Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction.

Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behavior of mural cells within the healing heart. In response to myocardial infarction, mural cells adopt an altered state closely associated with the infarct and retain a distinct lineage from fibroblasts. This response is concurrent with vascular rarefaction and reduced vascular coverage by mural cells. Positional transcriptomics reveals that the infarcted heart is governed by regional-dependent and temporally regulated programs. While the remote zone acts as an important source of pro-angiogenic signals, the infarct zone is accentuated by chronic activation of anti-angiogenic, pro-fibrotic, and inflammatory cues. Together, our work unveils the spatiotemporal programs underlying cardiac repair and establishes an association between vascular deterioration and mural cell dysfunction.

Demographics, Usage Patterns, and Safety of Male Users of Clomiphene in the United States.

PURPOSE: The aim of this study was to characterize the demographics, usage patterns and complication rates of clomiphene use in male patients. MATERIALS AND METHODS: We retrospectively analyzed male patients from ages 20 to 55 years old who were prescribed clomiphene citrate from 2001 to 2014 using the Truven Health MarketScan, a US claims database. We collected data regarding associated medical diagnoses, diagnostic testing, duration of use, and reported side effects including thrombotic events, vision problems, gynecomastia, mental disorders, liver disease, nausea, or skin problems. RESULTS: In total, 12,318 men took clomiphene and represented the primary study cohort, with a mean age of 37.8 years. The percentage of men prescribed clomiphene increased over the study period, as did the average age of clomiphene users. Associated diagnoses included male infertility (52.0%), testicular hypofunction (13.5%), erectile dysfunction (2.4%), and low libido (0.4%). Associated testing included semen analysis (43.7%), testosterone (23.5%), luteinizing hormone (19.3%), and follicle-stimulating hormone (21.1%) levels. The median time of clomiphene use was 3.6 months, with 63% of men stopping within 6 months. No increased risk of reported clomiphene side effects were apparent in men taking the medication. CONCLUSIONS: There is a rising prevalence of clomiphene usage without associated adverse side effects in the US. The variability in associated diagnoses, diagnostic testing, and duration of use suggest a need for greater awareness of the proper evaluation and treatment of the men who are prescribed clomiphene.

Exploring Gaps in Concussion Knowledge and Knowledge Translation Among Coaches of Youth Female Hockey.

OBJECTIVE: To better understand the level of concussion knowledge of youth female hockey coaches and to identify preferred methods of knowledge translation for this population. DESIGN: Cross-sectional survey. SETTING: Participants independently completed written surveys before in-person concussion information sessions or online surveys through link provided in emails. PARTICIPANTS: Convenience sampling yielded 130 coaches of youth female hockey from Canada. MAIN OUTCOME MEASURES: Knowledge level on concussion, resources from which coaches obtained information on concussion, opinions on the current level of concussion knowledge, and knowledge translation. RESULTS: Coaches demonstrated adequate knowledge on concussion, achieving 84% correct on true-false questions and 92% correct on symptom identification accuracy. However, coaches showed limited awareness of concussion specific to mechanisms for injury (identification) and postconcussion symptoms. Internet resources were rated as the most used resources for concussion yet were not rated very helpful. Nonetheless, coaches indicated online courses and web sites as the most preferred method for concussion knowledge translation. CONCLUSIONS: Youth female hockey coaches have overall adequate knowledge of concussion; however, gaps in knowledge do exist. Future efforts to raise the concussion knowledge among coaches of female youth hockey should include information specific to the mechanism of injury, along with sign and symptom identification, with particular attention paid to emotional symptoms. Given the reported preferences and the widespread availability of the Internet, further exploration and research validation of online courses and web sites tailored to the youth female hockey community is encouraged.

Sports-related Male Infertility.

Many common sports and sports-related behaviors and practices represent potential sources of male infertility. Clinicians should be aware of these associations in the evaluation of idiopathic infertility in men.

Using observational data for personalized medicine when clinical trial evidence is limited.

Randomized clinical trials are considered the preferred approach for comparing the effects of treatments, yet data from high-quality clinical trials are often unavailable and many clinical decisions are made on the basis of evidence from observational studies. Using clinical examples about the management of infertility, we discuss how we can use observational data from large and information-rich health-care databases combined with modern epidemiological and statistical methods to learn about the effects of interventions when clinical trial evidence is unavailable or not applicable to the clinically relevant target population. When trial evidence is unavailable, we can conduct observational analyses emulating the hypothetical pragmatic target trials that would address the clinical questions of interest. When trial evidence is available but not applicable to the clinically relevant target population, we can transport inferences from trial participants to the target population using the trial data and a sample of observational data from the target population. Clinical trial emulations and transportability analyses can be coupled with methods for examining heterogeneity of treatment effects, providing a path toward personalized medicine.

The Research Implications of Prostate Specific Antigen Registry Errors: Data from the Veterans Health Administration.

PURPOSE: We sought to characterize the effects of prostate specific antigen registry errors on clinical research by comparing cohorts based on cancer registry prostate specific antigen values with those based directly on results in the electronic health record. MATERIALS AND METHODS: We defined sample cohorts of men with prostate cancer using data from the Veterans Health Administration, including those with a prostate specific antigen value less than 4.0, 4.0 to 10.0, 10.0 to 20.0 and 20.0 to 98.0 ng/ml, respectively. We compared the composition of each cohort and overall patient survival when using prostate specific antigen values from the Veteran Affairs Central Cancer Registry vs the gold standard electronic health record laboratory file results. RESULTS: There was limited agreement among cohorts when defined by cancer registry prostate specific antigen values vs the laboratory file of the electronic health record. The least agreement of 58% was seen in patients with prostate specific antigen less than 4.0 ng/ml and greatest agreement of 89% was noted among patients with prostate specific antigen between 4.0 and 10.0 ng/ml. In each cohort patients assigned to a cohort based only on the cancer registry prostate specific antigen value had significantly different overall survival when compared with patients assigned based on registry and laboratory file prostate specific antigen values. CONCLUSIONS: Cohorts based exclusively on cancer registry prostate specific antigen values may have high rates of misclassification that can introduce concerning differences in key characteristics and result in measurable differences in clinical outcomes.

Hypertension and Male Fertility.

As the age of paternity rises in the developed world, issues of chronic disease may affect prospective fathers. Given the high prevalence of hypertension, researchers have begun to explore the relationship between hypertensive disease and male fertility. The current literature suggests an association between hypertension and semen quality. The use of various antihypertensive medications has also been linked to impaired semen parameters, making it difficult to discern whether the association exists with hypertension or its treatment. Further investigation is warranted to determine whether the observed associations are causal.

Urodynamics of men with urinary retention.

OBJECTIVES: To describe the urodynamic characteristics of men with urinary retention, and to show the diverse treatment plans based on urodynamic findings. METHODS: We carried out a 3-year retrospective review of men with urinary retention who were referred to our clinic for urodynamic evaluation. Men with a history of neurogenic voiding dysfunction or major pelvic surgery were excluded. Multichannel videourodynamic studies were carried out, and the subsequent treatment modality offered was recorded. RESULTS: A total of 67 men with urinary retention and a median age of 68 years underwent urodynamic evaluation. The median maximum flow rate was 3 mL/s, and the median detrusor pressure at maximum flow was 54 cm H2 O. Bladder outlet obstruction was diagnosed in 60%. Detrusor underactivity was present in 73% according to the bladder contractility index; however, just 29% were classified as having detrusor underactivity according to isometric detrusor pressure, an alternative measure of contractility. A total of 76% of patients had low detrusor reserve (<20 cm H2 O). Based on urodynamic findings, just 57% of patients were offered de-obstructive surgery. CONCLUSIONS: In the present cohort, just 60% of men with urinary retention showed urodynamic evidence of bladder outlet obstruction. Depending on how contractility is measured (bladder contractility index vs isometric detrusor pressure), the rate of detrusor underactivity varies. The majority of men with retention had a low detrusor reserve. Given the wide spectrum of urodynamic findings in men with retention, surgical intervention might not be necessary for all. Furthermore, a careful consideration of urodynamics can assist in the selection of optimal treatment.

Intermittent Projectile Urethraggia: An Unusual Sequela of a Skateboarding Accident in an Adolescent Male.

Our patient suffered a perineal straddle injury, resulting in right cavernosal artery pseudoaneurysm in combination with a cavernosal-urethral fistula. The urethra failed to heal after several weeks, and the patient presented with severe intermittent urethral bleeding. The pseudoaneurysm was successfully treated by coil embolization, with resolution of the bleeding. The patient recovered completely, with normal erectile and voiding function. This type of injury is very rare in the literature: traumatic cavernosal arterial pseudoaneurysm is known to cause high flow priapism, but in this case additional cavernosal-urethral fistula resulted in a severe urethraggia. This is the only case, to our knowledge, of delayed urethral bleeding from cavernosal artery pseudoaneursym in combination with a cavernosal-urethral fistula.

Racial Variation in Semen Quality at Fertility Evaluation.

OBJECTIVE: To identify racial differences in semen quality among men living in the same geographic area and seeking fertility evaluation. METHODS: Men obtaining a semen analysis for infertility evaluation or treatment between 2012 and 2016 at a single center were identified, and demographic data including height, weight, body mass index (BMI), and age were described. Mean semen parameters and the proportions of men with suboptimal parameters based on the World Health Organization's fifth edition criteria were also compared based on race. Multivariable regression analysis was conducted incorporating age, BMI, and year of evaluation. Further subanalyses based on BMI were subsequently performed. RESULTS: White men produced greater volumes of semen on average; however, Asian men had higher sperm concentrations and total sperm count. A lower proportion of Asian men compared to white men had semen quality in the suboptimal range for most semen parameters, whereas a higher proportion of white men were found to have azoospermia. Stratification by BMI groups attenuated the observed differences between whites and Asians, yet Asian male semen quality remained higher. CONCLUSION: Among men evaluated for infertility at a single center, Asians had lower volume but higher sperm concentrations compared with whites, which was influenced by differences in azoospermia prevalence. Although anthropometric and demographic factors attenuated the differences, even after adjustment, the contrasts remained. Our study suggests that racial differences exist in semen quality at the time of infertility evaluation.

The Relationship Between Offspring Sex Ratio and Vasectomy Utilization.

OBJECTIVE: To determine if there was an association between vasectomy utilization and offspring sex ratio (male offspring : total offspring), as offspring sex preference may have an impact on family planning in the United States. METHODS: Using data from the National Institutes of Health-AARP Diet and Health Study, we calculated the number of sons and daughters of all men stratified by vasectomy status. We utilized a logistic regression model to determine if vasectomy utilization varies based on offspring sex ratio while accounting for known factors that impact vasectomy utilization. RESULTS: Of these men, 30,927 (30.8%) underwent vasectomy. Marital status, race, age, education level, region or state, and number of offspring were all significantly correlated with vasectomy utilization (P < .01). The sex ratio for vasectomized fathers (51.3%) was significantly higher than for fathers who had not undergone vasectomy (50.7%, P < .01). This difference remained even after we stratified by the total number of offspring: vasectomized men with 4 or more children had a sex ratio of 947 girls per 1000 boys, whereas the no vasectomy group had a sex ratio of 983 girls per 1000 boys (P < .01). For men with at least 2 children, each additional son increased the likelihood of vasectomy by 4% (P < .01), whereas each additional daughter led to a 2% decrease in vasectomy utilization (P = .03). CONCLUSION: Vasectomized fathers have a higher proportion of sons compared with non-vasectomized fathers, suggesting that offspring sex ratio is associated with a man's decision to undergo vasectomy. Further research is indicated to understand how offspring sex ratio impacts a man's contraceptive decisions.

Relationship between Vasectomy and Sexual Frequency.

INTRODUCTION: Men who are considering vasectomy as a means of contraception may have significant anxiety about their future sexual potency. As a result, couples may choose other forms of contraception with lower efficacy. AIM: We sought to determine the relationship between vasectomy and the frequency of sexual intercourse. METHODS: We analyzed data from cycles 6 (2002) to 7 (2006-2008) of the National Survey of Family Growth to compare the frequency of sexual intercourse of men who had undergone vasectomy with men who had not. Analysis was performed using data from male and female responders, and excluded men who had never had sex and those below age 25. We constructed a multivariate logistic regression model to adjust for demographic, socioeconomic, reproductive, and health factors. MAIN OUTCOME MEASURE: The main outcome measure was the sexual frequency in the last 4 weeks. RESULTS: Among male responders, a total of 5838 men met criteria for our study; 353 had undergone vasectomy. For vasectomized men, the average frequency of sexual intercourse was 5.9 times per month compared with 4.9 times for nonvasectomized men. After adjusting for age, marital status, race, education, health, body mass index, children, and income, vasectomized men had an 81% higher odds (95% confidence interval [CI] 6-201%) of having intercourse at least once a week compared with nonvasectomized men. A total number of 5211 female respondents reported 670 of their partners had undergone vasectomy. For partners of vasectomized men, the average frequency of intercourse was 6.3 times per month, compared with 6.0 times for partners of nonvasectomized men. After adjustment, women with vasectomized partners had a 46% higher odds (95% CI 5-103%) of having sexual intercourse at least once a week compared with women with nonvasectomized partners (P = 0.024). CONCLUSION: Vasectomy is not associated with decreased sexual frequency. This finding may be helpful to couples as they consider contraceptive options.

Patterns of urinary catheter consults in a tertiary care hospital.

INTRODUCTION: We reviewed the consultation patterns for difficult urethral catheter placement in tertiary care hospitals and developed a treatment algorithm for this common request. MATERIALS AND METHODS: We identified all urethral catheter consults obtained by urology residents at three tertiary care hospitals from October 2009 through October 2010. Only consults for inability to place urethral catheter by the referring team were included; hematuria or clot retention were excluded. Patient age, date of consultation, consulting service, prior urologic history, initial number of attempts, and final outcome were recorded. RESULTS: Eighty-one consults were recorded. Seventy-seven (96%) were male; the median age was 65 years. The most common consulting services were internal medicine (35%), intraoperative consults (17%), and the intensive care unit (17%). In 90% of cases, an initial attempt at catheter placement was attempted; 62% of these were made by nurses. Over half of patients had known urologic pathology. In 70% of cases, successful placement without other adjuncts was achieved by the urology resident. Twenty percent of patients required cystoscopic manipulation; nine percent required suprapubic tube placement. CONCLUSIONS: Catheterization was achieved without adjunct procedures in the majority of consults. These results support an algorithm in which all patients without a prior history of lower urinary tract pathology should undergo an initial placement attempt by the primary service physician. They also underscore the need for educational efforts to improve non-urologists' comfort level with placement of a standard Foley or Coudé catheter.

Peptides inhibitory for the transcriptional regulatory function of human papillomavirus E2.

PURPOSE: Human papillomavirus (HPV) infections are associated with cervical neoplasia. Cellular and viral proteins are known to interact with the papillomavirus E2 protein to initiate transcription and DNA replication in the HPV life cycle. Our aim was to identify peptides that bind to the HPV16 E2 protein and thereby inhibit its ability to alter the transcriptional activity of other genes. EXPERIMENTAL DESIGN: The HPV16 E2 protein was expressed and purified to near homogeneity in bacteria. We screened a phage display library of random peptides for ones that bound to HPV16 E2 protein. Among the isolated phage clones, we found that tryptophan-rich peptide sequences appeared repetitively in successive cycles of phage library panning. Replacement of the tryptophan amino acids in these dodecapeptides reduced the degree to which these peptides bound to the E2 protein. These E2-binding peptides were tested for their ability to inhibit the transcriptional regulatory function of E2 in a test cell line, which contained an E2 gene and a luciferase reporter gene driven by an E2-dependent transcriptional promoter. RESULTS: Delivery of four of the E2 binding peptides into the intracellular compartment of the test cell line resulted in suppression of the E2-dependent luciferase expression. Deletion of the tryptophan residues from these peptides reduced their E2 binding and their ability to suppress E2-dependent luciferase expression in the test cell line. CONCLUSIONS: These results suggest a strategy for the development of chemical inhibitors of E2-dependent transcription of viral genes in HPV-infected cells as an approach to the therapy of chronic HPV infections.