Monroevilhelmsen5006

For female students, the association between drinking and suicidality did not significantly differ by sexual identity; for male students, it was significant regardless of sexual identity and most pronounced among not sure youth. this website Conclusions These results emphasize the need for additional research into the relationship between contemporaneous alcohol use and suicidality, with attention to differences based on sex, sexual orientation, and other factors that may impact these relationships. There is a particular need for research to examine the temporal nature of the association such that evidence-informed, high-impact interventions can be developed to improve suicidality outcomes among sexual minority youth.Introduction To improve the management of overweight and obesity in the primary care setting, an analysis of patient perceptions of weight status and predictors of weight loss attempts for those with overweight and obesity is needed. Methods Primary care patients (n=949) across 5 health systems in the Mid-Atlantic region of the U.S. were surveyed in 2015; data analysis was performed in 2018. Survey data was combined with data via the electronic health record to understand patients' perceptions of weight, factors associated with weight loss efforts, and provider counseling practices. Results Most participants with overweight or obesity perceived themselves as weighing too much and reported trying to lose weight. Furthermore, most participants with obesity reported receiving advice to lose weight by a provider in the past 12 months. However, less than half of patients with overweight reported receiving advice to lose weight, maintain weight, or develop healthy eating and physical activity patterns from a health professional in the past 12 months. Among participants with overweight and obesity, multivariable logistic regression analysis demonstrated that the perception of being overweight and receiving healthcare advice to lose weight had the highest odds of reporting attempted weight loss (OR=5.5, 95% CI=2.7, 11.2 and OR=3.9, 95% CI=1.9, 7.9, respectively). Conclusions The findings emphasize the importance of provider attention to weight management counseling and identifies patients with overweight as needing increased attention by providers.RNA interference (RNAi) plays a key role in insect defense against viruses and transposable elements, and it is being applied as an experimental tool and for insect pest control. However, RNAi efficiency is highly variable for some insects, notably the pea aphid Acyrthosiphon pisum. In this study, we used natural variation in RNAi susceptibility of pea aphids to identify genes that influence RNAi efficiency. Susceptibility to orally-delivered dsRNA against the gut aquaporin gene AQP1 (ds-AQP1) varied widely across a panel of 83 pea aphid genotypes, from zero to total mortality. Genome-wide association between aphid performance on ds-AQP1 supplemented diet and aphid genetic variants yielded 103 significantly associated single nucleotide polymorphisms (SNPs), including variants in 55 genes, at the 10-4 probability cut-off. When ds-AQP1 was co-administered with dsRNA against six candidate genes, aphid mortality was reduced for three (50%) genes the orthologs of the Drosophila genes trachealess (CG8192), headcase (CG 15532) and a gene coding a peritrophin-A domain (CG 8192), indicating that these genes function to promote RNAi efficiency against AQP1 in the pea aphid. Aphid susceptibility (quantified as mortality) to ds-AQP1 was correlated with RNAi against a further gene, snakeskin with essential gut function unrelated to AQP1, for some but not all aphid genotypes tested, suggesting that the determinants of RNAi efficiency may be partly gene-specific. This study demonstrates high levels of natural variation in susceptibility to RNAi and demonstrates the value of harnessing this variation to identify genes influencing RNAi efficiency.The Hippo pathway regulates myriad biological processes in diverse species and is a key cancer signaling network in humans. Although Hippo has been linked to multiple aspects of cancer, its role in this disease is incompletely understood. Large-scale pan-cancer analyses of core Hippo pathway genes reveal that the pathway is mutated at a high frequency only in select human cancers, including malignant mesothelioma and meningioma. Hippo pathway deregulation is also enriched in squamous epithelial cancers. We discuss cancer-related functions of the Hippo pathway and potential explanations for the cancer-restricted mutation profile of core Hippo pathway genes. Greater understanding of Hippo pathway deregulation in cancers will be essential to guide the imminent use of Hippo-targeted therapies.Introduction Data shows that interactions between dietary factors and genetic variants can modulate the association of polymorphisms such as the Melanocortin-4 receptor (MC4R) gene with obesity. Considering the limited data available on this topic we aimed to investigate interactions between dietary patterns (DPs) and MC4R polymorphisms in relation to obesity phenotypes. Methods This cohort study was performed in the framework of Tehran Lipid and Glucose Study; for eligible participants in this study (n=3850), the median follow-up was 4 years. DPs were determined using factor analysis. The genotypes of polymorphisms (17782313rs and 12970134rs) were identified and their interaction with DPs were assessed in relation to incidence of obesity phenotypes including central obesity, general obesity and visceral adiposity dysfunction. Results The mean age of participants (62.5% females) were 37.0±13.7 years. Two main DPs (healthy and unhealthy) were extracted. C-allele carriers of rs17782313 in higher quartiles of the healthy DP score had a significant decrease in the incidence of general obesity, compared to those who had the TT genotype (HR=0.61, 95% CI=0.42-0.89, P interaction=0.01). For rs12970134 A-allele carriers, subjects in the second compared to the first quartile of the healthy DP score, had a significant decrease in the incidence of general obesity (HR=0.68, 95% CI=0.46-0.99). There were no significant interaction between DPs and MC4R variants in relation to other obesity phenotypes. Conclusion Our results indicate that the healthy DP could interact with rs17782313 in relation to incidence of general obesity.Integrated modeling of metabolism and gene regulation continues to be a major challenge in computational biology. While there exist approaches like regulatory flux balance analysis (rFBA), dynamic flux balance analysis (dFBA), resource balance analysis (RBA) or dynamic enzyme-cost flux balance analysis (deFBA) extending classical flux balance analysis (FBA) in various directions, there have been no constraint-based methods so far that allow predicting the dynamics of metabolism taking into account both macromolecule production costs and regulatory events. In this paper, we introduce a new constraint-based modeling framework named regulatory dynamic enzyme-cost flux balance analysis (r-deFBA), which unifies dynamic modeling of metabolism, cellular resource allocation and transcriptional regulation in a hybrid discrete-continuous setting. With r-deFBA, we can predict discrete regulatory states together with the continuous dynamics of reaction fluxes, external substrates, enzymes, and regulatory proteins needed to achieve a cellular objective such as maximizing biomass over a time interval. The dynamic optimization problem underlying r-deFBA can be reformulated as a mixed-integer linear optimization problem, for which there exist efficient solvers.In cell-intrinsic antiviral immunity, cytoplasmic receptors such as retinoic acid-inducible gene I (RIG-I) detect viral double-stranded RNA (dsRNA) and trigger a signaling cascade activating the interferon (IFN) system. This leads to the transcription of hundreds of interferon-stimulated genes (ISGs) with a wide range of antiviral effects. This recognition of dsRNA not only has to be very specific to discriminate foreign from self but also highly sensitive to detect even very low numbers of pathogenic dsRNA molecules. Previous work indicated an influence of the dsRNA length on the binding behavior of RIG-I and its potential to elicit antiviral signaling. However, the molecular mechanisms behind the binding process are still under debate. We compare two hypothesized RIG-I binding mechanisms by translating them into mathematical models and analyzing their potential to describe published experimental data. The models consider the length of the dsRNA as well as known RIG-I binding motifs and describe RIG-I pathway activation after stimulation with dsRNA. We show that internal RIG-I binding sites in addition to cooperative RIG-I oligomerization are essential to describe the experimentally observed RIG-I binding behavior and immune response activation for different dsRNA lengths and concentrations. The combination of RIG-I binding to internal sites on the dsRNA and cooperative oligomerization compensates for a lack of high-affinity binding motifs and triggers a strong antiviral response for long dsRNAs. Model analysis reveals dsRNA length-dependency as a potential mechanism to discriminate between different types of dsRNAs It allows for sensitive detection of small numbers of long dsRNAs, a typical by-product of viral replication, while ensuring tolerance against non-harming small dsRNAs.Wilson's disease is an autosomal recessive disease characterized by excess copper accumulated in the liver and brain. It is caused by mutations in the copper transporter gene ATP7B. However, based on the poor understanding of the transcriptional program involved in the pathogenesis of Wilson's disease and the lack of more safe and efficient therapies, the identification of novel pathways and the establishment of complementary model systems of Wilson's disease are urgently needed. Herein, we generated two zebrafish atp7b-mutant lines using the CRISPR/Cas9 editing system, and the mutants developed hepatic and behavioral deficits similar to those observed in humans with Wilson's disease. Interestingly, we found that atp7b-deficient zebrafish embryos developed liver steatosis under low-dose Cu exposure, and behavioral deficits appeared under high-dose Cu exposure. Analyses of publicly available transcriptomic data from ATP7B-knockout HepG2 cells demonstrated that the HIF-1 signaling pathway is downregulated in ATP7B-knockout HepG2 cells compared with wildtype cells following Cu exposure. The HIF-1 signaling pathway was also downregulated in our atp7b-deficient zebrafish mutants following Cu exposure. Furthermore, we demonstrate that activation of the HIF-1 signaling pathway with the chemical compound FG-4592 or DMOG ameliorates liver steatosis and reduces accumulated Cu levels in zebrafish atp7b deficiency models. These findings introduce a novel prospect that modulation of the HIF-1 signaling pathway should be explored as a novel strategy to reduce copper toxicity in Wilson's disease patients.Purpose To evaluate 4-year outcomes of Descemet membrane endothelial keratoplasty (DMEK) in eyes with prior glaucoma surgery. Design Retrospective, comparative case series METHODS Patients with prior trabeculectomy or glaucoma-drainage-device (GDD) implantation, who later underwent DMEK (study group) were matched for follow-up duration with Fuch's dystrophy DMEK patients (control group). Minimum follow-up was 18 months. Primary outcomes graft survival and rejection rates. Secondary outcomes rates of detachment/rebubble, endothelial cell loss, best spectacle-corrected visual acuity, intraocular pressure and glaucoma medications/surgeries. Sub-group analysis compared eyes with and without a GDD. Results Ninety-four eyes of 91 patients were included. Fifty-one eyes of 49 patients in the study group (GDD=32 eyes, No GDD=19 eyes) and 43 eyes of 42 patients in the control group. Mean follow-up was 37.9±15.2 and 33.8±13.5 months, respectively (p=0.322). Graft-survival probability of the study group at 12, 24, 36, and 48 months was 75%, 60%, 43% and 27%, respectively, compared with a consistent 88% in the control group (p less then 0.