Bilateral orchiectomy deteriorates the structure and function of seminal vesicles in a rat model.

The effects of hormone levels on ejaculation are known. In addition to thyroid hormone levels, testosterone levels are also associated with ejaculation, but no consensus has been reached on this issue. Thus, we investigated the effect of decreased testosterone levels due to bilateral orchiectomy on the chemical stimulation-induced ejaculation phases in rats. Twenty-one male Wistar rats were randomized into the orchiectomy, sham, and control groups, with seven rats in each group. Bilateral orchiectomy was performed. The ejaculation parameters were evaluated 5 days after the sham and bilateral orchiectomy operations and the waiting period in the control group. The seminal vesicle (SV) phasic contraction number and increase in basal pressure amplitude were significantly lower in the orchiectomy group (6.9 ± 3.3 and 0.6 ± 0.3 mmHg) than in the sham and control groups (11.2 ± 1.7 and 1.0 ± 0.4 mmHg, and 14.5 ± 6.6 and 1.1 ± 0.2 mmHg, respectively; p = 0.016 and p = 0.03, respectively). The interval between the SV contractions was significantly longer in the orchiectomy group (166.2 ± 104.3 s) than in the sham and control groups (76.0 ± 15.5 s and 63.1 ± 31.1 s, respectively; p = 0.014 (between groups), orchiectomy vs sham p = 0.040 and orchiectomy vs control p = 0.018). The SV weights of the rats were significantly lower in the orchiectomy group (0.14 ± 0.01 g) than in the sham and control groups (0.37 ± 0.05 g and 0.48 ± 0.03 g respectively; p < 0.0001 (between groups), orchiectomy vs sham p < 0.0001 and orchiectomy vs control p < 0.0001). The groups showed no significant differences in ejaculation time, SV basal pressure, SV maximum amplitude, and bulbospongiosus muscle contraction electromyographic activity. Our results partially clarified the relationship between decreased testosterone levels and ejaculation. Decreased testosterone levels caused statistically significant changes in SV functions and affected the ejaculation emission phase.

X-linked myotubular myopathy is associated with epigenetic alterations and is ameliorated by HDAC inhibition.

X-linked myotubular myopathy (XLMTM) is a fatal neuromuscular disorder caused by loss of function mutations in MTM1. At present, there are no directed therapies for XLMTM, and incomplete understanding of disease pathomechanisms. To address these knowledge gaps, we performed a drug screen in mtm1 mutant zebrafish and identified four positive hits, including valproic acid, which functions as a potent suppressor of the mtm1 zebrafish phenotype via HDAC inhibition. We translated these findings to a mouse XLMTM model, and showed that valproic acid ameliorates the murine phenotype. These observations led us to interrogate the epigenome in Mtm1 knockout mice; we found increased DNA methylation, which is normalized with valproic acid, and likely mediated through aberrant 1-carbon metabolism. Finally, we made the unexpected observation that XLMTM patients share a distinct DNA methylation signature, suggesting that epigenetic alteration is a conserved disease feature amenable to therapeutic intervention.

Natural history of a mouse model of X-linked myotubular myopathy.

X-linked myotubular myopathy (XLMTM) is a severe monogenetic disorder of the skeletal muscle. It is caused by loss-of-expression/function mutations in the myotubularin (MTM1) gene. Much of what is known about the disease, as well as the treatment strategies, has been uncovered through experimentation in pre-clinical models, particularly the Mtm1 gene knockout mouse line (Mtm1 KO). Despite this understanding, and the identification of potential therapies, much remains to be understood about XLMTM disease pathomechanisms, and about the normal functions of MTM1 in muscle development. To lay the groundwork for addressing these knowledge gaps, we performed a natural history study of Mtm1 KO mice. This included longitudinal comparative analyses of motor phenotype, transcriptome and proteome profiles, muscle structure and targeted molecular pathways. We identified age-associated changes in gene expression, mitochondrial function, myofiber size and key molecular markers, including DNM2. Importantly, some molecular and histopathologic changes preceded overt phenotypic changes, while others, such as triad structural alternations, occurred coincidentally with the presence of severe weakness. In total, this study provides a comprehensive longitudinal evaluation of the murine XLMTM disease process, and thus provides a critical framework for future investigations.

Nation-wide analysis of the impact of Covid-19 pandemic on daily urology practice in Turkey.

OBJECTIVE: To present a nation-wide analysis of the workload of urology departments in Turkey week-by-week during Covid-19 pandemic. METHODOLOGY: The centres participating in the study were divided into three groups as tertiary referral centres, state hospitals and private practice hospitals. The number of outpatients, inpatients, daily interventions and urological surgeries were recorded prospectively between 9-March-2020 and 31-May-2020. All these variables were recorded for the same time interval of 2019 as well. The weekly change of the workload of urology during pandemic period was evaluated, also the workload of urology and the distributions of certain urological surgeries were compared between the pandemic period and the same time interval of the year 2019. RESULTS: A total of 51 centres participated in the study. The number of outpatients, inpatients, urological surgeries and daily interventions were found to be dramatically decreased by the 3rd week of pandemics in state hospitals and tertiary referral centres; however, the daily urological practice were similar in private practice hospitals throughout the pandemic period. When the workload of urology in pandemic period and the same time interval of the year 2019 were compared, a huge decrease was observed in all variables during pandemic period. However, temporary measures like ureteral stenting, nephrostomy placement and percutaneous cystostomy have been found to increase during Covid-19 pandemic compared with normal life. CONCLUSIONS: Covid-19 pandemic significantly affected the routine daily urological practice likewise other subspecialties and priority was given to emergent and non-deferrable surgeries by urologists in concordance with published clinical guidelines.