Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.

Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB

Does the Spiritual Values/Religion Subscale of the Self-Description Questionnaire III Function Differentially Across Heterosexual and Non-Heterosexual Young Adults? A Measurement Invariance Study

We evaluated the dimensionality and measurement invariance of the Spiritual Values/Religion (SVR) subscale from the Self-Description Questionnaire III across heterosexual and non-heterosexual young adults. We found a one-factor model provided adequate fit to the data for each group, with the SVR items exhibiting configural, metric, and scalar invariance across the two groups. Given that we established measurement invariance, we examined the latent mean difference on the construct and found the heterosexual group reported significantly higher levels of spiritual value/ religion than the non-heterosexual group. Our results provided empirical support for the theorized factor structure of the SVR items and the use of the SVR subscale across heterosexual and non-heterosexual young adults, making the scale a viable option for researchers studying religiosity in these specific subpopulations

Gonorrhoea: tackling the global epidemic in the era of rising antimicrobial resistance.

This Special Issue of Sexual Health aims to collate the latest evidence base focussed on understanding the current epidemic and transmission of gonorrhoea, choice of treatment, molecular epidemiology application, concerns about antimicrobial resistance and alternative prevention and control for gonorrhoea

Antenatal Determinants of Childhood Obesity in High-Risk Offspring: Protocol for the DiGest Follow-Up Study.

Childhood obesity is an area of intense concern internationally and is influenced by events during antenatal and postnatal life. Although pregnancy complications, such as gestational diabetes and large-for-gestational-age birthweight have been associated with increased obesity risk in offspring, very few successful interventions in pregnancy have been identified. We describe a study protocol to identify if a reduced calorie diet in pregnancy can reduce adiposity in children to 3 years of age. The dietary intervention in gestational diabetes (DiGest) study is a randomised, controlled trial of a reduced calorie diet provided by a whole-diet replacement in pregnant women with gestational diabetes. Women receive a weekly dietbox intervention from enrolment until delivery and are blinded to calorie allocation. This follow-up study will assess associations between a reduced calorie diet in pregnancy with offspring adiposity and maternal weight and glycaemia. Anthropometry will be performed in infants and mothers at 3 months, 1, 2 and 3 years post-birth. Glycaemia will be assessed using bloodspot C-peptide in infants and continuous glucose monitoring with HbA1c in mothers. Data regarding maternal glycaemia in pregnancy, maternal nutrition, infant birthweight, offspring feeding behaviour and milk composition will also be collected. The DiGest follow-up study is expected to take 5 years, with recruitment finishing in 2026

Preventing obesity in infants: the growing healthy feasibility trial protocol

INTRODUCTION: Early childhood is an important period for establishing behaviours that will affect weight gain and health across the life course. Early feeding choices, including breast and/or formula, timing of introduction of solids, physical activity and electronic media use among infants and young children are considered likely determinants of childhood obesity. Parents play a primary role in shaping these behaviours through parental modelling, feeding styles, and the food and physical activity environments provided. Children from low socio-economic backgrounds have higher rates of obesity, making early intervention particularly important. However, such families are often more difficult to reach and may be less likely to participate in traditional programs that support healthy behaviours. Parents across all socio-demographic groups frequently access primary health care (PHC) services, including nurses in community health services and general medical practices, providing unparalleled opportunity for engagement to influence family behaviours. One emerging and promising area that might maximise engagement at a low cost is the provision of support for healthy parenting through electronic media such as the Internet or smart phones. The Growing healthy study explores the feasibility of delivering such support via primary health care services. METHODS: This paper describes the Growing healthy study, a non-randomised quasi experimental study examining the feasibility of an intervention delivered via a smartphone app (or website) for parents living in socioeconomically disadvantaged areas, for promoting infant feeding and parenting behaviours that promote healthy rather than excessive weight gain. Participants will be recruited via their primary health care practitioner and followed until their infant is 9 months old. Data will be collected via web-based questionnaires and the data collected inherently by the app itself. ETHICS AND DISSEMINATION: This study received approval from the University of Technology Sydney Ethics committee and will be disseminated via peer-reviewed publications and conference presentations

Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan.

The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes

Eating disorder outcomes : findings from a rapid review of over a decade of research

Background Eating disorders (ED), especially Anorexia Nervosa (AN), are internationally reported to have amongst the highest mortality and suicide rates in mental health. With limited evidence for current pharmacological and/or psychological treatments, there is a grave responsibility within health research to better understand outcomes for people with a lived experience of ED, factors and interventions that may reduce the detrimental impact of illness and to optimise recovery. This paper aims to synthesise the literature on outcomes for people with ED, including rates of remission, recovery and relapse, diagnostic crossover, and mortality. Methods This paper forms part of a Rapid Review series scoping the evidence for the field of ED, conducted to inform the Australian National Eating Disorders Research and Translation Strategy 2021–2031, funded and released by the Australian Government. ScienceDirect, PubMed and Ovid/MEDLINE were searched for studies published between 2009 and 2022 in English. High-level evidence such as meta-analyses, large population studies and Randomised Controlled Trials were prioritised through purposive sampling. Data from selected studies relating to outcomes for people with ED were synthesised and are disseminated in the current review. Results Of the over 1320 studies included in the Rapid Review, the proportion of articles focused on outcomes in ED was relatively small, under 9%. Most evidence was focused on the diagnostic categories of AN, Bulimia Nervosa and Binge Eating Disorder, with limited outcome studies in other ED diagnostic groups. Factors such as age at presentation, gender, quality of life, the presence of co-occurring psychiatric and/or medical conditions, engagement in treatment and access to relapse prevention programs were associated with outcomes across diagnoses, including mortality rates. Conclusion Results are difficult to interpret due to inconsistent study definitions of remission, recovery and relapse, lack of longer-term follow-up and the potential for diagnostic crossover. Overall, there is evidence of low rates of remission and high risk of mortality, despite evidence-based treatments, especially for AN. It is strongly recommended that research in long-term outcomes, and the factors that influence better outcomes, using more consistent variables and methodologies, is prioritised for people with ED

A systematic review and secondary data analysis of the interactions between the serotonin transporter 5-HTTLPR polymorphism and environmental and psychological factors in eating disorders

Objectives: to summarize and synthesize the growing gene x environment (GxE) research investigating the promoter region of the serotonin transporter gene (5-HTTLPR) in the eating disorders (ED) field, and overcome the common limitation of low sample size, by undertaking a systematic review followed by a secondary data meta-analysis of studies identified by the review. Method: a systematic review of articles using PsycINFO, PubMed, and EMBASE was undertaken to identify studies investigating the interaction between 5-HTTLPR and an environmental or psychological factor, with an ED-related outcome variable. Seven studies were identified by the systematic review, with complete data sets of five community (n = 1750, 64.5% female) and two clinical (n = 426,100% female) samples combined to perform four secondary-data analyses: 5-I-M1PR x Traumatic Life Events to predict ED status (n = 909), 5-HTTLPR x Sexual and Physical Abuse to predict bulimic symptoms (n = 1097), 5-HTTLPR x Depression to predict bulimic symptoms (n = 1256), and 5-HTTLPRx Impulsiveness to predict disordered eating (n = 1149). Results: under a multiplicative model, the low function (s) allele of 5-HTTLPR interacted with traumatic life events and experiencing both sexual and physical abuse (but not only one) to predict increased likelihood of an ED and bulimic symptoms, respectively. However, under an additive model there was also an interaction between sexual and physical abuse considered independently and 5-HTTLPR, and no interaction with traumatic life events. No other GxE interactions were significant. Conclusion: early promising results should be followed-up with continued cross-institutional collaboration in order to achieve the large sample sizes necessary for genetic research

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD

Proteomic Analysis of Neisseria gonorrhoeae Biofilms Shows Shift to Anaerobic Respiration and Changes in Nutrient Transport and Outermembrane Proteins

Neisseria gonorrhoeae, the causative agent of gonorrhea, can form biofilms in vitro and in vivo. In biofilms, the organism is more resistant to antibiotic treatment and can serve as a reservoir for chronic infection. We have used stable isotope labeling by amino acids in cell culture (SILAC) to compare protein expression in biofilm and planktonic organisms. Two parallel populations of N. gonorrhoeae strain 1291, which is an arginine auxotroph, were grown for 48 h in continuous-flow chambers over glass, one supplemented with 13C6-arginine for planktonic organisms and the other with unlabeled arginine for biofilm growth. The biofilm and planktonic cells were harvested and lysed separately, and fractionated into three sequential protein extracts. Corresponding heavy (H) planktonic and light (L) biofilm protein extracts were mixed and separated by 1D SDS-PAGE gels, and samples were extensively analyzed by liquid chromatography-mass spectrometry. Overall, 757 proteins were identified, and 152 unique proteins met a 1.5-fold cutoff threshold for differential expression with p-values <0.05. Comparing biofilm to planktonic organisms, this set included 73 upregulated and 54 downregulated proteins. Nearly a third of the upregulated proteins were involved in energy metabolism, with cell envelope proteins making up the next largest group. Of the downregulated proteins, the largest groups were involved in protein synthesis and energy metabolism. These proteomics results were compared with our previously reported results from transcriptional profiling of gonococcal biofilms using microarrays. Nitrite reductase and cytochrome c peroxidase, key enzymes required for anaerobic growth, were detected as highly upregulated in both the proteomic and transcriptomic datasets. These and other protein expression changes observed in the present study were consistent with a shift to anaerobic respiration in gonococcal biofilms, although changes in membrane proteins not explicitly related to this shift may have other functions