medicine, Okayama University HospitalS.SaekiDepartment of Respiratory Medicine, Kumamoto University HospitalM.YamaguchiDepartment of Thoracic Oncology, National Hospital Organization Kyushu Cancer CenterD.HaradaDepartment of Thoracic Oncology, National Hospital Organization Shikoku Cancer CenterA.BesshoDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalK.TanakaDepartment of Respiratory Medicine, Kyushu University HospitalK.InoueDepartment of Respiratory Medicine, Kitakyushu Municipal Medical CenterK.GembaDepartment of Respiratory Medicine, Chugoku Central HospitalM.ShiojiriDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalY.KatoCenter for Innovative Clinical Medicine, Okayama University HospitalT.NinomiyaDepartment of Respiratory Medicine, Okayama University HospitalT.KuboDepartment of Respiratory Medicine, Okayama University HospitalJ.KishimotoCenter for Clinical and Translational Research, Kyushu University HospitalY.ShioyamaClinical Radiology, Radiology Informatics and Network, Graduate School of Medical Sciences, Kyushu UniversityK.KatsuiDepartment of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJ.SasakiResearch and Development Center for New Medical Frontiers, Kitasato University School of MedicineK.KiuraDepartment of Respiratory Medicine, Okayama University HospitalK.SugioDepartment of Thoracic and Breast Surgery, Oita UniversityNo potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1471-22532212022Histidine-rich glycoprotein as a novel predictive biomarker of postoperative complications in intensive care unit patients: a prospective observational study232ENMasahikoOiwaDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKosukeKurodaDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoyaKawanoueDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground Decrease in histidine-rich glycoprotein (HRG) was reported as a cause of dysregulation of the coagulation-fibrinolysis and immune systems, leading to multi-organ failure, and it may be a biomarker for sepsis, ventilator-associated pneumonia, preeclampsia, and coronavirus disease 2019. However, the usefulness of HRG in perioperative management remains unclear. This study aimed to assess the usefulness of HRG as a biomarker for predicting postoperative complications. <br>
Methods This was a single-center, prospective, observational study of 150 adult patients who were admitted to the intensive care unit after surgery. Postoperative complications were defined as those having a grade II or higher in the Clavien-Dindo classification, occurring within 7 days after surgery. The primary outcome was HRG levels in the patients with and without postoperative complications. The secondary outcome was the ability of HRG, white blood cell, C-reactive protein, procalcitonin, and presepsin to predict postoperative complications. Data are presented as number and median (interquartile range). <br>
Results The incidence of postoperative complications was 40%. The HRG levels on postoperative day 1 were significantly lower in patients who developed postoperative complications (n = 60; 21.50 [18.12-25.74] mu g/mL) than in those who did not develop postoperative complications (n = 90; 25.46 [21.05-31.63] mu g/mL). The Harrell C-index scores for postoperative complications were HRG, 0.65; white blood cell, 0.50; C-reactive protein, 0.59; procalcitonin, 0.73; and presepsin, 0.73. HRG was independent predictor of postoperative complications when adjusted for age, the presence of preoperative cardiovascular comorbidities, American Society of Anesthesiologists Physical Status Classification, operative time, and the volume of intraoperative bleeding (adjusted hazard ratio = 0.94; 95% confidence interval, 0.90-0.99). <br>
Conclusions The HRG levels on postoperative day 1 could predict postoperative complications. Hence, HRG may be a useful biomarker for predicting postoperative complications.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2297-055X92022Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms904215ENNaofumiAmiokaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokoYonezawaDepartment of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMegumiKondoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiAkagiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasashiYoshidaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukihiroSaitoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazufumiNakamuraDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, on AAA formation and rupture. <br>
Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE(-)(/)(-) mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). <br>
Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-alpha in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPAR alpha significantly attenuated the anti-oxidative effect of pemafibrate. <br>
Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7632022A Case of Mediastinal Localized Malignant Pleural Mesothelioma Successfully Treated by Chemotherapy and Conversion Surgery343347ENYuhoMakiDepartment of Thoracic Surgery, National Hospital Organization Shikoku Cancer CenterYosukeKiriyamaDepartment of Thoracic Surgery, National Hospital Organization Shikoku Cancer CenterTsuyoshiUenoDepartment of Thoracic Surgery, National Hospital Organization Shikoku Cancer CenterHiroshiSuehisaDepartment of Thoracic Surgery, National Hospital Organization Shikoku Cancer CenterHisayukiShigematsuDepartment of Thoracic Surgery, National Hospital Organization Shikoku Cancer CenterKazuhikoSaekiDepartment of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer CenterDaijiroHaradaDepartment of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer CenterToshiyukiKozukiDepartment of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer CenterNorihiroTeramotoDepartment of Pathology, National Hospital Organization Shikoku Cancer CenterMotohiroYamashitaDepartment of Thoracic Surgery, National Hospital Organization Shikoku Cancer CenterCase Report10.18926/AMO/63746Localized malignant mesothelioma is a rare disease and little is known about its treatment strategy. We herein report a case of localized malignant pleural mesothelioma that had infiltrated into the anterior mediastinum, which was successfully treated using chemotherapy and conversion surgery. A 63-year-old man with a mediastinal tumor was referred to our hospital. Pathologic analysis of the biopsy specimen showed malignant mesothelioma. Significant tumor shrinkage by cisplatin and pemetrexed was observed and he underwent radical surgery via a median sternotomy. The patient has been disease free for 12 months.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7632022A Case of a Solitary Cortical Tuber with No Other Manifestations of Tuberous Sclerosis Complex Mimicking Focal Cortical Dysplasia Type II with Calcification323328ENKakeruHosomotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsuyaSasakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiKawaiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeOkazakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiHyodoDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiShibataDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuSasadaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoYasuharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuhiroKobayashiDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiYanaiDepartment of Diagnostic Pathology,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIsaoDateDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/63742Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7632022Intrathecal Administration of the α1 Adrenergic Antagonist Phentolamine Upregulates Spinal GLT-1 and Improves Mirror Image Pain in SNI Model Rats255263ENKosukeNakatsukaDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshikazuMatsuokaDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakoKuritaKinoshita Pain ClinicRuilinWangDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChikaTsuboiDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobutakaSueDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyujiKakuDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/63719Mirror image pain (MIP) is a type of extraterritorial pain that results in contralateral pain or allodynia. Glutamate transporter-1 (GLT-1) is expressed in astrocytes and plays a role in maintaining low glutamate levels in the synaptic cleft. Previous studies have shown that GLT-1 dysfunction induces neuropathic pain. Our previous study revealed bilateral GLT-1 downregulation in the spinal cord of a spared nerve injury (SNI) rat. We hypothesized that spinal GLT-1 is involved in the mechanism of MIP. We also previously demonstrated noradrenergic GLT-1 regulation. Therefore, this study aimed to investigate the effect of an α1 adrenergic antagonist on the development of MIP. Rats were subjected to SNI. Changes in pain behavior and GLT-1 protein levels in the SNI rat spinal cords were then examined by intrathecal administration of the α1 adrenergic antagonist phentolamine, followed by von Frey test and western blotting. SNI resulted in the development of MIP and bilateral downregulation of GLT-1 protein in the rat spinal cord. Intrathecal phentolamine increased contralateral GLT-1 protein levels and partially ameliorated the 50% paw withdrawal threshold in the contralateral hind paw. Spinal GLT-1 upregulation by intrathecal phentolamine ameliorates MIP. GLT-1 plays a role in the development of MIPs.No potential conflict of interest relevant to this article was reported.歴史学研究会Acta Medica Okayama0386-9237813響きあう声 : オーラル・ヒストリーの可能性 : 「事実」確定と歴史文書 : タイメン鉄道におけるコレラ患者‘射殺’事件を例証に 1729ENTomoyoNakaoOkayama UniversityNo potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1471-230X2212022Endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without Helicobacter pylori infection: a retrospective observational study294ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesChiakiKusumotoDepartment of Gastroenterology, Nippon Kokan Fukuyama HospitalMasahiroNakagawaDepartment of Endoscopy, Hiroshima City HospitalKazuhiroMatsuedaDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalSayoKobayashiDepartment of Internal Medicine, Fukuyama City HospitalMasaoYoshiokaDepartment of Internal Medicine, Okayama Saiseikai General HospitalTomokiInabaDepartment of Gastroenterology, Kagawa Prefectural Central HospitalTatsuyaToyokawaDepartment of Gastroenterology, Fukuyama Medical CenterChihiroSakaguchiDepartment of Endoscopy, National Hospital Organization Shikoku Cancer CenterShouichiTanakaDepartment of Gastroenterology, Iwakuni Clinical CenterTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type have not been fully investigated in relation to Helicobacter pylori infection status. We compared the morphology, color, and location of these lesions between patients with and without H. pylori infection. Methods We retrospectively enrolled 165 patients (180 lesions) from 10 institutions. We divided the patients into the (i) Hp group (patients with current H. pylori infection [active gastritis, n = 13] and those with past infection [inactive gastritis, n = 76]) and (ii) uninfected group (H. pylori-uninfected patients, n = 52). We compared the clinical and endoscopic features of the two groups. We also performed an analysis between (i) lesions with atrophy of the surrounding gastric mucosa (atrophy group) and (ii) lesions without atrophy of the surrounding gastric mucosa (non-atrophy group). Results The average age was older in the Hp group than in the uninfected group (68.1 +/- 8.1 vs. 63.4 +/- 8.7 years, p < 0.01). Although the difference was not statistically significant (p = 0.09), multiple lesions were observed in 9 of 89 patients (10.1%) in the Hp group and in only 1 of 52 patients (1.9%) in the uninfected group. Meanwhile, significant differences were observed in the prevalence of lesions located in the gastric fornix or cardia (uninfected group: 67.3% vs. Hp group: 38.0%, p < 0.01), with an elevated morphology (80.0% vs. 56.0%, p < 0.01), with a subepithelial-like appearance (78.2% vs. 42.0%, p < 0.01), and with a color similar to that of the peripheral mucosa (43.6% vs. 25.0%, p = 0.02). The male-to-female ratio, lesion size, and presence or absence of vascular dilatation or black pigmentation on the surface were not different between the two groups. In the analysis comparing lesions with and without mucosal atrophy, the prevalence of multiple lesions was significantly higher (p = 0.02) in the atrophy group (5/25 patients, 20.0%) than in the non-atrophy group (7/141 patients, 5.0%). Conclusions The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without H. pylori infection.No potential conflict of interest relevant to this article was reported.The Japan Society for Analytical ChemistryActa Medica Okayama0910-63402021Microfluidic Paper-based Analytical Devices Coupled with Coprecipitation Enrichment Show Improved Trace Analysis of Copper Ions in Water SamplesENAbdellahMUHAMMEDCenter for Environmental Science, College of Natural and Computational Sciences, Addis Ababa UniversityAhmedHUSSENCenter for Environmental Science, College of Natural and Computational Sciences, Addis Ababa UniversityTakashiKanetaDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityThe present study was focused on improving sensitivity to trace levels of Cu(II) by subjecting microfluidic paper based analytical devices (μ PADs) to a preconcentration process via coprecipitation using aluminum hydroxide. The experimental conditions were optimized for the pH of the coprecipitation, centrifugation, and amounts of reagents that were deposited onto µ PADs for Cu(II) assay. The resultant limit of detection reached as low as 0.003 mg L 1 with a linear range of 0.01 2.00 mg L 1 . The relative standard deviations for intra and inter day precision were 3.2 and 4.6%, respectively (n = 9). Spiked water samples were analyzed using the μ PADs after coprecipitation preconcentration. The results were verified by comparing them with thos e of inductively coupled plasma optical emission spectrometry (ICP OES). Recoveries ranged from 97.1 104% and from 98.7 105% using the present method and ICP OES, respectively. These results suggest that the simple, highly sensitive, and inexpensive propos ed method would be helpful for analyzing trace levels of Cu(II) in water samples in poorly equipped laboratories.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1742-464X289192022Substrate recognition by Arg/Pro‐rich insert domain in calcium/calmodulin‐dependent protein kinase kinase for target protein kinases59715984ENRikuKaneshigeApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySatomiOhtsukaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYuheiHaradaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityIsseiKawamataDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityMasakiMagariApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNaokiKanayamaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNaoyaHatanoApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHiroyukiSakagamiDepartment of Anatomy, Kitasato University School of MedicineHiroshiTokumitsuApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityCalcium/calmodulin-dependent protein kinase kinases (CaMKKs) activate CaMKI, CaMKIV, protein kinase B/Akt, and AMP-activated protein kinase (AMPK) by phosphorylating Thr residues in activation loops to mediate various Ca2+-signaling pathways. Mammalian cells expressing CaMKK alpha and CaMKK beta lacking Arg/Pro-rich insert domain (RP-domain) sequences showed impaired phosphorylation of AMPK alpha, CaMKI alpha, and CaMKIV, whereas the autophosphorylation activities of CaMKK mutants remained intact and were similar to those of wild-type CaMKKs. Liver kinase B1 (LKB1, an AMPK kinase) complexed with STRAD and MO25 and was unable to phosphorylate CaMKI alpha and CaMKIV; however, mutant LKB1 with the RP-domain sequences of CaMKK alpha and CaMKK beta inserted between kinase subdomains II and III acquired CaMKI alpha and CaMKIV phosphorylating activity in vitro and in transfected cultured cells. Furthermore, ionomycin-induced phosphorylation of hemagglutinin (HA)-CaMKI alpha at Thr177, HA-CaMKIV at Thr196, and HA-AMPK alpha at Thr172 in transfected cells was significantly suppressed by cotransfection of kinase-dead mutants of CaMKK isoforms, but these dominant-negative effects were abrogated with RP-deletion mutants, suggesting that sequestration of substrate kinases by loss-of-function CaMKK mutants requires the RP-domain. This was confirmed by pulldown experiments that showed that dominant-negative mutants of CaMKK alpha and CaMKK beta interact with target kinases but not RP-deletion mutants. Taken together, these results clearly indicate that both CaMKK isoforms require the RP-domain to recognize downstream kinases to interact with and phosphorylate Thr residues in their activation loops. Thus, the RP-domain may be a promising target for specific CaMKK inhibitors.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2041-17231312022Structural basis for different types of hetero-tetrameric light-harvesting complexes in a diatom PSII-FCPII supercomplex1764ENRyoNagaoResearch Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama UniversityKojiKatoResearch Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama UniversityMinoruKumazawaGraduate School of Biostudies, Kyoto UniversityKentaroIfukuGraduate School of Agriculture, Kyoto UniversityMakioYokonoInstitute of Low Temperature Science, Hokkaido UniversityTakehiroSuzukiBiomolecular Characterization Unit, RIKEN Center for Sustainable Resource ScienceNaoshiDohmaeBiomolecular Characterization Unit, RIKEN Center for Sustainable Resource ScienceFusamichiAkitaResearch Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama UniversitySeijiAkimotoGraduate School of Science, Kobe UniversityNaoyukiMiyazakiLife Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of TsukubaJian-RenShenResearch Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama UniversityFucoxanthin chlorophyll (Chl) a/c-binding proteins (FCPs) function as light harvesters in diatoms. The structure of a diatom photosystem II-FCPII (PSII-FCPII) supercomplex have been solved by cryo-electron microscopy (cryo-EM) previously; however, the FCPII subunits that constitute the FCPII tetramers and monomers are not identified individually due to their low resolutions. Here, we report a 2.5 angstrom resolution structure of the PSII-FCPII supercomplex using cryo-EM. Two types of tetrameric FCPs, S-tetramer, and M-tetramer, are identified as different types of hetero-tetrameric complexes. In addition, three FCP monomers, m1, m2, and m3, are assigned to different gene products of FCP. The present structure also identifies the positions of most Chls c and diadinoxanthins, which form a complicated pigment network. Excitation-energy transfer from FCPII to PSII is revealed by time-resolved fluorescence spectroscopy. These structural and spectroscopic findings provide insights into an assembly model of FCPII and its excitation-energy transfer and quenching processes. Fucoxanthin chlorophyll a/c-binding proteins (FCPs) harvest light energy in diatoms. The authors analyzed a structure of PSII-FCPII supercomplex at high resolution by cryo-EM, which identified each FCP subunit and pigment network in the supercomplex.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7622022Retrospective Cohort Study of Clinical Efficacy and Safety of Cefozopran for Treating Febrile Neutropenia during Chemotherapy in Patients with Lung Cancer167172ENTsukasaHigashionnaDepartment of Pharmacy, Okayama University HospitalSoichiroUshioDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalKiminakaMurakawaDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalOriginal Article10.18926/AMO/63410Febrile neutropenia (FN) is a serious side effect in patients undergoing cancer chemotherapy and frequently proves fatal. Since infection control is crucial in the management of FN, the antimicrobial agent cefozopran (CZOP) has been recommended but not approved for routine use in clinical care of FN in Japan. However, few studies of CZOP in the management of FN have used a thrice daily dose schedule. The aim of this study was to retrospectively compare the efficacy and safety of CZOP at a dose of 1 g three times daily to those of cefepime (CFPM) in the treatment of FN in our lung cancer patients. The response rates of the CZOP and CFPM groups were 89.5% (17/19 cases) and 83.0% (39/47 cases), respectively, with no significant difference between the two groups. The median duration of antimicrobial treatment was 6 days (4-10 days) in the CZOP group and 7 days (3-13 days) in the CFPM group, with no significant difference between groups. The incidence rates of adverse events were 21.1% (4/19 cases) in the CZOP group and 19.1% (9/47 cases) in the CFPM group. No adverse events of Grade 3 or higher were observed in either group. The findings of the present study suggest that CZOP administration at a dose of 1 g three times per day as an antimicrobial treatment alternative against FN.No potential conflict of interest relevant to this article was reported.岡山大学大学院社会文化科学研究科Acta Medica Okayama1881-1671532022「すればいい」を述語にする文のモーダルな意味3756ENSeiryuMiyagi10.18926/63387No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221212022Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways4819ENHiroyukiMiyaharaDepartment of Pediatrics, Okayama University HospitalKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalMasatoYashiroDepartment of Pediatrics, Okayama University HospitalToshiakiOharaDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesUnder normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of beta-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS.No potential conflict of interest relevant to this article was reported.岡山大学教師教育開発センターActa Medica Okayama2186-1323122022令和３年度「工業科教育法（応用T，応用U）」の実践報告329341ENSeitaroKobayashiCenter for Teacher Education and Development, Okayama UniversityKyogoAkagiOkayama University Academic Research Institute Education Department (Practice of teaching profession)10.18926/CTED/63317「工業科教育法（応用T，応用U）」は令和３年度に初めて受講生があり，２名の教員で授業を行った。この授業では，学生に教科指導力を身に付けさせるとともに，幅広く工業に関する知識を養うことを目的としている。このため，「何ができるようになるのか」「何を学ぶのか」「どのように学ぶのか」「一人一人の発達をどのように支援するのか」「何が身に付いたのか」「実施するために何が必要か」の６つの観点で，授業をつくり上げる力の育成を目指した。実践報告を通じて成果と課題を明確にし，改善を図ることで来年度以降の授業の充実に繋げたい。No potential conflict of interest relevant to this article was reported.岡山大学教師教育開発センターActa Medica Okayama2186-1323122022日本における病弱教育の発展経緯とその背景 ―養護学校教育義務制の実施をめぐる動向を中心に―4757ENWenhaoLiuShanghai Ouqiao Food Co., Ltd. (Graduated from Okayama University Graduate School of Education)MunehisaYoshitoshiGraduate School of Education, Okayama University10.18926/CTED/63297結核予防を目的として発生した病弱教育の取り組みは，第二次世界大戦の影響により衰退しつつあった。戦後，新たな教育制度の改革により，病弱教育のための養護学校や特殊学級の数も増加傾向を示した。とくに，1979年の養護学校義務教育制により，病弱教育の制度的基盤が確立することになるが，その過程では福祉施設や訪問教育を含む多様な教育の場が展開された。しかし，義務制に至るまでの病弱教育の発展の経緯には，様々な課題の解決が必要であった。義務教育制度の導入はもちろんのこと，養護学校の対象としての病弱児の法的位置づけが遅れた要因として，主に国や地方公共団体の財政上の問題があった。加えて，病弱教育のための学校・学級の具体的な仕組みづくり，対象となる児童生徒の障害の程度，教師の専門性，指導方針・方法が確立されてこなかったことも影響したことが明らかになった。No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0022-22754442003Circulating oxidized LDL forms complexes with β(2)-glycoprotein I: implication as an atherogenic autoantigen716726ENKazukoKobayashiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryMakotoKishiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryTatsuyaAtsumiDepartment of Medicine II, Hokkaido University Graduate School of MedicineMaria L.BertolacciniLupus Research Unit, The Rayne Institute, St. Thomas' Hospital LondonHirofumiMakinoDepartment of Medicine and Clinical Science, Okayama University Graduate School of Medicine and DentistryNobuoSakairiDivision of Bioscience, Graduate School of Environment Earth Science, Hokkaido UniversityItaruYamamotoDepartment of Immunochemistry, Faculty of Pharmaceutical Science, Okayama UniversityTatsujiYasudaDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryMunther A.KhamashtaLupus Research Unit, The Rayne Institute, St. Thomas' Hospital LondonGraham R. V.HughesLupus Research Unit, The Rayne Institute, St. Thomas' Hospital LondonTakaoKoikeDepartment of Medicine II, Hokkaido University Graduate School of MedicineDennis R.VoelkerProgram in Cell Biology, Department of Medicine, National Jewish Medical and Research CenterEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistrybeta(2)-glycoprotein I (beta(2)-GPI) is a major antigen for antiphospholipid antibodies (Abs, aPL) present in patients with antiphospholipid syndrome (APS). We recently reported (I. Lipid Res., 42: 697, 200 1; J Lipid Res., 43: 1486, 2002) that beta(2)-GPI specifically binds to Cu2+-oxidized LDL (oxLDL) and that the beta(2)-GPI ligands are omega-carboxylated 7-ketocholesteryl esters. In the present study, we demonstrate that oxLDL forms stable and nondissociable complexes with beta(2)-GPI in serum, and that high serum levels of the complexes are associated with arterial thrombosis in APS. A conjugated ketone function at the 7-position of cholesterol as well as the omega-carboxyl function of the beta(2)-GPI ligands was necessary for beta(2)-GPI binding. The ligand-mediated noncovalent interaction of beta(2)-GPI and oxLDL undergoes a temperature- and time-dependent conversion to much more stable but readily dissociable complexes in vitro at neutral pH. In contrast, stable and nondissociable beta(2)-GPI-oxLDL complexes were frequently detected in sera from patients with APS and/or systemic lupus erythematodes. Both the presence Of beta(2)-GPI-oxLDL complexes and IgG Abs recognizing these complexes were strongly associated with arterial thrombosis. Further, these same Abs correlated with IgG immune complexes containing beta(2)-GPI or LDL.jlr Thus, the beta(2)-GPI-oxLDL complexes acting as an autoantigen are closely associated with autoimmune-mediated atherogenesis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0022-22754392002ω-Carboxyl variants of 7-ketocholesteryl esters are ligands for β2-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages14861495ENQingpingLiuDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryKazukoKobayashiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryJun-ichiFurukawaDivision of Bioscience, Graduate School of Environment Earth Science, Hokkaido UniversityJunkoInagakiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryNobuoSakairiDivision of Bioscience, Graduate School of Environment Earth Science, Hokkaido UniversityAkimasaIwadoGraduate School of Natural Science and Technology, Okayama UniversityTatsujiYasudaDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryTakaoKoikeDepartment of Medicine II, Hokkaido University Graduate School of MedicineDennis R.VoelkerProgram in Cell Biology, Department of Medicine, National Jewish Medical and Research CenterEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistrybeta(2)-Glycoprotein I (beta(2)-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome. We recently reported that beta(2)-GPI specifically binds to oxidized LDL (oxLDL) and that the beta(2)-GPI's major ligand, oxLig-1 is 7-ketocholesteryl-9-carboxynonanoate (Kobayashi, K, E. Matsuura, Q. P. Liu, J. Furukawa, K. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Welker, and T. Koike. 2001. A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. J Lipid Res. 42: 697-709). In the present study, we demonstrate that omega-carboxylated 7-ketocholesteryl esters are critical for beta(2)-GPI binding. A positive ion mass spectrum of a novel ligand, designated oxLig-2, showed fragmented ions at m/z 383 and 441 in the presence of acetone, which share features of oxLig-1 and 7-ketocholesterol. In the negative ion mode, ions at m/z 627, 625, and 243 were observed. oxLig-2 was most likely 7-ketocholesteryl-12-carboxy (keto) dodecanoate. These ligands were recognized by beta(2)-GPI. Liposome binding to macrophages was significantly increased depending on the ligand's concentration, in the presence of beta(2)-GPI and an anti-beta(2)-GPI Ab. Synthesized variant, 7-ketocholesteryl-13-carboxytxidecanoate (13-COOH-7KC), also showed a significant interaction with beta(2)-GPI and a similar binding profile with macrophages. Methylation of the carboxyl function diminished all of the specific ligand interactions with beta(2)-GPI. Thus, omega-carboxyl variants of 7-ketocholesteryl esters can mediate anti-beta(2)-GPI Ab-dependent uptake of oxLDL by macrophages, and autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7612022Fixed Partial Denture Designed by Combining the Whole 3D Digital Surface Morphology of the Provisional Restoration and Abutment Teeth Surfaces7984ENKanaTokumotoDepartment of Oral Rehabilitation and Implantology, Okayama University HospitalTakuyaMinoDepartment of Oral Rehabilitation and Implantology, Okayama University HospitalYokoKurosakiDepartment of Oral Rehabilitation and Implantology, Okayama University HospitalKojiIzumiSHIKEN CorporationKenjiMaekawaDepartment of Oral Rehabilitation and Implantology, Okayama University HospitalTomohitoNakanoDental Technician Laboratory, Okayama University HospitalJunichiSejimaDental Technician Laboratory, Okayama University HospitalAkihiroUedaDental Technician Laboratory, Okayama University HospitalAyaKimura-OnoDepartment of Oral Rehabilitation and Implantology, Okayama University HospitalTaeHyung KimDental Technician Laboratory, Okayama University HospitalTakuoKubokiDepartment of Oral Rehabilitation and Implantology, Okayama University HospitalCase Report10.18926/AMO/63215We introduce a new digital workflow to fabricate a fixed partial denture (FPD) utilizing the three-dimensional surface morphology of provisional restoration (PR) and abutment teeth. Scanned images of the full maxilla with abutment teeth, full maxilla with PR, and PR alone were superimposed. The surfaces of the final FPD were designed based on the entire morphology of the PR and abutment teeth surfaces. The inner and outer surfaces converged at the margin lines of the abutment teeth. Fine modifications to the final FPD design were performed manually, and the final FPD was fabricated and successfully installed in the patient.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7612022Chidamide and Decitabine in Combination with a HAG Priming Regimen for Acute Myeloid Leukemia with TP53 Mutation6370ENBeiZhangDepartment of Hematology, Jiaozuo People’s HospitalZhixinPeiDepartment of Hematology, Jiaozuo People’s HospitalHongxiaWangDepartment of Hematology, Jiaozuo People’s HospitalHuiminWuDepartment of Hematology, Jiaozuo People’s HospitalJunjieWangDepartment of Hematology, Jiaozuo People’s HospitalJunjunBaiDepartment of Hematology, Jiaozuo People’s HospitalQinglinSongDepartment of Hematology, Jiaozuo People’s HospitalOriginal Article10.18926/AMO/63213We analyzed the treatment effects of chidamide and decitabine in combination with a HAG (homoharringtonine, cytarabine, G-CSF) priming regimen (CDHAG) in acute myeloid leukemia (AML) patients with TP53 mutation. Seven TP53 mutated AML patients were treated with CDHAG. The treatment effects were assessed using hemogram detection and bone marrow aspirate. The possible side effects were evaluated based on both hematological and non-hematological toxicity. Four of the seven patients were classified as having achieved complete remission after CDHAG treatment; one patient was considered to have achieved partial remission, and the remaining two patients were considered in non-remission. The overall response rate (ORR) to CDHAG was 71.4%. Regarding the side effects, the hematological toxicity level of the seven patients ranged from level III to level IV, and infections that occurred at lung, blood, and skin were recorded. Nausea, vomiting, liver injury, and kidney injury were also detected. However, all side effects were attenuated by proper management. The CDHAG regimen clearly improved the ORR (71.4%) of TP53-mutated AML patients, with no severe side effects.No potential conflict of interest relevant to this article was reported.