Springer Acta Medica Okayama 0918-9440 2026 CDPKs as Ca2+ signaling decoders in guard cell signaling EN Izumi C. Mori Institute of Plant Science and Resources, Okayama University Stomatal movements are essential for balancing photosynthetic carbon dioxide uptake with water conservation and defense against pathogens. These processes are controlled by complex signaling networks in guard cells, in which calcium ions (Ca2+) act as a ubiquitous second messenger. Although stimulus-specific Ca2+ signatures have been well documented, how these signals are decoded into distinct physiological responses remains a central question in plant biology. Increasing evidence highlights calcium-dependent protein kinases (CDPKs) as key signal decoders in guard cell signaling. This mini-review summarizes recent advances in our understanding of how CDPKs perceive and translate Ca2+ fluctuations into stomatal responses. We focus on the roles of CDPKs in signaling pathways triggered by diverse stimuli, including phytohormones such as abscisic acid ABA, jasmonates, and salicylic acid, as well as biotic cues such as microbe- or pathogen-associated molecular patterns (MAMPs/PAMPs) and pathogen infection. We also discuss how gaseous signals and metabolic cues are integrated into CDPK-mediated pathways. In addition to their established role as downstream decoders of Ca2+ signals, emerging studies suggest that CDPKs can act upstream of Ca2+ oscillations and may also function through Ca2+-independent mechanisms. Together, these findings highlight the context-dependent and integrative roles of CDPKs in regulating stomatal behavior, contributing to plant fitness under fluctuating environmental conditions. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-7004 74 7 2025 Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages 193 EN Hiroya Kondo Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Kure Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Demiya Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Hata Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Uotani Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshioka Department of Molecular and Cellular Medicine, Tokyo Medical University Toshifumi Ozaki Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osteosarcoma (OS) is the most common malignant tumor of bone in children and adolescents. Although lung metastasis is a major obstacle to improving the prognosis of OS patients, the underlying mechanism of lung metastasis of OS is poorly understood. Tumor-associated macrophages (TAMs) with M2-like characteristics are reportedly associated with lung metastasis and poor prognosis in OS patients. In this study, we investigated the metastasis-associated tumor microenvironment (TME) in orthotopic OS tumor models with non-metastatic and metastatic OS cells. Non-metastatic and metastatic tumor cells derived from mouse OS (Dunn and LM8) and human OS (HOS and 143B) were used to analyze the TME associated with lung metastasis in orthotopic OS tumor models. OS cell-derived secretion factors were identified by cytokine array and enzyme-linked immunosorbent assay (ELISA). Orthotopic tumor models with metastatic LM8 and 143B cells were analyzed to evaluate the therapeutic potential of a neutralizing antibody in the development of primary and metastatic tumors. Metastatic OS cells developed metastatic tumors with infiltration of M2-like TAMs in the lungs. Cytokine array and ELISA demonstrated that metastatic mouse and human OS cells commonly secreted CCL2, which was partially encapsulated in extracellular vesicles. In vivo experiments demonstrated that while primary tumor growth was unaffected, administration of CCL2-neutralizing antibody led to a significant suppression of lung metastasis and infiltration of M2-like TAMs in the lung tissue. Our results suggest that CCL2 plays a crucial role in promoting the lung metastasis of OS cells via accumulation of M2-like TAMs. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-7004 74 7 2025 HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses 192 EN Yuehua Chen Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Hamada Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuze Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Noma Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Tazawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1 alpha, thereby augmenting antitumor effector functions. HIF-1 alpha upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response.<br> Methods The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms.<br> Results HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4+ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8+ T cells.<br> Conclusion Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1435-0211 71 1 2025 Quantitative assessment of adhesive effects on partial and full compressive strength of LVL in the edge-wise direction 19 EN Ryutaro Sudo Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Kohta Miyamoto Forestry and Forest Products Research Institute Hirofumi Ido Forestry and Forest Products Research Institute Laminated 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.

Springer Acta Medica Okayama 1029-8479 2024 12 2024 Elliptic virtual structure constants and generalizations of BCOV-Zinger formula to projective Fano hypersurfaces 135 EN Masao Jinzenji Department of Mathematics, Okayama University Ken Kuwata Department of General Education, National Institute of Technology, Kagawa College In this paper, we propose a method for computing genus 1 Gromov-Witten invariants of Calabi-Yau and Fano projective hypersurfaces using the B-model. Our formalism is applicable to both Calabi-Yau and Fano cases. In the Calabi-Yau case, significant cancellation of terms within our formalism occurs, resulting in an alternative representation of the BCOV-Zinger formula for projective Calabi-Yau hypersurfaces. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-7004 74 3 2025 Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone 96 EN Tomohiko Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Nogi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuki Taniguchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kanto Suemori Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuto Fujita Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression.<br> Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils.<br> Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells.<br> Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 10 1 2024 Gastro-tracheal fistula following esophageal cancer surgery through the retrosternal route: a case report 252 EN Seitaro Nishimura Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuhiro Noma Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kento Kawasaki Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masashi Hashimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuya Kato Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Naoaki Maeda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Tanabe Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuhiro Shirakawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Gastro-tracheal fistula is a rare but serious complication after esophageal surgery, often requiring long-term treatment and invasive procedures. Gastro-tracheal fistula usually occurs through the posterior mediastinal route and rarely through the retrosternal route. No previous reports have described gastro-tracheal fistula after retrosternal route reconstruction was cured by conservative treatment.<br> Case presentation A 70-year-old man with lower thoracic esophageal cancer underwent thoracoscopic esophagectomy in the prone position and gastric tube reconstruction through the retrosternal route with neck anastomosis after neoadjuvant chemotherapy. Despite anastomotic leakage on postoperative day 10, his general condition was stable, and he was managed conservatively with antibiotics and gastric tube decompression. On day 29, he presented with high fever and a gastro-tracheal fistula was observed by esophagography. Conservative management was continued because the patient remained stable. On day 48, esophagography showed that the fistula was undetectable. The patient was able to take fluids orally. He progressed well on an oral diet and was transferred to a different hospital.<br> Conclusions A gastro-tracheal fistula, although rare, can occur after retrosternal route reconstruction. When a patient is stable, gastro-tracheal fistula after retrosternal route reconstruction may be cured by conservative treatment. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 10 1 2024 Primary ileal myeloid sarcoma presenting with bowel obstruction: a case report 229 EN Hitoshi Minagi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nobuhiko Kanaya Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshitaka Kondo Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryohei Shoji Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hajime Kashima Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Matsumi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoru Kikuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Fuminori Teraishi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Kagawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Myeloid sarcoma (MS) is an extramedullary tumor constituted by myeloid blasts or immature myeloid cells. It frequently occurs in conjunction with acute myeloid leukemia (AML); however, it can exceptionally manifest in patients without leukemia. Here, we present a rare case of primary MS originating in the small bowel without evidence of bone marrow involvement.<br> Case representation A 33 year-old female with no relevant medical history was admitted to our hospital with recurrent abdominal pain. Computed tomography (CT) revealed bowel obstruction due to thickening of the ileum wall, which was suspected to be an ileal tumor. Initially, ectopic endometriosis was suspected because of abdominal pain associated with the menstrual cycle and changes observed on a follow-up CT scan. The lesion could not be detected by double-balloon endoscopy. Despite conservative treatment, the obstruction persisted, and laparoscopic partial ileal resection was performed, which revealed extensive involvement of the ileum and mesentery. Additionally, the mesentery of the resected ileum was extremely thickened. Histopathological and immunohistochemical examinations of the surgical specimen indicated ileal MS. Bone marrow aspiration after discharge was negative for cytological findings of leukemia, leading to a final diagnosis of primary ileal MS. Her postoperative course was uneventful, and she is currently undergoing systemic chemotherapy tailored to AML at another hospital.<br> Conclusions Even though MS of the small bowel is rare and may not be considered preoperatively, similar surgical treatment to that of other small bowel malignancies can ensure proper postoperative diagnosis and appropriate chemotherapy. Given the potential need for chemotherapy, ensuring surgical safety that allows for its rapid initiation is critical. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 10 1 2024 Central pancreatectomy of the remnant pancreas without reconstruction after pancreatoduodenectomy 214 EN Kinji Hirono Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Jiro Kimura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background There are several reports on the safety and feasibility of pancreatoduodenectomy (PD) without reconstruction of the small remnant pancreas. However, a few studies have explored central pancreatectomy (CP) for non-reconstructed small remnant pancreases after PD. This study presents a case of CP without pancreatic reconstruction after PD.<br> Case presentation A 58-year-old man with cerebral palsy underwent PD for distal cholangiocarcinoma. Three years postoperatively, a 12-mm tumor was detected in the remnant pancreatic body and diagnosed as a pancreatic neuroendocrine neoplasm. Surgical resection was performed, because the tumor was enlarged and chemotherapy resistant. The afferent loop with pancreatojejunostomy anastomosis was dissected, and CP, including pancreatojejunostomy anastomosis, was performed. Given the remnant pancreas was hard and atrophic, the pancreatic tail was transected using a stapler without reconstructing the small remnant pancreas. The patient experienced no postoperative complications including postoperative pancreatic fistula, and the endocrine function of the pancreas was preserved.<br> Conclusions We present a case of remnant pancreatic CP that did not require reconstruction after PD. Preservation of the small remnant pancreas without reconstruction during CP may be feasible to maintain endocrine function in select patients after PD. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-4034 10 1 2024 Long-term follow-up of a patient with Parkinson's disease under nursing care after replacement of fixed implant-supported prostheses with an implant overdenture: a case report 37 EN Kana Tokumoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Takuya Mino Okayama University Dental School Ikue Tosa Okayama University Dental School Ko Omori Department of Oral Rehabilitation and Regenerative Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Michiyo Yamamoto Dental Clinic, AINOSATO Clinic Kazuki Takaoka Department of Oral and Maxillofacial Surgery, Shiga University of Medical Science Kenji Maekawa Department of Removable Prosthodontics and Occlusion, Osaka Dental University Takuo Kuboki Okayama University Dental School Hiromitsu Kishimoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Background In older patients with progressive neurodegeneration, replacing fixed implant-supported prostheses (FIP) with implant overdentures (IOD) has been proposed to prevent future mucosal injury and create an oral environment that is easier for caregivers to clean. However, there have been no reports on the progress after replacing FIP with IOD. In this report, we present the progress of an older patient with Parkinson’s disease in whom FIP was replaced with IOD.<br> Case presentation An 81-year-old male patient with Parkinson’s disease presented to our outpatient clinic with bruxism and crossbites. FIPs, with five Brånemark system implants, were placed in the bilateral lower molars. The FIP was replaced with an IOD with two locator attachments to create an oral environment that was easier for caregivers to clean and allow easy recovery of masticatory function if residual teeth were fractured in the care environment. As his systemic condition deteriorated, treatment was changed from outpatient to in-home visits. During dental care visits, professional oral cleaning and denture repair were continued, and good nutritional status was maintained. However, the patient developed cholecystitis and was hospitalized. During hospitalization, gastrostomy was performed because he developed aspiration pneumonia. After discharge from the hospital, the patient remained in bed all day and could not wear an IOD, resulting in buccal mucosa ulceration due to abrasion of the locator abutment. We decided to replace the abutment with cover screws; however, not all the implants could sleep submucosally. Although regular oral cleaning was resumed, new ulcers developed even when cover screws were installed. Additionally, swelling and drainage were observed at the peri-implant mucosal site where peri-implantitis had once occurred during an outpatient visit. The patient was readmitted to the hospital for a urinary tract infection, and subsequent visits were abandoned.<br> Conclusions By replacing FIP with IOD in an older patient with Parkinson’s disease, we addressed a barrier to caregiver-provided oral management. The removable prosthesis facilitated smooth oral care by caregivers and functional recovery in the event of trouble with residual teeth. However, it could not completely avoid the recurrence of buccal mucosal ulcers or peri-implantitis. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 10 1 2024 Subtotal esophagectomy and concurrent reconstruction with free jejunal flap for primary esophageal cancer after pancreatoduodenectomy 128 EN Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tasuku Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Pancreatoduodenectomy and subtotal esophagectomy are widely considered the most invasive and difficult surgical procedures in gastrointestinal surgery. Subtotal esophagectomy after pancreatoduodenectomy is expected to be extremely difficult due to complicated anatomical changes, and selecting an appropriate intestinal reconstruction method will also be a difficult task. Therefore, perhaps because the method is considered impossible, there have been few reports of subtotal esophagectomy after pancreatoduodenectomy.<br> Case presentation A 73-year-old man with a history of pancreatoduodenectomy was diagnosed with superficial thoracic esophageal squamous cell carcinoma. Definitive chemoradiation therapy was recommended at another hospital; however, he visited our department to undergo surgery. We performed the robot-assisted thoracoscopic subtotal esophagectomy. There were some difficulties with the reconstruction: the gastric tube could not be used, the reconstruction was long, and the organs reconstructed in the previous surgery had to be preserved. However, the concurrent reconstruction was achieved with the help of a free jejunal flap and vascular reconstruction. All reconstructions from the previous surgery, including the remnant stomach, were preserved via regional abdominal lymph node dissection. After reconstruction, intravenous indocyanine green showed that circulation in the reconstructed intestines was preserved. On postoperative day 1, no recurrent nerve paralysis was observed during laryngoscopy. The patient could start oral intake smoothly 2 weeks after surgery and did not exhibit any postoperative complications related to the reconstruction. The patient was transferred to another hospital on postoperative day 21.<br> Conclusions Owing to the free jejunal flap interposition method, we safely performed one stage subtotal esophagectomy and concurrent reconstruction, preservation of the remnant stomach, and pancreaticobiliary reconstruction in patients with a history of pancreatoduodenectomy. We believe that this method is acceptable and useful for patients undergoing complicated reconstruction. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2090-4762 55 1 2024 Evaluating the index of panoramic X-ray image quality using K-means clustering method 4 EN Satoshi Imajo Division of Radiology, Medical Support Department, Okayama University Hospital Yoshinori Tanabe Faculty of Medicine, Graduate School of Health Sciences, Okayama University Nobue Nakamura Division of Radiology, Medical Support Department, Okayama University Hospital Mitsugi Honda Division of Radiology, Medical Support Department, Okayama University Hospital Masahiro Kuroda Faculty of Medicine, Graduate School of Health Sciences, Okayama University Background A panoramic X-ray image is generally considered optimal when the occlusal plane is slightly arched, presenting with a gentle curve. However, the ideal angle of the occlusal plane has not been determined. This study provides a simple evaluation index for panoramic X-ray image quality, built using various image and cluster analyzes, which can be used as a training tool for radiological technologists and as a reference for image quality improvement.<br> Results A reference panoramic X-ray image was acquired using a phantom with the Frankfurt plane positioned horizontally, centered in the middle, and frontal plane centered on the canine teeth. Other images with positioning errors were acquired with anteroposterior shifts, vertical rotations of the Frankfurt plane, and horizontal left/right rotations. The reference and positioning-error images were evaluated with the cross-correlation coefficients for the occlusal plane profile, left/right angle difference, peak signal-to-noise ratio (PSNR), and deformation vector fields (DVF). The results of the image analyzes were scored for positioning-error images using K-means clustering analysis. Next, we analyzed the correlations between the total score, cross-correlation analysis of the occlusal plane curves, left/right angle difference, PSNR, and DVF. In the scoring, the positioning-error images with the highest quality were the ones with posterior shifts of 1 mm. In the analysis of the correlations between each pair of results, the strongest correlations (r = 0.7–0.9) were between all combinations of PSNR, DVF, and total score.<br> Conclusions The scoring of positioning-error images using K-means clustering analysis is a valid evaluation indicator of correct patient positioning for technologists in training. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2168-8184 15 11 2023 Risk Factors for Anterior Skull Base Injury in Endoscopic Sinus Surgery e49273 EN Seiichiro Makihara Otolaryngology-Head and Neck Surgery, Okayama University Hospital Kensuke Uraguchi Otolaryngology-Head and Neck Surgery, Okayama University Hospital Tomoyuki Naito Otolaryngology-Head and Neck Surgery, Kagawa Rosai Hospital Aiko Shimizu Otolaryngology-Head and Neck Surgery, Okayama University Hospital Aya Murai Otolaryngology-Head and Neck Surgery, Okayama University Hospital Takaya Higaki Otolaryngology-Head and Neck Surgery, Okayama University Hospital Yohei Noda Otolaryngology-Head and Neck Surgery, Fukuyama City Hospital Shin Kariya Otolaryngology, Kawasaki Medical School Mitsuhiro Okano Otolaryngology, School of Medicine, International University of Health and Welfare Mizuo Ando Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Objectives<br> This retrospective study aimed to investigate the relationships between the Keros classification, the Gera classification, the vertical height of the posterior ethmoid roof (ER), and anterior ethmoidal artery (AEA) types in Japanese patients.<br> Methods<br> We investigated the computed tomography (CT) slices of paranasal sinuses (120 sides) of 60 patients; measured the cribriform plate (CP) depth, lateral lamella CP angle (LLCPA), and vertical height of the lateral ER from the hard palate (LERHP) at the coronal plane of the posterior ethmoidal artery (PEA); and reviewed the AEA types, whether floating or non-floating.<br> Results<br> CP depth was positively correlated with LLCPA (r=0.63; p<0.01) and the height of LERHP (r=0.19; p<0.05). The height of the LERHP in females was significantly lower than that in males. With increased CP depth, floating AEAs became prevalent (p<0.001).<br> Conclusion<br> In females, low height of the posterior ethmoid sinus roof, where cerebrospinal fluid (CSF) leaks occurred while penetrating the basal lamella, often existed; the heights positively correlated with the Keros classification in Japanese patients. The Keros and Gera classifications, AEA type, and posterior ER height do not individually constitute a complete risk assessment but may correlate, preventing major complications, such as CSF leak and orbital hemorrhage. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2730-6011 14 1 2023 Geriatric nutritional risk index as a prognostic marker of first-line immune checkpoint inhibitor combination therapy in patients with renal cell carcinoma: a retrospective multi-center study 204 EN Shogo Watari Department of Urology, National Hospital Organization Okayama Medical Center Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Shiraishi Department of Urology, National Hospital Organization Okayama Medical Center Moto Tokunaga Department of Urology, National Hospital Organization Okayama Medical Center Risa Kubota Department of Urology, National Hospital Organization Okayama Medical Center Norihiro Kusumi Department of Urology, National Hospital Organization Okayama Medical Center Takaharu Ichikawa Department of Urology, National Hospital Organization Okayama Medical Center Tomoyasu Tsushima Department of Urology, National Hospital Organization Okayama Medical Center Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose This study aimed to investigate the effectiveness of the Geriatric Nutritional Risk Index (GNRI) in predicting the efficacy of first-line immune checkpoint inhibitor (ICI) combination therapy for metastatic or unresectable renal cell carcinoma (RCC) and associated patient prognosis.<br> Methods A retrospective study was conducted using data from 19 institutions. The GNRI was calculated using body mass index and serum albumin level, and patients were classified into two groups using the GNRI values, with 98 set as the cutoff point.<br> Results In all, 119 patients with clear cell RCC who received first-line drug therapy with ICIs were analyzed. Patients with GNRI >= 98 had significantly better overall survival (OS) (p = 0.008) and cancer-specific survival (CSS) (p = 0.001) rates than those with GNRI < 98; however, progression-free survival (PFS) did not differ significantly. Inverse probability of treatment weighting analysis showed that low GNRI scores were significantly associated with poor OS (p = 0.004) and CSS (p = 0.015). Multivariate analysis showed that the Karnofsky performance status (KPS) score was a better predictor of prognosis (OS; HR 5.17, p < 0.001, CSS; HR 4.82, p = 0.003) than GNRI (OS; HR 0.36, p = 0.066, CSS; HR 0.35, p = 0.072). In a subgroup analysis of patients with a good KPS and GNRI >= 98 vs < 98, the 2-year OS rates were 91.4% vs 66.9% (p = 0.068), 2-year CSS rates were 91.4% vs 70.1% (p = 0.073), and PFS rates were 39.7% vs 21.4 (p = 0.27), respectively.<br> Conclusion The prognostic efficiency of GNRI was inferior to that of the KPS score at the initiation of the first-line ICI combination therapy for clear cell RCC. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-4034 9 1 2023 Accuracy of a novel modified single computed tomography scanning method for assisting dental implant placement: a retrospective observational study 42 EN Hiroaki Shimizu Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Mino Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Kurosaki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikaru Arakawa Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kana Tokumoto Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aya Kimura-Ono Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Maekawa Department of Remov‑ able Prosthodontics and Occlusion, Osaka Dental University Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose　The aim of this study is to compare dental implant placement accuracy of three surgical guide fabrication methods: single (SCT) and double computed tomography (DCT), and a newly developed modified SCT (MSCT) scan method.<br> Methods　A total of 183 cases (183 surgical guides, and 485 implants) of static-guide-assisted implant placement surgery using the SCT, DCT, or MSCT methods in a dental clinic were included in the study. Three-dimensional (3D) deviations (mm) at the entry and tip of the implant body between preoperative simulation and actual placement were measured as surrogate endpoints of implant placement accuracy. The following survey details were collected from medical records and CT data: sex, age at implant placement surgery, surgical guide fabrication method, number of remaining teeth, implant length, implant location, alveolar bone quality, and bone surface inclination at implant placement site in preoperative simulation, etc. Risk factors for reducing implant placement accuracy were investigated using generalized estimating equations.<br> Results　The SCT and DCT methods (odds ratios [ORs] vs. MSCT method: 1.438, 1.178, respectively), posterior location (OR: 1.114), bone surface buccolingual inclination (OR: 0.997), and age at implant placement surgery (OR: 0.995) were significant risk factors for larger 3D deviation at the entry; the SCT (OR: 1.361) and DCT methods (OR: 1.418), posterior location (OR: 1.190), implant length (OR: 1.051), and age at implant placement surgery (OR: 0.995) were significant risk factors for larger 3D deviation at the tip of the implant body.<br> Conclusions　Implant placement accuracy was better using the MSCT method compared to the SCT and DCT methods. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2199-4536 10 1 2023 Data-driven evolutionary computation for service constrained inventory optimization in multi-echelon supply chains 825 846 EN Ziang Liu Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tatsushi Nishi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Supply chain digital twin has emerged as a powerful tool in studying the behavior of an actual supply chain. However, most studies in the field of supply chain digital twin have only focused on what-if analysis that compares several different scenarios. This study proposes a data-driven evolutionary algorithm to efficiently solve the service constrained inventory optimization problem using historical data that generated by supply chain digital twins. The objective is to minimize the total costs while satisfying the required service level for a supply chain. The random forest algorithm is used to build surrogate models which can be used to estimate the total costs and service level in a supply chain. The surrogate models are optimized by an ensemble approach-based differential evolution algorithm which can adaptively use different search strategies to improve the performance during the computation process. A three-echelon supply chain digital twin on the geographic information system (GIS) map in real-time is used to examine the efficiency of the proposed method. The experimental results indicate that the data-driven evolutionary algorithm can reduce the total costs and maintain the required service level. The finding suggests that our proposed method can learn from the historical data and generate better inventory policies for a supply chain digital twin. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 9 1 2023 Adenocarcinoma arising from widespread heterotopic gastric mucosa in the cervicothoracic esophagus: a case report 132 EN Shohei Nogi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Surgery, Hiroshima City Hiroshima Citizens Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background　In Japan, about 6% of esophageal cancers are adenocarcinomas, although most of them arise from Barrett's epithelium. Adenocarcinoma arising from heterotopic gastric mucosa (HGM) is very rare. Due to its rarity, there is no unified view on its treatment strategy and prognosis.<br> Case presentation　A 57-year-old man presented with a protruding lesion in the cervicothoracic esophagus that was detected by an upper gastrointestinal series at a medical checkup. Esophagoscopy revealed a 30 mm Type 1 tumor circumferentially surrounded by widespread HGM. Computed tomography (CT) and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed no metastasis or invasion of the surrounding organs. We diagnosed the lesion as cT2N0M0 cStageIIB [Union for International Cancer Control (UICC) 8th Ed] cancer and performed subtotal esophagectomy with three-field lymph node dissection. The tumor was determined to be a well-differentiated adenocarcinoma arising from HGM, with deep invasion of the submucosa. The patient underwent no adjuvant therapy and has currently survived without any evidence of recurrence for 15 months.<br> Conclusions　Although the treatment for adenocarcinoma arising from HGM is basically the same as that for squamous cell carcinoma (SCC) of the esophagus, it is important to determine the treatment strategy based on the characteristics of the adenocarcinoma arising from HGM. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2168-8184 15 5 2023 Collagenous Colitis in a Patient With Gastric Cancer Who Underwent Chemotherapy e39466 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Hospital Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shoko Inoo Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Herein, we present a case of collagenous colitis in a patient who underwent chemotherapy for gastric cancer, comprising five cycles of S-1 plus oxaliplatin and trastuzumab, followed by five cycles of paclitaxel and ramucirumab and seven cycles of nivolumab. The subsequent initiation of trastuzumab deruxtecan chemotherapy led to the development of grade 3 diarrhea after the second cycle of treatment. Collagenous colitis was diagnosed via colonoscopy and biopsy. The patient's diarrhea improved following the cessation of lansoprazole. This case highlights the importance of considering collagenous colitis as a differential diagnosis, in addition to chemotherapy-induced colitis and immune-related adverse event (irAE) colitis, in patients with similar clinical presentations. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2168-8184 15 5 2023 Laparoscopic Surgical Options as a Minimally Invasive Procedure for a Patient With Recurrent Postoperative Pain in Anterior Cutaneous Nerve Entrapment Syndrome: A Case Report e39366 EN Yoshitaka Kondo Sr. Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences This report presents a case of a 70-year-old woman who developed anterior cutaneous nerve entrapment syndrome (ACNES) three years ago and had an anterior cutaneous neurectomy in the left Th10 region. Postoperatively, the pain had improved entirely, but 10 weeks later, she developed a recurrence in the vicinity of the wound. The anterior intercostal nerve branch (Th10), located between the transversus abdominis and internal oblique muscles, was dissected laparoscopically six months after the initial surgery. There was no re-recurrence of pain for four months postoperatively. The postoperative recurrence of ACNES was refractory to various treatments, including surgical neurectomy, and is often difficult to treat. In cases in which transversus abdominis plane block is effective, laparoscopic neurectomy through an intraperitoneal approach may be effective, and minimally invasive laparoscopic treatment may be an effective surgical option for patients with recurrent and refractory ACNES who have a low pain threshold and are prone to prolonged complaints due to wound pain. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 9 1 2023 Safe and curative modified two-stage operation for T4 esophageal cancer after definitive chemoradiotherapy: a case report 119 EN Tasuku Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background　The prognosis of esophageal cancer (EC) with organ invasion is extremely poor. In these cases, definitive chemoradiotherapy (CRT) followed by salvage surgery can be planned; however, the issue of high morbidity and mortality rates persists. Herein, we report the long-term survival of a patient with EC and T4 invasion who underwent a modified two-stage operation after definitive CRT.<br> Case presentation　A 60-year-old male presented with type 2 upper thoracic EC with tracheal invasion. First, definitive CRT was performed, which resulted in tumor shrinkage and improvement in the tracheal invasion. However, an esophagotracheal fistula subsequently developed, and the patient was treated with fasting and antibiotics. Although the fistula recovered, severe esophageal stenoses made oral intake impossible. To improve quality of life and cure the EC, a modified two-stage operation was planned. In the first surgery, an esophageal bypass was performed using a gastric tube with cervical and abdominal lymph node dissections. After confirming improved nutritional status and absence of distant metastasis, the second surgery was performed with subtotal esophagectomy, mediastinal lymph node dissection, and tracheobronchial coverage of the fistula. The patient discharged without major complications after radical resection and has been recurrence-free for 5 years since the start of treatment.<br> Conclusion　A standard curative strategy could be difficult for EC with T4 invasion due to differences in the invaded organs, presence of complications, and patient condition. Therefore, patient-tailored treatment plans are needed, including a modified two-stage operation. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2168-8184 15 4 2023 Laparoscopic and Endoscopic Cooperative Surgery for Gastric Submucosal Tumor Near Esophagogastric Junction With Sliding Hiatal Hernia e37902 EN Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The usefulness of laparoscopic and endoscopic cooperative surgery (LECS) for gastric submucosal tumors in the cardiac region has been reported in recent years. However, LECS for submucosal tumors at the esophagogastric junction with hiatal sliding esophageal hernia has not been reported, and its validity as a treatment method is unknown. The patient was a 51-year-old man with a growing submucosal tumor in the cardiac region. Surgical resection was indicated because a definitive diagnosis of the tumor was not determined. The lesion was a luminal protrusion tumor, located on the posterior wall of the stomach 20 mm from the esophagogastric junction, and had a maximum diameter of 16.3 mm on endoscopic ultrasound examination. Because of the hiatal hernia, the lesion could not be detected from the gastric side by endoscopy. Local resection was considered to be feasible because the resection line did not extend into the esophageal mucosa and the resection site could be less than half the circumference of the lumen. The submucosal tumor was resected completely and safely by LECS. The tumor was diagnosed as a gastric smooth muscle tumor finally. Nine months after surgery, a follow-up endoscopy showed reflux esophagitis. LECS was a useful technique for submucosal tumors of the cardiac region with hiatal hernia, but fundoplication might be considered for preventing backflow of gastric acid. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2196-4092 10 1 2023 Absence of Cretaceous hairpin in the apparent polar wander path of southwest Japan: consistency in paleomagnetic pole positions 21 EN Koji Uno Department of Earth Sciences, Okayama University Honoka Ohara Department of Earth Sciences, Okayama University Kuniyuki Furukawa Faculty of Business Administration, Aichi University Tatsuo Kanamaru Department of Earth and Environmental Sciences, Nihon University To test the hypothesis that a Cretaceous hairpin turn is absent in the apparent polar wander path (APWP) of the inner arc of southwestern Japanese island (southwest Japan), we refined a mid-Cretaceous (100 Ma) paleomagnetic pole from southwest Japan. Red mudstone samples from the 100 Ma Hayama Formation were collected for paleomagnetic analysis from eight sites in the Hayama area in the central part of southwest Japan. A high-temperature remanent magnetization component carried by hematite was isolated from these sites and was found to be of primary mid-Cretaceous origin. The primary nature of the magnetization is supported by the detrital character of the magnetic carrier. The primary directions provided a paleomagnetic pole (35.0 degrees N, 209.6 degrees E, A(95) = 6.1 degrees, N = 8), which represented southwest Japan at 100 Ma. This pole falls into a cluster of Cretaceous poles in southwest Japan. An APWP for southwest Japan between 110 and 70 Ma was updated to ascertain the stationarity of the pole positions for this region. Therefore, it is unlikely that the APWP for southwest Japan experienced a hairpin turn during the Cretaceous. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2168-8184 15 2 2023 A Seat Belt Injury Causing a Large Breast Hematoma: A Case Report e35440 EN Shunki Yamamoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Kosaki Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takenori Uehara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seat belts with shoulder restraints have decreased the frequency of life-threatening severe chest trauma caused by car accidents. However, the introduction of seat belt legislation has led to an increase in a specific pattern of blunt trauma known as seat belt syndrome, which includes rib, clavicle, spine, and sternum fractures, as well as rupture of hollow pelvic and abdominal viscera, mesenteric tears, and major vessel injuries. The shoulder restraint part of the three-point seat belt commonly rests near or over the female and male breast. A 54-year-old female presented to our emergency department complaining of swelling and pain in her left breast immediately after a traffic accident. The patient had used a seat belt with a shoulder restraint. Bruising was noted along her chest where there had been seat belt contact. Her breast hematoma was most likely caused by breast tissue compression between her rib and the seat belt. Contrast-enhanced computed tomography demonstrated a sizable breast hematoma with active arterial contrast material extravasation, as well as multiple left rib fractures. The patient was conservatively treated with analgesic and anti-inflammatory drugs. Complete resolution was achieved, and her breast returned to its normal appearance. Although endovascular treatment and surgical hemostasis have been proposed for the treatment of breast injuries with active bleeding, conservative treatment such as compression hemostasis may be feasible. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2363-9024 9 1 2023 Therapeutic plasma exchange in postpartum HELLP syndrome: a case report 9 EN Nana Kojima Department of Anesthesiology and Resuscitology, Okayama University Hospital Kosuke Kuroda Department of Anesthesiology and Resuscitology, Okayama University Hospital Makiko Tani Department of Anesthesiology and Resuscitology, Okayama University Hospital Tomoyuki Kanazawa Department of Anesthesiology and Resuscitology, Okayama University Hospital Kazuyoshi Shimizu Department of Anesthesiology and Resuscitology, Okayama University Hospital Jota Maki Department of Obstetrics and Gynecology, Okayama University Hospital Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Hospital Hiroshi Morimatsu Department of Obstetrics and Gynecology, Okayama University Hospital BackgroundPostpartum hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is more difficult to treat than HELLP syndrome during pregnancy. We describe a case of postpartum HELLP syndrome that responded to plasma exchange (PE) therapy.Case presentationA 30-year-old primipara woman was hospitalized for gestational hypertension at 33 weeks of gestation and underwent an emergent cesarean section at 36 weeks and 6 days of gestation due to rapidly progressing pulmonary edema. After delivery, liver dysfunction and a rapid decrease in platelet count were observed, and the patient was diagnosed with severe HELLP syndrome. She experienced multiple organ failure despite intensive care, and PE therapy was initiated. Her general condition dramatically stabilized within a few hours of PE therapy.ConclusionIt is controversial whether PE therapy should be used primarily in the management of HELLP syndrome, but early initiation of PE therapy could be effective for severe HELLP syndrome. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2363-9024 9 1 2023 Anesthetic management of a patient with Osler-Weber-Rendu syndrome with multiple pulmonary arteriovenous malformations and pheochromocytoma for femoral artificial bone replacement: a case report 6 EN Toshiharu Hiyoshi Department of Anesthesiology and Resuscitology, Okayama University Hospital Kazuyoshi Shimizu Department of Anesthesiology and Resuscitology, Okayama University Hospital Satoshi Kimura Department of Anesthesiology and Resuscitology, Okayama University Hospital Toshiki Naritani Department of Anesthesiology and Resuscitology, Okayama University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Hospital Background<br> Osler-Weber-Rendu syndrome is characterized by mucocutaneous telangiectasia and arteriovenous malformations in organs. Anesthesia for patients with Osler-Weber-Rendu syndrome is challenging due to complications and physiological changes.<br><br> Case presentation<br> The case was a 49-year-old female with Osler-Weber-Rendu syndrome, multiple pulmonary arteriovenous malformations and pheochromocytoma who presented for femoral bone head fracture with metastatic adenocarcinoma. The patient was scheduled to undergo bone tumor resection and artificial bone replacement, being positioned laterally with a planned operation duration of 5 h. Anesthesia was managed with spinal and epidural anesthesia, combined with sedation by sevoflurane using a supraglottic airway (SGA) device under spontaneous breathing. Her intraoperative and postoperative courses were uneventful.<br><br> Conclusion<br> Neuraxial anesthesia combined with general anesthesia using an SGA device to maintain spontaneous ventilation in order to minimize the risk of rupture of pulmonary arteriovenous malformations could be an option. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2191-0855 12 1 2022 Efficient depolymerization of polyethylene terephthalate (PET) and polyethylene furanoate by engineered PET hydrolase Cut190 134 EN Fusako Kawai Graduate School of Environmental and Life Sciences, Okayama University Yoshitomo Furushima Toray Research Center, Inc Norihiro Mochizuki Toray Research Center, Inc Naoki Muraki Toray Research Center, Inc Mitsuaki Yamashita Faculty of Agriculture, Kindai University Akira Iida Faculty of Agriculture, Kindai University Rie Mamoto Division of Clinical Nutrition, Faculty of Nutrition, Kobe Gakuin University Takehiko Tosha RIKEN SPring-8 Center Ryo Iizuka Graduate School of Science, The University of Tokyo Sakihito Kitajima Graduate School of Science and Technology, Kyoto Institute of Technology The enzymatic recycling of polyethylene terephthalate (PET) can be a promising approach to tackle the problem of plastic waste. The thermostability and activity of PET-hydrolyzing enzymes are still insufficient for practical application. Pretreatment of PET waste is needed for bio-recycling. Here, we analyzed the degradation of PET films, packages, and bottles using the newly engineered cutinase Cut190. Using gel permeation chromatography and high-performance liquid chromatography, the degradation of PET films by the Cut190 variant was shown to proceed via a repeating two-step hydrolysis process; initial endo-type scission of a surface polymer chain, followed by exo-type hydrolysis to produce mono/bis(2-hydroxyethyl) terephthalate and terephthalate from the ends of fragmented polymer molecules. Amorphous PET powders were degraded more than twofold higher than amorphous PET film with the same weight. Moreover, homogenization of post-consumer PET products, such as packages and bottles, increased their degradability, indicating the importance of surface area for the enzymatic hydrolysis of PET. In addition, it was required to maintain an alkaline pH to enable continuous enzymatic hydrolysis, by increasing the buffer concentration (HEPES, pH 9.0) depending on the level of the acidic products formed. The cationic surfactant dodecyltrimethylammonium chloride promoted PET degradation via adsorption on the PET surface and binding to the anionic surface of the Cut190 variant. The Cut190 variant also hydrolyzed polyethylene furanoate. Using the best performing Cut190 variant (L136F/Q138A/S226P/R228S/D250C-E296C/Q123H/N202H/K305del/L306del/N307del) and amorphous PET powders, more than 90 mM degradation products were obtained in 3 days and approximately 80 mM in 1 day. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 8 1 2022 A case of esophageal atresia with the bronchial-like lower esophagus which originates from the left lower lobe bronchus 156 EN Terutaka Tanimoto Department of Pediatric Surgery, Okayama University Hospital Takuo Noda Department of Pediatric Surgery, Okayama University Hospital Reisuke Imaji Department of Pediatric Surgery, Hiroshima City Hiroshima Citizens Hospital Hiroshi Nouso Department of Pediatric Surgery, Okayama University Hospital Background Esophageal atresia with or without a trachea-esophageal fistula occurs due to the failure of separation or incomplete development of the foregut. Therefore, esophageal atresia is often associated with various forms of tracheobronchial anomalies. We report an extremely rare case of esophageal atresia. Case presentation A female infant was born at 37 weeks of gestation and weighed 2596 g. A diagnosis of esophageal atresia and total anomalous pulmonary vein return type III were confirmed. The infant had respiratory distress that required tracheal intubation and ventilatory support soon after birth. Temporary banding of the gastroesophageal junction and gastrostomy were performed on the second day of life. However, her respiratory condition deteriorated due to atelectasis of the left lung and compensatory hyperinflation of the right lung. Preoperative examinations showed the unilobe and atelectatic left lung. The trachea was trifurcated in three directions, and the branch that was expected to be the left main bronchus was blind-ended. The dorsal branch was cartilaginous and bifurcated into the left lower lobe bronchus and lower esophagus approximately 1 cm distal from the tracheal trifurcation. The cartilaginous tissue continued to the lower esophagus. The diagnosis of esophageal atresia with the lower esophagus which originated from the left lower lobe bronchus was made. Esophageal atresia repair was performed when the patient was 4 months of age. The esophagus was dissected distally to the bifurcation of the left lower lobe bronchus via right thoracotomy. The lower esophagus was bronchial-like in appearance, transitioning to the normal esophageal wall approximately 7 mm distal to the transected edge. The cartilage tissue was completely resected during surgery, and a primary end-to-end anastomosis of the esophagus was successfully performed. Histopathological findings revealed that the extracted specimen was surrounded by tracheal cartilage and that the inner surface was covered by stratified squamous epithelium that originated from the esophagus. Conclusions In cases of esophageal atresia with an atypical clinical presentation, there may be unique structural abnormalities of the foregut. We emphasize the importance of a preoperative surgical planning since an inadequate operation can lead to fatal complications. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 8 1 2022 Verrucous carcinoma of the esophagus with complete response after chemoradiotherapy 128 EN Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Sakurama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background : Verrucous carcinoma of the esophagus (VCE) is a rare tumor that is difficult to diagnose. In most cases, biopsies show nonspecific inflammatory and hyperkeratotic changes and do not show malignant findings. Most VCEs are slowly growing, locally advanced tumors with few metastases. Treatments for VCE are the same as for normal esophageal cancer, involving combined chemotherapy, surgical resection, and radiation therapy. However, it has been reported that VCE has a poor response to radiation or chemoradiotherapy (CRT). A case of VCE with complete response (CR) after CRT is presented. <br> Case presentation : A 70-year-old man was found to have white, irregular esophageal mucosa 4 years earlier. He had been followed up as an outpatient as having candidal esophagitis. However, his tumor grew gradually, and biopsy was performed by endoscopic mucosal resection (EMR). He was finally diagnosed with VCE. He had no metastases to distant organs, but some lymph node metastases were suspected. The tumor invaded his left bronchus. The esophagostomy and gastrostomy were constructed as emergent procedures. The patient then underwent definitive CRT. 4 weeks after the end of CRT, two-stage esophagectomy was performed. First, he underwent esophagectomy with thoracic lymph node dissection. A latissimus dorsi flap was patched to the bronchus after primary suture of the hole. 6 weeks later, reconstruction of the gastric tube was performed through the antethoracic route. The pathological findings showed CR to CRT, with no proliferative cancer cells in the specimen. The patient has had no recurrence for three and half years after the resection. <br> Conclusions : We presented a locally advanced VCE that achieved CR to CRT. In cases that have some difficulty for local resection, CRT might be an appropriate treatment for VCE. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2363-9024 8 1 2022 Temporary hypotension and ventilation difficulty during endoscopic injection sclerotherapy for esophageal varices in a child with Fontan circulation: a case report 48 EN Nanako Yasutomi Department of Anesthesiology, Japanese Red Cross Kobe Hospital Tatsuhiko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Hospital Tomoyuki Kanazawa Department of Anesthesiology and Resuscitology, Okayama University Hospital Kazuyoshi Shimizu Department of Anesthesiology and Resuscitology, Okayama University Hospital Tatsuo Iwasaki Department of Anesthesiology and Resuscitology, Okayama University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Hospital Background : Endoscopic procedures are rarely performed in children with congenital heart disease (CHD); therefore, the associated complications are unknown. We report an abrupt change in circulatory and respiratory condition during endoscopic injection sclerotherapy for esophageal varices. <br> Case presentation : A 9-year-old boy with a history of total anomalous pulmonary venous connection (TAPVC) repair and Fontan procedure for asplenia and a single ventricle with TAPVC underwent endoscopic injection sclerotherapy under general anesthesia for esophageal varices. Systolic blood pressure decreased from 70 to 50 mmHg following a sclerosant injection; a second injection reduced his peripheral oxygen saturation from 93 to 79% secondary to ventilation difficulty. Although we suspected anaphylaxis intraoperatively, postoperative imaging suggested that balloon dilation performed to prevent sclerosing agent leakage caused compression of the pulmonary venous chamber and trachea owing to the anomalous intrathoracic organ anatomy.<br> Conclusion : Thorough understanding of the complex anatomy is important before performing endoscopic procedures in children with CHD to preoperatively anticipate possible intraoperative complications and select the optimal therapeutic approach and anesthesia management. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 8 1 2022 Surgical resection of mixed neuroendocrine-non-neuroendocrine neoplasm in the biliary system: a report of two cases 38 EN Ayano Tamaki Center for Graduate Medical Education, Okayama University Hospital Yuma Tani Department of Gastroenterological Surgery, Okayama University Hospital Hiroki Sato Department of Gastroenterological Surgery, Okayama University Hospital Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Hospital Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Takashi Kuise Department of Gastroenterological Surgery, Okayama University Hospital Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Hospital Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Hospital Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Hospital Kenjiro Kumano Department of Gastroenterological Surgery, Okayama University Hospital Kosei Takagi Department of Gastroenterological Surgery, Okayama University Hospital Takahito Yagi Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Background Mixed neuroendocrine-non-neuroendocrine neoplasm (MINEN) is a rare disease and there is scarce literature on its diagnosis, treatment, and prognosis. We encountered two unusual cases of MINEN in the biliary tract, one in the ampulla of Vater and the other in the distal bile duct. In this report, we describe the clinical course of these two cases in detail. Case presentation Case 1: A 69-year-old woman presented with a chief complaint of epigastric pain. When endoscopic sphincterotomy and retrograde biliary drainage were performed for gallstone pancreatitis, an ulcerated lesion was found in the ampulla of the Vater. Based on the biopsy results, the lesion was diagnosed as the ampulla of Vater carcinoma and subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed. Postoperative histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, consistent with the diagnosis of MINEN. In addition, lymph node metastasis was found on the dorsal side of the pancreas and the metastatic component was adenocarcinoma. Adjuvant chemotherapy with etoposide and cisplatin was administered for 6 months, and presently the patient is alive without recurrence 64 months after surgery. Case 2: A 79-year-old man presented with a chief complaint of anorexia. Cholangiography showed severe stenosis of the distal bile duct. A biopsy was conducted from the stenotic lesion and it revealed the lesion to be adenocarcinoma. A diagnosis of distal bile duct carcinoma was made, and SSPPD was performed. Histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, and the tumor was confirmed as MINEN of the distal bile duct. No adjuvant chemotherapy was administered due to the poor performance status. 7 months later, the patient was found to have a liver metastasis. Conclusion We experienced two valuable cases of biliary MINEN. To identify better treatments, it is important to consider the diversity of individual cases and to continue sharing a variety of cases with different presentations. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 313 2021 Physical Memory Management with Two Page Sizes in Tender OS 238 248 EN Koki Kusunoki Graduate School of Natural Science and Technology, Okayama University Toshihiro Yamauchi Graduate School of Natural Science and Technology, Okayama University Hideo Taniguchi Graduate School of Natural Science and Technology, Okayama University Physical memory capacity has increased owing to large-scale integration. In addition, memory footprints have increased in size, as multiple programs are executed on a single computer. Many operating systems manage physical memory by paging a 4 KB page. Therefore, the number of entries in the virtual address translation table for virtual to physical increases along with the size of the memory footprints. This cause a decrease in the translation lookaside buffer (TLB) hit ratio, resulting in the performance degradation of the application. To address this problem, we propose the implementation of physical memory management with two page sizes: 4 KB and 4 MB. This allows us to expand range of addresses to be translated by a single TLB entry, thereby improving the TLB hit rate. This paper describes the design and implementation of the physical memory management mechanism that manages physical memory using two page sizes on The ENduring operating system for Distributed EnviRonment (Tender OS). Our results showed that when the page size is 4 MB, the processing time of the memory allocation can be reduced by as much as approximately 99.7%, and the processing time for process creation can be reduced by as much as approximately 51%, and the processing time of the memory operation could be reduced by as much as 91.9%. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2363-9024 7 1 2021 Intact survival from severe cardiogenic shock caused by the first attack of atrial tachycardia treated with extracorporeal membrane oxygenation and surgical left atrium appendage resection: a case report 81 EN Tatsuhiko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Kanazawa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takanobu Sakura Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyoshi Shimizu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuo Iwasaki Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Atrial tachycardia (AT) is rare in children and can usually be reversed to sinus rhythm with pharmacotherapy and cardioversion. We report a rare case of severe left-sided heart failure due to refractory AT. Case presentation A 12-year-old boy had AT with a heart rate of 180 beats/minute, which was refractory to any medication and defibrillation despite the first attack. Due to rapid cardiorespiratory collapse shortly after arriving at our hospital, central extracorporeal membrane oxygenation (ECMO) with left arterial venting was started immediately. Although AT persisted after that, it stopped on the 3rd day after admission following surgical resection of the left atrial appendage thought to be the source of AT. He was weaned off ECMO on the 7th day and ventilator on the 14th day. Conclusions The appropriate timing of central ECMO and surgical ablation were effective in saving this child from a life-threatening situation caused by refractory AT. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2363-9024 7 1 2021 Veno-venous extracorporeal membrane oxygenation in the management of refractory bilateral bronchial dehiscence after lung transplant: a case report 77 EN Makiko Tani Department of Anesthesiology and Resuscitology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Background<br> Bronchial dehiscence is a life-threatening complication after lung transplant. If it is not treated by placement of stent or reanastomosis, the chance of survival will depend on the availability of a new graft. However, retransplant is not a practical management option in Japan, where waiting time for lung transplant is extensive. We described a case of refractory bilateral bronchial dehiscence managed by veno-venous extracorporeal oxygenation membrane (VV ECMO) while allowing the dehiscence to heal.<br> <br> Case presentation<br> A 25-year-old man with idiopathic pulmonary arterial hypertension underwent a bilateral lung transplant. The patient developed bilateral bronchial dehiscence. Open reanastomosis was not successful, and air leakage recurred under low positive pressure ventilation. VV ECMO was established to maintain oxygenation with spontaneous breathing until both dehiscence were closed by adhesions.<br> <br> Conclusion<br> In a patient with refractory bilateral bronchial dehiscence, VV ECMO may provide bronchial rest and serve as a bridge therapy to recovery. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 7 1 2021 Gastroenteropancreatic neuroendocrine tumor of the accessory papilla of the duodenum: a case report 156 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroki Sato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takahito Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences BackgroundContrary to the increasing incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), GEP-NETs of the accessory papilla of the duodenum are extremely rare. Furthermore, there have been no recommendations regarding the treatment strategy for GEP-NETs of the accessory papilla of the duodenum. We present a case of GEP-NET of the accessory papilla of the duodenum successfully treated with robotic pancreatoduodenectomy.Case presentationA case of a 70-year-old complaining of no symptoms was diagnosed with GEP-NET of the accessory papilla of the duodenum. A 8-mm tumor was located at the submucosal layer with a biopsy demonstrating a neuroendocrine tumor grade 1. The patient underwent robotic pancreatoduodenectomy as curative resection for the tumor. The total operative time was 406 min with an estimated blood loss of 150 mL. The histological examination revealed a well-differentiated neuroendocrine tumor with low Ki-67 index (<1%). In the posterior areas of the pancreas, the lymph node metastases were detected. The patient was followed up for 6 months with no recurrence postoperatively.ConclusionsConsidering the potential risks of the lymph node metastases, the standard treatment strategy for GEP-NETs of the accessory papilla of the duodenum should be radical resection with pancreatoduodenectomy. Minimally invasive approach can be the alternative to the conventional open surgery. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 7 1 2021 Long-term survival without recurrence after surgery for gastric yolk sac tumor-like carcinoma: a case report 111 EN Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuya Yano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiko Nishizaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Gastric yolk sac tumor (YST)-like carcinoma is extremely rare, and its prognosis is poor, because most patients have widespread metastases at the time of diagnosis. We report a case of gastric YST-like carcinoma with an adenocarcinoma component without metastases in which curative resection was performed. Case presentation A 77-year-old man complaining of melena and dizziness due to anemia was diagnosed with poorly differentiated adenocarcinoma in the gastric cardia, with a benign ulcer in the gastric body. He underwent total gastrectomy with D2 lymph node dissection for the tumor. Histological examination of the resected specimens revealed a mixture of reticular and glandular neoplastic components morphologically. In the reticular area, an endodermal sinus pattern and some Schiller-Duval bodies were confirmed. Gastric YST-like carcinoma with adenocarcinoma components, T2N0M0 Stage IB, was diagnosed. Immunohistochemical analysis showed that the YST was positive for carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and p53. In contrast, the adenocarcinoma was positive for p53 and negative for CEA and AFP. The patient remained healthy as of 7 years postoperatively, with no recurrence. Conclusions Routine medical examinations or endoscopic examinations for accidental symptom may be helpful for early diagnosis and good prognosis for gastric YST-like carcinoma, although the prognosis is generally poor. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1618-2642 413 2021 Speciation of chromium in water samples using microfluidic paper-based analytical devices with online oxidation of trivalent chromium 3339 3347 EN Abdellah Muhammed Center for Environmental Science, College of Natural and Computational Sciences, Addis Ababa University Ahmed Hussen Center for Environmental Science, College of Natural and Computational Sciences, Addis Ababa University Takashi Kaneta Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Speciation of chromium (Cr) was demonstrated using microfluidic paper-based analytical devices (μ-PADs) that permit the colorimetric determination of hexavalent chromium (Cr(VI)) and trivalent chromium (Cr(III)) via online oxidation. The μ-PADs consist of left and right channels that allow the simultaneous measurements of Cr(VI) and total Cr based on the colorimetric reaction of Cr(VI) with 1,5-diphenylcarbazide (DPC). For the determination of Cr(VI), a sample solution was directly reacted with DPC in the left channels whereas total Cr was determined in the right channels, which permitted online oxidation in the pretreatment zone containing cerium (IV) (Ce(IV)) followed by a colorimetric reaction with DPC. We found that the online oxidation of Cr(III) proceeded 100% whereas Ce(IV) inhibited the reaction of Cr(VI) with DPC. Therefore, speciation can be achieved by measuring the Cr(VI) and total Cr in the left and right channels followed by the subtraction of Cr(VI) from total Cr. The limits of detection and quantification were 0.008 and 0.02 mg L−1 for Cr(VI) and 0.07 and 0.1 mg L−1 for Cr(III) or total Cr, respectively. The linear dynamic ranges were 0.02–100 mg L−1 and 0.1–60 mg L−1 for Cr(VI) and Cr(III), respectively. The RSDs were less than 7.5%. The results obtained using μ-PADs were in good agreement with those obtained via ICP-OES with recoveries of 92–108% for Cr(III) and 108–110% for Cr (VI) using μ-PADs, and 106–110% for total Cr using ICP-OES. Thus, the μ-PADs could potentially be utilized for the speciation of chromium in developing countries where environmental pollution and the availability of sophisticated instruments are significant problems. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0941-1291 2021 Role of surgery in a novel multimodal therapeutic approach to complete cure of advanced lung cancer: current and future perspectives EN Masaomi Yamane Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Non-small cell lung cancer (NSCLC) is considered potentially curable by multimodal therapy in a subset of patients, including those with locally advanced (LA) disease or nodal spread, who would otherwise have a poor prognosis. Guidelines recommend perioperative chemotherapy with platinum-based regimens, with or without radiotherapy, as the standard treatment modality for high-risk resectable LA-NSCLC. Although the classical regimens of adjuvant chemotherapy have been platinum-based doublet or oral agents such as tegafur/uracil, some molecular targeted therapeutic agents and immune checkpoint inhibitors have been developed recently with an expected favorable effect. Recent trials of perioperative therapy using these agents have demonstrated favourable anticancer efficacy for LA-NSCLC with an acceptable adverse events profile. The ideal timing of perioperative therapy administration, before or after surgery, is still controversial. Because some speculation and concepts have arisen from basic research, several trials are ongoing to clarify the efficacy of newly developed agents in the adjuvant or neoadjuvant setting. This review discusses the role of surgery in the new era and analyzes when and which optimal perioperative multimodal therapy, including chemotherapy, radiotherapy, molecular-targeted therapy, and immunotherapy, should be administered for resectable or potentially resectable NSCLC to provide possible complete cure. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2399-3642 4 1 2021 High-resolution cryo-EM structure of photosystem II reveals damage from high-dose electron beams 382 EN Koji Kato Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Naoyuki Miyazaki Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba Tasuku Hamaguchi Biostructural Mechanism Laboratory, RIKEN Spring-8 Center Yoshiki Nakajima Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Fusamichi Akita Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Koji Yonekura Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Jian-Ren Shen Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Photosystem II (PSII) plays a key role in water-splitting and oxygen evolution. X-ray crystallography has revealed its atomic structure and some intermediate structures. However, these structures are in the crystalline state and its final state structure has not been solved. Here we analyzed the structure of PSII in solution at 1.95 Å resolution by single-particle cryo-electron microscopy (cryo-EM). The structure obtained is similar to the crystal structure, but a PsbY subunit was visible in the cryo-EM structure, indicating that it represents its physiological state more closely. Electron beam damage was observed at a high-dose in the regions that were easily affected by redox states, and reducing the beam dosage by reducing frames from 50 to 2 yielded a similar resolution but reduced the damage remarkably. This study will serve as a good indicator for determining damage-free cryo-EM structures of not only PSII but also all biological samples, especially redox-active metalloproteins. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1619-7070 46 9 2019 The next era of renal radionuclide imaging: novel PET radiotracers 1773 1786 EN Rudolf A. Werner Department of Nuclear Medicine/Comprehensive Heart Failure Center, University of Wuerzburg Xinyu Chen Department of Nuclear Medicine/Comprehensive Heart Failure Center, University of Wuerzburg Constantin Lapa Department of Nuclear Medicine/Comprehensive Heart Failure Center, University of Wuerzburg Kazuhiro Koshino Department of Biomedical Imaging, National Cardiovascular and Cerebral Center Steven P. Rowe Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine Martin G. Pomper Mehrbod S. Javadi Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine Takahiro Higuchi Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School Although single-photon-emitting radiotracers have long been the standard for renal functional molecular imaging, recent years have seen the development of positron emission tomography (PET) agents for this application. We provide an overview of renal radionuclide PET radiotracers, in particular focusing on novel 18F-labelled and 68Ga-labelled agents. Several reported PET imaging probes allow assessment of glomerular filtration rate, such as [68Ga]ethylenediaminetetraacetic acid ([68Ga]EDTA), [68Ga]IRDye800-tilmanocept and 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS)). The diagnostic performance of [68Ga]EDTA has already been demonstrated in a clinical trial. [68Ga]IRDye800-tilmanocept shows receptor-mediated binding to glomerular mesangial cells, which in turn may allow the monitoring of progression of diabetic nephropathy. [18F]FDS shows excellent kidney extraction and excretion in rats and, as has been shown in the first study in humans. Further, due to its simple one-step radiosynthesis via the most frequently used PET radiotracer 2-deoxy-2-[18F]fluoro-d-glucose, [18F]FDS could be available at nearly every PET centre. A new PET radiotracer has also been introduced for the effective assessment of plasma flow in the kidneys: Re(CO)3-N-([18F]fluoroethyl)iminodiacetic acid (Re(CO)3([18F]FEDA)). This compound demonstrates similar pharmacokinetic properties to its 99mTc-labelled analogue [99mTc](CO)3(FEDA). Thus, if there is a shortage of molybdenum-99, Re(CO)3([18F]FEDA would allow direct comparison with previous studies with 99mTc. The PET radiotracers for renal imaging reviewed here allow thorough evaluation of kidney function, with the tremendous advantage of precise anatomical coregistration with simultaneously acquired CT images and rapid three-dimensional imaging capability. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0941-1291 51 2021 The prognostic impact of sarcopenia on elderly patients undergoing pulmonary resection for non-small cell lung cancer 1203 1211 EN Akihiro Miura Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Sato Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Tomioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshio Shiotani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaomi Yamane Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose</br> The number of elderly patients who undergo surgery is increasing, even though they are at a high risk due to a decreased physical strength. Furthermore, sarcopenia is generally associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC).</br> Methods</br> This study included NSCLC patients  ≥ 65 years old who underwent pulmonary resection in our hospital between 2012 and 2015. Sarcopenia was assessed using the psoas muscle mass index based on computed tomography at the level of the third lumbar vertebra. We elucidated the impact of sarcopenia on short- and long-term outcomes after surgery.</br> Results</br> We enrolled 259 patients, including 179 with sarcopenia. Patients with sarcopenia before surgery tended to have postoperative complications (p = 0.0521), although they did not show a poor prognosis. In patients with sarcopenia, a multivariate analysis revealed that postoperative complications and the progression of sarcopenia 1 year after surgery were significant risk factors for a poor prognosis (p = 0.0169 and 0.00370, respectively).</br> Conclusions</br> The progression of sarcopenia after surgery is associated with a poor prognosis in elderly NSCLC patients with sarcopenia. A strategy to prevent postoperative progressive sarcopenia may be necessary for improving the clinical outcome of this population. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0941-1291 51 2021 The prognostic nutritional index is correlated negatively with the lung allocation score and predicts survival after both cadaveric and living-donor lobar lung transplantation 1610 1618 EN Haruchika Yamamoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Junichi Soh Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Toshio Shiotani Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shinji Otani Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Masaomi Yamane Shinichi Toyooka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Purpose</br> The prognostic nutritional index (PNI), calculated based on the serum albumin levels and the total lymphocyte count, has been identified as a predictor of clinical outcomes in various fields of surgery. In this study, we investigated the relationship between the PNI and the lung allocation score (LAS) as well as the impact of the PNI on the outcomes of both cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT).</br> Methods</br> We reviewed retrospective data for 127 recipients of lung transplantation (LT), including 71 recipients of CLT and 56 recipients of LDLLT.</br> Results</br> The PNI was correlated significantly and negatively with the LAS (r = − 0.40, P = 0.0000037). Multivariate analysis revealed that age (P = 0.00093), BMI (P = 0.00087), and PNI (P = 0.0046) were independent prognostic factors of a worse outcome after LT. In a subgroup analysis, survival after both CLT (P = 0.015) and LDLLT (P = 0.041) was significantly worse in the low PNI group than in the high PNI group.</br> Conclusion</br> Preoperative nutritional evaluations using the PNI can assist with the assessment of disease severity in LT recipients and may predict survival after both CLT and LDLLT. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2363-9024 7 1 2021 Two cases of intraoperative hemodynamic instability during combined thoracoscopic-laparoscopic surgery for esophagogastric junction carcinoma 16 EN Makiko Tani Department of Anesthesiology and Resuscitology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yoshikazu Matsuoka Department of Anesthesiology and Resuscitology, Okayama University Hospital Mayu Sugihara Department of Anesthesiology and Resuscitology, Okayama University Hospital Ayaka Fujii Department of Anesthesiology and Resuscitology, Okayama University Hospital Tomoyuki Kanazawa Department of Anesthesiology and Resuscitology, Okayama University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Background</br> Intraoperative complications during combined thoracoscopic-laparoscopic surgery for esophagogastric junction (EGJ) carcinoma have not been reported as compared to those during surgery for esophageal carcinoma. We present two cases which had surgery-related hemodynamic instability during laparoscopic proximal gastrectomy and intra-mediastinal valvuloplastic esophagogastrostomy (vEG) with thoracoscopic mediastinal lymphadenectomy for EGJ carcinoma.</br> Case presentation</br> In case 1, the patient fell into hypotension with hypoxemia during laparoscopic vEG due to pneumothorax caused by entry of intraabdominal carbon dioxide. In case 2, ventricular arrythmia and ST elevation occurred during laparoscopic vEG. Pericardium retraction to secure surgical field during reconstruction compressed the coronary artery, which caused coronary malperfusion. These two events were induced by the surgical procedure, characterized by the following: (1) connection of the thoracic and abdominal cavities and (2) cardiac displacement during vEG.</br> Conclusion</br> These cases indicated tension pneumothorax and coronary ischemia are possible intraoperative complications specific to combined thoracoscopic-laparoscopic surgery for EGJ carcinoma. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2045-2322 11 1 2021 Direct evidence of electronic ferroelectricity in YbFe2O4 using neutron diffraction and nonlinear spectroscopy 4277 EN K. Fujiwara Graduate School of Natural Science and Technology, Okayama University Y. Fukada Graduate School of Natural Science and Technology, Okayama University Y. Okuda Graduate School of Natural Science and Technology, Okayama University R. Seimiya Graduate School of Natural Science and Technology, Okayama University N. Ikeda Graduate School of Natural Science and Technology, Okayama University K. Yokoyama Department of Chemistry, Tokyo Institute of Technology H. Yu Department of Chemistry, Tokyo Institute of Technology S. Koshihara Department of Chemistry, Tokyo Institute of Technology Y. Okimoto Department of Chemistry, Tokyo Institute of Technology We report the first observation of room temperature spontaneous electric polarization in an electronic ferroelectric material, a YbFe2O4 single crystal. The observation was based on second harmonic generation (SHG), a nonlinear optical process. Tensor analysis of the SHG signal revealed that this material has a polar charge superstructure with Cm symmetry. This result settles the long-term discussion on the uncertainty about electronic ferroelectric properties, including the charge order structure. We present a complete picture of the polar charge ordering of this material via consistent results from two different characterization methods. The SHG signal shows the same temperature dependence as the superlattice signal observed in neutron diffraction experiments. These results prove ferroelectric coupling to electron ordering in YbFe2O4, which results in electronic ferroelectricity which is enabled by the real space ordering of iron cations with different valences. The existence of electronic ferroelectricity holds promise for future electronics technologies where devices run a thousand times faster than frequency of the present CPU (a few gigahertz) embedded in smartphones, etc. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1615-5262 20 2021 Web access monitoring mechanism via Android WebView for threat analysis 833 847 EN Yuta Imamura Graduate School of Natural Science and Technology, Okayama University Rintaro Orito Graduate School of Natural Science and Technology, Okayama University Hiroyuki Uekawa Graduate School of Natural Science and Technology, Okayama University Kritsana Chaikaew Faculty of Engineering, Kasetsart University Pattara Leelaprute Faculty of Engineering, Kasetsart University Masaya Sato Graduate School of Natural Science and Technology Toshihiro Yamauchi Graduate School of Natural Science and Technology, Okayama University Many Android apps employ WebView, a component that enables the display of web content in the apps without redirecting users to web browser apps. However, WebView might also be used for cyberattacks. Moreover, to the best of our knowledge, although some countermeasures based on access control have been reported for attacks exploiting WebView, no mechanism for monitoring web access via WebView has been proposed and no analysis results focusing on web access via WebView are available. In consideration of this limitation, we propose a web access monitoring mechanism for Android WebView to analyze web access via WebView and clarify attacks exploiting WebView. In this paper, we present the design and implementation of this mechanism by modifying Chromium WebView without any modifications to the Android framework or Linux kernel. The evaluation results of the performance achieved on introducing the proposed mechanism are also presented here. Moreover, the result of threat analysis of displaying a fake virus alert while browsing websites on Android is discussed to demonstrate the effectiveness of the proposed mechanism. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-5761 95 4 2021 Spatiotemporal analysis of the UPR transition induced by methylmercury in the mouse brain 1241 1250 EN Hideki Hiraoka Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Nomura Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobumasa Takasugi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Akai Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University Takao Iwawaki Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University Yoshito Kumagai Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba Masatake Fujimura Department of Basic Medical Science, National Institute for Minamata Disease Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Methylmercury (MeHg), an environmental toxicant, induces neuronal cell death and injures a specific area of the brain. MeHg-mediated neurotoxicity is believed to be caused by oxidative stress and endoplasmic reticulum (ER) stress but the mechanism by which those stresses lead to neuronal loss is unclear. Here, by utilizing the ER stress-activated indicator (ERAI) system, we investigated the signaling alterations in the unfolded protein response (UPR) prior to neuronal apoptosis in the mouse brain. In ERAI transgenic mice exposed to MeHg (25 mg/kg, S.C.), the ERAI signal, which indicates activation of the cytoprotective pathway of the UPR, was detected in the brain. Interestingly, detailed ex vivo analysis showed that the ERAI signal was localized predominantly in neurons. Time course analysis of MeHg exposure (30 ppm in drinking water) showed that whereas the ERAI signal was gradually attenuated at the late phase after increasing at the early phase, activation of the apoptotic pathway of the UPR was enhanced in proportion to the exposure time. These results suggest that MeHg induces not only ER stress but also neuronal cell death via a UPR shift. UPR modulation could be a therapeutic target for treating neuropathy caused by electrophiles similar to MeHg. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0049-6979 232 1 2021 Enhancement of Zinc Ion Removal from Water by Physically Mixed Particles of Iron/Iron Sulfide 17 EN Yuya Kamba Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Miharu Ueta Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Md. Azhar Uddin Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Yoshiei Kato Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Zinc (Zn) removal by physically mixed particles of zero-valent iron (Fe) and iron sulfide (FeS) was investigated as one technology for Zn removal from waste groundwater. The effects of the Fe/FeS mass ratio, including a single Fe and FeS particles, and pH on changes in the concentrations of Zn, Fe, and S were examined by a batch test and column tests, and the mechanism of Zn elimination was discussed. Among all the mixing fractions of Fe and FeS, Zn was eliminated most effectively by 3Fe/7FeS (mass ratio of Fe/FeS = 3/7). The Zn removal rate decreased in the order of 3Fe/7FeS, FeS, and Fe, whereas the Fe concentration decreased in the order of Fe, FeS, and 3Fe/7FeS. The S concentration of FeS was larger than that of 3Fe/7FeS. The Zn removal rate by physically mixed 3Fe/7FeS particles was enhanced by a local cell reaction between the Fe and FeS particles. The electrons caused by Fe corrosion moved to the FeS surface and reduced the dissolved oxygen in the solution. Zn2+, Fe2+, and OH− ions in the solution were then coprecipitated on the particles as ZnFe2(OH)6 and oxidized to ZnFe2O4. Moreover, Zn2+ was sulfurized as ZnS by both the Fe/FeS mixture and the simple FeS particles. The Zn removal rate increased with increasing pH in the range from pH 3 to 7. From a kinetic analysis of Zn removal, the rate constant of anode (Fe)/cathode (FeS) reaction was almost the same as that of ZnS formation and slightly larger than that of Fe alone. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0930-2794 2020 A novel difficulty grading system for laparoscopic living donor nephrectomy EN Kosei Takagi Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hendrikus J. A. N. Kimenai Department of Surgery, Division of HPB & Transplant Surgery, University Medical Centre Rotterdam Turkan Terkivatan Department of Surgery, Division of HPB & Transplant Surgery, University Medical Centre Rotterdam Khe T. C. Tran Department of Surgery, Division of HPB & Transplant Surgery, University Medical Centre Rotterdam Jan N. M. Ijzermans Department of Surgery, Division of HPB & Transplant Surgery, University Medical Centre Rotterdam Robert C. Minnee Department of Surgery, Division of HPB & Transplant Surgery, University Medical Centre Rotterdam Background</br> Several difficulty grading systems have been developed as a useful tool for selecting patients and training surgeons in laparoscopic procedures. However, there is little information on predicting the difficulty of laparoscopic donor nephrectomy (LDN). The aim of this study was to develop a grading system to predict the difficulty of LDN.</br> Methods</br> Data of 1741 living donors, who underwent pure or hand-assisted LDN between 1994 and 2018 were analyzed. Multivariable analyses were performed to identify factors associated with prolonged operative time, defined as a difficulty index with 0 to 8. The difficulty of LDN was classified into three levels based on the difficulty index.</br> Results</br> Multivariable analyses identified that male (odds ratio [OR] 1.69, 95% CI 1.37–2.09, P < 0.001), BMI > 28 (OR 1.36, 95% CI 1.08–1.72, P = 0.009), pure LDN (OR 1.99, 95% CI 1.53–2.60, P < 0.001), multiple renal arteries (OR 2.38, 95% CI 1.83–3.10, P < 0.001) and multiple renal veins (OR 2.18, 95% CI 1.52–3.16, P < 0.001) were independent risk factors influencing prolonged operative time. The difficulty index based on these factors was calculated and categorized into three levels: low (0–2), intermediate (3–5), and high (6–8) difficulty. Operative time was significantly longer in the high difficulty group (225 min) than in the low (169 min, P < 0.001) and intermediate difficulty group (194 min, P < 0.001). The conversion rate was higher in the high difficulty group (4.4%) than in the low (2.1%, P = 0.04) and the intermediate difficulty group (3.0%, P = 0.27). No significant difference in major complications was found between the groups.</br> Conclusion</br> We developed a novel grading system with simple preoperative donor factors to predict the difficulty of LDN. This grading system may help surgeons in patient selection to advance their experiences and/or teach fellows from simple to difficult LDN. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2095-0055 12 2 2021 Long-Term Improvement in Precautions for Flood Risk Mitigation: A Case Study in the Low-Lying Area of Central Vietnam 250 266 EN Cong Dinh Nguyen Graduate School of Environmental and Life Science, Okayama University Fumikazu Ubukata Graduate School of Environmental and Life Science, Okayama University Quang Tan Nguyen International School, Hue University Hoang Ha Vo Faculty of Economics and Development Studies, University of Economics, Hue University Local actors appear as inseparable components of the integrated flood risk mitigation strategy in Vietnam. Recognizing this fact, this study examined the long-term improvement in precautions taken by commune authorities and households between two major floods in 1999 and 2017 by applying both quantitative and qualitative methods. Two flood-prone villages were selected for a survey; one in a rural area and the other in a suburban area of Thua Thien Hue Province, central Vietnam. The findings indicate that most villagers doubted the structural works' efficacy and were dissatisfied with the current efforts of local authorities. Households' self-preparation thus became the decisive factor in mitigating risk. While most households have paid greater attention to flood precautions in 2017, others seem to be lagging. Poverty-related barriers were the root causes restraining households in both rural and suburban villages. The suburban riverine residents were further identified as vulnerable by their limitations in upgrading structural measures, which was ascribed to the inconsistency in the ancient town's preservation policy. This multidimensional comparison, in terms of vulnerability, emphasized the importance of space-function links in the suburb and the contradictions of different policy initiatives, such as landscape rehabilitation, disaster prevention, and livelihood maintenance. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1880-6546 70 1 2020 Effectiveness of impedance parameters for muscle quality evaluation in healthy men 53 EN Hiroki Sato Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Takao Nakamura Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Toshimasa Kusuhara Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Kobara Kenichi Department of Physical Therapist, Faculty of Rehabilitation, Kawasaki University of Medical Welfare Katsushi Kuniyasu Department of Physical Therapist, Faculty of Rehabilitation, Kawasaki University of Medical Welfare Takaki Kawashima Department of Physical Therapist, Kawasaki Junior College of Rehabilitation Kozo Hanayama Department of Rehabilitation Medicine, Kawasaki Medical School, 577, Matsushim We investigated the relationship between impedance parameters and skeletal muscle function in the lower extremities, as well as the effectiveness of impedance parameters in evaluating muscle quality. Lower extremity impedance of 19 healthy men (aged 23–31 years) measured using the direct segmental multi-frequency bioelectrical impedance analysis were arc-optimized using the Cole–Cole model, following which phase angle (PA), Ri/Re, and β were estimated. Skeletal muscle function was assessed by muscle thickness, muscle intensity, and isometric knee extension force (IKEF). IKEF was positively correlated with PA (r = 0.58, p < 0.01) and β (r = 0.34, p < 0.05) was negatively correlated with Ri/Re (r = − 0.43, p < 0.01). Stepwise multiple regression analysis results revealed that PA, β, and Ri/Re were correlated with IKEF independently of muscle thickness. This study suggests that arc-optimized impedance parameters are effective for evaluating muscle quality and prediction of muscle strength. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1612-9059 18 1 2020 Association of dental occlusal support with the Prognostic Nutritional Index in patients with esophageal cancer who underwent esophagectomy 49 55 EN Reiko Yamanaka-Kohno Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Inoue-Minakuchi Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aya Yokoi Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Misato Muro Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Hirotaka Kosaki Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Morita Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background</br> The Prognostic Nutritional Index is useful for predicting surgical risk and overall survival based on preoperative immunological and nutritional status in patients undergoing digestive organ cancer surgery. The purpose of this study was to examine the association between the Prognostic Nutritional Index and dental status in patients with esophageal cancer who underwent esophagectomy.</br> Methods</br> This retrospective case–control study included 73 patients who underwent resection of esophageal cancer (69 males, 4 females; age 36–83). General and dental status were evaluated. The Prognostic Nutritional Index was calculated based on the serum albumin concentration and the total lymphocyte count, and subjects were divided into two groups based on index scores: a higher group, characterized by scores ≥ 45 (n = 54); and a lower group, characterized by scores < 45 (n = 19). Univariate analysis and multiple logistic regression analyses were used to compare between groups.</br> Results</br> Total protein, C-reactive protein, the number of sound and total decayed, missing and filled teeth, and the rate of patients with poor dental occlusal support showed significant differences between the lower and higher Prognostic Nutritional Index groups (p < 0.05). Stepwise logistic regression analysis by backward selection approach showed that low total protein, few sound teeth, and poor status of dental occlusal support were significantly associated with the lower Prognostic Nutritional Index (p = 0.007, 0.042, and 0.009, respectively).</br> Conclusion</br> Dental status, especially dental occlusal support and the number of sound teeth, showed a positive relationship with the Prognostic Nutritional Index in esophageal cancer patients who underwent esophagectomy. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0166-8595 147 1 2021 Phos-tag-based approach to study protein phosphorylation in the thylakoid membrane 107 124 EN Keiji Nishioka Institute of Plant Science and Resources (IPSR), Okayama University Yusuke Kato Institute of Plant Science and Resources (IPSR), Okayama University Shin-ichiro Ozawa Institute of Plant Science and Resources (IPSR), Okayama University Yuichiro Takahashi Research Institute for Interdisciplinary Science, Okayama University Wataru Sakamoto Institute of Plant Science and Resources (IPSR), Okayama University Protein phosphorylation is a fundamental post-translational modification in all organisms. In photoautotrophic organisms, protein phosphorylation is essential for the fine-tuning of photosynthesis. The reversible phosphorylation of the photosystem II (PSII) core and the light-harvesting complex of PSII (LHCII) contribute to the regulation of photosynthetic activities. Besides the phosphorylation of these major proteins, recent phosphoproteomic analyses have revealed that several proteins are phosphorylated in the thylakoid membrane. In this study, we utilized the Phos-tag technology for a comprehensive assessment of protein phosphorylation in the thylakoid membrane of Arabidopsis. Phos-tag SDS-PAGE enables the mobility shift of phosphorylated proteins compared with their non-phosphorylated isoform, thus differentiating phosphorylated proteins from their non-phosphorylated isoforms. We extrapolated this technique to two-dimensional (2D) SDS-PAGE for detecting protein phosphorylation in the thylakoid membrane. Thylakoid proteins were separated in the first dimension by conventional SDS-PAGE and in the second dimension by Phos-tag SDS-PAGE. In addition to the isolation of major phosphorylated photosynthesis-related proteins, 2D Phos-tag SDS-PAGE enabled the detection of several minor phosphorylated proteins in the thylakoid membrane. The analysis of the thylakoid kinase mutants demonstrated that light-dependent protein phosphorylation was mainly restricted to the phosphorylation of the PSII core and LHCII proteins. Furthermore, we assessed the phosphorylation states of the structural domains of the thylakoid membrane, grana core, grana margin, and stroma lamella. Overall, these results demonstrated that Phos-tag SDS-PAGE is a useful biochemical tool for studying in vivo protein phosphorylation in the thylakoid membrane protein. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0941-4355 29 2020 Demand for weekend outpatient chemotherapy among patients with cancer in Japan 1287 1297 EN Hideki Katayama Department of Palliative and Supportive Care, Okayama University Hospital Masahiro Tabata Department of Palliative and Supportive Care, Okayama University Hospital Toshio Kubo Department of Allergy and Respiratory Medicine, Okayama University Hospital Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Junji Matsuoka Department of Palliative and Supportive Care, Okayama University Hospital Yoshinobu Maeda Department of Palliative and Supportive Care, Okayama University Hospital Background</br> Advanced cancer therapeutics have improved patient survival, leading to an increase in the number of patients who require long-term outpatient chemotherapy. However, the available schedule options for chemotherapy are generally limited to traditional business hours.</br> Method</br> In 2017, we surveyed 721 patients with cancer in Okayama, Japan, regarding their preferences for evening and weekend (Friday evening, Saturday, and Sunday) chemotherapy appointments.</br> Results</br> A preference for evening and weekend appointment options was indicated by 37% of the respondents. Patients who requested weekend chemotherapy were younger, female, with no spouse or partner, living alone, employed, and currently receiving treatment. Among these factors, age and employment status were significantly associated with a preference for weekend chemotherapy, according to multivariate analysis.</br> Conclusion</br> Our findings reveal a demand for evening and weekend outpatient chemotherapy, especially among young, employed patients. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1617-4615 296 2021 Cluster II che genes of Pseudomonas syringae pv. tabaci 6605, orthologs of cluster I in Pseudomonas aeruginosa, are required for chemotaxis and virulence 299 312 EN Stephany Angelia Tumewu Graduate School of Environmental and Life Science, Okayama University Yujiro Ogawa Faculty of Agriculture, Okayama University Takumi Okamoto Faculty of Agriculture, Okayama University Yuka Sugihara Faculty of Agriculture, Okayama University Hajime Yamada Faculty of Agriculture, Okayama University Fumiko Taguchi Graduate School of Environmental and Life Science, Okayama University Hidenori Matsui Graduate School of Environmental and Life Science, Okayama University Mikihiro Yamamoto Graduate School of Environmental and Life Science, Okayama University Yoshiteru Noutoshi Graduate School of Environmental and Life Science, Okayama University Kazuhiro Toyoda Graduate School of Environmental and Life Science, Okayama University Yuki Ichinose Graduate School of Environmental and Life Science, Okayama University Pseudomonas syringae pv. tabaci 6605 (Pta6605) is a causal agent of wildfire disease in host tobacco plants and is highly motile. Pta6605 has multiple clusters of chemotaxis genes including cheA, a gene encoding a histidine kinase, cheY, a gene encoding a response regulator, mcp, a gene for a methyl-accepting chemotaxis protein, as well as flagellar and pili biogenesis genes. However, only two major chemotaxis gene clusters, cluster I and cluster II, possess cheA and cheY. Deletion mutants of cheA or cheY were constructed to evaluate their possible role in Pta6605 chemotaxis and virulence. Motility tests and a chemotaxis assay to known attractant demonstrated that cheA2 and cheY2 mutants were unable to swarm and to perform chemotaxis, whereas cheA1 and cheY1 mutants retained chemotaxis ability almost equal to that of the wild-type (WT) strain. Although WT and cheY1 mutants of Pta6605 caused severe disease symptoms on host tobacco leaves, the cheA2 and cheY2 mutants did not, and symptom development with cheA1 depended on the inoculation method. These results indicate that chemotaxis genes located in cluster II are required for optimal chemotaxis and host plant infection by Pta6605 and that cluster I may partially contribute to these phenotypes. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0938-7994 30 3 2019 Robotic CT-guided out-of-plane needle insertion: comparison of angle accuracy with manual insertion in phantom and measurement of distance accuracy in animals 1342 1349 EN Toshiyuki Komaki Department of Radiology, Okayama University Medical School Takao Hiraki Department of Radiology, Okayama University Medical School Tetsushi Kamegawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takayuki Matsuno Graduate School of Natural Science and Technology, Okayama University Jun Sakurai Center for Innovative Clinical Medicine, Okayama University Hospital Ryutaro Matsuura Graduate School of Health Sciences, Okayama University Medical School Takuya Yamaguchi Division of Radiology, Department of Medical Technology, Okayama University Hospital Takanori Sasaki Collaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Soichiro Okamoto Department of Radiology, Okayama University Medical School Mayu Uka Department of Radiology, Okayama University Medical School Yusuke Matsui Department of Radiology, Okayama University Medical School Toshihiro Iguchi Department of Radiology, Okayama University Medical School Hideo Gobara Division of Medical Informatics, Okayama University Hospital Susumu Kanazawa Department of Radiology, Okayama University Medical School Objectives</br> To evaluate the accuracy of robotic CT-guided out-of-plane needle insertion in phantom and animal experiments.</br> Methods</br> A robotic system (Zerobot), developed at our institution, was used for needle insertion. In the phantom experiment, 12 robotic needle insertions into a phantom at various angles in the XY and YZ planes were performed, and the same insertions were manually performed freehand, as well as guided by a smartphone application (SmartPuncture). Angle errors were compared between the robotic and smartphone-guided manual insertions using Student’s t test. In the animal experiment, 6 robotic out-of-plane needle insertions toward targets of 1.0 mm in diameter placed in the kidneys and hip muscles of swine were performed, each with and without adjustment of needle orientation based on reconstructed CT images during insertion. Distance accuracy was calculated as the distance between the needle tip and the target center.</br> Results</br> In the phantom experiment, the mean angle errors of the robotic, freehand manual, and smartphone-guided manual insertions were 0.4°, 7.0°, and 3.7° in the XY plane and 0.6°, 6.3°, and 0.6° in the YZ plane, respectively. Robotic insertions in the XY plane were significantly (p < 0.001) more accurate than smartphone-guided insertions. In the animal experiment, the overall mean distance accuracy of robotic insertions with and without adjustment of needle orientation was 2.5 mm and 5.0 mm, respectively.</br> Conclusion</br> Robotic CT-guided out-of-plane needle insertions were more accurate than smartphone-guided manual insertions in the phantom and were also accurate in the in vivo procedure, particularly with adjustment during insertion. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1536-1632 22 3 2019 Initial Evaluation of AF78: a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter 602 611 EN Xinyu Chen Department of Nuclear Medicine, University Hospital of Würzburg Alexander Fritz Institute of Pharmacy and Food Chemistry, University of Würzburg Rudolf A. Werner Department of Nuclear Medicine, University Hospital of Würzburg Naoko Nose Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Yagi Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University Hiroyuki Kimura Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University Steven P. Rowe Division of Nuclear Medicine and Molecular Imaging, Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine Kazuhiro Koshino Department of Systems and Informatics, Hokkaido Information University Michael Decker Institute of Pharmacy and Food Chemistry, University of Würzburg Takahiro Higuchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose</br> Taking full advantage of positron emission tomography (PET) technology, fluorine-18-labelled radiotracers targeting norepinephrine transporter (NET) have potential applications in the diagnosis and assessment of cardiac sympathetic nerve conditions as well as the delineation of neuroendocrine tumours. However, to date, none have been used clinically. Drawbacks of currently reported radiotracers include suboptimal kinetics and challenging radiolabelling procedures.</br> Procedures</br> We developed a novel fluorine-18-labelled radiotracer targeting NET, AF78, with efficient one-step radiolabelling based on the phenethylguanidine structure. Radiosynthesis of AF78 was undertaken, followed by validation in cell uptake studies, autoradiography, and in vivo imaging in rats.</br> Results</br> [18F]AF78 was successfully synthesized with 27.9 ± 3.1 % radiochemical yield, > 97 % radiochemical purity and > 53.8 GBq/mmol molar activity. Cell uptake studies demonstrated essentially identical affinity for NET as norepinephrine and meta-iodobenzylgaunidine. Both ex vivo autoradiography and in vivo imaging in rats showed homogeneous and specific cardiac uptake.</br> Conclusions</br> The new PET radiotracer [18F]AF78 demonstrated high affinity for NET and favourable biodistribution in rats. A structure-activity relationship between radiotracer structures and affinity for NET was revealed, which may serve as the basis for the further design of NET targeting radiotracers with favourable features. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0300-9564 127 6 2020 Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements 851 873 EN Xinyu Chen Department of Nuclear Medicine, University Hospital of Würzburg Takashi Kudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Constantin Lapa Department of Nuclear Medicine, University Hospital of Würzburg Andreas Buck Department of Nuclear Medicine, University Hospital of Würzburg Takahiro Higuchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The norepinephrine transporter (NET) is a major target for the evaluation of the cardiac sympathetic nerve system in patients with heart failure and Parkinson's disease. It is also used in the therapeutic applications against certain types of neuroendocrine tumors, as exemplified by the clinically used 123/131I-MIBG as theranostic single-photon emission computed tomography (SPECT) agent. With the development of more advanced positron emission tomography (PET) technology, more radiotracers targeting NET have been reported, with superior temporal and spatial resolutions, along with the possibility of functional and kinetic analysis. More recently, fluorine-18-labelled NET tracers have drawn increasing attentions from researchers, due to their longer radiological half-life relative to carbon-11 (110 min vs. 20 min), reduced dependence on on-site cyclotrons, and flexibility in the design of novel tracer structures. In the heart, certain NET tracers provide integral diagnostic information on sympathetic innervation and the nerve status. In the central nervous system, such radiotracers can reveal NET distribution and density in pathological conditions. Most radiotracers targeting cardiac NET-function for the cardiac application consistent of derivatives of either norepinephrine or MIBG with its benzylguanidine core structure, e.g. 11C-HED and 18F-LMI1195. In contrast, all NET tracers used in central nervous system applications are derived from clinically used antidepressants. Lastly, possible applications of NET as selective tracers over organic cation transporters (OCTs) in the kidneys and other organs controlled by sympathetic nervous system will also be discussed. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1068-9265 28 2020 A Simple Prognostic Benefit Scoring System for Sarcoma Patients with Pulmonary Metastases: Sarcoma Lung Metastasis Score 3884 3890 EN Haruchika Yamamoto Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Junichi Soh Department of Thoracic Surgery, Okayama University Hospital Etsuji Suzuki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Namba Department of Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Shinji Otani Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Masaomi Yamane Department of Thoracic Surgery, Okayama University Hospital Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhito Takahashi Center for Multidisciplinary Treatment of Sarcoma, Department of Sarcoma Medicine, Kameda Medical Center Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background</br> Pulmonary metastasectomy could be considered one of the treatment options for disease control in sarcoma patients with pulmonary metastases; however, there is little consensus regarding the suitable criteria for predicting the likely outcomes in these patients. The aim of this study was to establish a prognostic benefit scoring system based on preoperatively examined prognostic factors for sarcoma patients with pulmonary metastases.</br> Methods</br> This was a single-center, retrospective cohort study conducted in a cohort of 135 sarcoma patients who underwent a first pulmonary metastasectomy at Okayama University Hospital between January 2006 and December 2015. Based on the results of a multivariable logistic regression analysis performed to determine the factors influencing 3-year mortality, a Sarcoma Lung Metastasis Score was created and its correlation with 3-year survival was analyzed.</br> Results</br> The results of the multivariate analysis revealed significant differences in the disease-free interval (< 2 years vs. ≥ 2 years; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.67–10.70), maximum tumor diameter (≥ 15 mm vs. < 15 mm; OR 3.86, 95% CI 1.75–8.52), and number of pulmonary metastases (≥ 6 vs. < 6; OR 2.65, 95% CI 1.06–6.620). The Sarcoma Lung Metastasis Score, which was defined as the total score of these three factors, reliably predicted 3-year survival (score: 0, 89.5%; 1, 63.2%; 2, 39.0%; 3, 10.5%).</br> Conclusions</br> Our newly proposed simple Sarcoma Lung Metastasis Score appears to be a useful prognostic predictor for sarcoma patients with pulmonary metastases, in that it could be helpful for the selection of appropriate treatments for these patients. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0930-2794 35 2020 Treatment outcomes, including risk factors of stone recurrence, for hepatolithiasis using balloon-assisted endoscopy in patients with hepaticojejunostomy (with video) 1895 1902 EN Yuki Ishihara Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hironari Kato Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takeshi Tomoda Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akihiro Matsumi Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuya Miyamoto Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yosuke Saragai Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Fujii Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Uchida Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shigeru Horiguchi Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroyuki Okada Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background and study aimsa</br> Endoscopic treatment outcomes for hepatolithiasis in patients with altered anatomy are not well known. The aim of this study was to evaluate the treatment outcomes of hepatolithiasis in patients with hepaticojejunostomy (HJ) using short-type double-balloon endoscopy (sDBE) and to assess the risk factors for stone recurrence.</br> Patients and methods</br> This was a retrospective cohort study that consisted of 73 patients with hepatolithiasis who underwent bowel reconstruction with HJ at an academic center. Stone removal was performed using sDBE. After balloon-occluded cholangiography using sDBE, peroral direct cholangioscopy (PDCS) using ultraslim endoscopy was performed to check for residual stones, depending on the bowel reconstruction method. Recurrence was defined as the development of cholangitis from stones.</br> Results</br> The success rate of reaching the HJ site was 92% (67/73), and the complete stone removal rate was 93% (62/67) with multiple sessions (mean number 1.5 ± 0.9). The occurrence rate of procedure-related adverse events was 6.8%. Among 58 patients evaluated for stone recurrence, 13 (22%) developed recurrence during a median follow-up period of 2.7 years (interquartile range: 1.5–4.8). Multivariate analyses determined that a stone diameter ≥ 8 mm [odds ratio (OR), 5.57; 95% confidence interval (CI), 1.39–37.2; p = 0.013] and performing PDCS (OR, 0.16; 95% CI, 0.0084–0.90; p = 0.036) were significant factors for stone recurrence.</br> Conclusions</br> Endoscopic treatment using sDBE for hepatolithiasis was effective and safe. PDCS might reduce the rate of stone recurrence by detecting stones that are too small to confirm on fluoroscopic images. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-7004 70 2020 Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma 1405 1417 EN Yusuke Mochizuki Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Demiya Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Kure Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kondo Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Komatsubara Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhisa Sugiu Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Sports Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Aki Yoshida Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc, Shunsuke Kagawa Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1) antibody have recently improved clinical outcome in certain cancer patients; however, osteosarcoma (OS) patients are refractory to PD-1 blockade. Oncolytic virotherapy has emerged as novel immunogenic therapy to augment antitumor immune response. We developed a telomerase-specific replication-competent oncolytic adenovirus OBP-502 that induces lytic cell death via binding to integrins. In this study, we assessed the combined effect of PD-1 blockade and OBP-502 in OS cells. The expression of coxsackie and adenovirus receptor (CAR), integrins αvβ3 and αvβ5, and programmed cell death ligand 1 (PD-L1) was analyzed in two murine OS cells (K7M2, NHOS). The cytopathic activity of OBP-502 in both cells was analyzed using the XTT assay. OBP-502-induced immunogenic cell death was assessed by analyzing the level of extracellular ATP and high-mobility group box protein B1 (HMGB1). Subcutaneous tumor models for K7M2 and NHOS cells were used to evaluate the antitumor effect and number of tumor-infiltrating CD8+ cells in combination therapy. K7M2 and NHOS cells showed high expression of integrins αvβ3 and αvβ5, but not CAR. OBP-502 significantly suppressed the viability of both cells, in which PD-L1 expression and the release of ATP and HMGB1 were significantly increased. Intratumoral injection of OBP-502 significantly augmented the efficacy of PD-1 blockade on subcutaneous K2M2 and NHOS tumor models via enhancement of tumor-infiltrating CD8+  T cells. Our results suggest that telomerase-specific oncolytic virotherapy is a promising antitumor strategy to promote the efficacy of PD-1 blockade in OS. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0942-2056 29 2020 Transtibial pullout repair of medial meniscus posterior root tears: effects on the meniscus healing score and ICRS grade among patients with mild osteoarthritis of the knee 3001 3009 EN Yuya Kodama Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Shota Takihira Department of Orthopaedic Surgery, Okayama University Hospital Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Hospital Shinichi Miyazawa Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Purpose</br> To assess the effects of transtibial pullout repair for medial meniscus posterior root tears (MMPRTs) among patients with early osteoarthritis of the knee as measured by the meniscus healing score and to determine whether the meniscus healing score correlates with the International Cartilage Repair Society (ICRS) grade progression.</br> Methods</br> Forty-seven patients with mild osteoarthritic knees (Kellgren–Lawrence grade ≤ 2 and varus alignment < 5°) who underwent transtibial pullout repair less than 3 months after MMPRT onset were assessed. The association between meniscus healing scores at 1 year postoperatively and cartilage damage of the medial compartment (medial femoral condyle [MFC] and medial tibial plateau [MTP]) were evaluated. The MFC was divided into six zones (A to F) and the MTP into two zones (G and H). The mean ICRS grade for each zone was compared between the primary surgery and second-look arthroscopy. The correlation between cartilage damage and meniscus healing status at the time of second-look arthroscopy in each zone was analysed.</br> Results</br> The mean time interval from injury to surgery was 63 days, and all clinical scores showed significant improvement. There were no significant differences in the extent of cartilage damage in areas B, C, E, or F (n.s.) for MFC or in areas G and H (n.s.) for MTP. The meniscus healing score and cartilage damage were correlated in the loading areas (B, C, E, and H; − 0.53, − 0.45, − 0.33, and − 0.38, respectively; p < 0.05).</br> Conclusion</br> Transtibial pullout repair of MMPRTs among patients with mild osteoarthritic knees improved the clinical outcomes and showed a negative correlation between high meniscus healing scores and ICRS grades in the medial compartment loading area. This study suggests that early surgery should be undertaken for patients with mild osteoarthritic knee who develop MMPRTs. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2197-7364 7 1 2020 Performance evaluation of fifth-generation ultra-high-resolution SPECT system with two stationary detectors and multi-pinhole imaging 64 EN Jan, V Hoffmann Department of Nuclear Medicine, University Hospital Würzburg Jan P. Janssen Department of Nuclear Medicine, University Hospital Würzburg Takayuki Kanno Comprehensive Heart Failure Center, University Hospital Würzburg Takayuki Shibutani Department of Quantum Medical Technology, Graduate School of Medical Sciences Masahisa Onoguchi Department of Quantum Medical Technology, Graduate School of Medical Sciences Constantin Lapa Nuclear Medicine, Medical Faculty, University of Augsburg Jan-Peter Grunz Department of Diagnostic and Interventional Radiology, University Hospital Würzburg Andreas K. Buck Department of Nuclear Medicine, University Hospital Würzburg Takahiro Higuchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT+). Methods The new U-SPECT5-E with two stationary detectors was used for acquiring data with Tc-99m-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT+ for comparison. Results Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT+. In the visually analysed sections of the reconstructed mini Derenzo phantoms, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7% (XUHR-M), 29.1% (GP-M, U-SPECT5-E), 16.3% (GP-M, U-SPECT+) and 23.0% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60 to 1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR. Conclusions While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1345-2630 87 2020 HopH1 effectors of Pseudomonas syringae pv. tomato DC3000 and pv. syringae B728a induce HR cell death in nonhost eggplant Solanum torvum 24 29 EN Kamrun Nahar Graduate School of Natural Science and Technology, Okayama University Takafumi Mukaihara Research Institute for Biological Sciences, Okayama (RIBS) Fumiko Taguchi Graduate School of Environmental and Life Science, Okayama University Hidenori Matsui Graduate School of Environmental and Life Science, Okayama University Mikihiro Yamamoto Graduate School of Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Natural Science and Technology, Okayama University Yoshiteru Noutoshi Graduate School of Environmental and Life Science, Okayama University Tomonori Shiraishi Research Institute for Biological Sciences, Okayama (RIBS) Yuki Ichinose Graduate School of Natural Science and Technology, Okayama University HopH1 is an effector protein of Pseudomonas syringae pv. tomato DC3000 and P. syringae pv. syringae B728a and is a homolog of the putative Zn-dependent protease effector Rip36 of Ralstonia solanacearum, which induces hypersensitive response (HR) cell death in a nonhost plant, Solanum torvum Sw. cv. Torubamubiga. Although P. syringae pv. phaseolicola (Pph) 1448A neither produces HopH1 nor induces HR cell death, hopH1-introduced Pph 1448A acquired the ability to induce HR. These results indicate that the putative Zn-protease HopH1 effector induces HR cell death in nonhost S. torvum. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0289-0771 39 2020 Arousal from death feigning by vibrational stimuli: comparison of Tribolium species 107 113 EN Ryo Ishihara Department of Evolutionary Ecology, Graduate School of Environmental and Life Science, Okayama University Kentarou Matsumura Department of Evolutionary Ecology, Graduate School of Environmental and Life Science, Okayama University Jordan Elouise Jones Department of Evolution, Ecology and Behaviour, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool Ji Yuhao Department of Evolutionary Ecology, Graduate School of Environmental and Life Science, Okayama University Ryusuke Fujisawa School of Computer Science and Systems Engineering, Kyushu Institute of Technology Naohisa Nagaya Faculty of Information Science and Engineering, Kyoto Sangyo University Takahisa Miyatake Department of Evolutionary Ecology, Graduate School of Environmental and Life Science, Okayama University Death feigning (or tonic immobility) is an effective antipredator strategy. However, prolonged immobility on the ground increases the risk of being parasitized or eaten by predators, and thus, insects must rouse themselves when appropriate stimulation is provided. Very few studies on the effect of stimulus intensity on arousal from death feigning have been conducted. A previous study using Tribolium castaneum showed an existing threshold for the intensity of the stimulus that causes arousal from death feigning. Whether there are differences between species in the threshold for arousal is an interesting question. In the present study, we, therefore, compared the effect of stimulus strength on arousal from death feigning in two closely related species, namely, T. confusum and T. freemani, which are established strains that have been artificially selected for longer duration of death feigning. Also, part of the study was to determine whether there was a positive association between intensity of stimulus needed to rouse and the duration of death feigning. We discuss why there is a difference in the strength of the stimulus needed for arousal from death feigning among Tribolium species, for which we included the data for T. castaneum from a previous study. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0168-8162 30 1-3 2003 Orchid Fleck Virus: Brevipalpus californicus Mite Transmission, Biological Properties and Genome Structure 215 223 EN Hideki Kondo Research Institute for Bioresources, Okayama University Takanori Maeda Research Institute for Bioresources, Okayama University Tetsuo Tamada Research Institute for Bioresources, Okayama University Orchid fleck virus (OFV) causes necrotic or chlorotic ring spots and fleck symptoms in many orchid species world-wide. The virus has non-enveloped, bacilliform particles of about 40 nm × 100–150 nm and is sap-transmissible to several plant species. OFV is transmitted by the mite Brevipalpus californicus (Banks) in a persistent manner and efficiently transmitted by both adults and nymphs, but not by larvae. Viruliferous mites retain their infectivity for 3 weeks on a virus-immune host. The genome of OFV consists of two molecules of 6431 (RNA1) and 6001 nucleotides (RNA2). The RNAs have conserved and complementary terminal sequences. RNA1 contains five open reading frames (ORF), and RNA2 encodes a single ORF. Although some of the encoded proteins of OFV have sequences similar to those of proteins of plant rhabdoviruses, OFV differs from viruses in the family Rhabdoviridae in having a bipartite genome. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0304-8608 154 1 2008 Identification and characterization of structural proteins of orchid fleck virus 37 45 EN Hideki Kondo Research Institute for Bioresources, Okayama University Takanori Maeda College of Bioresource Sciences, Nihon University Tetsuo Tamada Research Institute for Bioresources, Okayama University Orchid fleck virus (OFV) has a bipartite negative-sense RNA genome with sequence similarities to plant rhabdoviruses. The non-enveloped bullet-shaped particles of OFV are similar to those of the internal ribonucleoprotein (RNP)-M protein structure of rhabdoviruses, but they are about half the size of typical plant rhabdoviruses. Purified preparations contained intact bullet-shaped and filamentous particles. The filamentous particles showed a tightly coiled coil structure or a coiled structure with a helical twist, which resembles the RNP complex of rhabdoviruses. OFV bullet-shaped particles were structurally stable in solutions containing 2% Triton X-100 and 0.8 M NaCl. Western blot analyses revealed that the bullet-shaped particles contained N, P and M proteins, while filamentous particles contained mainly N and P proteins. In addition, a small amount of the L protein was detected in both types of particles. Thus, the structural proteins of OFV have properties similar to those of rhabdoviruses, except that the particles are non-enveloped and are relatively resistant to detergent-treatment under high-salt conditions. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2192-3183 2020 Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome EN Tomoko Yoshihama Department of Obstetrics and Gynecology, Keio University School of Medicine Akira Hirasawa Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kokichi Sugano Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute Teruhiko Yoshida Department of Genetic Medicine and Services, National Cancer Center Hospital Mineko Ushiama Department of Genetic Medicine and Services, National Cancer Center Hospital Arisa Ueki Center for Medical Genetics, Keio University School of Medicine Tomoko Akahane Department of Obstetrics and Gynecology, Keio University School of Medicine Yoshiko Nanki Department of Obstetrics and Gynecology, Keio University School of Medicine Kensuke Sakai Department of Obstetrics and Gynecology, Keio University School of Medicine Takeshi Makabe Department of Obstetrics and Gynecology, Keio University School of Medicine Wataru Yamagami Department of Obstetrics and Gynecology, Keio University School of Medicine Nobuyuki Susumu Department of Obstetrics and Gynecology, Keio University School of Medicine Kaori Kameyama Department of Pathology, Showa University Northern Yokohama Hospital Kenjiro Kosaki Center for Medical Genetics, Keio University School of Medicine Daisuke Aoki Department of Obstetrics and Gynecology, Keio University School of Medicine There has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as a BRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39 years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, Lynch syndrome was suspected. However, germline multigene panel testing revealed a pathogenic BRCA2 variant rather than pathogenic variants in mismatch repair genes. In this case, with conventional genetic risk assessment, we were unable to determine whether the patient had a high risk of hereditary breast and ovarian cancer; thus, germline multigene panel testing may provide valuable information to improve disease management strategies for patients in clinical settings. Particularly, germline multigene panel testing may be useful for detecting hereditary tumor syndromes if a patient does not present with a typical family history of cancer. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2016 2016 HeapRevolver: Delaying and Randomizing Timing of Release of Freed Memory Area to Prevent Use-After-Free Attacks 219 234 EN Toshihiro Yamauchi Graduate School of Natural Science and Technology, Okayama University Yuta Ikegami Graduate School of Natural Science and Technology, Okayama University Recently, there has been an increase in use-after-free (UAF) vulnerabilities, which are exploited using a dangling pointer that refers to a freed memory. Various methods to prevent UAF attacks have been proposed. However, only a few methods can effectively prevent UAF attacks during runtime with low overhead. In this paper, we propose HeapRevolver, which is a novel UAF attack-prevention method that delays and randomizes the timing of release of freed memory area by using a memory-reuse-prohibited library, which prohibits a freed memory area from being reused for a certain period. In this paper, we describe the design and implementation of HeapRevolver in Linux and Windows, and report its evaluation results. The results show that HeapRevolver can prevent attacks that exploit existing UAF vulnerabilities. In addition, the overhead is small. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0341-2695 44 2 2019 Sacral chordoma: do the width of surgical margin and the use of photon/proton radiotherapy affect local disease control? 381 389 EN Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Tsuda Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Jonathan Stevenson Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Michael Parry Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Lee Jeys Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Purpose</br> Chordoma is a rare but highly aggressive primary bone sarcoma that arises commonly from the sacrum. While en bloc resection has been the mainstay of the treatment, the role of resection margin in millimetres with/without adjuvant radiotherapy (RT) has been unknown. We investigated the prognostic impact of surgical margin width, adjuvant RT, and their combined factor for sacral chordoma.</br> Methods</br> Forty-eight patients who underwent surgical treatment between 1996 and 2016 were studied. Of these, 11 patients (23%) received adjuvant RT; photon RT in 7 (15%) and proton RT in 4 (8%). Margins were microscopically measured in millimetres from the resection surface to the closest tumour on histologic slides.</br> Results</br> The five year and ten year disease-specific survival was 88% and 58%, respectively, and the local recurrence (LR) rate was 48%. The LR rate with 0-mm, < 1.5-mm, and ≥ 1.5-mm margin was 50% (group 1), 50% (group 2: RT−, 61%; group 3: RT+, 14%), and 0% (group 4), respectively. We observed a significantly lower LR rate in patients with adjuvant photon/proton RT (18%) than without it (57%; p = 0.026), and no LR was observed after post-operative proton RT. The combined factor of margin with RT clearly stratified the LR risk: patients of group 1 (positive margin) and 2 (< 1.5-mm margin, RT−) had approximately 7.5× LR risk (p = 0.049) compared with those of group 3 (< 1.5-mm margin, RT+) and 4 (≥ 1.5-mm margin).</br> Conclusion</br> This study identified the lowest risk of local failure in tumour resection with ≥ 1.5-mm margin or negative but < 1.5-mm margin with the use of adjuvant photon/proton radiotherapy for sacral chordoma. Early results of adjuvant proton RT demonstrated excellent local control. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1863-6705 69 2020 Lung transplantation for Kartagener syndrome: technical aspects and morphological adaptation of the transplanted lungs 588 592 EN Haruchika Yamamoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shinji Otani Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Masaomi Yamane Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital While technical considerations in lung transplantation for Kartagener syndrome have been discussed, little information is available about the postoperative morphological changes of the grafted lungs. Herein, we discuss both the technical aspects and postoperative morphological adaptation of the grafted lungs in a case of Kartagener syndrome. A 46-year-old male patient with Kartagener syndrome underwent bilateral cadaveric lung transplantation. The right arterial anastomosis for transplantation of the size-matched grafts required technical elaboration. After the transplantation, we found a free space in the cardiac notch of the left lung and partial collapse of the lower lobe of the right lung due to dextrocardia. Follow-up computed tomography performed on day 42 after the transplantation demonstrated resolution of the atelectasis and morphological adaptation of the grafts into the recipient’s chest cavity with dextrocardia. Considering such early morphological adaptation of size-matched grafts, lobar reduction could be avoided in lung transplantation for Kartagener syndrome. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2019 Region of Interest Growing Neural Gas for Real-Time Point Cloud Processing 82 91 EN Yuichiro Toda Okayama University Xiang Li Okayama University Takayuki Matsuno Okayama University Mamoru Minami Okayama University This paper proposes a real-time topological structure learning method based on concentrated/distributed sensing for a 2D/3D point cloud. First of all, we explain a modified Growing Neural Gas with Utility (GNG-U2) that can learn the topological structure of 3D space environment and color information simultaneously by using a weight vector. Next, we propose a Region Of Interest Growing Neural Gas (ROI-GNG) for realizing concentrated/distributed sensing in real-time. In ROI-GNG, the discount rates of the accumulated error and utility value are variable according to the situation. We show experimental results of the proposed method and discuss the effectiveness of the proposed method. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0942-2056 28 11 2019 Transtibial fixation for medial meniscus posterior root tear reduces posterior extrusion and physiological translation of the medial meniscus in middle-aged and elderly patients 3416 3425 EN Yuya Kodama Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Shin Masuda Department of Orthopaedic Surgery, Okayama University Hospital Yoshiki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Hospital Shinichi Miyazawa Department of Orthopaedic Surgery, Okayama University Hospital Masaharu Yasumitsu Department of Orthopaedic Surgery, Iwakuni Clinical Center Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Purpose</br> To investigate changes in meniscal extrusion during knee flexion before and after pullout fixation for medial meniscus posterior root tear (MMPRT) and determine whether these changes correlate with articular cartilage degeneration and short-term clinical outcomes.</br> Methods</br> Twenty-two patients (mean age 58.4 ± 8.2 years) diagnosed with type II MMPRT underwent open magnetic resonance imaging preoperatively, 3 months after transtibial fixation and at 12 months after surgery, when second-look arthroscopy was also performed. The medial meniscus medial extrusion (MMME) and the medial meniscus posterior extrusion (MMPE) were measured at knee 10° and 90° flexion at which medial meniscus (MM) posterior translation was also calculated. Articular cartilage degeneration was assessed using International Cartilage Research Society grade at primary surgery and second-look arthroscopy. Clinical evaluations included Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee subjective knee evaluation form, Lysholm score, Tegner activity level scale, and pain visual analogue scale.</br> Results</br> MMPE at 10° knee flexion was higher 12 months postoperatively than preoperatively (4.8 ± 1.5 vs. 3.5 ± 1.2, p = 0.01). MMPE at 90° knee flexion and MM posterior translation were smaller 12 months postoperatively than preoperatively (3.5 ± 1.1 vs. 4.6 ± 1.3, 7.2 ± 1.7 vs. 8.9 ± 2.0, p < 0.01). Articular cartilage degeneration of medial femoral condyle correlated with MMME in knee extension (r = 0.5, p = 0.04). All clinical scores significantly improved 12 months postoperatively. However, correlations of all clinical scores against decreased MMPE and increased MMME were not detected.</br> Conclusions</br> MMPRT transtibial fixation suppressed the progression of MMPE and cartilage degeneration and progressed MMME minimally in knee flexion position at 1 year. However, in the knee extension position, MMME progressed and correlated with cartilage degeneration of medial femoral condyle. MMPRT transtibial fixation contributes to the dynamic stability of the MM in the knee flexion position. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0914-8779 39 2020 Changes in the intra- and peri-cellular sclerostin distribution in lacuno-canalicular system induced by mechanical unloading 148 159 EN Ryuta Osumi Department of Orthodontics, Okayama University Hospital Ziyi Wang Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihito Ishihara Department of Orthodontics, Okayama University Hospital Naoya Odagaki Department of Orthodontics, Okayama University Hospital Tadahiro Iimura Department of Pharmacology, Graduate School of Dental Medicine, Hokkaido University Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction</br> Mechanical stimuli regulate Sclerostin (Scl), a negative regulator of bone formation, expression in osteocytes. However, the detailed Scl distribution in osteocytes in response to mechanical unloading remains unclear.</br> Materials and methods</br> Twelve-week-old male rats were used. The sciatic and femoral nerves on the right side were excised as mechanical unloading treatment. A sham operation was performed on the left side. One week after neurotrauma, the bone density of the femora was evaluated by peripheral quantitative computed tomography, and immunofluorescence was performed in coronal sections of the femoral diaphysis. The mean fluorescence intensity and fluorescent profile of Scl from the marrow to the periosteal side were analyzed to estimate the Scl expression and determine to which side (marrow or periosteal) the Scl prefers to distribute in response to mechanical unloading. The most sensitive region indicated by the immunofluorescence results was further investigated by transmission electron microscopy (TEM) with immunogold staining to show the Scl expression changes in different subcellular structures.</br> Results</br> In femur distal metaphysis, neurotrauma-induced mechanical unloading significantly decreased the bone density, made the distribution of Scl closer to the marrow on the anterior and medial side, and increased the Scl expression only on the lateral side. TEM findings showed that only the expression of Scl in canaliculi was increased by mechanical unloading.</br> Conclusions</br> Our results showed that even short-term mechanical unloading is enough to decrease bone density, and mechanical unloading not only regulated the Scl expression but also changed the Scl distribution in both the osteocyte network and subcellular structures. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1749-799X 15 1 2020 Short-term outcomes of mirogabalin in patients with peripheral neuropathic pain: a retrospective study 191 EN Tomoko Tetsunaga Department of Orthopedic Surgery, Okayama University Hospital Tomonori Tetsunaga Department of Orthopedic Surgery, Okayama University Hospital Keiichiro Nishida Department of Orthopedic Surgery, Okayama University Hospital Haruo Misawa Department of Orthopedic Surgery, Okayama University Hospital Tomoyuki Takigawa Department of Orthopedic Surgery, Okayama University Hospital Kentaro Yamane Department of Orthopedic Surgery, Okayama University Hospital Hironori Tsuji Department of Orthopedic Surgery, Okayama University Hospital Yoshitaka Takei Department of Orthopedic Surgery, Kurashiki Municipal Hospital Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Hospital Background</br> Mirogabalin, which is approved for the treatment of peripheral neuropathic pain in Japan, is a ligand for the α2δ subunit of voltage-gated calcium channels. Both pregabalin and mirogabalin act as nonselective ligands at the α2δ-1 and α2δ-2 subunits. Mirogabalin has a unique binding profile and long duration of action. Pregabalin has been reported to produce intolerable adverse effects in some patients. This study investigated outcomes associated with mirogabalin administration in patients with peripheral neuropathic pain who ceased treatment with pregabalin.</br> Methods</br> We retrospectively assessed peripheral neuropathic pain using the neuropathic pain screening questionnaire (NeP score) in 187 patients (58 men, 129 women) who were treated with mirogabalin. All patients had switched from pregabalin to mirogabalin due to lack of efficacy or adverse events. Differences in the treatment course (i.e., numeric rating scale (NRS) scores) were compared using one-way analysis of variance with Bonferroni post hoc tests.</br> Results</br> The mean age of the patients was 72.3 years (range, 30–94 years), and the mean duration of disease was 37 months (range, 3–252 months). After treatment with mirogabalin for 1 week, NRS scores significantly decreased compared with baseline and continued to decrease over time. After 8 weeks, NRS scores improved by ≥ 30% from baseline in 113 patients (69.3%). Twenty-four patients (12.8%) stopped mirogabalin treatment due to adverse events. Somnolence (26.7%), dizziness (12.3%), edema (5.9%), and weight gain (0.5%) were noted as adverse events of mirogabalin.</br> Conclusions</br> The results of this investigation indicate that mirogabalin is safe and effective for reducing peripheral neuropathic pain. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0175-7598 104 2020 Channel-pore cation selectivity is a major determinant of Bacillus thuringiensis Cry46Ab mosquitocidal activity 8789 8799 EN Tohru Hayakawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Midoka Miyazaki Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Syoya Harada Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mami Asakura Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toru Ide Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Cry46Ab from Bacillus thuringiensis TK-E6 is a new mosquitocidal toxin with an aerolysin-type architecture, and it is expected to be used as a novel bioinsecticide. Cry46Ab acts as a functional pore-forming toxin, and characteristics of the resulting channel pores, including ion selectivity, have been analyzed. However, the relationship between channel-pore ion selectivity and insecticidal activity remains to be elucidated. To clarify the effects of charged amino acid residues on the ion permeability of channel-pores and the resulting insecticidal activity, in the present study, we constructed Cry46Ab mutants in which a charged amino acid residue within a putative transmembrane β-hairpin region was replaced with an oppositely charged residue. Bioassays using Culex pipiens mosquito larvae revealed that the mosquitocidal activity was altered by the mutation. A K155E Cry46Ab mutant exhibited toxicity apparently higher than that of wild-type Cry46Ab, but the E159K and E163K mutants exhibited decreased toxicity. Ions selectivity measurements demonstrated that the channel pores formed by both wild-type and mutant Cry46Abs were cation selective, and their cation preference was also similar. However, the degree of cation selectivity was apparently higher in channel pores formed by the K155E mutant, and reduced selectivity was observed with the E159K and E163K mutants. Our data suggest that channel-pore cation selectivity is a major determinant of Cry46Ab mosquitocidal activity and that cation selectivity can be controlled via mutagenesis targeting the transmembrane β-hairpin region. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2020 MKM: Multiple Kernel Memory for Protecting Page Table Switching Mechanism Against Memory Corruption 97 116 EN Hiroki Kuzuno Graduate School of Natural Science and Technology, Okayama University Toshihiro Yamauchi Graduate School of Natural Science and Technology, Okayama University Countermeasures against kernel vulnerability attacks on an operating system (OS) are highly important kernel features. Some kernels adopt several kernel protection methods such as mandatory access control, kernel address space layout randomization, control flow integrity, and kernel page table isolation; however, kernel vulnerabilities can still be exploited to execute attack codes and corrupt kernel memory. To accomplish this, adversaries subvert kernel protection methods and invoke these kernel codes to avoid administrator privileges restrictions and gain complete control of the target host. To prevent such subversion, we present Multiple Kernel Memory (MKM), which offers a novel security mechanism using an alternative design for kernel memory separation that was developed to reduce the kernel attack surface and mitigate the effects of illegal data manipulation in the kernel memory. The proposed MKM is capable of isolating kernel memory and dedicates the trampoline page table for a gateway of page table switching and the security page table for kernel protection methods. The MKM encloses the vulnerable kernel code in the kernel page table. The MKM mechanism achieves complete separation of the kernel code execution range of the virtual address space on each page table. It ensures that vulnerable kernel code does not interact with different page tables. Thus, the page table switching of the trampoline and the kernel protection methods of the security page tables are protected from vulnerable kernel code in other page tables. An evaluation of MKM indicates that it protects the kernel code and data on the trampoline and security page tables from an actual kernel vulnerabilities that lead to kernel memory corruption. In addition, the performance results show that the overhead is 0.020μs to 0.5445μs, in terms of the system call latency and the application overhead average is 196.27 μs to 6,685.73 μs , for each download access of 100,000 Hypertext Transfer Protocol sessions. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2020 Improvement and Evaluation of a Function for Tracing the Diffusion of Classified Information on KVM 338 349 EN Hideaki Moriyama National Institute of Technology, Ariake College Toshihiro Yamauchi Graduate School of Natural Science and Technology, Okayama University Masaya Sato Graduate School of Natural Science and Technology, Okayama University Hideo Taniguchi Graduate School of Natural Science and Technology, Okayama University The increasing amount of classified information currently being managed by personal computers has resulted in the leakage of such information to external computers, which is a major problem. To prevent such leakage, we previously proposed a function for tracing the diffusion of classified information in a guest operating system (OS) using a virtual machine monitor (VMM). The tracing function hooks a system call in the guest OS from the VMM, and acquiring the information. By analyzing the information on the VMM side, the tracing function makes it possible to notify the user of the diffusion of classified information. However, this function has a problem in that the administrator of the computer platform cannot grasp the transition of the diffusion of classified processes or file information. In this paper, we present the solution to this problem and report on its evaluation. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0941-1291 2020 The neutrophil-to-lymphocyte ratio as a novel independent prognostic factor for multiple metastatic lung tumors from various sarcomas EN Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Kei Namba Department of Thoracic Surgery, Okayama University Hospital Haruchika Yamamoto Department of Thoracic Surgery, Okayama University Hospital Tomohiro Toji Department of Diagnostic Pathology, Okayama University Hospital Junichi Soh Department of Thoracic Surgery, Okayama University Hospital Kazuhiko Shien Department of Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Takeshi Kurosaki Department of Thoracic Surgery, Okayama University Hospital Shinji Otani Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Masaomi Yamane Department of Thoracic Surgery, Okayama University Hospital Katsuhito Takahashi Center for Multidisciplinary Treatment of Sarcoma, Department of Sarcoma Medicine, Kameda Medical Center Toshiyuki Kunisada Department of Orthopedic Surgery, Okayama University Hospital Takahiro Oto Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Purpose</br> Sarcomas are among the most refractory malignant tumors and often recur as pulmonary metastasis. Although the presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with the prognosis of several malignancies, the relationship between the NLR and sarcoma with pulmonary metastasis is unclear. We investigated the impact of the NLR in patients who underwent surgical resection for metastatic lung tumors from various sarcomas.</br> Methods</br> The subjects of this retrospective study were 158 patients with metastatic lung tumors from various sarcomas, who underwent initial pulmonary metastasectomy between 2006 and 2015. We examined the clinicopathological variables, including the NLR and the characteristics of surgical procedures. Survival was estimated by the Kaplan–Meier method and prognostic factors were evaluated by multivariate analysis.</br> Results</br> Multivariate analysis revealed significantly better survival of the group with an NLR < 2.26 immediately before the most recent pulmonary metastasectomy, in addition to such factors as the largest resected lesion being < 22 mm, a disease-free interval of > 2 years, and 3 or more pulmonary metastasectomies.</br> Conclusion</br> The NLR immediately before the most recent pulmonary metastasectomy is a novel independent prognostic factor, which may be helpful when considering repeated pulmonary metastasectomy. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0043-2288 64 6 2020 Effect of numerical aperture on molten area characteristics in micro-joining of glass by picosecond pulsed laser 937 947 EN Yasuhiro Okamoto Graduate School of Natural Science and Technology, Okayama University Zhiyong Ouyang Graduate School of Natural Science and Technology, Okayama University Takumi Fujiwara Graduate School of Natural Science and Technology, Okayama University Akira Okada Graduate School of Natural Science and Technology, Okayama University Glass products with precise and sophisticated shapes are highly demanded in the field of MEMS due to their excellent properties. Ultrashort pulsed laser has been expected to be a powerful and reliable tool for micro-welding of glass. Focusing condition such as numerical aperture (N.A.) is a critical parameter that controls how ultrashort laser pulses interact with and propagate in glass, and it has a great influence on the laser micro-welding characteristics of glass. In order to investigate the quality of welding process, it is important to understand the dependence of the mechanical strength of molten area created in glass specimen with various numerical apertures. Therefore, the mechanical strength of molten area with various numerical apertures was evaluated in micro-welding of glass by picosecond pulsed laser. Higher bending strength could be obtained under an appropriate volume ratio of molten area and glass specimen, when continuous molten areas were formed. In addition, high density and large size of molten area without crack led to higher breaking stress. It is concluded that superior focusing characteristics such as N.A. 0.65 enable a long region of high power density in beam axis, which can satisfy both high mechanical strength and high processing speed. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0361-5235 2020 Failure Characteristics of PZT Ceramic During Cyclic Loading EN Mitsuhiro Okayasu Graduate School of Natural Science and Technology, Okayama University Tsukasa Ogawa Graduate School of Natural Science and Technology, Okayama University Failure characteristics of PbZrTiO3 (PZT) ceramic plates are investigated under cyclic loading with rods of different diameters, i.e., different contact areas (0–20 mm). The voltage generated under loading by the rod with the smallest diameter (contact area) is higher than those for the larger contact areas. This is due to the high strain induced in the PZT ceramic. However, the opposite trend is seen when the loading exceeds 60 N, i.e., the voltage obtained for the smallest contact area is lower. This is caused by failure of the PZT ceramic. The voltage generated under cyclic loading by the 5-mm, 10-mm, 15-mm, and 20-mm rods drops by about 10% in the early cyclic loading stage, but then remains constant until 10,000 cycles. The reduction in voltage is influenced mainly by 90° domain switching. In this case, many grains (about 15% of the total) are switched: a random domain orientation is switched to the ⟨100⟩ direction perpendicular to the ceramic plate, i.e., a crystalline texture is formed. In contrast, there is significant reduction in voltage under loading by the 0-mm rod (point contact). As the extent of domain switching for the 0-mm rod is similar to that for the other rods, the reduction in electrical generation can be attributed to crack generation resulting from the high deformation. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1615-5262 20 2020 Additional kernel observer: privilege escalation attack prevention mechanism focusing on system call privilege changes 461 473 EN Toshihiro Yamauchi Graduate School of Natural Science and Technology, Okayama University Yohei Akao Graduate School of Natural Science and Technology, Okayama University. NTT Communications Corporation Ryota Yoshitani raduate School of Natural Science and Technology, Okayama University Yuichi Nakamura Hitachi Ltd. Masaki Hashimoto Graduate School of Information Security, Institute of Information Security Cyberattacks, especially attacks that exploit operating system vulnerabilities, have been increasing in recent years. In particular, if administrator privileges are acquired by an attacker through a privilege escalation attack, the attacker can operate the entire system and cause serious damage. In this paper, we propose an additional kernel observer (AKO) that prevents privilege escalation attacks that exploit operating system vulnerabilities. We focus on the fact that a process privilege can be changed only by specific system calls. AKO monitors privilege information changes during system call processing. If AKO detects a privilege change after system call processing, whereby the invoked system call does not originally change the process privilege, AKO regards the change as a privilege escalation attack and applies countermeasures against it. AKO can therefore prevent privilege escalation attacks. Introducing the proposed method in advance can prevent this type of attack by changing any process privilege that was not originally changed in a system call, regardless of the vulnerability type. In this paper, we describe the design and implementation of AKO for Linux x86 64-bit. Moreover, we show that AKO can be expanded to prevent the falsification of various data in the kernel space. Then, we present an expansion example that prevents the invalidation of Security-Enhanced Linux. Finally, our evaluation results show that AKO is effective against privilege escalation attacks, while maintaining low overhead. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0344-5704 86 1 2020 Influences of preoperative metformin on immunological factors in early breast cancer 55 63 EN Takahiro Tsukioki Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadahiko Shien Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Yoko Suzuki Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yukiko Kajihara Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Minami Hatono Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kengo Kawada Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mariko Kochi Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takayuki Iwamoto Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokuni Ikeda Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naruto Taira Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyoshi Doihara Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Toyooka Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose</br> Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer.</br> Method</br> We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen.</br> Result</br> There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08).</br> Conclusion</br> Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0942-2056 29 2020 Steep medial tibial slope and prolonged delay to surgery are associated with bilateral medial meniscus posterior root tear 1052 1057 EN Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Tadashi Yamawaki Department of Orthopaedic Surgery, Kousei Hospital Yoshiki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Yuya Kodama Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Purpose</br> Contralateral medial meniscus posterior root tear (MMPRT) can sometimes occur after primary surgeries for MMPRT and lead to unsatisfactory outcomes. The incidence rate and risk factors for contralateral MMPRT have not been well investigated, despite their clinical importance. Therefore, the incidence and predictors of bilateral MMPRT were aimed to be evaluated.</br> Methods</br> Fourteen patients with bilateral MMPRT (group B) and 169 patients with unilateral MMPRT (group U) were enrolled in this study. Sex, age, body mass index, time between injury and surgery, and medial tibial slope angle (MTSA) were compared between the groups. MTSA was measured using lateral radiographs.</br> Results</br> The incidence rate of bilateral MMPRT was 6.2% among all patients with MMPRTs. Multivariate logistic regression analysis showed that a prolonged time between injury and surgery (odds ratio [OR], 1.0; 95% confidence interval [CI] 1.00–1.01; P < 0.05) and steeper MTSA (OR, 1.85; 95% CI 1.21–2.64; P < 0.01) were significantly associated with the development of bilateral MMPRT. Receiver operating characteristic curve analysis showed that MTSA > 10.0° was associated with bilateral MMPRT, with a sensitivity of 93% and specificity of 69%.</br> Conclusion</br> A longer time between injury and surgery and steeper MTSA were risk factors for the development of bilateral MMPRT. Surgeons need to pay close attention to the contralateral knee in addition to the primary injured knees when treating knees with steep MTSA. Besides, early meniscal repair of primary MMPRT would be important to prevent the events of contralateral MMPRT. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0914-7187 34 2020 Improvement of biodistribution profile of a radiogallium-labeled, αvβ6 integrin-targeting peptide probe by incorporation of negatively charged amino acids 575 582 EN Shunsuke Nakamura Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Aya Matsuno Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masashi Ueda Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Objective</br> Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Since αvβ6 integrin has been reported as a promising target for PDAC diagnosis, we previously developed H-Cys(mal-NOTA-67Ga)-(Gly)6-A20FMDV2-NH2 ([67Ga]CG6) as an αvβ6 integrin-targeting probe. Although [67Ga]CG6 specifically binds to αvβ6 integrin-positive xenografts, the uptake of [67Ga]CG6 in the organs surrounding the pancreas, such as the liver and spleen, was comparable to that in the αvβ6 integrin-positive xenografts. We hypothesized that the undesirable accumulation of [67Ga]CG6 in those organs was caused by the positive charges of [67Ga]CG6 (+ 3). In this study, we aimed to decrease [67Ga]CG6 uptake in the liver and spleen by reducing the electric charges of the probe.</br> Methods</br> We synthesized H-Cys(mal-NOTA-67Ga)-(Asp)6-A20FMDV2-NH2 ([67Ga]CD6) and evaluated its affinity to αvβ6 integrin via in vitro competitive binding assay. Isoelectric points of the probes were determined by electrophoresis. Biodistribution study, autoradiography, and immunostaining for β6 integrin were conducted using αvβ6 integrin-positive and negative tumor-bearing mice.</br> Results</br> In vitro competitive binding assay showed that the alteration of the linker had a negligible impact on the affinity of [67Ga]CG6 to αvβ6 integrin. The results of electrophoresis revealed that [67Ga]CG6 was positively charged whereas [67Ga]CD6 was negatively charged. In the biodistribution study, the uptake of [67Ga]CD6 in the αvβ6 integrin-positive xenografts was significantly higher than that in the αvβ6 integrin-negative ones at 60 and 120 min. The uptake of [67Ga]CD6 in the liver and spleen was more than two-fold lower than that of [67Ga]CG6 at both time points. In the immunohistochemistry study, the radioactivity accumulated areas in the autoradiogram of the αvβ6 integrin-positive xenograft roughly coincided with β6 integrin-expressing areas.</br> Conclusion</br> We have successfully reduced the nonspecific uptake in the liver and spleen by altering the linker amino acid from G6 to D6. [67Ga]CD6 overcame the drawbacks of [67Ga]CG6 in its biodistribution. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0167-6806 182 2 2020 NSAS-BC02 substudy of chemotherapy-induced amenorrhea (CIA) in premenopausal patients who received either taxane alone or doxorubicin(A) cyclophosphamide(C) followed by taxane as postoperative chemotherapy 325 332 EN Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Fumikata Hara Breast Medical Oncology Department, Cancer Institute Hospital of JFCR Yukari Uemura Department of Clinical Research, National Center for Global Health and Medicine Hirofumi Mukai Department of Breast and Medical Oncology, National Cancer Center Hospital Toru Watanabe Department of Medical Oncology, Hamamatsu Oncology Center Yasuo Ohashi Department of Integrated Science and Engineering for Sustainable Society, Chuo University Background</br> Chemotherapy-induced amenorrhea (CIA) is one of the critical side effects from the chemotherapy in premenopausal patients with breast cancer. The goals of our study are the following: (1) to investigate the factors affecting the incidence of CIA; and (2) to evaluate the prognostic role of CIA in premenopausal patients with breast cancer.</br> Methods</br> We conducted a post hoc retrospective substudy to examine the incidence of the CIA and the relationship between CIA and prognosis in NSAS-BC02 that compared taxane alone to Doxorubicin(A) Cyclophosphamide(C) followed by taxane in postoperative patients with node-positive breast cancer</br> Results</br> Of 395 premenopausal women, 287 (72.7%) had CIA due to protocol treatment. Regarding type of protocol regimen, proportion of CIA was 76.9% in AC Paclitaxel(P), 75.2% in AC Docetaxel(D), 62.8% in PTX, and 75.2% in DTX. Predictive factors of CIA were age increase by 5 years (OR 1.50), ER positivity (OR 2.08), and HER2 3 + ( OR 0.40) according to logistic regression analysis. According to the log rank test and the Cox proportional hazards model, CIA group had significantly better disease-free survival than non-CIA group (P < .0001). However, according to time-dependent Cox model that was used to reduce guarantee-time bias, CIA was not a statistically significant prognostic factor in both ER-positive and ER-negative patients.</br> Conclusion</br> Treatment with taxane alone caused high frequency of CIA in premenopausal women with breast cancer. CIA did not turn out to be an independent prognostic factor, taking guarantee-time bias into consideration. Further clinical studies are needed to validate these findings. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1435-0211 66 2020 Color measurements according to three sections of wood EN Seiji Hirata Okayama University Graduate School of Education Saori Hayashi People Software Corporation Masamitsu Ohta Former Graduate School of Agricultural and Life Sciences, The University of Tokyo The purpose of this study was to measure each color of three sections of wood with instruments, and to examine whether there were differences between each color of three sections. The total number of tree species measured was 60, with the same number of conifers and broadleaf trees. A test piece, which was a cube with one side of 34 mm, was prepared for each tree species. End grain, edge grain, bark side and pith side of each test piece were flattened by a hand planer. Then, lightness L* and hue/saturation (a*, b*) in the L*a*b* color space were measured with a spectrophotometer. The results showed that the end grain had a lower L* compared to the other planes. The end grain was reddish and yellowish because it had a large a* and small b*. When chroma C* and hue angle h in the L*C*h color space were calculated from a* and b*, the end grain had a small dullness with less vividness because C* was smaller than the other planes. L*, a*, b*, C* and h on the other planes excluding the end grain were almost equal for each plane. Furthermore, it was found that the plane whose lightness L* had the strongest correlation with the density of the test piece was the end grain. Therefore, the correlation diagrams between the density, average of annual ring width, and L*of the end grain of each test piece were shown. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2363-9024 5 1 2019 Anesthetic management of a patient with sodium-channel myotonia: a case report 77 EN Naohisa Matsumoto Department of Anesthesiology and Resuscitology, Okayama University Hospital Rei Nishimoto Department of Anesthesiology and Resuscitology, Okayama University Hospital Yoshikazu Matsuoka Departments of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine Yoshimasa Takeda Department of Anesthesiology and Resuscitology, Okayama University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Hospital Background: Sodium-channel myotonia (SCM) is a nondystrophic myotonia, characterized by pure myotonia without muscle weakness or paramyotonia. The prevalence of skeletal muscle channelopathies is approximately 1 in 100,000, and the prevalence of SCM is much lower. To our knowledge, this is the first report on anesthetic management of a patient with SCM. </br> Case presentation: A 23-year-old woman with congenital nasal dysplasia and SCM was scheduled to undergo rhinoplasty with autologous costal cartilage. Total intravenous anesthesia without muscle relaxants was administered followed by continuous intercostal nerve block. Although transient elevation of potassium level in the blood was observed during surgery, the patient did not show exacerbation of myotonic or paralytic symptoms in the postoperative period. </br> Conclusion: Total intravenous anesthesia and peripheral nerve block can be administered safely to a patient with SCM. However, careful monitoring of the symptoms and electrolytes is recommended. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 09422056 29 2020 Placement of an anatomic tibial tunnel significantly improves the medial meniscus posterior extrusion at 90° of knee flexion following medial meniscus posterior root pullout repair 1025 1034 EN Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Hospital Yoshiki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Yuya Kodama Department of Orthopaedic Surgery, Okayama University Hospital Tomohito Hino Department of Orthopaedic Surgery, Okayama University Hospital Shin Masuda Department of Orthopaedic Surgery, Okayama University Hospital Shinichi Miyazawa Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Purpose</br> The purpose of this study was to evaluate the influence of tibial tunnel position in pullout repair for a medial meniscus (MM) posterior root tear (MMPRT) on postoperative MM extrusion.</br></br> Methods</br> Thirty patients (median age 63 years, range 35–72 years) who underwent transtibial pullout repairs for MMPRTs were included. Three-dimensional computed tomography images of the tibial surface were evaluated using a rectangular measurement grid for assessment of tibial tunnel position and MM posterior root attachment. Preoperative and postoperative MM medial extrusion (MMME) and posterior extrusion (MMPE) at 10° and 90° knee flexion were measured using open magnetic resonance imaging.</br></br> Results</br> Tibial tunnel centers were located more anteriorly and more medially than the anatomic center (median distance 5.8 mm, range 0–9.3 mm). The postoperative MMPE at 90° knee flexion was significantly reduced after pullout repair, although there was no significant reduction in MMME or MMPE at 10° knee flexion after surgery. In the correlation analysis of the displacement between the anatomic center to the tibial tunnel center and improvements in MMME, and MMPE at 10° and 90° knee flexion, there was a significant positive correlation between percentage distance and improvement of MMPE at 90° knee flexion.</br></br> Conclusion</br> This study demonstrated that the nearer the tibial tunnel position to the anatomic attachment of the MM posterior root, the more effective the reduction in MMPE at 90° knee flexion. Our results emphasize that an anatomic tibial tunnel should be created in the MM posterior root to improve the postoperative MMPE and protect the articular cartilage in a knee flexion position. Placement of an anatomic tibial tunnel significantly improves the MMPE at 90° of knee flexion after MM posterior root pullout repair. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0301634X 59 3 2020 Comparison of antioxidative effects between radon and thoron inhalation in mouse organs EN Yusuke Kobashi Graduate School of Health Sciences, Okayama University Takahiro Kataoka Graduate School of Health Sciences, Okayama University Norie Kanzaki Graduate School of Health Sciences, Okayama University Tsuyoshi Ishida Graduate School of Health Sciences, Okayama University Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Hiroshi Tanaka Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Yuu Ishimori Prototype Fast Breeder Reactor Monju, Japan Atomic Energy Agency Fumihiro Mitsunobu Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kiyonori Yamaoka Graduate School of Health Sciences, Okayama University Radon therapy has been traditionally performed globally for oxidative stress-related diseases. Many researchers have studied the beneficial effects of radon exposure in living organisms. However, the effects of thoron, a radioisotope of radon, have not been fully examined. In this study, we aimed to compare the biological effects of radon and thoron inhalation on mouse organs with a focus on oxidative stress. Male BALB/c mice were randomly divided into 15 groups: sham inhalation, radon inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3, and thoron inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3 were carried out. Immediately after inhalation, mouse tissues were excised for biochemical assays. The results showed a significant increase in superoxide dismutase and total glutathione, and a significant decrease in lipid peroxide following thoron inhalation under several conditions. Additionally, similar effects were observed for different doses and inhalation times between radon and thoron. Our results suggest that thoron inhalation also exerts antioxidative effects against oxidative stress in organs. However, the inhalation conditions should be carefully analyzed because of the differences in physical characteristics between radon and thoron. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 16181247 109 2020 Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis 239 249 EN Daichi Isoshima Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Keisuke Yamashiro Okayama University Hospital Kazuyuki Matsunaga Okayama University Hospital Makoto Taniguchi Oral Microbiome Center, Taniguchi Dental Clinic Takehiro Matsubara Okayama University Hospital Shuta Tomida Okayama University Hospital Shinzo Ota Department of Neurology, Brain Attack Center Ota Memorial Hospital Michiyoshi Sato Department of Neurology, Brain Attack Center Ota Memorial Hospital Yutaka Shimoe Department of Neurology, Brain Attack Center Ota Memorial Hospital Tatsuo Kohriyama Department of Neurology, Brain Attack Center Ota Memorial Hospital Zulema Arias Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Omori Okayama University Hospital Tadashi Yamamoto Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shogo Takashiba Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques (APs). We investigated the general and oral conditions from each patient and performed next-generation sequencing (NGS) analysis for all bacterial samples. There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the tongue surface were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. These results suggested that oral bacteria did not affect the formation of atheromatous plaques directly. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 14795876 17 2019 Analysis of the role of the Hippo pathway in cancer 116 EN Yanyan Han Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Cancer is a serious health issue in the world due to a large body of cancer-related human deaths, and there is no current treatment available to efficiently treat the disease as the tumor is often diagnosed at a serious stage. Moreover, Cancer cells are often resistant to chemotherapy, radiotherapy, and molecular-targeted therapy. Upon further knowledge of mechanisms of tumorigenesis, aggressiveness, metastasis, and resistance to treatments, it is necessary to detect the disease at an earlier stage and for a better response to therapy. The hippo pathway possesses the unique capacity to lead to tumorigenesis. Mutations and altered expression of its core components (MST1/2, LATS1/2, YAP and TAZ) promote the migration, invasion, malignancy of cancer cells. The biological significance and deregulation of it have received a large body of interests in the past few years. Further understanding of hippo pathway will be responsible for cancer treatment. In this review, we try to discover the function of hippo pathway in different diversity of cancers, and discuss how Hippo pathway contributes to other cellular signaling pathways. Also, we try to describe how microRNAs, circRNAs, and ZNFs regulate hippo pathway in the process of cancer. It is necessary to find new therapy strategies for cancer. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 09302794 35 1 2020 Correction to: Outcomes of endoscopic treatment for malignant biliary obstruction in patients with surgically altered anatomy: analysis of risk factors for clinical failure 239 240 EN Takeshi Tomoda Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Eijiro Ueta Department of Gastroenterology and Hepatology, Okayama University Hospital Yuuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Yousuke Saragai Department of Gastroenterology and Hepatology, Okayama University Hospital Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 13406868 27 5 2020 The efficacy of sequential second-line endocrine therapies (ETs) in postmenopausal estrogen receptor-positive and HER2-negative metastatic breast cancer patients with lower sensitivity to initial ETs 973 981 EN Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tomomi Fujisawa Department of Breast Oncology, Gunma Prefectural Cancer Center Tadahiko Shien Okayama University Hospital Kazuhiro Araki Department of Medical Oncology, Gunma Prefectural Cancer Center Kentaro Sakamaki Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo Takafumi Sangai Department of Breast and Thyroid Surgery, Chiba University Hospital Yuichiro Kikawa Department of Breast Surgery, Kobe City Medical Center General Hospital Shintaro Takao Department of Breast Surgery, Hyogo Cancer Center Reiki Nishimura Department of Breast Oncology, Kumamoto Shinto General Hospital Masato Takahashi Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center Tomohiko Aihara Breast Center, Aihara Hospital Hirofumi Mukai Division of Breast and Medical Oncology, National Cancer Center Hospital East Naruto aira Department of Breast and Endocrine Surgery, Okayama University Hospital, Purpose</br> Second-line endocrine therapy (ET) for estrogen receptor (ER)-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (MBC) is offered based on the response to first-line ET. However, no clinical trials have evaluated the efficacy and safety of secondary ETs in patients with poor responses to initial ET. This study evaluated the efficacy of second-line ET in ER-positive and HER2-negative postmenopausal MBC patients with low or very low sensitivity to initial ET.</br> Methods</br> This multicenter prospective observational cohort study evaluated the response of 49 patients to second-line ETs in postmenopausal MBC patients with low or very low sensitivity to initial ET. The primary endpoint was the clinical benefit rate (CBR) for 24 weeks.</br> Results</br> Of the 49 patients assessed, 40 (82%) received fulvestrant in the second line, 5 (10%) received selective estrogen receptor modulators, 3 (6%) received aromatase inhibitors (AIs) alone, and 1 received everolimus with a steroidal AI. The overall CBR was 44.9% [90% confidence interval (CI): 34.6–57.6, p = 0.009]; CBR demonstrated similar significance across the progesterone receptor-positive (n = 39, 51.3%, 90% CI: 39.6–65.2, p = 0.002), very low sensitivity (n = 17, 58.8%, 90% CI: 42.0–78.8, p = 0.003), and non-visceral metastases (n = 25, 48.0%, 90% CI: 34.1–65.9, p = 0.018) groups. The median progression-free survival was 7.1 months (95% CI: 5.6–10.6).</br> Conclusion</br> Second-line ET might be a viable treatment option for postmenopausal patients with MBC with low and very low sensitivity to initial ET. Future studies based on larger and independent cohorts are needed to validate these findings. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 02545330 284 2019 Portfolio allocation problems between risky and ambiguous assets 63 79 EN Takao Asano Faculty of Economics, Okayama University Yusuke Osaki Faculty of Commerce, Waseda University This paper considers a portfolio allocation problem between a risky asset and an ambiguous asset, and investigates how greater ambiguity aversion influences the optimal proportion invested in the two assets. We derive several sufficient conditions under which greater ambiguity aversion decreases the optimal proportion invested in the ambiguous asset. Furthermore, we consider an international diversification problem as an application and show that ambiguity aversion partially resolves the home bias puzzle. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0721832X 257 2019 Magnetic resonance imaging findings of age-related distance esotropia in Japanese patients with high myopia 662 662 EN Reika Kono Department of Ophthalmology, Medical School, Okayama University Hiroshi Ohtsuki Division of Ophthalmology, Okayama Saiseikai General Hospital Fumiko Kishimoto Division of Ophthalmology, Ibara City Hospital Ichiro Hamasaki Department of Ophthalmology, Okayama University Hospital Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Fumio Shiraga Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose<br/> This study aimed to investigate the characteristics of the extraocular muscles and the orbital connective tissue pulleys in Japanese patients with age-related distance esotropia (ARDE) and high myopia using magnetic resonance imaging (MRI).<br/> Methods<br/> This was a retrospective case-series study. High-resolution coronal MRI scans of 12 orbits were obtained in 6 patients with ARDE and high myopia (age range: 51–69 years). We analyzed the images to determine the positions of the rectus muscle pulleys relative to the center of the globe, the integrity of the lateral rectus-superior rectus muscle (LR-SR) band, and the LR angle (the angle between the major axis of the LR and the vertical plane).<br/> Results<br/> The distance esotropia ranged from 4 to 25∆, and 3 cases exhibited vertical deviations. The mean (±standard deviation (SD)) axial length was 28.5 (± 1.6) mm. The mean positions of the medial rectus muscle pulley and LR pulley were 1.3 mm inferior and 1.4 mm inferior, respectively, to those seen in the normal control group in our previous study (P = 0.002 and P = 0.05, respectively). All 12 orbits had abnormal elongated LR-SR bands, and 8 orbits (67%) displayed ruptured LR-SR bands. The LR angle (mean±SD; 18.8° ± 8.5°) increased significantly with the inferior displacement of the LR pulley (R2 = 0.77, P = 0.0002).<br/> Conclusions<br/> Inferior displacement of the LR pulley and abnormal LR-SR bands were seen in Japanese ARDE patients with high myopia, as was found in ARDE patients without high myopia. The LR angle might be useful for judging the degree of LR pulley displacement. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 09422056 28 2020 Medial meniscus posterior root repair restores the intra-articular volume of the medial meniscus by decreasing posteromedial extrusion at knee flexion 3435 3442 EN Yoshiki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Takatsugu Yamauchi Division of Radiology, Medical Technology Department, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School Yusuke Kamatsuki Department of Orthopaedic Surgery, Kochi Health Science Center Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Graduate School Yuya Kajiki Department of Orthopaedic Surgery, Okayama University Graduate School Ximing Zhang Department of Orthopaedic Surgery, Okayama University Graduate School Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School Purpose</br> Transtibial repair of a medial meniscus posterior root tear (MMPRT) can improve clinical outcomes, although meniscal extrusion remains. However, few studies have investigated the volume of meniscal extrusion. This study aimed to evaluate the effect of transtibial repair in reducing the volume using three-dimensional (3D) magnetic resonance imaging, at 10° and 90° knee flexion.</br> Methods</br> Twenty patients with MMPRTs and 16 volunteers with normal knees participated. The 3D models of meniscus were constructed using SYNAPSE VINCENT®. The meniscal extrusion and its volume were measured at 10° and 90° knee flexion. Differences between the pre- and postoperative examinations were assessed using the Wilcoxon signed-rank test. The postoperative parameters were compared to those in patients with normal knees.</br> Results</br> There were no significant pre- and postoperative differences in any parameter at 10° knee flexion. At 90° knee flexion, the posterior extrusion and its meniscal volume were decreased significantly after transtibial repair (p < 0.05), even though these parameters were larger than in the normal knees. On the other hand, intra-articular meniscal volume calculated by the extrusion volume was increased to the level of the normal knee.</br> Conclusions</br> This study demonstrated that transtibial repairs improved the intra-articular/intra-tibial surface volume of the medial meniscus by reducing the posteromedial extrusion during knee flexion. This 3D analysis is clinically relevant in evaluating that, while transtibial root repair has a limited ability to reduce meniscal extrusion, it can restore the functional volume of the medial meniscus which contributes to the shock absorber postoperatively. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1863-6705 68 1 2019 Prolonged warm ischemia exacerbated acute rejection after lung transplantation from donation after cardiac death in a mouse 57 62 EN Yutaka Hirano Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery, Okayama University Hospital Sumiharu Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Okada Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Otani Department of Organ Transplant Center, Okayama University Hospital Toshiaki Ohara Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaomi Yamane Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Oto Department of Organ Transplant Center, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: In lung transplantation (LTx) from donation after cardiac death (DCD), the donor lungs are inevitably exposed to warm ischemic time (WIT) between the cardiac arrest and the initiation of cold preservation. We conducted this study to examine the effect of prolonged WIT on lung allograft rejection in a murine model of LTx from DCD.<br/> Methods: Allogeneic BALB/c → B6 LTx from DCD was performed with a WIT of 15 min (WIT15 group, n = 5) or 60 min (WIT60 group, n = 5). Recipients were immunosuppressed by perioperative costimulatory blockade. The lung allografts were analyzed by histology and flow cytometry on day 7 after the LTx.<br/> Results: Histologically, the rejection grade in the WIT60 group was significantly higher than that in the WIT15 group (3.4 ± 0.4 vs. 2.2 ± 0.2, P = 0.0278). Moreover, the intragraft CD8+ to CD4+ T cell ratio in the WIT60 group was significantly higher than that in the WIT15 group (2.3 ± 0.12 vs. 1.2 ± 0.11, P < 0.0001).<br/> Conclusions: Prolonged WIT could exacerbate the severity of lung allograft rejection after LTx from DCD. Minimization of the WIT could improve the outcomes after LTx from DCD. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2190-1678 11 2 2019 The hypoglycemia-prevention effect of sensor-augmented pump therapy with predictive low glucose management in Japanese patients with type 1 diabetes mellitus: a short-term study 97 104 EN Akihiro Katayama Diabetes Center, Okayama University Hospital Atsuhito Tone Diabetes Center, Okayama Saiseikai General Hospital Mayu Watanabe Department of Primary Care and Medical Education, Okayama University Sanae Teshigawara Diabetes Center, Okayama Saiseikai General Hospital Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuko Nakatsuka Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Jun Wada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aims/introduction</br> The predictive low glucose management (PLGM) system was introduced in March 2018 in Japan. Although there are some reports demonstrating the benefit of PLGM in preventing hypoglycemia, no data are currently available in Japanese patients with type 1 diabetes mellitus (T1DM). The aim of the present study is to evaluate the effect of PLGM with sensor-augmented pump therapy in the prevention of hypoglycemia in Japanese patients.</br> Materials and methods</br> We included 16 patients with T1DM who used the MiniMed®640G system after switching from the MiniMed®620G system. We retrospectively analysed the data of the continuous glucose monitoring system in 1 month after switching to MiniMed®640G.</br> Results</br> The area under the curve (AUC) of hypoglycemia of < 70 mg/dL was lowered from 0.42 ± 0.43 mg/dL day to 0.18 ± 0.18 mg/dL day (P = 0.012). Correspondingly, the duration of severe hypoglycemia (< 54 mg/dL) was reduced significantly from 15.3 ± 21.7 min/day to 4.8 ± 6.9 min/day (P = 0.019). The duration of hypoglycemia was reduced, but the reduction was not significant. Regarding the AUC for hyperglycemia > 180 mg/dL and the duration of hyperglycemia did not change. With the PLGM function, 79.3% of the predicted hypoglycemic events were avoided.</br> Conclusions</br> The hypoglycemia avoidance rate was comparable to those in previous reports. In addition, we demonstrated that PLGM can markedly suppress severe hypoglycemia without deteriorating glycemic control in Japanese T1DM patients. It is necessary to further investigate the effective use of the PLGM feature such as establishing a lower limit and the timing of resumption. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2199-3823 5 4 2019 Separation Between Silicon and Aluminum Powders Contained Within Pulverized Scraped Silicon-Based Waste Solar Cells by Flotation Method 551 560 EN Sho Harada Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Md. Azhar Uddin Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Yoshiei Kato Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Takanori Kawanishi Wet Process Division, Toho Kasei Co., Ltd Yoshiaki Hayashi Wet Process Division, Toho Kasei Co., Ltd There are few study examples on the separation of metals by floating method. In this study, separation of silicon and aluminum, which are the main components of silicon-based solar cell module, was carried out by floating method in order to purify silicon from waste solar cell module. The selection of surfactant, control of electric charge, wettability of the solid particles, surface tensions, and bubble surface area are important for separation of solids by floating method. Sodium dodecyl sulfate (SDS) can increase the hydrophobicity of aluminum powder due to the difference of surface potentials between silicon and aluminum. SDS behaves as a collector of aluminum as well as a frothing agent to decrease the bubble size. At a SDS concentration of 2 g/L and sample dipping time of 10 min, 80.1 mass% of aluminum was floated and separated, and the sedimentary silicon reached a purity of 90.7% from a mixture of 50 mass% aluminum and 50 mass% silicon. Finally, at a pH value of 7.0, SDS concentration between 1.0 and 2.5 g/L and air flow rate of 2.5 L/min (STP) were suitable experimental conditions to purify silicon from a mixture of silicon and aluminum by flotation separation method. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0003-6862 54 4 2019 Characterization of the channel-pores formed by Bacillus thuringiensis Cry46Ab toxin in planar lipid bilayers 389 398 EN Akira Sakakibara Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University So Takebe Graduate School of Biology-Oriented Science and Technology, Kindai University Toru Ide Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tohru Hayakawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Cry46Ab from Bacillus thuringiensis TK-E6 is a new mosquitocidal toxin with aerolysin-type architecture, and has been shown that co-administration of Cry46Ab with other mosquitocidal Cry toxins results in synergistic toxicity against Culex pipiens Coquillett (Diptera: Culicidae) mosquito larvae. Cry46Ab, therefore, is expected to find use in improving the insecticidal activity of B. thuringiensis-based bioinsecticides. In the present study, the mode of action of Cry46Ab was explored by single-channel measurements of Cry46Ab channel-pores. The single-channel conductances of channel-pores formed in planar lipid bilayers by Cry46Ab were determined to be 31.8 +/- 2.7 pS in 150 mM NaCl and 24.2 +/- 0.7 pS in 150 mM CaCl2. Ion-selectivity measurements revealed that the channel-pores formed by Cry46Ab were cation selective. The permeability ratio of K+ to Cl-was approximately 4, and the preferences for cations were K+ > Na+, K+ > Ca2+, and Ca2+ > Na+. A calcein release assay using liposomes suggested that Cry46Ab influences the integrity of membrane vesicles. Formation of cation-selective channel-pores has been observed with other insecticidal Cry toxins that have structures distinct from those of Cry46Ab; the capability of forming such pores may be a property required of insecticidal toxins. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1536-1632 21 3 2018 Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer's Disease 519 528 EN Yuki Matsuura Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masashi Ueda Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yusuke Higaki Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Sano Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University Hideo Saji Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University Shuichi Enomoto Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University PURPOSE:<br/> In patients with Alzheimer's disease (AD), the loss of cerebral nicotinic acetylcholine receptors (nAChRs) that are implicated in higher brain functions has been reported. However, it is unclear if nAChR deficits occur in association with cognitive impairments. The purpose of this study was to assess the relationship between nAChR deficits and cognitive impairments in a mouse model of AD (APP/PS2 mice).<br/> PROCEDURES:<br/> The cognitive abilities of APP/PS2 and wild-type mice (aged 2-16 months) were evaluated using the novel object recognition test. Double-tracer autoradiography analyses with 5-[125I]iodo-A-85380 ([125I]5IA: α4β2 nAChR imaging probe) and 2-deoxy-2-[18F]fluoro-D-glucose were performed in both mice of different ages. [123I]5IA-single-photon emission tomography (SPECT) imaging was also performed in both mice at 12 months of age. Furthermore, each age cohort was investigated for changes in cognitive ability and expression levels of α7 nAChRs and N-methyl-D-aspartate receptors (NMDARs). <br/>RESULTS:<br/> No significant difference was found between the APP/PS2 and wild-type mice at 2-6 months of age in terms of novel object recognition memory; subsequently, however, APP/PS2 mice showed a clear cognitive deficit at 12 months of age. [125I]5IA accumulation decreased in the brains of 12-month-old APP/PS2 mice, i.e., at the age at which cognitive impairments were first observed; this result was supported by a reduction in the protein levels of α4 nAChRs using Western blotting. nAChR deficits could be noninvasively detected by [123I]5IA-SPECT in vivo. In contrast, no significant changes in glycometabolism, expression levels of α7 nAChRs, or NMDARs were associated with cognitive impairments in APP/PS2 mice.<br/> CONCLUSION:<br/> A decrease in cerebral α4β2 nAChR density could act as a biomarker reflecting cognitive impairments associated with AD pathology. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0941-1291 49 8 2019 Impact of chronic lung allograft dysfunction, especially restrictive allograft syndrome, on the survival after living-donor lobar lung transplantation compared with cadaveric lung transplantation in adults: a single-center experience 686 693 EN Seiichiro Sugimoto Department of General Thoracic Surgery, Okayama University Hospital Haruchika Yamamoto Department of General Thoracic Surgery, Okayama University Hospital Takeshi Kurosaki Department of Organ Transplant Center, Okayama University Hospital Shinji Otani Department of Organ Transplant Center, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery, Okayama University Hospital Masaomi Yamane Department of General Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Okayama University Hospital Takahiro Oto Department of Organ Transplant Center, Okayama University Hospital PURPOSE:<br/> The differences in chronic lung allograft dysfunction (CLAD) between living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT) remain unclear. We conducted this study to compare the impact of CLAD on the outcomes after LDLLT vs. CLT. <br/> METHODS:<br/> We conducted a retrospective review of the data of 97 recipients of bilateral lung transplantation, including 51 recipients of LDLLT and 46 recipients of CLT.<br/> RESULTS:<br/> The CLAD-free survival and overall survival after LDLLT were similar to those after CLT. CLAD and restrictive allograft syndrome (RAS), but not bronchiolitis obliterans syndrome (BOS), developed significantly later after LDLLT than after CLT (p = 0.015 and p = 0.035). Consequently, patients with CLAD and RAS, but not those with BOS, after LDLLT had a significantly better overall survival than those after CLT (p = 0.037 and p = 0.0006). Furthermore, after the diagnosis of CLAD, the survival of patients with RAS after LDLLT tended to be better than that after CLT (p = 0.083).<br/> CONCLUSION:<br/> CLAD, especially RAS, appears to develop later after LDLLT than after CLT and seems to have a lower impact on the overall survival after LDLLT than that after CLT. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0941-1291 49 3 2018 Feasibility of lung transplantation from donors mechanically ventilated for prolonged periods 254 260 EN Seiichiro Sugimoto Department of General Thoracic SurgeryOkayama University Hospital Takeshi Kurosaki Department of Organ Transplant CenterOkayama University Hospital Shinji Otani Department of Organ Transplant CenterOkayama University Hospital Shin Tanaka Department of General Thoracic SurgeryOkayama University Hospital Yukiko Hikasa Department of Anesthesiology and ResuscitologyOkayama University Hospital Masaomi Yamane Department of General Thoracic SurgeryOkayama University Hospital Shinichi Toyooka Department of General Thoracic SurgeryOkayama University Hospital Motomu Kobayashi Department of Anesthesiology and ResuscitologyOkayama University Hospital Takahiro Oto Department of Organ Transplant CenterOkayama University Hospital PURPOSE:<br/> When patients are mechanically ventilated for more than 5 days, they are usually declined as donors for lung transplantation (LTx); thus, the long-term outcomes of LTx from such donors remain unclear. We investigated the feasibility of LTx from donors that had been mechanically ventilated for prolonged periods.<br/> METHODS:<br/> The subjects of this retrospective comparative investigation were 31 recipients of LTx from donors who had been mechanically ventilated for < 5 days (short-term group) and 50 recipients of LTx from donors who had been mechanically ventilated for ≥ 5 days (long-term group).<br/> RESULTS:<br/> The median duration of donor mechanical ventilation was 3 days in the short-term group and 8.5 days in the long-term group. However, other than the difference in the duration of donor ventilation, there were no significant differences in the clinical characteristics of the donors or recipients between the groups. The overall survival rate after LTx was comparable between the long-term group and short-term group (5-year survival rate, 66.6% vs. 75.2%).<br/> CONCLUSION:<br/> The potential inclusion of donors who have been on mechanical ventilation for more than 5 days could be a feasible strategy to alleviate donor organ shortage. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2363-9024 5 51 2019 Early detection of cerebral ischemia due to pericardium traction using cerebral oximetry in pediatric minimally invasive cardiac surgery: a case report 53 EN Fumiaki Hayashi Department of Anesthesiology and Resuscitology, Okayama University Hospital, Rei Nishimoto Department of Anesthesiology and Resuscitology, Okayama University Hospital, Kazuyoshi Shimizu Department of Anesthesiology and Resuscitology, Okayama University Hospital, Tomoyuki Kanazawa Department of Anesthesiology and Resuscitology, Okayama University Hospital, Tatsuo Iwasaki Department of Anesthesiology and Resuscitology, Okayama University Hospital, Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Hospital, Background<br/> Minimally invasive cardiac surgery (MICS) for simple congenital heart defects has become popular, and monitoring of regional cerebral oxygen saturation (rSO2) is crucial for preventing cerebral ischemia during pediatric MICS. We describe a pediatric case with a sudden decrease in rSO2 during MICS.<br/> Case presentation<br/> An 8-month-old male underwent minimally invasive ventricular septal defect closure. He developed a sudden decrease in rSO2 and right radial artery blood pressure (RRBP) without changes in other parameters following pericardium traction. The rSO2 and RRBP immediately recovered after removal of pericardium fixation. Obstruction of the right innominate artery secondary to the pericardium traction would have been responsible for it.<br/> Conclusions<br/> Pericardium traction, one of the common procedures during MICS, triggered rSO2 depression alerting us to the risk of cerebral ischemia. We should be aware that pericardium traction during MICS can lead to cerebral ischemia, which is preventable by cautious observation of the patient. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0936-8051 140 4 2019 External iliac artery thrombosis following open reduction of acetabular fracture: a case report and literature review 481 485 EN Norio Yamamoto Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Tomoyuki Noda Department of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taichi Saito Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Takenori Uehara Department of Emergency Healthcare and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yasunori Shimamura Department of Sports Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science BACKGROUND:<br/> Postoperative thrombosis of the external iliac artery (EIA) following open reduction and internal fixation for acetabular fracture is extremely rare.<br/> PURPOSE:<br/> To report a patient with EIA thrombosis following open reduction and internal fixation using the modified ilioinguinal approach for acetabular fractures.<br/> STUDY DESIGN:<br/> This is a case report of a 69-year-old male with a left acetabular fracture who was treated surgically.<br/> METHODS:<br/> A 69-year-old male presented with left hip pain after a 1.5-m fall. Radiographs revealed left acetabular anterior wall and posterior hemitransverse fractures with dome impaction. Computed tomography (CT) showed atherosclerotic changes in many arteries. Open reduction and internal fixation were performed using the modified ilioinguinal approach. Adhesion around the external iliac vessels was severe, and the external iliac vein (EIV) ruptured during exposure. After EIV repair, anatomical reduction was achieved and the fracture was fixed using a reconstruction plate. Nine hours after surgery, the left lower limb showed acute ischemic symptoms. Contrast-enhanced CT indicated complete occlusion of the left EIA. The patient was immediately taken for a thrombectomy via EIA cut-down using a Fogarty catheter. Postoperatively, he had palpable dorsalis pedis and posterior tibial pulses; however, post-reperfusion compartment syndrome developed. Fasciotomy of the left leg was performed.<br/> RESULTS:<br/> At the 2-year and 4-month follow-up, he was pain-free in his hip and leg. Although he was walking with a cane, activity was limited due to a mild foot drop.<br/> CONCLUSIONS:<br/> It is very important for surgeons to consider EIA thrombosis as a potential complication following open reduction and internal fixation. In this case, EIA thrombosis could be explained by preoperative atherosclerotic changes and intraoperative vascular handling procedures. Preoperative screening and management, and meticulous surgical procedures are necessary for patients with a high risk of thrombosis. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 14384957 21 6 2019 Current status and behavior modeling on household solid-waste separation: a case study in Da Nang city, Vietnam 1462 1476 EN Vu Chi Mai Tran Graduate School of Environmental and Life Science, Okayama University Hoang Son Le University of Science and Technology, The University of Danang Yasuhiro Matsui Graduate School of Environmental and Life Science, Okayama University This study focused on household solid-waste recycling in Da Nang city, Vietnam to assess the existing separation behavior and clarify the factors influencing the separation behavior. The authors conducted a questionnaire survey for 150 households in 6 urban districts, which consisted of household attributes, separation behavior, and the household's attitude on recycling and the environment. The waste separation rates were determined for leftover food and 13 recyclable items and the recyclable disposal habit was also assessed. The separation rate of leftover food was 77.3%. Among 13 surveyed recyclable items, plastic bottles and metal cans were two popular items with higher separation rate (72.5% and 63.8%, respectively). To identify the conscious structure and determinants of separation behavior, the authors developed a predictive model on the separation behavior of leftover food and recyclables by logistic and multiple linear regression analyses. The positive factors included behavior intention, sympathy for the collector, incentive brought by recycling, goal intention, internal norm, and perception of responsibility and seriousness. The negative factor was evaluation of trouble. The authors also analyzed the differences in separation rates among attributes. Based on the significant influence factors and attributes, the authors suggested how to promote separation behavior. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2194-5357 2018 A Proposal of Code Completion Problem for Java Programming Learning Assistant System 855 864 EN Htoo Htoo Sandi Kyaw Department of Information Science and TechnologyUniversity of Technology Yatanarpon Cyber City Shwe Thinzar Aung Department of Information Science and TechnologyUniversity of Technology Yatanarpon Cyber City Hnin Aye Thant Department of Electrical and Communication Engineering Okayama University Nobuo Funabiki Department of Electrical and Communication Engineering Okayama University To enhance Java programming educations in schools, we have developed a Web-based Java Programming Learning Assistant System (JPLAS) that provides a variety of programming assignments to cover different learning stages. For the first stage, JPLAS offers the element fill-in-blank problem where students study the grammar and code reading through filling the blank elements, composed of reserved words, identifiers, and control symbols, in a high-quality code. Unfortunately, it has been observed that students can fill the blanks without reading the code carefully, because the choice is limited for each blank. In this paper, we propose a code completion problem as a generalization of the element fill-in-blank problem. To solve the drawback, it does not explicitly show blank locations in the code, which expects students to carefully read the code to understand the grammar and code structure. The correctness of the answer is verified through string matching of each statement with the filled elements and the corresponding correct one. Besides, to encourage students to study readable code writing, the correct statement satisfies the coding rules including the spaces. For evaluations, we generated six code completion and element fill-in-blank problems respectively, and asked ten students in two universities to solve them. Their solution results show that the code completion problem is much harder than the element fill-in-blank problem, and requires far deeper code reading and understanding of coding rules. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0289-0771 36 2 2018 Responses to relaxed and reverse selection in strains artificially selected for duration of death-feigning behavior in the red flour beetle, Tribolium castaneum 161 168 EN Kentarou Matsumura Graduate School of Environmental and Life Science, Okayama University Takahisa Miyatake Graduate School of Environmental and Life Science, Okayama University Divergent lines selected artificially for many generations make it possible to answer two questions: (1) whether genetic variation still exists within the selected population; and (2) whether the selection itself is costly for the selected strain. In previous studies, the red flour beetle Tribolium castaneum was divergently selected artificially for duration of death-feigning, and strains selected for longer (L-strain) and shorter (S-strain) durations of death-feigning have been established (Miyatake et al. 2004, 2008). Because the selection experiments have been conducted for more than 27 generations, genetic variation may be eroded. Furthermore, because another previous study reported physiological costs to L-strains, the L-strains selected artificially for longer duration of death-feigning may have suffered more costs than the S-strains. In the present study, therefore, we relaxed the selection pressure after the 27th or 30th generation of S- and L-strains. We also carried out reverse selection during the most recent eight generations of S- and L-strains. The results showed that each strain clearly responded to relaxation of selection and reverse selection, suggesting that (1) additive genetic variation still existed in both strains after long-term selection, and (2) selection for shorter and longer duration of death-feigning was costly. These results suggest that anti-predator behavior is controlled by many loci, and longer or shorter duration of death-feigning is costly in a laboratory without predators. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1346-4523 46 4 2019 Contrast-enhanced harmonic endoscopic ultrasound using time–intensity curve analysis predicts pathological grade of pancreatic neuroendocrine neoplasm 449 458 EN Saimon Takada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yosuke Saragai Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichiro Muro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeshi Tomoda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Noriyuki Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences PURPOSE:<br/> Histological grading is important for the treatment algorithm in pancreatic neuroendocrine neoplasms (PNEN). The present study examined the efficacy of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and time-intensity curve (TIC) analysis of PNEN diagnosis and grading.<br/> METHODS:<br/> TIC analysis was performed in 30 patients using data obtained from CH-EUS, and a histopathological diagnosis was made via EUS-guided fine-needle aspiration or surgical resection. The TIC parameters were analyzed by dividing them into G1/G2 and G3/NEC groups. Then, patients were classified into non-aggressive and aggressive groups and evaluated.<br/> RESULTS:<br/> Twenty-six patients were classified as G1/G2, and four as G3/NEC. From the TIC analysis, five parameters were obtained (I: echo intensity change, II: time for peak enhancement, III: speed of contrast, IV: decrease rate for enhancement, and V: enhancement ratio for node/pancreatic parenchyma). Three of these parameters (I, IV, and V) showed high diagnostic performance. Using the cutoff value obtained from the receiver-operating characteristic (ROC) analysis, the correct diagnostic rates of parameters I, IV, and V were 96.7%, 100%, and 100%, respectively, between G1/G2 and G3/NEC. A total of 21 patients were classified into the non-aggressive group, and nine into the aggressive group. Using the cutoff value obtained from the ROC analysis, the accurate diagnostic rates of I, IV, and V were 86.7%, 86.7%, and 88.5%, respectively, between the non-aggressive and aggressive groups. <br/> CONCLUSION:<br/> CH-EUS and TIC analysis showed high diagnostic accuracy for grade diagnosis of PNEN. Quantitative perfusion analysis is useful to predict PNEN grade diagnosis preoperatively. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0942-2056 27 2 2018 Meniscal repair concurrent with anterior cruciate ligament reconstruction restores posterior shift of the medial meniscus in the knee-flexed position 361 368 EN Yoshiki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School Shinichi Miyazawa Department of Orthopaedic Surgery, Okayama University Graduate School Yuya Kodama Department of Orthopaedic Surgery, Okayama University Graduate School Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama University Graduate School Tomohito Hino Department of Orthopaedic Surgery, Okayama University Graduate School Shin Masuda Department of Orthopaedic Surgery, Okayama University Graduate School Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School PURPOSE:<br/> The purpose of this study was to evaluate the shape and shift of the medial meniscus before and after meniscal repair concurrent with anterior cruciate ligament (ACL) reconstruction using magnetic resonance imaging (MRI) at 90° of knee flexion.<br/> METHODS:<br/> This study included 18 patients with ACL-deficient knees without meniscus tears (group A), 11 patients with medial meniscus tears alone (group M), and 15 patients with ACL-deficient knees complicated with medial meniscus tears (group AM). The posterior segment shape was evaluated using open MRI at 90° of knee flexion preoperatively and at 3 months postoperatively. The length, height, width, and posterior extrusion of the medial meniscus and posterior tibiofemoral distance were measured. These measurements were compared between the three groups.<br/> RESULTS:<br/> On preoperative MRI, a significant difference was observed in the posterior extrusion of the medial meniscus (group A, 1.2 ± 0.5 mm; group M, 1.7 ± 0.3 mm; group AM, 4.1 ± 1.5 mm, p < 0.001). All parameters did not differ between the three groups on postoperative MRI. In addition, the posterior width and extrusion of the medial meniscus were decreased significantly after meniscal repair concurrent with ACL reconstruction.<br/> CONCLUSIONS:<br/> This study demonstrated that the medial meniscus shifted posteriorly at 90° of knee flexion in ACL-deficient knees complicated with medial meniscus tears. Medial meniscal repair concurrent with ACL reconstruction improved the deformed morphology and posterior extrusion. MRI measurements of the posterior extrusion at the knee-flexed position may be clinically useful to assess the functional improvement of the medial meniscus following meniscal repair combined with ACL reconstruction. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 03412695 43 5 2018 Arthroscopic scoring system of meniscal healing following medial meniscus posterior root repair 1239 1245 EN Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Shinichi Miyazawa Department of Orthopaedic Surgery, Okayama University Hospital Masataka Fujii Department of Orthopaedic Surgery, Okayama University Hospital Takaaki Tanaka Department of Orthopaedic Surgery, Okayama University Hospital Yuya Kodama Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital PURPOSE:<br/> Medial meniscus posterior root tear (MMPRT) leads to a rapid degradation of articular cartilage. In the treatment of MMPRT, transtibial pullout repair demonstrates a high clinical survival rate. However, there is no reliable method to evaluate the meniscal healing after surgery. We propose an arthroscopic scoring system for evaluating the meniscal healing status. The aim of this study was to investigate the correlations between second-look arthroscopic scores and clinical outcomes after transtibial pullout repair.<br/> METHODS:<br/> Twenty patients who had MMPRTs underwent transtibial pullout repairs. Clinical outcomes were assessed using the Japanese Knee Injury and Osteoarthritis Outcome Score (KOOS) and pain score evaluated by visual analogue scale at preoperatively and 1 year postoperatively. The healing status of repaired MM was assessed at one year post-operatively using a semi-quantitative arthroscopic scoring system (total, 10 points) composed of three evaluation criteria: (i) anteroposterior width of bridging tissues, (ii) stability of the MM posterior root, and (iii) synovial coverage of the sutures. Linear regression analysis was used to assess the correlation between second-look arthroscopic scores and clinical outcomes.<br/> RESULTS:<br/> Transtibial pullout repairs of MMPRTs significantly improved clinical evaluation scores at one year post-operatively. A median of second-look arthroscopic scores was 6.5 (5.75-8). A good correlation was observed between the arthroscopic score and KOOS quality of life (QOL) subscale. A moderate negative correlation between the arthroscopic score and pain score was observed.<br/> CONCLUSIONS:<br/> This study demonstrated that our semi-quantitative scoring system of meniscal healing correlated with the KOOS QOL subscale following MMPRT transtibial pullout repair. Our results suggest that the second-look arthroscopic score using this system may be a useful scale to determine and compare the healing status of the MM posterior root. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0302-766X 375 3 2018 Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice 743 754 EN Fumiya Ojima Department of Biology, The Graduate School of Natural Science and Technology, Okayama University Yuka Saito Department of Biology, The Graduate School of Natural Science and Technology, Okayama University Yukiko Tsuchiya Department of Biology, The Graduate School of Natural Science and Technology, Okayama University Maho Ogoshi Department of Biology, The Graduate School of Natural Science and Technology, Okayama University Hiroshi Fukamachi The Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University Kenichi Inagaki The Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumio Otsuka The Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sakae Takeuchi Department of Biology, The Graduate School of Natural Science and Technology, Okayama University Sumio Takahashi Department of Biology, The Graduate School of Natural Science and Technology, Okayama University We previously demonstrated that female Runx3 knockout (Runx3-/-) mice were anovulatory and their uteri were atrophic and that Runx3 mRNA was expressed in granulosa cells. To clarify how Runx3 regulates folliculogenesis and ovulation, we examine the effects of Runx3 knockout on the gene expression of growth factors associated with folliculogenesis and enzymes associated with steroidogenesis. In Runx3-/- mouse ovaries, the numbers of primary and antral follicles were lower than those in wild-type (wt) mice at 3 weeks of age, indicating that the loss of Runx3 affects folliculogenesis. The expression of genes encoding activin and inhibin subunits (Inha, Inhba and Inhbb) was also decreased in ovaries from the Runx3-/- mice compared with that in wt mice. Moreover, the expression of the genes Cyp11a1 and Cyp19a1 encoding steroidogenic enzymes was also decreased. In cultured granulosa cells from 3-week-old mouse ovaries, Cyp19a1 mRNA levels were lower in Runx3-/- mice than those in wt mice. Follicle-stimulating hormone (FSH) treatment increased Cyp19a1 mRNA levels in both wt and Runx3-/- granulosa cells in culture but the mRNA level in Runx3-/- granulosa cells was lower than that in wt ones, indicating that granulosa cells could not fully function in the absence of Runx3. At 3 weeks of age, gonadotropin α subunit, FSHβ subunit and luteinizing hormone (LH) β subunit mRNA levels were decreased in Runx3-/- mice. These findings suggest that Runx3 plays a key role in female reproduction by regulating folliculogenesis and steroidogenesis in granulosa cells. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1345-2630 79 5 2013 Biological and genetic diversity of plasmodiophorid-transmitted viruses and their vectors 307 320 EN Tetsuo Tamada Institute of Plant Science and Resources (IPSR)Okayama University Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University About 20 species of viruses belonging to five genera, Benyvirus, Furovirus, Pecluvirus, Pomovirus and Bymovirus, are known to be transmitted by plasmodiophorids. These viruses have all positive-sense, single-stranded RNA genomes that consist of two to five RNA components. Three species of plasmodiophorids are recognized as vectors: Polymyxa graminis, P. betae, and Spongospora subterranea. The viruses can survive in soil within the long-lived resting spores of the vector. There are biological and genetic variations in both virus and vector species. Many of the viruses are causal agents of important diseases in major crops such as rice, wheat, barley, rye, sugar beet, potato, and groundnut. Control is dependent on the development of resistant cultivars. During the last half century, several virus diseases have rapidly spread worldwide. For six major virus diseases, we address their geographical distribution, diversity, and genetic resistance. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0304-8608 159 1 2013 Complete genome sequence of Habenaria mosaic virus, a new potyvirus infecting a terrestrial orchid (Habenaria radiata) in Japan 163 166 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Takanori Maeda College of Bioresource SciencesNihon University I Wayan Gara Institute of Plant Science and Resources (IPSR)Okayama University Sotaro Chiba Institute of Plant Science and Resources (IPSR)Okayama University Kazuyuki Maruyama Institute of Plant Science and Resources (IPSR)Okayama University Tetsuo Tamada Institute of Plant Science and Resources (IPSR)Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University The complete genomic sequence of Habenaria mosaic virus (HaMV), which infects terrestrial orchids (Habenaria radiata), has been determined. The genome is composed of 9,499 nucleotides excluding the 3'-terminal poly(A) tail, encoding a large polyprotein of 3,054 amino acids with the genomic features typical of a potyvirus. Putative proteolytic cleavage sites were identified by sequence comparison to those of known potyviruses. The HaMV polyprotein showed 58 % amino acid sequence identity to that encoded by the most closely related potyvirus, tobacco vein banding mosaic virus. Phylogenetic analysis of the polyprotein amino acid sequence and its coding sequences confirmed that HaMV formed a cluster with the chilli veinal mottle virus group, most of which infect solanaceous plants. These results suggest that HaMV is a distinct member of the genus Potyvirus. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0304-8608 160 8 2015 Cymbidium chlorotic mosaic virus, a new sobemovirus isolated from a spring orchid (Cymbidium goeringii) in Japan. 2099 104 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Shogo Takemoto Institute of Plant Science and Resources (IPSR)Okayama University Kazuyuki Maruyama Institute of Plant Science and Resources (IPSR)Okayama University Sotaro Chiba Institute of Plant Science and Resources (IPSR)Okayama University Ida Bagus Andika Institute of Plant Science and Resources (IPSR)Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Cymbidium chlorotic mosaic virus (CyCMV), isolated from a spring orchid (Cymbidium goeringii), was characterized molecularly. CyCMV isometric virions comprise a single, positive-strand RNA genome of 4,083 nucleotides and 30-kDa coat protein. The virus genome contains five overlapping open reading frames with a genomic organization similar to that of sobemoviruses. BLAST searches and phylogenetic analysis revealed that CyCMV is most closely related to papaya lethal yellowing virus, a proposed dicot-infecting sobemovirus (58.8 % nucleotide sequence identity), but has a relatively distant relationship to monocot-infecting sobemoviruses, with only modest sequence identities. This suggests that CyCMV is a new monocot-infecting member of the floating genus Sobemovirus. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1345-2630 85 6 2019 A class III peroxidase PRX34 is a component of disease resistance in Arabidopsis 405 412 EN Lei Zhao Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University Le Thi Phuong Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University Mai Thanh Luan Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University Aprilia Nur Fitrianti Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University Hidenori Matsui Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University Hirofumi Nakagami RIKEN Center for Sustainable Resource Science Yoshiteru Noutoshi Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University Mikihiro Yamamoto Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University Yuki Ichinose Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University Tomonori Shiraishi Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University Kazuhiro Toyoda Laboratory of Plant Pathology and Genetic Engineering, Graduate School of Environmental and Life ScienceOkayama University PRX34 mediates the oxidative burst in Arabidopsis. Here we characterized two additional Arabidopsis prx34 null mutants (prx34-2, prx34-3), besides the well-studied prx34-1. Due to a decrease in corresponding peroxidase, the activity that generates reactive oxygen species (ROS) was significantly lower in cell wall extracts of prx34-2 and prx34-3 plants. Consistently, the prx34-2 and prx34-3 exhibited reduced accumulation both of ROS and callose in Flg22-elicitor-treated leaves, leading to enhanced susceptibility to bacterial and fungal pathogens. In contrast, ectopic expression of PRX34 in the wild type caused enhanced resistance. PRX34 is thus a component for disease resistance in Arabidopsis. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 14346044 79 2019 Raman stimulated neutrino pair emission 684 EN Hideaki Hara Research Institute for Interdisciplinary ScienceOkayama University Motohiko Yoshimura Research Institute for Interdisciplinary ScienceOkayama University A new scheme using macroscopic coherence is proposed to experimentally determine the neutrino mass matrix, in particular the absolute value of neutrino masses, and the mass type, Majorana or Dirac. The proposed process is a collective, coherent Raman scattering followed by neutrino-pair emission from | e of a long lifetime to | g ;.0 + | e .. + i j.i. j + | g with.i. j consisting of six massive neutrino-pairs. Calculated angular distribution has six (i j) thresholds which showup as steps at different angles. Angular locations of thresholds and event rates of the angular distribution make it possible to experimentally determine the smallest neutrino mass to the level of less than several meV, (accordingly all threemasses using neutrino oscillation data), the mass ordering pattern, normal or inverted, and to distinguish whether neutrinos are ofMajorana or Dirac type. Event rates of neutrino-pair emission, when the mechanism of macroscopic coherence amplification works, may become large enough for realistic experiments by carefully selecting certain types of target. The problem to be overcome is macro-coherently amplified quantum electrodynamic background of the process,.0 + | e .. +.2 +.3 + | g , when two extra photons,.2,.3, escape detection. We illustrate our idea using neutral Xe and trivalent Ho ion doped in dielectric crystals. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 13452630 86 2019 PsyR, a transcriptional regulator in quorum sensing system, binds lux box-like sequence in psyI promoter without AHL quorum sensing molecule and activates psyI transcription with AHL in Pseudomonas syringae pv. tabaci 6605 124 133 EN Yuki Ichinose Graduate School of Environmental and Life ScienceOkayama University Yousuke Tasaka Graduate School of Environmental and Life ScienceOkayama University Satoru Yamamoto Graduate School of Environmental and Life ScienceOkayama University Yuko Inoue Faculty of AgricultureOkayama University Motohiro Takata Graduate School of Environmental and Life ScienceOkayama University Yukiko Nakatsu Graduate School of Environmental and Life ScienceOkayama University Fumiko Taguchi Graduate School of Environmental and Life ScienceOkayama University Mikihiro Yamamoto Graduate School of Environmental and Life ScienceOkayama University Kazuhiro Toyoda Graduate School of Environmental and Life ScienceOkayama University Yoshiteru Noutoshi Graduate School of Environmental and Life ScienceOkayama University Hidenori Matsui Graduate School of Environmental and Life ScienceOkayama University Quorum sensing (QS) is a mechanism for bacterial cell-cell communication using QS signals. N-acyl-homoserine lactones (AHLs), QS signals in Pseudomonas syringae pv. tabaci (Pta) 6605, are synthesized by an AHL synthase (PsyI) and recognized by the cognate transcription factor PsyR. To reveal the role of PsyR in virulence, we generated a psyR mutant and complemented strains of Pta 6605 and found that the psyR mutant is remarkably reduced in AHL production and ability to cause disease and propagate in host tobacco leaves. The phenotypes of complemented strains were restored to that of the wild type (WT). Because the psyR mutant lost nearly all AHL production, we investigated the function of PsyR in the transcription of psyI and production of AHL. Electrophoretic mobility shift assays suggested that the recombinant PsyR protein binds the promoter region of psyI but not psyR without AHL. The addition of AHL did not significantly affect this binding. The binding core sequence of this region was identified as a 20-bp lux box-like sequence. To reveal the function of PsyR and AHL on psyI transcription, we constructed a psyI promoter::lacZYA chimeric reporter gene, and inserted it into the WT and psyI mutant of Pta 6605. beta-galactosidase activity increased in a bacterial density-dependent manner in the WT and also in a psyI mutant after the addition of exogenous AHL. These results indicate that the solo PsyR binds the lux box in the psyI promoter and activates transcription in the concomitant presence of AHL. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 09411291 49 3 2018 A single-nucleotide polymorphism in a gene modulating glucocorticoid sensitivity is associated with the decline in total lung capacity after lung transplantation. 268 274 EN Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological SurgeryOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic SurgeryOkayama University Hospital Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological SurgeryOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeshi Kurosaki Department of Organ Transplant CenterOkayama University Hospital Shinji Otani Department of Organ Transplant CenterOkayama University Hospital Masaomi Yamane Department of General Thoracic Surgery and Breast and Endocrinological SurgeryOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naruto Taira Department of Breast and Endocrinological SurgeryOkayama University Hospital Takahiro Oto Department of Organ Transplant CenterOkayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological SurgeryOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences PURPOSE:</br> Glucocorticoids are used to prevent chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). Our study was aimed at assessing the association between the glucocorticoid-induced transcript 1 gene (GLCCI1) variant, which modulates glucocorticoid sensitivity, and the postoperative lung function and development of CLAD after LT. </br> METHODS:</br> A total of 71 recipients of LT were genotyped for the GLCCI1 variant (rs37972) and divided into three groups: the homozygous mutant allele (TT) group, the heterozygous mutant allele (CT) group, and the wild-type allele (CC) group. The results of pulmonary function tests were compared with the postoperative baseline values. </br> RESULTS:</br> The total lung capacity (TLC) in the TT group was significantly lower than that in the CC group at 3 years after LT (P = 0.029). In the recipients of cadaveric LT, the TLC and forced expiratory volume in 1 s in the TT group were significantly lower than those in the CC groups, resulting in a significant worse CLAD-free survival at 3 years after LT (P = 0.016). </br> CONCLUSION:</br> The GLCCI1 variant was associated with a significant decrease of the TLC at 3 years after LT and the development of CLAD at 3 years, especially in patients undergoing cadaveric LT. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 09593993 30 2 2014 Effects of temperature, growth phase and luxO-disruption on regulation systems of toxin production in Vibrio vulnificus strain L-180, a human clinical isolate 681 691 EN Abdelaziz Elgaml Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama University Kazutaka Higaki Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama University Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama University Vibrio vulnificus is a halophilic estuarine bacterium while it causes fatal septicemia or necrotizing wound infections in humans. This pathogen secretes the metalloprotease (V. vulnificus protease: VVP) and the cytolysin (V. vulnificus hemolysin: VVH) as protein toxins; however, their production was coordinated in response to the bacterial cell density. This regulation is termed quorum sensing (QS) and is mediated by the small diffusible molecule called autoinducer 2 (AI-2). In the present study, we investigated effects of disruption of luxO encoding a central response regulator of the QS circuit, as well as effects of temperature and growth phase, on the toxin production by V. vulnificus. Disruption of luxO was found to increase VVP production and expression of its gene vvpE. The expression of smcR, crp and rpoS, of which products positively regulate vvpE expression, and luxS encoding the AI-2 synthetase were also significantly increased. On the other hand, the luxO disruption resulted in reduction of VVH production and expression of its gene vvhA. Expression of other two genes affecting the QS circuit, luxT and rpoN, were also significantly decreased. The regulation systems of VVP production were found to exert their action during the stationary phase of the bacterial growth and to be operated strongly at 26 °C. By contrast, those of VVH production apparently started at the log phase and were operated more effectively at 37 °C. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0941-4355 22 12 2014 With regard to our manuscripts on the commercial saliva substitute, Oralbalance®--its formula has been changed 3121 3122 EN Yuko Sugiura Division of Dental Hygienist, Clinical Support DepartmentOkayama University Hospital Yoshihiko Soga Division of Hospital Dentistry, Central Clinical DepartmentOkayama University Hospital Ichiro Tanimoto Division of DentistryNational Sanatorium Oku-Komyoen Susumu Kokeguchi Department of Global Health and Environmental Sciences, Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama University Sachiko Morishige-Nishide Department of NursingKagawa University Hospital Kotoe Itami-Kono Department of NursingSanyo Gakuen University Kanayo Takahashi Department of NursingOkayama University Hospital Nobuharu Fujii Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama University Fumihiko Ishimaru Japanese Red Cross Tokyo Metropolitan Blood Center Mitsune Tanimoto Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama University Kokoro Yamabe Department of DentistryRakuwakai Otowa Hospital Soichiro Tsutani Kogita Dental Clinic Fusanori Nishimura Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental ScienceKyushu University Shogo Takashiba Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama University No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0723-4864 57 11 2016 Wavelet analysis of transonic buffet on a two-dimensional airfoil with vortex generators 166 EN Toshinori Kouchi Department Mechanical and System Engineering, Okayama University Shingo Yamaguchi Department Mechanical and System Engineering, Okayama University Shunske Koike Next Generation Aeronautical Innovation Hub Center, Aeronautical Technology Directorate, JAXA Tsutomu Nakajima Aerodynamics Research Unit, Aeronautical Technology Directorate, JAXA Mamoru Sato Aerodynamics Research Unit, Aeronautical Technology Directorate, JAXA Hiroshi Kanda Aerodynamics Research Unit, Aeronautical Technology Directorate, JAXA Shinichiro Yanase Department Mechanical and System Engineering, Okayama University We visualized the shock buffets on a two-dimensional transonic airfoil with and without vortex generators (VGs) by using a fast-framing focusing schlieren imaging. The focusing schlieren visualization showed that the flow three-dimensionality around the airfoil became remarkable with installing the VGs. This implies that narrow depth of focus of imaging systems was a key to accurately capture the characteristics of the shock oscillation due to the buffet for the cases with VGs. The time-resolved imaging also revealed that non-periodic components were included in the shock oscillation due to the buffet for the cases with VGs. This prevented Fourier analysis from being applied. We used wavelet analysis to extract the characteristic of the shock oscillation for the cases with VGs. The wavelet spectrograms revealed that the low-frequency oscillation having the buffet frequency was still included intermittently in the shock oscillation even when VG controlled the buffet. The rate of appearing the low-frequency oscillation increased with increasing both the interval between VGs and the angle of attack. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1432-1114 56 12 2015 Focusing-schlieren Visualization in A Dual-mode Scramjet 211 EN Toshinori Kouchi Department of Mechanical and System Engineering, Okayama University Christopher P. Goyne Department of Mechanical and Aerospace Engineering, University of Virginia Robert D. Rockwell Department of Mechanical and Aerospace Engineering, University of Virginia James C. McDaniel Department of Mechanical and Aerospace Engineering, University of Virginia Schlieren imaging is particularly suited to measuring density gradients in compressible flowfields and can be used to capture shock waves and expansion fans, as well as the turbulent structures of mixing and wake flows. Conventional schlieren imaging, however, has difficulty clearly capturing such structures in long-duration supersonic combustion test facilities. This is because the severe flow temperatures locally change the refractive index of the window glass that is being used to provide optical access. On the other hand, focusing-schlieren imaging presents the potential of reduced sensitivity to thermal distortion of the windows and to clearly capture the flow structures even during a combustion test. This reduced sensitivity is due the technique’s ability to achieve a narrow depth of focus. As part of this study, a focusing-schlieren system was developed with a depth of focus near ±5 mm and was applied to a direct-connect, continuous-flow type, supersonic combustion test facility with a stagnation temperature near 1200 K. The present system was used to successfully visualize the flowfield inside a dual-mode scramjet. The imaging system captured combustion-induced volumetric expansion of the fuel jet and an anchored bifurcated shock wave at the trailing edge of the ramp fuel injector. This is the first time successful focusing-schlieren measurements have been reported for a dual-mode scramjet. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 07234864 58 8 2017 Extracting dominant turbulent structures in supersonic flow using two-dimensional Fourier transform 98 EN Toshinori Kouchi Department Mechanical and System Engineering, Okayama University Goro Masuya Department Mechanical and Aerospace EngineeringTohoku University Shinichiro Yanase Department Mechanical and System Engineering, Okayama University A new image process for quantifying both convection velocities (U C) and scales (λ d) of turbulent structures captured in a fast-framing schlieren movie is presented. We obtained 90 time-series schlieren images of a transverse jet into a Mach 2 supersonic flow with 1-MHz sampling. The schlieren images captured not only the shock and expansion waves but also the turbulent structures within the jet and the boundary layer. The image intensities were extracted along the outer edges of the jet and the boundary layer and were remapped as a time–space intensity map. The time–space map exhibited swept stripe patterns, indicating that stable turbulent structures were periodically generated and convected downstream. The angle and interval of the stripe patterns were efficiently extracted using the two-dimensional Fourier transform, which corresponded to U C and λ d of the dominant structures. The zero-padding fast Fourier transform and the sub-pixel estimation of the spectral peak positions in the Fourier domain improved the accuracy for evaluating the angle and interval of the stripes, which resulted in the accurate evaluation of U C and λ d. The proposed method was validated by comparing U C obtained using the proposed method to those obtained via schlieren image velocimetry for both the transverse jet and the supersonic boundary layer. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 16174615 293 4 2018 MexEF-OprN multidrug efflux pump transporter negatively controls N-acyl-homoserine lactone accumulation in pseudomonas syringae pv. Tabaci 6605 1 11 EN Takahiro Sawada Graduate School of Environmental and Life ScienceOkayama University Miho Eguchi Graduate School of Environmental and Life ScienceOkayama University Seiya Asaki Faculty of AgricultureOkayama University Ryota Kashiwagi Faculty of AgricultureOkayama University Kousuke Shimomura Faculty of AgricultureOkayama University Fumiko Taguchi Graduate School of Environmental and Life ScienceOkayama University Hidenori Matsui Graduate School of Environmental and Life ScienceOkayama University Mikihiro Yamamoto Graduate School of Environmental and Life ScienceOkayama University Yoshiteru Noutoshi Graduate School of Environmental and Life ScienceOkayama University Kazuhiro Toyoda Graduate School of Environmental and Life ScienceOkayama University Yuki Ichinose Graduate School of Environmental and Life ScienceOkayama University Our previous studies revealed that flagellar-motility-defective mutants such as ∆fliC of Pseudomonas syringae pv. tabaci 6605 (Pta6605) have remarkably reduced production of N-acyl-homoserine lactones (AHL), quorum-sensing molecules. To investigate the reason of loss of AHL production in ∆fliC mutant, we carried out transposon mutagenesis. Among approximately 14,000 transconjugants, we found 11 AHL production-recovered (APR) strains. In these APR strains, a transposon was inserted into either mexE or mexF, genes encoding for the multidrug efflux pump transporter MexEF-OprN, and mexT, a gene encoding a putative transcriptional activator for mexEF-oprN. These results suggest that MexEF-OprN is a negative regulator of AHL production. To confirm the negative effect of MexEF-OprN on AHL production, loss- and gain-of-function experiments for mexEF-oprN were carried out. The ∆fliC∆mexF and ∆fliC∆mexT double mutant strains recovered AHL production, whereas the mexT overexpressing strain abolished AHL production, although the psyI, a gene encoding AHL synthase, is transcribed as wild type. Introduction of a mexF or mexT mutation into another flagellar-motility- and AHL production-defective mutant strain, ∆motCD, also recovered the ability to produce AHL. Furthermore, introduction of the mexF mutation into other AHL production-defective mutant strains such as ∆gacA and ∆aefR also recovered AHL production but not to the ∆psyI mutant. These results indicate that MexEF-OprN is a decisive negative determinant of AHL production and accumulation. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1438-4957 18 4 2016 Gasification and reforming of biomass and waste samples by means of a novel catalyst 646 654 EN Katsuya Kawamoto Environmental Management CenterOkayama University Baowang Lu Hydrogen Isotope Research Center, Organization for Promotion of ResearchUniversity of Toyama This study conducted gasification and catalytic reforming experiments with the expectation of obtaining new advantages on energy recovery and aimed for the development of an effective catalyst. Initially, the use of thermal gasification technology for waste treatment in line with waste-to-energy strategies was reviewed. Technological systems which have gasification were classified and their current status was discussed. Then, the results of gasification and reforming experiments showed that product gas with 50 % H2 or more was obtained using a Ni catalyst on a mesoporous silica–based SBA-15 support (NiO/SBA-15), which we newly developed. Experiments using wood feedstock revealed that H2 production by the catalyst was better when the NiO content was 20 % (W/W) or more than when another catalyst or the Ni catalyst with a lower Ni loading was used. Tar formation as a by-product was also well controlled by the catalyst, and use of a catalyst with 40 % NiO reduced the tar concentration to less than 0.2 g/ m3NmN3 . Experiments using a mixed feedstock of wood and RPF resulted in an increase in hydrocarbon concentration because of insufficient reforming. This finding suggests that future work is required to find a better solution to wood and RPF co-gasification. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0721-7714 36 4 2017 Selection of transformation-efficient barley genotypes based on TFA (transformation amenability) haplotype and higher resolution mapping of the TFA loci 611 620 EN Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Brigid Meints Department Crop and Soil Sciences, Washington State University Matthew J. Moscou The Sainsbury Laboratory Luis Cistue Department Genetica y Produccion Vegetal Begoña Echávarri Kazuhiro Sato Institute of Plant Science and Resources, Okayama University Patrick M. Hayes Department Crop and Soil Science, Oregon State University Key message: The genetic substitution of transformation amenability alleles from ‘Golden Promise’ can facilitate the development of transformation-efficient lines from recalcitrant barley cultivars. Abstract: Barley (Hordeum vulgare) cv. ‘Golden Promise’ is one of the most useful and well-studied cultivars for genetic manipulation. In a previous report, we identified several transformation amenability (TFA) loci responsible for Agrobacterium-mediated transformation using the F2 generation of immature embryos, derived from ‘Haruna Nijo’ × ‘Golden Promise,’ as explants. In this report, we describe higher density mapping of these TFA regions with additional SNP markers using the same transgenic plants. To demonstrate the robustness of transformability alleles at the TFA loci, we genotyped 202 doubled haploid progeny from the cross ‘Golden Promise’ × ‘Full Pint.’ Based on SNP genotype, we selected lines having ‘Golden Promise’ alleles at TFA loci and used them for transformation. Of the successfully transformed lines, DH120366 came the closest to achieving a level of transformation efficiency comparable to ‘Golden Promise.’ The results validate that the genetic substitution of TFA alleles from ‘Golden Promise’ can facilitate the development of transformation-efficient lines from recalcitrant barley cultivars. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 00016268 159 7 2017 De novo vertebral artery dissecting aneurysm after internal trapping of the contralateral vertebral artery 1329 1333 EN Naoya Kidani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Hishikawa Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishihiro Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Takahashi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences We present the case of a de novo vertebral artery dissecting aneurysm (VADA) after endovascular trapping of a ruptured VADA on the contralateral side. The first ruptured VADA involved the posterior inferior cerebellar artery, which was successfully treated by endovascular internal trapping using a stent. A follow-up study at 3 months revealed a de novo VADA on the contralateral side. The second VADA was successfully embolized using coils while normal arterial flow in the vertebral artery was preserved using a stent. Increased hemodynamic stress may cause the development of a de novo VADA on the contralateral side. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2210-7703 37 6 2015 Exploring autistic-like traits relating to empathic attitude and psychological distress in hospital pharmacists 1258 1266 EN Yuji Higuchi Department of NeuropsychiatryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Uchitomi Innovation Center for Supportive, Palliative and Psychosocial CareNational Cancer Center Maiko Fujimori Center for Suicide Prevention, National Institute of Mental HealthNational Center for Neurology and Psychiatry Toshihiro Koyama Department of Clinical PharmacyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitomi Kataoka Department of Primary Care and Medical EducationOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Clinical PharmacyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical PharmacyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masatoshi Inagaki Department of NeuropsychiatryOkayama University Hospital BACKGROUND: Pharmacists are expected to play a key role in modern cancer care. Research suggests that an empathic approach and attitude in medical staff improves the quality of patient care. An empathic attitude and psychological distress are thought to be associated with autistic-like traits, but little is known about such traits. OBJECTIVE: In this study, we aimed to clarify the associations among autistic-like traits, empathic attitude in a medical context, and psychological health in hospital pharmacists. SETTING: Eligibility criteria for inclusion were certified pharmacists working at hospitals for patient care who returned their questionnaires. METHOD: Eight hundred and twenty-three hospital pharmacists completed a number of self-administered questionnaires anonymously by mail. MAIN OUTCOME MEASURES: Scores were obtained on the Autism-Spectrum Quotient, the Jefferson Scale of Empathy, the General Health Questionnaire-12, and subscales of the Interpersonal Reactivity Index (Perspective Taking, IRI-Empathic Concern, IRIPersonal Distress). We performed correlation and mediation analyses to confirm that the empathy and general health questionnaires were associated with autism-spectrum quotient scores, and with each IRI subscale. RESULTS: Complete responses were obtained from 379 pharmacists comprising 151 males (39.8 %) with a mean age of 37.7 ± 10.8 years (missing data, n = 13) and a median of 11 years after qualification as a pharmacist. Autism-Spectrum Quotient scores were inversely correlated with empathy (r = -0.22, p < 0.001) and positively correlated with general health scores (r = 0.40, p < 0.001). In the models with mediation, the inverse correlation between autism-spectrum quotient and empathy scores was mediated indirectly by IRI-Perspective Taking and IRI-Empathic Concern, and the positive correlation between autism-spectrum quotient and general health was mediated indirectly by IRI-Personal Distress. There were also direct effects, with significant effects of autism-spectrum quotient on empathy and general health scores. CONCLUSION: Our findings suggest that autistic-like traits affect both empathic attitude in a medical context and the psychological health of pharmacists. We recommend that to improve empathy in those with high levels of autistic-like traits, we may need to develop specialized interventions, such as improving communication skills training. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0236-5731 313 1 2017 In vitro analysis of radioprotective effect of monoterpenes 169 174 EN Ken-ichi Kudo Tadashi Hanafusa Department of Radiation Research, Advanced Science Research CenterOkayama University Toshiro Ono Department of Radiation Research, Advanced Science Research CenterOkayama University Monoterpenes are naturally occurring hydrocarbons composed of two units of isoprenes. They exhibit antioxidant activity to scavenge reactive oxygen species, such as hydroxyl radicals. We investigated the potential of monoterpenes such as thymol, linalool, and menthol to act as radioprotectants. The proliferation of EL4 cells, a mouse lymphoma cell line, treated with linalool at a concentration of 500 μM or more was not affected by X-ray irradiation. Plasmid-nicking assay performed using formamidopyrimidine-DNA glycosylase showed that linalool prevented single strand breaks and oxidized purines on pUC19 plasmid DNA. These findings indicate that linalool has the ability to scavenge reactive oxygen species and is a potential radioprotector. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1029-8428 26 3 2014 Neuroprotective Effects of Metallothionein Against Rotenone-Induced Myenteric Neurodegeneration in Parkinsonian Mice 285 298 EN Shinki Murakami Ikuko Miyazaki Norio Sogawa Ko Miyoshi Masato Asanuma Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as well as non-motor symptoms that precede the onset of motor symptoms. Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD pathology in the central nervous system (CNS) and enteric nervous system (ENS). We reported previously that metallothioneins (MTs) released from astrocytes can protect dopaminergic neurons against oxidative stress. The present study examined the changes in MT expression by chronic systemic rotenone administration in the striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6 weeks caused neurodegeneration, increased MT expression with astrocytes activation in the striatum and myenteric plexus. MT KO mice showed more severe myenteric neuronal damage by rotenone administration after 4 weeks than wild-type mice, accompanied by reduced astroglial activation. In primary cultured mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in dopaminergic neurons, which was complemented by addition of recombinant protein. The present results suggest that MT seems to provide protection against neurodegeneration in ENS of rotenone-induced PD model mice. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0167-6806 143 2 2014 Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers 403 409 EN Mitsuya Itoh Takayuki Iwamoto Junji Matsuoka Tomohiro Nogami Takayuki Motoki Tadahiko Shien Naruto Taira Naoki Niikura Naoki Hayashi Shoichiro Ohtani Kenji Higaki Toshiyoshi Fujiwara Hiroyoshi Doihara W. Fraser Symmans Lajos Pusztai We examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I-III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (<Emphasis Type="ItalicUnderline">n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20-25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0171-5216 138 5 2012 DNA methylation status of REIC/Dkk-3 gene in human malignancies 799 809 EN Tatsuro Hayashi Hiroaki Asano Shinichi Toyooka Kazunori Tsukuda Junichi Soh Tadahiko Shien Naruto Taira Yuho Maki Norimitsu Tanaka Hiroyoshi Doihara Yasutomo Nasu Nam-ho Huh Shinichiro Miyoshi The REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/Dkk-3 type-a in a broad range of human malignancies. We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed. The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2'-deoxycytidine treatment. We found that estrogen receptor-positive breast cancers were significantly more common among the methylated group than among the non-methylated group. REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0341-2695 37 1 2013 Comparison between normal and loose fragment chondrocytes in proliferation and redifferentiation potential 159 165 EN Kenichiro Sakata Takayuki Furumatsu Shinichi Miyazawa Yukimasa Okada Masataka Fujii Toshifumi Ozaki Loose fragments in osteochondritis dissecans (OCD) of the knee require internal fixation. On the other hand, loose fragments derived from spontaneous osteonecrosis of the knee (SONK) are usually removed. However, the difference in healing potential between OCD- and SONK-related loose fragments has not been elucidated. In this study, we investigated proliferative activity and redifferentiation potential of normal cartilage-derived and loose fragment-derived chondrocytes. Cells were prepared from normal articular cartilages and loose fragment cartilages derived from knee OCD and SONK. Cellular proliferation was compared. Redifferentiation ability of pellet-cultured chondrocytes was assessed by real-time PCR analyses. Mesenchymal differentiation potential was investigated by histological analyses. Positive ratio of a stem cell marker CD166 was evaluated in each cartilaginous tissue. Normal and OCD chondrocytes showed a higher proliferative activity than SONK chondrocytes. Chondrogenic pellets derived from normal and OCD chondrocytes produced a larger amount of safranin O-stained proteoglycans compared with SONK-derived pellets. Expression of chondrogenic marker genes was inferior in SONK pellets. The CD166-positive ratio was higher in normal cartilages and OCD loose fragments than in SONK loose fragments. The OCD chondrocytes maintained higher proliferative activity and redifferentiation potential compared with SONK chondrocytes. Our results suggest that chondrogenic properties of loose fragment-derived cells and the amount of CD166-positive cells may affect the repair process of osteochondral defects. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1342-1751 17 1 2013 Current status of the treatment of microscopic polyangiitis and granulomatosis with polyangiitis in Japan 51 58 EN Koichi Sugiyama Ken-ei Sada Michiko Kurosawa Jun Wada Hirofumi Makino This study aimed to describe the epidemiologic characteristics of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in Japan. We used the database of the Ministry of Health, Labour and Welfare (MHLW) from 2006 to 2008, and analyzed data from 938 patients (MPA = 697, GPA = 241) who fulfilled the MHLW diagnostic criteria and had registered within a year after onset. The mean ages of the MPA and GPA patients were 69.4 +/- A 0.4 and 58.4 +/- A 1.1 years, respectively. Renal (86.9 %), chest (73.7 %), and nervous system (45.2 %) symptoms were common in MPA patients. Ear, nose, and throat (86.7 %), chest (78.0 %), and renal (60.6 %) symptoms were frequently observed in GPA patients. The concomitant use of cyclophosphamide (CY) with corticosteroids was observed in 22.2 % of the MPA patients and 58.5 % of the GPA patients. In multivariate analysis, the concomitant use of CY was associated with a younger age and pulmonary hemorrhage in MPA patients, and the avoidance of CY was associated with nervous system symptoms and rapidly progressive glomerulonephritis in GPA patients. Plasma exchanges were inducted in 5.2 % of the MPA patients and 4.1 % of the GPA patients. The addition of plasma exchange was associated with elevation of the serum creatinine level in patients with both MPA and GPA. A dominance of MPA and a reduced frequency of renal involvement in GPA patients may be significant features of the Japanese population. Clinical practice relating to MPA and GPA in Japan can be characterized as follows: CY is used less commonly, and plasma exchange is employed for patients with deteriorated renal function. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1342-1751 16 5 2012 Mizoribine, tacrolimus, and corticosteroid combination therapy successfully induces remission in patients with lupus nephritis 760 766 EN Hidetoshi Kagawa Tsutomu Hiromasa Takayuki Hara Ayako Takaki Ryutaro Yamanaka Ken-ei Sada Hirofumi Makino Conventional cyclophosphamide-based treatment regimens for lupus nephritis (LN) are still not considered to be optimal. The aim of this study was to evaluate the efficacy and safety of mizoribine, tacrolimus, and corticosteroid combination therapy for LN. We retrospectively evaluated a combination treatment of mizoribine and tacrolimus with corticosteroids as induction therapy in eight newly diagnosed systemic lupus erythematosus (SLE) patients with biopsy-proven LN. All patients were women, and their mean [standard deviation (SD)] age was 48.5 (20) years. All patients (100 %) had positive anti-double-stranded DNA (anti-dsDNA) antibody titers, and four (50.0 %) were nephrotic. Mean (SD) serum creatinine and daily proteinuria levels were 0.72 (0.4) mg/dl (range 0.33-1.55 mg/dl) and 4.56 (2.8) g (range 0.77-8.2 g), respectively. By month 2, significant improvements in the anti-dsDNA antibody titers, levels of proteinuria, serum albumin, and C3, and SLE disease activity index score were observed. By month 6, seven patients (87.5 %) were in complete remission, with normalized levels of both proteinuria and serum creatinine. This pilot study suggests that mizoribine and tacrolimus treatment with corticosteroids is well tolerated and may prove to be an optimal alternative remission-inducing regimen for LN. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1342-1751 16 5 2012 Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney 739 748 EN Ryo Nagase Nobuo Kajitani Kenichi Shikata Daisuke Ogawa Ryo Kodera Shinichi Okada Yuichi Kido Hirofumi Makino Inflammatory process is involved in pathogenesis of diabetic nephropathy, although the activation and phenotypic change of macrophages in diabetic kidney has remained unclear. Sialoadhesin is a macrophage adhesion molecule containing 17 extracellular immunoglobulin-like domains, and is an I-type lectin which binds to sialic acid ligands expressed on hematopoietic cells. The aim of this study is to clarify the activation and phenotypic change of macrophages in the progression of diabetic nephropathy. We examined the expression of surface markers for pan-macrophages, resident macrophages, sialoadhesin, major histocompatibility complex class II and alpha-smooth muscle actin in the glomeruli of diabetic rats using immunohistochemistry at 0, 1, 4, 12, and 24 weeks after induction of diabetes by streptozotocin. Expression of type IV collagen and the change of mesangial matrix area were also measured. The mechanism for up-regulated expression of sialoadhesin on macrophages was evaluated in vitro. The number of macrophages was increased in diabetic glomeruli at 1 month after induction of diabetes and the increased number was maintained until 6 months. On the other hand, sialoadhesin-positive macrophages were increased during the late stage of diabetes concomitantly with the increase of alpha-smooth muscle actin-positive mesangial cells, mesangial matrix area and type IV collagen. Gene expression of sialoadhesin was induced by stimulation with interleukin (IL)-1 beta and tumor necrosis factor-alpha but not with IL-4, transforming growth factor-beta and high glucose in cultured human macrophages. The present findings suggest that sialoadhesin-positive macrophages may contribute to the progression of diabetic nephropathy. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0959-3993 28 4 2012 An extracellular serine protease produced by Vibrio vulnificus NCIMB 2137, a metalloprotease-gene negative strain isolated from a diseased eel 1633 1639 EN Shin-ichi Miyoshi Wang Jiyou Keizo Katoh Mitsutoshi Senoh Tamaki Mizuno Yoko Maehara Vibrio vulnificus is a ubiquitous estuarine microorganism but causes fatal systemic infections in immunocompromised humans, cultured eels or shrimps. An extracellular metalloprotease VVP/VvpE has been reported to be a potential virulence factor of the bacterium; however, a few strains isolated from a diseased eel or shrimp were recently found to produce a serine protease termed VvsA, but not VVP/VvpE. In the present study, we found that these strains had lost the 80 kb genomic region including the gene encoding VVP/VvpE. We also purified VvsA from the culture supernatant through ammonium sulfate fractionation, gel filtration and ion-exchange column chromatography, and the enzyme was demonstrated to be a chymotrypsin-like protease, as well as those from some vibrios. The gene vvsA was shown to constitute an operon with a downstream gene vvsB, and several Vibrio species were found to have orthologues of vvsAB. These findings indicate that the genes vvp/vvpE and vvsAB might be mobile genetic elements. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 13 2010 Mechanisms of Acido-Tolerance and Characteristics of Photosystems in an Acidophilic and Thermophilic Red Alga, Cyanidium Caldarium 373 389 EN Isao Enami Hideyuki Adachi Jian-Ren Shen In this chapter, we describe the mechanisms of acido-tolerance in an acidophilic- and thermophilic red alga, Cyanidium caldarium. In spite of the extremely acidic environments it inhabits, the intracellular pH of Cyanidium cells is kept neutral by pumping out the protons previously leaked into the cells according to the steep pH gradient. The H+ pump is driven by the plasma membrane ATPase, utilizing intracellular ATP produced by both oxidative phosphorylation and cyclic photophosphorylation via photosystem I. We also describe the characteristics and function of the two photosystems, Photosystem I (PSI) and II (PSII), in Cyanidium caldarium in comparison with those of cyanobacteria, other eukaryotic algae, and higher plants, based on the crystal structures of the two complexes reported so far. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0304-8608 155 2 2009 Molecular characterization of the VP1, VP2, VP4, VP6, NSP1 and NSP2 genes of bovine group B rotaviruses: identification of a novel VP4 genotype 159 167 EN S Ghosh N Kobayashi S Nagashima M Chawla-Sarkar T Krishnan B Ganesh TN Naik Studies on bovine group B rotaviruses (GBRs) are limited. To date, only the VP6 gene of a single bovine GBR strain and the VP7 and NSP5 genes of a few bovine GBR strains have been sequenced and analyzed. In the present study, using a single-primer amplification method, we have determined the full-length nucleotide sequences of the VP1, VP2, VP4, VP6, NSP1 and NSP2 genes of three bovine GBR strains from eastern India. In all six of these genes, the bovine GBR strains shared high genetic relatedness among themselves but exhibited high genetic diversity with cognate genes of human, murine and ovine GBRs. Interestingly, as with group A rotaviruses, the bovine GBR VP1, VP2, VP6 and NSP2 genes appeared to be more conserved than the VP4 and NSP1 genes among strains of different species. The present study provides important insights into the genetic makeup and diversity of bovine GBRs, and also identifies a novel GBR VP4 genotype. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0911-6028 26 2 2010 The utility of three-dimensional dynamic contrast-enhanced 110 115 EN Yoshinobu Yanagi Mariko Fujita Miki Hisatomi Hidenobu Matsuzaki Hironobu Konouchi Naoki Katase Hitoshi Nagatsuka Jun-ichi Asaumi Aneurysmal bone cysts (ABCs) are classified as bone-related lesions based on the 2005 World Health Organization histological classification of odontogenic tumors. Most ABCs are diagnosed using a combination of conventional radiography, computed tomography, magnetic resonance imaging (MRI), and digital subtraction angiography. ABCs should be differentiated from true cysts or other pseudocysts because their treatment is different. Additionally, unlike other cysts, ABCs pose a hemorrhagic risk in surgery; thus, preoperative evaluation of intralesional blood flow is required. Here we report a case of a mandibular ABC in a 39-year-old woman and focus on its dynamic contrast-enhanced MRI (DCE-MRI) features. On DCE-MRI, the lesion was divided into two areas according to the enhancement pattern: the blood-pooling and blood-flow areas. The series of DCE-MR images of the blood-pooling area showed marked enhancement of the margin, but no enhancement in the inner part of the cavity. Additionally, the time-signal intensity curve (TIC) demonstrated no change in the signal intensity (SI) until approximately 15 min after gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) administration. In contrast, the series of DCE-MR images of the blood-flow area exhibited marked enhancement in the cyst cavity in the early phase. The TIC showed a rapid increase in SI in the early phase, followed by a rapid decrease until 150 s, and finally a gradual decrease until approximately 15 min after Gd-DTPA administration. Thus, in the current patient, preoperative DCE-MRI clearly delineated the vessel-rich area within the lesion. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0167-6806 128 3 2011 Associations among baseline variables, treatment-related factors and health-related quality of life 2 years after breast cancer surgery 735 747 EN Naruto Taira Kojiro Shimozuma Takeru Shiroiwa Shozo Ohsumi Katsumasa Kuroi Shigehira Saji Mitsue Saito Shigemichi Iha Takanori Watanabe Noriyuki Katsumata Provision of social support and rehabilitation for patients with physical, mental, and functional problems after cancer treatment is important for long-term health-related quality of life (HRQOL). Effective use of human and financial healthcare resources requires identification of patients requiring rehabilitation. The objectives of the current study were to clarify the patterns of physical and psychosocial recovery over time, to evaluate the associations among baseline variables, treatment-related factors and HRQOL at 6 months, 1, and 2 years after breast cancer surgery, and to identify the significant factors predicting HRQOL at each point. A multicenter longitudinal study was performed to evaluate physical conditions, anxiety, depression, and HRQOL at 1 month (baseline), 6 months, 1, and 2 years after surgery in 196 patients (mean age: 53.3 years old) with early breast cancer and no postoperative recurrence. Physical conditions were evaluated using a patient-reported symptom checklist. HRQOL was rated using the functional assessment of cancer treatment scalegeneral (FACT-G) and the breast cancer subscale (FACTB). Anxiety and depression were rated using the hospital anxiety and depression scale (HADS). More than 50% of patients had local problems of "tightness", "arm weakness." and "arm lymphedema", and systemic problems of "reduced energy, fatigue, and general weakness" postoperatively. The HRQOL score significantly improved 1 year after surgery, and scores for physical, emotional and functional well-being also increased with time, whereas the score for social well-being was the highest at baseline and decreased with time. Depression and anxiety significantly improved with time. Concomitant disease, marital status, and the presence of a partner, anxiety and depression at baseline, pathological lymph node involvement, and adjuvant intravenous chemotherapy were significant factors predicting FACT-G scores at 6 months, 1, and 2 years after surgery. Depression at baseline was a strong predictor of HRQOL up to 2 years after surgery. These results suggest that physical rehabilitation is required for tightness and lymphedema to improve long-term postoperative physical function. A further study of psychosocial interventions is required to improve depression and social well-being after breast cancer surgery. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0025-2611 136 1-2 2011 Cut loci and conjugate loci on Liouville surfaces 115 141 EN Jin-ichi Itoh Kazuyoshi Kiyohara In the earlier paper (Itoh and Kiyohara, Manuscr Math 114:247–264, 2004), we showed that the cut locus of a general point on two-dimensional ellipsoid is a segment of a curvature line and proved "Jacobi’s last geometric statement" on the singularities of the conjugate locus. In the present paper,we showthat a wider class of Liouville surfaces possess such simple cut loci and conjugate loci. The results include the determination of cut loci and the set of poles on two-sheeted hyperboloids and elliptic paraboloids. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 279 4 2008 Gac two-component system in Pseudomonas syringae pv. tabaci is required for virulence but not for hypersensitive reaction 313 322 EN Mizuri Marutani Fumiko Taguchi Yujiro Ogawa Mijan Md. Hossain Inagaki Yoshishige Kazuhiro Toyoda Tomonori Shiraishi Yuki Ichinose <p>Pseudomonas syringae pv. tabaci 6605 causes wildfire disease on host tobacco plants. To investigate the regulatory mechanism of the expression of virulence, Gac two-Component system-defective mutants, Delta gacA and Delta gacS, and a double mutant, Delta gacA Delta gacS, were generated. These mutants produced smaller amounts of N-acyl homoserine lactones required for quorum sensing, had lost swarming motility, and had reduced expression of virulence-related hrp genes and the algT gene required for exopolysaccharide production. The ability of the mutants to cause disease symptoms in their host tobacco plant was remarkably reduced, while they retained the ability to induce hypersensitive reaction (HR) in the nonhost plants. These results indicated that the Gac two-component system of P. syringae pv. tabaci 6605 is indispensable for virulence on the host plant, but not for HR induction in the nonhost plants.</p> No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0300-8177 280 1-2 2005 Versican is induced in infiltrating monocytes in myocardial infarction 47 56 EN Kenichi Toeda Keigo Nakamura Satoshi Hirohata Omer F. Hatipoglu Kadir Demircan Hitoshi Yamawaki Hiroko Ogawa Shozo Kusachi Yasushi Shiratori Yoshifumi Ninomiya Versican, a large chondroitin sulfate proteoglycan, plays a role in conditions such as wound healing and tissue remodelling. To test the hypothesis that versican expression is transiently upregulated and plays a role in the infarcted heart, we examined its expression in a rat model of myocardial infarction. Northern blot analysis demonstrated increased expression of versican mRNA. Quantitative real-time RT-PCR analysis revealed that versican mRNA began to increase as early as 6 h and reached its maximal level 2 days after coronary artery ligation. Versican mRNA then gradually decreased, while the mRNA of decorin, another small proteoglycan, increased thereafter. Versican mRNA was localized in monocytes, as indicated by CD68-positive staining, around the infarct tissue. The induction of versican mRNA was accelerated by ischemia/reperfusion (I/R), which was characterized by massive cell infiltration and enhanced inflammatory response. To examine the alteration of versican expression in monocytes/macrophages, we isolated human peripheral blood mononuclear cells and stimulated them with granulocyte/macrophage colony-stimulating factor (GM-CSF). Stimulation of mononuclear cells with GM-CSF increased the expression of versican mRNA as well as cytokine induction. The production of versican by monocytes in the infarct area represents a novel finding of the expression of an extracellular matrix gene by monocytes in the infarcted heart. We suggest that upregulation of versican in the infarcted myocardium may have a role in the inflammatory reaction, which mediates subsequent chemotaxis in the infarcted heart. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0065-2598 2007 C. elegans model for studying tropomyosin and troponin regulations of muscle contraction and animal behavior 153 161 EN Hiroaki Kagawa Tomohide Takaya Razia Ruksana Frederick Anokye-Danso Md. Ziaul Amin Hiromi Terami No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0344-5704 56 1 2005 Effects of histone deacetylase inhibitor FR901228 on expression level of telomerase reverse transcriptase in oral cancer 22 28 EN Jun Murakami Jun-ichi Asaumi Noriko Kawai Hidetsugu Tsujigiwa Yoshinobu Yanagi Hitoshi Nagatsuka Tetsuyoshi Inoue Susumu Kokeguchi Shoji Kawasaki Masahiro Kuroda Noriaki Tanaka Nagahide Matsubara Kanji Kishi We speculated whether or not the expression level of telomerase reverse transcriptase (hTERT) would be modulated by agents targeting epigenetics in oral cancer cell lines. Although hTERT is known to be targeted by epigenetic changes, it remains unclear how chemoagents targeting epigenetics work on hTERT transcription. In the present study, the epigenetic effects of histone deacetylase (HDAC) inhibitor FR901228 on hTERT transcription were analysed by RT-PCR in oral cancer cell lines. The mRNA expression of hTERT was upregulated after exposure to FR901228 in hTERT-negative Hep2 cells, even in the hTERT highly expressed SAS and KB cells. Moreover, co-treatment of protein synthesis inhibitor cycloheximide (CHX) resulted in the induction of hTERT transcription by FR901228. This suggests that the induction of hTERT by FR901228 requires de novo protein synthesis to some extent and is more likely a direct than an indirect effect on epigenetic changes such as histone acetylation / deacetylation. We further examined the effect of FR901228 on c-myc protein, which is one of the main hTERT transcription activators. FR901228 repressed c-myc protein only in the absence of CHX, dependent of the enhancement of de novo protein synthesis. Our results indicate that c-myc protein is repressed indirectly by FR901228 but may not contribute FR901228-induced hTERT transcription. The present study showed that the HDAC inhibitor FR901228 induced the hTERT gene by a complex mechanism that involved other transcription factors except for c-myc, in addition to the inhibition of histone deacetylation. No potential conflict of interest relevant to this article was reported.