Prolonged warm ischemia exacerbated acute rejection after lung transplantation from donation after cardiac death in a mouse

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. 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. 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 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

Influence of Diabetes Mellitus on Surgical Outcomes in Patients with Cervical Myelopathy: A Prospective, Multicenter Study

[Study Design] Multicenter, prospective study. [Purpose] To investigate the effects of diabetes mellitus (DM) on surgical outcomes in patients with cervical myelopathy. [Overview of Literature] To date, few studies have investigated the influence of postoperative blood glucose or glycated hemoglobin (HbA1c) levels on surgical outcomes. [Methods] The participants were patients who underwent surgery for the treatment of cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. The 61 cases were evaluated preoperatively and 1 year postoperatively using the Japanese Orthopaedic Association (JOA) scores and the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The study variables included fasting blood glucose and HbA1c levels measured preoperatively and at 1 week, 4 weeks, and 1 year postoperatively; the F-wave conduction velocity, latency, rate of occurrence, and M-wave latency in the ulnar and tibial nerves were measured preoperatively and at 1 year postoperatively. The patients were divided into a group without diabetes (N group, 42 patients) and a group with diabetes (DM group, 19 patients). We then assessed the associations between the surgical outcomes and each of the study variables. [Results] JOA scores significantly improved in both groups; however, no significant between-group differences were found. There was no significant improvement in the JOACMEQ scores, which assessed cervical function, upper and lower limb function, and bladder function in both groups. We then subdivided the DM group into those with a good control of HbA1c after 1 year (DMG group, 12 patients) and those with HbA1c deterioration after 1 year (DMB group, seven patients), prior to comparing the surgical outcomes. The JOACMEQ scores for upper and lower limb function significantly improved in the DMG group (p<0.01). Compared with the DMB group, there were no significant increases in upper or lower limb function scores in the DMG group. [Conclusions] Poor glycemic control might prevent postoperative functional recovery of the spinal cord

Gene Expression Analysis of the Activating Factor 3/Nuclear Protein 1 Axis in a Non-alcoholic Steatohepatitis Mouse Model

[Background] Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is a chronic liver disease related to metabolic syndrome that can progress to liver cirrhosis. The involvement of the endoplasmic reticulum (ER) stress response in NAFLD progression and the roles played by activating factor 3 (ATF3) and the downstream nuclear protein 1 (NUPR1) are poorly understood. The aim of this study was to determine the gene expression profiles around the ATF3/NUPR1 axis in relation to the development of NAFLD using novel mouse models. [Methods] Fatty liver Shionogi (FLS) mice (n = 12) as a NAFLD model and FLS-ob/ob mice (n = 28) as a NASH model were fed a standard diet. The FLS mice were sacrificed at 24 weeks of age as a control, whereas the FLS-ob/ob mice were sacrificed at 24, 36, and 48 weeks of age. Hepatic steatosis, inflammation, and fibrosis were evaluated by biochemical, histological, and gene expression analyses. The expression levels of the ER-stress related genes Jun proto-oncogene (C-jun), Atf3, Nupr1, and C/EBP homologous protein (Chop) were measured in liver tissue. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. [Results] Control mice demonstrated hepatic steatosis alone without apparent fibrosis. On the other hand, FLS-ob/ob mice showed severe steatohepatitis at both 24 and 36 weeks of age and severe fibrosis at both 36 and 48 weeks of age. The expression levels of Atf3, Nupr-1, and C-jun significantly increased from 24 to 48 weeks of age in FLS-ob/ob mice compared with control mice. The expression level of Chop was already high in FLS mice and maintained similar levels in FLS-ob/ob mice; the expression level was consistent with the percentage of TUNEL-positive cells. [Conclusion] The ATF3/NUPR1 axis plays a pivotal role in NASH progression in association with C-jun and Chop and appears to induce apoptosis from early steatosis in the NASH model mice

Protective Effects of Ipragliflozin, a Sodium-glucose Cotransporter 2 Inhibitor, on a Non-alcoholic Steatohepatitis Mouse Model

[Background] The options for the treatment of nonalcoholic steatohepatitis (NASH) are limited. We examined the effects of ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, on the fatty liver Shionogi (FLS)-ob/ob mice, a non-alcoholic steatohepatitis mouse model. [Methods] FLS-ob/ob male mice were treated with vehicle (n = 10) and ipragliflozin (n = 8). Serum metabolic markers, histopathology of the liver, hepatic cholesterol and triglyceride levels and hepatic mRNA levels related to fibrosis, lipid metabolism and endoplasmic reticulum (ER) stress were compared between the two groups. [Results] The body weight and hepatic cholesterol and triglyceride levels were significantly decreased in the ipragliflozin group compared with the control group. Hepatic steatosis and fibrosis were significantly ameliorated by the treatment with ipragliflozin. Hepatic infiltration of macrophage, expression levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and hepatic mRNA levels of ER stress markers were not significantly modulated by the treatment with ipragliflozin. [Conclusion] Ipragliflozin can be a therapeutic option for patients with NASH. The precise mechanisms of action need to be clarified in future studies

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Factors Explaining the English Proficiency of Senior High School Students : An Empirical Study

This paper explores empirical factors that explain the English proficiency of senior high school students studying English at a high school in Hiroshima Prefecture, Japan. Two studies are reported. Study 1 comprised a factor analysis and a multiple regression analysis, addressing students' reading strategy. A factor analysis revealed 9 factors : (1) understanding of main points, (2) ample input/output, (3) focus on key information, (4) reading with questions in mind, (5) top-down strategy, (6) bottom-up strategy, (7) confidence in Japanese reading ability, (8) word-by-word reading and (9) basic study. A multiple regression analysis revealed three factors to explain reading comprehension ability. These factors were : (1) understanding of main points, (2) reading with questions in mind, and (3) top-down strategy. Study 2 comprised a multiple regression analysis, exploring factors to explain the students' comprehensive English ability. This study afforded an explanation by three factors : (1) English lexico-syntactic ability, (2) modern Japanese ability and (3) motivational intensity

Postural abnormality as a risk marker for leg deep venous thrombosis in Parkinson's disease.

BACKGROUND: Pulmonary thromboembolism is a common cause of death in patients with autopsy-confirmed Parkinsonism. This study investigated the incidence of leg deep vein thrombosis in Parkinson's disease and relationships between deep vein thrombosis and clinical/laboratory findings, including postural abnormalities as assessed by photographic measurements. METHODS: This cross-sectional study assessed the presence of deep vein thrombosis using bilateral leg Doppler ultrasonography in 114 asymptomatic outpatients with Parkinson's disease. RESULTS: Deep vein thrombosis was detected in 23 patients (20%) with Parkinson's disease. Deep vein thrombosis was located in the distal portion in 18 patients and in the proximal portion in 5 patients. No significant differences in age, sex, body mass index, disease duration, Hoehn-Yahr stage, anti-Parkinson's drugs, or daily levodopa-equivalent dose were seen between deep vein thrombosis-positive and -negative groups. Univariate analysis for developing deep vein thrombosis in patients with Parkinson's disease identified the following markers: long-term wheelchair use, bent knee, bent spine, and D-dimer elevation. Bending angles were significantly greater in the deep vein thrombosis-positive group at the knee and spine than in the deep vein thrombosis-negative group. Half of Parkinson's disease patients with camptocormia had deep vein thrombosis. Among diabetes mellitus cases, long-term wheelchair use, bent knee over 15°, camptocormia, D-dimer elevation, the more risk markers were associated with a higher incidence of DVT. The presence of risk markers contributed to the development of deep vein thrombosis. On multivariate logistic regression analysis, a bent knee posture was strongly associated with an increased risk of deep vein thrombosis. CONCLUSION: Presence of leg deep vein thrombosis correlated with postural abnormalities in Parkinson's disease. We recommend non-invasive ultrasonographic screening for leg deep vein thrombosis in these high-risk patients with Parkinson's disease