Vas deferens to rete testis anastomosis for obstructive azoospermia

ABSTRACT Purpose: This video aims to present an in-depth, step-by-step tutorial on microsurgical reconstruction for obstructive azoospermia, featuring a distinctive case involving anastomosis from vas deferens to rete testis. The primary aim of this endeavor is to offer thorough and practical insights for healthcare professionals and researchers within the realm of reproductive medicine. The video endeavors to disseminate expertise, methodologies, and perspectives that can be advantageous to individuals grappling with obstructive azoospermia, providing a significant contribution to the progress of reproductive medicine and the augmentation of existing treatment alternatives. Materials and Methods: Surgical footage was recorded using the ORBEYE 4K 3D Orbital Camera System by Olympus America, with patient consent acquired for research purposes. Additionally, a retrospective examination of patient records was undertaken to compile relevant medical histories. Results: This video furnishes an exhaustive guide to microsurgical reconstruction for obstructive azoospermia, encompassing a distinctive instance of anastomosis from vas deferens to rete testis. State-of-the-art technology, such as the ORBEYE 4K 3D Orbital Camera, heightens procedural transparency, accentuating the significance of advanced instrumentation. The ethical underpinning is emphasized by obtaining patient consent for footage utilization, and a retrospective chart review augments the repository of valuable patient data. This comprehensive approach serves as an invaluable reservoir of knowledge for medical professionals and underscores excellence in clinical and ethical healthcare research. Conclusions: Anastomosis from vas deferens to rete testis emerges as a viable surgical reconstruction alternative for obstructive azoospermia, particularly when confronted with non-dilated tubules within the epididymis.

The cryoEM structure of the Hendra henipavirus nucleoprotein reveals insights into paramyxoviral nucleocapsid architectures.

We report the first cryoEM structure of the Hendra henipavirus nucleoprotein in complex with RNA, at 3.5 Å resolution, derived from single particle analysis of a double homotetradecameric RNA-bound N protein ring assembly exhibiting D14 symmetry. The structure of the HeV N protein adopts the common bi-lobed paramyxoviral N protein fold; the N-terminal and C-terminal globular domains are bisected by an RNA binding cleft containing six RNA nucleotides and are flanked by the N-terminal and C-terminal arms, respectively. In common with other paramyxoviral nucleocapsids, the lateral interface between adjacent Ni and Ni+1 protomers involves electrostatic and hydrophobic interactions mediated primarily through the N-terminal arm and globular domains with minor contribution from the C-terminal arm. However, the HeV N multimeric assembly uniquely identifies an additional protomer-protomer contact between the Ni+1 N-terminus and Ni-1 C-terminal arm linker. The model presented here broadens the understanding of RNA-bound paramyxoviral nucleocapsid architectures and provides a platform for further insight into the molecular biology of HeV, as well as the development of antiviral interventions.

Vas deferens to rete testis anastomosis for obstructive azoospermia.

PURPOSE: This video aims to present an in-depth, step-by-step tutorial on microsurgical reconstruction for obstructive azoospermia, featuring a distinctive case involving anastomosis from vas deferens to rete testis. The primary aim of this endeavor is to offer thorough and practical insights for healthcare professionals and researchers within the realm of reproductive medicine. The video endeavors to disseminate expertise, methodologies, and perspectives that can be advantageous to individuals grappling with obstructive azoospermia, providing a significant contribution to the progress of reproductive medicine and the augmentation of existing treatment alternatives. MATERIALS AND METHODS: Surgical footage was recorded using the ORBEYE 4K 3D Orbital Camera System by Olympus America, with patient consent acquired for research purposes. Additionally, a retrospective examination of patient records was undertaken to compile relevant medical histories. RESULTS: This video furnishes an exhaustive guide to microsurgical reconstruction for obstructive azoospermia, encompassing a distinctive instance of anastomosis from vas deferens to rete testis. State-of-the-art technology, such as the ORBEYE 4K 3D Orbital Camera, heightens procedural transparency, accentuating the significance of advanced instrumentation. The ethical underpinning is emphasized by obtaining patient consent for footage utilization, and a retrospective chart review augments the repository of valuable patient data. This comprehensive approach serves as an invaluable reservoir of knowledge for medical professionals and underscores excellence in clinical and ethical healthcare research. CONCLUSIONS: Anastomosis from vas deferens to rete testis emerges as a viable surgical reconstruction alternative for obstructive azoospermia, particularly when confronted with non-dilated tubules within the epididymis.

Low-dose prednisone is an effective rescue for deteriorating semen parameters following vasovasostomy

ABSTRACT Objective: This retrospective study aimed to evaluate the effectiveness of low-dose prednisone as a rescue therapy for patients with deteriorating semen parameters following vasovasostomy. Materials and Methods: Electronic medical records were queried at the University of Miami with documented CPT code 55400 (Bilateral Vasovasostomy) between January 2016 and April 2023. Records were then reviewed to identify patients who demonstrated ≥50% decrease in semen parameters, specifically sperm concentration, motility and total motile sperm count. Patients who were treated with 6 weeks of low-dose prednisone were identified, and baseline semen parameters and subsequent changes after prednisone therapy were assessed. A Mann-Whitney U Test was used to compare semen parameter changes before and after prednisone. Adverse effects associated with prednisone were monitored. Results: A total of 8 patients were identified with deteriorating semen parameters who were treated with 6 weeks of low-dose prednisone. Following prednisone therapy, all patients demonstrated improvements in total motile sperm count (TMSC), with a median improvement of 6 million. The median relative improvement in TMSC was 433%. Sperm concentration and motility also improved compared to post-operative baseline. No adverse effects were reported during the treatment period. Conclusions: Low-dose prednisone therapy appears to be a safe and effective intervention for managing deteriorating semen parameters following VV. The observed improvements in TMSC suggest the potential of prednisone to rescue patients with delayed failure after VV. Further research with larger sample sizes is warranted to confirm the safety and efficacy of low-dose prednisone as a rescue therapy in this specific patient population. Optimizing VV outcomes is crucial in male infertility, and further exploration of steroid therapy and innovative biotechnologies is warranted.

Low-dose prednisone is an effective rescue for deteriorating semen parameters following vasovasostomy.

OBJECTIVE: This retrospective study aimed to evaluate the effectiveness of low-dose prednisone as a rescue therapy for patients with deteriorating semen parameters following vasovasostomy. MATERIALS AND METHODS: Electronic medical records were queried at the University of Miami with documented CPT code 55400 (Bilateral Vasovasostomy) between January 2016 and April 2023. Records were then reviewed to identify patients who demonstrated ≥50% decrease in semen parameters, specifically sperm concentration, motility and total motile sperm count. Patients who were treated with 6 weeks of low-dose prednisone were identified, and baseline semen parameters and subsequent changes after prednisone therapy were assessed. A Mann-Whitney U Test was used to compare semen parameter changes before and after prednisone. Adverse effects associated with prednisone were monitored. RESULTS: A total of 8 patients were identified with deteriorating semen parameters who were treated with 6 weeks of low-dose prednisone. Following prednisone therapy, all patients demonstrated improvements in total motile sperm count (TMSC), with a median improvement of 6 million. The median relative improvement in TMSC was 433%. Sperm concentration and motility also improved compared to post-operative baseline. No adverse effects were reported during the treatment period. CONCLUSIONS: Low-dose prednisone therapy appears to be a safe and effective intervention for managing deteriorating semen parameters following VV. The observed improvements in TMSC suggest the potential of prednisone to rescue patients with delayed failure after VV. Further research with larger sample sizes is warranted to confirm the safety and efficacy of low-dose prednisone as a rescue therapy in this specific patient population. Optimizing VV outcomes is crucial in male infertility, and further exploration of steroid therapy and innovative biotechnologies is warranted.

Whisker kinematics in the cerebellum.

The whisker system is widely used as a model system for understanding sensorimotor integration. Purkinje cells in the crus regions of the cerebellum have been reported to linearly encode whisker midpoint, but it is unknown whether the paramedian and simplex lobules as well as their target neurons in the cerebellar nuclei also encode whisker kinematics and if so which ones. Elucidating how these kinematics are represented throughout the cerebellar hemisphere is essential for understanding how the cerebellum coordinates multiple sensorimotor modalities. Exploring the cerebellar hemisphere of mice using optogenetic stimulation, we found that whisker movements can be elicited by stimulation of Purkinje cells in not only crus1 and crus2, but also in the paramedian lobule and lobule simplex; activation of cells in the medial paramedian lobule had on average the shortest latency, whereas that of cells in lobule simplex elicited similar kinematics as those in crus1 and crus2. During spontaneous whisking behaviour, simple spike activity correlated in general better with velocity than position of the whiskers, but it varied between protraction and retraction as well as per lobule. The cerebellar nuclei neurons targeted by the Purkinje cells showed similar activity patterns characterized by a wide variety of kinematic signals, yet with a dominance for velocity. Taken together, our data indicate that whisker movements are much more prominently and diversely represented in the cerebellar cortex and nuclei than assumed, highlighting the rich repertoire of cerebellar control in the kinematics of movements that can be engaged during coordination. KEY POINTS: Excitation of Purkinje cells throughout the cerebellar hemispheres induces whisker movement, with the shortest latency and longest duration within the paramedian lobe. Purkinje cells have differential encoding for the fast and slow components of whisking. Purkinje cells encode not only the position but also the velocity of whiskers. Purkinje cells with high sensitivity for whisker velocity are preferentially located in the medial part of lobule simplex, crus1 and lateral paramedian. In the downstream cerebellar nuclei, neurons with high sensitivity for whisker velocity are located at the intersection between the medial and interposed nucleus.

Primer on Female Infertility for the Reproductive Urologist.

This review is intended to serve as an aid in decision-making and patient counseling for the reproductive urologist when female factor infertility is found concurrently with male factor infertility. This review pairs the pathophysiology of female infertility with its implications for the treatment of male infertility, which most commonly includes ovulatory disorders, tubal abnormalities, and uterine abnormalities. By gaining a deeper understanding of these factors, reproductive urologists can employ a tailored approach to managing male factor infertility, taking into account the female partner's specific medical history.

Sensitivity of Individual and Composite Test Scores from the Cogstate Brief Battery to Mild Cognitive Impairment and Dementia Due to Alzheimer's Disease.

BACKGROUND: The Cogstate Brief Battery (CBB) is a computerized cognitive test battery used commonly to identify cognitive deficits related to Alzheimer's disease (AD). However, AD and normative samples used to understand the sensitivity of the CBB to AD in the clinic have been limited, as have the outcome measures studied. OBJECTIVE: This study investigated the sensitivity of CBB outcomes, including potential composite scores, to cognitive impairment in mild cognitive impairment (MCI) and dementia due to AD, in carefully selected samples. METHODS: Samples consisted of 4,871 cognitively unimpaired adults and 184 adults who met clinical criteria for MCI (Clinical Dementia Rating (CDR) = 0.5) or dementia (CDR > 0.5) due to AD and CBB naive. Speed and accuracy measures from each test were examined, and theoretically- and statistically-derived composites were created. Sensitivity and specificity of classification of cognitive impairment were compared between outcomes. RESULTS: Individual CBB measures of learning and working memory showed high discriminability for AD-related cognitive impairment for CDR 0.5 (AUCs ∼ 0.79-0.88), and CDR > 0.5 (AUCs ∼ 0.89-0.96) groups. Discrimination ability for theoretically derived CBB composite measures was high, particularly for the Learning and Working Memory (LWM) composite (CDR 0.5 AUC = 0.90, CDR > 0.5 AUC = 0.97). As expected, statistically optimized linear composite measures showed strong discrimination abilities albeit similar to the LWM composite. CONCLUSIONS: In older adults, the CBB is effective for discriminating cognitive impairment due to MCI or AD-dementia from unimpaired cognition with the LWM composite providing the strongest sensitivity.

Changes in Running Kinematics and Kinetics Following a 10 km Run.

Background: Little is known about changes in kinetics or kinematics following a 10 km training run. This information has implications on risk of running-related injury. Purpose: The purpose of this study was to examine the effect of a 10 km run on running kinematics and kinetics in a sample of experienced runners. Study Design: Cross-Sectional Study. Subjects: Nineteen runners ages 18-48 (7 female, 12 male) consented to participate including eight (3 female, 5 male) ultra-runners, and 11 (4 female, 7 male) recreational runners. Methods: Following collection of demographic data and completion of a short running survey, participants did a 6-minute run at their self-selected running speed to acclimate to the instrumented treadmill. Reflective markers were placed over designated anatomical landmarks on both sides of the pelvis as well as the left lower extremity and marked with a skin pen. Subjects then ran on the treadmill and 30 seconds of video data were recorded at 240 frames/sec using a high-speed camera for the sagittal plane and the frontal plane. Simultaneously, ground reaction forces (GRFs) were recorded at 1200 Hz through the treadmill's embedded force plates. Each runner then ran 10 km on a paved trail at their self-selected pace. Immediately following the run, reflective markers were reattached, guided by markings placed before the run, and a 30-second post-run trial of the video and GRF data were recorded. Video data were analyzed using Kinovea software to measure the kinematic variables of interest. Paired t-tests with Bonferroni corrections were used to find if significant differences existed between pre- and post-run data for all kinematic and kinetic variables. Results: No significant or clinically relevant differences existed between the pre- and post-run measurements for the kinematic or kinetic variables. The only significant difference noted between the ultra-runners and recreational runners was that the ultra-runners had significantly higher cadence (p=0.045). Conclusions: A 10 km run at a self-selected pace did not result in change in the mean kinematic or kinetic variables in this group of experienced runners. Ultra-runners employ higher cadence than recreational runners, but their kinematics and kinetics are similar. Level of Evidence: Level 3.

Biopsychosocial approach to male chronic pelvic pain syndrome: recent treatments and trials.

INTRODUCTION: Chronic pelvic pain syndrome (CPPS) is a common urologic condition that can cause significant disability in affected individuals. Physiologic explanations of chronic pain are often incomplete; appropriate management of CPPS includes recognition of biological, psychological, and social elements, known as the biopsychosocial model. OBJECTIVE: The aim of this narrative review is to investigate treatments for men with CPPS, with a special focus on those utilizing the biopsychosocial model of care. METHODS: A comprehensive literature search was conducted on the electronic databases PubMed, Embase, and Cochrane Library, using relevant Medical Subject Heading terms and keywords related to CPPS treatments. The search was limited to studies published in English from inception to January 2023. Additionally, reference lists of selected studies were manually reviewed to find studies not identified by the initial search. Studies were included if they investigated pharmacologic or nonpharmacologic treatments for men with CPPS. RESULTS: A total of 30 studies met the inclusion criteria. Antibiotics, α-blockers, nonsteroidal anti-inflammatory drugs, gabapentinoids, antidepressants, and phosphodiesterase type 5 inhibitors were among the pharmacologic agents included in trials attempting to reduce symptoms of male CPPS. Studies that focused on treating CPPS without medication included interventions such as shockwave therapy, acupuncture, physical therapy, botulinum toxin, cryotherapy, electrotherapy, exercise, and cognitive behavioral therapy. CONCLUSION: α-Blockers and nonsteroidal anti-inflammatory drugs have shown promising results in treating CPPS in men, while the effectiveness of antibiotics remains controversial. Antidepressants and phosphodiesterase type 5 inhibitors may also be useful in decreasing symptoms in patients with CPPS. Treatments such as pelvic floor muscle therapy, acupuncture, shockwave therapy, and cognitive behavioral therapy must be considered effective complements to medical management in men with CPPS. While these interventions demonstrate benefits as monotherapies, the individualization and combination of treatment modalities are likely to result in reduced pain and improved quality of life.

Fertility outcomes in men with prior history of anabolic steroid use.

OBJECTIVE: To study sperm parameters recovery and fertility outcomes in men with azoospermia or severe oligospermia caused by anabolic steroid use who underwent a standardized treatment regimen for spermatogenesis recovery. DESIGN AND SUBJECTS: A retrospective analysis of a cohort of men with a prior history of anabolic steroid use and infertility complaints (between 2018 and 2022) was conducted. EXPOSURE: The standardized treatment approach involved discontinuing testosterone replacement therapy and administering a combination regimen of clomiphene citrate and human chorionic gonadotropin for a minimum of 3 to 6 months. MAIN OUTCOME MEASURES: The main outcome measures included changes in sperm parameters, predominantly sperm concentration, and subsequent pregnancy outcomes. RESULTS: A total of 45 men (median age 37 years, IQR 32-45) met the inclusion criteria for this analysis. Median duration of prior T use was 4 years (IQR 1.3-10), with the 2 most common modalities consisting of injection therapy (43.5%) and oral therapy (34.8%). The median initial sperm concentration was 0 million/cc (IQR 0-1.15), and 23 (51.1%) men initially presented with azoospermia. The median duration of combination human chorionic gonadotropin/clomid therapy was 5 months (IQR 3-12). In initially azoospermic men (N: 23), 5 were lost to follow-up, 6 (33.3%) progressed to severe oligospermia (<5 million/cc), 6 (33.3%) to oligospermia (<15 million/cc), 1 (5.6%) to normozoospermia (>15 million/cc), and 5 (27.8%) remained azoospermic after medical treatment for 6 months. Among the 24 couples who responded to the follow-up call, a total of 9 (37.5%) achieved a successful subsequent pregnancy. Of these, 33.3% (3 couples) used assisted reproductive technology, whereas 66.7% (6 couples) conceived naturally. On logistic regression analysis, no significant predictors for improved sperm parameters or successful pregnancy were identified. CONCLUSION: Despite appropriate treatment regimens, a significant proportion of men with a prior history of anabolic steroid use continue to exhibit severe oligospermia, with more than half showing limited improvement in semen parameters after 6 months of treatment. Only a fraction of men achieves normozoospermia after treatment. Further research is needed to explore predictors for improved sperm parameters and successful pregnancy outcomes in men with a history of anabolic steroid use.

Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study.

Introduction Infertility and hypogonadism in males can greatly affect their reproductive health and overall well-being. Since exogenous testosterone administration for hypogonadism management may disrupt the normal hormonal cascade necessary for spermatogenesis, clomiphene citrate (CC) and enclomiphene citrate (EC) are medications often used to manage hypogonadism and male infertility. This study aims to directly compare the effects of CC and EC on serum testosterone levels and semen parameters in men to determine which medication may have an advantage in managing these conditions. Materials and methods We retrospectively analyzed ≥18-year-old men presenting with primary infertility, abnormal semen parameters, or hypogonadism who received CC or EC monotherapy for at least three months between January 2021 and December 2022. We compared baseline and follow-up hormone levels, semen parameters, and demographics. Variables were compared using paired and unpaired t-tests. Significance was assessed at p<0.05. Results A total of 46 men received EC and 32 men received CC. The median age was 42 (IQR: 34-47.75) years in men who received EC and 41 (IQR: 36-44) years in men who received CC (p=0.450). The two treatment groups exhibited a significant increase in serum total testosterone, while only EC had a statistically significant increase in FSH and LH. Semen volume and concentration did not significantly change with either treatment. Sperm motility increased in both groups, but total motile sperm count (TMSC) only significantly increased in men who received EC.  Conclusions Our study found that EC and CC are effective treatments in increasing total testosterone without negatively affecting spermatogenesis. EC demonstrated to be more effective in raising gonadotropin levels and TMSC.

Purkinje cell microzones mediate distinct kinematics of a single movement.

The classification of neuronal subpopulations has significantly advanced, yet its relevance for behavior remains unclear. The highly organized flocculus of the cerebellum, known to fine-tune multi-axial eye movements, is an ideal substrate for the study of potential functions of neuronal subpopulations. Here, we demonstrate that its recently identified subpopulations of 9+ and 9- Purkinje cells exhibit an intermediate Aldolase C expression and electrophysiological profile, providing evidence for a graded continuum of intrinsic properties among PC subpopulations. By identifying and utilizing two Cre-lines that genetically target these floccular domains, we show with high spatial specificity that these subpopulations of Purkinje cells participate in separate micromodules with topographically organized connections. Finally, optogenetic excitation of the respective subpopulations results in movements around the same axis in space, yet with distinct kinematic profiles. These results indicate that Purkinje cell subpopulations integrate in discrete circuits and mediate particular parameters of single movements.

Exploring representation of underrepresented minority men in a restorative therapy clinical trial for erectile dysfunction: addressing barriers and promoting inclusion.

This retrospective descriptive analysis explores underrepresented minority men in our clinical trial for restorative therapy for erectile dysfunction and to identify strategies to promote diversity and inclusion in the study population. Demographic data were collected from all participants and the prevalence in our population was compared to the source population. The proportion of individuals taking part in our clinical trial was compared to the overall disease population using the participation to prevalence ratio. Among the 61 participants enrolled in the Platelet-Rich Plasma for Erectile Dysfunction trial, 72.1% were Hispanic compared to 39.9% in the national source population. There were 27.9% non-Hispanic participants, and 41.2% non-Hispanic men in the local South Florida population. The racial composition of our study shows 80.3% of PRP participants identify as White, 16.4% as Black, and 3.4% as Asian. In the national source population, 61.8% of patients were White, 27.5% are black, and 1.5% are Asian. Through the implementation of strategies such as having Hispanic team members on the clinical trial staff and providing education and outreach materials both in Spanish and English, we were able to overcome barriers to participation in Hispanic men and potentially improve health outcomes for underrepresented minority men with erectile dysfunction.

Deep Brain Stimulation of the Interposed Cerebellar Nuclei in a Conditional Genetic Mouse Model with Dystonia.

Dystonia is a neurological disease that is currently ranked as the third most common motor disorder. Patients exhibit repetitive and sometimes sustained muscle contractions that cause limb and body twisting and abnormal postures that impair movement. Deep brain stimulation (DBS) of the basal ganglia and thalamus can be used to improve motor function when other treatment options fail. Recently, the cerebellum has garnered interest as a DBS target for treating dystonia and other motor disorders. Here, we describe a procedure for targeting DBS electrodes to the interposed cerebellar nuclei to correct motor dysfunction in a mouse model with dystonia. Targeting cerebellar outflow pathways with neuromodulation opens new possibilities for using the expansive connectivity of the cerebellum to treat motor and non-motor diseases.