All-cause and liver-related mortality risk factors in excessive drinkers: Analysis of data from the UK biobank

Background: High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol. Methods: We obtained information from the UK Biobank on approximately 500,000 participants aged 40–70 years at baseline assessment in 2006–2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis. Results: Mortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89–2.17) for all causes, 1.89 (1.69–2.12) for any cancer, 1.87 (1.61–2.17) for any circulatory disease, and 9.40 (7.00–12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment. Conclusions: People with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality

Posterior Decompression and Fusion: Whole-Spine Functional and Clinical Outcomes

The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group

Parenting Styles: A Closer Look at a Well-Known Concept

Although parenting styles constitute a well-known concept in parenting research, two issues have largely been overlooked in existing studies. In particular, the psychological control dimension has rarely been explicitly modelled and there is limited insight into joint parenting styles that simultaneously characterize maternal and paternal practices and their impact on child development. Using data from a sample of 600 Flemish families raising an 8-to-10 year old child, we identified naturally occurring joint parenting styles. A cluster analysis based on two parenting dimensions (parental support and behavioral control) revealed four congruent parenting styles: an authoritative, positive authoritative, authoritarian and uninvolved parenting style. A subsequent cluster analysis comprising three parenting dimensions (parental support, behavioral and psychological control) yielded similar cluster profiles for the congruent (positive) authoritative and authoritarian parenting styles, while the fourth parenting style was relabeled as a congruent intrusive parenting style. ANOVAs demonstrated that having (positive) authoritative parents associated with the most favorable outcomes, while having authoritarian parents coincided with the least favorable outcomes. Although less pronounced than for the authoritarian style, having intrusive parents also associated with poorer child outcomes. Results demonstrated that accounting for parental psychological control did not yield additional parenting styles, but enhanced our understanding of the pattern among the three parenting dimensions within each parenting style and their association with child outcomes. More similarities than dissimilarities in the parenting of both parents emerged, although adding psychological control slightly enlarged the differences between the scores of mothers and fathers

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

NOD2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation

Staphylococcus aureus is a major cause of community-acquired and nosocomial infections including the life-threatening conditions endocarditis, necrotizing pneumonia, necrotizing fasciitis, and septicemia. Toll-like receptor (TLR)-2, a membrane-bound microbial sensor, detects staphylococcal components, but macrophages lacking TLR2 or both TLR2 and TLR4 remain S. aureus responsive, suggesting that an alternative microbial recognition receptor might be involved. The cytoplasmic sensor nucleotide-binding oligomerization domain containing (NOD) 2/caspase recruitment domain (CARD) 15 detects muramyl dipeptide from bacterial peptidoglycans and mediates cytokine responses to S. aureus in vitro, but the physiological significance of these observations is not well defined. Here we show that NOD2-deficient mice exhibit a delayed but ultimately exacerbated ulcerative response and impaired bacterial clearance after s.c. infection with S. aureus. NOD2-dependent recognition of S. aureus and muramyl dipeptide is facilitated by alpha-toxin (alpha-hemolysin), a pore-forming toxin and virulence factor of the pathogen. The action of NOD2 is dependent on IL-1beta-amplified production of IL-6, which promotes rapid bacterial killing by neutrophils. These results significantly broaden the physiological importance of NOD2 in innate immunity from the recognition of bacteria that primarily enter the cytoplasm to the detection of bacteria that typically reside extracellularly and demonstrate that this microbial sensor contributes to the discrimination between commensal bacteria and bacterial pathogens that elaborate pore-forming toxins