Osamu Yamamura

This study evaluated changes in the skeletal muscle mass index (SMI) in community residents who received a photos-based dietary guidance system, personalized exercise plans, and meal photography feedback to address sarcopenia. These findings indicated a possible upward trend in SMI within 3 months.

Nivolumab blocks inhibitors of T-cell activation and restores antitumor immunity but promotes T-cell activity in host tissues by blocking inhibition of the T-cell function, resulting in immune-related adverse effects. We herein report an 80-year-old man presenting with nivolumab-related myasthenia gravis with anti-muscular voltage-gated potassium channel-complex (Kv1.4) antibodies. On day 29 after nivolumab administration, he simultaneously developed rapidly progressing right ptosis and left facial paralysis. Nivolumab administration was discontinued. He subsequently presented with bulbar paralysis, dyspnea, and muscle weakness and received intravenous immunoglobulin, methylprednisolone, and plasma exchange. The severity of nivolumab-related myasthenia gravis with anti-Kv1.4 antibodies presented with diverse clinical findings.

This report presents a unique finding of an incidental right internal carotid artery dissection in an asymptomatic 69-year-old man. The report highlights the possible trigger and long-term outcomes of this condition. The patient had participated in Japanese archery competitions for many years. His medical history included hypertension and a prior ischemic stroke in the left lateral medulla, resulting in Wallenberg syndrome. During a routine visit, head magnetic resonance angiography revealed right internal carotid artery dissection. He was managed conservatively with antiplatelet therapy and close monitoring. Follow-up imaging after 10 years showed no changes, and the patient remained asymptomatic. Therefore, routine screening for incidental findings is important even in asymptomatic patients. Archery competitions may be a possible trigger for internal carotid artery dissection. The presence of re-entry in the lesion at the time of onset can be a predictor of a good long-term prognosis.

Ultrasonography and computed tomography of the lower extremities revealed fresh and chronic mixed-vein thrombosis (FCMVTs) presenting the "Blowfish sign," accompanied by pulmonary embolism. FCMVTs presenting the "Blowfish sign" may increase the risk of fatal pulmonary embolism, and its detection by ultrasonography is important for preventing pulmonary embolism.

Vitamin B₁₂ deficiency is associated with cognitive impairment, hyperhomocysteinemia, and hippocampal atrophy. However, the recovery of cognition with vitamin B₁₂ supplementation remains controversial. Of the 1716 patients who visited our outpatient clinic for dementia, 83 had vitamin B₁₂ deficiency. Among these, 39 patients (mean age, 80.1 ± 8.2 years) had undergone Mini-Mental State Examination (MMSE) and laboratory tests for vitamin B₁₂, homocysteine (Hcy), and folic acid levels. The hippocampal volume was estimated using the z-score of the MRI-voxel-based specific regional analysis system for Alzheimer’s disease. This is multi-center, open-label, single-arm study. All the 39 patients were administered vitamin B₁₂ and underwent reassessment to measure the retested for MMSE and Hcy after 21−133 days (median = 56 days, interquartile range (IQR) = 43–79 days). After vitamin B₁₂ supplementation, the mean MMSE score improved significantly from 20.5 ± 6.4 to 22.9 ± 5.5 (p < 0.001). Hcy level decreased significantly from 22.9 ± 16.9 nmol/mL to 11.5 ± 3.9 nmol/mL (p < 0.001). Significant correlation was detected between the extent of change in MMSE scores and baseline Hcy values. The degree of MMSE score was not correlated with hippocampal atrophy assessed by the z-score. While several other factors should be considered, vitamin B₁₂ supplementation resulted in improved cognitive function, at least in the short term, in patients with vitamin B₁₂ deficiency.

Objective: This study aimed to examine the prevalence of deep vein thrombosis (DVT) among evacuees in Minamiaso, a village which was temporarily isolated after the earthquakes, from the acute to recovery phase after the 2016 Kumamoto Earthquakes (GLIDE no: EQ-2016-000033-JPN).Methods: This prospective study, which was approved by Fukui University Medical Research Ethics Committee (approval no. 20160024 and 20160089), enrolled 181 evacuees (73.9 ± 11.6 y) who participated in a series of 3 DVT screenings using portable ultrasound machines conducted over 19 mo. All participants completed a questionnaire before the screenings, and none of the participants attended all 3 screenings. Data analysis was performed using EZR version 1.41.Results: The DVT prevalence was 14.3% (79.4 ± 8.2 y) at first screening of evacuees staying in shelters and 18.5% (71.5 ± 13.1 y) and 12.2% (72.8 ± 10.9 y) in second and third screenings of evacuees staying in temporary housing, respectively. Multivariate analysis revealed age ≥75 y and alcohol consumption as independent risk factors in the entire cohort and in patients aged ≤74 y, respectively.Conclusions: A high DVT prevalence over a long time period of 19 mo was observed where survivors were temporarily isolated after the disaster.

The neuropathological hallmarks of Alzheimer’s disease (AD) are senile plaques (SPs), which are composed of amyloid β protein (Aβ), and neurofibrillary tangles (NFTs), which consist of highly phosphorylated tau protein. As bio-metal imbalance may be involved in the formation of NFT and SPs, metal regulation may be a direction for AD treatment. Clioquinol (CQ) is a metal-protein attenuating compound with mild chelating effects for Zn²⁺ and Cu²⁺, and CQ can not only detach metals from SPs, but also decrease amyloid aggregation in the brain. Previous studies suggested that Cu²⁺ induces the hyperphosphorylation of tau. However, the effects of CQ on tau were not fully explored. To examine the effects of CQ on tau metabolism, we used a human neuroblastoma cell line, M1C cells, which express wild-type tau protein (4R0N) via tetracycline-off (TetOff) induction. In a morphological study and ATP assay, up to 10 μM CQ had no effect on cell viability; however, 100 μM CQ had cytotoxic effects. CQ decreased accumulation of Cu⁺ in the M1C cells (39.4% of the control), and both total and phosphorylated tau protein. It also decreased the activity of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) (37.3% and 60.7% levels of the control, respectively), which are tau kinases. Of note, activation of protein phosphatase 2A (PP2A), which is a tau phosphatase, was also observed after CQ treatment. Fractionation experiments demonstrated a reduction of oligomeric tau in the tris insoluble, sarkosyl soluble fraction by CQ treatment. CQ also decreased caspase-cleaved tau, which accelerated the aggregation of tau protein. CQ activated autophagy and proteasome pathways, which are considered important for the degradation of tau protein. Although further studies are needed to elucidate the mechanisms responsible for the effects of CQ on tau, CQ may shed light on possible AD therapeutics.

This study presents a new blood pressure (BP) estimation algorithm utilizing machine learning (ML). A cuffless device that can measure BP without calibration would be precious for portability, continuous measurement, and comfortability, but unfortunately, it does not currently exist. Conventional BP measurement with a cuff is standard, but this method has various problems like inaccurate BP measurement, poor portability, and painful cuff pressure. To overcome these disadvantages, many researchers have developed cuffless BP estimation devices. However, these devices are not clinically applicable because they require advanced preparation before use, such as calibration, do not follow international standards (81060-1:2007), or have been designed using insufficient data sets. The present study was conducted to combat these issues. We recruited 127 participants and obtained 878 raw datasets. According to international standards, our diverse data set included participants from different age groups with a wide variety of blood pressures. We utilized ML to formulate a BP estimation method that did not require calibration. The present study also conformed to the method required by international standards while calculating the level of error in BP estimation. Two essential methods were applied in this study: (a) grouping the participants into five subsets based on the relationship between the pulse transit time and systolic BP by a support vector machine ensemble with bagging (b) applying the information from the wavelet transformation of the pulse wave and the electrocardiogram to the linear regression BP estimation model for each group. For systolic BP, the standard deviation of error for the proposed BP estimation results with cross-validation was 7.74 mmHg, which was an improvement from 17.05 mmHg, as estimated by the conventional pulse-transit-time-based methods. For diastolic BP, the standard deviation of error was 6.42 mmHg for the proposed BP estimation, which was an improvement from 14.05mmHg. The purpose of the present study was to demonstrate and evaluate the performance of the newly developed BP estimation ML method that meets the international standard for non-invasive sphygmomanometers in a population with a diverse range of age and BP.

Neurofibrillary tangles, which consist of highly phosphorylated tau protein, and senile plaques (SPs) are pathological hallmarks of Alzheimer’s disease (AD). In swollen axons, many autophagic vacuoles are observed around SP in the AD brain. This suggests that autophagy function is disturbed in AD. We used a neuronal cellular model of tauopathy (M1C cells), which harbors wild type tau (4R0N), to assess the effects of the lysosomotrophic agent NH4Cl, and autophagy inhibitors chloroquine and 3 methyladenine (3MA). It was found that chloroquine, NH4Cl and 3MA markedly increased tau accumulation. Thus, autophagy lysosomal system disturbances disturbed the degradation mechanisms of tau protein. Other studies also revealed that tau protein, including aggregated tau, is degraded via the autophagy lysosome system. Phosphorylated and C terminal truncated tau were also reported to disturb autophagy function. As a therapeutic strategy, autophagy upregulation was suggested. Thus far, as autophagy modulators, rapamycin, mTOCR1 inhibitor and its analogues, lithium, metformin, clonidine, curcumin, nicotinamide, bexaroten, and torehalose have been proposed. As a therapeutic strategy, autophagic modulation may be the next target of AD therapeutics.