Diet, Food Intake, and Exercise Mixed Interventions (DEMI) in the Enhancement of Wellbeing among Community-Dwelling Older Adults in Japan: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis discusses the available data on the efficacy of diet, food intake, and exercise mixed interventions (DEMI) for community-dwelling older adults in Japan and assesses the evidence level. We searched the literature regarding the research questions using electronic and hand-searching methods. To ensure the reliability and quality of the evidence, we used the Cochrane risk of bias tool and GRADE system. All studies included DEMI; other interventions included group activities, health education, and community participation. All interventions were categorized into three classifications, namely "Diet and food intake", "Exercise", and "Other". Programs included lectures, practical exercises, group activities, consulting, and programs that could be implemented at home. By comparing groups and measuring outcomes at various time points, most studies reported positive results regarding the impact of the interventions. Specifically, usual gait speed, Food Frequency Questionnaire Score, and Diet Variety Score demonstrated significant improvement. Additionally, three studies demonstrated improvement in frailty. This review suggests that DEMI resulted in improvements in some outcome variables. However, the efficacy of all variables was not fully examined. The results of the meta-analysis revealed positive outcomes for some variables, although the evidence level for these outcomes was considered moderate.

The relationship of single-family detached house prices with neighborhood walkability and disaster risk.

People's preferences regarding their neighborhood environment can vary depending on their socioeconomic status and the cities where they live. This study aims to discern the relationship between neighborhood environment factors and single-family detached house sales by sale price and by central and noncentral cities. We analyzed sale prices in the Tokyo Metropolitan Area from 2015 to 2020. The neighborhood environment was assessed using flood/sediment risk and neighborhood walkability measured by net residential density, intersection density, and facility density (walking opportunity). Flood and sediment risk is a major concern that restricts the available land and is included as a negative aspect of the neighborhood environment, taking the topographic features into consideration. A comparison of the results showed that the preference for neighborhood walkability varies by socioeconomic status as well as by target cities. For most facility types, the number of walking opportunities within walking distance from houses was found to be positively related to the sale price of single-family detached houses in all quantiles. The relationship of house price with population and intersection density was found to vary depending on the price level, with a negative relationship with the sale price of relatively more expensive houses being exhibited. People who considered buying houses with relatively higher sale prices were found to devalue houses located in flood/sediment-hazardous areas more. However, it was also found that the negative relationship was slightly mitigated in the highest quantile of sale prices for houses in areas with a moderate flood risk (maximum flooding depth: 3-5 m). Plains near rivers with amenities offer high walkability but pose a flood risk, resulting in a trade-off between flood risk and neighborhood walkability. The findings suggest the use of indices representing diverse preferences in accordance with the target socioeconomic status when policymakers assess the neighborhood environment.

Identification of a novel class of small compounds with anti-tuberculosis activity by in silico structure-based drug screening.

The enzymes responsible for biotin biosynthesis in mycobacteria have been considered as potential drug targets owing to the important role in infection and cell survival that the biotin synthetic pathway plays in Mycobacterium tuberculosis. Among the enzymes that comprise mycobacterium biotin biosynthesis systems, 7,8-diaminopelargonic acid synthase (DAPAS) plays an essential role during the stationary phase in bacterial growth. In this study, compounds that inhibit mycobacterial DAPAS were screened in the virtual chemical library using an in silico structure-based drug screening (SBDS) technique, and the antimycobacterial activity of the selected compounds was validated experimentally. The DOCK-GOLD programs utilized by in silico SBDS facilitated the identification of a compound, referred to as KMD6, with potent inhibitory effects on the growth of model mycobacteria (M. smegmatis). The subsequent compound search, which was based on the structural features of KMD6, resulted in identification of three additional active compounds, designated as KMDs3, KMDs9 and KMDs10. The inhibitory effect of these compounds was comparable to that of isoniazid, which is a first-line antituberculosis drug. The high antimycobacterial activity of KMD6, KMDs9 and KMDs10 was maintained on the experiment with M. tuberculosis. Of the active compounds identified, KMDs9 would be a promising pharmacophore, owing to its long-term antimycobacterial effect and lack of cytotoxicity.

In silico structure-based drug screening of novel antimycobacterial pharmacophores by DOCK-GOLD tandem screening.

BACKGROUND: Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB) agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1) is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids. MATERIALS AND METHODS: We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS). Following the selection of such compounds, their antimycobacterial activity was examined. RESULTS: With the in silico SBDS, for which we also used DOCK-GOLD programs and screening methods that utilized the structural similarity between the selected active compounds, we identified two compounds with potent inhibitory effects on mycobacterial growth. The antimycobacterial effect of the compounds was comparable to that of isoniazid, which is used as a first-line anti-TB drug. CONCLUSION: The compounds identified through SBDS were expected to be a novel class of anti-TB pharmacophores.

First synthesis of tepidopterin [2'-O-(2-acetamido-2-deoxy-beta-d-glucopyranosyl)-L-threo-biopterin].

N(2)-(N,N-Dimethylaminomethylene)-1'-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]-L-threo-biopterin (14) was prepared from L-xylose in an 11-step-sequence. The first synthesis of tepidopterin (3) was achieved by treatment of 14 with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the protecting groups.