Robust proteome profiling of cysteine-reactive fragments using label-free chemoproteomics.

Identifying pharmacological probes for human proteins represents a key opportunity to accelerate the discovery of new therapeutics. High-content screening approaches to expand the ligandable proteome offer the potential to expedite the discovery of novel chemical probes to study protein function. Screening libraries of reactive fragments by chemoproteomics offers a compelling approach to ligand discovery, however, optimising sample throughput, proteomic depth, and data reproducibility remains a key challenge.

Association of Body Mass Index between Adolescents and their Parents in Mumbai and Kolkata: A Population-based Study.

Introduction: Adolescent overweight and obesity as measured by body mass index (BMI) seem to be increasing at an alarming rate in urban populations. Parental BMI plays an important role in their adolescent's BMI. Overweight and obesity coexisting with undernutrition in adolescents is an important public health challenge in low- and middle-income countries (LMICs).

Person explanatory multidimensional item response theory with the instrument package in R.

We present the new R package instrument to perform Bayesian estimation of person explanatory multidimensional item response theory. The package implements an exploratory multidimensional item response theory model and a higher-order multidimensional item response theory model, a type of confirmatory multidimensional item response theory. Explanation of person parameters is accomplished by fixed and random effect linear regression models.

A Fragment-Based Competitive F LB-NMR Platform For Hotspot-Directed Ligand Profiling.

Ligand binding hotspots are regions of protein surfaces that form particularly favourable interactions with small molecule pharmacophores. Targeting interactions with these hotspots maximises the efficiency of ligand binding. Existing methods are capable of identifying hotspots but often lack assays to quantify ligand binding and direct elaboration at these sites.

Covalent fragment-based drug discovery for target tractability.

An important consideration in drug discovery is the prioritization of tractable protein targets that are not only amenable to binding small molecules, but also alter disease biology in response to small molecule binding. Covalent fragment-based drug discovery has emerged as a powerful approach to aid in the identification of such protein targets. The application of irreversible binding mechanisms enables the identification of fragment hits for challenging-to-target proteins, allows proteome-wide screening in a cellular context, and makes it possible to determine functional effects with modestly potent ligands without the requirement for extensive compound optimization.

Chemical Validation of Phosphopantetheine Adenylyltransferase Using Fragment Linking and CRISPR Interference.

The coenzyme A (CoA) biosynthesis pathway has attracted attention as a potential target for much-needed novel antimicrobial drugs, including for the treatment of tuberculosis (TB), the lethal disease caused by (). Seeking to identify inhibitors of phosphopantetheine adenylyltransferase (PPAT), the enzyme that catalyses the penultimate step in CoA biosynthesis, we performed a fragment screen. In doing so, we discovered three series of fragments that occupy distinct regions of the PPAT active site, presenting a unique opportunity for fragment linking.

EEG microstate quantifiers and state space descriptors during anaesthesia in patients with postoperative delirium: a descriptive analysis.

Postoperative delirium is a serious sequela of surgery and surgery-related anaesthesia. One recommended method to prevent postoperative delirium is using bi-frontal EEG recording. The single, processed index of depth of anaesthesia allows the anaesthetist to avoid episodes of suppression EEG and excessively deep anaesthesia.

A statewide study of disparities in local policies and tobacco, vape, and cannabis retail environments.

The current study: (1) assesses sociodemographic disparities in local policies related to tobacco and cannabis retail, and (2) examines the cross-sectional association between policy strength and retailer densities of tobacco, e-cigarette (vape), and cannabis retailers within California cities and county unincorporated areas (N = 539). We combined (a) American Community Survey data (2019 5-year estimates), (b) 2018 tobacco, vape, and cannabis retailer locations from a commercial data provider, (c) 2017 tobacco and vape retail environment policy data from American Lung Association, and (d) 2018 cannabis policy data from California Cannabis Local Laws Database. Conditional autoregressive models examined policy strength associations with sociodemographic composition and retailer density in California jurisdictions.

Awareness and Use of e-cigarettes among Adolescents and Their Adult Caregivers in Two Cities of India.

Introduction/objective: E-cigarette use poses an additional risk for individuals who are not cigarette smokers, especially adolescents. The marketing tactics of the industry have substantially increased the prevalence of e-cigarettes, use among adolescents. India banned e-cigarette in September 2019 that has been criticized by interested groups.

Randomized Comparative Effectiveness Trial of 2 Federally Recommended Strategies to Reduce Excess Body Fat in Overweight, Low-Income Patients: MyPlate.gov vs Calorie Counting.

Purpose: Since 2011, US authorities have supported the following 2 approaches to healthier body fat composition: the Centers for Disease Control and Prevention National Diabetes Prevention Program's calorie counting (CC) approach and the US Department of Agriculture's MyPlate (adherence to federal nutrition guidelines). The purpose of this study was to compare the effect of CC vs MyPlate approaches on satiety/satiation and on achieving healthier body fat composition among primary care patients.

Methods: We conducted a randomized controlled trial comparing the CC and MyPlate approaches from 2015 to 2017.

Chemical Validation of Mycobacterium tuberculosis Phosphopantetheine Adenylyltransferase Using Fragment Linking and CRISPR Interference.

The coenzyme A (CoA) biosynthesis pathway has attracted attention as a potential target for much-needed novel antimicrobial drugs, including for the treatment of tuberculosis (TB), the lethal disease caused by Mycobacterium tuberculosis (Mtb). Seeking to identify inhibitors of Mtb phosphopantetheine adenylyltransferase (MtbPPAT), the enzyme that catalyses the penultimate step in CoA biosynthesis, we performed a fragment screen. In doing so, we discovered three series of fragments that occupy distinct regions of the MtbPPAT active site, presenting a unique opportunity for fragment linking.

"Ancestral recipes": a mixed-methods analysis of MyPlate-based recipe dissemination for Latinos in rural communities.

Background: The Latinx population experiences some of the highest rates of chronic disease, including obesity and type II diabetes. Such conditions may be especially burdensome in rural Latinx communities that often face barriers to accessing disease prevention resources and public health programs.

Methods: Diverse stakeholders (i.

Development of potent inhibitors by fragment-linking strategies.

Fragment-based drug discovery (FBDD) is a method of identifying small molecule hits that can be elaborated rationally through fragment growing, merging and linking, to afford high-affinity ligands for biological targets. Despite the promised theoretical potential of fragment linking, examples are still surprisingly sparse and remain overshadowed by the successes of fragment growing. The aim of this review was to outline a number of key examples of fragment-linking strategies and discuss their strengths and limitations.

Structural Characterization of Phosphopantetheine Adenylyl Transferase Ligand Interactions: Implications for Fragment-Based Drug Design.

Anti-microbial resistance is a rising global healthcare concern that needs urgent attention as growing number of infections become difficult to treat with the currently available antibiotics. This is particularly true for mycobacterial infections like tuberculosis and leprosy and those with emerging opportunistic pathogens such as , where multi-drug resistance leads to increased healthcare cost and mortality. is a highly drug-resistant non-tuberculous which causes life-threatening infections in people with chronic lung conditions such as cystic fibrosis.

Using a multilevel implementation strategy to facilitate the screening and treatment of tobacco use in the outpatient urology clinic: A prospective hybrid type I study.

Background: Urologists frequently treat patients for tobacco-related conditions but infrequently engage in evidence-based practices (EBPs) that screen for and treat tobacco use. Improving the use of EBPs will help to identify smokers, promote cessation, and improve patients' health outcomes.

Methods: A prospective type I hybrid effectiveness-implementation study was performed to test the feasibility and effectiveness of using a multilevel implementation strategy to improve the use of tobacco EBPs.

Neighbourhood tobacco retail access and tobacco use susceptibility in young adolescents in urban India.

Background: Neighbourhood tobacco retail access may influence adolescent tobacco use. In India, we examined the association between neighbourhood tobacco retail access and cognitive risks for tobacco use during early adolescence.

Methods: In 2019-2020, a population-based sample (n=1759) of adolescents aged 13-15 years was surveyed from 52 neighbourhoods in Mumbai and Kolkata.

Macrocyclic [2]catenane btp structures: influence of (aryl) substitution on the self templation of btp ligands in macrocyclic synthesis.

The synthesis of four 2,6-bis(1,2,3-triazol-4-yl)pyridine (btp) olefin based ligands 3, 4, 11 and 12 is described and their attempted use to form mechanically interlocked molecules using ring closing metatheses (RCM) reactions. The btp ligands were modified in two ways, in 3 and 4 the aryl substitution pattern was changed from 4 position to 3 position and in the case of 11 and 12, the arms were replaced with aliphatic chains. Our study demonstrates that for all four ligands, the RCM reactions only result in the formation of macrocyclic structures, which in three of the cases, were structurally characterised in both solution (using NMR and HRMS) and in the solid-state using X-ray crystallography.

Prevalence and Correlates of Successful Smoking Cessation in Bladder Cancer Survivors.

Objective: To assess the prevalence and correlates of successful smoking cessation in bladder cancer survivors.

Materials And Methods: A population-based sample of bladder cancer survivors diagnosed over a 3 year period was obtained from the California Cancer Registry. Respondents completed a survey about their tobacco use and attempts at smoking cessation.

Incorporating an Increase in Plant-Based Food Choices into a Model of Culturally Responsive Care for Hispanic/Latino Children and Adults Who Are Overweight/Obese.

The national rate of obesity in US Hispanic/Latinos exceeds all other major ethnic subgroups and represents an important health disparity. Plant-based diet interventions that emphasize whole plant foods with minimal processing and less refined grains and sugar have shown great promise in control of obesity, but there is a paucity of data translating this treatment effect to disparate populations. The objective of our study was to evaluate the efficacy of the Healthy Eating Lifestyle Program (HELP) for accomplishing weight management in a hospital-based, family centered, culturally tailored, plant-based diet intervention for Hispanic/Latino children who were overweight or obese.

Undergraduate support for university smoke-free and vape-free campus policies and student engagement: a quasi-experimental intervention.

College campuses have policies restricting smoking/vaping on campus. Previous studies involving mostly European-American students showed smoking prevalence declines following implementation of such policies.To evaluate a social media campaign promotive of stronger campus support for an existing campus no-smoking/no-vaping policy where most (∼75%) of the undergraduates were non-European-American.

Cross-Sectional and Longitudinal Construct Validity of the Generic KINDL-A(dult)B(rief) Questionnaire in Adults with Thrombophilia or with Hereditary and Acquired Bleeding Disorders.

Background/aims: The newly adapted generic KINDL-A(dult)B(rief) questionnaire showed satisfactory cross-sectional psychometric properties in adults with bleeding disorders or thrombophilia. This investigation aimed to evaluate its cross-sectional and longitudinal construct validity.

Methods: After ethical committee approval and written informed consent, 335 patients (mean age 51.

Risk of developing pre-diabetes or diabetes over time in a cohort of Mexican health workers.

Aim: To determine the association between known risk factors (e.g., obesity, metabolic syndrome and its components) and the development of pre-diabetes or diabetes over time in a cohort of Mexican health workers.

Secondary analysis of an RCT on Emergency Department-Initiated Tobacco Control: Repeatedly assessed point-prevalence abstinence up to 12 months and extension of results through a 10-year follow-up.

Introduction: Emergency departments (EDs) are opportune places for tobacco control interventions. The 'Tobacco Control in an Urban Emergency Department' (TED) study, ISRCTN41527831, originally evaluated the effect of motivational interviewing on-site plus up to four booster telephone calls on 12-month abstinence. This study's aim was to evaluate the effect of the intervention on 7-day point-prevalence abstinence at 10 years follow-up (primary outcome) as well as on repeated point-prevalence abstinence at 1, 3, 6, 12 months and at 10 years (continual smoking abstinence, secondary outcome).