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Genome wide association studies show there is a genetic component to severe COVID-19. We find evidence that the genome-wide genetic association signal with severe COVID-19 is correlated with that of systemic lupus erythematosus (SLE), having formally tested this using genetic correlation analysis by LD score regression. To identify the shared associated loci and gain insight into the shared genetic effects, using summary level data we performed meta-analyses, a local genetic correlation analysis and fine-mapping using stepwise regression and functional annotation. This identified multiple loci shared between the two traits, some of which exert opposing effects. The locus with most evidence of shared association is TYK2 , a gene critical to the type I interferon pathway, where the local genetic correlation is negative. Another shared locus is CLEC1A , where the direction of effects is aligned, that encodes a lectin involved in cell signaling, and the anti-fungal immune response. Our analyses suggest that several loci with reciprocal effects between the two traits have a role in the defense response pathway, adding to the evidence that SLE risk alleles are protective against infection.

ObjectivesJuvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides.MethodsDense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed.ResultsWe identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA.ConclusionsThe findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.

This paper identifies rare climate challenges in the long-term history of seven areas, three in the subpolar North Atlantic Islands and four in the arid-to-semiarid deserts of the US Southwest. For each case, the vulnerability to food shortage before the climate challenge is quantified based on eight variables encompassing both environmental and social domains. These data are used to evaluate the relationship between the “weight” of vulnerability before a climate challenge and the nature of social change and food security following a challenge. The outcome of this work is directly applicable to debates about disaster management policy.

Abstract Study Objectives The behavioral and cognitive consequences of severe sleep deprivation are well understood. Surprisingly, relatively little is known about the neural correlates of mild and acute sleep restriction on tasks that require sustained vigilance for prolonged periods of time during the day. Methods and Results Event-related potential (ERP) paradigms can reveal insight into the neural correlates underlying visual processing and behavioral responding that is impaired with reduced alertness, as a consequence of sleep loss. Here, we investigated the impact of reduced vigilance following at-home mild sleep restriction to better understand the associated behavioral consequences and changes in information processing revealed by ERPs. As expected, vigilance was reduced (e.g. increased lapses and response slowing) that increased over the course of the experiment in the “sleep restricted” (5 hr sleep) compared with the “sleep-extension” (9 hr sleep) condition. Corresponding to these lapses, we found decreased positivity of visually evoked potentials in the Sleep Restriction vs. Sleep Extension condition emerging from 316 to 449 ms, maximal over parietal/occipital cortex. We also investigated electrophysiological signs of motor-related processing by comparing lateralized readiness potentials (LRPs) and found reduced positivity of LRPs in the Sleep Restriction vs. Sleep Extension condition at 70–40 ms before, and 115–158 ms after a response was made. Conclusions These results suggest that even a single night of mild sleep restriction can negatively affect vigilance, reflected by reduced processing capacity for decision making, and dulls motor preparation and execution.

Single nucleotide polymorphisms (SNPs) in MYH9 and APOL1 on chromosome 22 (c22) are powerfully associated with non-diabetic end-stage renal disease (ESRD) in African Americans (AAs). Many AAs diagnosed with type 2 diabetic nephropathy (T2DN) have non-diabetic kidney disease, potentially masking detection of DN genes. Therefore, genome-wide association analyses were performed using the Affymetrix SNP Array 6.0 in 966 AA with T2DN and 1,032 non-diabetic, non-nephropathy (NDNN) controls, with and without adjustment for c22 nephropathy risk variants. No associations were seen between FRMD3 SNPs and T2DN before adjusting for c22 variants. However, logistic regression analysis revealed seven FRMD3 SNPs significantly interacting with MYH9-a finding replicated in 640 additional AA T2DN cases and 683 NDNN controls. Contrasting all 1,592 T2DN cases with all 1,671 NDNN controls, FRMD3 SNPs appeared to interact with the MYH9 E1 haplotype (e.g., rs942280 interaction p-value = 9.3E⁻⁷ additive; odds ratio [OR] 0.67). FRMD3 alleles were associated with increased risk of T2DN only in subjects lacking two MYH9 E1 risk haplotypes (rs942280 OR = 1.28), not in MYH9 E1 risk allele homozygotes (rs942280 OR = 0.80; homogeneity p-value = 4.3E⁻⁴). Effects were weaker stratifying on APOL1. FRMD3 SNPS were associated with T2DN, not type 2 diabetes per se, comparing AAs with T2DN to those with diabetes lacking nephropathy. T2DN-associated FRMD3 SNPs were detectable in AAs only after accounting for MYH9, with differential effects for APOL1. These analyses reveal a role for FRMD3 in AA T2DN susceptibility and accounting for c22 nephropathy risk variants can assist in detecting DN susceptibility genes.

Background To optimize bariatric surgery results, experts recommend regular practice of physical activity. However, no precise recommendations are available for the pre-surgical period. We aimed to evaluate, in this pilot study, the feasibility of a supervised Pre-Surgical Exercise Training (PreSET) and its short-term clinical impacts in subjects awaiting bariatric surgery. Methods In addition to the usual interdisciplinary lifestyle management, eight women and four men [40.8 (37.6–47.5) years old, BMI = 51.4 (43.8–53.1) kg/m 2 ] underwent the PreSET, which combined both endurance and strength training. They were instructed to perform three physical activity sessions per week during 12 weeks, with at least two sessions per week on site and the possibility to complete missed sessions at home. Before and after the PreSET, anthropometric measures, body composition, physical fitness, quality of life, and physical exercise beliefs were assessed. Results The subjects participated in 57.3 % of the total supervised exercise sessions proposed and presented high satisfaction rates. Our program resulted in a significant improvement in weight ( p = 0.007), physical fitness ( p ≤ 0.05), and quality of life score ( p = 0.012) as well as for the emotions, social interactions, and sexual life subscales ( p < 0.03). Fear of injury ( p = 0.028) and embarrassment during physical activity ( p = 0.028) were significantly decreased, whereas no significant change in confidence in athletic ability and in beliefs in exercise benefits were noticed after the program. Conclusions PreSET is feasible in subjects awaiting bariatric surgery and, combined with an interdisciplinary management, results in several short-term benefits.

The aim of this study was to describe the occurrence and clinical characteristics of symptomatic internal hernias (IH) after laparoscopic bariatric procedures. We conducted a retrospective review of cases of IH after 1,064 laparoscopic gastric bypasses (LGB) and biliopancreatic diversions with duodenal switch (LBPD-DS) performed from September 1998 to August 2002. We documented 35 cases of IH (overall incidence of 3.3%). The IH occurred in 6.0% of patients with retrocolic procedures and 3.3% of patients with antecolic procedures. Most were in the Petersen defect (55.9%) and at the enteroenterostomy site (35.3%). A bimodal presentation was observed, with 22.9% of patients with IH diagnosed in the early postoperative period (2-58 days) and 77.1% in a delayed fashion (187-1,109 days). A laparoscopic approach to the repair of IH was possible in 60.0% of patients. Complications occurred in 18.8% of patients, including one death (2.9%). Complete closure of all mesenteric defects is strongly recommended during laparoscopic bariatric procedures to avoid IH and their associated complications.

BANK1 is a susceptibility gene for several systemic autoimmune diseases in several populations. Using the genome-wide association study (GWAS) data from Europeans (EUR) and African Americans (AA), we performed an extensive fine mapping of ankyrin repeats 1 (BANK1). To increase the SNP density, we used imputation followed by univariate and conditional analysis, combined with a haplotypic and expression quantitative trait locus (eQTL) analysis. The data from Europeans showed that the associated region was restricted to a minimal and dependent set of SNPs covering introns two and three, and exon two. In AA, the signal found in the Europeans was split into two independent effects. All of the major risk associated SNPs were eQTLs, and the risks were associated with an increased BANK1 gene expression. Functional annotation analysis revealed the enrichment of repressive B cell epigenomic marks (EZH2 and H3K27me3) and a strong enrichment of splice junctions. Furthermore, one eQTL located in intron two, rs13106926, was found within the binding site for RUNX3, a transcriptional activator. These results connect the local genome topography, chromatin structure, and the regulatory landscape of BANK1 with co-transcriptional splicing of exon two. Our data defines a minimal set of risk associated eQTLs predicted to be involved in the expression of BANK1 modulated through epigenetic regulation and splicing. These findings allow us to suggest that the increased expression of BANK1 will have an impact on B-cell mediated disease pathways.

Background Over 70 % of people who undergo bariatric surgery (BS) develop excess skin (ES). The physical and psychosocial consequences of ES may become a barrier to the practice of physical activity (PA), which is highly recommended to optimize the results of BS. The purpose of this study was to evaluate the impact of ES on the practice of PA in women who have undergone BS. Methods Questionnaires administered to 26 women having undergone BS 2 ± 0.2 years before (BMI = 29.1 ± 0.8 kg/m 2 ) evaluated the impacts of ES, the practice of PA, physical self-perception, and physical exercise beliefs. We also used the 6-min walking test and muscular endurance tests to evaluate physical fitness and photographs with anatomical markers to quantify ES. Results Of the women, 76.9 % declared mobility limitations due to ES during the practice of PA and 45.2 % stated avoiding PA because of ES which caused flapping and unwelcome stares from others. The women who stated that they avoided PA because of ES had significantly lower physical self-perception and physical fitness and reported experiencing more embarrassment during PA despite no significant difference in the magnitude of ES ( p  = 0.06), BMI, daily life inconveniences, and energy expenditure compared to those women who did not avoid PA. Conclusion Although ES after BS is a barrier to the practice of PA for some women, it does not in itself prevent the regular practice of PA. The main reason women with ES avoid PA seems to have less to do with the magnitude of ES itself and more with psychosocial inconveniences.

Background/Objectives: Understanding influences on food habits is crucial to developing effective strategies to improve dietary quality. Past research shows that the predictors of food habits may be dependent on individuals’ age and sex. Young women are a population of particular concern, as they have one of the greatest disparities between actual and recommended diet. The purpose of this review is to better understand the current body of research on factors that may influence young women’s eating patterns. Methods: A systematic search on PubMed identified studies on the social, behavioral, and psychological predictors of food choices among females 13–24 years in the United States published between 2017 and 2022. Two researchers independently conducted a content analysis of the 48 final articles. The two researchers then jointly identified overarching themes in the literature, with consultation from a third researcher. Results: While social and psychological factors are frequently examined in the current literature, few studies evaluate behavioral influences on young women’s eating habits. Overall, little research has been conducted on diet quality influences among young women, as <2% of articles contained findings that met the inclusion criteria. Conclusions: This analysis indicates that additional research is needed to ascertain predictors of adolescent and young adult women’s food patterns and dietary choices.