Development and Evaluation of a Multi-Institutional Virtual Urology Course for Medical Students.

OBJECTIVE: Urological education has been declining in medical schools, leaving many students without adequate exposure to the fundamentals of the field. We aimed to create a virtual urology course for medical students preparing for subinternships. DESIGN: We created a 4-week curriculum of case-based urology modules with sections on hematuria, bladder cancer, kidney stones, vesicoureteral reflux, prostate cancer, urinary incontinence, and erectile dysfunction. Students completed precourse and postcourse surveys assessing confidence in content knowledge and 4 educational competencies. Faculty completed postcourse surveys. Confidence was scored on a 5-point Likert scale (0-4). SETTING: We offered the course in May 2022 and May 2023. The course was fully virtual and was offered at medical schools across the United States. PARTICIPANTS: The course included 157 medical students from 60 institutions and 44 faculty instructors from 30 institutions. All instructors were urologists representing a range of urological subspecialties. RESULTS: Surveys were completed by 61/157 students (39%) and 33/44 faculty (75%). Median student confidence in content knowledge increased across all disease processes: hematuria (3 vs. 2), bladder cancer (3 vs. 1), kidney stones (3 vs. 2), vesicoureteral reflux (3 vs. 1), prostate cancer (3 vs. 1), urinary incontinence (3 vs. 2), and erectile dysfunction (3 vs. 2) (all p < 0.001). Median confidence scores also increased across all 4 educational competencies: patient evaluation (3 vs. 2), pathophysiology (3 vs. 2), literature appraisal (3 vs. 2), and patient counseling (3 vs. 1) (all p < 0.001). Confidence increases in all areas were maintained at 7-month follow-up. Most students (85%) and faculty (91%) rated the course "excellent" or "very good." CONCLUSIONS: A multi-institutional virtual urology course for medical students led to a durable increase in confidence pertaining to content knowledge and various educational competencies.

The Impact of Single-Use Cystoscopes on Clinical Time Workflow in an Outpatient Setting.

OBJECTIVE: To evaluate the change in overall clinical encounter time and clinical capacity after transitioning to single-use cystoscopes (Ambu A/S, Ballerup, Denmark) in an outpatient urology setting. METHODS: A single-institution prospective study in an outpatient urology procedure clinic was performed. Discrete categories for each portion of nursing care responsibilities were defined, and time spent during each category was recorded. Two separate clinic days were observed and analyzed: one where the clinic exclusively used reusable cystoscopes and the other after the transition to single-use cystoscopes occurred. Additionally, clinic schedules were reviewed from all procedure clinics in the 3-month periods before and after the transition to single-use cystoscopes. Outcomes included overall clinical encounter time and the number of procedures per clinic day. RESULTS: There were 12 flexible cystoscopies performed during each of the observed clinic days. Preliminary cystoscope cleaning and transportation tasks by nursing staff were eliminated when utilizing single-use cystoscopes. Average total encounter time decreased from 66 to 44 minutes, resulting in a 34% reduction in clinical encounter time. The median number of flexible cystoscopy procedures increased after the transition from 9 (IQR 7-12) to 16 (IQR 11-17), representing a 78% increase (P = .003). CONCLUSION: Transition to a completely single-use cystoscopy outpatient procedure clinic improved clinical efficiency and facilitated an increased number of procedures per clinic day.

Capsid-mediated control of adeno-associated viral transcription determines host range.

Adeno-associated virus (AAV) is a member of the genus Dependoparvovirus, which infects a wide range of vertebrate species. Here, we observe that, unlike most primate AAV isolates, avian AAV is transcriptionally silenced in human cells. By swapping the VP1 N terminus from primate AAVs (e.g., AAV8) onto non-mammalian isolates (e.g., avian AAV), we identify a minimal component of the AAV capsid that controls viral transcription and unlocks robust transduction in both human cells and mouse tissue. This effect is accompanied by increased AAV genome chromatin accessibility and altered histone methylation. Proximity ligation analysis reveals that host factors are selectively recruited by the VP1 N terminus of AAV8 but not avian AAV. Notably, these include AAV essential factors implicated in the nuclear factor κB pathway, chromatin condensation, and histone methylation. We postulate that the AAV capsid has evolved mechanisms to recruit host factors to its genome, allowing transcriptional activation in a species-specific manner.

Trends in Opioid and Nonsteroidal Anti-Inflammatory Drug Use for Patients with Kidney Stones in United States Emergency Departments from 2015 to 2021.

Introduction: Renal colic is frequently treated with opioids; however, narcotic analgesic use can lead to dependence and abuse. We evaluated use trends of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management of kidney stones in United States emergency departments (EDs) from 2015 to 2021. Methods: Kidney stone encounters were identified using National Hospital Ambulatory Medical Care Survey data. We applied a multistage survey weighting procedure to account for selection probability, nonresponse, and population weights. Medication use trends were estimated through logistic regressions on the timing of the encounter, adjusted for selected demographic and clinical characteristics. Results: Between 2015 and 2021, there were an estimated 9,433,291 kidney stone encounters in United States EDs. Opioid use decreased significantly (annual odds ratio [OR]: 0.87, p = 0.003), and there was no significant trend in NSAID use. At discharge, male patients were more likely than females (OR: 1.93, p = 0.001) to receive opioids, and Black patients were less likely than White patients (OR: 0.34, p = 0.010) to receive opioids. Regional variation was also observed, with higher odds of discharge prescriptions in the West (OR: 3.15, p = 0.003) and Midwest (OR: 2.49, p = 0.010), compared with the Northeast. Thirty-five percent of patients received opioids that were stronger than morphine. Conclusion: These results suggest improved opioid stewardship from ED physicians in response to the national opioid epidemic. However, regional variation as well as disparities in discharge prescriptions for Black and female patients underscore opportunities for continued efforts.

Associations Between Sexual Behavior Stigma and HIV Risk Behaviors, Testing, Treatment, and Infection Among Men Who have Sex with Men in Ukraine.

Stigma toward same-sex behaviors may be a structural driver of HIV epidemics among men who have sex with men (MSM) in Eastern Europe and has been linked to adverse HIV-outcomes elsewhere. We explored associations between sexual behavior stigma with HIV risk behaviors, testing, treatment, and infection. From November 2017 to February 2018, MSM across 27 Ukrainian cities were recruited to cross-sectional surveys using respondent driven sampling. Eligible participants were cisgender males aged ≥ 14 years residing in participating cities that reported ≥ 1 sexual contact with another man in the prior 6 months. Participants self-reported experience of stigma (ever) and various HIV-outcomes and were tested for HIV antibodies. Regression models were used to explore associations between three sexual behavior stigma variables with demographic and HIV-related variables. Of 5812 recruited cisgender MSM, 5544 (95.4%) were included. 1663 (30.0%) MSM reported having experienced stigma due to being MSM from family and friends, 698 (12.6%) reported anticipated healthcare stigma, and 1805 (32.6%) reported general public/social stigma due to being MSM (enacted). All forms of stigma were associated with heightened HIV risk behaviors; those experiencing stigma (vs not) had more anal sex partners in the prior month and were less likely to have used condoms during their last anal intercourse. Stigma was not associated with HIV infection, testing, or treatment variables. A sizeable proportion of Ukrainian MSM reported ever experiencing stigma due to being MSM. MSM that had experienced stigma had higher odds of HIV sexual risk behaviors. Further study using longitudinal designs is required to determine causality.

Traumatic Brain Injury-Induced Fear Generalization in Mice Involves Hippocampal Memory Trace Dysfunction and Is Alleviated by (R,S)-Ketamine.

BACKGROUND: Traumatic brain injury (TBI) is a debilitating neurological disorder caused by an impact to the head by an outside force. TBI results in persistent cognitive impairments, including fear generalization and the inability to distinguish between aversive and neutral stimuli. The mechanisms underlying fear generalization have not been fully elucidated, and there are no targeted therapeutics to alleviate this symptom of TBI. METHODS: To identify the neural ensembles mediating fear generalization, we utilized ArcCreERT2 × enhanced yellow fluorescent protein (EYFP) mice, which allow for activity-dependent labeling and quantification of memory traces. Mice were administered a sham surgery or the controlled cortical impact model of TBI. Mice were then administered a contextual fear discrimination paradigm and memory traces were quantified in numerous brain regions. In a separate group of mice, we tested if (R,S)-ketamine could decrease fear generalization and alter the corresponding memory traces in TBI mice. RESULTS: TBI mice exhibited increased fear generalization when compared with sham mice. This behavioral phenotype was paralleled by altered memory traces in the dentate gyrus, CA3, and amygdala, but not by alterations in inflammation or sleep. In TBI mice, (R,S)-ketamine facilitated fear discrimination, and this behavioral improvement was reflected in dentate gyrus memory trace activity. CONCLUSIONS: These data show that TBI induces fear generalization by altering fear memory traces and that this deficit can be improved with a single injection of (R,S)-ketamine. This work enhances our understanding of the neural basis of TBI-induced fear generalization and reveals potential therapeutic avenues for alleviating this symptom.

Current laser therapy options for endoscopic treatment of upper tract urothelial carcinoma.

Endoscopic management via retrograde ureteroscopic laser ablation of upper tract urothelial carcinoma (UTUC) has become the preferred treatment modality for low-risk tumors. The most popular ablative lasers over the past 15-20 years have been the holmium:yttrium-aluminum-garnet (Ho:YAG) and neodymium (Nd:YAG) lasers, but recently the thulium (Th:YAG) laser has emerged as a potential alternative. This review compares the mechanism of action, physiological properties and effects, and oncologic outcomes of Ho:YAG/Nd:YAG lasers versus the Th:YAG laser for UTUC treatment. Potential advantages of the Th:YAG laser over existing technologies are outlined, followed by a discussion of emerging laser technologies in UTUC management.

Longitudinal Changes in the Operative Experience for Junior Urology Residents.

OBJECTIVE: To evaluate longitudinal trends in surgical case volume among junior urology residents. There is growing perception that urology residents are not prepared for independent practice, which may be linked to decreased exposure to major cases early in residency. METHODS: Retrospective review of deidentified case logs from urology residency graduates from 12 academic medical centers in the United States from 2010 to 2017. The primary outcome was the change in major case volume for first-year urology (URO1) residents (after surgery internship), measured using negative binomial regression. RESULTS: A total of 391,399 total cases were logged by 244 residency graduates. Residents performed a median of 509 major cases, 487 minor cases, and 503 endoscopic cases. From 2010 to 2017, the median number of major cases performed by URO1 residents decreased from 64 to 49 (annual incidence rate ratio 0.90, P < .001). This trend was limited to oncology cases, with no change in reconstructive or pediatric cases. The number of major cases decreased more for URO1 residents than for residents at other levels (P-values for interaction <.05). The median number of endoscopic cases performed by URO1 residents increased from 85 to 194 (annual incidence rate ratio 1.09, P < .001), which was also disproportionate to other levels of residency (P-values for interaction <.05). CONCLUSION: There has been a shift in case distribution among URO1 residents, with progressively less exposure to major cases and an increased focus on endoscopic surgery. Further investigation is needed to determine if this trend has implications on the surgical proficiency of residency graduates.

Traumatic brain injury-induced fear generalization in mice involves hippocampal memory trace dysfunction and is alleviated by ( R,S )-ketamine.

INTRODUCTION: Traumatic brain injury (TBI) is a debilitating neurological disorder caused by an impact to the head by an outside force. TBI results in persistent cognitive impairments, including fear generalization, the inability to distinguish between aversive and neutral stimuli. The mechanisms underlying fear generalization have not been fully elucidated, and there are no targeted therapeutics to alleviate this symptom of TBI. METHODS: To identify the neural ensembles mediating fear generalization, we utilized the ArcCreER T2 x enhanced yellow fluorescent protein (EYFP) mice, which allow for activity-dependent labeling and quantification of memory traces. Mice were administered a sham surgery or the controlled cortical impact (CCI) model of TBI. Mice were then administered a contextual fear discrimination (CFD) paradigm and memory traces were quantified in numerous brain regions. In a separate group of mice, we tested if ( R,S )-ketamine could decrease fear generalization and alter the corresponding memory traces in TBI mice. RESULTS: TBI mice exhibited increased fear generalization when compared with sham mice. This behavioral phenotype was paralleled by altered memory traces in the DG, CA3, and amygdala, but not by alterations in inflammation or sleep. In TBI mice, ( R,S )-ketamine facilitated fear discrimination and this behavioral improvement was reflected in DG memory trace activity. CONCLUSIONS: These data show that TBI induces fear generalization by altering fear memory traces, and that this deficit can be improved with a single injection of ( R,S )-ketamine. This work enhances our understanding of the neural basis of TBI-induced fear generalization and reveals potential therapeutic avenues for alleviating this symptom.

Developing a machine learning model to detect diagnostic uncertainty in clinical documentation.

BACKGROUND AND OBJECTIVE: Diagnostic uncertainty, when unrecognized or poorly communicated, can result in diagnostic error. However, diagnostic uncertainty is challenging to study due to a lack of validated identification methods. This study aims to identify distinct linguistic patterns associated with diagnostic uncertainty in clinical documentation. DESIGN, SETTING AND PARTICIPANTS: This case-control study compares the clinical documentation of hospitalized children who received a novel uncertain diagnosis (UD) diagnosis label during their admission to a set of matched controls. Linguistic analyses identified potential linguistic indicators (i.e., words or phrases) of diagnostic uncertainty that were then manually reviewed by a linguist and clinical experts to identify those most relevant to diagnostic uncertainty. A natural language processing program categorized medical terminology into semantic types (i.e., sign or symptom), from which we identified a subset of these semantic types that both categorized reliably and were relevant to diagnostic uncertainty. Finally, a competitive machine learning modeling strategy utilizing the linguistic indicators and semantic types compared different predictive models for identifying diagnostic uncertainty. RESULTS: Our cohort included 242 UD-labeled patients and 932 matched controls with a combination of 3070 clinical notes. The best-performing model was a random forest, utilizing a combination of linguistic indicators and semantic types, yielding a sensitivity of 89.4% and a positive predictive value of 96.7%. CONCLUSION: Expert labeling, natural language processing, and machine learning methods combined with human validation resulted in highly predictive models to detect diagnostic uncertainty in clinical documentation and represent a promising approach to detecting, studying, and ultimately mitigating diagnostic uncertainty in clinical practice.

Faith Community Engagement to Mitigate COVID-19 Transmission Associated with Mass Gathering, Uman, Ukraine, September 2021.

Annually, ≈30,000 Hasidic and Orthodox Jews travel to Uman, Ukraine, during the Jewish New Year to pray at the burial place of the founder of the Breslov Hasidic movement. Many pilgrims come from the northeastern United States. The global health implications of this event were seen in 2019 when measles outbreaks in the United States and Israel were linked to the pilgrimage. The 2020 pilgrimage was cancelled as part of the COVID-19 travel restrictions imposed by the government of Ukraine. To prepare for the 2021 event, the National Public Health Institute, the Public Health Center of Ukraine, organized mitigation measures for pilgrims arriving in Uman, and the CDC COVID-19 International Task Force assisted with mitigation measures for pilgrims coming from the United States. We describe efforts to support COVID-19 mitigation measures before, during, and after this mass gathering and lessons learned for future mass gatherings during pandemics.

Prevalence and risk factors for non-collision injuries among bus commuters in Dar es Salaam, Tanzania.

BACKGROUND: Migration of people from rural to urban areas has led to the increase in demand for transportation services in the cities. However, authorities have failed to cope with this problem in a consistently manner. This has led to the increase in non-collision injuries among commuters. This study aimed at investigating the prevalence and risk factors for non-collision injuries among commuters using public transport in Dar es Salaam, Tanzania. METHODS: A cross sectional study was conducted in Dar es Salaam involving 290 commuters from 7 bus routes travelling to and from the city centre using public transport which are privately owned and commonly known as "daladala". Stratified random sampling was used to sample buses based on the passenger carrying capacity (i.e. 15-24, 25-34 and 35-45 passengers). Systematic random sampling was used to get a total of three commuters from each bus for the interview. RESULTS: Lifetime prevalence of non-collision injuries was 71%, while these rates were 70 and 39% in the last 12 and 6 months, respectively. Commuters aged between 18 and 28 years experienced non-collision injuries the most (56%) in the last 12 months. Most non-collision injuries occurred on weekdays in the evening from 5:00 pm to 10:00 pm. Strong association was observed between the occurrence of non-collision injuries and commuting time between 5:00 pm to 10:00 pm (adjusted OR = 9.24; 95% CI: 2.68-19.54); boarding and disembarking (adjusted OR = 9.21; 95% CI: 3.77-25.11) and scrambling during boarding (adjusted OR = 5.03; 95% CI: 2.51-21.32). The lower limbs (adjusted OR = 8.64; 95% CI: 2.72-21.76) and the upper limbs (adjusted OR = 13.55; 95% CI: 5.32-33.21) were the most affected body parts. CONCLUSIONS: This study has demonstrated high prevalence of non-collision injuries among commuters using public transport in Dar es Salaam. Travelling in the evening between 5:00 pm to 10:00 pm on the weekdays, boarding and disembarking especially when scrambling for the bus during boarding, overcrowding in the bus especially when the bus is already full with no seats available are the major risk factors for non-collision injuries.

Hypocholesterolemic phospholipid transfer protein knockout mice exhibit a normal glucocorticoid response to food deprivation.

OBJECTIVES: Glucocorticoids, adrenal-derived steroid hormones, facilitate the physiological response to stress. High-density lipoproteins (HDL) are considered the primary source of cholesterol used for glucocorticoid synthesis in mice. Phospholipid transfer protein (PLTP) is a key player in HDL formation. In the current study we tested the hypothesis that HDL deficiency associated with genetic lack of PLTP negatively impacts the adrenal steroid function. METHODS: We determined the glucocorticoid response to overnight food deprivation stress and the adrenal lipid and genetic phenotype of wild-type and PLTP knockout mice. RESULTS: Basal plasma corticosterone levels, adrenal weights, and adrenocortical neutral lipid stores were not different between wild-type and PLTP knockout mice. Strikingly, plasma corticosterone levels were also equally high in the two groups of mice under fasting conditions (two-way ANOVA genotype effect: P>0.05). However, compensatory mechanisms were active to overcome adrenal lipid depletion, since gene expression levels of cholesterol synthesis, acquisition and mobilization proteins were ~2-fold higher in PLTP knockout adrenals versus wild-type adrenals. In support of an overall similar glucocorticoid stress response, hepatic relative mRNA expression levels of the glucocorticoid receptor target/glucocorticoid-sensitive genes PEPCK, ANGPTL4, FGF21, TDO2 and HMGCS2 were also not different. CONCLUSIONS: We have shown that hypocholesterolemic PLTP knockout mice exhibit a normal glucocorticoid response to food deprivation. These novel data (1) highlight that the effect of HDL deficiency on adrenal glucocorticoid output in mice is model dependent and (2) imply that other (lipoprotein) cholesterol sources than HDL can also generate the pool utilized by adrenocortical cells to synthesize glucocorticoids.

Sexual reproduction is light-limited as marsh grasses colonize maritime forest.

Climate change is driving abiotic shifts that can threaten the conservation of foundation species and the habitats they support. Directional range shifting is one mechanism of escape, but requires the successful colonization of habitats where interspecific interactions may differ from those to which a species has adapted. For plants with multiple reproductive strategies, these range-edge interactions may alter the investment or allocation toward a given reproductive strategy. In this study, we quantified sexual reproduction of the clonal marsh grass Spartina patens across an inland colonization front into maritime forest being driven by sea-level rise. We find that flowering is variable across S. patens meadows, but consistently reduced in low light conditions like those of the forest understory. Observational surveys of S. patens flowering at four sites in the Delmarva Peninsula agreed with the results of two experimental manipulations of light availability (shading experiment in S. patens-dominated marsh and a forest dieback manipulation). These three approaches pinpointed light limitation as a principal control on S. patens flowering capacity, suggesting that light competition with taller upland species can suppress S. patens flowering along its upland migration front. Consequently, all propagation in shaded conditions must occur clonally or via seeds from the marsh, a reproductive restriction that could limit the potential for local adaptation and reduce genetic diversity. Future research is needed to determine whether the lack of flowering is the result of a trade-off between sexual and clonal reproduction or results from insufficient photosynthetic products needed to achieve either reproductive method.

Predicting Sepsis in Patients with Ureteral Stones in the Emergency Department.

Background: In the absence of overt infection signs, clinical criteria for early intervention in patients with ureteral stones are poorly defined. We aimed to develop a model that can identify patients who are at risk for developing sepsis if discharged home from the emergency department (ED). Materials and Methods: We retrospectively reviewed patients between January 2010 and December 2019 who were discharged from the ED after diagnosis of ureteral stones. The primary outcome was sepsis requiring urgent surgical decompression. We used multivariable logistic regression to identify predictors of sepsis. We refined the model using backward stepwise regression with a threshold p-value of 0.05. Results: We identified 1331 patients who were discharged from the ED with ureteral stones. Of these patients, 22 (2%) subsequently developed sepsis requiring urgent decompression. In the initial multivariable model, female gender (odds ratio [OR]: 2.82, p = 0.039) and urine white blood cells (WBCs) (OR: 1.02 per cell count, p < 0.001) were predictive of sepsis. After performing backward stepwise regression, female gender, urine WBCs, and leukocytosis (WBCs >15,000/mm3) met criteria for inclusion in the model. A logistic model including these variables predicted sepsis with an internally cross-validated area under the curve (AUC) of 0.79. Among patients with urine cultures completed in the ED, rates of sepsis were 9% in patients with positive cultures and 1% in patients with negative cultures (p < 0.001). Antibiotic usage was not protective against developing sepsis. Conclusions: Sepsis is a rare complication among patients with ureteral stones selected for conservative management. The presence of elevated urine WBCs and female gender can help identify patients who are at risk of developing sepsis. Patients with risk factors should be managed with an increased index of suspicion for infection and may benefit from early intervention to reduce the risk of sepsis. Sepsis is more common in patients with positive urine cultures.

Promoting Organizational Change: A Urology Department-wide Wellness Program to Reduce Burnout.

INTRODUCTION: We developed a comprehensive wellness initiative to address burnout with specific interventions targeted at faculty, residents, nurses, administrators, coordinators, and other departmental personnel. METHODS: A department-wide wellness initiative was implemented in October 2020. General interventions included monthly holiday-themed lunches, weekly pizza lunches, employee recognition events, and initiation of a virtual networking board. Urology residents received financial education workshops, weekly lunches, peer support sessions, and exercise equipment. Faculty were offered personal wellness days to use at their discretion at no penalty to their calculated productivity. Administrative and clinical staff were given weekly lunches and professional development sessions. Pre- and post-intervention surveys included a validated single-item burnout instrument and the Stanford Professional Fulfillment Index. Outcomes were compared using Wilcoxon rank-sum tests and multivariable ordinal logistic regression. RESULTS: Among 96 department members, 66 (70%) and 53 (55%) participants completed the pre- and post-intervention surveys, respectively. Burnout scores were significantly improved after the wellness initiative (mean 2.06 vs 2.42, mean difference -0.36, P = .012). An improvement was also observed in the sense of community (mean 4.04 vs 3.36, mean difference 0.68, P < .001). Adjusting for role group and gender, completion of the curriculum was associated with decreased burnout (OR 0.44, P = .025), increased professional fulfillment (OR 2.05, P = .038), and increased sense of community (OR 3.97, P < .001). The highest-rated components were monthly gatherings (64%), sponsored lunches (58%), and employee of the month (53%). CONCLUSIONS: A department-wide wellness initiative with group-specific interventions can help reduce burnout and may improve professional fulfillment and workplace community.