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

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

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

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

Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10

We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents

短期記憶および作業記憶の評価系の確立

Memory can be classified into at least short-term memory and long-term memory based on its retention time. Short-term memory usually disappears immediately, but when some event, gaze or novelty happens at the same time, it is selectively converted to long-term memory. Work memory is given as a very short memory retention, but this is used as temporary memory retention. In this research, we have established a fundamental research and evaluation system for short-term memory and work memory using spatial object recognition task and modified T-maze. These tests will be used to quantify cognitive deficits in transgenic strains of mice and evaluate novel chemical entities for their effects on cognition