Pharmacological Screening of Kv7.1 and Kv7.1/KCNE1 Activators as Potential Antiarrhythmic Drugs in the Zebrafish Heart.

Long QT syndrome (LQTS) can lead to ventricular arrhythmia and sudden cardiac death. The most common congenital cause of LQTS is mutations in the channel subunits generating the cardiac potassium current IKs. Zebrafish (Danio rerio) have been proposed as a powerful system to model human cardiac diseases due to the similar electrical properties of the zebrafish heart and the human heart. We used high-resolution all-optical electrophysiology on ex vivo zebrafish hearts to assess the effects of IKs analogues on the cardiac action potential. We found that chromanol 293B (an IKs inhibitor) prolonged the action potential duration (APD) in the presence of E4031 (an IKr inhibitor applied to drug-induced LQT2), and to a lesser extent, in the absence of E4031. Moreover, we showed that PUFA analogues slightly shortened the APD of the zebrafish heart. However, PUFA analogues failed to reverse the APD prolongation in drug-induced LQT2. However, a more potent IKs activator, ML-277, partially reversed the APD prolongation in drug-induced LQT2 zebrafish hearts. Our results suggest that IKs plays a limited role in ventricular repolarizations in the zebrafish heart under resting conditions, although it plays a more important role when the IKr is compromised, as if the IKs in zebrafish serves as a repolarization reserve as in human hearts. This study shows that potent IKs activators can restore the action potential duration in drug-induced LQT2 in the zebrafish heart.

Sexual Dysfunction Among Adolescent and Young Adult Men Diagnosed with Cancer.

Purpose: Adolescent and young adult (AYA) cancer patients frequently demonstrate sexual dysfunction; however, there is a lack of data quantifying the severity and frequency. Methods: Males aged 18-39 years, diagnosed with cancer of any kind and who were scheduled to begin, were actively receiving, or had completed cancer treatment within 6 months, were offered validated surveys during their oncology appointment. These surveys included the International Index of Erectile Function (IIEF-6), Masturbation Erection Index (MEI), 36-Item Short Form Survey, and 5-point Likert scales to assess their desire and ability to engage in sex and masturbation. Results: Forty subjects completed the IIEF survey with a mean score of 17.7 ± 11, erectile dysfunction (ED) prevalence accordingly was 58%. Thirty-eight subjects completed the MEI with a mean score of 25.3 ± 5.3, ED prevalence was again 58%. Age and IIEF scores demonstrated a statistically significant (p < 0.05, n = 38) Pearson's correlation coefficient of 0.40, patients younger than 30 years had an ED prevalence of 72% (mean IIEF 13), whereas patients aged 30 years and older had an ED prevalence of 45% (mean IIEF 22). All treatment modalities had ED rates >30%: chemotherapy demonstrated the highest prevalence at 64% (mean IIEF 17), whereas radiation therapy had the lowest prevalence at 33% (mean IIEF 23). Conclusion: This study demonstrates that the prevalence of sexual dysfunction among male AYA patients undergoing treatment for cancer is high. AYA oncologists should discuss potential sexual health concerns when treating this population. The exact cause of ED (non-organic vs. organic) within this group should be explored further.

Efficacy and Safety of Human Chorionic Gonadotropin Monotherapy for Men With Hypogonadal Symptoms and Normal Testosterone.

Background Male hypogonadism has a prevalence of about 6% and is defined by two-morning testosterone levels below 300 ng/dl associated with symptoms. This definition presents a challenging problem for patients without other medical problems but with symptoms of low testosterone (T) who do not meet the biochemical criteria for therapy. Objectives Our objective was to evaluate changes in symptoms and side effects in men with T levels >300ng/dL using human chorionic gonadotropin (hCG) monotherapy for the treatment of hypogonadal symptoms. Methods After IRB approval, 31 male patients treated with hCG monotherapy for low T symptoms were retrospectively reviewed. We evaluated changes in hormones, hypogonadal symptoms, and the incidence of thromboembolic events before and after starting hCG. Results We found subjective improvement in erectile dysfunction, 86% (19/22), and libido, 80% (20/25), with no patient experiencing a thromboembolic event. In addition, no change was observed in the follicle-stimulating hormone, luteinizing hormone, estradiol, hematocrit, hemoglobin A1c, and prostate-specific antigen. Conclusion Weekly treatment with hCG appears safe and can improve hypogonadal symptoms in patients with T >300 ng/dl without changes to hematocrit, prostate-specific antigen, and hemoglobin A1c.

The Safety of Human Chorionic Gonadotropin Monotherapy Among Men With Previous Exogenous Testosterone Use.

Background and objective Human chorionic gonadotropin (hCG) is homologous to luteinizing hormone (LH) and stimulates endogenous testosterone (T) production. Current American Urological Association (AUA) guidelines recommend hCG for T-deficient men who wish to preserve their fertility. However, there is no data available regarding the long-term efficacy and safety of hCG monotherapy in men with a history of exogenous T use. We hypothesized that transitioning to hCG would be a safe and effective option in this population. Methodology We performed a retrospective analysis involving 28 men with previous exogenous T use who were switched to hCG monotherapy and underwent follow-up lab work at least one month later. We evaluated changes in hormones [T, LH, follicle-stimulating hormone (FSH), and estradiol], hematocrit (HCT), glycated hemoglobin (HbA1c), and prostate-specific antigen (PSA). Results Among the entire cohort, we found no significant change in mean hormone levels (including T), HbA1c, or PSA. There was a significant (p<0.05) decrease in HCT (45.27 ±4.06 to 44.16 ±3.48%, n=15). No thromboembolic events were reported. Additionally, among men who had their baseline labs completed outside their previous T therapy therapeutic time window prior to starting hCG monotherapy, there was a statistically significant increase in mean T levels (307.36 ±148.74 to 422.11 ±268.15 ng/dL, n=30 and 31, pre- and post-hCG, respectively) and a statistically significant decrease in mean PSA levels (0.91 ±0.35 to 0.69 ±0.23 ng/mL, n=5). Conclusions These results suggest that hCG is a safe and effective alternative to traditional T therapy for men with a history of exogenous T use and may lead to an advantageous decrease in HCT. hCG may serve as an alternative form of T therapy with a lower risk for secondary erythrocytosis, and further research is warranted to gain deeper insights into the topic.

Persistent use of medical therapy after surgery for lower urinary tract symptoms: a retrospective database analysis.

PURPOSE: To determine how many men are able to remain off of medical therapy for lower urinary tract symptoms (LUTS) following surgery for benign prostatic obstruction (BPO). METHODS: The TriNetX Analytics Network was used to identify men who were taking medical therapy for BPO (at least one of: alpha-1 blockers, anticholinergics, B3 agonists, or 5-alpha-reductase inhibitors) and subsequently underwent surgery for BPO. They were then placed into one of six cohorts, classified based on the type of surgery they received: transurethral resection of the prostate (TURP), Laser vaporization of prostate (PVP), transurethral incision of the prostate (TUIP), prostatic urethral lift (PUL), water-vapor thermal therapy (WV), or Laser enucleation of the prostate (LEP). Our primary outcome was persistent use of medical therapy at 6-months-2-years postoperatively. Secondary outcome was surgical retreatment by 2 years postoperatively. Propensity-score matching (PSM) was used to control for various risk factors for lower urinary tract symptoms (LUTS). RESULTS: A total of 21,475 men were identified who were on medical therapy and subsequently underwent surgery, which included 12,294 TURP, 5290 PVP, 397 WV, 1308 PUL, 346 TUIP, and 1840 LEP. Medication use between 6 months and 2 years after surgery was 38% for LEP, 50% for WV, 61% for TURP, 63% for PUL, 65% for TUIP and 66% for PVP. All surgical modalities had higher odds of using medications when compared to LEP (p < 0.001). This remained significant after PSM for 9 potentially confounding variables. CONCLUSION: A large percentage of men continue medical therapy after surgery for BPO. Amongst multiple surgical modalities available, LEP appears to have the highest rates of medication discontinuation after surgery. In men who wish to avoid medications or who have cardiac risk factors, a discussion with their urologist to select the best option to minimize medical therapy should occur.

Peyronie's disease in a patient after COVID-19 infection: A case report.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV-2), which demonstrates the ability to invade endothelial cells and cause systemic inflammation. Many possible long-term sequelae of COVID-19 remain unidentified. We describe a case of a man who developed Peyronie's disease after a resolved COVID-19 infection. Erectile dysfunction was confirmed by the International Index of Erectile Function-15(IIEF) and Sexual Health Inventory for Men(SHIM) scores. A diagnosis was Peyronie's disease was confirmed on ultrasound. Furthermore, he was found to have low endothelial progenitor cells colony-forming units and low brachial artery flow-mediated vasodilation, both of that are indicative of endothelial dysfunction. This case suggests Peyronie's disease should be considered as a possible sequela of COVID-19 infection and providers should inquire about a history of COVID-19 infection in patients presenting with Peyronie's disease.

Is Female Wellness Affected When Men Blame Them for Erectile Dysfunction?

INTRODUCTION: Several studies have investigated the association between erectile dysfunction (ED), its treatment, and female sexual dysfunction, but the impact of males blaming their female partners for their ED remains unknown. AIMS: To investigate whether women who are blamed by their male partners for their ED experience worse overall sexual function and satisfaction. METHODS: We performed a global, cross-sectional web-based survey to investigate female perceptions of ED. We distributed the 30-item survey via email, Reddit, Amazon Mechanical Turk, and Facebook. Women 18 years of age or older were eligible to participate and answered questions based on a 5-point Likert scale. Women were grouped by ages 18-29, 30-39, and 40 and older. MAIN OUTCOME MEASURES: The survey collected data that included general demographics and questions regarding experiencing male blame for ED and its relationship with each subject's sexual health and wellness. RESULTS: A total of 13,617 females participated in the survey. Of the women surveyed, 79% have experienced their partner losing their erection during sexual activity and approximately 1 out of 7 women (14.7%) had experienced being blamed by their partner for loss of their erection. Women who were blamed for their partner's ED were more likely to end the sexual encounter, were less sexually satisfied, and were more likely to end relationships due to their partner's ED. CONCLUSION: Approximately 1 out of 7 women have experienced male blame for their partner's ED which is associated with negative impacts on female mental health, sexual satisfaction and the success of the overall partnership. Because of its widespread impact on female wellness, male blame should be considered during evaluation of female sexual history and men must be educated on the significant impact their reactions during intimacy have on their female partners and their relationships as a whole. Dubin JM, Wyant WA, Balaji NC, et al. Is Female Wellness Affected When Men Blame Them for Erectile Dysfunction?. Sex Med 2021;9:100352.

Implications of Calcification in Peyronie's Disease, A Review of the Literature.

A common characteristic of Peyronie's Disease (PD) is plaque calcification, which is associated with decreased response to treatments and higher rates of surgical intervention. Despite its prevalence in the PD population, the literature on plaque calcification is limited. While the diagnosis of PD is mostly clinical, imaging modalities such as ultrasound can be used to identify plaque calcification. The proper identification of plaque calcification is crucial for guiding management and setting therapeutic expectations for patients with PD. Herein we discuss what is known about PD plaque calcification, including epidemiology, etiology, diagnosis, and management.

Survey of Microsurgery Training Availability in US Urology Residency Programs.

PURPOSE: The Accreditation Council of Graduate Medical Education (ACGME) establishes surgical minimum numbers of cases for urologic training. Currently there is not a requirement for microsurgery, likely from a belief that programs do not offer exposure. In an effort to evaluate the availability of microsurgery training among urology residency programs we surveyed the programs. MATERIALS AND METHODS: We obtained a list of the 138 ACGME-accredited urology residencies and contact information the American Urology Association (AUA). We contacted the residency programs by phone and e-mail. For programs that did not reply, we performed a search of the program website. We answered 3-questions to assess resident subspecialty training in microsurgery and used penile implant and artificial urinary sphincters as a comparison. Data are reported as frequencies. RESULTS: We obtained data from 134 programs (97.1%). A total of 104 programs (77.6%) had fellowship-trained physicians for training in microsurgery, 86.6% for penile implants, and 88.8% for artificial urinary sphincters. The percentage of fellowship-trained microsurgeons per program did not vary significantly when comparing the different sections of the AUA. The northeast and southeast sections had the lowest percentage (67% and 68%). CONCLUSIONS: Nearly 80% of urology residency programs have a fellowship-trained microsurgeon on faculty, we therefore believe that microsurgery should be added as part of the ACGME minimums. In order to provide an equal exposure to all graduating urology residents, urology residency programs that lack microsurgery should identify potential faculty with fellowship training.

Using Artificial Intelligence to Predict Surgical Shunts in Men with Ischemic Priapism.

PURPOSE: Ischemic priapism is a urological emergency that requires prompt intervention to preserve erectile function. Characteristics that influence escalation to surgical intervention remain unclear. We identified factors and developed machine learning models to predict which men presenting with ischemic priapism will require shunting. MATERIALS AND METHODS: We identified men with ischemic priapism admitted to the emergency department of our large county hospital between January 2010 and June 2019. We collected patient demographics, etiology, duration of priapism prior to intervention, interventions attempted and escalation to shunting. Machine learning models were trained and tested using R to predict which patients require surgical shunting. RESULTS: A total of 334 encounters of ischemic priapism were identified. The majority resolved with intracavernosal phenylephrine injection and/or cavernous aspiration (78%). Shunting was required in 10% of men. Median duration of priapism before intervention was longer for men requiring shunting than for men who did not (48 vs 7 hours, p=0.030). Patients with sickle cell disease as the etiology were less likely to require shunting compared to all other etiologies (2.2% vs 15.2%, p=0.035). CONCLUSIONS: Men with longer duration of priapism before treatment more often underwent shunting. However, phenylephrine injection and aspiration remained effective for priapism lasting more than 36 hours. Having sickle cell disease as the etiology of priapism was protective against requiring shunting. We developed artificial intelligence models that performed with 87.2% accuracy and created an online probability calculator to determine which patients with ischemic priapism may require shunting.

Polymer Pen Lithography with Lipids for Large-Area Gradient Patterns.

Gradient patterns comprising bioactive compounds over comparably (in regard to a cell size) large areas are key for many applications in the biomedical sector, in particular, for cell screening assays, guidance, and migration experiments. Polymer pen lithography (PPL) as an inherent highly parallel and large area technique has a great potential to serve in the fabrication of such patterns. We present strategies for the printing of functional phospholipid patterns via PPL that provide tunable feature size and feature density gradients over surface areas of several square millimeters. By controlling the printing parameters, two transfer modes can be achieved. Each of these modes leads to different feature morphologies. By increasing the force applied to the elastomeric pens, which increases the tip-surface contact area and boosts the ink delivery rate, a switch between a dip-pen nanolithography (DPN) and a microcontact printing (µCP) transfer mode can be induced. A careful inking procedure ensuring a homogeneous and not-too-high ink-load on the PPL stamp ensures a membrane-spreading dominated transfer mode, which, used in combination with smooth and hydrophilic substrates, generates features with constant height, independently of the applied force of the pens. Ultimately, this allows us to obtain a gradient of feature sizes over a mm2 substrate, all having the same height on the order of that of a biological cellular membrane. These strategies allow the construction of membrane structures by direct transfer of the lipid mixture to the substrate, without requiring previous substrate functionalization, in contrast to other molecular inks, where structure is directly determined by the printing process itself. The patterns are demonstrated to be viable for subsequent protein binding, therefore adding to a flexible feature library when gradients of protein presentation are desired.

Lipid Multilayer Grating Arrays Integrated by Nanointaglio for Vapor Sensing by an Optical Nose.

Lipid multilayer gratings are recently invented nanomechanical sensor elements that are capable of transducing molecular binding to fluid lipid multilayers into optical signals in a label free manner due to shape changes in the lipid nanostructures. Here, we show that nanointaglio is suitable for the integration of chemically different lipid multilayer gratings into a sensor array capable of distinguishing vapors by means of an optical nose. Sensor arrays composed of six different lipid formulations are integrated onto a surface and their optical response to three different vapors (water, ethanol and acetone) in air as well as pH under water is monitored as a function of time. Principal component analysis of the array response results in distinct clustering indicating the suitability of the arrays for distinguishing these analytes. Importantly, the nanointaglio process used here is capable of producing lipid gratings out of different materials with sufficiently uniform heights for the fabrication of an optical nose.