Socio-Cultural, Organizational, and Community Level Influences on Physical Activity Levels of Latino Preschool-Age Children: A Qualitative Study

Objectives: As more children grow up in families with immigrant parents of Latino origin, there is a need to understand key influences on physical activity behaviors of young Latino children to prevent obesity in this high-risk group.Design: We conducted six focus groups with low-income Latina mothers (N = 33) whose preschool-aged children (2-5 years) were enrolled in the Supplemental Nutrition Program for Women, Infants and Children (WIC) program in Rhode Island. Data was analyzed using content analysis to identify recurrent themes.Results: Despite understanding the importance of physical activity for overall health, physical activity was not a top priority for the Latino mothers participating in the focus groups. Mothers reported facing numerous barriers to establishing and maintaining healthful physical activity habits for their preschool-aged children and themselves, particularly financial and socio-cultural barriers. Analyses revealed that Latina mothers perceive the WIC as a program focused on the development and maintenance of healthy eating habits and nutritional status of children and not physical activity.Conclusions: Recognizing the importance of socioeconomic position and the influence of cultural factors on physical activity is essential if effective prevention and intervention programs for Latino families and their children are to be designed. Study findings emphasize the importance of the family as a central unit of change and suggest that successful interventions to promote physical activity of low-income Latino preschool children must take into account the needs and constraints of the family unit as a whole. The WIC program has the potential to be a venue for promoting awareness of and educating low-income Latino parents about the importance of helping their children develop and maintain early healthful physical activity habits. The WIC program can also play an important role in facilitating access and creating programs and services that provide increased opportunities for physical activity of young children and their families

Using Mixed-Methods to Examine Factors that Influence Exercise Prescription from Healthcare Providers: A Community-Engaged Research Project

Background: The American College of Sports Medicine\u27s Exercise is Medicine initiative supports promotion of physical activity by health care providers (HCPs). Exercise is Medicine recommends HCPs utilize strategies such as exercise prescriptions to increase and promote regular exercise and referrals to community-based exercise facilities (ExRx+). Research is needed to identify factors that will increase African-American patients\u27 ExRx+ engagement since little is known about factors that serve as facilitators or barriers to adherence. Aims: Using a community-engaged participatory research approach, the aims are to: 1) examine individual, interpersonal and environmental factors associated with ExRx+ adherence and 2) explore barriers and facilitators related to the referral process that are associated with ExRx+ adherence. Setting: Healthworks Community Fitness, a non-profit women\u27s fitness facility located in Dorchester, MA. Healthworks is the only gym in the Boston metro area which allows patients to exchange ExRx+ for a 3-month gym membership. Methods: Based on a socio-ecological framework, the mixed-methods protocol includes qualitative and quantitative methods implemented sequentially in two phases to explore factors associated with ExRx+ adherence. Adherence will be operationally defined as: 1) activation: patient redeems the ExRx+ for membership and 2) utilization: attendance during the 3 month membership. Quantitative data will focus on the patient\u27s individual (i.e, body mass index, self-efficacy) interpersonal (i.e, social support), and environmental (i.e, walkability, transportation) levels. Qualitative data will involve one-on-one interviews with patients, HCPs and Healthworks staff exploring facilitators and barriers to ExRx+ adherence. Results will inform the development of a culturally tailored intervention to promote ExRx+ adherence

Identification of three novel Toxoplasma gondii rhoptry proteins

The rhoptries are key secretory organelles from apicomplexan parasites that contain proteins involved in invasion and modulation of the host cell. Some rhoptry proteins are restricted to the posterior bulb (ROPs) and others to the anterior neck (RONs). As many rhoptry proteins have been shown to be key players in Toxoplasma invasion and virulence, it is important to identify, understand and characterise the biological function of the components of the rhoptries. In this report, we identified putative novel rhoptry genes by identifying Toxoplasma genes with similar cyclical expression profiles as known rhoptry protein encoding genes. Using this approach we identified two new rhoptry bulb (ROP47 and ROP48) and one new rhoptry neck protein (RON12). ROP47 is secreted and traffics to the host cell nucleus, RON12 was not detected at the moving junction during invasion. Deletion of ROP47 or ROP48 in a type II strain did not show major influence in in vitro growth or virulence in mice.United States. National Institutes of Health (R01-AI080621

A case study of adapting a health insurance decision intervention from trial into routine cancer care

OBJECTIVE: This study adapted Improving Cancer Patients\u27 Insurance Choices (I Can PIC), an intervention to help cancer patients navigate health insurance decisions and care costs. The original intervention improved knowledge and confidence making insurance decisions, however, users felt limited by choices provided in insurance markets. Using decision trees and frameworks to guide adaptations, we modified I Can PIC to focus on using rather than choosing health insurance. The COVID-19 pandemic introduced unforeseen obstacles, prompting changes to study protocols. As a result, we allowed users outside of the study to use I Can PIC (\u3e 1050 guest users) to optimize public benefit. This paper describes the steps took to conduct the study, evaluating both the effectiveness of I Can PIC and the implementation process to improve its impact. RESULTS: Although I Can PIC users had higher knowledge and health insurance literacy compared to the control group, results were not statistically significant. This outcome may be associated with systems-level challenges as well as the number and demographic characteristics of participants. The publicly available tool can be a resource for those navigating insurance and care costs, and researchers can use this flexible approach to intervention delivery and testing as future health emergencies arise

Clinical trial discrimination of physical function instruments for psoriatic arthritis:A systematic review

OBJECTIVES: Physical function (PF) is a core domain to be measured in randomized controlled trials (RCTs) of psoriatic arthritis (PsA), yet the discriminative performance of patient reported outcome measures (PROMs) for PF in RCTs has not been evaluated systematically. In this systematic review, we aimed to evaluate the clinical trial discrimination of PF-PROMs in PsA RCTs. METHODS: We searched PubMed and Scopus databases in English to identify all original RCTs on biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) conducted in PsA. We assessed quality in each article using the OMERACT good method checklist. Effect sizes (ES) for the PF-PROMs were calculated and appraised using a priori hypotheses. Evidence supporting clinical trial discrimination for each PF-PROM was summarized to derive recommendations. RESULTS: 35 articles from 31 RCTs were included. Four PF-PROMs had data for evaluation: HAQ-Disability Index (DI), HAQ-Spondyloarthritis (S), and Short Form 36-item Health Survey Physical Component Summary (SF-36 PCS) and Physical Functioning domain (SF-36 PF). As anticipated, higher ES values were observed for intervention groups than the control groups. Across all studies, for HAQ-DI, the median ES were -0.73 and -0.24 for intervention and control groups, respectively. Whereas for SF-36 PCS, the median ES were 0.77 and 0.23. For intervention and control groups, respectively. CONCLUSION: Clinical trial discrimination was supported for HAQ-DI and SF-36 PCS in PsA with low risk of bias; and for SF-36 PF and HAQ-S with some caution. More studies are required for HAQ-S

Initiating Evaluation of Composite Outcome Measures for Psoriatic Arthritis:2022 Updates From the GRAPPA-OMERACT Working Group

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) working group-comprising rheumatologists, dermatologists, methodologists, and patient research partners-provided updates at the GRAPPA 2022 annual meeting on its work to evaluate composite outcome measures for PsA. Ten composite outcome measures were considered. Initial steps were to define the population, the purpose of use, and the proposed pros and cons of the 10 candidate composite instruments for PsA. Preliminary Delphi exercises within the working group and GRAPPA stakeholders confirmed high priority for evaluating minimal disease activity (MDA); moderate priority for Disease Activity in PsA (DAPSA), American College of Rheumatology (ACR) response criteria, Psoriatic Arthritis Disease Activity Score (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), 3 visual analog scale (VAS), and 4VAS; and low priority for Disease Activity Score in 28 joints (DAS28), Psoriatic Arthritis Responder Criteria (PsARC), and Routine Assessment of Patient Index Data 3 (RAPID3). Further appraisal of candidate composite instruments is ongoing.</p

Global FKRP Registry: observations in more than 300 patients with Limb Girdle Muscular Dystrophy R9

Objective The Global FKRP Registry is a database for individuals with conditions caused by mutations in the Fukutin‐Related Protein (FKRP) gene: limb girdle muscular dystrophy R9 (LGMDR9, formerly LGMD2I) and congenital muscular dystrophies MDC1C, Muscle–Eye–Brain Disease and Walker–Warburg Syndrome. The registry seeks to further understand the natural history and prevalence of FKRP‐related conditions; aid the rapid identification of eligible patients for clinical studies; and provide a source of information to clinical and academic communities. Methods Registration is patient‐initiated through a secure online portal. Data, reported by both patients and their clinicians, include: age of onset, presenting symptoms, family history, motor function and muscle strength, respiratory and cardiac function, medication, quality of life and pain. Results Of 663 registered participants, 305 were genetically confirmed LGMDR9 patients from 23 countries. A majority of LGMDR9 patients carried the common mutation c.826C > A on one or both alleles; 67.9% were homozygous and 28.5% were compound heterozygous for this mutation. The mean ages of symptom onset and disease diagnosis were higher in individuals homozygous for c.826C > A compared with individuals heterozygous for c.826C > A. This divergence was replicated in ages of loss of running ability, wheelchair‐dependence and ventilation assistance; consistent with the milder phenotype associated with individuals homozygous for c.826C > A. In LGMDR9 patients, 75.1% were currently ambulant and 24.6%, nonambulant (unreported in 0.3%). Cardiac impairment was reported in 23.2% (30/129). Interpretation The Global FKRP Registry enables the collection of patient natural history data, which informs academics, healthcare professionals and industry. It represents a trial‐ready cohort of individuals and is centrally placed to facilitate recruitment to clinical studies.publishedVersio

A cell topography-based mechanism for ligand discrimination by the T cell receptor.

The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. Exactly how the TCR does this is unknown. In resting T cells, the TCR is largely unphosphorylated due to the dominance of phosphatases over the kinases expressed at the cell surface. However, when agonist peptides are presented to the TCR by major histocompatibility complex proteins expressed by antigen-presenting cells (APCs), very fast receptor triggering, i.e., TCR phosphorylation, occurs. Recent work suggests that this depends on the local exclusion of the phosphatases from regions of contact of the T cells with the APCs. Here, we developed and tested a quantitative treatment of receptor triggering reliant only on TCR dwell time in phosphatase-depleted cell contacts constrained in area by cell topography. Using the model and experimentally derived parameters, we found that ligand discrimination likely depends crucially on individual contacts being ∼200 nm in radius, matching the dimensions of the surface protrusions used by T cells to interrogate their targets. The model not only correctly predicted the relative signaling potencies of known agonists and nonagonists but also achieved this in the absence of kinetic proofreading. Our work provides a simple, quantitative, and predictive molecular framework for understanding why TCR triggering is so selective and fast and reveals that, for some receptors, cell topography likely influences signaling outcomes.This work was funded by The Wellcome Trust, the UK Medical Research Council, the UK Biotechnology and Biological Sciences Research Council and Cancer Research UK. We thank the Wolfson Imaging Centre, University of Oxford, for access to their microscope facility. We would like to thank the Wellcome Trust for the Sir Henry Dale Fellowship of R.A.F. (WT101609MA), the Royal Society for the University Research Fellowship of S.F.L. (UF120277) and acknowledge a GSK Professorship (D.K.). We are also grateful to Doug Tischer (UCSF, US) and Muaz Rushdi (Georgia Tech, US) for their critical comments on the manuscript

A human gut bacterial genome and culture collection for improved metagenomic analyses

Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota

A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence

Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal analysis of diffuse gliomas from 77 patients (200 tumors) to enlighten the epigenome-based malignant transformation of initially lower-grade gliomas. Intra-subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify predictive biomarkers for assessing the risk of malignant recurrence at early stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic phenotype, and genomic instability. Molecular abnormalities of longitudinal G-CIMP offer possibilities to defy glioblastoma progression