Explore the vast range of titles available.

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila . Developmental deletion of both GSK3 isoforms (α and β) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila . Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-β-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function. Glycogen Synthase Kinase 3 (GSK3) has conserved functions across species but its role in the kidney is unclear. Here, the authors show that in the kidney podocyte cell of mice and related nephrocyte in Drosophila that GSK3 is a master regulator of function both during development and in maturity.

Summary We examined whether men with anabolic‐steroid‐induced hypogonadism (ASIH) seeking testosterone supplementation therapy (TST) regretted their decision to use anabolic‐androgenic steroids (AAS) and what their reasons were for this regret. An anonymous, prospective survey was distributed to 382 men seeking follow‐up treatment for hypogonadism. Prior AAS use was confirmed by self‐report, and men were categorised based upon whether they regretted (R) or did not regret (NR) their use of AAS. The average patient age was 40 ± 0.9 years (n = 79) and 15.2% expressed regret over AAS use. No demographic differences were identified between those who regretted AAS use (n = 12) and those who did not (n = 67). Regret was not related to ASIH diagnosis or to AAS‐related side effects like increased aggression, mood disorders, erectile dysfunction, acne, fluid retention or dyslipidemia. Those who regretted AAS use were significantly more likely to have not comprehended the negative impact on future fertility (P < 0.030). Actual fertility issues were comparable in men who regretted AAS use (16.7%) and those who did not (13%). A total of 15.2% of men regretted using AAS. A lack of awareness regarding the negative long‐term effects on fertility was the primary factor related to regret of AAS use in men with ASIH.

The incidence of hypogonadism and use of testosterone replacement therapy (TRT) are rising, while data evaluating the complexity and quality of health-care information available to patients on the Internet for hypogonadism or TRT are lacking. This study focuses on characterizing the readability, credibility and quality of patient-centered information for hypogonadism on the Internet. A Google search was performed to identify top-ranked websites offering patient-centered information on hypogonadism and TRT. Readability was quantified by reading grade level using several validated instruments. Credibility and quality were determined by several additional criteria, including authorship, references, health-care information quality certification and breadth of topic discussion. Twenty of 75 total sites identified (27%) met the inclusion and exclusion criteria and were evaluated. The mean reading grade level was 13.1 (interquartile range 11.7–15.1), with all websites demonstrating reading levels significantly above recommended levels. Less than half (45%) of the sites were neither authored nor reviewed by a physician, 60% contained at least one reference and 40% were certified for displaying quality health-care information. Over half (55%) did not comprehensively discuss management of hypogonadism or mention treatment-associated risks. In conclusion, the majority of patient-centered information available on the Internet regarding hypogonadism or TRT is of poor quality and too complex for the average patient to comprehend. These results highlight a critical shortage in easily accessible, high-quality, comprehensible online patient health-care information on hypogonadism and TRT.

Endothelial cell dysfunction is associated with cardiovascular disease and vasculogenic erectile dysfunction (ED). Measured via peripheral artery tonometry (PAT), endothelial dysfunction in the penis is an independent predictor of future cardiovascular events. The aim of the study was to determine whether measurement of endothelial dysfunction differentiates men with vasculogenic ED identified by duplex ultrasound from those without. A total of 142 men were retrospectively assessed using patient history, penile duplex ultrasonography (US) and PAT (EndoPAT 2000). ED was self-reported and identified on history. Vasculogenic ED was identified in men who exhibited a peak systolic velocity (PSV) of ⩽25 cm s −1 at 15 min following vasodilator injection. The reactive hyperemia index (RHI), a measurement of endothelial dysfunction in medium/small arteries, and the augmentation index (AI), a measurement of arterial stiffness, were recorded via PAT. Penile duplex US was used to categorize men into those with ED ( n =111) and those without ED ( n =31). The cohort with ED had a PSV of 21±1 cm s −1 (left cavernous artery) and 22±1 cm s −1 (right cavernous artery). The control group without ED had values of 39±2 cm s −1 (left) and 39±2 cm s −1 (right). Given the potential for altered endothelial function in diabetes mellitus, we confirmed that hemoglobin A1c, urinary microalbumin and vibration pulse threshold were not different in men with vasculogenic ED and those without. RHI in patients with ED (1.85±0.06) was significantly decreased compared to controls (2.15±0.2) ( P <0.05). The AI was unchanged when examined in isolation, and when standardized to heart rate. Measurement of endothelial function with EndoPAT differentiates men with vasculogenic ED from those without. RHI could be used as a non-invasive surrogate in the assessment of vasculogenic ED and to identify those patients with higher cardiovascular risk.

Background: The previous epidemiological study of paediatric nephrolithiasis in Britain was conducted more than 30 years ago. Aims: To examine the presenting features, predisposing factors, and treatment strategies used in paediatric stones presenting to a British centre over the past five years. Methods: A total of 121 children presented with a urinary tract renal stone, to one adult and one paediatric centre, over a five year period (1997–2001). All children were reviewed in a dedicated stone clinic and had a full infective and metabolic stone investigative work up. Treatment was assessed by retrospective hospital note review. Results: A metabolic abnormality was found in 44% of children, 30% were classified as infective, and 26% idiopathic. Bilateral stones on presentation occurred in 26% of the metabolic group compared to 12% in the infective/idiopathic group (odds ratio 2.7, 95% CI 1.03 to 7.02). Coexisting urinary tract infection was common (49%) in the metabolic group. Surgically, minimally invasive techniques (lithotripsy, percutaneous nephrolithotomy, and endoscopy) were used in 68% of patients. Conclusions: There has been a shift in the epidemiology of paediatric renal stone disease in the UK over the past 30 years. Underlying metabolic causes are now the most common but can be masked by coexisting urinary tract infection. Treatment has progressed, especially surgically, with sophisticated minimally invasive techniques now employed. All children with renal stones should have a metabolic screen.

PurposeThe understanding of the role of plasma antioxidant levels in male fertility in the USA is limited. In a secondary analysis of the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial, we sought to determine whether serum levels of vitamin E (α-tocopherol), zinc, and selenium were correlated with semen parameters and couple fertility outcomes.MethodsThis study is a secondary analysis of the MOXI clinical trial. The primary endpoints in this secondary analysis include semen parameters, and DNA fragmentation and clinical outcomes including pregnancy and live birth. Analyses were completed using Wilcoxon’s rank-sum test and linear regression models.ResultsAt baseline, the analysis included plasma labs for vitamin E (n = 131), selenium (n = 124), and zinc (n = 128). All baseline plasma values were in the normal ranges. There was no association between selenium, zinc, or vitamin E levels and semen parameters or DNA fragmentation. Baseline antioxidant levels in the male partners did not predict pregnancy or live birth among all couples. Among those randomized to placebo, baseline male antioxidant levels did not differ between those couples with live birth and those that did not conceive or have a live birth.ConclusionsAmong men attending fertility centers in the USA, who have sufficient plasma antioxidant levels of zinc, selenium, or vitamin E, no association was observed between vitamins and semen parameters or clinical outcomes in couples with male infertility. Higher levels of antioxidants among men with circulating antioxidants in the normal range do not appear to confer benefit on semen parameters or male fertility.

Premature ejaculation (PE) represents a common sexual dysfunction and is associated with a negative impact on quality of life and relationships. Recent evidence suggests that on-demand dosing of tramadol is effective at increasing intra-vaginal ejaculatory latency time (IELT) and improving subjective measures of satisfaction. A literature review was performed of journal articles published between January 2000 and July 2014 that matched the keywords 'tramadol' and 'premature ejaculation'. We identified eight relevant articles with the criteria that each article be published in a peer-reviewed journal, represent original work and be written in English. IELT was used as the primary outcome in each of the papers reviewed for efficacy. Additional subjective outcome measures were reviewed where available. Safety was assessed using adverse event data from the individual studies. We found that tramadol in on-demand dosing is effective at lengthening IELT in men with varying degrees of PE and improves patient satisfaction. Tramadol was generally well tolerated, particularly among those taking 25 and 50 mg doses. Although there is a risk of abuse and dependence, these events are rare, particularly at low doses taken intermittently. In conclusion, tramadol is an effective oral therapy for PE that is overall safe and well tolerated.