Tritium concentration in monthly precipitation in Okinawa and Kagoshima, southern Japan.

This study aimed at understanding the background concentration level of tritium in precipitation in southern Japan, where precipitation samples were collected monthly in 2022 in Okinawa and Kagoshima. Tritium concentration in monthly precipitation collected in Okinawa since 2014 ranged from 0.05 to 0.

Machine learning-based muscle mass estimation using gait parameters in community-dwelling older adults: A cross-sectional study.

Background: Loss of skeletal muscle mass is associated with numerous factors such as metabolic diseases, lack of independence, and mortality in older adults. Therefore, developing simple, safe, and reliable tools for assessing skeletal muscle mass is needed. Some studies recently reported that the risks of the incidence of geriatric conditions could be estimated by analyzing older adults' gait; however, no studies have assessed the association between gait parameters and skeletal muscle loss in older adults.

Self-Standing Nanomembranes of Super-Tough Plastics.

Nanomembranes are effective coating materials for protecting substrates from external stimuli; however, they are generally not self-standing owing to their low mechanical toughness. Self-standing nanomembranes would be an innovative development in the field of nanotechnology including miniaturized devices. In this study, self-standing nanomembranes were developed by spin-casting supertough polyamides over dimethylformamide solution.

Association between Mixing Ability of Masticatory Functions Measured Using Color-Changing Chewing Gum and Frailty among Japanese Older Adults: The Kyoto-Kameoka Study.

The relationship between mixing ability of masticatory functions and frailty has not been well evaluated. This study investigated the prevalence of physical and comprehensive frailty and its association with mixing ability in 1106 older adults aged ≥65 years who underwent physical examination as part of the Japanese Kyoto-Kameoka Study. Mixing ability was assessed using color-changing chewing gum (1-5 points, 5 representing the best mixing ability).

Comprehensive geriatric intervention in community-dwelling older adults: a cluster-randomized controlled trial.

Background: In longevity societies, one of the most serious social issues is sarcopenia and/or frailty. Preventing them is important for maintaining independence and quality of life in the older population. This study investigated the effect of a self-monitoring comprehensive geriatric intervention programme (CGIP) on physical function and muscle size in community-dwelling older adults.

Effects of Capsinoids on Daily Physical Activity, Body Composition and Cold Hypersensitivity in Middle-Aged and Older Adults: A Randomized Study.

Sedentary/inactive lifestyle leads middle-aged and older adults to metabolic syndrome and frailty. Capsinoids from nonpungent chili pepper cultivar have been reported to reduce body fat mass, promote metabolism, and improve unidentified complaints of chills. Additionally, they have an anti-inflammation effect; therefore, we hypothesized that continuous oral ingestion of capsinoids alleviates age-related inflammation in the brain and improves the physical activity (PA) in middle-aged and older adults.

Repetition of Prediabetes Enhances the Risk of Developing Diabetes.

We attempted to clarify the severity of the risk of diabetes mellitus (DM) in the individuals who repeatedly fulfill the criteria for prediabetes in both fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). The subjects were 2347 individuals who underwent annual health checkup at our hospital. They were classified as normal glucose tolerance or prediabetes as their yearly status of glucose tolerance for three years; furthermore, the individuals classified as prediabetes were subclassified into 3 groups.

Discovery of Clinical Candidate 2-(4-(2-((1 H-Benzo[ d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)- N-(6-methyl-2,4-bis(methylthio)pyridin-3-yl)acetamide Hydrochloride [K-604], an Aqueous-Soluble Acyl-CoA:Cholesterol O-Acyltransferase-1 Inhibitor.

2-(4-(2-((1 H-Benzo[ d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)- N-(6-methyl-2,4-bis(methylthio)pyridin-3-yl)acetamide hydrochloride (K-604, 2) has been identified as an aqueous-soluble potent inhibitor of human acyl-coenzyme A:cholesterol O-acyltransferase (ACAT, also known as SOAT)-1 that exhibits 229-fold selectivity for human ACAT-1 over human ACAT-2. In our molecular design, the insertion of a piperazine unit in place of a 6-methylene chain in the linker between the head (pyridylacetamide) and tail (benzimidazole) moieties led to a marked enhancement of the aqueous solubility (up to 19 mg/mL at pH 1.2) and a significant improvement of the oral absorption (the C of 2 was 1100-fold higher than that of 1 in fasted dogs) compared with those of the previously selected compound, 1.

Design, synthesis and pharmacology of aortic-selective acyl-CoA: Cholesterol O-acyltransferase (ACAT/SOAT) inhibitors.

We describe our molecular design of aortic-selective acyl-coenzyme A:cholesterol O-acyltransferase (ACAT, also abbreviated as SOAT) inhibitors, their structure-activity relationships (SARs) and their pharmacokinetic (PK) and pharmacological profiles. The connection of two weak ligands-N-(2,6-diisopropylphenyl)acetamide (50% inhibitory concentration [IC] = 8.6 μM) and 2-(methylthio)benzo[d]oxazole (IC = 31 μM)-via a linker comprising a 6 methylene group chains yielded a highly potent molecule, 9-(benzo[d]oxazol-2-ylthio)-N-(2,6-diisopropylphenyl)nonanamide (3h) that exhibited high potency (IC = 0.

Comprehensive geriatric intervention program with and without weekly class-style exercise: research protocol of a cluster randomized controlled trial in Kyoto-Kameoka Study.

Objective: The number of long-term care (LTC) users and the associated expenditures in Japan are increasing dramatically. The national government recommends LTC prevention through activation of communities. However, there is no clear evidence of the effect of population-based comprehensive geriatric intervention program (CGIP) for restraints of LTC users and the associated expenditures in the future.

Sociodemographic and physical predictors of non-participation in community based physical checkup among older neighbors: a case-control study from the Kyoto-Kameoka longitudinal study, Japan.

Background: It is difficult to obtain detailed information on non-participants in physical and health examination checkups in community-based epidemiological studies. We investigated the characteristics of non-participants in a physical and health examination checkup for older adults in a nested study from the Japanese Kyoto-Kameoka Longitudinal Study.

Methods: We approached a total of 4831 people aged ≥65 years in 10 randomly selected intervention regions.

Prevalence of Frailty Assessed by Fried and Kihon Checklist Indexes in a Prospective Cohort Study: Design and Demographics of the Kyoto-Kameoka Longitudinal Study.

Objective: The Kyoto-Kameoka Study was launched in 2011-2012 to identify the associations among food intake, nutritional status, physical activity, oral function, quality of life or social capital, the use of long-term care insurance (LTCI) system, and healthy lifespan in community-dwelling older people as a part of the World Health Organization Safe Community program.

Design: A prospective cohort study, reporting baseline demographics (cross-sectional data).

Setting And Participants: We conducted 2 mailed self-administered questionnaire surveys; one is a complete population survey with a comprehensive survey of needs in the sphere of daily life (NSDL) that included 2 different frailty indexes, the Kihon Checklist (KCL) and the Fried phenotype, socioeconomic status, general and psychological health, and social relationships; followed by the more detailed Health and Nutrition Survey.

Mechanism of lipid-lowering action of the dipeptidyl peptidase-4 inhibitor, anagliptin, in low-density lipoprotein receptor-deficient mice.

Aims/introduction: Dipeptidyl peptidase-4 inhibitors are used for treatment of patients with type 2 diabetes. In addition to glycemic control, these agents showed beneficial effects on lipid metabolism in clinical trials. However, the mechanism underlying the lipid-lowering effect of dipeptidyl peptidase-4 inhibitors remains unclear.

[Fall risk factors and sex differences among community-dwelling elderly individuals in Japan. A Kameoka study].

Objectives: Although factors associated with falls might differ between men and women, no large-scale studies were conducted to examine the sex difference of risk factors for falls in Japanese elderly. The purpose of this study was to examine fall risk factors and sex differences among community-dwelling elderly individuals using a complete survey of the geriatric population in Kameoka city.

Methods: A self-administered questionnaire survey was conducted with 18,231 community-dwelling elderly individuals aged 65 years or over in Kameoka city, Kyoto Prefecture, between July and August 2011, excluding people who were publicly certified with a long-term care need of grade 3 or higher.

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus.

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1.

Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.

Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene.

Sulfated polysaccharide, curdlan sulfate, efficiently prevents entry/fusion and restricts antibody-dependent enhancement of dengue virus infection in vitro: a possible candidate for clinical application.

Curdlan sulfate (CRDS), a sulfated 1→3-β-D glucan, previously shown to be a potent HIV entry inhibitor, is characterized in this study as a potent inhibitor of the Dengue virus (DENV). CRDS was identified by in silico blind docking studies to exhibit binding potential to the envelope (E) protein of the DENV. CRDS was shown to inhibit the DENV replication very efficiently in different cells in vitro.

Monitoring of S protein maturation in the endoplasmic reticulum by calnexin is important for the infectivity of severe acute respiratory syndrome coronavirus.

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, a fatal pulmonary disorder with no effective treatment. We found that SARS-CoV spike glycoprotein (S protein), a key molecule for viral entry, binds to calnexin, a molecular chaperone in the endoplasmic reticulum (ER), but not to calreticulin, a homolog of calnexin. Calnexin bound to most truncated mutants of S protein, and S protein bound to all mutants of calnexin.

Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS) coronavirus S protein neutralizes the virus in a rhesus macaque SARS model.

Background: There is still no effective method to prevent or treat severe acute respiratory syndrome (SARS), which is caused by SARS coronavirus (CoV). In the present study, we evaluated the efficacy of a fully human monoclonal antibody capable of neutralizing SARS-CoV in vitro in a Rhesus macaque model of SARS.

Methods: The antibody 5H10 was obtained by vaccination of KM mice bearing human immunoglobulin genes with Escherichia coli-producing recombinant peptide containing the dominant epitope of the viral spike protein found in convalescent serum samples from patients with SARS.

Pitavastatin increases ABCA1 expression by dual mechanisms: SREBP2-driven transcriptional activation and PPARα-dependent protein stabilization but without activating LXR in rat hepatoma McARH7777 cells.

Hepatic ATP-binding cassette transporter A1 (ABCA1) plays a key role in high-density lipoprotein (HDL) production by apolipoprotein A-I (ApoA-I) lipidation. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, increase ABCA1 mRNA levels in hepatoma cell lines, but their mechanism of action is not yet clear. We investigated how statins increase ABCA1 in rat hepatoma McARH7777 cells.

A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice.

Acyl-coenzyme A:cholesterol O-acyltransferase-1 (ACAT-1) plays an essential role in macrophage foam cell formation and progression of atherosclerosis. We developed a potent and selective ACAT-1 inhibitor, K-604, and tested its effects in apoE-knockout mice. Administration of K-604 to 8-week-old apoE-knockout mice for 12 weeks at a dose of 60 mg/kg/day significantly reduced macrophage-positive area and increased collagen-positive area in atherosclerotic plaques in the aorta without affecting plasma cholesterol levels or lesion areas, indicating direct plaque-modulating effects of K-604 on vascular walls independent of plasma cholesterol levels.

Temporary scaphotrapezoidal joint fixation for adolescent Kienböck's disease.

Purpose: There are few therapeutic guidelines for adolescent Kienböck's disease. The purpose of our study was to investigate the clinical and radiographic outcomes of temporary scaphotrapezoidal (ST) joint fixation for adolescent Kienböck's disease.

Methods: This was a retrospective review of 6 adolescent patients with Kienböck's disease treated by temporary ST joint fixation.