Think before you pop: Outcomes of non-operative management of ureteroceles.

INTRODUCTION/BACKGROUND: Ureteroceles are often diagnosed antenatally and incidentally and treated in a minimally invasive fashion with endoscopic puncture. Recent literature suggests that observation, or non-operative management, is an effective and viable management option in select patients with ureteroceles and certain radiologic findings, however there is no consensus on how to best select patients for non-operative management. OBJECTIVE: To 1) determine if pediatric ureteroceles managed non-operatively require less or sooner secondary surgical intervention than those managed with up-front incision, 2) describe characteristics of success and failure in pediatric ureteroceles managed non-operatively, and 3) identify risk factors associated with receiving intervention and time to intervention. RESULTS: Of 287 ureteroceles, 65 (23%) were managed non-operatively and underwent secondary surgical intervention less frequently (9% vs. 34%, P < 0.01) and later (median age 40 vs. 20 months) than those managed with puncture. Successful non-operative management was associated with fewer comorbidities, smaller ureterocele size, absence of vesicoureteral reflux (VUR) and high-grade VUR, single collecting system, lesser degree of hydronephrosis, ipsilateral MCDK and intravesical location. For all ureteroceles, high-grade VUR, duplex system, and female sex were associated with shorter time to secondary intervention (intervention after initial management). DISCUSSION: In the largest retrospective review of ureterocele management, smaller ureterocele size, absence of high-grade VUR, single system, ipsilateral MCDK and minimal hydronephrosis were factors that increased the efficacy of non-operative management of select pediatric ureteroceles. Furthermore, time to event analysis showed that non-operative management did not predispose patients to sooner secondary intervention (Figure). Lack of a standardized protocol for ureterocele management is a limitation of this single institution retrospective study as it introduces selection bias to the results, however few patients with low risk characteristics underwent puncture and no high risk patients were observed. CONCLUSION: Smaller ureterocele size, absence of high-grade VUR, single system, ipsilateral MCDK and minimal hydronephrosis are factors that may increase the efficacy of non-operative management of select pediatric ureteroceles, which may delay or avoid secondary surgical intervention.

ALDH1A3 is the switch that determines the balance of ALDH+ and CD24-CD44+ cancer stem cells, EMT-MET, and glucose metabolism in breast cancer.

Plasticity is an inherent feature of cancer stem cells (CSCs) and regulates the balance of key processes required at different stages of breast cancer progression, including epithelial-to-mesenchymal transition (EMT) versus mesenchymal-to-epithelial transition (MET), and glycolysis versus oxidative phosphorylation. Understanding the key factors that regulate the switch between these processes could lead to novel therapeutic strategies that limit tumor progression. We found that aldehyde dehydrogenase 1A3 (ALDH1A3) regulates these cancer-promoting processes and the abundance of the two distinct breast CSC populations defined by high ALDH activity and CD24-CD44+ cell surface expression. While ALDH1A3 increases ALDH+ breast cancer cells, it inversely suppresses the CD24-CD44+ population by retinoic acid signaling-mediated gene expression changes. This switch in CSC populations induced by ALDH1A3 was paired with decreased migration but increased invasion and an intermediate EMT phenotype. We also demonstrate that ALDH1A3 increases oxidative phosphorylation and decreases glycolysis and reactive oxygen species (ROS). The effects of ALDH1A3 reduction were countered with the glycolysis inhibitor 2-deoxy-D-glucose (2DG). In cell culture and tumor xenograft models, 2DG suppresses the increase in the CD24-CD44+ population and ROS induced by ALDH1A3 knockdown. Combined inhibition of ALDH1A3 and glycolysis best reduces breast tumor growth and tumor-initiating cells, suggesting that the combination of targeting ALDH1A3 and glycolysis has therapeutic potential for limiting CSCs and tumor progression. Together, these findings identify ALDH1A3 as a key regulator of processes required for breast cancer progression and depletion of ALDH1A3 makes breast cancer cells more susceptible to glycolysis inhibition.

Accelerated competency-based education in primary care (ACE-PC): a 3-year UC Davis and Kaiser permanente partnership to meet California's primary care physician workforce needs.

PROBLEM: Our nation faces an urgent need for more primary care (PC) physicians, yet interest in PC careers is dwindling. Students from underrepresented in medicine (UIM) backgrounds are more likely to choose PC and practice in underserved areas yet their representation has declined. Accelerated PC programs have the potential to address workforce needs, lower educational debt, and diversify the physician workforce to advance health equity. APPROACH: With support from Kaiser Permanente Northern California (KPNC) and the American Medical Association's Accelerating Change in Medical Education initiative, University of California School of Medicine (UC Davis) implemented the Accelerated Competency-based Education in Primary Care (ACE-PC) program - a six-year pathway from medical school to residency for students committed to health equity and careers in family medicine or PC-internal medicine. ACE-PC accepts 6-10 students per year using the same holistic admissions process as the 4-year MD program with an additional panel interview that includes affiliated residency program faculty from UC Davis and KPNC. The undergraduate curriculum features: PC continuity clinic with a single preceptor throughout medical school; a 9-month longitudinal integrated clerkship; supportive PC faculty and culture; markedly reduced student debt with full-tuition scholarships; weekly PC didactics; and clinical rotations in affiliated residency programs with the opportunity to match into specific ACE-PC residency tracks. OUTCOMES: Since 2014, 70 students have matriculated to ACE-PC, 71% from UIM groups, 64% are first-generation college students. Of the graduates, 48% have entered residency in family medicine and 52% in PC-internal medicine. In 2020, the first graduates entered the PC workforce; all are practicing in California, including 66% at federally qualified health centers, key providers of underserved care.

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.

BACKGROUND: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. METHODS: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. RESULTS: Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. CONCLUSION: These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.

Dismenorrea, un dolor que incapacita / Dysmenorrhea: a disabling pain

La dismenorrea es una afección menstrual común en mujeres de edad reproductiva, caracterizada por dolor pélvico durante el ciclo menstrual. En este artículo, se revisan los factores de riesgo, la clínica y el diagnóstico de la dismenorrea primaria con el objetivo de proponer un enfoque de tratamiento multimodal para esta condición. La dismenorrea primaria es el dolor pélvico asociado al período menstrual sin una patología pélvica subyacente. La dismenorrea secundaria es el dolor pélvico que se presenta como síntoma de otras afecciones ginecológicas. El diagnóstico se basa en la historia clínica, la exploración física y ginecológica, y se pueden realizar pruebas complementarias en casos específicos. El tratamiento de la dismenorrea primaria es multimodal y tiene como objetivo aliviar el dolor y mejorar la calidad de vida de las pacientes. Los fármacos antiinflamatorios no esteroideos son la primera línea de tratamiento, aunque se pueden utilizar otros enfoques terapéuticos(AU)

Dysmenorrhea is a common menstrual condition in women of reproductive age, characterized by pelvic pain during the menstrual cycle. This article reviews the risk factors, clinic and diagnosis of primary dysmenorrhea to propose a multimodal treatment approach for this condition. Primary dysmenorrhea is pelvic pain associated with the menstrual period without underlying pelvic pathology. In contrast, secondary dysmenorrhea refers to pelvic pain that presents as a symptom of other gynecologic conditions. Diagnosis is based on detailed clinical history, physical and gynecological examination, and complementary tests may be performed in specific cases. Treatment of primary dysmenorrhea is multimodal and aims to relieve pain and improve the patient's quality of life. Nonsteroidal anti-inflammatory drugs are the first line of treatment, although other therapeutic approaches can be employed(AU)

Experiences of Leaders in Diversity, Equity, and Inclusion in US Academic Health Centers.

Importance: The murder of George Floyd in 2020 spurred an outpouring of calls for racial justice in the United States, including within academic medicine. In response, academic health centers announced new antiracism initiatives and expanded their administrative positions related to diversity, equity, and/or inclusion (DEI). Objective: To understand the experiences of DEI leaders at US allopathic medical schools and academic health centers, ie, the structure of their role, official and unofficial responsibilities, access to resources, institutional support, and challenges. Design, Setting, and Participants: This qualitative study used key informant interviews with participants who held formal DEI positions in their school of medicine, health system, or department. Interviews were conducted from December 2020 to September 2021. Transcripts were coded using a phenomenographic approach, with iterative concurrent analysis to identify thematic categories across participants. Data were analyzed from January to December 2021. Exposure: Formal DEI role. Main Outcomes and Measures: Questions elicited reflection on the responsibilities of the role and the strengths and challenges of the unit or office. Results: A total of 32 participants (18 of 30 [56%] cisgender women; 16 [50%] Black or African American, 6 [19%] Latinx or Hispanic, and 8 [25%] White) from 27 institutions with a mean (range) of 14 (3-43) years of experience in medical education were interviewed. More than half held a dean position (17 [53%]), and multiple participants held 2 or more titled DEI roles (4 [13%]). Two-thirds self-identified as underrepresented in medicine (20 [63%]) and one-third as first generation to attend college (11 [34%]). Key themes reflected ongoing challenges for DEI leaders, including (1) variability in roles, responsibilities, and access to resources, both across participants and institutions as well as within the same position over time; (2) mismatch between institutional investments and directives, including insufficient authority, support staff, and/or funding, and reduced efficacy due to lack of integration with other units within the school or health system; (3) lack of evidence-based practices, theories of change, or standards to guide their work; and (4) work experiences that drive and exhaust leaders. Multiple participants described burnout due to increasing demands that are not met with equivalent increase in institutional support. Conclusions and Relevance: In this qualitative study, DEI leaders described multiple institutional challenges to their work. To effectively address stated goals of DEI, medical schools and academic centers need to provide leaders with concomitant resources and authority that facilitate change. Institutions need to acknowledge and implement strategies that integrate across units, beyond one leader and office. Policymakers, including professional organizations and accrediting bodies, should provide guidance, accountability mechanisms, and support for research to identify and disseminate evidence for best practices. Creating statements and positions, without mechanisms for change, perpetuates stagnation and injustice.

Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.

Cancer stem cells (CSCs) represent a subpopulation within tumors that promote cancer progression, metastasis, and recurrence due to their self-renewal capacity and resistance to conventional therapies. CSC-specific markers and signaling pathways highly active in CSCs have emerged as a promising strategy for improving patient outcomes. This review provides a comprehensive overview of the therapeutic targets associated with CSCs of solid tumors across various cancer types, including key molecular markers aldehyde dehydrogenases, CD44, epithelial cellular adhesion molecule, and CD133 and signaling pathways such as Wnt/ß-catenin, Notch, and Sonic Hedgehog. We discuss a wide array of therapeutic modalities ranging from targeted antibodies, small molecule inhibitors, and near-infrared photoimmunotherapy to advanced genetic approaches like RNA interference, CRISPR/Cas9 technology, aptamers, antisense oligonucleotides, chimeric antigen receptor (CAR) T cells, CAR natural killer cells, bispecific T cell engagers, immunotoxins, drug-antibody conjugates, therapeutic peptides, and dendritic cell vaccines. This review spans developments from preclinical investigations to ongoing clinical trials, highlighting the innovative targeting strategies that have been informed by CSC-associated pathways and molecules to overcome therapeutic resistance. We aim to provide insights into the potential of these therapies to revolutionize cancer treatment, underscoring the critical need for a multi-faceted approach in the battle against cancer. This comprehensive analysis demonstrates how advances made in the CSC field have informed significant developments in novel targeted therapeutic approaches, with the ultimate goal of achieving more effective and durable responses in cancer patients.

Deep Few-view High-resolution Photon-counting Extremity CT at Halved Dose for a Clinical Trial.

The latest X-ray photon-counting computed tomography (PCCT) for extremity allows multi-energy high-resolution (HR) imaging for tissue characterization and material decomposition. However, both radiation dose and imaging speed need improvement for contrast-enhanced and other studies. Despite the success of deep learning methods for 2D few-view reconstruction, applying them to HR volumetric reconstruction of extremity scans for clinical diagnosis has been limited due to GPU memory constraints, training data scarcity, and domain gap issues. In this paper, we propose a deep learning-based approach for PCCT image reconstruction at halved dose and doubled speed in a New Zealand clinical trial. Particularly, we present a patch-based volumetric refinement network to alleviate the GPU memory limitation, train network with synthetic data, and use model-based iterative refinement to bridge the gap between synthetic and real-world data. The simulation and phantom experiments demonstrate consistently improved results under different acquisition conditions on both in- and off-domain structures using a fixed network. The image quality of 8 patients from the clinical trial are evaluated by three radiologists in comparison with the standard image reconstruction with a full-view dataset. It is shown that our proposed approach is essentially identical to or better than the clinical benchmark in terms of diagnostic image quality scores. Our approach has a great potential to improve the safety and efficiency of PCCT without compromising image quality.

A Practical Guide to Understanding and Treating Peripheral Artery Disease.

ABSTRACT: Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic morbidity after coronary heart disease and stroke yet is widely underdiagnosed and undertreated. Treatment of risk factors such as diabetes and cigarette smoking can benefit patients with PAD. Patients should have adequate blood pressure and lipid control to decrease clinical manifestations and symptoms of PAD. Use of antithrombotic medications should be individualized to the patient depending on the presence of symptoms, revascularization, and comorbidities. All patient care providers, including physicians, pharmacists, nurse practitioners, and physician assistants, should incorporate PAD screening in their at-risk patients to improve access for appropriate earlier diagnosis, initiation of guideline directed therapy, and risk factor modification to reduce both major adverse CV and limb outcomes. The purpose of this narrative review is to provide an overview of PAD and summarize clinical trial evidence and guideline recommendations for screening and treatment to increase awareness among health care providers to ultimately have a positive impact on patient care.

A systematic review of therapeutic enoxaparin dosing in obesity.

Enoxaparin is a hydrophilic drug with obesity having little effect on its apparent volume of distribution, therefore patients with obesity receiving standard 1 mg/kg dosing may be at a higher risk of supratherapeutic dosing. Conversely, dose reducing patients with obesity could place already at risk patients at higher risk of a thrombotic event. Data and recommendations are variable for the most appropriate weight-based dose of therapeutic enoxaparin in obese patients, particularly those a weight > 100 kg or a body mass index (BMI) ≥ 40 kg/m2. The purpose of this systematic review was to globally evaluate these data to surmise optimal dosing recommendations for patients with obesity. A systematic review of English language studies was conducted and identified articles via Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) searches. Studies were included if they reported therapeutic enoxaparin use in adult patients with a BMI ≥ 40 kg/m2 or body weight > 100 kg and the percentage of patients achieving a therapeutic anti-Xa based on a weight-based dose or the weight-based dose required to produce a therapeutic anti-Xa level. Therapeutic attainment of anti-Xa levels were assessed across enoxaparin weight-based dosing categories including a very low dose group: < 0.75 mg/kg, low dose group: 0.75-0.85 mg/kg, and standard dose group: ≥ 0.95 mg/kg. Rates of bleeding and thrombosis were also evaluated. A total of eight studies were included. For anti-Xa level assessment, 682 patients were included. A total of 62% of anti-Xa levels were therapeutic in the very low dose group, 66% in the low dose group, and 42% in the standard dose group. Overall rates of total bleeding and thrombosis were assessed in 798 patients. A total of 29 bleedings (3.6%) occurred, and 27 reported a relationship to dose. Most bleedings, 85.2% (n = 23/27), occurred with doses in the standard dose group (≥ 0.95 mg/kg). Thrombosis occurred in 5 patients (0.6%). Utilization of a reduced weight-based dosing strategy for therapeutic enoxaparin in obese patients may increase the percentage of patients with a therapeutic anti-Xa level.

The Effects of Stigma: Older Persons and Medicinal Cannabis.

Cannabis has long been stigmatized as an illicit drug. Since legalization in Canada for both medical and recreational purposes, older adults' cannabis consumption has increased more than any other age group. Yet, it is unclear how the normalization of cannabis has impacted perceptions of stigma for older adults consuming cannabis medicinally. Qualitative description was used to elucidate the experiences of older Canadians aged 60+ related to stigma and their consumption of cannabis for medicinal purposes. Data collection involved semi-structured interviews. Data analysis examined how participants managed stigma related to cannabis use. Perceived stigma was evident in many participants' descriptions of their perceptions of cannabis in the past and present, and influenced how they accessed and consumed cannabis and their comfort in discussing its use with their healthcare providers. Participants employed several distinct strategies for managing stigma-concealing, re-framing, re-focusing, and proselytizing. Findings suggest that while medical cannabis consumption is becoming increasingly normalized among older adults, stigma related to cannabis persists and continues to shape older adults' experiences. A culture shift needs to occur among healthcare providers so that they are educated about cannabis and willing to discuss the possibilities of medicinal cannabis consumption with older adults. Otherwise, older adults may seek advice from recreational or other non-medical sources. Healthcare providers require education about the use of medical cannabis, so they can better advise older adults regarding its consumption for medicinal purposes.

Implications of neonatal absence of innate immune mediated NFκB/AP1 signaling in the murine liver.

BACKGROUND: The developmental immaturity of the innate immune system helps explains the increased risk of infection in the neonatal period. Importantly, innate immune signaling pathways such as p65/NFκB and c-Jun/AP1 are responsible for the prevention of hepatocyte apoptosis in adult animals, yet whether developmental immaturity of these pathways increases the risk of hepatic injury in the neonatal period is unknown. METHODS: Using a murine model of endotoxemia (LPS 5 mg/kg IP x 1) in neonatal (P3) and adult mice, we evaluated histologic evidence of hepatic injury and apoptosis, presence of p65/NFκB and c-Jun/AP1 activation and associated transcriptional regulation of apoptotic genes. RESULTS: We demonstrate that in contrast to adults, endotoxemic neonatal (P3) mice exhibit a significant increase in hepatic apoptosis. This is associated with absent hepatic p65/NFκB signaling and impaired expression of anti-apoptotic target genes. Hepatic c-Jun/AP1 activity was attenuated in endotoxemic P3 mice, with resulting upregulation of pro-apoptotic factors. CONCLUSIONS: These results demonstrate that developmental absence of innate immune p65/NFκB and c-Jun/AP1 signaling, and target gene expression is associated with apoptotic injury in neonatal mice. More work is needed to determine if this contributes to long-term hepatic dysfunction, and whether immunomodulatory approaches can prevent this injury. IMPACT: Various aspects of developmental immaturity of the innate immune system may help explain the increased risk of infection in the neonatal period. In adult models of inflammation and infection, innate immune signaling pathways such as p65/NFκB and c-Jun/AP1 are responsible for a protective, pro-inflammatory transcriptome and regulation of apoptosis. We demonstrate that in contrast to adults, endotoxemic neonatal (P3) mice exhibit a significant increase in hepatic apoptosis associated with absent hepatic p65/NFκB signaling and c-Jun/AP1 activity. We believe that these results may explain in part hepatic dysfunction with neonatal sepsis, and that there may be unrecognized developmental and long-term hepatic implications of early life exposure to systemic inflammatory stress.

Understanding nurses' experience of climate change and then climate action in Western Canada.

AIM: To understand nurses' personal and professional experiences with the heat dome, drought and forest fires of 2021 and how those events impacted their perspectives on climate action. DESIGN: A naturalistic inquiry using qualitative description. METHOD: Twelve nurses from the interior of British Columbia, Canada, were interviewed using a semi-structured interview guide. Thematic analysis was employed. No patient or public involvement. RESULTS: Data analysis yielded three themes to describe nurses' perspective on climate change: health impacts; climate action and system influences. These experiences contributed to nurses' beliefs about climate change, how to take climate action in their personal lives and their challenges enacting climate action in their workplace settings. CONCLUSIONS: Nurses' challenges with enacting environmentally responsible practices in their workplace highlight the need for engagement throughout institutions in supporting environmentally friendly initiatives. IMPACT: The importance of system-level changes in healthcare institutions for planetary health.

NAPLEX Preparatory Perceptions from Recent Graduates at One College of Pharmacy.

OBJECTIVES: The current study assessed how students prepared for the North American Pharmacist Licensure Examination (NAPLEX), and examined factors associated with first-time pass rates. In addition, updated information on student perceptions of several currently available NAPLEX preparation resources was collected. METHODS: A survey was administered to 2022 graduates from 1 school, which collected data on student demographics, and NAPLEX-related items regarding when the exam was taken and how students prepared, including resources used. The association between first-time success (pass, no pass) and grade point average (GPA), timing of test date after graduation, effort toward exam, and number of hours studied was examined. In addition, student ratings of NAPLEX preparation resources in terms of usefulness, representativeness to actual examination, and monetary value were reported. RESULTS: A total of 52 individuals completed the survey. Pharmacy GPA over 3.5, taking the NAPLEX within 60 days of graduation, and exerting moderate to extensive effort to pass the NAPLEX were all associated with higher first-time pass rates. All students reported using at least 1 RxPrep resource, which students rated highly and suggested the school provide as a resource for NAPLEX preparation. CONCLUSION: This study found that taking the NAPLEX examination within 60 days of graduation, contributing moderate to extensive effort to pass the examination, as well as a cumulative GPA of 3.5 (out of 4) or above were related to success on the NAPLEX. Additionally, students reported high satisfaction with RxPrep resources.

GSK3ß/NF-κB -dependent transcriptional regulation of homeostatic hepatocyte Tnf production.

Maintenance of hepatocyte homeostasis plays an important role in mediating the pathogenesis of many diseases. A growing body of literature has established a critical role played by tumor necrosis factor-α (TNFα) in maintaining hepatocyte homeostasis; however, the transcriptional mechanisms underlying constitutive Tnf expression are unknown. Whole liver fractions and primary hepatocytes from adult control C57BL/6 mice and the murine hepatocyte cell line AML12 were assessed for constitutive Tnf expression. Impacts of glycogen synthase kinase-3 ß (GSK3ß) and nuclear factor κB (NF-κB) inhibition on constitutive Tnf expression were assessed in AML12 cells. Finally, AML12 cell proliferation following GSK3ß and NF-κB inhibition was evaluated. Constitutive Tnf gene expression is present in whole liver, primary hepatocytes, and cultured AML12 hepatocytes. Cytokine-induced Tnf gene expression is regulated by NF-κB activation. Pharmacological inhibition of GSK3ß resulted in a time- and dose-dependent inhibition of Tnf gene expression. GSK3ß inhibition decreased nuclear levels of the NF-κB subunits p65 and p50. We determined that NF-κB transcription factor subunit p65 binds to consensus sequence elements present in the murine TNFα promoter and inhibition of GSK3ß decreases binding and subsequent Tnf expression. Finally, AML12 cell growth was significantly reduced following GSK3ß and NF-κB inhibition. These results demonstrate that GSK3ß and NF-κB are essential for mediating Tnf expression and constitutive hepatocyte cell growth. These findings add to a growing body of literature on TNFα mediated hepatocyte homeostasis and identify novel molecular mechanisms involved in mediating response to various disease states in the liver.NEW & NOTEWORTHY Maintenance of hepatocyte homeostasis plays an important role in controlling the pathogenesis of many diseases. Our findings add to a growing body of literature on tumor necrosis factor-α (TNFα)-mediated hepatocyte homeostasis and identify novel molecular mechanisms involved in regulating this response.

Case of Urethral Hypoplasia in Prune Belly Syndrome Successfully Managed With Vesicoamniotic Shunts and a Progressive Augmentation by Dilation Urethra Anterior Procedure.

Urethral atresia is a rare but clinically significant cause of congenital lower urinary tract obstruction. Initial management options include urinary diversion until definitive urethral reconstruction or progressive urethral dilation. Given the overall rarity of the condition, there are no evidence-based guidelines for the immediate and long-term management of urethral atresia, and clinical practice varies widely. We present an illustrative case managed with progressive urethral dilation alongside urinary diversion to highlight key factors in shared clinical decision making. Ultimately, pooled multi-institutional long-term outcomes data are needed to better guide practice for these patients and their families.

Establishing Population Values for Chlorine Exposure in the United States (2015-2016) Using 2 Chlorine Biomarkers, 3-Chlorotyrosine and 3,5-Dichlorotyrosine.

BACKGROUND: In the United States, 12 million short tons of chlorine are manufactured and transported each year. Due to the volume of this volatile chemical, large- and small-scale chemical exposures occur frequently. To diagnose and treat potentially exposed individuals, reference range values for confirmatory biomarkers are required to differentiate between normal and abnormal exposure levels. METHODS: Serum surplus samples (n = 1780) from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 were measured for 2 chlorine biomarkers, 3-chlorotyrosine (Cl-Tyr) and 3,5-dichlorotyrosine (Cl2-Tyr), by liquid chromatography coupled to a triple quadrupole mass spectrometer. We evaluated demographic factors associated with elevated biomarker levels. RESULTS: Participant samples were analyzed for the chlorine biomarkers Cl-Tyr and Cl2-Tyr. In the unweighted analysis of these samples, 1349 (75.8%) were under the limit of detection (< LOD) of 2.50 ng/mL for Cl-Tyr and 1773 (99.6%) were < LOD for Cl2-Tyr. Samples within the method reportable range were 2.50 to 35.6 ng/mL for Cl-Tyr and 2.69 to 11.2 ng/mL for Cl2-Tyr. Since only 7 of the 1780 participants had detectable Cl2-Tyr, statistical analysis was limited to Cl-Tyr. Of the demographic characteristics examined, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), and sex exhibited statistically significant differences in the weighted prevalence of detectable Cl-Tyr. CONCLUSIONS: This is the first reported set of Cl-Tyr and Cl2-Tyr population values for the United States. This population range coupled with NHANES demographic information could help healthcare professionals distinguish between normal and abnormal chlorine biomarker levels in an emergency. With this information, an inference could be made when determining acute chlorine exposure in individuals.

Extreme heat reduces host and parasite performance in a butterfly-parasite interaction.

Environmental temperature fundamentally shapes insect physiology, fitness and interactions with parasites. Differential climate warming effects on host versus parasite biology could exacerbate or inhibit parasite transmission, with far-reaching implications for pollination services, biocontrol and human health. Here, we experimentally test how controlled temperatures influence multiple components of host and parasite fitness in monarch butterflies (Danaus plexippus) and their protozoan parasites Ophryocystis elektroscirrha. Using five constant-temperature treatments spanning 18-34°C, we measured monarch development, survival, size, immune function and parasite infection status and intensity. Monarch size and survival declined sharply at the hottest temperature (34°C), as did infection probability, suggesting that extreme heat decreases both host and parasite performance. The lack of infection at 34°C was not due to greater host immunity or faster host development but could instead reflect the thermal limits of parasite invasion and within-host replication. In the context of ongoing climate change, temperature increases above current thermal maxima could reduce the fitness of both monarchs and their parasites, with lower infection rates potentially balancing negative impacts of extreme heat on future monarch abundance and distribution.

Prenatal Presentation of a Covered Cloacal Exstrophy Variant; Early Diagnostic Challenges Within the Broad Spectrum of the Exstrophy-Epispadias Complex.

There is a broad range of variant phenotypes that can occur within the bladder exstrophy and epispadias complex spectrum. Accurate prenatal detection helps prepare families and to coordinate subspecialty resources. Here, we present the case of a patient with prenatally diagnosed patient with covered cloacal exstrophy variant along with four additional cases illustrating the nonlinear spectrum from isolated epispadias to cloacal exstrophy. Given the rarity of these variants overall and of each subtype within the spectrum, there is a need for long-term multi-institutional outcomes data to improve detection, characterization, and prognostication for these patients.