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Duplex collecting systems are common congenital abnormalities of the urinary tract but are infrequently reported in adult populations. This abnormality can present with hydroureteronephrosis secondary to urinary tract obstruction or concomitant vesicoureteral reflux (VUR), recurrent urinary tract infections (UTIs), and urinary incontinence. Options for surgical management include common-sheath ureteral reimplantation, uretero-ureterostomy, pyelostomy, and heminephroureterectomy. We report the case of a 39-year-old female with a duplex kidney who presented with severe hydroureteronephrosis following a sacrocolpopexy.

Background:. Although education is critical to the mission of academic medical centers in the United States, it is often not quantified and monetized as are their research and clinical missions. We undertook this survey to assess the perceived valuation of educational endeavors of plastic surgeon faculty at the U.S. academic medical centers. Methods:. A survey using Qualtrics software (Qualtrics, Provo, UT) was distributed to faculty members of the American Council of Academic Plastic Surgeons by electronic mail in February 2015. A total of 16 questions included both demographic information and Likert-item questions of perception of valuation of educational activities. For analysis, responses were grouped according to an adapted Net Promoter Score including “unsupportive” (0–6), “neutral” (7–8), and “supportive” (9–10). Results:. Sixty-five surveys were completed out of a total of 406, with an overall response rate of 16%. Kruskal-Wallis statistical analysis demonstrated that region and rank were not significant in perception of hospital or departmental support for educational activities. Respondents rated their departments as more supportive than their institutions (P < 0.05), and average perceived value rating of institutions was “unsupportive.” Financial support was associated with higher ratings with respect to support of institutions and departments. Mid-career faculty displayed a trend toward lower ratings of perception of support. Conclusions:. The majority of respondents perceived their institutions and departments as unsupportive of educational effort. Direct compensation to physicians for teaching efforts may improve faculty retention in academia and reduce physician burnout.

Purpose: This study aimed to assess the impact of a culturally targeted lifestyle course on the dietary and weight outcomes of Asian Americans., Design: This was an observational study of participants for a culturally targeted lifestyle course taught online by a Nutrition Scientist and Board-Certified Holistic Health Practitioner., Setting: From 2021 to 2022, 284 participants were recruited through 4 community organizations in Texas and completed the informed consent., Subjects: 140 Chinese Americans finished 3 surveys before, after, and 6 months after the course., Measures: Participants' fruit and vegetable consumption was assessed using the questionnaire from the Behavioral Risk Factor Surveillance System and their physical activities were evaluated by the Godin-Shephard Leisure-Time Exercise Questionnaire., Analysis: We conducted repeated measures ANOVA to compare participants' dietary and weight outcomes before, after, and 6 months after the course. Paired t -tests were performed to investigate how the outcomes differed from the baseline., Results: The participants' weights and BMI values at the 6-month follow-up were significantly lower than the baseline, though the changes were not significant immediately after the course. Rice consumption dropped significantly both after the class and at the 6-month follow-up. Participants also significantly reduced their intake of 100% juice and fried potatoes immediately after the class., Conclusion: Community-based Participatory Approaches might be used to improve the dietary and weight outcomes of Asian Americans., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Bladder cancer, a common urologic malignancy, has poor morbidity and mortality in sexual and gender minority (SGM) individuals, stemming from higher risk, poor access to care and lack of quality cancer care. To begin addressing this disparity, this review offers key considerations for evaluation, diagnosis and treatment of SGM individuals with bladder cancer. In addition to thorough medical and surgical history, initial evaluation should include discussion of patient goals for sexual function and organ preservation, as well as an evaluation of sexual function. Prior gender affirming surgery and patient specific sexual function goals will impact diagnosis and treatment approaches, including surgical and radiation therapy. Throughout care for SGM individuals with bladder cancer, it is critical to acknowledge the systemic discrimination that may be experienced by these individuals and approach conversations with sensitivity and humility and incorporate mental and social support as appropriate., Competing Interests: Declaration of competing interest All authors, except for Dr. Laura Bukavina, declare that they have no conflicts of interest related to this manuscript. Dr. Laura Bukavina discloses the following: she has served as a consultant for Charite and UroGen Pharma, holds the position of Associate Editor at European Urology, and is a member of the Editorial Board for Urology Times. Additionally, Dr. Bukavina has received funding from the Bladder Cancer Advocacy Network. These affiliations do not influence the scientific integrity of the work presented in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Isonitrile lipopeptides discovered from Actinobacteria have attracted wide attention due to their fascinating biosynthetic pathways and relevance to the virulence of many human pathogens including Mycobacterium tuberculosis. Specifically, the identification of the new class of isonitrile-forming enzymes that belong to non-heme iron (II) and α-ketoglutarate dependent dioxygenases has intrigued several research groups to investigate their catalytic mechanism. Here we summarize the recent studies on the biosynthesis of isonitrile lipopeptides from Streptomyces and Mycobacterium. The latest research on the core and tailoring enzymes involved in the pathway as well as the isonitrile metabolic enzymes are discussed in this review., Competing Interests: Declaration of competing interest The authors declare no competing financial interest or conflict of interest that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to evaluate cardiovascular disease (CVD) risk modification in patients with optimal weight loss (OWL) versus suboptimal weight loss SWL following MBS., Methods: This was a retrospective analysis. The 10-year risk CVD was estimated before and after one year of surgery using the "Framingham Score"., Results: 191 patients were included in our study. Mean baseline Framingham score was 7.2 ​± ​6.9%. According to the score, 54% of patients were classified as low risk (n ​= ​104), 23% as moderate (n ​= ​43), 20% moderately high (n ​= ​39) and 3% as high risk (n ​= ​5). One year after surgery, 91% of the patients showed reduction of their Framingham score. Mean CVD risk score decreased significantly to 4.1 ​± ​3.7% when compared to baseline (p-value is ​< ​0.001); 80% of patients classified as low risk (n ​= ​153), 13% as moderate (n ​= ​25), 7% moderately high (n ​= ​13) and 0% as high risk (n ​= ​0)., Conclusion: Weight loss after bariatric surgery reduces CVD risk scores and the magnitude of effect correlates with the degree of weight loss., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: Polygenic risk scores (PRSs) have been developed to identify men with the highest risk of prostate cancer. Our aim was to compare the performance of 16 PRSs in identifying men at risk of developing prostate cancer and then to evaluate the performance of the top-performing PRSs in differentiating individuals at risk of aggressive prostate cancer., Methods: For this case-control study we downloaded 16 published PRSs from the Polygenic Score Catalog on May 28, 2021 and applied them to Michigan Genomics Initiative (MGI) patients. Cases were matched to the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to obtain granular clinical and pathological data. MGI prospectively enrolls patients undergoing surgery at the University of Michigan, and MUSIC is a multi-institutional registry that prospectively tracks demographic, treatment, and clinical variables. The predictive performance of each PRS was evaluated using the area under the covariate-adjusted receiver operating characteristic curve (aAUC), and the association between PRS and disease aggressiveness according to prostate biopsy data was measured using logistic regression., Key Findings and Limitations: We included 18 050 patients in the analysis, of whom 15 310 were control subjects and 2740 were prostate cancer cases. The median age was 66.1 yr (interquartile range 59.9-71.6) for cases and 56.6 yr (interquartile range 42.6-66.7) for control subjects. The PRS performance in predicting the risk of developing prostate cancer according to aAUC ranged from 0.51 (95% confidence interval 0.51-0.53) to 0.67 (95% confidence interval 0.66-0.68). By contrast, there was no association between PRS and disease aggressiveness., Conclusions and Clinical Implications: Prostate cancer PRSs have modest real-world performance in identifying patients at higher risk of developing prostate cancer; however, they are limited in distinguishing patients with indolent versus aggressive disease., Patient Summary: Risk scores using data for multiple genes (called polygenic risk scores) can identify men at higher risk of developing prostate cancer. However, these scores need to be refined to be able to identify men with the highest risk for clinically significant prostate cancer., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To assess efficacy, comfort, and symptoms of a novel ureteral stent (RELIEF) substituting the distal semirigid coil of a traditional double-J for a floating, monofilament tether allowing coaptation of the ureteral orifice. Ureteral instrumentation notoriously cause discomfort, urgency, frequency, dysuria, and hematuria; prolonged morbidity is likely related to stent-associated vesicoureteral reflux (VUR). We hypothesized this design would eliminate VUR, be safe and provide comfort following intervention., Methods: Twenty-eight patients within a single institution were enrolled. Passive cystography was performed pre- and post-stent placement assessing VUR. Patients completed Ureteric Stent Symptoms Questionnaires (USSQ) before placement (baseline), postop day 1, and day of removal., Results: Twenty RELIEF stents were placed (11 female and 9 male). 95% demonstrated no VUR following placement. No unexpected adverse complications occurred; 1 patient opted for early stent removal for significant discomfort. Average total USSQ scores demonstrated statistically significant improvement between first and third surveys (P < .001). Statistically significant improvement in body pain, general health, and work performance scores were noted as well (P < .05)., Conclusion: The RELIEF stent eliminates VUR with similar stent-related morbidity and overall well-tolerance. RELIEF-associated USSQ scores were below published mean symptom scores for standard double-J stents and appear safe in this preliminary clinical trial., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Current literature demonstrates low rates of compliance with postvasectomy semen analysis (PVSA). This study sought to determine factors that correlate with noncompliance with PVSA., Methods: A retrospective chart review was conducted for patients who underwent vasectomy within our institution. ArcGIS was used to securely calculate the shortest driving time from each patient's home to the single PVSA drop-off site. Kruskal-Wallis and chi-square tests analyzed characteristics of patients who did and did not submit PVSA samples, and odds ratios were calculated via multivariable logistic regression., Results: Overall, 515 of 850 patients met inclusion criteria and 219 (42.5%) of these had no recorded PVSA. Of those with a PVSA, 59% were completed within 16 weeks. Compliance with PVSA was associated with a shorter median driving time (30.6 minutes vs 34.2 minutes), more vasectomy in the operating room (19% vs 10%), and attending a follow-up appointment (40% vs 17%) (P < .005 for all). Age at vasectomy, race, ethnicity, BMI, paternity, and location of preoperative consultation did not significantly differ between the groups. Each 30 minutes of driving time was associated with a 48% reduction in the odds of a patient submitting PVSA at any time (OR 0.52 [0.37, 0.73])., Conclusion: As driving time to a drop-off center appears to be a significant barrier to PVSA compliance, providers should consider alternative collection methods such as at-home or in-office semen analysis., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction and Hypothesis: The objective was to comprehensively analyze YouTube™ videos focusing on genital gender-affirmation surgery (GAS) from the perspective of urologists and gynecologists and to utilize results to create educational videos for transgender individuals with accurate and engaging content., Methods: A YouTube search was performed using the keywords "Metoidioplasty," "Phalloplasty," "Gender affirmation surgery," "Transgender surgery," "Vaginoplasty," and "Male-to-female surgery." Video results that were duplicated, non-English, of low relevance, non-audio, and/or short duration (under 2 min) were excluded. The upload source was classified as university/nonprofit physician or organization, health information websites, medical advertisement/for-profit organizations, or individual patient experience. Viewer engagement metrics were obtained for each video. Each video was evaluated using the DISCERN, Global Quality Score (GQS), and Patient Education Materials Assessment Tool for audio-visual content (PEMAT A-V) tools., Results: A total of 273 videos were evaluated. Viewer engagement metrics of videos from the patient experience group were higher than those of both universities/nonprofit physicians and medical advertisement/for-profit groups. DISCERN and GQS scores were significantly lower in videos uploaded by the patient experience group than in each of the other upload sources. More videos covered female-to-male (FtM) transition (168, 61.5%) than covered male-to-female (MtF; 71, 26.0%), and both (34, 12.5%). MtF transition videos had significantly higher total view counts than videos from the other groups (p<0.001). The like counts of videos were significantly higher in both MtF transition and FtM transition groups than for videos explaining both types of transition within the same video. The total DISCERN score was significantly lower in FtM transition videos than in the other content groups. Two educational videos were prepared, informed by the tools and results of this study, and hosted on YouTube., Conclusions: The findings suggest that genital GAS videos with less technical content have higher audience engagement. This information should be used to aid medical organizations when creating YouTube content to provide accurate information to larger audiences in the transgender community., (© 2023. The International Urogynecological Association.)

RC significantly negatively impacts sexual function (SF) in both men and women. While significant research resources have been allocated to examine the deleterious effects of post prostatectomy erectile dysfunction, little attention has been directed towards female sexual function and organ preservation post cystectomy. These academic shortcomings often result in poor provider awareness and inadequate preoperative assessment. As such, it is crucial for all providers involved in female RC care to understand the necessary and available tools for preoperative evaluation, in addition to the anatomic and reconstructive techniques. This review aims to summarize the current preoperative evaluation and available tools of SF assessment and describe in detail the varying operative techniques in the preservation or restoration of SF in women after RC. The review explores the intricacies of preoperative evaluation tools, and intraoperative techniques for organ- and nerve-sparing during radical cystectomy in females. Particular emphasis on vaginal reconstruction after partial or complete resection is provided, including split-thickness skin (STF) graft vaginoplasy, pedicled flaps, myocutaneous flaps and use of bowel segments. In conclusion, this narrative review highlights the importance of understanding anatomic considerations and nerve-sparing strategies in promoting postoperative SF and quality of life. Furthermore, the review describes the advantages and limitations of each organ- and nerve-sparing technique and their impact on sexual function and overall well-being., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To describe the outcomes of Same-Day Discharge (SDD) following Holmium Laser Enucleation of the Prostate (HoLEP) in patients during the COVID-19 pandemic., Methods: A retrospective review of HoLEP surgeries at a single institution between January 2021 and March 2022 was performed. Patient demographic and operative data were collected, and postoperative outcomes were evaluated in terms of safety and efficacy and compared in both groups using a t-test and chi-square test. Logistic regression was also performed to identify factors that correlate with the failure of SDD., Results: A total of 155 patients were identified; 135 patients were successfully discharged on the same day and 20 were admitted (87% SDD rate). Admitted HoLEP patients had a significantly higher median prostate-specific antigen (5.7 vs 3.9 ng/dL, P < 0.001), prostate volume (152.3 vs 100.6 mL, P < 0.001), and enucleated tissue weight (90.3 vs 56.9 g, P = 0.04) compared to the SDD group. The SDD group had a 2.9% (n = 4) readmission rate and a 5.2% (n = 7) Emergency Department (ED) visit rate. There was no significant difference in the rate of postoperative ED visits (P = 0.64), readmissions (P = 0.98), complications, and catheterization time (P = 0.98) between both groups. Preoperative predictors of SDD failure included prostate gland volume > 150 mL (OR = 7.17; CI 2.01-25.67; P < 0.01) and history of antiplatelet/anticoagulation use (OR = 6.59; CI 2.00-21.67; P < 0.01)., Conclusion: Same-day discharge following HoLEP is a safe and effective approach that can be performed in most patients using a liberal discharge criteria and relying on postoperative findings only., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Gender disparities in editorial board composition exist across a variety of surgical subspecialties., Objective: To investigate temporal variation in gender representation on the editorial boards of urology journals and assess the relationship between editorial board composition and female authorship., Design, Setting, and Participants: We analyzed female authorship and editorial board composition between 2002 and 2020 among eight high-impact urology journals. Female publication status was assessed using publication records retrieved from PubMed. Editorial board information was manually extracted and titles were grouped for comparison as Editor-in-Chief, mid-level editor, and consulting editors., Outcome Measurements and Statistical Analysis: Female representation across different editorial levels was analyzed via hierarchical logistic regression with additional terms to test for between-journal differences in overall representation and change over time. The relationship between representation on editorial boards and as publication authors was assessed at the journal level via correlation., Results and Limitations: Eight journals and 49 412 articles were analyzed. No female has held the title of Editor-in-Chief for any of these eight journals in 18 yr. Significant growth was seen for mid-level editors, whereas no growth was seen for consulting editors. Neurourology and Urodynamics and Journal of Sexual Medicine had significantly higher than average female editorial board representation (p < 0.05). Across the eight journals, there was a statistically significant correlation between the proportion of overall female authors and female editors (r = 0.93, 95% confidence interval 0.65-0.99). For all journals, the proportion of female contributing authors is greater than the proportion of female editorial board members., Conclusions: Women in urology represent a small but increasing presence as editorial board members. Clear differences exist between journals, potentially attributable to specialty-specific demographics. Despite increasing representation, no female has ever been appointed Editor-in-Chief for any of the eight journals evaluated. At the journal-specific level, a positive correlation was observed between female editorial staff and female authorship. Given the implication of both academic authorship and editorial board assignment on academic advancement, actionable changes are outlined to guide improvement in gender diversity at the journal level., Patient Summary: Females are under-represented on the editorial boards for urology journals, although some roles have seen growth over time. Moreover, female editorial board membership is associated with representation of females among article authors. Gender disparities in both are noteworthy because they affect career paths and contribute to the gender gap in urology., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Academic authorship is a critical productivity metric used for academic promotion., Objective: To characterize temporal changes in female representation in academic authorship in ten primary urology journals as the complement of female urologists is increasing., Design, Setting, and Participants: Publication records were retrieved from 2002 to 2020 for the ten urology journals with the highest impact factor. The names of all authors were gathered and gender was inferred using first names., Outcome Measurements and Statistical Analysis: Trends in first and last/senior authorship by gender were evaluated overall, within journals, and by geographic region., Results: A total of 59,375 articles were analyzed, of which 94.1% had gender information for the first author and 94.2% had gender information for the last author. The percentage of overall female authors increased positively from 17.2% (95% highest density interval [HDI] 12.9-21.4%) in 2002 to 27.2% (HDI 21.7-33.6%; p < 0.01) in 2020. Overall female first authorship increased from 15.2% (95% HDI 11.0-19.5%) to 28.5% (95% HDI 21.8-35.6%; p < 0.01). There was also significant growth for female senior authors from 10.4% (95% HDI 7.6-13.5%) to 18.6% (95% HDI 13.6-23.8%; p < 0.01). Assessment of journal-specific changes revealed that Neurourology and Urodynamics (12.6%, 95% HDI 9.9-15.1%) and The Journal of Sexual Medicine (16.2%, 95% HDI 13.6-19.0%) had significantly higher growth in female authorship when compared to Journal of Endourology (7.2%, 95% HDI 5.5-8.7%) and Urologic Oncology (4.5%, 95% HDI 2.0-6.8%; p < 0.05)., Conclusions: Although overall female authorship increased between 2002 and 2020, women remain underrepresented in urology authorship. The percentage of females in senior (last) author positions is less than the percentage of females in first author positions. Journal-specific differences can probably be attributed to gender-based differences in subspecialized fields., Patient Summary: In this study, we characterized the underrepresentation of women as authors in urology journals and analyzed the change in female authorship for ten academic urology journals over the course of 18 years. Although the proportion of female authors has increased over that time, the percentage of females in senior authorship roles is less than the percentage of females in first author positions., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The All of Us Research Program seeks to advance precision medicine and reduce health disparities by recruiting people in demographic categories that are underrepresented in biomedical research. Asian Americans, Native Hawaiians and Pacific Islanders are the most understudied of all racial/ethnic groups in the United States. We propose a national engagement strategy for the recruitment of Asian Americans, Native Hawaiians and Pacific Islanders into biomedical research using a community-based participatory research approach., Methods: We partnered with Asian serving community-based organizations across the United States to increase education and awareness and developed a culturally and linguistically tailored approach for the engagement of AANHPIs into All of Us Research Program., Results: In the first year, our national engagement strategy reached more than 35,000 AANHPIs through promotional events and educational sessions., Conclusions: Our success is a result of our equal and mutually beneficial partnership with community-based organizations who have access to rich, local knowledge and hold a unique role within the community.

Pressure injuries are a significant problem following spinal cord injury (SCI). High interface pressures while lying on a spine board during emergency transport appear to play a major role in their formation. The aim of the present study was to assess the interface pressures and sensing area between the body and the standard spine board (SSB) and a proof of concept spine board prototype ( P -5). Twenty-one able-bodied subjects were assessed on each board. Interface pressures and sensing area were recorded every minute over 15 min. The mean peak pressure was higher on the SSB at the head, scapulothoracic (S-T), sacroiliac (S-I), and heels (227.6 mmHg, 148.9 mmHg, 360.3 mmHg, and 179.3 mmHg) compared to P -5 (51.9 mmHg, 60.1 mmHg, 66.8 mmHg, and 60.2 mmHg). The peak pressure index (PPI) at the head, S-T and S-I was higher on the SSB (100.2 mmHg, 101.6 mmHg, and 270.6 mmHg) compared to P -5 (41.6 mmHg, 51.9 mmHg and 58.7 mmHg). An analysis using pairwise comparisons for repeated measures showed that interface pressures ( p < .05) and PPI ( p < .001) were reduced at all locations. Modifications of a spine board incorporated in P -5 can dramatically reduce interface pressures and reduce pressure injury formation.

Objective: To better understand the interplay of socioeconomic and demographic traits on bladder cancer outcomes utilizing the Ohio state cancer registry, Ohio Cancer Incidence Surveillance System (OCISS)., Methods: We obtained demographic, clinical and outcome data on 47,182 bladder cancer cases diagnosed from 1996 to 2016 from OCISS. Multivariable Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between sex, race and poverty and survival, adjusting age, stage, and primary treatment., Results: Within the OCISS database, there were 47,182 patients with a diagnosis of bladder cancer identified, with females representing 12,056 (26%) of the population. There were a total of 9255(35.2%) deaths due to bladder cancer, with median follow-up time of 4.4 years. After adjusting for confounding variables, women were statistically significantly less likely to die from any cause (HR: 0.94, 95% CI: 0.91-0.96), compared with men, but more likely to die from bladder cancer (HR: 1.21, 95% CI: 1.15-1.27). We also found that after adjusting for confounding variables, including sex and poverty, black race was statistically significantly associated with a higher risk of overall (HR: 1.12, 95% CI: 1.06-1.18) and bladder cancer-specific mortality (HR: 1.25, 95% CI: 1.15-1.36)., Conclusion: Using the OCISS database, female gender, self-reported black race, and neighborhood poverty level were associated with worse bladder cancer-specific survival. By recognizing these disparities, we can prospectively address risk factors in efforts to improve survival among these patient populations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Asian Americans are the fastest growing racial/ethnic group in the USA, as this population increased by 72% between 2000 and 2015. Chinese Americans are the largest Asian subgroup, with a high immigrant proportion (63%), a high poverty rate (14%), and a large percentage of low English competency (41%). Colorectal cancer (CRC) is the second most commonly diagnosed cancer and cause of cancer death among Chinese Americans. As CRC has a genetic predisposition, family health history (FHH) has been proposed as a preventive tool to stratify CRC risk and guide personalized screening and behavioral modifications. The purpose of this study was to adopt a community-based participatory research (CBPR) approach to develop the first culturally and linguistically appropriate FHH-based CRC prevention program for Chinese Americans in Texas. The program development involved five CBPR steps: (1) establishment of partnership and research team, (2) literature review and needs assessment, (3) creation of a theoretical framework of the FHH-based CRC prevention, (4) development a culturally and linguistically appropriate intervention, and (5) program evaluation. Key components of this program included two intervention activities: (1) a culturally and linguistically appropriate FHH-based CRC prevention workshop and (2) a follow-up individualized phone consultation and health insurance enrollment and navigation services (if needed). The pilot study suggested feasibility of the program. This CBPR-grounded, FHH-based CRC prevention project can serve as a model for future cancer prevention programs targeting other types of cancers that also have FHH components.

RIP1 kinase regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including inflammatory and neurological diseases. Currently, RIP1 kinase inhibitors have advanced into early clinical trials for evaluation in inflammatory diseases such as psoriasis, rheumatoid arthritis, and ulcerative colitis and neurological diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. In this paper, we report on the design of potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitors starting from a high-throughput screen and the lead-optimization of this series from a lead with minimal rat oral exposure to the identification of dihydropyrazole 77 with good pharmacokinetic profiles in multiple species. Additionally, we identified a potent murine RIP1 kinase inhibitor 76 as a valuable in vivo tool molecule suitable for evaluating the role of RIP1 kinase in chronic models of disease. DHP 76 showed efficacy in mouse models of both multiple sclerosis and human retinitis pigmentosa.

Introduction and Hypothesis: Transvaginal bladder-neck closure is a definitive surgical option for urethral erosion due chronic bladder catheterization in patients with neurogenic bladder. Surgeons who perform female pelvic reconstructive surgery have limited exposure to this procedure in their training. The purpose of this video is to demonstrate a transvaginal bladder-neck closure due to urethral erosion in a patient with neurogenic bladder due to persistent neuropathy from Guillain-Barré syndrome managed with prolonged catheter drainage., Methods: We used a live-action surgical demonstration to describe transvaginal bladder-neck closure with urinary diversion., Results: This video provides a step-by-step approach to transvaginal bladder-neck closure as treatment for urethral erosion from chronic catheterization. This video can be used to educate and train those performing female pelvic reconstructive surgery., Conclusions: Surgeons who perform female pelvic surgery should be familiar with the complications of chronic Foley catheterization and treatment options that include transvaginal bladder-neck closure. This video may be used to facilitate reproducibility and comprehension of this procedure.

Although Asian Americans generally have the lowest cancer incidence rates and mortality rates, cancer is the leading cause of death among Asian Americans. The goal of this pilot study was to engage Chinese American cancer survivors (CACS) in systematic changes toward desired health behaviors through a healthy lifestyle intervention delivered by a community-based organization. The Reach out to ENhanceE Wellness (RENEW) program workbook was translated into Mandarin Chinese with additional physical activity (PA) and dietary information that are culturally appropriate (RENEW-C). Fifty-five Chinese cancer survivors were recruited from the greater Houston area to participate in this 50-week program and 50 of them completed both the baseline and postintervention surveys in 2013 and 2014, respectively. Paired sample t tests were used to assess changes in 5 groups of outcomes: (1) patient knowledge (measured by Health Education Impact Questionnaire [heiQ]), (2) dietary intake (Automated Self-Administered 24-Hour [ASA24] Dietary Assessment Tool), (3) PA (Community Healthy Activities Model Program for Seniors [CHAMPS]), (4) body mass index, and (5) quality of life (36-item Short-Form Survey [SF-36]). Compared with the baseline, participants reported significantly higher consumption of vegetables and higher frequency of PAs at the postintervention survey. They also showed improved mental health and lower limitation in doing their work or other activities due to physical health or emotional problems. Despite the small sample size, this pilot study demonstrated the effectiveness of using a community-based participatory approach in a healthy lifestyle intervention tailored for CACS.

Therapies that suppress RIPK1 kinase activity are emerging as promising therapeutic agents for the treatment of multiple inflammatory disorders. The ability to directly measure drug binding of a RIPK1 inhibitor to its target is critical for providing insight into pharmacokinetics, pharmacodynamics, safety and clinical efficacy, especially for a first-in-class small-molecule inhibitor where the mechanism has yet to be explored. Here, we report a novel method for measuring drug binding to RIPK1 protein in cells and tissues. This TEAR1 (Target Engagement Assessment for RIPK1) assay is a pair of immunoassays developed on the principle of competition, whereby a first molecule (ie, drug) prevents the binding of a second molecule (ie, antibody) to the target protein. Using the TEAR1 assay, we have validated the direct binding of specific RIPK1 inhibitors in cells, blood and tissues following treatment with benzoxazepinone (BOAz) RIPK1 inhibitors. The TEAR1 assay is a valuable tool for facilitating the clinical development of the lead RIPK1 clinical candidate compound, GSK2982772, as a first-in-class RIPK1 inhibitor for the treatment of inflammatory disease., (© 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Chronic inflammation may contribute to insulin resistance via molecular cross-talk between pathways for pro-inflammatory and insulin signaling. Interleukin 1 receptor-associated kinase 1 (IRAK-1) mediates pro-inflammatory signaling via IL-1 receptor/Toll-like receptors, which may contribute to insulin resistance, but this hypothesis is untested. Here, we used male Irak1 null (k/o) mice to investigate the metabolic role of IRAK-1. C57BL/6 wild-type (WT) and k/o mice had comparable body weights on low-fat and high-fat diets (LFD and HFD, respectively). After 12 weeks on LFD (but not HFD), k/o mice ( versus WT) had substantially improved glucose tolerance (assessed by the intraperitoneal glucose tolerance test (IPGTT)). As assessed with the hyperinsulinemic euglycemic glucose clamp technique, insulin sensitivity was 30% higher in the Irak1 k/o mice on chow diet, but the Irak1 deletion did not affect IPGTT outcomes in mice on HFD, suggesting that the deletion did not overcome the impact of obesity on glucose tolerance. Moreover, insulin-stimulated glucose-disposal rates were higher in the k/o mice, but we detected no significant difference in hepatic glucose production rates (± insulin infusion). Positron emission/computed tomography scans indicated higher insulin-stimulated glucose uptake in muscle, but not liver, in Irak1 k/o mice in vivo Moreover, insulin-stimulated phosphorylation of Akt was higher in muscle, but not in liver, from Irak1 k/o mice ex vivo In conclusion, Irak1 deletion improved muscle insulin sensitivity, with the effect being most apparent in LFD mice., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Objective: To test whether alcohol advertising expenditures and the degree of exposure to alcohol advertisements affect alcohol consumption by youth., Design: Longitudinal panel using telephone surveys., Setting: Households in 24 US media markets, April 1999 to February 2001., Participants: Individuals aged 15 to 26 years were randomly sampled within households and households within media markets. Markets were systematically selected from the top 75 media markets, representing 79% of the US population. The baseline refusal rate was 24%. Sample sizes per wave were 1872, 1173, 787, and 588. Data on alcohol advertising expenditures on television, radio, billboards, and newspapers were collected., Main Exposures: Market alcohol advertising expenditures per capita and self-reported alcohol advertising exposure in the prior month., Main Outcome Measure: Self-reported number of alcoholic drinks consumed in the prior month., Results: Youth who saw more alcohol advertisements on average drank more (each additional advertisement seen increased the number of drinks consumed by 1% [event rate ratio, 1.01; 95% confidence interval, 1.01-1.02]). Youth in markets with greater alcohol advertising expenditures drank more (each additional dollar spent per capita raised the number of drinks consumed by 3% [event rate ratio, 1.03; 95% confidence interval, 1.01-1.05]). Examining only youth younger than the legal drinking age of 21 years, alcohol advertisement exposure and expenditures still related to drinking. Youth in markets with more alcohol advertisements showed increases in drinking levels into their late 20s, but drinking plateaued in the early 20s for youth in markets with fewer advertisements. Control variables included age, gender, ethnicity, high school or college enrollment, and alcohol sales., Conclusion: Alcohol advertising contributes to increased drinking among youth.

The transcriptional activator protein Bas2 is required to express more than 20 genes in pathways for purine nucleotide and histidine biosynthesis, phosphate utilization, and the HO endonuclease by acting with co-regulator proteins Bas1, Pho4, and Swi5. The role that Bas2 plays in transcriptional activation may be to unmask latent activation domains in the co-regulator and to promote ternary complex formation between Bas2, the co-regulator, and DNA. We show that Bas2 also contributes to transcriptional activation by providing an activation domain. We localize this domain in Bas2 to the C-terminal 156 amino acids using deletion analysis and fusion to a heterologous DNA binding domain. Additionally, we show that Bas2 makes direct contacts with Bas1. This interaction is detected by co-immunoprecipitation and by two-hybrid analysis. We localize the interaction region to the central portion of Bas2, from amino acids 112 to 404.