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Jensen Blum posted an update 6 months, 3 weeks ago
GAS5 and p27 levels were found lower in the endometrium samples from patients with endometriosis. Primary ESCs from patients with endometriosis had increased viability, reduced apoptosis, and a relatively uncontrolled cell cycle. Gain- and loss-of-function studies confirmed that GAS5 regulated p27 expression in ESCs. Furthermore, GAS5 level was relatively low in primary endothelial cells from patients with endometriosis and GAS5 acted as an angiogenesis inhibitor by regulating the miR-181c-TIMP3 axis. Thus, lower GAS5 level in endometrium might be related to endometriosis by regulating cell proliferation, apoptosis, cell cycle, and angiogenesis.The current study investigated whether stressful life events and everyday discrimination experiences were associated with using one or more substances in the past 30-days and substance use disorder (SUD) among adults experiencing homelessness. We obtained survey data from adults (N = 501) seeking services at a day shelter. Participants self-reported whether they used cigarettes, other tobacco products, cannabis, alcohol, opioids, amphetamine, and cocaine/crack in the past 30-days, and the total number of substances used were also calculated. We measured stressful life events and everyday discrimination using validated scales. We used multivariable logistic and negative binomial regression analyses to evaluate hypothesised associations. Results indicated that reporting a higher number of stressful life events was associated with past 30-days cannabis, tobacco, alcohol, and other substance use, screening positive for a SUD, and using a greater number of substances in the past 30 days. After accounting for stressful life events, everyday discrimination was associated with only past 30-days cannabis use. Overall, we found that reporting stressful life events was related to current substance use and screening positive for a SUD. Findings suggest that life stressors, and discrimination to a lesser extent, were associated with substance use and SUD among adults experiencing homelessness.Menstrual symptoms include some rhythmical changes and stress perception but women differ in duration and severity of these symptoms. It is not known whether these differences are associated with cortisol awakening response (CAR). The aim of the current study was to follow young women daily for the CAR and menstrual parameters throughout the whole menstrual cycle. Healthy and regularly cycling young women (n = 16, 17 to 31-year-old) participated in the current study. The daily records of severity of problems (DRSP) was filled in daily by the participants. CAR was also assessed daily form the salivary samples collected at a 0-, 15-, 30- and 60-min post-awakening. In terms of daily awakening cortisol profiles, women had either 2-20 (n = 3), or 20-200 (n = 8) or 200-2000 (n = 5) ng/ml cortisol according to the median levels throughout their cycle. CAR was weakly and negatively correlated with DRSP scores but strongly and positively with oestradiol (R2 = 0.300; p = 0.000) and progesterone (R2 = 0.490; p = 0.000) concentrations. Individuals with higher oestradiol and progesterone concentrations did not have high DRSP scores. In conclusion, CAR had a very high between-subject difference but had a low within-subject difference throughout the days of menstrual cycle, suggesting that CAR is a relatively stable personal trait. Moreover, the interplay between cortisol, progesterone and oestradiol appears to be important for the severity of menstrual symptoms.Osteosarcoma is the most common bone tumor in children and young adults. Metastatic and relapsed disease confer poor prognosis, and there have been no improvements in outcomes for several decades. The disease’s biological complexity, lack of drugs developed specifically for osteosarcoma, imperfect preclinical models, and limits of existing clinical trial designs have contributed to lack of progress. The Children’s Oncology Group Bone Tumor Committee established the New Agents for Osteosarcoma Task Force to identify and prioritize agents for inclusion in clinical trials. The group identified multitargeted tyrosine kinase inhibitors, immunotherapies targeting B7-H3, CD47-SIRPα inhibitors, telaglenastat, and epigenetic modifiers as the top agents of interest. Only multitargeted tyrosine kinase inhibitors met all criteria for frontline evaluation and have already been incorporated into an upcoming phase III study concept. The task force will continue to reassess identified agents of interest as new data become available and evaluate novel agents using this method.Homocysteine is an independent risk factor for cardiovascular and cerebrovascular disease and has been proposed to contribute to vascular dysfunction. Dactolisib ic50 We sought to determine in a real-world clinical setting whether homocysteine levels were associated with hypertension mediated organ damage (HMOD) and could guide treatment choices in hypertension. We performed a cross-sectional analysis of prospectively collected data in 145 hypertensive patients referred to our tertiary hypertension clinic at Royal Perth Hospital and analyzed the association of homocysteine with HMOD, renin-angiotensin-aldosterone system (RAAS), and RAAS blockade. The average age of participants was 56 ± 17 years, and there was a greater proportion of males than females (89 vs. 56). Regression analysis showed that homocysteine was significantly associated with PWV (β = 1.99; 95% CI 0.99-3.0; p less then .001), albumin-creatinine ratio (lnACR β = 1.14; 95% CI 0.47, 1.8; p less then .001), 24 h urinary protein excretion (β = 0.7; 95% CI 0.48, 0.92; p less then .001), and estimated glomerular filtration rate (β = -29.4; 95% CI -36.35, -22.4; p less then .001), which persisted after adjusting for potential confounders such as age, sex, 24 h BP, inflammation, smoking, diabetes mellitus (DM), and dyslipidemia. A positive predictive relationship was observed between plasma homocysteine levels and PWV, with every 1.0 µmol/L increase in homocysteine associated with a 0.1 m/s increase in PWV. Homocysteine was significantly associated with elevated aldosterone concentration (β = 0.26; p less then .001), and with attenuation of ACEi mediated systolic BP lowering and regression of HMOD compared to angiotensin receptor blockers in higher physiological ranges of homocysteine. Our results indicate that homocysteine is associated with hypertension mediated vascular damage and could potentially serve to guide first-line antihypertensive therapy.