Although there are multiple histochemical tracers available to label plaques and tangles in the brain to evaluate neuropathology in Alzheimer disease (AD), few of them are versatile in nature and compatible with immunohistochemical procedures. Congo Red (CR) is an anisotropic organic stain discovered to label amyloid beta (Aβ) plaques in the brain. Unfortunately, its use is underappreciated due to its low resolution and brightness as stated in previous studies using bright field microscopy. Here, we modified a previous method to localize both plaques and tangles in brains from humans and a transgenic rodent model of AD for fluorescence microscopic visualization. The plaque staining affinities displayed by CR were compared with fibrillar pattern labeling seen with Thioflavin S. This study summarizes the optimization of protocols in which various parameters have been finetuned. To determine the target CR potentially binds, we have performed double labeling with different antibodies against Aβ as well as phosphorylated Tau. The plaque staining affinities exhibited by CR are compared with those associated with the diffuse pattern of labeling seen with antibodies directed against different epitopes of Aβ. Neither CP13, TNT2 or TOC1 binds all the neurofibrillary tangles as revealed by CR labeling in the human brain. Additionally, we also evaluated double labeling with AT8, AT180, and PHF1. Interestingly, PHF-1 shows 40% colocalization and AT8 shows 15% colocalization with NFT. Thus, CR is a much better marker to detect AD pathologies in human and rodent brains with higher fluorescence intensity relative to other conventional fluorescence markers.
  The impact of reduction of systolic blood pressure or body weight on reduction of cardiovascular events during the treatment with glucagon-like peptide1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter2 inhibitors (SGLT2is) for type2 diabetes is unclear.
 
  We searched Embase and PubMed. We performed meta-analysis using hazard ratio (HR) and 95% confidence interval (CI) as effect size stratified by drug class on six endpoints of interest, which were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), cardiovascular death (CVD), myocardial infarction (MI), stroke, and all-cause death (ACD). We performed meta-regression to assess the difference between GLP-1RAs and SGLT2is, and the impact of reduction of systolic blood pressure or body weight on reduction of cardiovascular events.
 
  We included 11 randomized trials. Compared with placebo, SGLT2is reduced HHF by 32% (HR 0.68, 95% CI 0.60-0.76) whereas GLP-1RAs reduced HHF by only 9% (HR 0.91, 95% CI 0.83-0.99). The bnd ACD in adults with type 2 diabetes. The benefit from SGLT2is on HHF is greater than that from GLP-1RAs, while GLP-1RAs vs. placebo significantly reduce stroke whereas SGLT2is do not. The two drug classes reduce cardiovascular events independent of reductions of systolic blood pressure and body weight.Drug therapies for people with heart failure and preserved ejection fraction (HFpEF) are often limited to diuretics to improve symptoms as no therapies demonstrate a mortality benefit in this cohort. People with diabetes have a high risk of developing HFpEF and vice versa, suggesting shared pathophysiological mechanisms exist, which in turn engenders the potential for shared treatments. Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor which has demonstrated significantly improved cardiovascular and hospitalisation for heart failure (HHF) outcomes in previous cardiovascular outcome trials (CVOTs). These CVOTs include the DECLARE-TIMI and DAPA-HF studies which observed significant benefits for people with heart failure and specifically those with heart failure and reduced ejection fraction (HFrEF), respectively. The ongoing DELIVER study is evaluating the use of dapagliflozin specifically in people with HFpEF, which may have enormous implications for treatment and considerable economic consequences. This will complement previous and other ongoing CVOTs evaluating dapagliflozin use. In this review we discuss the use of SGLT2 inhibitors in HFrEF and HFpEF with a focus on the DELIVER study and its potential health and economic implications.
  Older patients with type 2 diabetes (T2D) are at increased risk of diabetic nephropathy and mild renal insufficiency. This analysis compared the anti-hyperglycemic efficacy and safety of sitagliptin with dapagliflozin in patients ≥ 65years of age with T2D and mild renal insufficiency.
 
  This was a post hoc analysis of data from 410 patients ≥ 65years old who participated in a 24-week, randomized, double-blind clinical trial (CompoSIT-R [comparison of sitagliptin with dapagliflozin in mild renal impairment]; NCT02532855) in T2D patients with mild renal insufficiency and on metformin ± a sulfonylurea; the primary efficacy end point was change in HbA1c at week 24.
 
  Treatment groups were well balanced at baseline (mean HbA1c = 7.7/7.7% and eGFR = 79/76ml/min/1.73m
  for sitagliptin/dapagliflozin). At week 24, LS mean (95% CI) change in HbA1c and percentage of patients with HbA1c < 7% were greater with sitagliptin, - 0.48% and 41%, respectively, compared with dapagliflozin, - 0.36% and 28%; between-group difagliflozin that is consistent with that previously observed in the overall population. Both treatments were generally well tolerated.
  A single-procedure session combining EUS and ERCP (EUS/ERCP) for tissue diagnosis and biliary decompression for pancreatic duct adenocarcinoma (PDAC) is technically feasible. While EUS/ERCP may offer expedience and convenience over an approach of separate procedures sessions, the technical success and risk for complications of a combined approach is unclear.
 
  Compare the effectiveness and safety of EUS/ERCP versus separate session approaches for PDAC.
 
  Study patients (2010-2015) were identified within our ERCP database. Patients were analyzed in three groups based on approach Group A Single-session EUS-FNA and ERCP (EUS/ERCP), Group B EUS-FNA followed by separate, subsequent ERCP (EUS then ERCP), and Group C ERCP with/without separate EUS (ERCP ± EUS).  https://www.selleckchem.com/products/pf-07104091.html  Rates of technical success, number of procedures, complications, and time to initiation of PDAC therapies were compared between groups.
 
  Two hundred patients met study criteria. EUS/ERCP approach (Group A) had a longer index procedure duration (median 66min, p = 0.