Doughertyhamrick0696

We explored the functions and mechanisms of N-myc downstream-regulated gene 4 (NDRG4) in an amyloid beta 1-40 induced Alzheimer's disease cell model. The levels of total and phosphorylated Tau protein were significantly up-regulated and cell activity was decreased with increasing Aβ1-40 treatment in SH-SY5Y cells. The expression of NDRG4 mRNA and protein levels were significantly decreased that induced by Aβ1-40 in these cells. NDRG4 overexpression significantly alleviated Aβ1-40-induced SH-SY5Y apoptosis rates and caspases-3/7 activities. Equally, Reactive oxygen species, Mitochondrial membrane potential and Microscale malondialdehyde levels were significantly down-regulated, and Superoxide dismutase activity was increased by NDRG4 overexpression. BDNF protein level and phosphorylation levels of AKT and ERK1/2 were enhanced by NDRG4 overexpression. We also determined that the inhibitory effects of NDRG4 on cell apoptosis and Reactive oxygen species release were partially reversed by BDNF silencing, and by application of the PI3K specific inhibitor (LY294002) or ERK inhibitor (PD98059). These data indicate that NDRG4 attenuates Aβ1-40-induced cell apoptosis and Reactive oxygen species release release, as well as oxidative stress injury. These effects may be mediated through BDNF-induced PI3K/AKT and MEK/ERK pathways.BACKGROUND To determine whether transcatheter aortic valve implantation (TAVI) improves early (30-day) and midterm (1-year) mortality compared with surgical aortic valve replacement (SAVR), we performed an updated meta-analysis of all the currently available randomised controlled trials (RCTs). METHODS To identify all RCTs providing both 30-day and 1‑year mortality after TAVI versus SAVR, PubMed and ClinicalTrials.gov were searched up to and including July 2019. A risk difference (RD) and its 95% confidence interval were generated using data of prespecified outcomes in both the TAVI and SAVR groups. Study-specific estimates were pooled using inverse variance-weighted averages of RDs in the random-effects model. RESULTS We identified seven eligible high-quality RCTs including a total of 7631 as-treated patients. Pooled analyses demonstrated significantly lower 30-day (RD -0.60%; p = 0.046) and 1‑year all-cause mortality (RD -1.12%; p = 0.03) after TAVI than after SAVR. No funnel plot asymmetry was detected for 30-day and 1‑year mortality. Androgen Receptor Antagonist Meta-regression analyses indicated that RDs of 30-day and 1‑year mortality between TAVI and SAVR were not modulated by mean Society of Thoracic Surgeons Predicted Risk of Mortality score. Bleeding complications at 30 days and 1 year and stage 2/3 acute kidney injury at 30 days were significantly less frequent after TAVI than after SAVR, whereas major vascular complications and new permanent pacemaker implantation at 30 days and 1 year were significantly more frequent after TAVI than after SAVR. CONCLUSION The best evidence from the present meta-analysis of all the currently available RCTs suggests that TAVI may reduce 30-day and 1‑year all-cause mortality compared with SAVR.BACKGROUND Chronotropic response to pharmacological stress test is blunted in patients with autonomic neuropathy. The relationship between heart rate (HR) changes during pharmacological stress test and cardiac autonomic dysfunction has not been fully investigated. We assessed the potential interplay between HR response (HRR) and myocardial innervation in patients with suspected or known coronary artery disease (CAD). METHODS AND RESULTS We studied 71 patients with suspected or known CAD referred to pharmacological stress myocardial perfusion imaging and 123I metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy. HRR was calculated as the maximum percent change from baseline according to the formula (peak HR - rest HR)/rest HR × 100. 123I-MIBG heart-to-mediastinum (H/M) ratio was calculated and a late H/M ratio less then  1.6 was considered abnormal. HRR progressively decreased with decreasing late H/M ratio (P for trend = 0.02) and a significant correlation between HRR and late H/M ratio (P = 0.03) was observed. The addition of HRR to a model including age, diabetes, known CAD, left ventricular ejection fraction, and stress-induced ischemia added incremental value in predicting an abnormal late H/M ratio, increasing the global chi-square from 8.09 to 13.8 (P = 0.02). CONCLUSIONS The relationship between HRR and cardiac sympathetic innervation in patients with suspected or known CAD confirms a strong interplay between cardiac response to stress tests and cardiac autonomic activation. This finding suggests that HRR may be used as a surrogate for assessing cardiac sympathetic function.OBJECTIVES To investigate the role of serum fatty acid-binding protein-4 (FABP-4) as a surrogate of obesity and metabolic syndrome in the prediction of the outcome of prostate biopsy. METHODS A prospective pilot study was conducted for patients undergoing prostate needle biopsy (PNB) for clinically suspected prostate cancer (PCa) between June 2016 and August 2017. Fifty consecutive patients with biopsy-proven PCa were included as study group and 50 consecutive patients with negative biopsy were included as a control group. Receiver Operating Characteristic (ROC) curve was used to calculate the area under the curve (AUC) to compare the accuracy of the different parameters in the diagnosis as well as the presence of high-grade PCa (Gleason score 8-9) at PNB. Predictors of the outcome were analyzed using univariate and multivariate logistic regression analysis. RESULTS FABP-4 (AUC 0.75; P  32.3 ng/ml OR 9.2; 95% CI 1.8-45; P = 0.006) and %Free-PSA ≤ 21.9 (OR 5.5; 95% CI 1.1-27; P = 0.03). CONCLUSIONS FABP-4 is an independent predictor for both the diagnosis and high-grade Gleason score at PNB. This novel biomarker might have a promising role in optimizing PNB outcomes.BACKGROUND Penile adhesions may cause pain, bleeding, disfigurement and distress. In the setting of lichen sclerosus (LS), they often recur but current treatment options are limited. We present a novel surgical technique for treatment of recurrent penile adhesions using sub-coronal buccal mucosal graft (BMG) resurfacing. METHODS A retrospective, international multi-institutional study was conducted to include patients with refractory penile adhesions who were treated with this technique. Patients with > 12-month follow-up were included in analysis. The procedure involved circumferential excision of the diseased skin and replacement with a BMG. The primary outcomes were recurrence and surgical complications. Secondary outcomes were patient-reported outcome measures (PROMs) including Sexual Health Inventory for Men (SHIM) questionnaire and Global Response Assessment (GRA) questionnaire measuring functional and esthetic outcomes. RESULTS Twenty-five men underwent the procedure across six institutions between 3/2014 and 11/2019.