Healthy, Wealthy, and Wise? Socioeconomic Status and Morbidity/Mortality

No abstract.

PRimary Care Opioid Use Disorders treatment (PROUD) trial protocol: a pragmatic, cluster-randomized implementation trial in primary care for opioid use disorder treatment

BACKGROUND: Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. METHODS: PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16-90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be \u3e 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims ( electronic health records, [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. DISCUSSION: The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis

The Impact of Long-Term Exposure to Space Environment on Adult Mammalian Organisms: A Study on Mouse Thyroid and Testis

Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis

Palmitoylation Regulates Epidermal Homeostasis and Hair Follicle Differentiation

Palmitoylation is a key post-translational modification mediated by a family of DHHC-containing palmitoyl acyl-transferases (PATs). Unlike other lipid modifications, palmitoylation is reversible and thus often regulates dynamic protein interactions. We find that the mouse hair loss mutant, depilated, (dep) is due to a single amino acid deletion in the PAT, Zdhhc21, resulting in protein mislocalization and loss of palmitoylation activity. We examined expression of Zdhhc21 protein in skin and find it restricted to specific hair lineages. Loss of Zdhhc21 function results in delayed hair shaft differentiation, at the site of expression of the gene, but also leads to hyperplasia of the interfollicular epidermis (IFE) and sebaceous glands, distant from the expression site. The specific delay in follicle differentiation is associated with attenuated anagen propagation and is reflected by decreased levels of Lef1, nuclear β-catenin, and Foxn1 in hair shaft progenitors. In the thickened basal compartment of mutant IFE, phospho-ERK and cell proliferation are increased, suggesting increased signaling through EGFR or integrin-related receptors, with a parallel reduction in expression of the key differentiation factor Gata3. We show that the Src-family kinase, Fyn, involved in keratinocyte differentiation, is a direct palmitoylation target of Zdhhc21 and is mislocalized in mutant follicles. This study is the first to demonstrate a key role for palmitoylation in regulating developmental signals in mammalian tissue homeostasis

The daily association between affect and alcohol use: a meta-analysis of individual participant data

Influential psychological theories hypothesize that people consume alcohol in response to the experience of both negative and positive emotions. Despite two decades of daily diary and ecological momentary assessment research, it remains unclear whether people consume more alcohol on days they experience higher negative and positive affect in everyday life. In this preregistered meta-analysis, we synthesized the evidence for these daily associations between affect and alcohol use. We included individual participant data from 69 studies (N = 12,394), which used daily and momentary surveys to assess affect and the number of alcoholic drinks consumed. Results indicate that people are not more likely to drink on days they experience high negative affect, but are more likely to drink and drink heavily on days high in positive affect. People self-reporting a motivational tendency to drink-to-cope and drink-to-enhance consumed more alcohol, but not on days they experienced higher negative and positive affect. Results were robust across different operationalizations of affect, study designs, study populations, and individual characteristics. These findings challenge the long-held belief that people drink more alcohol following increases in negative affect. Integrating these findings under different theoretical models and limitations of this field of research, we collectively propose an agenda for future research to explore open questions surrounding affect and alcohol use.The present study was funded by the Canadian Institutes of Health Research Grant MOP-115104 (Roisin M. O’Connor), Canadian Institutes of Health Research Grant MSH-122803 (Roisin M. O’Connor), John A. Hartford Foundation Grant (Paul Sacco), Loyola University Chicago Research Support Grant (Tracy De Hart), National Institute for Occupational Safety and Health Grant T03OH008435 (Cynthia Mohr), National Institutes of Health (NIH) Grant F31AA023447 (Ryan W. Carpenter), NIH Grant R01AA025936 (Kasey G. Creswell), NIH Grant R01AA025969 (Catharine E. Fairbairn), NIH Grant R21AA024156 (Anne M. Fairlie), NIH Grant F31AA024372 (Fallon Goodman), NIH Grant R01DA047247 (Kevin M. King), NIH Grant K01AA026854 (Ashley N. Linden-Carmichael), NIH Grant K01AA022938 (Jennifer E. Merrill), NIH Grant K23AA024808 (Hayley Treloar Padovano), NIH Grant P60AA11998 (Timothy Trull), NIH Grant MH69472 (Timothy Trull), NIH Grant K01DA035153 (Nisha Gottfredson), NIH Grant P50DA039838 (Ashley N. Linden-Carmichael), NIH Grant K01DA047417 (David M. Lydon-Staley), NIH Grant T32DA037183 (M. Kushner), NIH Grant R21DA038163 (A. Moore), NIH Grant K12DA000167 (M. Potenza, Stephanie S. O’Malley), NIH Grant R01AA025451 (Bruce Bartholow, Thomas M. Piasecki), NIH Grant P50AA03510 (V. Hesselbrock), NIH Grant K01AA13938 (Kristina M. Jackson), NIH Grant K02AA028832 (Kevin M. King), NIH Grant T32AA007455 (M. Larimer), NIH Grant R01AA025037 (Christine M. Lee, M. Patrick), NIH Grant R01AA025611 (Melissa Lewis), NIH Grant R01AA007850 (Robert Miranda), NIH Grant R21AA017273 (Robert Miranda), NIH Grant R03AA014598 (Cynthia Mohr), NIH Grant R29AA09917 (Cynthia Mohr), NIH Grant T32AA07290 (Cynthia Mohr), NIH Grant P01AA019072 (P. Monti), NIH Grant R01AA015553 (J. Morgenstern), NIH Grant R01AA020077 (J. Morgenstern), NIH Grant R21AA017135 (J. Morgenstern), NIH Grant R01AA016621 (Stephanie S. O’Malley), NIH Grant K99AA029459 (Marilyn Piccirillo), NIH Grant F31AA022227 (Nichole Scaglione), NIH Grant R21AA018336 (Katie Witkiewitz), Portuguese State Budget Foundation for Science and Technology Grant UIDB/PSI/01662/2020 (Teresa Freire), University of Washington Population Health COVID-19 Rapid Response Grant (J. Kanter, Adam M. Kuczynski), U.S. Department of Defense Grant W81XWH-13-2-0020 (Cynthia Mohr), SANPSY Laboratory Core Support Grant CNRS USR 3413 (Marc Auriacombe), Social Sciences and Humanities Research Council of Canada Grant (N. Galambos), and Social Sciences and Humanities Research Council of Canada Grant (Andrea L. Howard)

Contribution of Individual and Environmental Factors to Physical Activity Level among Spanish Adults

BACKGROUND: Lack of physical activity (PA) is a major risk for chronic disease and obesity. The main aims of the present study were to identify individual and environmental factors independently associated with PA and examine the relative contribution of these factors to PA level in Spanish adults. METHODOLOGY/PRINCIPAL FINDINGS: A population-based cross-sectional sample of 3,000 adults (18-75 years old) from Gran Canaria (Spain) was selected using a multistage stratified random sampling method. The participants were interviewed at home using a validated questionnaire to assess PA as well as individual and environmental factors. The data were analyzed using bivariate and multivariate logistic regression. One demographic variable (education), two cognitive (self-efficacy and perceived barriers), and one social environmental (organized format) were independently associated with PA in both genders. Odds ratios ranged between 1.76-2.07 in men and 1.35-2.50 in women (both p<0.05). Individual and environmental factors explained about one-third of the variance in PA level. CONCLUSIONS/SIGNIFICANCE: Self-efficacy and perceived barriers were the most significant factors to meet an adequate level of PA. The risk of insufficient PA was twofold greater in men with primary or lesser studies and who are employed. In women, living in rural environments increased the risk of insufficient PA. The promotion of organized PA may be an efficient way to increase the level of PA in the general population. Improvement in the access to sport facilities and places for PA is a prerequisite that may be insufficient and should be combined with strategies to improve self-efficacy and overcome perceived barriers in adulthood