Shared and unique genetic and environmental influences on binge eating and night eating: A Swedish twin study

We applied twin methodology to female and male twin pairs to further understand the nature of the relation between two behaviors associated with eating disorders—binge eating (BE) and night eating (NE) in an effort to determine the extent of overlap of genetic and environmental factors influencing liability to these behaviors. We calculated heritability estimates for males and females for each behavior and applied bivariate twin modeling to the female data to estimate the genetic and environmental correlation between these two traits. Data on BE and NE were derived from the Swedish Twin Study of Adults: Genes and Environment (STAGE) of the Swedish Twin Registry (STR; N = 11604). Prevalence estimates revealed sex differences with females more likely to endorse BE and males more likely to endorse NE. In males, we were only able to estimate univariate heritabilities due to small sample sizes: The heritability for BE was .74 [95% CI = (0.36, 0.93)] and for NE was .44 [95% CI = (0.24, 0.61)]. The best fitting bivariate model for females included additive genetic and unique environmental factors as well as the genetic correlation between BE and NE. Heritability estimates were 0.70 [95% CI = (0.26, 0.77)] for BE and 0.35 [95% CI = (0.17, 0.52)] for NE. The genetic correlation, 0.66 [95% CI = (0.48, 0.96)] suggests considerable overlap in the genetic factors influencing liability to BE and NE. In females, there is considerable overlap in the genetic factors that contribute to these traits, but the incomplete overlap allows for the influence of independent genetic and environmental factors as well. BE and NE in females are therefore best conceptualized as related but not identical traits

A first assessment of the safe brain initiative care bundle for addressing postoperative delirium in the postanesthesia care unit.

BACKGROUND Postoperative delirium (POD) following surgery is a prevalent and distressing condition associated with adverse patient outcomes and an increased healthcare burden. OBJECTIVES To assess the effectiveness of the Safe Brain Initiative care bundle (SBI-CB) in reducing POD in the postanesthesia care unit (PACU). DESIGN A multicenter, quality-improvement initiative with retrospective analysis of collected data. SETTING The study was conducted in the operating rooms and postanesthesia care units (PACUs) of four hospitals across Denmark and Turkey. PATIENTS The convenience sample of patients were aged ≥18 years, scheduled for surgery, and could communicate verbally. Age, sex, preoperative delirium, and the American Society for Anesthesiology physical status classification were used in statistical methods to control for potential confounding influences. INTERVENTION The SBI-CB, 18 delirium-reducing recommendations aligned with international guidelines. The intervention included patient education, staff training, coordination meetings across centers, and a dashboard for the monitoring of outcomes in the PACU. MAIN OUTCOME MEASURES The primary outcome was the POD trend in the PACU during implementation months, assessed through Nu-DESC screening at up to three time points in the PACU. We also examined the length of hospital stay. RESULTS Data were collected from 18,697 adult patients across four hospitals. Initial POD incidence in the PACU after the first three months was 16.36% across all sites (n = 1021). POD in the PACU was observed across all age groups, with peak incidence in younger (18-35 years) and older (>75 years) patients. General anesthesia and longer surgical duration (>1 h) were identified as significant risk factors for POD in the PACU. Matched patients who experienced POD in the PACU had longer stays in hospital, with a mean increase from 35 to 69 h (p < 0.001). Implementation of the SBI-CB was associated with a decreased risk of POD in the PACU for each month of SBI-CB implementation (adjusted odds ratio 0.96, 95% confidence interval: [0.94, 0.97], p < 0.001). CONCLUSIONS The presented pragmatic implementation of a multidisciplinary care bundle, encompassing pre-, intra-, and postoperative measures alongside outcome monitoring, has the potential to significantly reduce the incidence of POD in the PACU. Improved patient outcomes may be achieved for general surgical departments with patient cohorts not typically considered at risk for developing POD. TRIAL REGISTRATION Clinicaltrials.gov, identifier NCT05765162

The Etiology of Multiple Sclerosis: Genetic Evidence for the Involvement of the Human Endogenous Retrovirus HERV-Fc1

We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis

Infliximab Induces Clonal Expansion of γδ-T Cells in Crohn's Disease: A Predictor of Lymphoma Risk?

BACKGROUND: Concominant with the widespread use of combined immunotherapy in the management of Crohn's disease (CD), the incidence of hepato-splenic gamma-delta (γδ)-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process resulting in the selection of malignant γδ-T cell clones. We hypothesised that repeated infusion of anti-TNF-α agents may induce clonal selection and that concurrent treatment with immunomodulators further predisposes patients to γδ-T cell expansion. METHODOLOGY/PRINCIPAL FINDINGS: We investigated dynamic changes in the γδ-T cells of patient with CD following treatment with infliximab (Remicade®; n=20) or adalimumab (Humira®; n=26) using flow cytometry. In patients with a high γδ-T cell level, the γδ-T cells were assessed for clonality. Of these 46 CD patients, 35 had a γδ-T cells level (mean 1.6%) comparable to healthy individuals (mean 2.2%), and 11 CD patients (24%) exhibited an increased level of γδ-T cells (5-15%). In the 18 patients also receiving thiopurines or methotrexate, the average baseline γδ-T cell level was 4.4%. In three male CD patients with a high baseline value, the γδ-T cell population increased dramatically following infliximab therapy. A fourth male patient also on infliximab monotherapy presented with 20% γδ-T cells, which increased to 25% shortly after treatment and was 36% between infusions. Clonality studies revealed an oligoclonal γδ-T cell pattern with dominant γδ-T cell clones. In support of our clinical findings, in vitro experiments showed a dose-dependent proliferative effect of anti-TNF-α agents on γδ-T cells. CONCLUSION/SIGNIFICANCE: CD patients treated with immunomodulators had constitutively high levels of γδ-T cells. Infliximab exacerbated clonal γδ-T cell expansion in vivo and induced γδ-T cell proliferation in vitro. Overall, young, male CD patients with high baseline γδ-T cell levels may be at an increased risk of developing malignant γδ-T cell lymphomas following treatment with anti-TNF-α agents

Infection after primary hip arthroplasty: A comparison of 3 Norwegian health registers

Background and purpose: The aim of the present study was to assess incidence of and risk factors for infection after hip arthroplasty in data from 3 national health registries. We investigated differences in risk patterns between surgical site infection (SSI) and revision due to infection after primary total hip arthroplasty (THA) and hemiarthroplasty (HA). Materials and methods: This observational study was based on prospective data from 2005–2009 on primary THAs and HAs from the Norwegian Arthroplasty Register (NAR), the Norwegian Hip Fracture Register (NHFR), and the Norwegian Surveillance System for Healthcare–Associated Infections (NOIS). The Norwegian Patient Register (NPR) was used for evaluation of case reporting. Cox regression analyses were performed with revision due to infection as endpoint for data from the NAR and the NHFR, and with SSI as the endpoint for data from the NOIS. Results: The 1–year incidence of SSI in the NOIS was 3.0% after THA (167/5,540) and 7.3% after HA (103/1,416). The 1–year incidence of revision due to infection was 0.7% for THAs in the NAR (182/24,512) and 1.5% for HAs in the NHFR (128/8,262). Risk factors for SSI after THA were advanced age, ASA class higher than 2, and short duration of surgery. For THA, the risk factors for revision due to infection were male sex, advanced age, ASA class higher than 1, emergency surgery, uncemented fixation, and a National Nosocomial Infection Surveillance (NNIS) risk index of 2 or more. For HAs inserted after fracture, age less than 60 and short duration of surgery were risk factors of revision due to infection. Interpretation: The incidences of SSI and revision due to infection after primary hip replacements in Norway are similar to those in other countries. There may be differences in risk pattern between SSI and revision due to infection after arthroplasty. The risk patterns for revision due to infection appear to be different for HA and THA

Osteopenia, decreased bone formation and impaired osteoblast development in Sox4 heterozygous mice

The transcription factor Sox4 is vital for fetal development, as Sox4–/– homozygotes die in utero. Sox4 mRNA is expressed in the early embryonic growth plate and is regulated by parathyroid hormone, but its function in bone modeling/remodeling is unknown. We report that Sox4+/– mice exhibit significantly lower bone mass (by dual-energy X-ray absorptiometry) from an early age, and fail to obtain the peak bone mass of wild-type (WT) animals. Microcomputed tomography (μCT), histomorphometry and biomechanical testing of Sox4+/– bones show reduced trabecular and cortical thickness, growth plate width, ultimate force and stiffness compared with WT. Bone formation rate (BFR) in 3-month-old Sox4+/– mice is 64% lower than in WT. Primary calvarial osteoblasts from Sox4+/– mice demonstrate markedly inhibited proliferation, differentiation and mineralization. In these cultures, osterix (Osx) and osteocalcin (OCN) mRNA expression was reduced, whereas Runx2 mRNA was unaffected. No functional defects were found in osteoclasts. Silencing of Sox4 by siRNA in WT osteoblasts replicated the defects observed in Sox4+/– cells. We demonstrate inhibited formation and altered microarchitecture of bone in Sox4+/– mice versus WT, without apparent defects in bone resorption. Our results implicate the transcription factor Sox4 in regulation of bone formation, by acting upstream of Osx and independent of Runx2

Renal function at the time of a myocardial infarction maintains prognostic value for more than 10 years

<p>Abstract</p> <p>Background</p> <p>Renal function is an important predictor of mortality in patients with myocardial infarction (MI), but changes in the impact over time have not been well described.</p> <p>We examined the importance of renal function by estimated GFR (eGFR) and se-creatinine as an independent long-term prognostic factor.</p> <p>Methods</p> <p>Prospective follow-up of 6653 consecutive MI patients screened for entry in the Trandolapril Cardiac Evaluation (TRACE) study. The patients were analysed by Kaplan-Meier survival analysis, landmark analysis and Cox proportional hazard models. Outcome measure was all-cause mortality.</p> <p>Results</p> <p>An eGFR below 60 ml per minute per 1.73 m², consistent with chronic renal disease, was present in 42% of the patients. We divided the patients into 4 groups according to eGFR. Overall, Cox proportional-hazards models showed that eGFR was a significant prognostic factor in the two groups with the lowest eGFR, hazard ratio 1,72 (confidence interval (CI) 1,56-1,91) in the group with the lowest eGFR. Using the eGFR group with normal renal function as reference, we observed an incremental rise in hazard ratio. We divided the follow-up period in 2-year intervals. Landmark analysis showed that eGFR at the time of screening continued to show prognostic effect until 16 years of follow-up. By multivariable Cox regression analysis, the prognostic effect of eGFR persisted for 12 years and of se-creatinine for 10 years. When comparing the lowest group of eGFR with the group with normal eGFR, prognostic significance was present in the entire period of follow-up with a hazard ratio between 1,97 (CI 1,65-2,35) and 1,35 (CI 0,99-1,84) in the 2-year periods.</p> <p>Conclusions</p> <p>One estimate of renal function is a strong and independent long-term prognostic factor for 10-12 years following a MI.</p

Differentiating Protein-Coding and Noncoding RNA: Challenges and Ambiguities

The assumption that RNA can be readily classified into either protein-coding or non-protein–coding categories has pervaded biology for close to 50 years. Until recently, discrimination between these two categories was relatively straightforward: most transcripts were clearly identifiable as protein-coding messenger RNAs (mRNAs), and readily distinguished from the small number of well-characterized non-protein–coding RNAs (ncRNAs), such as transfer, ribosomal, and spliceosomal RNAs. Recent genome-wide studies have revealed the existence of thousands of noncoding transcripts, whose function and significance are unclear. The discovery of this hidden transcriptome and the implicit challenge it presents to our understanding of the expression and regulation of genetic information has made the need to distinguish between mRNAs and ncRNAs both more pressing and more complicated. In this Review, we consider the diverse strategies employed to discriminate between protein-coding and noncoding transcripts and the fundamental difficulties that are inherent in what may superficially appear to be a simple problem. Misannotations can also run in both directions: some ncRNAs may actually encode peptides, and some of those currently thought to do so may not. Moreover, recent studies have shown that some RNAs can function both as mRNAs and intrinsically as functional ncRNAs, which may be a relatively widespread phenomenon. We conclude that it is difficult to annotate an RNA unequivocally as protein-coding or noncoding, with overlapping protein-coding and noncoding transcripts further confounding this distinction. In addition, the finding that some transcripts can function both intrinsically at the RNA level and to encode proteins suggests a false dichotomy between mRNAs and ncRNAs. Therefore, the functionality of any transcript at the RNA level should not be discounted

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age : A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first-and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.Peer reviewe