Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis

Background: The results of meta-analyses conducted by previous association studies between total homocysteine and schizophrenia suggest that an elevated total homocysteine level is a risk factor for schizophrenia. However, observational studies have potential limitations, such as confounding and reverse causation. In the present study, we evaluated a causal relationship between plasma total homocysteine and schizophrenia by conducting a Mendelian randomization analysis. Methods: We used the MTHFR C677T polymorphism as an instrumental variable, which affects the plasma total homocysteine levels. To calculate the risk estimate for the association of this single nucleotide polymorphism (SNP) with schizophrenia, we conducted a meta-analysis of case–control studies that comprise a total of 11,042 patients with schizophrenia and 14,557 control subjects. We obtained an estimate for the association of this SNP with the plasma total homocysteine levels from a meta-analysis of genome-wide association studies comprising 44,147 individuals. Results: By combining these two estimates, we demonstrated a significant effect of the plasma total homocysteine on schizophrenia risk, representing an OR of 2.15 (95 % CI = 1.39–3.32; p = 5.3 x 10−4) for schizophrenia per 1-SD increase in the natural log-transformed plasma total homocysteine levels. Conclusions: We provided evidence of a causal relationship between the plasma total homocysteine and schizophrenia, and this result will add insight into the pathology and treatment of schizophrenia

Magnetic and structural studies on two-dimensional antiferromagnets (MCl)LaNb₂O₇ (M = Mn, Co, Cr)

We report magnetic and structural studies on the two-dimensional antiferromagnets (MCl)LaNb₂O₇ (M = Mn, Cr, Co), prepared by topochemical reactions of a layered perovskite RbLaNb2O7. Electron diffraction of these oxyhalides revealed a superstructure with a √2a × √2a cell for M = Mn and Co, and a √2a × √2a cell for M = Cr, indicating that the MCl networks are distorted from an ideal square lattice. Neutron diffraction experiments showed that M = Mn and Co exhibit a(π 0 π) antiferromagnetic order as observed for the S = 1/2 counterparts. (CoCl)LaNb₂O₇ with a strong spin anisotropy shows an antiferro to weak-ferromagnetic transition at low field, followed by novel two-step metamagnetic transitions likely associated with a 1/2 plateau for 27-54 T. Possible spin structures under magnetic field are discussed in terms of an Ising-type model. By contrast, (CrCl)LaNb₂O₇ exhibits a (π π π) order, which is the first observation among related oxyhalides, and a spin-flop transition at 12 T due to a weak spin anisotropy. These results suggest that a slight difference in the MCl structure and spin anisotropy provides a crucial influence on the magnetic properties

Am80, a retinoic acid receptor agonist, activates the cardiomyocyte cell cycle and enhances engraftment in the heart

ヒトiPS細胞由来心筋細胞の生着能改善に向けた新しい方法. 京都大学プレスリリース. 2023-07-14.Am80, a retinoic acid receptor agonist, activates cell cycle in induced cardiomyocytes and enhances heart tissue engraftment. 京都大学プレスリリース. 2023-07-14.Human induced pluripotent stem cell-derived (hiPSC) cardiomyocytes are a promising source for regenerative therapy. To realize this therapy, however, their engraftment potential after their injection into the host heart should be improved. Here, we established an efficient method to analyze the cell cycle activity of hiPSC cardiomyocytes using a fluorescence ubiquitination-based cell cycle indicator (FUCCI) system. In vitro high-throughput screening using FUCCI identified a retinoic acid receptor (RAR) agonist, Am80, as an effective cell cycle activator in hiPSC cardiomyocytes. The transplantation of hiPSC cardiomyocytes treated with Am80 before the injection significantly enhanced the engraftment in damaged mouse heart for 6 months. Finally, we revealed that the activation of endogenous Wnt pathways through both RARA and RARB underlies the Am80-mediated cell cycle activation. Collectively, this study highlights an efficient method to activate cell cycle in hiPSC cardiomyocytes by Am80 as a means to increase the graft size after cell transplantation into a damaged heart

Are regional variations in activity of dispatcher-assisted cardiopulmonary resuscitation associated with out-of-hospital cardiac arrests outcomes? A nation-wide population-based cohort study

Aim: Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) impacts the rates of bystander CPR (BCPR) and survival after out-of-hospital cardiac arrests (OHCAs). This study aimed to elucidate whether regional variations in indexes for BCPR and emergency medical service (EMS) may be associated with OHCA outcomes. Methods: We conducted a population-based observational study involving 157,093 bystander-witnessed, resuscitation-attempted OHCAs without physician involvement between 2007 and 2011. For each index of BCPR and EMS, we classified the 47 prefectures into the following three groups: advanced, intermediate, and developing regions. Nominal logit analysis followed by multivariable logistic regression including OHCA backgrounds was employed to examine the association between neurologically favourable 1-month survival, and regional classifications based on BCPR- and EMS-related indexes. Results: Logit analysis including all regional classifications revealed that the number of BLS training course participants per population or bystander\u27s own performance of BCPR without DA-CPR was not associated with the survival. Multivariable logistic regression including the OHCA backgrounds known to be associated with survival (BCPR provision, arrest aetiology, initial rhythm, patient age, time intervals of witness-to-call and call-to-arrival at patient), the following regional classifications based on DA-CPR but not on EMS were associated with survival: sensitivity of DA-CPR [adjusted odds ratio (95% confidence intervals) for advanced region; those for intermediate region, with developing region as reference, 1.277 (1.131-1.441); 1.162 (1.058-1.277)]; the proportion of bystanders to follow DA-CPR [1.749 (1.554-1.967); 1.280 (1.188-1.380)]. Conclusions: Good outcomes of bystander-witnessed OHCAs correlate with regions having higher sensitivity of DA-CPR and larger proportion of bystanders to follow DA-CPR. © 2015 Elsevier Ireland Ltd.Embargo Period 12 month

iPSC screening for drug repurposing identifies anti‐RNA virus agents modulating host cell susceptibility

RNAウイルスの感染を阻害する既存薬の同定 --複数の異なるRNAウイルスに対して宿主細胞の感受性を下げることにより感染を抑制する薬剤--. 京都大学プレスリリース. 2021-04-07.iPS cells in drug screenings for COVID-19. 京都大学プレスリリース. 2021-04-07.Human pathogenic RNA viruses are threats to public health because they are prone to escaping the human immune system through mutations of genomic RNA, thereby causing local outbreaks and global pandemics of emerging or re‐emerging viral diseases. While specific therapeutics and vaccines are being developed, a broad‐spectrum therapeutic agent for RNA viruses would be beneficial for targeting newly emerging and mutated RNA viruses. In this study, we conducted a screen of repurposed drugs using Sendai virus (an RNA virus of the family Paramyxoviridae), with human‐induced pluripotent stem cells (iPSCs) to explore existing drugs that may present anti‐RNA viral activity. Selected hit compounds were evaluated for their efficacy against two important human pathogens: Ebola virus (EBOV) using Huh7 cells and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) using Vero E6 cells. Selective estrogen receptor modulators (SERMs), including raloxifene, exhibited antiviral activities against EBOV and SARS‐CoV‐2. Pioglitazone, a PPARγ agonist, also exhibited antiviral activities against SARS‐CoV‐2, and both raloxifene and pioglitazone presented a synergistic antiviral effect. Finally, we demonstrated that SERMs blocked entry steps of SARS‐CoV‐2 into host cells. These findings suggest that the identified FDA‐approved drugs can modulate host cell susceptibility against RNA viruses

A multicenter prospective registry of Borden type I dural arteriovenous fistula: results of a 3-year follow-up study

PURPOSE: Although intracranial dural arteriovenous fistula (DAVF) without retrograde leptomeningeal venous drainage (Borden type I) is reported to have a benign nature, no study has prospectively determined its clinical course. Here, we report a 3-year prospective observational study of Borden type I DAVF. METHODS: From April 2013 to March 2016, consecutive patients with DAVF were screened at 13 study institutions. We collected data on baseline characteristics, clinical symptoms, angiography, and neuroimaging. Patients with Borden type I DAVF received conservative care while palliative intervention was considered when the neurological symptoms were intolerable, and were followed at 6, 12, 24, and 36 months after inclusion. RESULTS: During the study period, 110 patients with intracranial DAVF were screened and 28 patients with Borden type I DAVF were prospectively followed. None of the patients had conversion to higher type of Borden classification or intracranial hemorrhage during follow-up. Five patients showed spontaneous improvement or disappearance of neurological symptoms (5/28, 17.9%), and 5 patients showed a spontaneous decrease or disappearance of shunt flow on imaging during follow-up (5/28, 17.9%). Stenosis or occlusion of the draining sinuses on initial angiography was significantly associated with shunt flow reduction during follow-up (80.0% vs 21.7%, p = 0.02). CONCLUSION: In this 3-year prospective study, patients with Borden type I DAVF showed benign clinical course; none of these patients experienced conversion to higher type of Borden classification or intracranial hemorrhage. The restrictive changes of the draining sinuses at initial diagnosis might be an imaging biomarker for future shunt flow reduction