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Aims: The ALIMENT‐HF trial aims to determine whether high‐calorie and high‐protein oral nutritional supplements (ONS) are safe and beneficial for older adult outpatients with heart failure (HF). Methods and results: This multicentre, single‐arm, interventional pilot trial is designed to evaluate the tolerance, efficacy, and safety of ONS in older adult outpatients with chronic HF, malnutrition, and anorexia. In total, 80 outpatients with HF regardless of their left ventricular ejection fraction will be treated with ONS, including high‐energy (900 kcal/day) and high protein (36 g/day) supplementation, at eight sites in Japan. Inclusion criteria are as follows: age, ≥65 years; outpatients receiving maximally tolerated guideline‐directed medical therapy for HF and without change in their diuretic dosage during the last 3 months; outpatients at risk of malnutrition, defined as a Malnutrition Universal Screening Tool score ≥1 point, and anorexia, defined using a Simplified Nutritional Appetite Questionnaire for the Japanese Elderly (SNAQ‐JE) score of ≤14 points. Nutritional intervention will continue for up to 120 days, with an observational period lasting for a further 60 days. The primary outcome is a change in body weight between baseline and day 120. Conclusions: The ALIMENT‐HF trial will evaluate the tolerance, efficacy, and safety of high‐calorie and high‐protein‐rich ONS in older outpatients with HF co‐morbid with malnutrition and anorexia and will provide insightful information for future randomized controlled trials. [ABSTRACT FROM AUTHOR]

Abstract: 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (PACA), pharmacological inhibitor of phospholipase A2 (PLA2), inhibits epinephrine-stimulated thromboxane production in human platelets. In this study, we investigated the effect of PACA on meiotic maturation individually in stages V and VI oocytes. PACA prevented the maturation in stage V but merely delayed the process in stage VI oocytes. This was associated with the strong inhibition of Mos synthesis at both stages. Besides, PACA-induced inhibition of MAPK activation was evident in stage V but not in stage VI oocytes. PACA also inhibited the activation of Cdc2 kinase (Cdc2) in stage V but merely delayed the process in stage VI oocytes. Furthermore, 5 μM and higher concentrations of PACA completely inhibited the activation of MAPK and Cdc2 only in stage V, not in stage VI, oocytes. Moreover, we propose PACA as a new tool for the study of Xenopus oocyte maturation, which can also play a unique role for the studies of the stage-specific activation of MAPK and Cdc2. [Copyright &y& Elsevier]

Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in the salvage pathway for nicotinamide adenine dinucleotide (NAD+) biosynthesis, and thereby regulates the deacetylase activity of sirtuins. Here we show accommodative regulation of myocardial NAD+ by monocyte-derived extracellular Nampt (eNampt), which is essential for hemodynamic compensation to pressure overload. Although intracellular Nampt (iNampt) expression was decreased in pressure-overloaded hearts, myocardial NAD+ concentration and Sirt1 activity were preserved. In contrast, iNampt was up-regulated in spleen and monocytes, and circulating eNampt protein and nicotinamide mononucleotide (NMN), a key precursor of NAD+, were significantly increased. Pharmacological inhibition of Nampt by FK866 or depletion of monocytes/macrophages by clodronate liposomes disrupted the homeostatic mechanism of myocardial NAD+ levels and NAD+-dependent Sirt1 activity, leading to susceptibility to cardiomyocyte apoptosis and cardiac decompensation in pressure-overloaded mice. These biochemical and hemodynamic defects were prevented by systemic administration of NMN. Our studies uncover a crucial role of monocyte-derived eNampt in myocardial adaptation to pressure overload, and highlight a potential intervention controlling myocardial NAD+ against heart failure. [ABSTRACT FROM AUTHOR]

In various pathological events, particularly in oxygen radical-mediated cell injury, both apoptosis and necrosis play essential roles. Apoptosis and some types of necrosis are induced via increases in mitochondrial membrane permeability, called mitochondrial outer membrane permeabilization (MOMP) and permeability transition pore (PTP) opening, respectively. To search for small compounds that inhibit both MOMP-mediated apoptosis and PTP-mediated necrosis, we performed a mitochondria-based high-throughput screening of a chemical library. We identified TMD#7538, a small compound that inhibits both MOMP and PTP opening. Consistent with the fact that this compound inhibited both apoptosis and necrosis, it efficiently suppressed H 2 O 2 -induced cell death in mouse embryonic fibroblasts and rat neonatal cardiomyocytes. [ABSTRACT FROM AUTHOR]

Objective General fatigue is one of the most frequent chief complaints in primary care, and an accurate assessment of fatigue has a direct impact on a patient's quality of life and treatment decisions. The Fatigue Assessment Scale (FAS), a measure of general fatigue, is useful for assessing fatigue in diverse cultures and diseases. However, there has been no study showing the reliability and validity of the scale in the Japanese context. The present study assessed the reliability and validity of the Japanese version of the FAS. Methods This study was conducted on 649 patients with long COVID who had a high frequency of general fatigue. To test the structural validity of the FAS, the patients were randomly divided into two groups: one in which an exploratory factor analysis (EFA) was conducted and one in which a confirmatory factor analysis (CFA) was conducted. Cronbach's alpha was calculated to assess internal consistency reliability. Results As 58 patients had missing values, we analyzed the data of 591 patients. The EFA led to an FAS comprising two factors. The CFA showed an acceptable fit for this two-factor model. The internal consistency was found to be good (Cronbach's alpha =0.89). Conclusion This study verified the structural validity and internal consistency and reliability of the Japanese version of the FAS. The results indicate that the Japanese version of the FAS is useful for assessing general fatigue in patients with long COVID in Japan.

Background: Although percutaneous endoscopic gastrostomy (PEG) placement is still widely practiced in Japan, studies from Western countries report that it is less beneficial for patients in end-of-life care with cognitive decline. Decisions regarding PEG placement are largely influenced by physician judgment., Objectives: The aim of this study was to investigate the background and perceptions of Japanese physicians regarding PEG for older adults in end-of-life care and to identify the factors associated with differences in physician judgment regarding PEG., Design: The study employed a cross-sectional design., Setting/subjects: A questionnaire on PEG for older adults in end-of-life care was sent to Japanese physicians. Logistic regression analysis was used to calculate the odds ratios (ORs) and confidence intervals (CIs) of the association between PEG recommendations and each factor., Results: PEG placement was advised for bedridden patients and older adults with cognitive decline by 26% of the physicians who responded to the survey. Differences in physician perceptions of PEG feeding were associated with the recommendation for PEG, benefits of preventing aspiration pneumonia (OR: 4.9; 95% CI: 3.1-8.2), impact on post-discharge accommodation decisions (OR: 6.1; 95% CI: 1.9-30.9), and hesitancy to recommend a PEG placement (OR: 1.9; 95% CI: 1.3-4.5). Working in a facility with PEG placement (OR: 2.0; 95% CI: 1.2-3.5) was an associated background factor., Conclusions: Differences in Japanese physicians' attitudes toward using PEG feeding for older adults in end-of-life care were significantly associated with differences in their perceptions of the impact of PEG feeding and working in a facility with PEG placement., (© Yoko Sakamoto et al., 2024; Published by Mary Ann Liebert, Inc.)

Background: Excessive psychological stress in medical students affects their mental health and causes problems such as burnout and depression. Furthermore, changes in the learning environment to online learning due to the COVID-19 pandemic have had a psychological effect on medical students. However, the relationships between medical students' perceived stress and different methods of communication, including in-person and online communication, remain unclear. The purpose of this study was to investigate the differences in stress perception of medical students depending on in-person communication and online communication during the COVID-19 pandemic., Methods: This study was a cross-sectional study conducted from September to October in 2020. All of the students of Okayama University School of Medicine were asked to participate in a questionnaire survey. The explanatory variables were the frequency and length of communications with others (by in-person or online communication), empathy, and lifestyle. The main outcome measure was perceived stress. Subgroup analysis was conducted for students who preferred to be by themselves and students who preferred to study together and interact with other people. Univariate analysis and multivariate multiple regression analysis were conducted. Gender and grade, which have been shown to be associated with stress in previous studies, were used as covariates for multiple regression analysis., Results: Valid responses to the questionnaire survey were received from 211 (29.4%) of the 717 students. There was no significant association between perceived stress and online communication, but the number of people with which students had in-person communication (1-2 people compared to 0 as a control, regression coefficient [B] = -4.4, 95% confidence interval [CI]; -7.8, -1.1, more than 10 people, B = -12, 95% CI: -18, -5.8) and the length of communication (more than 120 min, B = -4.5, 95% CI: -8.1, -0.92) were associated with a reduction in perceived stress. In subgroup analysis, the number of people with in-person communication and the length of communication had significant associations with stress reduction even in the group of students who had a preference for being by themselves., Conclusion: In-person communications rather than online communications were associated with a lower level of perceived stress. In subgroup analysis, this trend was statistically significant in the group of students who had a preference for being by themselves.

We propose a new oral immunotherapy (OIT) method that includes a small amount of a food allergen in the diet. However, it is not clear whether this method will induce oral desensitization and immune tolerance. Therefore, we investigated the therapeutic effectiveness using a 1% food allergen diet in an allergic mouse model. C3H/HeJ mice were sensitized to ovomucoid (OM) in alum four times at 12-d intervals. Sensitized mice were divided into two groups: the OIT group (19% casein diet with 1% OM) and the non-treated group (20% casein diet without OM). The non-sensitized mice served as the non-allergy group. The OIT treatment was performed for 4 wk. To assess desensitization and immune tolerance, we performed oral and intraperitoneal OM challenges, assessed vascular permeability of the dorsal skin, and measured allergic biomarkers. The OIT group exhibited significantly lower oral symptom scores and vascular permeability than the non-treated group, but the two groups did not differ in intraperitoneal allergy symptom scores. Furthermore, the OIT group had significantly higher OM-specific IgA levels in their plasma than the non-treated group. However, the plasma levels of OM-specific IgE, IgG1, and IgG2a were not significantly different between the OIT and the non-treated groups. These results suggest that the proposed OIT using an OM-supplemented diet may induce desensitization, but not immune tolerance, in an OM allergic mouse model.

Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in the salvage pathway for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, and thereby regulates the deacetylase activity of sirtuins. Here we show accommodative regulation of myocardial NAD(+) by monocyte-derived extracellular Nampt (eNampt), which is essential for hemodynamic compensation to pressure overload. Although intracellular Nampt (iNampt) expression was decreased in pressure-overloaded hearts, myocardial NAD(+) concentration and Sirt1 activity were preserved. In contrast, iNampt was up-regulated in spleen and monocytes, and circulating eNampt protein and nicotinamide mononucleotide (NMN), a key precursor of NAD(+), were significantly increased. Pharmacological inhibition of Nampt by FK866 or depletion of monocytes/macrophages by clodronate liposomes disrupted the homeostatic mechanism of myocardial NAD(+) levels and NAD(+)-dependent Sirt1 activity, leading to susceptibility to cardiomyocyte apoptosis and cardiac decompensation in pressure-overloaded mice. These biochemical and hemodynamic defects were prevented by systemic administration of NMN. Our studies uncover a crucial role of monocyte-derived eNampt in myocardial adaptation to pressure overload, and highlight a potential intervention controlling myocardial NAD(+) against heart failure.

Enzymatic proteolysis by calpains, Ca(2+)-dependent intracellular cysteine proteases, has been implicated in pathological processes such as cellular degeneration or death. Here, we investigated the role of calpain activation in the hearts subjected to myocardial infarction. We produced myocardial infarction in Cast(-/-) mice deficient for calpastatin, the specific endogenous inhibitory protein for calpains, and Cast(+/+) mice. The activity of cardiac calpains in Cast(+/+) mice was not elevated within 1 day but showed a gradual elevation after 7 days following myocardial infarction, which was further pronounced in Cast(-/-) mice. Although the prevalence of cardiomyocyte death was indistinguishable between Cast(-/-) and Cast(+/+) mice, Cast(-/-) mice exhibited profound contractile dysfunction and chamber dilatation and showed a significant reduction in survival rate after myocardial infarction as compared with Cast(+/+) mice. Notably, immunofluorescence revealed that at 28 days after myocardial infarction, calpains were activated in cardiomyocytes exclusively at the border zone and that Cast(-/-) mice showed higher intensity and a broader extent of calpain activation at the border zone than Cast(+/+) mice. In the border zone of Cast(-/-) mice, pronounced activation of calpains was associated with a decrease in N-cadherin expression and up-regulation of molecular markers for cardiac hypertrophy and fibrosis. In cultured rat neonatal cardiomyocytes, calpain activation by treatment with ionomycin induced cleavage of N-cadherin and decreased expression levels of β-catenin and connexin 43, which was attenuated by calpain inhibitor. These results thus demonstrate that activation of calpains disassembles cell-cell adhesion at intercalated discs by degrading N-cadherin and thereby promotes left ventricular remodeling after myocardial infarction., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

The octapeptide angiotensin II (Ang II) plays a homeostatic role in the regulation of blood pressure and water and electrolyte balance, and also contributes to the progression of cardiovascular remodeling. Ang II activates Ang II type 1 (AT1) receptor and type 2 (AT2) receptor, both of which belong to the seven-transmembrane, G protein-coupled receptor family. Most of the actions of Ang II such as promotion of cellular prolifaration, hypertrophy, and fibrosis are mediated by AT1 receptor. However, in some pathological situations, AT2 receptor shows an increase in tissue expression and functions to antagonize the actions induced by AT1 receptor. Recent studies have advanced our understanding of the molecular mechanisms underlying receptor activation and signal transduction of AT1 and AT2 receptor in the cardiovascular system.

The aim of this study was to examine the relationship between menses-associated health problems of women, such as premenstrual symptoms, menstrual pain and irregular menstrual cycles, and psychosocial stress. A cross-sectional study was conducted among Japanese college students, measuring psychosocial stress levels by means of IMPS (The Inventory to Measure Psychosocial Stress). A total of 264 female students (mean age 19.4 years), who were invited to participate in the study in October 2007, completed the questionnaire, which dealt with anthropometric data, lifestyle, menstrual history, and menstrual health status. Forty-three students were excluded due to missing data, and the remaining 221 were analyzed. The proportions of students who reported premenstrual symptoms, menstrual pain, and the experience of irregular menstrual cycles were 79%, 79%, and 63%, respectively. Students who reported premenstrual symptoms, menstrual pain, and the experience of irregular menstrual cycles had higher stress scores than those who did not. Multiple logistic regression analyses were used to identify independent factors associated with having premenstrual symptoms, menstrual pain, and the experience of irregular menstrual cycles. Stress score, heavy menstrual flow, and menstrual pain were significant predictors for premenstrual symptoms, while age at menarche and having premenstrual symptoms were significant predictors for menstrual pain. Both stress score and body mass index were found to be significant predictors for having experienced irregular menstrual cycles. The results suggest that psychosocial stress is independently associated with premenstrual symptoms and the experience of irregular menstrual cycles among college students, implying that changes in the functional potentiality of women as a result of stress are related with changes in their menstrual function.

The aim of this study was to examine the relationship between psychosocial stress and intraocular pressure among apparently healthy subjects. Psychosocial stress among 1,461 public school workers (883 men and 578 women) was measured using the inventory to measure psychosocial stress (IMPS) and intraocular pressure was measured using a non-contact tonometer (Topcon CT-90). After controlling for the effects of likely confounding variables such as age, body mass index (BMI), glycosylated hemoglobin, systolic blood pressure, alcohol consumption, smoking status, and exercise, partial correlations and hierarchical multiple regression analysis were performed in order to test the hypothesis that IMPS-measured stress score was associated with intraocular pressure. IMPS-measured stress score was found to correlate positively with intraocular pressure in women after controlling for the effects of confounding variables, whereas this relationship was not found in men. Hierarchical multiple regression analysis indicated that IMPS-measured stress score was positively associated with intraocular pressure in women independent of confounding variables, but not in men. Perturbations of the hypothalamic-pituitary-adrenal (HPA) axis associated with stress are considered to be partly responsible for an increase in intraocular pressure among people suffering from psychosocial stress. Further research is needed to elucidate the relationship between this stress-associated increase in intraocular pressure and open-angle glaucoma.

In order to study the phosphorylated proteins in the resting Xenopus laevis oocytes, the proteins detected by Western blotting using phospho-(Ser/Thr) PKA substrate antibody (PKA substrate antibody) in forskolin-stimulated oocytes were purified and identified by mass spectrometry. Several proteins (ribosomal S6 protein, elongation factor-2 (EF-2), poly A binding protein, releasing factor 1) were identified, and the phosphorylation of EF-2 was further studied. Partially purified Xenopus EF-2 (xEF-2) was phosphorylated by PKA in vitro and this phosphorylation was detected by Western blotting using PKA substrate antibody. The phosphorylation of Thr-57 in xEF-2 (corresponding to Thr-56 of the mammalian enzyme) was detected in the partially purified xEF-2 from the resting oocytes, but this xEF-2 did not react with the PKA substrate antibody. These results suggest that Thr-57 in xEF-2 was phosphorylated, but xEF-2 does not seem to be phosphorylated by PKA in resting oocytes although PKA can phosphorylate xEF-2 in vitro and probably in forskolin-treated oocytes.

The aim of this study was to examine the relationship between the stress score measured using the Inventory to Measure Psychosocial Stress (IMPS) and biomedical parameters regarding health status among apparently healthy subjects in order to evaluate the validity of the IMPS. Out of the 1,941 public school workers in Kyushu and Okinawa, Japan, who were admitted to a hospital for medical check-ups, 1,499 workers responded to questionnaires which assessed the degree of stress response (i.e., stress score) measured using the IMPS, and the degree of stress tolerance capacity (i.e., stress intolerance score) measured using the Inventory to Measure Stress Tolerance Capacity (IMST). One thousand two-hundred and one workers (684 men and 517 women) were analyzed, excluding 298 subjects who were taking medication for hypertension, hyperuricemia, hyperlipidemia and diabetes, or had a value for glycosylated hemoglobin (HbA1c)>or=6.0 percent. An increase in the stress score was positively associated with an increase in both body fat percentage and glycosylated hemoglobin values among men, while it was positively associated with an increase in plasma triglyceride concentrations among women. The stress score significantly correlated with the value for glycosylated hemoglobin even after controlling for age, body mass index, alcohol consumption, smoking, and exercise among men. An increase in the stress intolerance score was positively associated with an increase in body fat percentage among men, while it was positively associated with an increase in body weight, body mass index, and body fat percentage among women. Our result that the stress score measured using the IMPS was associated with obesity and unfavorable glycemic changes is in congruency with the model that psychosocial stress has a detrimental effect on humans by inducing obesity and insulin resistance, suggesting that the IMPS is a valid means to evaluate psychosocial stress levels among an otherwise healthy population.

A sensitive enzyme immunoassay (EIA) specific for hepatitis B virus core antigen (HBcAg) and hepatitis B e antigen (HBeAg) was developed. We designated the precore/core gene products as hepatitis B virus (HBV) core-related antigens (HBcrAg). In order to detect HBcrAg even in anti-HBc/e antibody-positive specimens, the specimens were pretreated in detergents. The antibodies are inactivated by this pretreatment and, simultaneously, the antigens are released and the epitopes are exposed. The assay demonstrated 71 to 112% recovery using HBcrAg-positive sera. We observed no interference from the tested anticoagulants or blood components. When the cutoff value was tentatively set at 10(3) U/ml, all healthy control (HBsAg/HBV-DNA negative; n = 108) and anti-HCV antibody-positive (n = 59) sera were identified as negative. The assay showed a detection limit of 4 x 10(2) U/ml using recombinant antigen. Detection limits were compared in four serially diluted HBV high-titer sera. The HBcrAg assay demonstrated higher sensitivity than HBV-DNA transcription-mediated amplification (TMA) or HBeAg radio immunoassay (RIA) in the dilution test. HBcrAg concentrations correlated well with HBV-DNA TMA (r = 0.91, n = 29) and in-house real-time detection-PCR (r = 0.93, n = 47) in hepatitis B patients. On HBeAg/anti-HBe antibody seroconversion panels, the HBcrAg concentration changed in accordance with HBV-DNA levels. HBcrAg concentration provides a reflection of HBV virus load equivalent to HBV-DNA level, and the assay therefore offers a simple method for monitoring hepatitis B patients.