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Aim: Dysphagia is a problem typically associated with aging. The aim was to investigate the relationship between dysphagia and motor function using a simple assessment method that can be performed in the community setting, and to promote the early detection and prevention of dysphagia. Methods: Data from the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) were used. Those aged ≥65 years were included. Motor function was assessed using a grip strength test, single limb standing test (SLS), and timed up and go test (TUG). Swallowing function was assessed using the Japanese version of the 10‐item Eating Assessment Tool (EAT‐10). The association between motor function and swallowing function was analyzed. Results: In total, 1732 participants were included. In logistic regression modes in which grip strength, SLS, and TUG results were included separately, the odds ratio for dysphagia increased by 1.08 (P = 0.001) for each 1‐kg decrease in grip strength, and increased by 1.15 (P < 0.001) for each 1‐s increase in TUG time. No association was found for SLS. In the model in which grip strength and TUG were included simultaneously, the odds ratio for dysphagia increased by 1.06 (P = 0.01) in grip strength, and increased by 1.11 (P = 0.009) in TUG time. Conclusion: Our results suggest that skeletal muscle strength and dynamic balance function are associated with dysphagia in community‐dwelling older people. Geriatr Gerontol Int 2023; 23: 603–608. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors are standard therapeutic agents for non‐small cell lung cancer (NSCLC) patients with major EGFR mutations such as exon 19 deletions and a L858R mutation, whereas treatment strategies for cases with uncommon EGFR mutations remain to be fully established. Here, we report a long‐term (≥20 years from initial diagnosis) NSCLC survivor carrying EGFR L858R and L747V mutations. The patient received gefitinib monotherapy, systemic chemotherapy/chemoimmunotherapy, and local consolidative therapies for oligometastatic lesions, and responded to afatinib rechallenge with a progression‐free survival of 12 months. The current case suggests that afatinib is effective in NSCLC patients with EGFR L858R and L747V mutations and that a therapeutic approach combining appropriately timed systemic therapies with local consolidative therapies for oligometastatic lesions improves long‐term survival. [ABSTRACT FROM AUTHOR]

Objective: To verify the validity of the prediction of oral intake recovery for inpatients with aspiration pneumonia using the Hyodo‐Komagane score. Background: Patients admitted for treatment of aspiration pneumonia sometimes have difficulty in resuming oral intake due to decreased swallowing function. Predicting whether the swallowing function will recover enough to achieve oral ingestion at discharge is an important factor in developing a treatment strategy. No studies have investigated the prediction of oral intake recovery using videoendoscopic examination. Methods: Subjects were 65 patients who were admitted to an acute care hospital for the treatment of aspiration pneumonia. The patients were divided into two groups, the oral feeding group and the tube feeding group, according to their oral intake status at discharge or transfer. Logistic regression analysis was performed using the condition that tube feeding was not required as an objective variable and the items with significant differences between the two groups as explanatory variables. Additionally, the receiver operating characteristic curve was used to identify patients who could take food orally at discharge. Results: The odds ratios for the Hyodo‐Komagane score and the pharyngeal clearance score were 1.485 and 3.379, respectively. When the cut‐off values of the Hyodo‐Komagane score and the pharyngeal clearance score were 6 and 1, the sensitivity was 0.88 and 0.91, and the specificity was 0.64 and 0.70, respectively. Conclusion: The Hyodo‐Komagane score and especially the pharyngeal clearance score are useful indices to predict oral intake recovery for inpatients with aspiration pneumonia. [ABSTRACT FROM AUTHOR]

Glycine, a non-essential amino acid, exerts concentration-dependent biphasic effects on angiogenesis. Low-doses of glycine promote angiogenesis, whereas high-doses cause anti-angiogenesis. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling participates in angiogenesis of both physiological development, and pathological events including tumor and inflammation. We assessed the role of PI3K/Akt/mTOR signaling in vascular development, and the interaction with glycine, using transgenic zebrafish Tg(fli1a:Myr-mCherry) ncv1 embryos expressing fluorescent proteins in vascular endothelial cells. Treatment with inhibitors of mTORC1 (rapamycin and everolimus), mTORC1/mTORC2 (KU0063794), PI3K (LY29400), and Akt (Akt inhibitor) decreased the development of intersegmental vessels (ISVs). These inhibitors cancelled the angiogenic effects of a low-dose of glycine, while acted synergistically with a high-dose of glycine in anti-angiogenesis. mTOR signaling regulates the gene expression of vascular endothelial growth factor (VEGF) , a major angiogenic factor, and nitric oxide (NO) synthase (NOS) , an enzyme for the synthesis of an angiogenic mediator NO. Expressions of VEGF and NOS were consistent with the vascular features induced by glycine and an mTOR inhibitor. Our results suggest that PI3K/Akt/mTOR signaling may interact with dose-dependent biphasic effects of exogenous glycine on in vivo angiogenesis. mTOR signaling is a key target for cancer therapy, thus, the combining mTOR inhibitors with glycine may be a potential approach for controlling angiogenesis. • Inhibition of PI3K/Akt/mTOR signaling impairs vascular development. • Low-glycine induced angiogenesis is blocked by inhibition of mTOR signaling. • High-glycine induced anti-angiogenesis is enhanced by inhibition of mTOR signaling. • Combination of glycine and an mTOR inhibitor affects expression of VEGF and NOS genes. [ABSTRACT FROM AUTHOR]

Glycine, a non-essential amino acid, is involved in both angiogenesis and anti-angiogenesis. We hypothesized that glycine would exert dose-dependent different effects on angiogenesis. In this study, we investigated the effects of a broad range of concentrations of glycine on vascular development using transgenic zebrafish Tg(fli1a:Myr-mCherry) ncv1 embryos. Effects of glycine transporter (GlyT) inhibitors (sarcosine and bitopertin) and a glycine receptor (GlyR) inhibitor (strychnine) were also examined in embryos in the absence or presence of glycine. After exposure to glycine and inhibitors, intersegmental vessels (ISVs) were observed by fluorescent microscopy. Low concentrations of glycine promoted the development of ISVs, whereas high concentrations reduced it. These effects of glycine could generally be reversed by treatment with GlyT and GlyR inhibitors. Furthermore, expressions of vascular endothelial growth factor (VEGF) (an angiogenic factor) and nitric oxide synthase (NOS) (an enzyme for nitric oxide synthesis) were associated with the dose-dependent effects of glycine. Our results suggest that glycine exerts dose-dependent biphasic effects on vascular development, which rely on GlyTs and GlyRs, and correlate with the expression of VEGF and NOS genes. At low concentrations, glycine acted as an angiogenic factor. In contrast, at high concentrations, glycine induced anti-angiogenesis. This evidence provides a novel insight into glycine as a unique target in angiogenic and anti-angiogenic therapy. • Glycine exerts biphasic effects on the vascular development of zebrafish embryos. • Inhibition of glycine transporters and receptors impairs vascular development. • Effects of glycine are blocked by inhibition of glycine transporters and receptors. • Glycine affects the expression of VEGF and NOS genes. [ABSTRACT FROM AUTHOR]

Opsin3 (Opn3) is a transmembrane heptahelical G protein–coupled receptor (GPCR) with the potential to produce a nonvisual photoreceptive effect. Interestingly, anatomical profiling of GPCRs reveals that Opn3 mRNA is highly expressed in adipose tissue. The photosensitive functions of Opn3 in mammals are poorly understood, and whether Opn3 has a role in fat is entirely unknown. In this study, we found that Opn3-knockout (Opn3-KO) mice were prone to diet-induced obesity and insulin resistance. At the cellular level, Opn3-KO brown adipocytes cultured in darkness had decreased glucose uptake and lower nutrient-induced mitochondrial respiration than wild-type (WT) cells. Light exposure promoted mitochondrial activity and glucose uptake in WT adipocytes but not in Opn3-KO cells. Brown adipocytes carrying a defective mutation in Opn3's putative G protein–binding domain also exhibited a reduction in glucose uptake and mitochondrial respiration in darkness. Using RNA-sequencing, we identified several novel light-sensitive and Opn3-dependent molecular signatures in brown adipocytes. Importantly, direct exposure of brown adipose tissue (BAT) to light in living mice significantly enhanced thermogenic capacity of BAT, and this effect was diminished in Opn3-KO animals. These results uncover a previously unrecognized cell-autonomous, light-sensing mechanism in brown adipocytes via Opn3-GPCR signaling that can regulate fuel metabolism and mitochondrial respiration. Our work also provides a molecular basis for developing light-based treatments for obesity and its related metabolic disorders. Brown adipose tissue plays a pivotal role in energy homeostasis and serves as a metabolic sink for glucose and fatty acid. This study demonstrates a novel light-sensing mechanism in mice via the photoreceptor Opsin3 that regulates fuel utilization and mitochondrial activity of brown adipocytes. [ABSTRACT FROM AUTHOR]

Objectives Pneumonia remains a primary cause of death for under-five children. It is possible to reduce the mortality impact from childhood pneumonia if caregivers recognise the danger signs of pneumonia and obtain appropriate healthcare. Among caregivers, research on fathers' healthcare-seeking behaviours and perceptions are limited, whereas research on mothers is available. This study aims to reveal fathers' roles and perspectives with respect to the selection of care and treatment for children with pneumonia in a remote island of the Philippines. Design A qualitative research was carried out using semistructured interviews. Setting and participants The interviews were conducted with 12 fathers whose children had pneumonia-like episodes in the 6 months prior to the interview. Data analysis was performed using the concept analysis method to identify codes which were merged into subcategories and categories. Finally, the themes were identified. Results Three themes were identified as part of fathers' roles, and two were identified as fathers' perspectives on various treatment options. Fathers took care of their sick children by not entrusting care only to mothers because they considered this as part of their role. Notably, fathers considered that arranging money for the child's treatment was a matter of prime importance. They selected a particular treatment based on their experiences and beliefs, including herbal medicine, home treatment, and visiting traditional healers and health facilities. Their decision was influenced by not only their perception of the severity of illness but also cultural beliefs on the cause of illness. Visiting health facilities, particularly during hospital admissions, causes significant financial burden for the family which was the main concern of fathers. Conclusion It is crucial to consider the cultural background and also imperative to address issues related to medical cost and the credibility of health facilities to improve fathers' healthcare-seeking behaviour. [ABSTRACT FROM AUTHOR]

Eosinophilic granulomatosis with polyangiitis (EGPA) is systemic vasculitis caused by eosinophilia affecting small to medium-sized blood vessels, which damages the organs. Antineutrophil cytoplasmic antibody-associated vasculitis EGPA treatment guidelines added anti-interleukin-5 antibody mepolizumab to the standard treatment protocol for active-non-severe EGPA based on the MIRRA study. Nevertheless, the role of mepolizumab in treating patients with active severe EGPA has not been established. We treated a patient with EGPA complicated with small intestine perforation using steroid pulse intravenous, high-dose glucocorticoids, intravenous high-dose immunoglobulin therapy, and mepolizumab without immunosuppression agents; the patient went into remission, suggesting that mepolizumab is an effective therapeutic agent that could lead to remission in severe EGPA. [ABSTRACT FROM AUTHOR]