Congenital absence of the vas deferens (CAVD) is a heterogeneous disorder, largely due to mutations in the cystic fibrosis (CFTR) gene. Patients with unilateral absence of the vas deferens (CUAVD) and patients with CAVD in association with renal agenesis appear to have a different aetiology to those with isolated CAVD. We have studied 134 Spanish CAVD patients [110 congenital bilateral absence of the vas deferens (CBAVD) and 24 CUAVD], 16 of whom (six CBAVD, 10 CUAVD) had additional renal anomalies. Forty-two different CFTR mutations were identified, seven of them being novel. Some 45% of the CFTR mutations were specific to CAVD, and were not found in patients with cystic fibrosis or in the general Spanish population. CFTR mutations were detected in 85% of CBAVD patients and in 38% of those with CUAVD. Among those patients with renal anomalies, 31% carried one CFTR mutation. Anomalies in seminal vesicles and ejaculatory ducts were common in patients with CAVD. The prevalence of cryptorchidism and inguinal hernia appeared to be increased in CAVD patients, as well as nasal pathology and frequent respiratory infections. This study confirms the molecular heterogeneity of CFTR mutations in CAVD, and emphasizes the importance of an extensive CFTR analysis in these patients. In contrast with previous studies, this report suggests that CFTR might have a role in urogenital anomalies.

AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.

The involvement of the five thymidine (5T) variant in intron 8 of the cystic fibrosis membrane regulator (CFTR) gene in congenital bilateral absence of the vas deferens (CBAVD) phenotype has been extensively demonstrated. This variant leads to alternative splicing of the CFTR gene which results in a wild-type transcript and one without exon 9. Little is known about expression of the CFTR gene in the testis. We analysed the level of the aberrantly spliced transcripts in testicular biopsies and correlated it with disease expression. Quantitative RT-PCR analysis in testicular biopsies from control and CBAVD patients showed a correlation between the length of the IVS8-6(T) n tract and the level of alternatively spliced transcripts. Results from histological analysis also suggest an involvement of the alternative transcript in the spermatogenic status of patients, leading to a decreased number of mature sperm forms in the tubule.

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When infection of a prosthesis is suspected the diagnostic procedure should start with a WBC scan followed, if positive, by a BM scan. This procedure reduces the cost, the time required for a diagnosis, and the dose of radiation received by the patient.

Our data indicate that the KIT/KITLG system may be involved in a low sperm count trait in humans.

Introduction Long-term opioid therapy has been found to have a strong impact on the hypothalamic-pituitary-gonadal axis that can be manifested clinically by sexual dysfunction (SD). This event is rarely reported and thus unnoticed and undertreated. Aim To analyze the presence of SD in a large group of patients receiving long-term opioids. Methods A descriptive, cross-sectional pilot study of sexual health was conducted for 2 years in 750 consecutive ambulatory patients with chronic non-cancer pain (CNP) receiving opioids for at least 12 months. Cases that reported SD and matched controls were included. Standardized questionnaires and medical record reviews were used to assess rates of pain at diagnosis, daily morphine equivalent doses, and opioid adverse effects. Main Outcome Measures Sexual function was determined by the Female Sexual Function Index (FSFI; scores = 2–36) and the International Index of Erectile Function erectile function domain (IIEF-EF; scores = 1–30). Results Thirty-three percent of 33% of 750 patients with CNP recorded SD based on their spontaneous notification at the pain unit. Men reported SD significantly more frequently than women (33% vs 25%, respectively, P < .05), although they reported having a regular partner (84% vs 70%, P = .03) and a sexually active life (69% vs 34%, respectively, P = .00) significantly more often. FSFI scores were significantly influenced by sexual activity in lubrication and arousal. IIEF scores were significantly determined by age in satisfaction with sexual intercourse and overall satisfaction. The morphine equivalent dose was significant higher in men than in women (38%; median = 70 mg/d, interquartile range = 43.1–170, 115.5 ± 110.3 mg/d vs median = 60 mg/d, interquartile range = 30–100.6, 76.67 ± 63.79 mg/d, P = .016) at the same mean intensity of pain (P = .54), which correlated to FSFI scores (r = −0.313, P = .01). Conclusion SD is prevalent in patients with CNP and higher in men who received a significantly higher mean opioid dose at the same intensity pain level than women. The morphine equivalent dose was correlated to SD intensity. Evidence-based interventions to support sexual activity and function in CNP are needed.

Objective Abnormal pulmonary vasculature directly affects the development and progression of congenital diaphragmatic hernia (CDH)‐associated pulmonary hypertension (PH). Though overarching structural and cellular changes in CDH‐affected pulmonary arteries have been documented, the precise role of the extracellular matrix (ECM) in the pulmonary artery (PA) pathophysiology remains undefined. Here, we quantify the structural, compositional, and mechanical CDH‐induced changes in the main and distal PA ECM and investigate the efficacy of mesenchymal stem cell‐derived extracellular vesicles (MSC‐EVs) as a therapy to ameliorate pathological vascular ECM changes. Methods Pregnant Sprague‐Dawley rodents were administered nitrofen to induce CDH‐affected pulmonary vasculature in the offspring. A portion of CDH‐affected pups was treated with intravenous infusion of MSC‐EVs (1 × 1010/mL) upon birth. A suite of histological, mechanical, and transmission electron microscopic analyses were utilized to characterize the PA ECM. Results The CDH model main PA presented significantly altered characteristics—including greater vessel thickness, greater lysyl oxidase (LOX) expression, and a relatively lower ultimate tensile strength of 13.6 MPa compared to control tissue (25.1 MPa), suggesting that CDH incurs ECM structural disorganization. MSC‐EV treatment demonstrated the potential to reverse CDH‐related changes, particularly through rapid inhibition of ECM remodeling enzymes (LOX and MMP‐9). Additionally, MSC‐EV treatment bolstered structural aspects of the PA ECM and mitigated pathological disorganization as exhibited by increased medial wall thickness and stiffness that, while not significantly altered, trends away from CDH‐affected tissue. Conclusions These data demonstrate notable ECM remodeling in the CDH pulmonary vasculature, along with the capacity of MSC‐EVs to attenuate pathological ECM remodeling, identifying MSC‐EVs as a potentially efficacious therapeutic for CDH‐associated pulmonary hypertension.