TDP-43 is the major disease-associated protein involved in the pathogenesis and progression of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions linked to TDP-43 pathology (FTLD-TDP). Abnormal phosphorylation, truncation and cytoplasmic mis-localization are known to be the characteristics for the aggregated forms of TDP-43, and gain of toxic abnormal TDP-43 or loss of function of physiological TDP-43 have been suggested as the cause of neurodegeneration. However, most of the post-translational modifications or truncation sites in the abnormal TDP-43 in brains of patients remain to be identified by protein chemical analysis. In this study, we carried out a highly sensitive liquid chromatography-mass spectrometry analysis of Sarkosyl-insoluble pathological TDP-43 from brains of ALS patients and identified several novel phosphorylation sites, deamidation sites, and cleavage sites. Almost all modifications were localized in the Gly-rich C-terminal half. Most of the cleavage sites identified in this study are novel and are located in N-terminal half, suggesting that these sites may be more accessible to proteolytic enzymes. The data obtained in this study provide a foundation for the molecular mechanisms of TDP-43 aggregation and ALS pathogenesis.

Swallowing dysfunction caused by stroke is a risk factor for aspiration pneumonia. Tongue pressure measurement is a simple and noninvasive method for evaluating swallowing dysfunction. We have hypothesized that low tongue pressure may be able to predict pneumonia occurrence in acute stroke patients. Tongue pressure was measured using balloon-type equipment in 220 acute stroke patients. The modified Mann Assessment of Swallowing Ability (MASA) score was evaluated independently on the same day. Tongue pressure was measured every week thereafter. An improvement in tongue pressure was observed within the first 2 weeks. Receiver operating curve analysis was performed to determine the ability of tongue pressure to predict modified MASA score <95, which suggests swallowing dysfunction. The optimal cutoff for tongue pressure was 21.6 kPa (χ2 = 45.82, p<0.001, sensitivity 95.9%, specificity 91.8%, area under the curve = 0.97). The tongue pressure was significantly lower in patients with pneumonia than in those without pneumonia. Using a Cox proportional hazard model for pneumonia onset with a cutoff tongue pressure value of 21.6 kPa and adjustment for age, sex, and National Institutes of Health Stroke Scale score at admission, the tongue pressure had additional predictive power for pneumonia onset (hazard ratio, 7.95; 95% confidence interval, 2.09 to 52.11; p = 0.0013). In the group with low tongue pressure, 27 of 95 patients showed improvement of tongue pressure within 2 weeks. Pneumonia occurred frequently in patients without improvement of tongue pressure, but not in patients with improvement (31/68 and 2/27, p<0.001). Tongue pressure is a sensitive indicator for predicting pneumonia occurrence in acute stroke patients.

Synphilin-1 has neuroprotective effects on MPP +-induced Parkinson's disease model cells by inhibiting ROS production and apoptosis

No abstract

Objective To study the longitudinal seizure outcomes of people with epilepsy (PWE) following the acute and chronic phases of the coronavirus disease 2019 (COVID-19) pandemic. Methods Consecutive PWE who were treated at the epilepsy center of Hiroshima University Hospital between 2018 and 2021 were enrolled. We evaluated the incidence of seizure frequency increase or decrease following the pandemic during observational periods in 2020 and 2021. Data between 2018 and 2019 were used as a control set. The sustainability of the altered seizure frequency condition was evaluated throughout the study period. We analyzed the clinical, psychological, and social factors associated with PWE with seizure exacerbation or amelioration. Results Among the 223 PWE who were evaluated (mean age 37.8 ± 16.3 years), seizure frequency increased for 40 (16.8%) and decreased for 34 (15.2%) after the pandemic began. While seizure exacerbation tended to be a transient episode during 2020, seizure amelioration was likely to maintain excellent status over the observation periods; the sustainability of the altered seizure frequency condition was more prominent for amelioration than exacerbation ( p < 0.001). Seizure exacerbation was significantly associated with “no housemate” (odds ratio [OR] 3.37; p = 0.045) and “comorbidity of insomnia” (OR 5.80; p = 0.004). Conversely, “structural abnormality of MRI” (OR 2.57; p = 0.039) and “two-generation householding” (OR 3.70; p = 0.004) were independently associated with seizure amelioration. Conclusion This longitudinal observation confirmed that seizure exacerbation and amelioration emerged during the COVID-19 pandemic. The COVID-19 pandemic has shed light on the stark difference that social support systems can make on outcomes for PWE.