Bisphenol-A analogs induce lower urinary tract dysfunction in male mice.

Bisphenol-A (BPA), an estrogenic endocrine disrupting chemical, significantly impacts numerous diseases and abnormalities in mammals. Estrogens are known to play an important role in the biology of the prostate; however, little is known about the role of bisphenols in the etiology of prostate pathologies, including benign prostate hyperplasia (BPH) and associated lower urinary tract dysfunction (LUTD). Bisphenol-F (BPF) and bisphenol-S (BPS) are analogs often used as substitutes for BPA; they are both reported to have in vitro and in vivo estrogenic effects similar to or more potent than BPA. The objective of this study was to assess the role of these bisphenols in the development of LUTD in adult male mice. In adult mice exposed to BPA, BPS or BPF, we examined urinary tract histopathology and physiological events associated with urinary dysfunction. Mice treated with bisphenols displayed increased bladder (p < 0.005) and prostate (p < 0.0001) mass, and there was an increased number of prostatic ducts in the prostatic urethra (p < 0.05) and decreased size of the urethra lumen (p < 0.05) compared to negative controls. After two months of bisphenol exposure, mice displayed notable differences in cystometric tracings compared to controls, consistent with LUTD. Treatment of male mice with all bisphenols also induced voiding dysfunction manifested by detrusor instability and histologic changes in the prostatic urethra of male rodents, consistent with LUTD. Our results implicate BPA and its replacements in the development and progression LUTD in mice and provide insights into the development and progression of BPH/LUTS in men.

Complication and Sequelae of COVID-19: What Should We Pay Attention to in the Post-Epidemic Era.

COVID-19 is widespread worldwide and seriously affects the daily life and health of humans. Countries around the world are taking necessary measures to curb the spread. However, COVID-19 patients often have at least one organ complication and sequelae in addition to respiratory symptoms. Controlling the epidemic is only a phased victory, and the complication and sequelae of COVID-19 will need more attention in the post-epidemic era. We collected general information from over 1000 articles published in 2020 after the COVID-19 outbreak and systematically analyzed the complication and sequelae associated with eight major systems in COVID-19 patients caused by ACE2 intervention in the RAS regulatory axis. The autoimmune response induced by 2019-nCoV attacks and damages the normal tissues and organs of the body. Our research will help medical workers worldwide address COVID-19 complication and sequelae.

Predicting severe outcomes using national early warning score (NEWS) in patients identified by a rapid response system: a retrospective cohort study.

There are insufficient data in managing patients at high risk of deterioration. We aimed to investigate that national early warning score (NEWS) could predict severe outcomes in patients identified by a rapid response system (RRS), focusing on the patient's age. We conducted a retrospective cohort study from June 2019 to December 2020. Outcomes were unplanned intensive care unit (ICU) admission, ICU mortality, and in-hospital mortality. We analyzed the predictive ability of NEWS using receiver operating characteristics (ROC) curve and the effect of NEWS parameters using multivariable logistic regression. A total of 2,814 RRS activations were obtained. The predictive ability of NEWS for unplanned ICU admission and in-hospital mortality was fair but was poor for ICU mortality. The predictive ability of NEWS showed no differences between patients aged 80 years or older and under 80 years. However, body temperature affected in-hospital mortality for patients aged 80 years or older, and the inverse effect on unplanned ICU admission was observed. The NEWS showed fair predictive ability for unplanned ICU admission and in-hospital mortality among patients identified by the RRS. The different presentations of patients 80 years or older should be considered in implementing the RRS.

Role of α- and ß-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease.

The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and ß-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and ß-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease. Video abstract.

A RETROSPECTIVE REVIEW OF POST-METAMORPHIC MOUNTAIN CHICKEN FROG (LEPTODACTYLUS FALLAX) NECROPSY FINDINGS FROM EUROPEAN ZOOLOGICAL COLLECTIONS, 1998 TO 2018.

The mountain chicken frog (Leptodactylus fallax) is the largest endemic amphibian species in the Western Hemisphere. Since 1998, this critically endangered species has been maintained as a European Endangered Species Programme, but low breeding success and a high mortality rate threaten the sustainability of the captive frog population. In the current study, we analyzed gross and histopathologic postmortem information from 212 mountain chicken frogs that died in European zoological collections from 1998 to 2018. Thin body condition was the most commonly reported finding across all submissions, observed in 125 frogs. The gastrointestinal and urinary systems were reported to have the highest prevalence of pathologic findings on gross and histopathologic examination. Inflammatory disease was the most frequent diagnosis after histopathologic examination of relevant tissues, with intestinal inflammatory disease (n = 76) followed by tubulointerstitial nephritis (n = 26) being the most commonly reported. Neoplasia was reported in 42 of 212 (19.8%) frogs, all of which were adults. A defined cause of death, or reason for euthanasia, was proposed for 164 of 212 (77.4%) frogs, with inflammatory diseases processes (74 of 212; 34.9%) most commonly implicated. Intestinal adenocarcinoma, seemingly restricted to the colon, caused the deaths of 31 adult frogs. Further investigations to determine factors contributing to the high incidence of inflammatory disease processes and neoplasia are advocated to improve the health and sustainability of the captive mountain chicken frog population.

Pathophysiological Role of K2P Channels in Human Diseases.

The family of two-pore domain potassium (K2P) channels is critically involved in central cellular functions such as ion homeostasis, cell development, and excitability. K2P channels are widely expressed in different human cell types and organs. It is therefore not surprising that aberrant expression and function of K2P channels are related to a spectrum of human diseases, including cancer, autoimmune, CNS, cardiovascular, and urinary tract disorders. Despite homologies in structure, expression, and stimulus, the functional diversity of K2P channels leads to heterogeneous influences on human diseases. The role of individual K2P channels in different disorders depends on expression patterns and modulation in cellular functions. However, an imbalance of potassium homeostasis and action potentials contributes to most disease pathologies. In this review, we provide an overview of current knowledge on the role of K2P channels in human diseases. We look at altered channel expression and function, the potential underlying molecular mechanisms, and prospective research directions in the field of K2P channels.

Fetal body MRI and its application to fetal and neonatal treatment: an illustrative review.

This Review depicts the evolving role of MRI in the diagnosis and prognostication of anomalies of the fetal body, here including head and neck, thorax, abdomen and spine. A review of the current literature on the latest developments in antenatal imaging for diagnosis and prognostication of congenital anomalies is coupled with illustrative cases in true radiological planes with viewable three-dimensional video models that show the potential of post-acquisition reconstruction protocols. We discuss the benefits and limitations of fetal MRI, from anomaly detection, to classification and prognostication, and defines the role of imaging in the decision to proceed to fetal intervention, across the breadth of included conditions. We also consider the current capabilities of ultrasound and explore how MRI and ultrasound can complement each other in the future of fetal imaging.

Urological service provision during the COVID-19 period: the experience from an Irish tertiary centre.

PURPOSE: Urological service provision has changed dramatically with the advent of the SARS-CoV-2, necessitating restructuring and reorganization. The aim of this study was to review the reorganization of our unit, map the change in volume of departmental activities and discuss potential solutions. METHODS: Departmental activities over the months of April and May 2020 and 2019 were analysed. Details of admissions, operations, diagnostic procedures, outpatient reviews, morbidities and mortalities were recorded. Operations were performed on two sites, with elective operation transferred to an offsite, COVID-free hospital. RESULTS: Seventy-four emergency operations were performed onsite, with 85 elective operations outsourced. A total of 159 operations were performed, compared with 280 in the same period in 2019. Five (5.0%) of 101 admitted patients to the COVID hospital contracted COVID-19. No patients outsourced to the COVID-free hospital were infected there. Outpatient referrals to urology service decreased from 928 to 481. There was a 66% decrease in new cancer diagnoses. A virtual review clinic was established, with remaining outpatients reviewed through a telephone clinic platform. CONCLUSION: Compared with 2019, we performed fewer operations and outpatient procedures, had fewer admissions and diagnosed fewer patients with new cancers. However, outsourcing elective operation to designated non-COVID hospitals prevented the infection of any patient with COVID-19 in the post-operative period. The use of virtual clinic and telephone clinic has had some success in replacing traditional outpatient visits. The overall significant decrease in operative volume will likely precipitate a mismatch between demand and service provision in the coming months, unless capacity is increased.

Cellular Senescence in Renal and Urinary Tract Disorders.

Cellular senescence is a state of cell cycle arrest induced by repetitive cell mitoses or different stresses, which is implicated in various physiological or pathological processes. The beneficial or adverse effects of senescent cells depend on their transitory or persistent state. Transient senescence has major beneficial roles promoting successful post-injury repair and inhibiting malignant transformation. On the other hand, persistent accumulation of senescent cells has been associated with chronic diseases and age-related illnesses like renal/urinary tract disorders. The deleterious effects of persistent senescent cells have been related, in part, to their senescence-associated secretory phenotype (SASP) characterized by the release of a variety of factors responsible for chronic inflammation, extracellular matrix adverse remodeling, and fibrosis. Recently, an increase in senescent cell burden has been reported in renal, prostate, and bladder disorders. In this review, we will summarize the molecular mechanisms of senescence and their implication in renal and urinary tract diseases. We will also discuss the differential impacts of transient versus persistent status of cellular senescence, as well as the therapeutic potential of senescent cell targeting in these diseases.

Purine nucleoside phosphorylase inhibition ameliorates age-associated lower urinary tract dysfunctions.

In the aging population, lower urinary tract (LUT) dysfunction is common and often leads to storage and voiding difficulties classified into overlapping symptom syndromes. Despite prevalence and consequences of these syndromes, LUT disorders continue to be undertreated simply because there are few therapeutic options. LUT function and structure were assessed in aged (>25 months) male and female Fischer 344 rats randomized to oral treatment with a purine nucleoside phosphorylase (PNPase inhibitor) 8-aminoguanine (8-AG) or vehicle for 6 weeks. The bladders of aged rats exhibited multiple abnormalities: tactile insensitivity, vascular remodeling, reduced collagen-fiber tortuosity, increased bladder stiffness, abnormal smooth muscle morphology, swelling of mitochondria, and increases in urodamaging purine metabolites. Treatment of aged rats with 8-AG restored all evaluated histological, ultrastructural, and physiological abnormalities toward that of a younger state. 8-AG is an effective treatment that ameliorates key age-related structural and physiologic bladder abnormalities. Because PNPase inhibition blocks metabolism of inosine to hypoxanthine and guanosine to guanine, likely uroprotective effects of 8-AG are mediated by increased bladder levels of uroprotective inosine and guanosine and reductions in urodamaging hypoxanthine and xanthine. These findings demonstrate that 8-AG has translational potential for treating age-associated LUT dysfunctions and resultant syndromes in humans.

A Review of Urologic Conditions in Remote and Austere Environments: Presentation, Evaluation, and Management.

The objective of this review is to provide recommendations on the evaluation and management of urologic conditions in a resource-poor or austere setting from the perspective of the urological literature. The material was synthesized predominantly from urologic society guidelines and journals to bring additional urology-focused insight to the topic to complement the currently available literature, which is largely based on recommendations from nonurologic specialties. We sought to provide a reference guide from a urology-based framework that encourages a collaborative multidisciplinary approach to the development of a resource that serves those in a wilderness, austere, or resource-poor setting.

Urinary System Manifestation of IgG4-Related Disease: Clinical, Laboratory, Radiological, and Pathological Spectra of a Chinese Single-Centre Study.

BACKGROUND: IgG4-related disease is a new disease entity, but little attention was drawn to urinary system involvement besides nephritis or nephropathy. Here, we described clinical, radiological, and pathological manifestations of IgG4-related urinary disease (IgG4-RUD) and assess its treatment responses. METHODS: We conducted a retrospective study enrolling 65 IgG4-RUD patients from an IgG4-related disease (IgG4-RD) cohort of the Peking Union Medical College Hospital. Clinical, laboratory, radiological, pathological data were collected, and treatment response to immunosuppressants were analysed. RESULTS: IgG4-related interstitial nephritis (TIN, 32.3%), glomerular nephritis (GN, 7.7%), renal pelvis and ureter involvement (21.5%), abnormal radiology with quiescent clinical presentation (13.8%), and renal parenchymal lesion plus retroperitoneal fibrosis (RPF, 18.5%) were major lesion types of IgG4-RUD. All patients had elevated serum IgG4, 76.9% had hyperglobulinemia, and 92.3% had elevated serum IgE at diagnosis. IgG4-TIN patients presented with renal dysfunction, and 94.3% had low serum complement C3 and IgG4-GN presented with nephrotic syndrome, while renal pelvis and ureter involvement had normal renal function and urinalysis. IgG4-RPF with renal parenchymal involvement presented with acute renal dysfunction and required emergency medical intervention. Renal cortex low-density areas, parenchyma or pelvis nodular mass, bilateral enlargement of the kidney, and renal pelvis and ureter mass/wall thickening were specific image patterns of IgG4-RUD. Infiltration of plasma lymphocytes and storiform fibrosis were histopathological features of IgG4-RUD. Patients showed satisfactory responses to immunosuppressive treatment, but complete recovery of renal function was difficult to achieve in IgG4-TIN. Four patients (6.2%) experienced clinical relapses during the maintenance period. CONCLUSION: IgG4-RUD had diverse lesion types and distinctive manifestations. Radiological examinations were helpful for diagnosis and treatment evaluation. Patients showed good initial response to immunosuppressive treatment but relapses could occur at the maintenance period.

Adenoma nefrogénico de vejiga. Un simulador de neoplasia urotelial vesical / Nephrogenic adenoma of the bladder. A simulator of urothelial bladder neoplasia

No disponible

Machine learning for syndromic surveillance using veterinary necropsy reports.

The use of natural language data for animal population surveillance represents a valuable opportunity to gather information about potential disease outbreaks, emerging zoonotic diseases, or bioterrorism threats. In this study, we evaluate machine learning methods for conducting syndromic surveillance using free-text veterinary necropsy reports. We train a system to detect if a necropsy report from the Wisconsin Veterinary Diagnostic Laboratory contains evidence of gastrointestinal, respiratory, or urinary pathology. We evaluate the performance of several machine learning algorithms including deep learning with a long short-term memory network. Although no single algorithm was superior, random forest using feature vectors of TF-IDF statistics ranked among the top-performing models with F1 scores of 0.923 (gastrointestinal), 0.960 (respiratory), and 0.888 (urinary). This model was applied to over 33,000 necropsy reports and was used to describe temporal and spatial features of diseases within a 14-year period, exposing epidemiological trends and detecting a potential focus of gastrointestinal disease from a single submitting producer in the fall of 2016.

Clinicopathologic study of 60 cases of urothelial neoplasms with inverted growth patterns: Reclassification by international consultation on urologic disease (ICUD) recommendations.

BACKGROUND: Most urothelial neoplasms of the bladder show an exophytic papillary pattern, but some show an inverted growth pattern. In 2004, the World Health Organization (WHO) released a detailed histologic classification system for papillary urothelial neoplasms, but not for inverted forms. The International Consultation on Urologic Disease (ICUD) recommendations of 2012 are applicable to inverted/endophytic papillary lesions as follows: 1) inverted papilloma (IP), 2) inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP), 3) inverted papillary urothelial carcinoma, low grade, non-invasive (IPUCLG-NI), 4) inverted papillary urothelial carcinoma, high grade, non-invasive (IPUCHG-NI), 5) inverted papillary urothelial carcinoma, high grade, invasive (IPUCHG-I). However, only atypical cellular morphology was considered for classification in the 2012 ICUD recommendations, and data to support to validate this new grading system are lacking. METHODS: Sixty cases of inverted urothelial papillary tumors were classified into 5 categories according to 2012 ICUD and 2016 WHO/ISUP recommendations to evaluate their clinical, pathological, and immunohistochemical characteristics. Two subgroups were defined as subgroup 1, IP and IPUNLMP, and subgroup 2, IPUCLG-NI, IPUCHG-NI, and IPUCHG-I. Clinical features (age, sex, history of urothelial carcinoma, smoking history, size, and multifocality) and histologic features (nuclear pleomorphism, mitotic count, mitosis level, apoptosis, luminal necrosis, trabecular thickening, anastomosing trabeculae, hypercellularity, loss of polarity, peripheral palisading, palisading with central streaming, and discohesiveness) were evaluated. Immunohistochemical stains for CK20, CD44, P53, p16, Ki-67, cyclin D1 and c-erbB2 were performed. RESULTS: A total of 60 cases were classified as 10 cases of IP, 29 cases of IPUNLMPs, 15 cases of IPUCLG-NI, 4 cases of IPUCHG-NI, and 2 cases of IPUCHG-I. Compared to subgroup 1, subgroup 2 showed larger tumor size, more nuclear irregularity, higher mitotic count (hot spot and per 10 high power fields), more upper level mitosis (>1/2), and more frequent apoptosis, luminal necrosis, surface papillary component, trabecular thickening, anastomosing irregular trabeculae, hypercellularity, loss of polarity, peripheral palisading with central streaming, and discohesiveness, and absence of umbrella cells and urothelial eddies. CK20, Ki67, and c-erbB2 were the only markers that were differently expressed in the two subgroups, with more expression in subgroup 2. CONCLUSIONS: The 2012 ICUD recommendations are valid to classify inverted papillary urothelial tumors. However, other histologic features besides atypical cellular morphology should also be considered to distinguish subgroup 1 and subgroup 2 inverted papillary urothelial tumors.

Disease Overview of the Urinary Tract in Exotic Companion Mammals and Tips on Clinical Management.

Diseases of the urinary tract are reviewed, covering infectious (bacterial, viral, parasitic), degenerative, congenital, metabolic, nutritional, neoplastic, obstructive, and toxic causes. Some clinical presentations and diagnostic procedures are described for ferrets, rabbits, guinea pigs, hamsters, mice, rats, chinchillas, hedgehogs, and sugar gliders, as well as therapies.

Review of the effect of 3D medical printing and virtual reality on urology training with 'MedTRain3DModsim' Erasmus + European Union Project

Background/aim: It is necessary to incorporate novel training modalities in medical education, especially in surgical fields, because of the limitations of cadaveric training. Traditional medical education has many drawbacks, such as residency working hour restrictions, patient safety conflicts with the learning needs, and the lack of hands-on workshops. The MedTRain3DModsim Project aimed to produce 3-dimensional (3D) medical printed models, simulations, and innovative applications for every level of medical training using novel worldwide technologies. It was aimed herein to improve the interdisciplinary and transnational approaches, and accumulate existing experience for medical education, postgraduate studies, and specialty training. Materials and methods: This project focused on models of solid organs and the urinary system, including the kidney, prostate, ureter, and liver. With 3D medical printing, it is possible to produce a body part from inert materials in just a few hours with the standardization of medical 3D modeling. Results: The target groups of this project included medical students and residents, graduate students from engineering departments who needed medical education and surgical training, and medical researchers interested in health technology or clinical and surgical an atomy. Conclusion: It was also intended to develop a novel imaging platform for education and training by reevaluating the existing data using new software and 3D modalities. Therefore, it was believed that our methodology could be implemented in all related medical fields.

Genitourinary Procedures.

Emergency medicine providers may encounter serious GU conditions that need rapid diagnosis and early intervention to avoid severe life- and limb-threatening complications. A fundamental knowledge of several key procedural interventions is incredibly important to optimal patient outcomes.