Bipolar Patient-Specific In Vitro Diagnostic Test Reveals Underlying Cardiac Arrhythmia Phenotype Caused by Calcium Channel Genetic Risk Factor.

A common genetic risk factor for bipolar disorder is CACNA1C, a gene that is also critical for cardiac rhythm. The impact of CACNA1C mutations on bipolar patient cardiac rhythm is unknown. Here, we report the cardiac electrophysiological implications of a bipolar disorder-associated genetic risk factor in CACNA1C using patient induced pluripotent stem cell-derived cardiomyocytes. Results indicate that the CACNA1C bipolar disorder-related mutation causes cardiac electrical impulse conduction slowing mediated by impaired intercellular coupling via connexin 43 gap junctions. In vitro gene therapy to restore connexin 43 expression increased cardiac electrical impulse conduction velocity and protected against thioridazine-induced QT prolongation. Patients positive for bipolar disorder CACNA1C genetic risk factors may have elevated proarrhythmic risk for adverse events in response to psychiatric medications that slow conduction or prolong the QT interval. This in vitro diagnostic tool enables cardiac testing specific to patients with psychiatric disorders to determine their sensitivity to off-target effects of psychiatric medications.

Bipolar disorder (BD) is associated with genetic risk factors that present as mutations in specific genes. One gene commonly associated with BD is the calcium channel gene CACNA1C, found in the brain and the heart. The impact of CACNA1C mutation on cardiac function in patients with BD is unclear. Here, we created a BD CACNA1C mutant patient "heart in a dish" using patient-specific stem cells. Gene editing was also used to correct the mutation to create an isogenic control cell line. We found that the BD calcium gene mutation caused slow electrical impulse propagation, reduced the function of the calcium channel, and was associated with low intercellular communication channels called connexin. Using connexin gene therapy in vitro, the the cardiac dysfunction could be corrected and cured. This new approach offers patient-specific hearts-in-a-dish that can be used to ensure that medications will not cause heart racing or arrhythmias.

Postpartum readmission risk: a comparison between stillbirths and live births.

BACKGROUND: Stillbirth occurs more commonly among pregnant people with comorbid conditions and obstetrical complications. Stillbirth also independently increases maternal morbidity and imparts a psychosocial hazard when compared with live birth. These distinct needs and burden may increase the risk for postpartum readmission after stillbirth. OBJECTIVE: This study aimed to examine the risk for maternal postpartum readmission after stillbirth in comparison with live birth and to identify indications for readmission and the associated risk factors. STUDY DESIGN: This was a retrospective cohort of patients with singleton stillbirths or live births, delivered at ≥20 weeks' gestation, who were identified from the 2019 Nationwide Readmissions Database. The primary outcome was all-cause readmission within 6 weeks of discharge from the childbirth hospitalization. The association between stillbirth (vs live birth) and risk for readmission was assessed using multivariable regression models with adjustment for maternal age, sociodemographic characteristics, maternal and obstetrical conditions, and delivery characteristics. Within the stillbirth group, risk factors for readmission were further examined using multivariable regression. The secondary outcomes included principal indication for readmission (categorized based on principal diagnosis code of the readmission hospitalization) and timing of readmission (number of weeks after childbirth hospitalization). Differences in these secondary outcomes were compared between the stillbirth and live birth groups using chi-square tests. All analyses accounted for the complex sample design to generate nationally representative estimates. RESULTS: Postpartum readmission occurred in 2.7% of 16,636 patients with stillbirths, whereas it occurred in 1.6% of 2,870,677 patients with live births (unadjusted risk ratio, 1.65; 95% confidence interval, 1.47-1.86). The higher risk for readmission after stillbirth (vs live birth) persisted after adjusting for maternal, obstetrical, and delivery characteristics (adjusted risk ratio, 1.27; 95% confidence interval, 1.11-1.46). The distribution of principal indication for readmission differed after stillbirth and after live birth and included hypertension (30.2% vs 39.5%; unadjusted risk ratio, 0.76; 95% confidence interval, 0.63-0.93), mental health or substance use disorders (6.8% vs 3.6%; unadjusted risk ratio, 1.90; 95% confidence interval, 1.15-3.16), and venous thromboembolism (5.8% vs 2.0%; unadjusted risk ratio, 2.87; 95% confidence interval, 1.60-5.17). Among patients with stillbirths, 56.0% of readmissions occurred within 1 week, 71.8% within 2 weeks, and 88.1% within 4 weeks; the timing of readmission did not differ significantly between the stillbirth and live birth cohorts. Pregestational diabetes (adjusted risk ratio, 1.87; 95% confidence interval, 1.20-2.93), gestational diabetes (adjusted risk ratio, 1.67; 95% confidence interval, 1.03-2.71), hypertensive disorders of pregnancy (adjusted risk ratio, 1.80; 95% confidence interval, 1.31-2.47), obesity (adjusted risk ratio, 1.46; 95% confidence interval, 1.01-2.12), and primary cesarean delivery (adjusted risk ratio, 1.74; 95% confidence interval, 1.17-2.58) were associated with a higher risk for readmission after stillbirth, whereas higher household income was associated with a lower risk for readmission (eg, adjusted risk ratio for income ≥$82,000 vs $1-$47,999, 0.48; 95% confidence interval, 0.30-0.77). CONCLUSION: When compared with live births, the risk for postpartum readmission was higher after stillbirths, even after adjustment for differences in the patient demographic and clinical characteristics. Readmission for mental health or substance use disorders and venous thromboembolism is more common after stillbirths than after live births.

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.

Evaluation of androgen receptor markers in erectile dysfunction.

BACKGROUND: Steroid hormones, such as testosterone, play a crucial role in modulating the development of male internal and external genitalia as well as secondary sex characteristics by binding to the androgen receptor. Once bound, androgen receptor operates as an inducible transcription factor, interacting with a multitude of co-regulators to initiate various downstream signaling pathways. The androgen saturation hypothesis posits that beyond a specific threshold, androgen receptor binding and functionality remain unaltered despite an increase in serum testosterone levels. OBJECTIVES: The objective of this study was to explore the expression of these proteins in penile tissue samples from men with severe erectile dysfunction to enhance our understanding of the influence of serum testosterone on androgen receptor function. MATERIALS AND METHODS: Patients undergoing surgical management for high-grade ED at our institution were invited to participate in the study. During inflatable penile prosthesis surgery, corpus cavernosum biopsy was obtained. Protein was extracted from each sample for western blot analysis which was probed with androgen receptor, heme oxygenase, inducible nitric oxide synthase, and phosphodiesterase type 5 antibodies with GAPDH for protein normalization. RESULTS: 12 men agreed to participate in this study. Serum testosterone levels were obtained from all participants on the morning of their surgery. The median testosterone level was 300.15 ng/dL. Our findings revealed a decrease in androgen receptor and inducible nitric oxide synthase expression at serum testosterone levels below 300 ng/dL (p = 0.022, 0.03). Similarly, hemeoxygenase and phosphodiesterase type 5 expression levels were significantly lower at serum T concentrations below 200 ng/dL (p = 0.017, 0.014). DISCUSSION AND CONCLUSION: These data showed a significant decrease in the expression of proteins downstream of the androgen receptor at lower serum T levels. This suggests a potential correlation between serum T concentration and androgen receptor signaling and supports a potential saturation value between 200 and 300 ng/dL.

Assessing Infertility Literacy and Knowledge Gaps Among Patients with Cystic Fibrosis.

OBJECTIVE: As patients with cystic fibrosis live longer into their reproductive years, fertility concerns are rising. We hypothesized that while patients with cystic fibrosis may be informed of the impact of their disease on their reproductive potential, they remain unaware of the promising role of assisted reproductive technology in helping them conceive biological children. METHODS: We distributed a voluntary and anonymous survey to cystic fibrosis patients and organizations to assess patient understanding of cystic fibrosis-related infertility. The survey questions aimed to capture demographic information, their reproductive education regarding cystic fibrosis, and their preferences for future fertility. RESULTS: Forty respondents completed the survey (median age of 36 ± 14 years). The median age reported for learning about cystic fibrosis-associated infertility was 18 years. Respondents preferred that reproductive and infertility education be provided early; 43% reported the optimal age of education was younger than 18 years while 50% reported between 18 and 24 years. Of the respondents trying to conceive, 43% of patients have been trying to conceive for 1-3 years qualifying for infertility. Yet, the majority of those patients (69%) have not been offered a semen analysis and 90% have not had previous fertility treatments. CONCLUSION: Our findings highlight that cystic fibrosis patients are knowledgeable about cystic fibrosis-related impacts on their fertility, with high-rated self-confidence. A fraction of patients still desire to conceive but have not been provided with assisted reproductive services. We recommend the establishment of active partnerships between cystic fibrosis care teams and fertility specialists to maximize their chances of conception.

Platelet-rich plasma for erectile dysfunction: a review of the current research landscape.

INTRODUCTION: Erectile dysfunction (ED) is the inability to achieve or maintain erection for satisfactory sexual performance. ED drastically reduces the quality of life for men and their partners and is commonly linked to comorbid conditions such as diabetes and cardiovascular disease. As a result, clinicians and researchers are working to improve treatments for ED. Current guideline-approved ED treatments include oral phosphodiesterase type 5 inhibitors, intraurethral alprostadil, penile intracavernosal injections, and penile prosthesis surgery. Today, there is increasing interest in restorative therapies such as intracavernosal platelet-rich plasma (PRP) for the management of ED. OBJECTIVES: This narrative review describes the current trials investigating intracavernosal PRP for ED and proposes future directions to increase the strength of evidence to support use of PRP in this population. METHODS: A comprehensive literature search of PubMed, Science Direct, and Scopus was performed to identify all randomized clinical trials using PRP for the treatment of ED. RESULTS: We identified 4 randomized clinical trials investigating the safety and efficacy of PRP for ED. We found significant heterogeneity among study protocols, including collection of PRP, dosing of PRP, and follow-up. CONCLUSION: While intracavernosal PRP is considered safe, its efficacy for the management of ED remains unknown due to variability among clinical trials.

Prevalence of Low Testosterone in Men With Cystic Fibrosis and Congenital Bilateral Absence of the Vas Deferens: A Cross-sectional Study Using a Large, Multi-institutional Database.

OBJECTIVE: To investigate the prevalence and treatment rates of low testosterone (T) in men with cystic fibrosis (CF). CF is a genetic disease with highly variable presentation that results from a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Phenotypic manifestations of CF include alterations in function of the lungs, liver, pancreas, and reproductive system. Despite the well-described association between CF and infertility secondary to congenital bilateral absence of the vas deferens (CBAVD), men with CF report further sexual and reproductive health concerns, many of which are often associated with low testosterone. METHODS: We queried the TrinetX database for men over 18years old with CF or CBAVD to assess what percentage of men had a T level measured, and if hypogonadal (below 300 ng/dL), what percentage received T therapy (TT). We hypothesized that low T would be under-evaluated in the CF population. RESULTS: Serum T levels were measured in 10.1% of men with CF and 8.9% of men with CBAVD. Within each group, 464 men with CF (32.7%) and 132 with CBAVD (43.0%) demonstrated low T. The majority of men with T < 300 ng/dL went on to appropriately receive TT: 59.3% of men with CF and 78% with CBAVD. CONCLUSION: Our data suggests that hypogonadism is highly prevalent in men with CF and CBAVD. Investigation and appropriate treatment of testosterone deficiency may significantly improve quality of life.

In vitro efficacy of intralesional Collagenase Clostridium Histolyticum for the treatment of calcified Peyronie's disease plaques.

Peyronie's disease (PD) is defined by penile plaque formation and curvature causing sexual dysfunction. The only FDA-approved intralesional treatment is Collagenase Clostridium histolyticum (CCh). CCh contains two collagenases, AUX1 and AUXII, that break down the type I and type III collagen contained in plaques, leading to plaque dissolution and reduction in penile curvature. Peyronie's plaques, however, also contain fibrin and calcium, which CCh cannot digest. It is unclear if plaque calcification prevents CCh from breaking down plaques. We collected ten tissue samples: five calcified penile plaques and five control samples of corpus cavernosum. They were incubated in CCh or PBS. Soluble collagen measurements and collagen staining assays were completed to measure tissue breakdown. Calcified plaques incubated in CCh showed significantly higher levels of soluble collagen (301.07 ug ± 21.28 vs. PBS: 32.82 ug ± 3.68, p = 0.02), and significantly lower levels of collagen (type I and III) compared to tissues incubated in PBS (0.12 ± 0.08, vs. 0.44 ± 0.17, p = 0.002). When comparing different tissues (calcified vs. control) incubated in CCh and PBS solutions, there were no significant differences in collagen staining or breakdown. Although higher collagen staining was seen in the calcified group, soluble collagen showed no significant differences between control and calcified tissues in the CCh group (control: 0.08 ± 0.02 vs. calcified: 0.17 ± 0.09, p = 0.08) or the PBS group (control: 0.50 ± 0.23 vs. calcified: 0.39 ± 0.39, p = 0.23). CCh exposure led to significantly more tissue breakdown in both tissue groups when compared to PBS however, there was no significant difference in plaque digestion found between calcified and control tissue exposed to CCh or PBS. This suggests that plaque calcification does not affect the action of CCh. Further research into CCh for calcified plaques is necessary to inform clinicians as to the optimal management of this population.

Transcriptional Differences in Identical Twins With Different Reproductive Capacities: A Case Report.

Disorders of sperm production can be classified quantitatively as oligospermia (low sperm count) or azoospermia (no sperm during ejaculation). Numerous genes have been implicated in spermatogenesis. We describe a case of two identical twins who presented with different reproductive capabilities. One brother was infertile due to azoospermia, and the other, although oligospermic, previously naturally fathered a child. They were found to have differential gene expression based on RNA sequencing analysis. In the man with azoospermia, we found elevated E2F1 and HOXB9 gene expressions when compared with his brother, suggesting that the increased RNA expression of these genes could influence sperm production.

The impact of cell-based therapy on female sexual dysfunction: a systematic review and meta-analysis.

INTRODUCTION: Female sexual dysfunction (FSD) is a complex issue affecting women of all ages; it involves several overlapping body systems and profoundly affects quality of life. The use of cell-based therapy, such as mesenchymal stem cells, has recently been investigated as a potential treatment for FSD. OBJECTIVES: This systematic review and meta-analysis aim to assess FSD outcomes following cell-based therapy. METHODS: We evaluated peer-reviewed articles from multiple online databases through November 2022 to identify studies that used cell-based therapy and reported sexual function outcomes in women. We performed a meta-analysis using data pooled from 3 clinical trials at our institution: CRATUS (NCT02065245), ACESO (NCT02886884), and CERES (NCT03059355). All 3 trials collected data from the Sexual Quality of Life-Female (SQOL-F) questionnaire as an exploratory outcome. RESULTS: Existing literature on this topic is scarce. Five clinical studies and 1 animal study were included in the systematic review, and only 2 clinical studies were considered good quality: 1 reported significant SQOL-F improvement in women 6 months after cell therapy, and 1 reported posttherapy sexual satisfaction in all women. When individual patient data were pooled in a meta-analysis from 29 women across 3 trials at our institution, the SQOL-F was not significantly improved. CONCLUSION: Despite growing interest in cell-based therapy for women's sexual health, this important issue is understudied in the literature. The optimal route, source, and dose of cell therapy to produce clinically meaningful change have yet to be determined, and further research is needed in larger randomized placebo-controlled clinical trials.

Sexual and Reproductive Health Among Men With Cystic Fibrosis.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Due to the distribution of the CFTR protein, CF presents with a heterogeneous phenotype. Men with CF may present with infertility due to congenital abnormalities of the vas deferens. In addition, they may experience testosterone deficiency. Today, they can father biological children with assisted reproductive technologies. We reviewed the current literature on the pathophysiology of these conditions, describe interventions that allow men with CF to conceive biological children, and provide recommendations for management of CF patients with reproductive health concerns.

Next-generation sequencing analysis of semen microbiome taxonomy in men with nonobstructive azoospermia vs. fertile controls: a pilot study.

OBJECTIVES: To study how the semen microbiome profile in men with nonobstructive azoospermia (NOA) differs from that of fertile controls (FCs). DESIGN: Using quantitative polymerase chain reaction and 16S ribosomal RNA, we sequenced semen samples from men with NOA (follicle-stimulating hormone >10 IU/mL, testis volume <10 mL) and FCs and performed a comprehensive taxonomic microbiome analysis. SETTING: All patients were identified during evaluation at the outpatient male andrology clinic at the University of Miami. PATIENTS: In total, 33 adult men, including 14 diagnosed with NOA and 19 with proven paternity undergoing vasectomy, were enrolled. MAIN OUTCOME MEASURES: Bacterial species in the semen microbiome were identified. RESULTS: Alpha-diversity was similar between the groups, suggesting similar diversity within samples, whereas beta-diversity was different, suggesting differences in taxa between samples. In the NOA men, the phyla Proteobacteria and Firmicutes were underrepresented, and Actinobacteriota were overrepresented compared with FC men. At the genus level, Enterococcus was the most common amplicon sequence variant in both groups, whereas 5 genera differed significantly between the groups, including Escherichia and Shigella, Sneathia, and Raoutella. CONCLUSION: Our study showed significant differences in the seminal microbiome between men with NOA and fertile men. These results suggest a loss of functional symbiosis may be associated with NOA. Further research into the characterization and clinical utility of the semen microbiome and its causal role in male infertility is necessary.

Safety Aspects and Rational Use of Testosterone Undecanoate in the Treatment of Testosterone Deficiency: Clinical Insights.

Testosterone deficiency is diagnosed by a serum total testosterone level below 300 ng/dL in combination with symptoms such as decreased energy and libido. These symptoms can be ameliorated by restoring serum testosterone to the physiologic range with testosterone therapy (TT). There are numerous forms of testosterone therapy, such as injectable, transdermal, nasal, and subcutaneous applications. There are also multiple formulations of injection, such as testosterone cypionate, testosterone enanthate, and testosterone undecanoate. Testosterone undecanoate (TU) is a long-acting ester formulation of testosterone that can be provided in an injectable or oral form. Oral testosterone undecanoate is marketed as Andriol, Jatenzo, Tlando, and Kyzatrex. Oral TU provides a convenient option for many patients, which may increase compliance with TT. Injectable testosterone undecanoate is marketed as Aveed and Nebido. Injectable TT remains the most cost-effective therapeutic option and is appropriate for most patients as an initial therapy. This review describes the pharmacokinetics of these testosterone undecanoate products and provides a guide for prescribers using these medications. While many forms of testosterone are appropriate for TT, a patient-centered discussion focused on goals of care should best guide physician prescription of these medications.

Severe Maternal Morbidity Review and Preventability Assessment in a Large Academic Center.

With the goal of identifying factors contributing to severe maternal morbidity (SMM) at our institution, we established a formal SMM review process. We performed a retrospective cohort study including all SMM cases as defined by American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine consensus criteria that were managed at Yale-New Haven Hospital over a 4-year period. Overall, 156 cases were reviewed. The SMM rate was 0.49% (95% CI 0.40-0.58). The leading causes of SMM were hemorrhage (44.9%) and nonintrauterine infection (14.1%). Two thirds of the cases were deemed to be preventable. Preventability was mostly associated with health care professional-level (79.4%) and system-level (58.8%) factors that could coexist. Detailed case review allowed for identification of preventable causes of SMM, revealed gaps in care, and allowed for implementation of practice changes targeting health care professional-level and system-level factors.

Whole Exome Sequencing Identifies a Rare CFTR Mutation in Brothers With Anomalies of the Vas Deferens: A Case Study.

Congenital bilateral absence of the vas deferens (CBAVD) occurs in almost all men with cystic fibrosis. Prevailing theories on this pathophysiology relate to pathogenic mutations in the cystic fibrosis transmembrane regulator gene leading to agenesis or obliteration of vas deferens in utero. In this study, we present a case of two brothers with congenital anomalies of the vas deferens who were found to have carried a rare, heterozygous cystic fibrosis transmembrane regulator variant p.r347h without pulmonary or gastrointestinal signs or symptoms of cystic fibrosis .

Developing a Physician-Led Model for Research Mentorship in Academic Urology.

PURPOSE OF REVIEW: Quality mentorship is difficult to attain amidst the conflicting demands of academic medicine. In this review, we sought to characterize mentor-mentee relationships and discuss their optimization towards productivity in the research team setting. RECENT FINDINGS: A high-value mentor, defined by exceptional commitment to both research productivity and mentoring, naturally attracts prospective mentees, who can demonstrate their interest by shadowing and completing delegated tasks. Once fully initiated, the mentee establishes expectations with the mentor, identifies their roles within the research team, and, over time, takes ownership of the mentor-mentee relationship and collaborates with near-peers. Mentorship is a dynamic, reciprocal relationship that enhances career development of both participants. In the research team setting, episodic virtual research meetings and prudent delegation orient the entire team, while the mentor-mentee relationship is upheld by embracing a culture of responsiveness, feedback, and collaboration.

For Aging Research and Equity: Lessons Learned in Undergraduate Research Education.

Mentoring underrepresented students in aging research during the COVID-19 pandemic affords many opportunities for innovation and learning, for both students and program leaders. Here, we describe lessons learned from an Advancing Diversity in Aging Research (ADAR) program at a women-centered, minority-serving undergraduate institution. We share program elements and assessment results related to scholars' education in aging, support through community-building and mentorship, and research experiences in gerosciences. Notably, we highlight lessons learned for retaining and training undergraduate students as graduate school-ready researchers: 1) draw students into a community focused on social justice, 2) show students that geroscience is inclusive and integrative, 3) model professionalism with flexibility, 4) keep open lines of communication, and 5) build a team of mentors around each scholar. By sharing insights from our community of practice in geroscience research and education, we hope to model best practices for URM student support in aging research.

Androgen Receptor Signaling is Similar in Human Corpus Cavernosum in Men with Different Serum Testosterone Levels.

BACKGROUND: Testosterone (T) plays an important role in male reproductive function and tissue development. Normal serum T levels vary between 300 and 1000 ng/dl. It is not known, however, if varying serum T levels alter androgen receptor (AR) signaling in tissue. OBJECTIVE: To measure AR signaling levels in human corpus cavernosal tissue in males with different serum T levels. DESIGN, SETTING, AND PARTICIPANTS: Participants were selected from a group of males undergoing surgical management for erectile dysfunction (ED; penile prosthesis placement). T levels were measured 1 week before surgery and a sample of corpus cavernosal tissue was procured during surgery. The tissue was homogenized, measured for protein concentration, and used for western blot analysis. VEGF was selected as an AR marker and actin was used for protein normalization. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: VEGF and actin expression levels were analyzed using western blot analysis and ImageJ was used for quantification of antibody expression. RESULTS AND LIMITATIONS: AR signaling was measured in terms of VEGF expression. Above a T level of 200 ng/dl, there was no significant difference found in VEGF expression. Only one patient had a T level less than 200 ng/dl, limiting the generalizability of these results. In addition, all patients had a history of ED, and controls (patients without ED) were not included in the study. CONCLUSIONS: Above a serum T level of 200 ng/dl, there was no significant difference in AR signaling. This finding suggests that there could be a saturation level present in corpus cavernosal tissue that is approximately 200 ng/dl. PATIENT SUMMARY: Serum testosterone levels above a certain threshold may not be necessary for biological functions. Instead, it is most likely that there is an approximate serum testosterone level that fully saturates tissue androgen receptors and results in peak function in men.

Effect of Radiofrequency Electromagnetic Radiation Emitted by Modern Cellphones on Sperm Motility and Viability: An In Vitro Study.

BACKGROUND: Cellphones emit radiofrequency electromagnetic radiation (RF-EMR) for transmission of data for social media communication, web browsing, and music/podcast streaming. Use of Bluetooth ear buds has probably prolonged the time during which cellphones reside in the trouser pockets of men. It has been postulated that RF-EMR increases oxidative stress and induces free radical formation. OBJECTIVE: To investigate the effect of wireless-spectrum (4G, 5G, and WiFi) RF-EMR emitted by modern smartphones on sperm motility and viability and explore whether these effects can be mitigated using a physical barrier or distance. DESIGN, SETTING, AND PARTICIPANTS: Semen samples were obtained from fertile normozoospermic men aged 25-35 yr. A current-generation smartphone in talk mode was used as the RF-EMR source. A WhatsApp voice call was made using either 4G, 5G, or WiFi wireless connectivity. We determined if exposure effects were mitigated by either a cellphone case or greater distance from the semen sample. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The semen samples were analyzed according to 2010 World Health Organization laboratory guidelines. Statistical analysis was performed using SPSS v.28. RESULTS AND LIMITATIONS: We observed decreases in sperm motility and viability with WiFi exposure but not with exposure to 4G or 5G RF-EMR. With large variability among smartphones, continued research on exposure effects is needed. CONCLUSIONS: Our exploratory study revealed that sperm motility and viability are negatively impacted by smartphones that use the WiFi spectrum for data transmission. PATIENT SUMMARY: We looked at the effect of cellphone use on sperm motility and viability. We found that cellphones using WiFi connectivity for data usage have harmful effects on semen quality in men.