Utility of Plain Chest Computed Tomography in Diagnosing Cardioembolic Stroke due to Paroxysmal Atrial Fibrillation

Background：Diagnosing cardioembolic stroke due to paroxysmal atrial fibrillation（PAF）is difficult, mainly due to low detection rate. We evaluated whether left atrial volume, which can be simply measured using non-contrast chest computed tomography（CT-LAV）, can contribute to the diagnosis of cardioembolic stroke due to PAF（PAF-CE）.Methods：Fifty-one consecutive patients with acute ischemic stroke within 24 h of onset were included in this study. Upon admission, we measured the left atrial diameter using transthoracic echocardiography（TTE-LAD）and CT-LAV. Patient background factors such as sex, age, and stroke risk factors were noted as well as brain natriuretic peptide（BNP）value and QTc interval were evaluated on admission. Utilities of BNP value, CT-ALV, and TTE-LAD in PAF-CE diagnosis were compared.Results：Patients were classified into three groups：cerebral thrombosis（CTB）group including large-artery atherosclerosis and small-vessel occlusion（n＝16）, cardioembolic stroke due to non-valvular atrial fibrillation（AF-CE）group（n＝20）, and cardioembolic stroke due to paroxysmal atrial fibrillation（PAF-CE）group（n＝15）. BNP value was highest in the AF-CE group（240.5 pg/mL）, followed by the PAF-CE（187.9 pg/mL）and CTB groups（35.0 pg/mL）（p＜0.001）. There was a significant difference in TTE-LAD among the groups（AF-CE group, 43.8 mm；PAF-CE group, 38.3 mm；CTB group, 34.1 mm）（p＜0.001）. CT-LAV was higher in the AF-CE group（142 mm3）than in the PAF-CE（95.8 mm3）and CTB groups（95.8 mm3）（p＜0.001）. In differentiating PAF-CE, the area under the receiver operating characteristic curve was 0.867, 0.742, and 0.845 for BNP value, TTE-LAD, and CT-LAV, respectively. A cut-off CT-LAV value of ≥ 69.6 mm3 had a high diagnostic rate（＞80％ of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy）.Conclusion：CT-LAV can be useful in diagnosing PAF-CE. Further studies with larger sample size are required to confirm our findings and determine better cut-off value for CT-LAV

Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial

Lower limb spasticity in post-stroke patients can impair ambulation and reduces activities of daily living (ADL) performance of patients. Botulinum toxin type A (BoNTA) has been shown effective for upper limb spasticity. This study assesses the treatment of lower limb spasticity in a large placebo-controlled clinical trial. In this multicenter, randomized, double-blind, parallel-group, placebo-controlled study, we evaluate the efficacy and safety of one-time injections of botulinum toxin type A (BoNTA) in Japanese patients with post-stroke lower limb spasticity. One hundred twenty patients with lower limb spasticity were randomized to a single treatment with BoNTA 300 U or placebo. The tone of the ankle flexor was assessed at baseline and through 12 weeks using the Modified Ashworth Scale (MAS). Gait pattern and speed of gait were also assessed. The primary endpoint was area under the curve (AUC) of the change from baseline in the MAS ankle score. Significant improvement in spasticity with BoNTA 300 U was demonstrated by a mean difference in the AUC of the change from baseline in the MAS ankle score between the BoNTA and placebo groups (−3.428; 95% CIs, −5.841 to −1.016; p = 0.006; t test). A significantly greater decrease from baseline in the MAS ankle score was noted at weeks 4, 6 and 8 in the BoNTA group compared to the placebo group (p < 0.001). Significant improvement in the Clinicians Global Impression was noted by the investigator at weeks 4, 6 and 8 (p = 0.016–0.048, Wilcoxon test), but not by the patient or physical/occupational therapist. Assessments of gait pattern using the Physician’s Rating Scale and speed of gait revealed no significant treatment differences but showed a tendency towards improvement with BoNTA. No marked difference was noted in the frequency of treatment-related adverse events between BoNTA and placebo groups. This was the first large-scale trial to indicate that BoNTA significantly reduced spasticity in lower limb muscles

MYCL promotes iPSC-like colony formation via MYC Box 0 and 2 domains

iPS細胞作製過程における初期化因子MYCLのタンパク質ドメインの機能解析. 京都大学プレスリリース. 2021-12-20.Protein domain structures affect the quality of stem cells. 京都大学プレスリリース. 2021-12-20.Human induced pluripotent stem cells (hiPSCs) can differentiate into cells of the three germ layers and are promising cell sources for regenerative medicine therapies. However, current protocols generate hiPSCs with low efficiency, and the generated iPSCs have variable differentiation capacity among different clones. Our previous study reported that MYC proteins (c-MYC and MYCL) are essential for reprogramming and germline transmission but that MYCL can generate hiPSC colonies more efficiently than c-MYC. The molecular underpinnings for the different reprogramming efficiencies between c-MYC and MYCL, however, are unknown. In this study, we found that MYC Box 0 (MB0) and MB2, two functional domains conserved in the MYC protein family, contribute to the phenotypic differences and promote hiPSC generation in MYCL-induced reprogramming. Proteome analyses suggested that in MYCL-induced reprogramming, cell adhesion-related cytoskeletal proteins are regulated by the MB0 domain, while the MB2 domain regulates RNA processes. These findings provide a molecular explanation for why MYCL has higher reprogramming efficiency than c-MYC

A stress-reduced passaging technique improves the viability of human pluripotent cells

Xeno-free culture systems have expanded the clinical and industrial application of human pluripotent stem cells (PSCs). However, reproducibility issues, often arising from variability during passaging steps, remain. Here, we describe an improved method for the subculture of human PSCs. The revised method significantly enhances the viability of human PSCs by lowering DNA damage and apoptosis, resulting in more efficient and reproducible downstream applications such as gene editing and directed differentiation. Furthermore, the method does not alter PSC characteristics after long-term culture and attenuates the growth advantage of abnormal subpopulations. This robust passaging method minimizes experimental error and reduces the rate of PSCs failing quality control of human PSC research and application

Ventriculoperitoneal Shunt Outcomes among Infants

Ventriculoperitoneal shunts (VPSs) are used for the treatment of hydrocephalus. Here we analyzed the outcomes of VPS placements in 24 infants to determine the risk factors for shunt failure. The infants had undergone the initial VPS operation in our hospital between March 2005 and December 2013. They were observed until the end of January 2014. We obtained Kaplan-Meier curves and performed a multivariate Cox regression analysis of shunt failure. Of the 24 cases, the median (range) values for gestational age, birth weight, and birth head circumference (HC) were 37 (27-39) wks, 2,736 (686-3,788) g, and 35.3 (23.0-45.3) cm, respectively. The total number of shunt procedures was 45. Shunt failure rates were 0.51/shunt and 0.0053/shunt/year. Shunt infection rates were 0.13/shunt and 0.0014/shunt/year. The Kaplan-Meier analysis revealed an increased risk for shunt failure in infants ＜1 month old or in the HC ＞90ｵtile. The Cox regression analysis yielded hazard ratios (HRs) of 2.93 (95ｵ confidence interval (CI), 0.96-10.95, p＝0.059) for age ＜1 month, and 4.46 (95ｵCI:1.20-28.91,p＝0.023) for the HC ＞90ｵtile. The multivariate Cox regression analysis showed adjusted HRs of 17.56 (95ｵCI:2.69-202.8, p＝0.001) for age ＜1 month, and 2.95 (95ｵCI:0.52-24.84, p＝0.228) for the HC ＞90ｵtile. Our findings thus revealed that the risk factors for shunt failure in infants include age ＜1 month at the initial VPS placement

pSNAP: Proteome-wide analysis of elongating nascent polypeptide chains

Cellular global translation is often measured using ribosome profiling or quantitative mass spectrometry, but these methods do not provide direct information at the level of elongating nascent polypeptide chains (NPCs) and associated co-translational events. Here, we describe pSNAP, a method for proteome-wide profiling of NPCs by affinity enrichment of puromycin- and stable isotope-labeled polypeptides. pSNAP does not require ribosome purification and/or chemical labeling, and captures bona fide NPCs that characteristically exhibit protein N-terminus-biased positions. We applied pSNAP to evaluate the effect of silmitasertib, a potential molecular therapy for cancer, and revealed acute translational repression through casein kinase II and mTOR pathways. We also characterized modifications on NPCs and demonstrated that the combination of different types of modifications, such as acetylation and phosphorylation in the N-terminal region of histone H1.5, can modulate interactions with ribosome-associated factors. Thus, pSNAP provides a framework for dissecting co-translational regulations on a proteome-wide scale

Changes in the Features of Invasive Pneumococcal Disease after Introduction of the Seven-valent Pneumococcal Conjugate Vaccine in a Regional Core Hospital of Kochi, Japan

Since the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in 2007, invasive pneumococcal disease has declined, but the incidence of Streptococcus pneumoniae serotype 19A has risen worldwide. The present study examined changes in the features of invasive pneumococcal disease since the introduction of the PCV7 in Kochi, Japan. Pediatric cases of invasive pneumococcal disease were investigated before and after vaccine introduction (January 2008 to December 2013). Cases of invasive pneumococcal disease tended to decrease after PCV7 introduction. In addition, before introduction of the vaccine, most serotypes causing invasive pneumococcal disease were those included in the vaccine. However, after the introduction, we found cases infected by serotypes not covered by vaccine. Penicillin-resistant S. pneumoniae was the predominant serotype causing invasive pneumococcal disease before introduction of the PCV7, and the susceptibility of this serotype to antibiotics improved after vaccine introduction. Serotype isolates identified after vaccine introduction were also relatively susceptible to antibiotic therapy, but decreased susceptibility is expected

Feeding habits of Netrostoma setouchianum (Kishinouye, 1902) collected from the central part of the Seto Inland Sea, Japan

根口クラゲ類エビクラゲの摂餌生態を解明するために，瀬戸内海産個体を用いて吸口構造および消化管内容物の観察を行った。吸口は長径約350μm，短径約130μm の楕円形に近い形であり，このサイズクラスの動物プランクトンが捕食されると推定される。採集した7個体の内，4個体の口腕水管内から小型浮遊性カイアシ類Paracalanus parvus s.l., Oithona sp. の2種が検出された。これらの体幅は吸口のサイズと一致する。The feeding habits of the rhizostome Netrostoma setouchianum (Kishinouye, 1902) collected from the central part of the Seto Inland Sea, Japan was examined based on observations of the structure of secondary mouths and contents in the canals and stomach. The mouths were oval, approximately 365 μm along the major axis and 130 μm along the minor axis. Small-sized planktonic copepods such as Paracalanus parvus s.l. and Oithona sp. were found in the canals and had body widths that fell well within the size of the mouths.本研究の一部は日本学術振興会科学研究補助金（基盤研究 B25304031，代表　大塚　攻；基盤研究B26304030，代表　西川　淳）によって行われた