Mcleoddencker9863

Objectives This study was conducted to evaluate the potential nephroprotective effects of febuxostat, mirtazapine, and their combination against gentamicin-induced nephrotoxicity.Methods Induction of nephrotoxicity was achieved via gentamicin injection (100 mg/kg, I.P., for 7 days). Two different doses of mirtazapine (15-30 mg/kg), febuxostat (5-10 mg/kg), and their combination were administered daily for 14 days prior to gentamicin injection and then concomitantly with gentamicin for additional 7 days. Nephrotoxicity was evaluated histopathologically and biochemically. Renal caspase-3, extracellular signal-regulated protein kinase 1/2 (ERK1/2), nuclear factor-kappa-β (NF-κβ), and monocyte chemoattractant protein (MCP-1) were assayed.Results Febuxostat and mirtazapine significantly (p less then 0.05) alleviated biochemical and histopathological alterations that were induced by gentamicin and, for the first time, significantly decreased the renal levels of ERK1/2 and MCP-1. Conclusion Febuxostat and mirtazapine were found to have a synergistic impact in reducing gentamicin-induced nephrotoxicity.Expert opinion The utility of nonpurine xanthine oxidase inhibitor, such as febuxostat and mirtazapine are offering a new potential opportunity for the future nephroprotective effects therapy Febuxostat and mirtazapine are found to have a synergistic impact in reducing gentamicin-induced nephrotoxicity.Introduction Pulmonary arterial hypertension (PAH) is a rare, progressive, and severe disease. Since the first demonstration of survival benefit of intravenous epoprostenol in monotherapy in 1996, prostanoids remain the cornerstone for PAH patients at high risk. This review is essential to understand the current situation of this drug among all the therapeutic possibilities concerning this entity.Areas covered The aim of this article is to review the pharmacological properties of epoprostenol and to update its clinical evidence in different specific clinical scenarios. A deep literature search was carried out on the MEDLINE database for published literature before March 2021.Expert opinion Epoprostenol is still the best treatment option for high-risk PAH patients. Nevertheless, there are many unsolved questions drug dosing, its use in combination therapy with other pulmonary vasodilators, and the utility in PAH associated with connective tissue disease, congenital heart disease, or pulmonary veno-occlusive disease are only a few examples. Its safety and efficacy are supported by clinical trials, observational work, and experience, both as monotherapy and in combination therapy. Epoprostenol should be considered a destination treatment in high-risk patients and not only as a bridge to pulmonary transplantation. However, it remains underused in clinical practice.Moral distress arises when constraints outside of healthcare professionals' control prohibit them from acting according to the ethically sound course of action. It can be triggered by poor communication and different perspectives between professionals. We examined whether and how taking the perspective of the other profession reduces moral distress among pediatric intensive care nurses and physicians. Using elements of a previously published scale, we created a Vignette-based Moral Distress Rating Scale (V-MDRS). Study participants from three sites included 105 nurses and 34 physicians who read a patient vignette with their own profession's perspective, completed the V-MDRS, then received the other profession's perspective and completed the V-MDRS again. We conducted semi-structured interviews with nine nurses and nine physicians who completed the V-MDRS to explore how interprofessional perspective-taking impacts moral distress. Nurses experienced higher baseline moral distress than physicians (mean ± standard deviation 31.1 ± 6.9 vs 26.4 ± 5, P less then .001), and at two study sites nurses' moral distress declined after reading the physician's perspective. Findings from interviews suggest that physicians were already sensitized to nurses' perspective and that perspective-taking may be particularly beneficial to cohesive teams with strong relationships. Thus, encouraging interprofessional perspective-taking may mitigate moral distress in healthcare professionals.Introduction This manuscript describes a Phase II, dose-ranging, randomized, double-blind, placebo- and active-controlled, parallel-group study conducted to identify the appropriate dose of beclomethasone dipropionate (BDP) to be used in a single-inhaler extrafine formulation triple combination of BDP, formoterol fumarate and glycopyrronium.Methods Patients aged 18-75 years with poorly-controlled asthma, receiving low/medium-dose inhaled corticosteroid (ICS), and who had forced expiratory volume in the 1st second (FEV1) 50-85% predicted, were randomized to inhale BDP 50, 200 or 400 µg twice daily (BID; total daily doses of 100, 400 and 800 µg), placebo, or the active comparator QVAR® 160 µg BID, all via pressurized metered-dose inhalers for 8 weeks. The primary objective was to evaluate superiority of BDP over placebo for change from baseline in pre-dose morning FEV1 at Week 8. ClinicalTrials.gov NCT03084718.Results Of 610 patients randomized, 559 (91.6%) completed the study. For pre-dose morning FEV1 at Week 8, BDP 200 µg BID was superior to placebo, with a statistically significant difference of 113 ml (95% CI 18, 209); differences vs placebo for BDP 50 and 400 µg BID were not significant (44 [-52, 140] and 93 [-3, 188] ml, respectively). Secondary efficacy endpoint results supported the primary endpoint in identifying BDP 200 µg BID as the appropriate dose. Adverse events were experienced by 23.5, 25.0 and 30.6% patients with BDP 50, 200 and 400 µg BID, 34.7% with placebo, and 30.6% with the active comparator.Conclusion In this dose-ranging study, BDP 200 µg BID offered the optimal balance of efficacy and safety in patients with asthma poorly controlled on low/medium-dose ICS.Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Residual inflammation is thought to promote endothelial dysfunction and cardiovascular disease risk among people living with HIV (PLWH) receiving antiretroviral therapy (ART). Whether the neutrophil-to-lymphocyte ratio (NLR), a putative marker of systemic inflammation, may be associated with endothelial dysfunction has not been investigated in PLWH on stable ART.

In this cross-sectional study, 210 PLWH (mean age 49years, 79% males, 88/7/5% Caucasians/Africans/Hispanics) on long-term ART (median ART duration 8years) were enrolled among those who were afferent to an Infectious Diseases outpatient clinic. The association between NLR and brachial flow-mediated dilation (bFMD) was analysed.

A curvilinear association was observed between logarithmic-NLR and logarithmic-bFMD (R square=0.034, p =0.027), with logarithmic-bFMD decreasing significantly with increasing logarithmic-NLR only in PLWH with high NLR (≥1.47, median NLR) (r=-0.369, p <0.001). AS-703026 However, NLR had a poor accuracy in the prediction of low bFMD (≤4.55, median bFMD) in PLWH with high NLR (55% sensitivity, 80% specificity, Youden index 0.35 for NLR 2.20).

Although there is an inverse association between NLR and bFMD among long-term ART-treated PLWH with high NLR, NLR has a low discriminatory ability toward endothelial dysfunction in this category of patients.

Although there is an inverse association between NLR and bFMD among long-term ART-treated PLWH with high NLR, NLR has a low discriminatory ability toward endothelial dysfunction in this category of patients.Recurrent pregnancy loss (RPL) is one of the most common reproductive failures affecting 1-5% of couples. Smad3 is an effector of signalling of the Transforming Growth Factors-β superfamily (TGF-β), regulating the transcription of several target genes of these cytokines. The objective of this study was to evaluate the influence of a variant on SMAD3 (rs17293443) in RPL. A case-control study was carried out with 149 women who experienced RPL and 159 controls, as well as bioinformatics tools to determine the role of this variant in this condition. Our study showed an allelic (p = 0.023) and genotypic (p  less then  0.01) association of this variant with the RPL. Our functional in silico predictions suggest that this variant causes a change in SMAD3 expression levels. Alterations in the expression of this gene can directly compromise the Smad3-dependent signalling pathway that is fundamental for key processes for gestation such as steroid hormone regulation and implantation, as demonstrated by ontologies analyses performed and the literature. Our findings regarding the involvement of Smad3 on RPL are a novelty in this field, and they seem to be promising to the clinical management of this condition.

To assess the relationship of breastfeeding duration with maternal ultrasound carotid intima-media thickness (CIMT) in later life.

PubMed, Scopus, Web of Science, Embase, and Cochrane Central database searching up to December 15, 2020, for eligible studies that reported on the breastfeeding duration and ultrasound measurement of CIMT in later life. The exposed group corresponded to breastfeeding duration ≥ 6 months whereas the control group was women with breastfeeding of shorter duration or nil breastfeeding. The methodological quality of reviewed articles was appraised using the Newcastle-Ottawa Scale (NOS). Results are reported as the mean difference (MD) or the standardized MD (SMD) and their 95% confidence intervals (CIs). The study was registered in the PROSPERO database.

Of 532 unique studies, three studies met inclusion criteria including 1721 women with a mean age ranging between 36.6 ± 6.9 and 55.7 ± 5.3 years, comparing breastfeeding duration ≥ 6 months

1-5 months (NOS 7-8). Common CIMT was lower in women who breastfed for a longer duration (SMD = -0.10, 95% CI -0.20 to -0.00). Circulating HDL-cholesterol was higher in women with longer breastfeeding duration (MD = 3.25, 95% CI 0.88-5.61). There were no significant differences for total cholesterol, LDL-cholesterol, triglycerides, glucose, and blood pressure between breastfeeding 6 or more months and the control group.

The available studies showed lower CIMT and higher HDL-cholesterol levels in women who breastfed for 6 or more months as compared to controls.

The available studies showed lower CIMT and higher HDL-cholesterol levels in women who breastfed for 6 or more months as compared to controls.Longitudinal Integrated Clerkships (LIC) are known to afford several educational advantages to healthcare students including superior team working skills. This paper explores the perceptions of undergraduate medical students who undertook a rural LIC in Scottish primary care setting, to develop an understanding of their interprofessional learning (IPL) during the LIC placement. A qualitative approach was used to explore the lived experience of five LIC alumni who participated in this longitudinal study. They shared their experiences through written and audio diaries over a period of 1-2 months followed by individual semi-structured interviews. Transcripts were thematically analyzed to identify key themes related to IPL during LIC placements. Data from 12 audio and 9 written diaries and 5 interviews generated the following inter-woven themes with regards to various contextual factors, and the prominent generative mechanisms underlying the positive IPL experience general practice setting afforded interprofessional interactions, longitudinality afforded interprofessional relationships, engagement in nurturing clinical teams, absence of hierarchy, flexibility and autonomy during the LIC, and 'goodwill' expressed toward the LIC programme.