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The aim of our study was to investigate whether low androgen level inhibits the erectile function of rats by regulating the expression of P2X receptors. Thirty-six 8-week-old male SD rats were randomly divided into six groups sham-operated groups (4w-sham, 8w-sham), castration groups (4w-cast, 8w-cast) and androgen replacement after castration groups (4w-cast + T, 8w-cast + T). The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), the levels of serum testosterone (T) and nitric oxide (NO), and the expression of P2X1, P2X2, P2X3, eNOS, p-eNOS, ROCK1 and ROCK2 in the cavernous tissue of rats were determined. The serum T, ICPmax/MAP and NO levels in penile corpus cavernosum in the castration groups were significantly lower than those in other groups (p less then .01). The protein expression of P2X1, P2X2, P2X3, ROCK1 and ROCK2 in the castration groups was significantly higher than those in other groups (p less then .01). P-eNOS/eNOS of the castration groups were significantly lower than those of other groups (p less then .01). The serum T level was negatively correlated with the expression of P2X1, P2X2 and P2X3 in the corpus cavernosum. Low androgen level inhibits erectile function by up-regulating the expression of P2X1, P2X2, P2X3 and RhoA/Rho-kinase resulting in reducing the ratio of p-eNOS/eNOS and the level of NO in corpus cavernosum of rats. © 2020 Blackwell Verlag GmbH.AIM Previous studies suggest that the use of low-dose aspirin before a colorectal cancer (CRC) diagnosis may be associated with a decreased risk of CRC progression. Data supporting this association, however, have been inconsistent. We evaluate whether the use of pre-diagnostic low-dose aspirin is associated with a lower risk of metastases and all-cause mortality in CRC patients. METHODS Using a large Italian population-based primary care database, we identified a cohort of 7478 patients newly diagnosed with non-metastatic CRC between 2000 and 2013. Use of pre-diagnostic low-dose aspirin was modelled as a time-varying variable and compared with no use of low-dose aspirin. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of incident metastasis and of all-cause mortality associated with pre-diagnostic low-dose aspirin use, both overall and by duration of use. RESULTS There were 314 incident metastatic events and 2189 deaths during a mean follow-up time of 4.4 and 4.7 years, respectively. Overall pre-diagnostic use of low-dose aspirin was not associated with a decreased risk of incident metastasis (HR 0.88; 95% CI 0.63-1.22) or all-cause mortality (HR 1.09; 95% CI 0.96-1.22) in CRC patients. Cumulative duration of aspirin use was not associated with a decreased risk of incident metastasis (p-trend=0.22) or all-cause mortality (p-trend=0.38). These findings remained consistent in sensitivity analyses. CONCLUSION In this real-world, population-based study, the pre-diagnostic use of low-dose aspirin was not associated with a decreased risk of incident metastasis or all-cause mortality in CRC patients. This article is protected by copyright. All rights reserved.Sex chromosome abnormality (SCA) is one of the major causes of male spermatogenesis dysfunction. In our study, we sought to investigate the novel X chromosome inversion leading to severe oligozoospermia. Here, we report two brothers with severe oligozoospermia without any other abnormal clinical phenotype. The chromosome karyotypes in peripheral blood of both brothers were 46, Y, inv (X) (p22.3, q22), and no Y chromosome microdeletion was found. The karyotype of their mother was 46, X, inv (X) (p22.3, q22) and that of their father was 46, XY. This is the first report in China that X chromosomal inversion, 46, Y, inv (X) (p22.3, q22), is associated with severe oligozoospermia. This inversion may be a direct genetic risk factor for spermatogenesis. © 2020 Blackwell Verlag GmbH.BACKGROUND Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity. OBJECTIVES To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed. METHODS This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy ( less then 20, 24-28, and 35-37 weeks of gestation). Offspring neonatal adiposity was estimated by the sum of four skinfolds. Structural equation modelling was conducted to evaluate the direct and indirect relationships among the variables of interest. RESULTS Data on 657 mother-infant pairs (50.7% boys) were analysed. Neonatal boys exhibited lower mean sum of skinfolds compared to girls (20.3 mm, 95% CI 19.7, 21.0 vs 21.5 mm, 95% CI 20.8, 22.2). In boys, maternal HOMA-IR at less then 20 weeks was directly associated with neonatal adiposity (β = 0.35 mm, 95% CI 0.01, 0.70). In girls, maternal HOMA-IR at 24-28 weeks was only indirectly associated with neonatal adiposity, which implies that this association was mediated via maternal HOMA-IR, glucose, triglycerides, and NEFA during pregnancy (β = 0.26 mm, 95% CI 0.08, 0.44). CONCLUSIONS The timing of the role of maternal insulin resistance on neonatal adiposity depends on fetal sex. Although the association was time-dependent, maternal insulin resistance was associated with neonatal adiposity in both sexes. Chk2 Inhibitor II datasheet © 2020 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.This study examined the relationship between oxidation-reduction potential (ORP) in frozen-thawed semen and the post-thaw sperm parameters. Levels of ORP were measured in 25 samples from men presenting for routine infertility work-up and were expressed as millivolt (mV)/106 sperm/ml. Frozen-thawed samples were examined for post-thaw total motility (TM%), progressive motility (PM%), total sperm count (TSC) and ORP. The cryo-survival rate (CSR) was calculated as post-thaw TM/pre-freeze TM × 100. Data are provided as median and interquartile range (25th and 75th percentiles). The post-thaw TM% (10.0% [4.00%, 15.1%]), PM% (5.88% [2.97%, 9.33%]) and TSC (12.5 [10.0, 17.5] × 106 sperm) were significantly lower than the pre-freeze TM% (45.9% [32.9%, 59.1%], PM% (31.5% [24.4%, 40.0%] and TSC (120 [90, 250] ×106 sperm) (p less then .001). Post-thaw ORP (2.62 [2.52, 3.13] mV/106 sperm/ml) was significantly higher than pre-freeze ORP (0.73 [0.54, 1.21] mV/106 sperm/ml; p less then .001). The CSR was 21.7% (11.3%, 31.9%). The post-thaw seminal ORP was negatively correlated with post-thaw TM% (r = -.5; p = .02), PM% (r = -.41; p = .03), TSC (r = -.60; p = .03) and CSR (r = -.52; p = .01). Increased levels of ORP are significantly correlated with poor post-thaw sperm quality and CSR. © 2020 Blackwell Verlag GmbH.We investigated the correlation between the presence of leucocytes in expressed prostatic secretion and the lower urinary tract symptom severity by retrospectively reviewing 699 men with lower urinary tract symptoms. The patients were evaluated by the International Prostate Symptoms Score and the Overactive Bladder Symptoms Score and underwent expressed prostatic secretion testing. Patients were classified into groups 1 and 2 based on the expressed prostatic secretion leucocyte count. The mean total and storage score of the International Prostate Symptoms Score, and mean total Overactive Bladder Symptoms Score were higher in group 1. Urine flow metrics showed that voided volume and maximum flow rate were lower in group 1. The scores for International Prostate Symptoms Score questions 4, 6 and 7 and Overactive Bladder Symptoms Score question 2 were higher in group 1 and showed a weak positive correlation with expressed prostatic secretion. Voided volume and maximum flow rate showed the strongest correlation, although International Prostate Symptoms Score question 7 and Overactive Bladder Symptoms Score question 2 were the only independent predictors of expressed prostatic secretion. Therefore, leucocytes in expressed prostatic secretion are associated with the lower urinary tract symptom severity, particularly nocturnal urination symptoms. © 2020 Blackwell Verlag GmbH.BACKGROUND Direct-acting anti-virals (DAA) are highly effective for hepatitis C virus (HCV) treatment, but perceived risks of medication non-adherence may restrict access to care. Digital medicine programme (DMP) has improved adherence and outcomes for some conditions. AIMS To conduct a prospective, single-arm, open-label study across the United States to assess the impact of DMP on adherence and efficacy in adults with chronic HCV infection at high risk for non-adherence. METHODS Eligible participants were placed on the DMP to evaluate real-time adherence; primary outcome was sustained virological response (SVR) at ≥10 weeks post-treatment. RESULTS Between August 2017 and April 2019, 288 participants (Medicaid, 64.9%; psychiatric disorders, 61.1%; homeless, 9.4%) received DAAs for 8-12 weeks (sofosbuvir/velpatasvir or ledipasvir, 45%; glecaprevir/pibrentasvir, 55%). SVR was achieved in 99.1% of 218 participants who had HCV RNA assessed at ≥10 weeks post-treatment; of the 70 participants who did not have SVR assessed, 17 had SVR4 with HCV RNA assessed at a median (IQR; interquartile range) 5.6 weeks (4.1, 7.9) post-treatment; one completed treatment but did not have HCV RNA assessed, and 52 discontinued treatment early without assessment. Overall, the primary analysed participants (n = 218) actively used the DMP for median (range) 92.9% (12.5%, 100%) of their prescribed treatment time, and overall pill-taking adherence was 95.0% (57.1%, 100%). Participants reported the programme was useful and easy to use through satisfaction surveys. CONCLUSIONS HCV treatment with DMP was accepted by patients and clinicians and may support HCV treatment outcomes among patients at high risk for treatment non-adherence (Clinical trials.gov NCT03164902). © 2020 John Wiley & Sons Ltd.Seminal plasma is intimately connected to sperm physiology and particularly in South American Camelids, has demonstrated to be involved in multiple physiological reproductive events. Different percentages of seminal plasma (0%, 10% and 50%) were added to thawed llama semen samples with the objective of evaluating the interaction with cryopreserved sperm over time (0, 1.5 and 3 hr at 37°C). A total of 20 ejaculates from five adult llama males (n = 5; r = 4) were evaluated. A significant decrease in sperm motility, membrane function and live sperm was observed in all thawed samples (0%, 10% and 50%) at 0 hr when compared to raw semen. Neither morphology nor chromatin condensation was altered in all thawed samples (p > .05), but a significant increase in the percentage of spermatozoa with fragmented DNA was observed after thawing all samples versus raw semen. When evaluating thawed samples over time, a significant decrease of motility and membrane function was observed, while the percentages of total live sperm were preserved over the 3 hr of incubation in all final concentrations evaluated.
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