Slothdougherty9595

In vitro analysis suggests FOLFIRINOX-driven selection of invasive subclones, erased by subsequent mDDRi treatment. Collectively, this preclinical trial substantiates mDDRi in a maintenance setting as a novel therapeutic option and extends the concept to non-germline BRCA1/2-mutant PDAC.Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disease caused by mutation of the COL7A1 gene. RDEB is associated with high levels of TGF-β1, which is likely to be involved in the fibrosis that develops in this disease. Endoglin (CD105) is a type III coreceptor for TGF-β1 and its overexpression in fibroblasts deregulates physiological Smad/Alk1/Alk5 signalling, repressing the synthesis of TGF-β1 and extracellular matrix (ECM) proteins. Raloxifene is a specific estrogen receptor modulator designated as an orphan drug for hereditary hemorrhagic telangiectasia, a rare vascular disease. Raloxifene stimulates endoglin synthesis, which could attenuate fibrosis. By contrast, the antioxidant N-acetylcysteine may have therapeutic value to rectify inflammation, fibrosis and endothelial dysfunction. Thus, we present here a repurposing strategy based on the molecular and functional screening of fibroblasts from RDEB patients with these drugs, leading us to propose the repositioning of these two well-known drugs currently in clinical use, raloxifene and N-acetylcysteine, to counteract fibrosis and inflammation in RDEB. Both compounds modulate the profibrotic events that may ultimately be responsible for the clinical manifestations in RDEB, suggesting that these findings may also be relevant for other diseases in which fibrosis is an important pathophysiological event.The financial and health burdens of stress associated with increased urbanization have led to a demand for mental health enhancement strategies. While some extant literature details mental health benefits of community gardening, a coherent narrative on the construct of resilience and its relationship with the mental health benefits of community gardening is lacking. The present study examined the relationship between community gardening and a number of mental health benefits, in the forms of subjective well-being, stress, resilience potentials, and resilience factors (self-esteem, optimism, and openness). A total of 111 residents in Singapore completed a survey. Results from Multivariate Analysis of Covariance (MANCOVA) and Pearson's correlation analyses show that, after controlling for age and levels of connection to nature, community gardeners reported significantly higher levels of subjective well-being than individual/home gardeners and non-gardeners, indicating that engagement in community gardening may be superior to individual/home gardening or non-gardening outdoor activities. Community gardeners reported higher levels of resilience and optimism than the non-gardening control group. These novel results indicate some potential for mental health benefits in urban environments, specifically in terms of subjective well-being and resilience. These findings have implications for future research in clinical psychology, mental health promotion, and policy.

There are limited clinical data on the association between serum testosterone concentrations and nonalcoholic fatty liver disease (NAFLD) in men. The main aim of this study was to evaluate the association between testosterone concentrations and NAFLD in adult men, in terms of noninvasive indices of NAFLD and hepatic fibrosis.

In this cross-sectional study, 98 men were recruited on an outpatient basis and were divided into low-testosterone (<12nmol/l or <346ng/dl, n=37) or high-testosterone groups (≥12nmol/l or ≥346ng/dl, n=61). Serum testosterone concentrations were measured by immuno-chemiluminescence. Hepatic steatosis index (HSI) and Triglyceride-to-HDL-C ratio (THR), as non-invasive indices of NAFLD, as well as AST-to-Platelet Ratio Index (APRI), fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), as non-invasive indices of hepatic fibrosis, were calculated based on standard formulas.

Both the non-invasive indices of NAFLD (HSI and THR) were higher in low-testosterone compared with high-testosterone group (HSI 47.5±2.9 vs. 38.4±1.0, p=0.005; THR 1.70±0.16 vs. 0.98±0.07, p<0.001). On the contrary, none of the non-invasive indices of hepatic fibrosis was different between groups. HSI (p=0.038), but not THR, remained inversely independently associated with serum testosterone, after adjustment for potential confounders, including sex hormone-binding globulin.

Men with low testosterone concentrations have higher non-invasive indices of NAFLD (HSI and THR), but not of hepatic fibrosis (APRI, FIB-4, NFS), compared with counterparts of high testosterone concentrations. HSI was inversely and independently associated with testosterone concentrations.

Men with low testosterone concentrations have higher non-invasive indices of NAFLD (HSI and THR), but not of hepatic fibrosis (APRI, FIB-4, NFS), compared with counterparts of high testosterone concentrations. Cell Cycle inhibitor HSI was inversely and independently associated with testosterone concentrations.Frailty is a broadly investigated geriatric condition, which is characterized by an increased vulnerability to stressors. It represents an extremely relevant public health issue, increasingly conceptualized in a multidimensional perspective. The concept of cognitive reserve (CR), as originally conceptualized by Stern, has been developed in the past decades as a potential factor able to determine individual differences in cognitive vulnerability and trajectories occurring with aging. Our purpose was to provide a comprehensive review of the literature exploring the relationship between CR dimensions, selected according to the Stern model, and frailty status. A review of the literature on the association between potential CR dimensions and frailty was carried out through PubMed, Web of Knowledge and Scopus. CR expressed in terms of education, occupation, premorbid intelligence quotient and leisure time activities was associated with frailty in both cross-sectional and longitudinal observations. The majority of reviewed evidence suggests a potential protective role of CR factors against the onset and the worsening of frailty among older adults.