Race- and sex-specific differences in heart failure (HF) risk may be related to differential burden and effect of risk factors. We estimated the population attributable fraction (PAF), which incorporates both prevalence and excess risk of HF associated with each risk factor (obesity, hypertension, diabetes, current smoking, and hyperlipidemia), in specific race-sex groups.
 
  A pooled cohort was created using harmonized data from 6 US longitudinal population-based cohorts. Baseline measurements of risk factors were used to determine prevalence. Relative risk of incident HF was assessed using a piecewise constant hazards model adjusted for age, education, other modifiable risk factors, and the competing risk of death from non-HF causes. Within each race-sex group, PAF of HF was estimated for each risk factor individually and for all risk factors simultaneously.
 
  Of 38 028 participants, 55% were female and 22% Black. Hypertension had the highest PAF among Black men (28.3% [95% CI, 18.7%-36.7%]) and women (25.8% [95% CI, 16.3%-34.2%]). In contrast, PAF associated with obesity was the highest in White men (21.0% [95% CI, 14.6%-27.0%]) and women (17.9% [95% CI, 12.8%-22.6%]). Diabetes disproportionately contributed to HF in Black women (PAF, 16.4% [95% CI, 12.7%-19.9%]).  https://www.selleckchem.com/products/gsk1070916.html  The cumulative PAF of all 5 risk factors was the highest in Black women (51.9% [95% CI, 39.3%-61.8%]).
 
  The observed differences in contribution of risk factors across race-sex groups can inform tailored prevention strategies to mitigate disparities in HF burden. This novel competing risk analysis suggests that a sizeable proportion of HF risk may not be associated with modifiable risk factors.
 The observed differences in contribution of risk factors across race-sex groups can inform tailored prevention strategies to mitigate disparities in HF burden. This novel competing risk analysis suggests that a sizeable proportion of HF risk may not be associated with modifiable risk factors.The use of telemedicine in Penitentiary Centers (PC) is an effective measure to improve quality access to specialized care (secondary prevention) and reduces the inherent costs derived from physical consultations of inmates in hospitals.A 41-year-old female patient under study for abdominal pain located in the epigastrium and mesogastrium with no other associated symptoms. There was no record of previous episodes of pancreatitis and she denied abdominal trauma. Laboratory tests were normal. A CT scan was performed showing an aneurysm of the superior mesenteric vein, varicose veins in the gastrohepatic ligament and left splenorenal shunt.We report a case of a COVID-19 patient presenting fever, headache and dyspnea evolving with severe acute abdominal pain; contrasted computed tomography (CT) scan diagnosed splenic infarction. We emphasize the importance of seeking the identification of complications of SARS-CoV-2 infection, notably thromboembolic events, with the potential to reduce the morbidity and mortality of the disease. Studies on radiological aspects involving the spleen and splenic infarctions associated with COVID-19 are scarce.A 69-year-old female complained of epigastric pain for 6 months. Esophagogastroduodenoscopy showed a transversal submucosal tumor (SMT) in the lower esophagus. Subsequently, endoscopic ultrasonography revealed that a hypoechoic echo lesion (25mm*12mm) originated from muscularis propria layer.To provide insights into the cause of e-cigarette (e-cig) associated lung injury, we examined the effects of propylene glycol (PG) and glycerol (G), two common solvent carriers used to deliver nicotine/flavor, on markers of oxidative stress and inflammation in female B6C3F1 mice which had been used successfully in tobacco smoke (TS)-induced lung carcinogenesis. Mice exposed to air and TS were used as negative and positive controls, respectively. Using LC-MS/MS, we showed that PG/G alone, in the absence of nicotine, significantly increased the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG or its tautomer 8-oxodG), a biomarker of DNA oxidative damage, in lung and plasma of mice; moreover, addition of nicotine (12 and 24 mg/mL) in e-cig liquid appears to suppress the levels of 8-oxodG. Exposure to e-cig aerosols or TS induced nonsignificant increases of plasma C-reactive protein (CRP), a biomarker of inflammation; nonetheless, the levels of fibronectin (FN), a biomarker of tissue injury, were significantly increased by e-cig aerosols or TS. Although preliminary, our data showed that exposure to e-cig aerosols induced a higher score of lung injury than did control air or TS exposure. Our results indicate that the B6C3F1 mouse model may be suitable for an in-depth examination of the impact of e-cig on lung injury associated with oxidative stress and inflammation and this study adds to the growing evidence that the use of e-cig can lead to lung damage.Targeted covalent inhibitors are an important class of drugs and chemical probes. However, relatively few electrophiles meet the criteria for successful covalent inhibitor design. Here we describe α-substituted methacrylamides as a new class of electrophiles suitable for targeted covalent inhibitors. While typically α-substitutions inactivate acrylamides, we show that hetero α-substituted methacrylamides have higher thiol reactivity and undergo a conjugated addition-elimination reaction ultimately releasing the substituent. Their reactivity toward thiols is tunable and correlates with the pKa/pKb of the leaving group. In the context of the BTK inhibitor ibrutinib, these electrophiles showed lower intrinsic thiol reactivity than the unsubstituted ibrutinib acrylamide. This translated to comparable potency in protein labeling, in vitro kinase assays, and functional cellular assays, with improved selectivity. The conjugate addition-elimination reaction upon covalent binding to their target cysteine allows functionalizing α-substituted methacrylamides as turn-on probes. To demonstrate this, we prepared covalent ligand directed release (CoLDR) turn-on fluorescent probes for BTK, EGFR, and K-RasG12C. We further demonstrate a BTK CoLDR chemiluminescent probe that enabled a high-throughput screen for BTK inhibitors. Altogether we show that α-substituted methacrylamides represent a new and versatile addition to the toolbox of targeted covalent inhibitor design.