Nicolaisensvensson5063

Intravascular hemolysis, a major manifestation of sickle cell disease (SCD) and other diseases, incurs the release of hemoglobin and heme from red blood cells, in turn triggering inflammatory processes. This study investigated the in vitro effects of heme, a major inflammatory DAMP, on the adhesive properties of isolated human neutrophils. Heme (20 and 50 µM) significantly increased the adhesion of neutrophils to fibronectin and to recombinant ICAM-1, under static conditions, even more efficiently than the potent pro-inflammatory cytokine, tumor necrosis factor-α (TNF); a microfluidic assay confirmed that heme stimulated neutrophil adhesion under conditions of shear stress. Heme-induced neutrophil adhesion was associated with the increased activities, but not expressions, of the Mac-1 and LFA-1 integrin subunits, CD11b and CD11a, on the cell surface. Notably, heme (50 µM) significantly induced NFκB translocation in neutrophils, and inhibition of NFκB activity with the BAY11-7082 molecule abolished heme-induced cell adhesion to fibronectin and significantly decreased CD11a activity. Flow cytometric analysis demonstrated major reactive oxygen species (ROS) generation in neutrophils following heme stimulation that could be inhibited by the antioxidant, α-tocopherol, and by BAY11-7082. Furthermore, co-incubation with α-tocopherol abrogated both heme-stimulated neutrophil adhesion and CD11a/CD11b activation. Thus, our data indicate that heme, at clinically relevant concentrations, is a potent activator of neutrophil adhesion, increasing the ligand affinity of the β2 integrins via a mechanism that may be partially mediated by an NFkB-dependent pathway and the generation of ROS. Given the fundamental role that the adhesion of neutrophils to the vascular wall plays in SCD vaso-occlusion and other vascular inflammatory processes, our findings provide further evidence that cell-free heme is a major therapeutic target in the hemolytic diseases.Previous research indicates that Euro-American women are more upset by imagining their male partners committing homosexual infidelities than heterosexual ones. The present studies sought to replicate these findings and extend them to two non-Western cultures wherein masculine men frequently engage in sexual interactions with feminine third-gender males. Across six studies in three cultural locales (Canada, Samoa, and the Istmo Zapotec), women were asked to rate their degree of upset when imagining that their partner committed infidelity that was heterosexual in nature, as well as infidelity that was homosexual. In two Canadian undergraduate samples, women reported greater upset at imagining partner infidelity with a female, whereas a community sample of middle-aged women reported equal upset across infidelity types. Samoan women reported substantially less upset at the thought of partner infidelity with a third-gender male (fa'afafine) than with a female. Istmo Zapotec women reported equal upset toward infidelity with a female or a third-gender male (muxe), whereas a second Zapotec sample reported slightly greater upset at the thought of infidelity with a muxe. Results illustrate how cultural contexts moderate the degree to which same-sex infidelity scenarios are upsetting to women.

Piperazine ferulate, a derivative of ferulic acid has been widely used in clinical practice for cardiovascular and kidney diseases in China. The objective of this meta-analysis was to investigate the benefits by adding piperazine ferulate to angiotensin receptor blockers (ARBs) in diabetic nephropathy patients.

PubMed, Embase, Cochrane Library, Wangfang, VIP, and CNKI database (until March 17, 2021) were comprehensively searched for randomized controlled trials investigating the effects of adding piperazine ferulate to ARBs in diabetic nephropathy patients.

Data were retrieved from 14 RCTs involving 1374 patients. When compared with ARBs alone, co-administration of piperazine ferulate and ARBs significantly reduced urinary albumin excretion rate (weighted mean differences [WMD] - 20.32μg/min; 95% confidence interval [CI] - 28.45 to - 12.19), 24-h proteinuria (WMD - 91.08mg; 95% CI - 107.24 to - 74.91), β2-microglobulin (standard mean difference [SMD] - 2.07; 95% CI - 2.51 to - 1.63), serum level of creatinine (WMD - 8.39μmol/L; 95% CI - 11.87 to - 4.92), fibrinogen (WMD - 0.40g/L; 95% CI - 0.46 to - 0.33), and plasma viscosity (WMD - 0.56mPas; 95% CI - 0.91 to - 0.21). Subgroup analysis showed that the effects of piperazine ferulate on UAER and serum creatinine were stronger in early diabetic nephropathy. However, piperazine ferulate had no significant effects on the serum blood urea nitrogen and fasting blood glucose.

Adding piperazine ferulate to ARBs may achieve additional renal protective benefits, particular in early diabetic nephropathy patients.

Adding piperazine ferulate to ARBs may achieve additional renal protective benefits, particular in early diabetic nephropathy patients.

Prostate cancer is the second most common cancer in men and sixth leading cause of mortality. If not recognized early, patients with advanced prostate cancer can experience debilitating complications which can otherwise be prevented by early androgen deprivation therapy. This research intends to define clear diagnostic tools that will guide practitioners in the rural community setting toward early management of advanced prostate cancer.

We conducted a cross-sectional observational study at three referral hospitals in Kigali, Rwanda on patients who presented with clinical suspicion of advanced prostate cancer over a period of 6months. All patients underwent prostate biopsy as well as metastatic work up (CT or MRI), for those who were eligible. Statistical analysis was done using STATA 14.2.

114 patients were included in the study. The median age was 70years (interquartile range 65-79years). In total 14 (12.3%) patients were found to have benign disease, while 100 (87.7%) patients were found to have canced PSA above 100ng/ml had advanced prostate cancer. Linderalactone Diagnosis of advanced prostate cancer is possible at the community level if PSA testing is utilized and practitioners are well trained.

The results show that there is a significant correlation between clinical findings and advanced prostate cancer. All patients with abnormal DRE and PSA above 100 ng/ml had advanced prostate cancer. Diagnosis of advanced prostate cancer is possible at the community level if PSA testing is utilized and practitioners are well trained.