Effectiveness of the lay health advisor program on oral function and quality of life in aboriginal older adults: A randomized controlled trial.

BACKGROUND: Aboriginal older adults residing in remote areas have poor oral function due to inadequate access to healthcare services. Lay health advisor (LHA) strategies can fill capacity shortages of healthcare professionals in rural communities and increase population acceptance of health care or healthy behaviours. OBJECTIVE(S): To evaluate the effectiveness the LHA program on oral function and oral health-related quality of life (OHRQoL) among older adults in aboriginal community. METHODS: Participants were randomly assigned to an experimental group (EG; n = 122) and a control group (CG; n = 118). All participants performed oral exercises, and the EG received additional one-on-one 30-min lessons by an LHA over 4 weeks. Data were collected through face-to-face interview and oral examination. The generalized estimating equation model was used to analyse changes in outcomes over time. RESULTS: The EG exhibited significantly greater improvement in swallowing (ß = .63) at the 6-month follow-up and in masticatory performance (ß = .52) and pronunciation of the syllable/pa/ (ß = 2.65) at the 2-week follow-up than the CG did. The EG had a significantly lower plaque control record (ß = -.14) and plaque index (ß = -.30) at the 3-month follow-up than the CG did. Moreover, the OHRQoL was significantly increased at 6-months follow-up in the EG (p = .010). CONCLUSION: The LHA program had positive effects on chewing, swallowing and plaque control in aboriginal older adults. LHA group also experienced positive long-term effect on OHRQoL after intervention.

Virtual reality-based simulation learning on geriatric oral health care for nursing students: a pilot study.

BACKGROUND: There is a great need for training and education in the nursing curriculum to improve nurses' knowledge and skills to provide oral health care. METHODS: A pilot study was conducted to evaluate the use of a virtual reality (VR)-based Oral Health Care Learning System to train geriatric oral health care among nursing students. Fifty undergraduate nursing students were randomly assigned to experimental (n = 25) and control (n = 25) groups. The experimental group received the VR-based simulation training on geriatric oral health care and the training was implemented twice at two weeks apart from March to November 2021. The control group did not receive the training intervention. Knowledge, attitude, and self-efficacy of geriatric oral health care as well as the intention to assist oral health care for older adults were assessed at the beginning, second, and fourth weeks. Generalized estimating equations were used to analyze the effectiveness of the VR-based simulation training. RESULTS: After the first round of training, students in the experimental group had significantly greater improvements in knowledge and self-efficacy of geriatric oral health care than in the control group. After the second round of training, students in the experimental group had significantly greater improvements in knowledge, attitude, and self-efficacy of geriatric oral health care as well as the intention to assist oral health care for older adult than in the control group. CONCLUSIONS: The VR-based simulation training was effective to improve undergraduate nursing students' knowledge, attitudes and self-efficacy of geriatric oral health as well as the intention to assist oral health care for older adults. The VR-based simulation learning system is an effective tool to provide practice experiences to build confidence and skills and to bridge the gap of understudied geriatric oral health content in entry-level nursing curricula. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05248542; registration date 21/02/2022).

Apoptosis pathways and osteoporosis: An approach to genomic analysis.

BACKGROUND: Osteoporosis is a disease of the bone system that causes a decrease in skeletal density and degrades skeletal tissue. Decreased bone quality, so that bones are easily broken, damaged and fractured, is an important public health problem. Previous studies have shown that the maintenance of adult bone mass is not only due to changes in bone marrow and bone cells. By regulating apoptosis, they change the lifespan of each individual. This study influences understanding of the function of apoptosis in the pathogenesis of osteoporosis and the importance of controlling the mechanisms of osteoporosis. METHODS: On the National Institute of Biotechnology Information website, Gene Expression Omnibus (GEO) microarray data and GSE551495 GEO profiles were collected. The gene set enrichment analysis tool was used to confirm the enrichment of genetic sets in relation to the gene set. The collection of C2 gene sets is compiled from the KEGG (https://www.gsea-msigdb.org/gsea/msigdb/human/search.jsp and https://www.kegg.jp/kegg/) online database and REACTOME (https://www.gsea-msigdb.org/gsea/msigdb/human/search.jsp and https://reactome.org/) pathway analysis. The Search Tool for the Retrieval of Interaction Genes (STRING) website was used to construct and select proteins and genes. The comparative toxicological genomic database (CTD) tools can be used to predict the relationship between apoptosis, osteoporosis-related genes and interactions between central genes and osteoporosis. RESULTS: These results generally expand our understanding of the path of apoptosis in osteoporosis. We have discovered genes CASP9, CASP8, CASP3, BAX and TP53 associated with osteoporosis. In activation of KEGG apoptosis and REACTOME, caspase activation through the extrinsic apoptotic signaling pathway is characterized by the identification of a subcollection of C2. Other STRINGs show the formation of protein networks and central gene selection, and CTD can accurately predict the relationship between these apoptosis pathways and central genes. CONCLUSIONS: Our research has highlighted the importance of the osteoporosis pathway associated with osteoporosis apoptosis with several analytical approaches. These results have broadened our understanding of the pathways of osteoporosis apoptosis. It is particularly possible to predict the sensitivity and vulnerability to osteoporosis.

Effect of non-pharmacological interventions on the prevention of sarcopenia in menopausal women: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Sarcopenia is a chronic disease marked by gradual muscle system and functional decline. Prior research indicates its prevalence in those under 60 varies from 8 to 36%. There is limited evidence on the effectiveness of non-pharmacological interventions for sarcopenia prevention in menopausal women aged 40-60. This study examines the influence of such interventions for sarcopenia prevention on these women. METHODS: PubMed, EMBASE, Medline, Cochrane Library, CINAHL, PEDro, and Airiti Library were searched from inception until May 5, 2023. Randomized controlled trials that examined exercise, vitamin D and protein supplementation effects on muscle mass, strength, and physical function. Quality assessment used the Cochrane risk of bias tool, and analysis employed Comprehensive Meta-Analysis version 2.0. RESULTS: A total of 27 randomized controlled trials, involving 1,989 participants were identified. Meta-analysis results showed exercise improved lean body mass (SMD = 0.232, 95% CI: 0.097, 0.366), handgrip strength (SMD = 0.901, 95% CI: 0.362, 1.441), knee extension strength (SMD = 0.698, 95% CI: 0.384, 1.013). Resistance training had a small effect on lean body mass, longer exercise duration (> 12 weeks) and higher frequency (60-90 min, 3 sessions/week) showed small to moderate effects on lean body mass. Vitamin D supplementation improved handgrip strength (SMD = 0.303, 95% CI: 0.130, 0.476), but not knee extension strength. There was insufficient data to assess the impact of protein supplementation on muscle strength. CONCLUSIONS: Exercise effectively improves muscle mass, and strength in menopausal women. Resistance training with 3 sessions per week, lasting 20-90 min for at least 6 weeks, is most effective. Vitamin D supplementation enhances small muscle group strength. Further trials are needed to assess the effects of vitamin D and protein supplementation on sarcopenia prevention. REGISTRATION NUMBER: This review was registered on PROSPERO CRD42022329273.

GATEKEEPER's Strategy for the Multinational Large-Scale Piloting of an eHealth Platform: Tutorial on How to Identify Relevant Settings and Use Cases.

BACKGROUND: The World Health Organization's strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs. OBJECTIVE: We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform. METHODS: The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities. RESULTS: Seven European countries were selected, covering Europe's geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence-based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors. CONCLUSIONS: This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space.

Effects of hypochlorous acid mouthwash on salivary bacteria including Staphylococcus aureus in patients with periodontal disease: a randomized controlled trial.

BACKGROUND: The effects of a low concentration of hypochlorous acid (HOCl) mouthwash on salivary bacteria remained unclear. We aimed to evaluate the antibacterial effects of 100 ppm HOCl mouthwash on salivary bacteria, including Staphylococcus aureus (S. aureus), in patients with periodontal disease (PD). METHODS: Patients with PD were randomized into mouthwash-only (MW, n = 26) and mouthwash with periodontal flosser (MWPF, n = 27) groups. Patients without PD were selected for the control group (n = 30). S. aureus culture and saliva samples (before and after the intervention) were collected for bacterial DNA extraction. A real-time polymerase chain reaction assay and serial dilutions of S. aureus culture and saliva samples were used to measure the salivary bacteria total count (SBTC) and confirm the antibacterial effects of the mouthwash using S. aureus. RESULTS: No significant difference in demographic data was observed among the three groups. Before the intervention, the baseline SBTC of the MW and MWPF groups was significantly higher than that of the control group. After the mouthwash rinses, the SBTC data significantly changed in the MW and MWPF groups only (by 62.4% and 77.4%, respectively). After the base-2 log-transformation of the SBTC data, a similar trend was observed. Linear regression revealed that baseline SBTC and the MWPF intervention significantly affected SBTC reduction percentage by volume. After incubation with 10% (v/v) of mouthwash, the survival rates of 106 and 107 colony-forming units/mL of S. aureus were 0.51% ± 0.06% and 1.42% ± 0.37%, respectively. CONCLUSIONS: These study results indicated that 100 ppm HOCl mouthwash treatment could effectively reduce SBTC in patients with PD and the abundance of S. aureus. It provides that the HOCl mouthwash can be an option for individuals to help control SBTC, especially in patients with PD. TRIAL REGISTRATION: The study protocol was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-F(I)-20200042) on 20/03/2020 and retrospectively registered at ClinicalTrial.gov (NCT05372835) on 13/05/2022.

[Effects of a Hybrid Health Education Program on Pain and Knee Angle in Elderly Patients After Total Knee Replacement Surgery].

BACKGROUND: Patients experience pain and limited knee angle after total knee replacement (TKR) surgery. The effectiveness of routine discharge health education remains limited. PURPOSE: This study was designed to assess the effect of hybrid health education on postoperative pain and knee angle in patients with TKR. METHODS: A single blind and randomized controlled trial study was used. Fifty-two patients with TKR were randomly assigned to either the experimental group (n = 26), which received standard care with hybrid health education and performed the multimedia-guided intervention for 30 min per day for 16 weeks, or the control group (n = 26), which received routine care only. The data collection times were at pretest (preoperative) and at the 1st week, 6th week, 12th week, 16th week after surgery. RESULTS: A total of 22 patients in the experimental group and 26 patients in the control group completed this study. After the 16-week hybrid health education intervention, the results of generalized estimating equations analysis showed that pain in the experimental and control groups differed significantly at week 12 (ß = -1.43, p = .025) and week 16 (ß = -1.52, p = .014); worst pain in the past week had significantly improved at week 12 (ß = -1.40, p = .041) and week 16 (ß = -1.55, p = .024); average pain over the past 1 week had significantly improved at week 16 (ß = -1.24, p = .035); and knee extension angle had significantly improved at week 16 (ß = -5.52, p = .033). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results of this study showed that elderly patients who received hybrid health education after TKR had significantly improved postoperative pain and knee angle and that degree of improvement in the experimental group was better than in the control group. It is recommended that the content and methods of hybrid health education developed in this study be incorporated into discharge interventions and that long-term outcomes be tracked for reference.

Effects of artificial intelligence-assisted dental monitoring intervention in patients with periodontitis: A randomized controlled trial.

AIM: To evaluate the effects of an at-home artificial intelligence (AI)-assisted dental monitoring application on treatment outcomes in patients with periodontitis. MATERIALS AND METHODS: Participants with periodontitis were recruited and randomly assigned to an AI (n = 16), AI and human counselling (AIHC; n = 17), or control (CG; n = 20) group. All participants received non-surgical periodontal treatment. We employed an AI-assisted tool called DENTAL MONITORING® (DM) intervention, a new technological AI monitoring product that utilizes smartphone cameras for intra-oral scanning and assessment. Patients in the AI and AIHC groups received additional (a) DM or (b) DM, respectively, with real-person counselling over 3 months. Periodontal parameters were collected at baseline and follow-ups. A mixed-design model analysed the follow-up effects over time. RESULTS: The AI and AIHC groups, respectively, exhibited greater improvement in probing pocket depth (PPD) (mean diff = -0.9 ± 0.4 and -1.4 ± 0.3, effect size [ES] = 0.76 and 1.98), clinical attachment level (mean diff = -0.8 ± 0.3 and -1.4 ± 0.3, ES = 0.84 and 1.77), and plaque index (mean diff = -0.5 ± 0.2 and - 0.7 ± 0.2, ES = 0.93 and 1.81) at 3-month follow-up than the CG did. The AIHC group had a greater reduction in PPD (ES = 0.46) and clinical attachment level (ES = 0.64) at the 3-month follow-up compared with the AI group. CONCLUSIONS: Using AI monitoring at home had a positive effect on treatment outcomes for patients with periodontitis. Patients who received AI-assisted health counselling exhibited better treatment outcomes than did patients who received AI monitoring alone.

Clinical-based oral rehabilitation programme improved the oral diadochokinesis and swallowing function of older patients with dementia: A randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a clinical-based oral function intervention on oral function and care behaviours in older patients with mild dementia. METHOD: Participants were randomly assigned to the experimental group (EG) and control group (CG). Both groups received a leaflet on oral health-related knowledge, and the EG also received an oral function intervention, which was a brief one-on-one lesson concerning oral exercise and preventive oral care. Oral exercise included turning the head, pouting lips, bulging cheeks, stretching tongue, articulation exercise and salivary gland massages. A reminder phone call was made every 2 weeks. Perceived xerostomia and dysphagia, plaque index (PI), Winkel tongue-coating index (WTCI), repetitive saliva-swallowing test (RSST), oral diadochokinesis (DDK) and oral care behaviours were recorded at baseline and at 3-month follow-up. Generalised Estimating Equations (GEE) were used to analyse the indicated effects. RESULTS: The EG (n = 59) exhibited greater improvement to the CG (n = 55) in RSST [ß = 0.7; effect size (ES) = 0.45], the syllables /pa/ (ß = 3.1; ES = 0.37) and /ka/ (ß = 2.7; ES = 0.40) in oral DDK, PI (ß = -0.2; ES = 0.52) and WTCI (ß = -0.8; ES = 0.38). Moreover, the EG exhibited better preventive behaviours in regular dental visits [adjusted odds ratio (aOR) = 2.2], daily mouth cleaning frequency (aOR = 1.6) and mouth cleaning before sleep (aOR = 1.3). CONCLUSION: The brief clinical-based intervention was effective in improving the swallowing function, oral DDK and plaque control of older patients with mild dementia at 3-month follow-up.

Contribution of insulin resistance to the relationship between sugar-sweetened beverage intake and a constellation of cardiometabolic abnormalities in adolescents.

BACKGROUND: Insulin resistance (IR) is a pathophysiological construct that derives a series of metabolic disturbances that promote cardiometabolic dysfunction. This study evaluated mediating and modifying effects of homeostatic model assessment-based IR (HOMA-IR) on the association between sugar-sweetened beverage (SSB) consumption and a constellation of adolescent cardiometabolic abnormalities. METHODS: Comprehensive data on sociodemographics, diet, physical activity, and anthropometric and biochemical parameters for 1454 adolescents were obtained from a large-scale representative study for adolescent metabolic syndrome (MetS) conducted in Taiwan. The original (HOMA1-IR) and updated nonlinear (HOMA2-IR) HOMA-IR indicators were used as IR biomarkers. Principal component (PC) analysis was employed to create reduced groups of variables and risk scores for retained PCs. RESULTS: Higher SSB intake was associated with higher levels of HOMA1-IR and HOMA2-IR, and the two IR biomarkers were positively correlated with metabolic dysfunction clustering. Compared with SSB nondrinkers, adolescents who consumed >500 mL/day of hand-shaken high-fructose corn syrup beverages (HHB) had a 0.22 increase in the number of abnormal MetS components, and HOMA-IR mediation explained 33.9-37.9% of the effect. IR biomarkers accounted for 26.5-31.0% of the relationship between >500 mL/day of SSB consumption and bodyweight-enhanced PC scores. The effects of HOMA-IR indicators on all bodyweight-related factors were consistently intensified among >350 mL/day HHB drinkers (all Pinteraction < 0.05). CONCLUSIONS: Fructose-rich SSB intake correlates with a constellation of cardiometabolic abnormalities in adolescents, and this association may be partly mediated by HOMA-IR levels. The adverse effects of HOMA-IR on bodyweight-associated cardiometabolic risk factors depend on the type of SSB consumption, with enhanced risks observed in the intake of high amounts of HFCS-containing SSBs.

Association between the dental occlusion and perceived ability to eat foods of Taiwanese older adults.

Tooth loss is a common problem among older adults that affects masticatory function (MF) and food selection. Financial burden is a reason that some older adults in Taiwan with this condition forgo dental restoration. To identify the number of posterior occlusal support areas (POSAs) associated with MF. Large-scale cross-sectional study included 1100 community-dwelling participants of Taiwan aged ≥65 years. Participants completed dental examination and questionnaires through personal interviews. Masticatory performance was evaluated using a colour-changeable chewing gum. Masticatory ability was evaluated on the basis of how many of 14 common foods the participants were able to eat. Participants were grouped into 10 categories (A1-A3, B1-B4 and C1-C3) according to the Eichner index (EI) of posterior occlusal contacts. Multivariable regression models were used to analyse the association between the EI groups and MF. More than 80% of the participants with two or more POSAs (those in groups A1-B2) could easily eat various foods. Compared with those in groups A1-B2, those in groups in B3, B4, C1, C2 and C3 exhibited a significantly different masticatory performance (all P < .001) and significantly higher difficulty in eating fruits and vegetables. A dose-response effect between POSAs and perceived masticatory ability to eat fruits and vegetables was observed (P < .05 for both trends). Preservation of at least two POSAs is essential for MF. Older adults with tooth loss can undergo the restoration of two POSAs to improve MF and increase food intake.

Effects of health-promoting school strategy on dental plaque control and preventive behaviors in schoolchildren in high-caries, rural areas of Taiwan: a quasi-experimental design.

BACKGROUND: We evaluated the effects of health-promoting school (HPS) strategy on plaque control and behavior change in high-caries schoolchildren in Taitung, Taiwan. METHODS: A quasi-experimental design was adopted; six intervention schools (intervention group [IG]) and six comparison schools (comparison group [CG]) were selected from elementary schools with higher-than-average caries rates (> 68%). The IG was selected using cluster sampling, and the CG was selected to match the IG. In total, the IG and CG groups included 166 and 174 children each. The selected schools implemented the HPS framework for 3 months in the 2019 academic year. An oral examination of dental plaque was administered, and a self-administered questionnaire regarding knowledge, attitude, self-efficacy, and behaviors was distributed at baseline and at 2-week follow-up. A linear and logistic regression model using generalized estimating equations (GEEs) was used to analyze the differences between baseline and the follow-up data. RESULTS: Compared with the CG, the IG had a greater reduction in plaque index among second graders (ß = - 0.36) and plaque control record scores among second, fourth, and sixth graders (ß = - 27.48, - 26.04, and - 18.38, respectively). The IG also exhibited a greater increase at follow-up with respect to oral health-related knowledge among second graders and fourth graders (ß = 1.46 and ß = 0.92, respectively), attitude toward oral hygiene behaviors among sixth graders (ß = 1.78), and self-efficacy regarding flossing for sixth graders (ß = 1.43). Sixth graders in the IG were significantly more likely to brush before sleeping (adjusted odds ratio [aOR] = 2.99) and use fluoride toothpaste (aOR = 5.88) than those in the CG. CONCLUSIONS: The HPS strategy was effective in reducing dental plaque and promoting preventing behaviors in rural high-caries schoolchildren.

Dysphagia and masticatory performance as a mediator of the xerostomia to quality of life relation in the older population.

BACKGROUND: The impact of poor oral health on older adults' quality of life is a public health problem. In this study, the mediating effects of dental status, occlusal condition, dysphagia, and masticatory performance on the association between xerostomia and oral health-related quality of life (OHRQoL) were assessed in the older adult population. METHODS: Stratified cluster sampling was used to recruit 1076 community-dwelling adults aged 65 years and older from Kaohsiung, Taiwan. Community care centers were randomly selected according to their geographic classifications (urban, rural, or mountainous areas). Assessments of dental status and occlusal condition were performed by dentists. Information on demographics, physical function, xerostomia, dysphagia and depression was collected through face-to-face interviews. Masticatory performance was evaluated using color-changeable chewing gum. OHRQoL was measured using the Geriatric Oral Health Assessment Index. Hierarchical regression models were used to assess the relationships between OHRQoL and physical function, dental status and oral function in older adults. Path analysis was used to estimate direct and indirect pathways between xerostomia and OHRQoL. RESULTS: Participants with xerostomia exhibited a 0.20 OHRQoL reduction (p < .001) compared with patients with no xerostomia, and the direct effect accounted for 83.3% of the total effect. Dysphagia and masticatory performance were found to exert significant mediating effects on the association between xerostomia and OHRQoL (ßs = 0.20 and - 0.12, respectively; both p < .001; ßs = 0.06 and - 0.09, respectively; both p < .05). Moreover, potential mediating effects of the number of functional teeth (ßs = - 0.11 and - 0.43, respectively; both p < .001) and occlusal condition (ßs = 0.09 and 0.13, respectively; both p < .05) on the relationship between xerostomia and masticatory performance were noted. CONCLUSIONS: Dysphagia and masticatory performance may serve as pathways through which xerostomia affects quality of life. Early oral function intervention may be a valuable and actionable target for older adults to maintain quality of life. Our results further suggest that checkup and screening for oral dysfunction are essential to prevent or delay the onset of complications.

Mechanism-based inactivator of isocitrate lyases 1 and 2 from Mycobacterium tuberculosis.

Isocitrate lyase (ICL, types 1 and 2) is the first enzyme of the glyoxylate shunt, an essential pathway for Mycobacterium tuberculosis (Mtb) during the persistent phase of human TB infection. Here, we report 2-vinyl-d-isocitrate (2-VIC) as a mechanism-based inactivator of Mtb ICL1 and ICL2. The enzyme-catalyzed retro-aldol cleavage of 2-VIC unmasks a Michael substrate, 2-vinylglyoxylate, which then forms a slowly reversible, covalent adduct with the thiolate form of active-site Cys191 2-VIC displayed kinetic properties consistent with covalent, mechanism-based inactivation of ICL1 and ICL2 with high efficiency (partition ratio, <1). Analysis of a complex of ICL1:2-VIC by electrospray ionization mass spectrometry and X-ray crystallography confirmed the formation of the predicted covalent S-homopyruvoyl adduct of the active-site Cys191.

Gender-specific factors associated with the suicidal ideation of children in Taiwan: A large-scale cross-sectional study.

We examined the relationship between suicidal ideation (SI) and the depressed mood, life stress and parenting styles in children. A large-scale survey was conducted including 5328 children from 65 elementary schools in Taiwan. SI was measured by asking children if any suicidal thoughts had occurred in the previous month. A series of regression models was analysed separately for male and female students. Compared with boys, girls demonstrated a higher proportion of SI. Among boys, SI was significantly associated with a high level of perceived environmental stress (adjusted odds ratio [aOR] = 2.61), a high degree of depressed mood (aOR = 2.39), authoritative (aOR = 1.72) and authoritarian (aOR = 2.53) parenting styles and two or more life-stress events (aOR = 1.45). A high level of perceived environmental stress (aOR = 2.09), a high degree of depressed mood (aOR = 2.89) and an authoritarian parenting style (aOR = 1.76) were significantly associated with the SI in girls. Gender-specific interventions aimed at preventing SI must enhance support systems at school and at home, particularly for students who suffer from a high degree of stress and depressed mood, and are subjected to an authoritarian parenting style.

Effects of insulin resistance on the association between the circulating retinol-binding protein 4 level and clustering of pediatric cardiometabolic risk factors.

OBJECTIVES: Retinol-binding protein 4 (RBP4) and insulin resistance (IR) are clinical parameters associated with cardiometabolic diseases. The mediating and modifying roles of IR on children's susceptibility to cardiometabolic disorders are undetermined. This study investigated the mediating and modifying effects of the homeostatic model assessment of IR (HOMA-IR) on the relationship between the serum RBP4 level and clustering of pediatric cardiometabolic risk factors. METHODS: We assessed the diet, physical activity, cardiometabolic risk factors, and clinical parameters of 272 randomly selected adolescents from a large-scale cross-sectional study (n = 2727). Two HOMA-IRs (HOMA1-IR and HOMA2-IR) were used to evaluate the designated effects. RESULTS: Levels of serum RBP4 positively correlated with the levels of the 2 HOMA-based-IRs, and HOMA-IR correlated to all components of pediatric metabolic syndrome (MetS), the number of abnormal components, and a body-weight-weighted principal component score extracted from 12 cardiometabolic risk factors. Increased RBP4 levels had positive effects on waist circumference (WC), triglyceride, and the number of abnormal MetS components (0.310 cm, 1.384 µg/dL, and 0.021 item elevations, respectively), and the HOMA-IRs explained 17.7% to 21.9%, 11.8% to 27.6%, and 23.8% to 25.0% of these effects. The association of WC and the number of abnormal MetS components with the serum RBP4 level was enhanced by higher HOMA-IR (ß for interaction, 0.13 and 0.01 for HOMA1-IR, and 0.32 and 0.02 for HOMA2-IR, respectively). CONCLUSIONS: HOMA-IR is associated with the circulating RBP4 level and cardiometabolic risk factors in adolescents. Pediatric HOMA-IR may have mediating and modifying effects on the positive correlations between RBP4 and the clustering of MetS components.

Anion-π Interactions in Computer-Aided Drug Design: Modeling the Inhibition of Malate Synthase by Phenyl-Diketo Acids.

Human infection by Mycobacterium tuberculosis (Mtb) continues to be a global epidemic. Computer-aided drug design (CADD) methods are used to accelerate traditional drug discovery efforts. One noncovalent interaction that is being increasingly identified in biological systems but is neglected in CADD is the anion-π interaction. The study reported herein supports the conclusion that anion-π interactions play a central role in directing the binding of phenyl-diketo acid (PDKA) inhibitors to malate synthase (GlcB), an enzyme required for Mycobacterium tuberculosis virulence. Using density functional theory methods (M06-2X/6-31+G(d)), a GlcB active site template was developed for a predictive model through a comparative analysis of PDKA-bound GlcB crystal structures. The active site model includes the PDKA molecule and the protein determinants of the electrostatic, hydrogen-bonding, and anion-π interactions involved in binding. The predictive model accurately determines the Asp 633-PDKA structural position upon binding and precisely predicts the relative binding enthalpies of a series of 2-ortho halide-PDKAs to GlcB. A screening model was also developed to efficiently assess the propensity of each PDKA analog to participate in an anion-π interaction; this method is in good agreement with both the predictive model and the experimental binding enthalpies for the 2-ortho halide-PDKAs. With the screening and predictive models in hand, we have developed an efficient method for computationally screening and evaluating the binding enthalpy of variously substituted PDKA molecules. This study serves to illustrate the contribution of this overlooked interaction to binding affinity and demonstrates the importance of integrating anion-π interactions into structure-based CADD.

Health-related behaviors moderate the association between age and self-reported health literacy among Taiwanese women.

The role of health-related behaviors in the association between age and health literacy has not been well-elucidated. The present cross-sectional study evaluated the interactions between age and health-related behaviors in 942 women in Taiwan between February and October 2013. Women aged 18-78 years were randomly sampled and recruited from the national administrative system. Self-reported health literacy was measured by the European Health Literacy Survey Questionnaire (HLS-EU-Q47) in Mandarin, asking about sociodemographics and essential health-related behaviors (watching health-related television, community involvement). The interviews were conducted confidentially by well-trained interviewers after having participants' consent. In multiple linear regression models adjusted for education attainment, self-perceived social status, ability to pay for medication, and health-related behaviors, health literacy was significantly negatively related to age (unstandardized regression coefficient, B = -0.04; 95% confidence interval [CI] = (-0.07; 0.00); p = .03). The lower health literacy among older women was significantly modified by watching health-related television programs (from "rarely/not-at-all", B = -0.08 (-0.12, -0.04), p < .001 to "often"; B = 0.10 (0.07, 0.12); p < .001) and community involvement (from "rarely/not-at-all", B = -0.06 (-0.10, -0.03); p = .001 to "often", B = 0.06 (0.03, 0.08); p < .001). Specific health behaviors were protective of older women's health literacy and likely their health.

Mycobacterium tuberculosis Malate Synthase Structures with Fragments Reveal a Portal for Substrate/Product Exchange.

Fragment screening and high throughput screening are complementary approaches that combine with structural biology to explore the binding capabilities of an active site. We have used a fragment-based approach on malate synthase (GlcB) from Mycobacterium tuberculosis and discovered several novel binding chemotypes. In addition, the crystal structures of GlcB in complex with these fragments indicated conformational changes in the active site that represent the enzyme conformations during catalysis. Additional structures of the complex with malate and of the apo form of GlcB supported that hypothesis. Comparative analysis of GlcB structures in complex with 18 fragments allowed us to characterize the preferred chemotypes and their binding modes. The fragment structures showed a hydrogen bond to the backbone carbonyl of Met-631. We successfully incorporated an indole group from a fragment into an existing phenyl-diketo acid series. The resulting indole-containing inhibitor was 100-fold more potent than the parent phenyl-diketo acid with an IC50 value of 20 nm.

Measuring health literacy in Asia: Validation of the HLS-EU-Q47 survey tool in six Asian countries.

BACKGROUND: Health literacy has been increasingly recognized as one of the most important social determinants for health. However, an appropriate and comprehensive assessment tool is not available in many Asian countries. This study validates a comprehensive health literacy survey tool European health literacy questionnaire (HLS-EU-Q47) for the general public in several Asian countries. METHODS: A cross-sectional survey based on multistage random sampling in the target countries. A total of 10,024 participants aged ≥15 years were recruited during 2013-2014 in Indonesia, Kazakhstan, Malaysia, Myanmar, Taiwan, and Vietnam. The questionnaire was translated into local languages to measure general health literacy and its three domains. To evaluate the validity of the tool in these countries, data were analyzed by confirmatory factor analysis, internal consistency analysis, and regression analysis. RESULTS: The questionnaire was shown to have good construct validity, satisfactory goodness-of-fit of the data to the hypothetical model in three health literacy domains, high internal consistency (Cronbach's alpha >0.90), satisfactory item-scale convergent validity (item-scale correlation ≥0.40), and no floor/ceiling effects in these countries. General health literacy index score was significantly associated with level of education (P from <0.001 to 0.011) and perceived social status (P from <0.001 to 0.016), with evidence of known-group validity. CONCLUSIONS: The HLS-EU-Q47 was a satisfactory and comprehensive health literacy survey tool for use in Asia.