Rationale and design of the AXIOMATIC-SSP phase II trial: Antithrombotic treatment with factor XIa inhibition to Optimize Management of Acute Thromboembolic events for Secondary Stroke Prevention

MRI; Milvexian; Stroke preventionResonancia magnética; Milvexian; Prevención de ictusRessonància magnètica; Milvexian; Prevenció d'ictusBackground Individuals with ischemic stroke or transient ischemic attack (TIA) have a high early risk of ischemic stroke despite dual antiplatelet therapy. The risk of ischemic stroke, and associated disability, represents a significant unmet clinical need. Genetic variants resulting in reduced factor XI levels are associated with reduced risk for ischemic stroke but are not associated with increased intracranial bleeding. Milvexian is an oral small-molecule inhibitor of FXIa that binds activated factor XI with high affinity and selectivity and may reduce the risk of stroke when added to antiplatelet drugs without significant bleeding. We aimed to evaluate the dose-response relationship of milvexian in participants treated with dual antiplatelets. Methods We began a phase II, double-blinded, randomized, placebo-controlled trial at 367 sites in 2019. Participants (N = 2366) with ischemic stroke (National Institutes of Health Stroke Scale score ≤7) or high-risk TIA (ABCD2 score ≥6) were randomized to 1 of 5 doses of milvexian or placebo for 90 days. Participants also received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg for 90 days. The efficacy endpoint was the composite of ischemic stroke or incident infarct on magnetic resonance imaging. Major bleeding, defined as type 3 or 5 bleeding according to the Bleeding Academic Research Consortium, was the safety endpoint. Participant follow-up will end in 2022. Conclusion The AXIOMATIC-SSP trial will evaluate the dose-response of milvexian for ischemic stroke occurrence in participants with ischemic stroke or TIA.This study is sponsored by Bristol Myers Squibb and Janssen Research & Development, LLC

Detrimental effect of anemia after mechanical thrombectomy on functional outcome in patients with ischemic stroke

BackgroundAnemia can occur due to an aspiration maneuver of blood with thrombi during mechanical thrombectomy (MT) for stroke. However, the association between postoperative anemia and stroke outcomes is unknown.MethodsIn a registry-based hospital cohort, consecutive patients with acute ischemic stroke who underwent MT were retrospectively recruited. Patients were divided into the following three groups according to their hemoglobin (Hb) concentrations within 24 h after MT; no anemia (Hb concentrations ≥13 g/dL for men and ≥ 12 g/dL for women), mild anemia (Hb concentrations of 11–13 g/dL and 10–12 g/dL, respectively), and moderate-to-severe anemia (Hb concentrations <11 g/dL and < 10 g/dL, respectively). A 3-month modified Rankin Scale score of 0–2 indicated a favorable outcome.ResultsOf 470 patients, 166 were classified into the no anemia group, 168 into the mild anemia group, and 136 into the moderate-to-severe anemia group. Patients in the moderate-to-severe anemia group were older and more commonly had congestive heart failure than those in the other groups. Patients in the moderate-to-severe anemia group also had more device passes than those in the other groups (p < 0.001). However, no difference was observed in the rate of final extended thrombolysis in cerebral infarction ≥2b reperfusion or intracranial hemorrhage among the groups. A favorable outcome was less frequently achieved in the moderate-to-severe anemia group than in the no anemia group (adjusted odds ratio, 0.46; 95% confidence interval, 0.26–0.81) independent of the baseline Hb concentration. A restricted cubic spline model with three knots showed that the adjusted odds ratio for a favorable outcome was lower in patients with lower Hb concentrations within 24 h after MT.ConclusionModerate-to-severe anemia within 24 h after MT is independently associated with a reduced likelihood of a favorable outcome.Clinical trial registrationhttps://www.clinicaltrials.gov, NCT02251665

Fermion Scattering off CP-Violating Electroweak Bubble Wall

A general prescription to solve the Dirac equation in the presence of CP-violating electroweak bubble wall is presented. The profile of the bubble wall is not specified except that the wall height is $m_0$ and zero deep in the broken- and the symmetric-phase regions, respectively, where $m_0$ is a fermion mass given by the Higgs-vacuum-expectation value and the Yukawa coupling. The CP-violating effects are evaluated by regarding CP-violating part of the bubble wall as a perturbation to CP-conserving solutions. The basic quantity, $R_{R\rightarrow L}-\bar R_{R\rightarrow L}$, which would contribute to the cosmological baryon asymmetry, is estimated for some typical profiles of the wall, where $R_{R\rightarrow L}$($\bar R_{R\rightarrow L}$) is the reflection coefficient of right-handed chiral fermion (anti-fermion).Comment: 30 pages, 2 figures ( uuencoded tar.Z file of PS files is appended ), plain TeX with phyzzx, tables and epsf,SAGA-HE-55--KYUSHU-HET-1

The identification and functional implications of human-specific "fixed" amino acid substitutions in the glutamate receptor family

<p>Abstract</p> <p>Background</p> <p>The glutamate receptors (GluRs) play a vital role in the mediation of excitatory synaptic transmission in the central nervous system. To clarify the evolutionary dynamics and mechanisms of the GluR genes in the lineage leading to humans, we determined the complete sequences of the coding regions and splice sites of 26 chimpanzee GluR genes.</p> <p>Results</p> <p>We found that all of the reading frames and splice sites of these genes reported in humans were completely conserved in chimpanzees, suggesting that there were no gross structural changes in humans after their divergence from the human-chimpanzee common ancestor. We observed low <it>K</it>_<it>A</it>/<it>K</it>_{<it>S </it>}ratios in both humans and chimpanzees, and we found no evidence of accelerated evolution. We identified 30 human-specific "fixed" amino acid substitutions in the GluR genes by analyzing 80 human samples of seven different populations worldwide. Grantham's distance analysis showed that <it>GRIN2C </it>and <it>GRIN3A </it>are the most and the second most diverged GluR genes between humans and chimpanzees. However, most of the substitutions are non-radical and are not clustered in any particular region. Protein motif analysis assigned 11 out of these 30 substitutions to functional regions. Two out of these 11 substitutions, D71G in <it>GRIN3A </it>and R727H in <it>GRIN3B</it>, caused differences in the functional assignments of these genes between humans and other apes.</p> <p>Conclusion</p> <p>We conclude that the GluR genes did not undergo drastic changes such as accelerated evolution in the human lineage after the divergence of chimpanzees. However, there remains a possibility that two human-specific "fixed" amino acid substitutions, D71G in <it>GRIN3A </it>and R727H in <it>GRIN3B</it>, are related to human-specific brain function.</p

チイキ レンケイ ニヨル ショネンジ キョウイク プログラム ノ ジッセンテキ ケンキュウ : ガクセイ ニヨル チイキ プロモーションビデオ セイサク

This research aims to develop a new program for first year education with a view to cultivating students\u27 abilities to work in groups, to conduct case studies, and to analyze and present their findings in a creative way. In this program, each group was assigned a case study of an NPO in Himeji area. Five or six students work in a group and conduct research on the target organization. They interviewed NPO workers and participate in social activities to deepen their understanding of the organization. In the end, each group shared the result of the study through powerpoint presentations and short films. Survey was conducted to analyze the responses of both students and local NPO workers to this educational experiment. The survey shows that this program contributed developing students\u27 interests in social activities. NPO workers also evaluated this attempt positively as an approach to co-develop project-based learning that could offer merits both for students and NPOs

The self-esteem and the activities of daily living in inpatients after an ischemic stroke

急性期の脳梗塞患者の自尊感情と日常生活動作の関連を明らかにするために,入院中の脳梗塞患者150人に調査協力を依頼した.調査協力の同意が得られなかった患者25人と調査前に退院された患者17人を除き,108人(72.0%)(男性74人,女性34人,平均年齢64.5(SD 12.5)才)にアンケート調査を実施した.自尊感情(Rosenberg のSelf-Esteem,以下RSE と記載)は平均29.9(SD 6.1)点,日常生活動作(Barthel index,以下BI と記載)は平均89.4(SD 16.0)点であり,RSE とBI の間にはBI が低いとRSE が低いという正の相関がみられた(Spearman のρ= 0.461,p < 0.001).また,BI が低いことと「女性である」「高齢である」「入院時の機能障害が重い」の関連が示唆された.急性期には,脳梗塞患者の日常生活動作の自立に向けた援助と,自尊感情を高める介入が必要であると考えられた.The purpose of this study was to investigate the relationship between self-esteem and the activities of daily living in inpatients after an ischemic stroke. The level of Rosenberg's Self-esteem and the Barthel index were examined. There were 108 respondents (74 males and 34 females). Based on these results, selfesteem was significantly correlated to the Barthel Index (Spearman's ρ=0.461, p<0.001). Findings indicated that low self-esteem related to dependence, and the level of dependence showed a negative association with women, the elderly and severe disability. These results suggested the necessity of rehabilitation for re-acquiring the skills of daily living and enhancement of self-esteem in patients who are dependent.広島保健学学会 特別講