帝京平成大学

Twelve side-chain fluorinated 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3 (AH-1) analogs were designed, synthesized, and evaluated regarding their biological activities. Synthesis was carried out employing the palladium-catalyzed Trost coupling reaction between side-chain fluorinated CD-ring bromo-olefins 41-52 and A-ring enyne 53. Some analogs, including C26,27-hexafluoro-AH-1 (31) and 24,24-difluoro-AH-1 (34), exhibited much higher human vitamin D receptor binding affinity, VDR-ligand binding domain transcriptional activity, osteocalcin promoter transactivation activity, and metabolic resistance to CYP24A1-mediated inactivation than 1α,25(OH)2D3.

BACKGROUND:This article presents the results of the modified Delphi study conducted by the GLIM Risk of Malnutrition Working Group to develop a consensus-based conceptual definition of "risk of malnutrition," as first step in revising the GLIM screening procedure. METHODS:Focus groups with nutritional care experts and patient/older adult representatives, and a literature exploration informed 46 statements on risk of malnutrition. Malnutrition experts (n = 112) evaluated these statements, using a five-point Likert scale. Statements with ≥75% agreement were accepted; those with ≥75% disagreement and/or neutrality were rejected. Remaining statements were marked "undecided" and re-evaluated in later rounds. RESULTS:In three questionnaire rounds (response rates 63%, 59%, and 54%), 26 statements were ultimately accepted to shape the conceptual definition of "risk of malnutrition". The GLIM Working Group and patient/older adult representatives reviewed the pre-final professional and layperson versions. Risk of malnutrition was defined as: A dynamic state, with or without unintentional weight loss, in which an individual has one or more risk factors, that is, nutrition impact symptoms, and/or disease-related, physical, psychological, social, demographic, and economic risk factors, that may result in malnutrition and may negatively impact clinical outcomes. In the layperson version, sentences were simplified to aid comprehension. CONCLUSION:GLIM has developed the first global (professional and layperson) conceptual definition of risk of malnutrition. This definition will guide future nutritional screening recommendations and a more preventive malnutrition approach. It also implies that screening tools covering "risk of malnutrition" should no longer be validated against signs or the diagnosis of malnutrition.

STUDY OBJECTIVES:To investigate the prescription patterns for hypnotics among patients <18 years in Japan. METHODS:We conducted a descriptive epidemiologic study using a claims database in Japan. We included patients aged 0-17 years with first-time prescriptions for hypnotics between June 2021 and June 2023. Hypnotics were classified as melatonin, melatonin receptor agonists (MRAs), dual orexin receptor antagonists (DORAs), Z-drugs, and benzodiazepines. We described the types of hypnotics, dosages, prescription duration, comorbidities, and concomitant medications for overall and by age groups. RESULTS:The study included 21 145 patients; 1983 aged 0-6 years, 3901 aged 7-11 years, 6664 aged 12-14 years, and 8597 aged 15-17 years. The initial prescribed hypnotics were melatonin (33.9%), MRAs (30.9%), DORAs (18.8%), Z-drugs (10.1%), and benzodiazepines (6.3%). Melatonin was more likely to be prescribed to patients age 0-11 years, MRAs to those aged 0-17 years, and DORAs to patients ages 15-17 years. The most common mental health-related comorbidities were autism spectrum disorder (32.5%), depression (23.4%), attention-deficit hyperactivity disorder (19.8%), and anxiety disorder (18.2%). CONCLUSIONS:Melatonin was most frequently prescribed in children for a longer duration than other hypnotics, while MRAs were prescribed across all age groups and DORAs mainly to adolescents. These age-specific patterns suggest that the drug selection was conducted according to patient's age, since pediatric insomnia might be correlated with psychiatric disorders related to developmental stage. Future research should investigate the long-term effects of hypnotic prescriptions with consideration of comorbid conditions.

Monitoring and modeling population health is essential for understanding the impact of lifestyle behaviors and pharmacologic therapies on chronic disease management. In this study, we used a nationwide Japanese health insurance claims and health checkup database to investigate the associations between physical activity and glycemic control among 24,830 treatment-naïve adults with type 2 diabetes receiving DPP-4 inhibitors, SGLT2 inhibitors, or metformin. The odds of achieving hemoglobin A1c (HbA1c) < 6.5

In this study, we developed a fabrication method for the formation of well-aligned sub-10 nm nanowire arrays by combining electron-beam lithography (EBL) with the directed self-assembly (DSA) of block copolymers, aimed at the realization of highly sensitive Si nanowire (SiNW) biosensors. Polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS) was employed to form sub-10 nm PDMS nanowires. The effects of the film thickness and reactive ion etching conditions were systematically investigated to determine the optimal fabrication parameters. To achieve well-aligned PDMS nanowires, hydrogen silsesquioxane (HSQ) guide lines were patterned between electrodes on a silicon-on-insulator (SOI) substrate to direct the orientation of the PDMS domains. Systematic investigations revealed that the morphology of the resulting PDMS nanostructures (dot, dot-and-line, or line) was strongly influenced by local variations in the effective film thickness. Furthermore, a quantitative linear relationship was established between the guide line spacing and the number of PDMS nanowires, demonstrating that the number of nanowires can be precisely controlled by geometric confinement. An incremental increase of approximately 15 nm in the guide line spacing was required for the formation of each additional nanowire. All PDMS nanowires exhibited uniform widths of 9-11 nm, achieving the sub-10 nm feature size required for next-generation biosensor applications. These studies provide a reliable and scalable route for fabricating ordered PDMS nanowire arrays and offer significant potential for the development of a nanoelectronic device with structural dimensions on the 10 nm scale.