Methotrexate, blood pressure and arterial function in rheumatoid arthritis: study protocol.

This article discusses the rationale and design of the study "Methotrexate, blood pressure, and arterial function in rheumatoid arthritis". The recognition that immune activation and excess inflammation favor atherosclerosis has stimulated a significant body of research not only to identify new drugs targeting these pathways but also to repurpose (reposition) existing immunomodulatory medications as atheroprotective agents. Observational studies in patients with rheumatoid arthritis have reported that treatment with methotrexate, a traditional disease-modifying antirheumatic drug, is associated with a significantly lower risk of cardiovascular morbidity and mortality when compared with other disease-modifying antirheumatic drugs.

Socioeconomic status across the early life course predicts gene expression signatures of disease and senescence.

Background: Socioeconomic status (SES) is associated with many chronic diseases, indicators of senescence and mortality. However, the changing salience of SES in the prediction of adult health is not well understood. Using mRNA-seq abundance data from wave V of the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examine the extent to which SES across the early life course is related to gene expression-based signatures for chronic diseases, senescence and inflammation in the late 30s.

Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory gut disorder. Molecular mechanisms underlying the clinical heterogeneity of CD remain poorly understood. MicroRNAs (miRNAs) are important regulators of gut physiology, and several have been implicated in the pathogenesis of adult CD.

Socioeconomic inequalities in early adulthood disrupt the immune transcriptomic landscape via upstream regulators.

Disparities in socio-economic status (SES) predict many immune system-related diseases, and previous research documents relationships between SES and the immune cell transcriptome. Drawing on a bioinformatically-informed network approach, we situate these findings in a broader molecular framework by examining the upstream regulators of SES-associated transcriptional alterations. Data come from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative sample of 4543 adults in the United States.

A Bayesian functional approach to test models of life course epidemiology over continuous time.

Background: Life course epidemiology examines associations between repeated measures of risk and health outcomes across different phases of life. Empirical research, however, is often based on discrete-time models that assume that sporadic measurement occasions fully capture underlying long-term continuous processes of risk.

Methods: We propose (i) the functional relevant life course model (fRLM), which treats repeated, discrete measures of risk as unobserved continuous processes, and (ii) a testing procedure to assign probabilities that the data correspond to conceptual models of life course epidemiology (critical period, sensitive period and accumulation models).

Integrative genome-scale analyses reveal post-transcriptional signatures of early human small intestinal development in a directed differentiation organoid model.

Background: MicroRNAs (miRNAs) are important post-transcriptional gene regulators controlling cellular lineage specification and differentiation during embryonic development, including the gastrointestinal system. However, miRNA-mediated regulatory mechanisms involved in early embryonic development of human small intestine (SI) remains underexplored. To explore candidate roles for miRNAs in prenatal SI lineage specification in humans, we used a multi-omic analysis strategy in a directed differentiation model that programs human pluripotent stem cells toward the SI lineage.

Socioeconomic inequalities in young adulthood disrupt the immune transcriptomic landscape via upstream regulators.

Disparities in socio-economic status (SES) predict many immune system-related diseases, and previous research documents relationships between SES and the immune cell transcriptome. Drawing on a bioinformatically-informed network approach, we situate these findings in a broader molecular framework by examining the upstream regulators of SES-associated transcriptional alterations. Data come from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative sample of 4,543 adults in the United States.

An integrative approach for the analysis of risk and health across the life course: challenges, innovations, and opportunities for life course research.

Life course epidemiology seeks to understand the intricate relationships between risk factors and health outcomes across different stages of life to inform prevention and intervention strategies to optimize health throughout the lifespan. However, extant evidence has predominantly been based on separate analyses of data from individual birth cohorts or panel studies, which may not be sufficient to unravel the complex interplay of risk and health across different contexts. We highlight the importance of a multi-study perspective that enables researchers to: (a) Compare and contrast findings from different contexts and populations, which can help identify generalizable patterns and context-specific factors; (b) Examine the robustness of associations and the potential for effect modification by factors such as age, sex, and socioeconomic status; and (c) Improve statistical power and precision by pooling data from multiple studies, thereby allowing for the investigation of rare exposures and outcomes.

Socioeconomic Inequalities and Molecular Risk for Aging in Young Adulthood.

Diverse manifestations of biological aging often reflect disparities in socioeconomic status (SES). In this paper, we examine associations between indicators of SES and an mRNA-based aging signature during young adulthood, before clinical indications of aging are common. We use data from wave V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of adults aged 33-43 years, with transcriptomic data from a subset of 2,491 participants.

Comprehensive microRNA analysis across genome-edited colorectal cancer organoid models reveals miR-24 as a candidate regulator of cell survival.

Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations.

Suprascapular nerve block for the treatment of adhesive capsulitis: a randomised double-blind placebo-controlled trial.

Objective: Adhesive capsulitis is a common painful shoulder condition. Treatment for the condition remains unsatisfactory. Suprascapular nerve block (SSNB) shows promise as a treatment option for adhesive capsulitis but there are no randomised controlled trials that examine its effect on pain or duration of the condition.

Socioeconomic inequalities in molecular risk for chronic diseases observed in young adulthood.

Many common chronic diseases of aging are negatively associated with socioeconomic status (SES). This study examines whether inequalities can already be observed in the molecular underpinnings of such diseases in the 30s, before many of them become prevalent. Data come from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a large, nationally representative sample of US subjects who were followed for over two decades beginning in adolescence.

Cohort Profile: The Zurich Project on the Social Development from Childhood to Adulthood (z-proso).

The Zurich Project on the Social Development from Childhood to Adulthood (z-proso) began in 2004 in response to the need for a better evidence base to support optimal child social development and prevent crime and violence. Since then, the study has tracked the development of a diverse sample of youths ( = 1,675 in the target sample; ~50% female) from age 7 ( = 1,360) to age 20 ( = 1,180), with primary data collection waves at ages 7, 8, 9, 10, 11, 12, 13, 15, 17, and 20. The study uses a multi-method, multi-informant design that combines teacher, youth, and parent reports with observational and behavioural measures, biosampling, functional imaging, and ecological momentary assessment.

Single-Cell Analysis Reveals Unexpected Cellular Changes and Transposon Expression Signatures in the Colonic Epithelium of Treatment-Naïve Adult Crohn's Disease Patients.

Background & Aims: The intestinal barrier comprises a monolayer of specialized intestinal epithelial cells (IECs) that are critical in maintaining mucosal homeostasis. Dysfunction within various IEC fractions can alter intestinal permeability in a genetically susceptible host, resulting in a chronic and debilitating condition known as Crohn's disease (CD). Defining the molecular changes in each IEC type in CD will contribute to an improved understanding of the pathogenic processes and the identification of cell type-specific therapeutic targets.

Explaining the Occupational Structure of Depressive Symptoms: Precarious Work and Social Marginality across European Countries.

The idea that socioeconomic differences are a "fundamental cause" of health and well-being is the basis for large volumes of research. However, one of the challenges in this area is that of linking socioeconomic positions to etiological mechanisms in theoretically informative ways. The situation is doubly challenging because the expression and meaning of socioeconomic positions and the mechanisms they activate change over time.

Real-Life Retention Rates and Reasons for Switching of Biological DMARDs in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis.

To determine real-life biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) retention rates in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), explore reasons for switching and to compare results to previously published data. Time-to-event analysis for mean treatment duration (estimated as the Restricted Mean Survival Time), b/tsDMARD failure, and b/tsDMARDs switching was performed for 230 patients ( = 147 RA, 46 PsA, 37 AS) who commenced their first b/tsDMARD between 2008 and 2018. Patients were managed in a dedicated "biologics" clinic in a tertiary hospital; the choice of b/tsDMARD was clinician driven based on medical factors and patient preferences.

Multiomic analysis defines the first microRNA atlas across all small intestinal epithelial lineages and reveals novel markers of almost all major cell types.

MicroRNA-mediated regulation is critical for the proper development and function of the small intestinal (SI) epithelium. However, it is not known which microRNAs are expressed in each of the cell types of the SI epithelium. To bridge this important knowledge gap, we performed comprehensive microRNA profiling in all major cell types of the mouse SI epithelium.

PGD2 and CRTH2 counteract Type 2 cytokine-elicited intestinal epithelial responses during helminth infection.

Type 2 inflammation is associated with epithelial cell responses, including goblet cell hyperplasia, that promote worm expulsion during intestinal helminth infection. How these epithelial responses are regulated remains incompletely understood. Here, we show that mice deficient in the prostaglandin D2 (PGD2) receptor CRTH2 and mice with CRTH2 deficiency only in nonhematopoietic cells exhibited enhanced worm clearance and intestinal goblet cell hyperplasia following infection with the helminth Nippostrongylus brasiliensis.

A Bayesian approach to comparing common models of life-course epidemiology.

Background: Life-course epidemiology studies people's health over long periods, treating repeated measures of their experiences (usually risk factors) as predictors or causes of subsequent morbidity and mortality. Three hypotheses or models often guide the analyst in assessing these sequential risks: the accumulation model (all measurement occasions are equally important for predicting the outcome), the critical period model (only one occasion is important) and the sensitive periods model (a catch-all model for any other pattern of temporal dependence).

Methods: We propose a Bayesian omnibus test of these three composite models, as well as post hoc decompositions that identify their best respective sub-models.

The Early Life Course of Body Weight and Gene Expression Signatures for Disease.

We examined the way body-weight patterns through the first 4 decades of life relate to gene expression signatures of common forms of morbidity, including cardiovascular disease (CVD), type 2 diabetes (T2D), and inflammation. As part of wave V of the nationally representative National Longitudinal Study of Adolescent to Adult Health (1997-2018) in the United States, mRNA abundance data were collected from peripheral blood (n = 1,132). We used a Bayesian modeling strategy to examine the relative associations between body size at 5 life stages-birth, adolescence, early adulthood, young adulthood, and adulthood-and gene expression-based disease signatures.

Shoulder range of movement in the general population: age and gender stratified normative data using a community-based cohort.

Background: An understanding of the average range of movement of the shoulder that is normally achievable is an important part of treatment for shoulder disorders. The average range of active shoulder flexion, abduction and external rotation was measured in a population cohort aged 20 years and over without shoulder pain and/or stiffness in order to provide normative shoulder range data.

Methods: Cross-sectional analysis using participants in a community-based longitudinal cohort study.

Decreased Colonic Activin Receptor-Like Kinase 1 Disrupts Epithelial Barrier Integrity in Patients With Crohn's Disease.

Background & Aims: Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn's disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown.

A case series of suprascapular nerve block (with an historical comparator) for shoulder pain in motor neurone disease.

Background: Shoulder pain is a distressing but under-reported and poorly managed symptom in people with motor neurone disease.

Objectives: This study aimed to assess the efficacy of suprascapular nerve block for the management of shoulder pain in patients with motor neurone disease.

Methods: A total of 27 patients with motor neurone disease and shoulder pain were offered a suprascapular nerve block.

Population-based RNA profiling in Add Health finds social disparities in inflammatory and antiviral gene regulation to emerge by young adulthood.

Health in later life varies significantly by individual demographic characteristics such as age, sex, and race/ethnicity, as well as by social factors including socioeconomic status and geographic region. This study examined whether sociodemographic variations in the immune and inflammatory molecular underpinnings of chronic disease might emerge decades earlier in young adulthood. Using data from 1,069 young adults from the National Longitudinal Study of Adolescent to Adult Health (Add Health)-the largest nationally representative and ethnically diverse sample with peripheral blood transcriptome profiles-we analyzed variation in the expression of genes involved in inflammation and type I interferon (IFN) response as a function of individual demographic factors, sociodemographic conditions, and biobehavioral factors (smoking, drinking, and body mass index).