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Abstract Introduction Metabolic syndrome (MetS) is a metabolic disorder related to obesity and insulin resistance and is the primary determinant of the development of low-intensity chronic inflammation. This continuous inflammatory response culminates in neuroimmune-endocrine dysregulation responsible for the metabolic abnormalities and morbidities observed in individuals with MetS. Events such as the accumulation of visceral adipose tissue, increased plasma concentrations of free fatty acids, tissue hypoxia, and sympathetic hyperactivity in individuals with MetS may contribute to the activation of the innate immune response, which compromises cerebral microcirculation and the neurovascular unit, leading to the onset or progression of neurodegenerative diseases. Objective This study aimed to evaluate the effects of chronic treatment with a GLP-1 receptor agonist (semaglutide) on cerebral microcirculation and neurovascular unit (NVU) integrity. Methods C57BL/6 mice were fed a standard normolipidic diet or a high-fat diet (HFD) for 24 weeks and then treated for 4 weeks with semaglutide (HFD SEMA) or saline solution (HFD SAL). At the end of pharmacological treatment, biochemical analyses, immunohistochemistry analysis, and intravital microscopy of the brain microcirculation were carried out to quantify leukocyte–endothelium interactions and to assess structural capillary density, astrocyte coverage on cerebral vessels and microglial activation. Results We observed that SEMA attenuates high-fat diet-induced metabolic alterations in mice fed with HFD for 24 weeks. SEMA also reversed cerebral microcirculation effects of HFD by reducing capillary rarefaction and the interaction of leukocytes in postcapillary brain venules. The HFD-SEMA group exhibited improved astrocyte coverage on vessels. However, SEMA did not reverse microglial activation. Conclusions Semaglutide can reverse microvascular rarefaction in metabolic syndrome by restoring the integrity of the neurovascular unit. Adverse dietary stimuli can compromise microglial homeostasis that is not reversed by semaglutide.

Abstract Background Postoperative antibiotic prophylaxis (PAP) involves using antibiotics after surgery to prevent surgical site infections (SSIs). However, studies have shown that PAP offers no additional benefits compared to discontinuation after surgical incision closure, prompting its de-implementation to prevent unnecessary antibiotic use that may contribute to antibiotic resistance. We conducted this review to synthesize evidence for guiding the design and implementation of effective strategies for discontinuing PAP practice and optimizing antibiotic use in surgical settings. Methods This umbrella review searched for articles from PubMed/MEDLINE and Scopus, focusing on reviews conducted on human subjects on PAP to prevent SSIs, published in English language from 2019 to 5th July 2024. This review followed guidelines from PRISMA-P and PRIOR. The risk of bias (methodological quality) was assessed using AMSTAR-2. The pooled risk ratio (RR) was estimated using a fixed-effects model (Mantel–Haenszel method), while I 2 was used to assess the heterogeneity between reviews. This review was registered with PROSPERO (CRD42024566124). Results In our umbrella review, we screened 1156 articles, with 28 review articles found eligible for final analysis, involving over 457 primary studies. About 80,483 patients were involved in 9 meta-analysis reviews, which were used to estimate the pooled RR. We found no significant benefits to patients from continuing PAP beyond 24-h post-surgery compared to immediate discontinuation, RR: 1.07 (95% CI: 0.97–1.17, I 2: 25%, p-value: 0.22). Strategies such as regularly assessing and refining guidelines to fit specific surgical settings and patients’ characteristics, multidisciplinary collaboration, availability of resources needed for best practices, education and training healthcare workers on SSI prevention and antibiotic stewardship, and patient education in SSI prevention and proper antibiotic use were recommended to improve best practices in surgical settings. Conclusions Prolonging antibiotic prophylaxis beyond 24-h post-surgery did not show significant protective benefits against SSIs. Our findings support the 2018 WHO recommendation for the immediate discontinuation of PAP following surgical incision closure in clean and clean-contaminated procedures. Further de-implementation research studies are needed to guide the effective discontinuation of PAP practice.

Abstract Background Horseshoe kidney is the most common renal fusion anomaly, occurring in approximately 1 in 500 individuals worldwide. It is characterized by abnormalities in kidney position, rotation, and vascular supply. While often asymptomatic, horseshoe kidneys can lead to urological complications, primarily due to ureteric obstruction and impaired urinary drainage.Although ureteropelvic junction obstruction (UPJO) is uncommon in horseshoe kidneys, its occurrence presents unique diagnostic and management challenges. This case explores the etiology, clinical presentation, and surgical management of UPJO in a patient with a horseshoe kidney, highlighting the critical role of urologists in addressing these anatomical and functional complexities. Case presentation We report the case of a 3-month-old African male infant who presented with a two-month history of excessive crying and symmetrical abdominal distension. Radiological evaluation revealed a horseshoe kidney with decreased parenchymal thickness in the left kidney and marked hydronephrosis of the pelvis and calyces, with abrupt cessation at the left ureteropelvic junction. Surgical correction of the obstruction was performed successfully. The patient was followed for six months, during which he remained symptom-free with normal renal function tests. Conclusion Ureteropelvic junction obstruction in a horseshoe kidney presents unique anatomical challenges. Symptomatic cases require thorough imaging for diagnosis and surgical planning. Pyeloplasty is the typical surgical intervention, meticulously planned to address these complexities. This ensures effective relief of obstructions and proper urinary drainage.

ABSTRACT Wilms' tumor (WT), also known as nephroblastoma, is a malignant embryonal kidney tumor composed of embryonic cells and is the most prevalent tumor among children, but isolated cases occur infrequently in the adult population. Adult WT is defined according to the criteria of Kilton, Matthews, and Cohen, which comprise age above 15 years and histological patterns characteristic of WT. We report a case of an adult WT with venous thrombus on an incomplete duplex collecting system. To the best of our knowledge, this is the first case of adult WT with such a presentation. A 28‐year‐old female patient presented to our department with a 4‐month history of right flank pain and flank mass and was diagnosed by abdominal contrasted CT to have a right renal tumor with tumor thrombi in the renal vein and the inferior vena cava. The CT scan also revealed a bilateral duplex collecting system with a partial (ureter fissus proximalis) on the tumor side and a complete duplex system on the contralateral side. Right radical nephrectomy with complete tumor thrombectomy via venacavotomy was performed successfully. Histopathological examination of the specimen revealed a triphasic nephroblastoma with immunohistochemistry confirmation. Postoperatively, adjuvant chemotherapy was initiated. The increasing incidence of non‐syndromic WT cases associated with duplex collecting systems suggests a potential shared pathogenesis, necessitating further research.

This study aims to assess the favourable ecosystem for supporting OS in Tanzania and the factors hindering its adoption and implementation. Employing a cross-sectional research design, the study evaluates the enabling environment for Open Science adoption and practices within Tanzania. The study population comprises academicians, researchers, students, librarians, and science communicators. A total of 144 participants took part in the survey, predominantly early career researchers affiliated with both public and private institutions. The findings underscore that to some extent several institutions within Tanzania provides some kind of support for open science practices. This support manifests through the provision of Institutional Repositories, online journal publishing systems, financial coverage for publishing processing charges, and the establishment of improved mechanisms for researchers to share their publications and data. Nonetheless, the results also highlight several challenges. These include a lack of awareness regarding OS practices, absence of institutional policies, inadequate budget allocation to cover article processing charges (APCs), and the high costs associated with publishing in prestigious Open Access (OA) journals. Concerted efforts at both national and institutional levels to foster the widespread adoption of OS practices in Tanzania should be put in place. The efforts should focus on enhancing awareness, developing comprehensive policies, allocating adequate budgets to support APCs, and exploring strategies to mitigate the financial barriers associated with publishing in prestigious OA journals. By addressing these challenges proactively, Tanzania can pave the way for a more robust and inclusive research ecosystem aligned with the principles of Open Science.

Objectives To evaluate the cost-effectiveness of percutaneous repair (PR) for secondary mitral regurgitation.Design An economic evaluation using a time-varying Markov model comprising three states to assess the cost and effectiveness of PR added to guideline-directed medical treatment (GDMT) compared with GDMT alone. Clinical outcomes considered within the model were overall survival and heart failure (HF) hospitalisations (HFH), and the incremental cost-effectiveness ratio (ICER) was calculated. Cost data were derived from a literature search. Sensitivity analyses were undertaken.Setting The French healthcare system perspective assuming a lifetime horizon.Participants Published data at 5 years obtained from patients enrolled in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation study.Results In our base case, we chose cubic spline models to extrapolate overall survival, and we used log-logistic models to estimate cumulative HFH. After discounting, the model generated life-years of 3.843 years and 3.055 years for PR+GDMT and GDMT, respectively. Discounted total quality-adjusted life-year (QALY) values were 2.572 and 1.945 for PR+GDMT and GDMT, respectively (incremental 0.627 QALY). Discounted total costs were €42 709 and €20 732 for the intervention and the control groups, respectively (incremental €21,977), resulting in an ICER of €35,068/QALY. At a threshold of €50 000 per QALY, PR had a 0.85 probability of being cost-effective.Conclusion Updated trial data have enabled investigators to provide a more reliable estimation of the ICER, which suggests that PR has good value for money compared with GDMT alone.

BackgroundProstate cancer is a common cancer among men globally and its treatment affects quality of life. Poor patients’ perception of prostate cancer services may lead to their late presentation for care, often presenting with the advanced stage of the disease. This may vary from one region to another.ObjectiveThis study, therefore, aimed to explore patients’ perceptions of the quality of care for prostate cancer in Tanzania.MethodsThis qualitative case study was conducted in five tertiary hospitals in Tanzania in November 2023. In-depth interviews were conducted with prostate cancer patients on treatment for not less than 6 months. Data on patients’ perception of prostate cancer, quality of prostate cancer services, and quality of life among prostate cancer patients were collected. Thematic analysis used a hybrid inductive and deductive reasoning approach through NVivo 14 software.ResultsA total of 17 interviews were conducted, resulting in four themes. These were perception of prostate cancer on the causes and diagnostic methods, delays of care leading to late presentation, perception of quality of life after treatment for prostate cancer recovery versus cancer progression, and quality of service in terms of organization of service delivery for prostate cancer at tertiary hospitals in Tanzania.ConclusionQuality of services for prostate cancer was well-perceived, especially communication for psychosocial support. A good perception of the quality of service was found to influence the uptake of prostate cancer services. Prostate cancer patients have mixed perceptions about the quality of life after treatment, which delays health seeking, leading to late presentation. Despite efforts in awareness campaigns through different platforms, more effort is needed in determining the causes of prostate cancer, the diagnostic/screening methods necessary for prostate cancer, timely health seeking, the available treatment options for prostate cancer, and the expected quality of life after treatment.

Summary: Background: Mucormycosis is a deadly invasive fungal infection recently included in the WHO priority pathogen list. Here we sought to describe epidemiological trends of mucormycosis in France, and to evaluate factors associated with mortality. Methods: From 2012 to 2022, we implemented a nationwide prospective surveillance programme for mucormycosis in France, focusing on epidemiology, species, seasonal variations. Factors associated with 3-month mortality were studied by univariable and multivariable logistic regression. Findings: Among 550 cases of mucormycosis, the main underlying conditions were haematological malignancy (HM, 65.1%, 358/550), trauma (8%, 44/550), diabetes (7.5%, 41/550) and solid-organ transplants (6.5%, 36/550). Site of infection was pulmonary in 52.4% (288/550), rhinocerebral in 14.5% (80/550), and cutaneo-articular in 17.1% (94/550). Main species identified were Rhizopus arrhizus (21%, 67/316), Rhizopus microsporus (13.6%, 43/316), Lichtheimia corymbifera and Mucor circinelloides (13.3%, 42/316 each), Rhizomucor pusillus (12%, 38/316), and Lichtheimia ramosa (10.8%, 34/316). We found associations between underlying condition, site of infection, and infecting species, including a previously undescribed triad of trauma, cutaneo-articular localisations, and L. ramosa/M. circinelloides. Diagnostic contribution of Polymerase Chain Reaction (PCR) increased from 16% (4/25) in 2012 to 91% (61/67) in 2022, with more than 50% of diagnoses relying solely on PCR in 2022. We also found seasonal variations with relatively more cases in autumn. Ninety-day mortality was 55.8% (276/495). Independent prognostic factors were age, diagnosis in Intensive Care Unit (ICU), and HM while diagnosis after 2015 (i.e. large implementation of PCR) and surgery were associated with reduced mortality. Interpretation: This study reveals major mucormycosis epidemiological changes in France, with a large predominance of HM patients, and a parallel between PCR multicentre implementation and improved prognosis. We also evidence new associations between species, localisations and risk factors, as well as seasonal variations. Funding: Recurrent financial support from Santé Publique France and Institut Pasteur.

Objectives The objectives are to determine the prevalence of urinary tract infection (UTI) and associated factors among patients diagnosed with benign prostatic hyperplasia and prostate cancer.Design Hospital-based cross-sectional study.Settings Urology clinic and urology ward at Muhimbili National Hospital, which is the main tertiary hospital in Tanzania’s largest city.Participants Patients with benign prostate hyperplasia and prostate cancer presenting with genitourinary symptoms.Main outcome measure The primary outcome was the occurrence of UTI and factors associated with UTI in patients with benign prostatic hyperplasia and prostate cancer.Results 402 participants were enrolled, with a median age of 68 years and IQR of 61–75 years. The proportion of UTI was 46.5% (95% CI 41.56% to 51.53%). UTI was more prevalent among inpatients, patients with indwelling urinary catheters, patients with prostate size>80 cm3 and those with residual urine volume of >100 mL. In multivariate analysis, age>60 years (adjusted OR (aOR)=2.0, 95% CI 1.13 to 3.55, p=0.018), post-void residual urine volume>100 mL (aOR 1.32, 95% CI 0.67 to 2.59 p=0.001), patient with incomplete bladder emptying (aOR=2.57, 95% CI 1.44 to 4.59, p=0.001) and prolonged catheter duration (aOR=1.24, 95% CI 1.11 to 1.38, p=0.005) were significantly associated with UTI.Conclusion Almost half of the patients with an enlarged prostate and genitourinary symptoms had a laboratory-confirmed UTI. The risk of UTI increases with age, incomplete bladder emptying and increased duration of catheterisation. A 1-day increase in the duration of catheterisation increased the risk of UTI by 24%.

The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. We show that a host-constructed physical niche in the foregut selectively binds bacteria with strain-level specificity, stabilizing their colonization. Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. Our results provide a mechanistic framework for understanding the establishment and stability of a multi-species intestinal microbiome.

I. INTRODUCTION 437 II. GENDER DISPARITY IN PRISON PROGRAMS 438 A. CLAIMS UNDER THE FOURTEENTH AMENDMENT'S EQUAL 439 PROTECTION CLAUSE B. CLAIMS UNDER TITLE IX OF THE EDUCATION AMENDMENTS ACT [...]

Abstract Objective The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke‐unit (SU)—access, acute reperfusion therapy—use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. Methods AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris‐area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age‐, initial NIHSS‐ and sex‐matched HIV‐uninfected controls (HUCs). Outcome was the 90‐day modified Rankin Scale score. Results Among 126 PLHIVs with confirmed first‐ever AIS, ~80% were admitted outside the thrombolysis‐administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small‐vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%–30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well‐tolerated. Interpretation The high uncontrolled HIV‐infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

Abstract Objective Central pontine myelinolysis (CPM) is a rare demyelinating disease that affects the pons and which can cause extreme disabilities such as locked‐in syndrome (LIS) in the initial phase. The aim of the study was to describe the evolution over a 12‐month period of two patients with CPM causing an initial LIS. Method We retrospectively report the unexpected clinical outcome of these two patients in relation with the anatomical damages documented by brain MRI, associated with diffusion tensor imaging and reconstruction of corticospinal tracts in tractography. The following clinical parameters systematically assessed at 3, 6, 9, and 12 months: muscle testing on 12 key muscles (Medical Research Council), prehension metrics (box and block test and purdue pegboard), and independence for acts of daily living (functional independence measure). Results Both patients showed a progressive recovery beginning between 2 and 3 months after the onset of symptoms, leading to almost complete autonomy at 12 months (FIM > 110), with motor strength greater than 4/5 in all joint segments (MRC > 50/60). On brain MRI with tractography, CST appeared partially preserved at pons level. Interpretation The possibility of a near‐complete functional recovery at 12 months is important to consider given the ethical issues at stake and the discussions about limiting care that may take place initially. It seems to be the consequence of reversible myelin damage combined with partially preserved neurons. Development of collateral pathways or resolution of conduction block may explain this recovery. MRI comprising DTI and tractography could play a key role in the prognosis of motor recovery.

Key Clinical Message Conservative nonsurgical therapy ensures that the resolution is nearly 80% for vesicoureteral reflux grades I and II and 30%–50% for vesicoureteral reflux grades III and V within 4–5 years of follow‐up. Open surgical reimplantation of ureters of grades IV and V is a highly successful procedure, with reported correction rates ranging from 95% to 99% regardless of the severity of vesicoureteral reflux. Abstract Patients with vesicoureteral reflux present with a wide range of severity. With an incidence of approximately 1%, vesicoureteral reflux is a relatively common urological abnormality in children. Postnatal diagnosis of vesicoureteral reflux is typically made following a diagnosis of a urinary tract infection and less frequently following family screening. Voiding cystourethrograms remain the gold standard for diagnosing vesicoureteral reflux. To preserve the kidney and prevent the need for potential renal replacement therapy, infants with a single kidney require significantly more assessments and prompt decision‐making. Surgical correction is advised for patients with vesicoureteral reflux grades IV and V, while vesicoureteral reflux grades I, II, and III are managed conservatively.

Key Clinical Message The “gold standard” treatment for Squamous cell carcinoma (SCC) is radical cystectomy and different management approaches that combine chemotherapy and radiation in a neoadjuvant or adjuvant setting have been attempted with varying degrees of effectiveness. For certain individuals, partial cystectomy offers sufficient local control for muscle‐invasive bladder cancer. Lifelong follow‐up with cystoscopy is advised due to the possibility of potentially fatal late recurrence. Abstract Squamous cell carcinoma (SCC) of the bladder is a rare urologic malignancy that is estimated to affect 3%–5% of the bladder cases. SCC of the bladder remains the most common subtype throughout Africa. Most of the literatures focused on the management of Urothelial carcinoma (UC), with fewer discussions on SCC management. UC typically presents with painless hematuria, whereas SCC presents with painful hematuria, bladder mass, and necroturia. SCC is mostly radioresistant and does not respond to chemotherapy. The mainstay treatment is partial cystectomy or radical cystectomy, which can be performed through open surgery or laparoscopic or robot‐assisted approaches, all of which have acceptable results. We report a patient with a favorable outcome following partial cystectomy who was managed by open surgery. At the 12‐month follow‐up, the patient remained asymptomatic with good surgical outcomes.

The purpose of this study was to comprehensively appraise and synthesize studies on hand hygiene practices among primary and secondary school students in sub-Saharan Africa (SSA). This is a thorough review of scientific papers published between 2015 and 2023 from primary databases such as the Web of Science, Science Direct, PubMed, and Google Scholar. The review criteria were met by 26 out of 63 studies assessed for legibility. The review demonstrated that students in SSA had moderate and good hand washing practices in terms of regular hand washing, cleaning hands after defecation, and before and after eating. Furthermore, the review pinpoints hand washing practices as influenced by factors such as knowledge, hand washing facilities and materials, influences from parents and teachers or others, personal and social factors, media, gender, age, and other factors such as location, attitudes, and school modernity. Furthermore, the reviewed studies highlighted recommendations for improving hand hygiene practices, such as enhancing hand hygiene and environmental health education, mobilizing resources for hand washing, creating and implementing health policy, and conducting further studies. This review provides data for policymakers on how to improve student hand hygiene and adds to existing knowledge on hand hygiene practices. HIGHLIGHTS This study presents evidence from the existing literature on school students’ hand hygiene practices in sub-Saharan Africa (SSA).; The review covered papers published in SSA from 2015 to 2023.; The hand hygiene practices of students were shown to be moderate and good.; The hand hygiene practices are subject to several factors including knowledge.; The findings encourage further efforts to promote hand hygiene at the school and home levels.;

INTRODUCTION: There is paucity of culturally adapted tools for assessing depression and anxiety in children and adolescents in low-and middle-income countries. This hinders early detection, provision of appropriate and culturally acceptable interventions. In a partnership with the University of Nairobi, Nairobi County, Kenyatta National Hospital, and UNICEF, a rapid cultural adaptation of three adolescent mental health scales was done, i.e., Revised Childrens Anxiety and Depression Scale, Patient Health Questionnaire-9 and additional scales in the UNICEF mental health module for adolescents. MATERIALS AND METHODS: Using a qualitative approach, we explored adolescent participants views on cultural acceptability, comprehensibility, relevance, and completeness of specific items in these tools through an adolescent-centered approach to understand their psychosocial needs, focusing on gender and age-differentiated nuances around expression of distress. Forty-two adolescents and 20 caregivers participated in the study carried out in two primary care centers where we conducted cognitive interviews and focused group discussions assessing mental health knowledge, literacy, access to services, community, and family-level stigma. RESULTS: We reflect on process and findings of adaptations of the tools, including systematic identification of words adolescents did not understand in English and Kiswahili translations of these scales. Some translated words could not be understood and were not used in routine conversations. Response options were changed to increase comprehensibility; some statements were qualified by adding extra words to avoid ambiguity. Participants suggested alternative words that replaced difficult ones and arrived at culturally adapted tools. DISCUSSION: Study noted difficult words, phrases, dynamics in understanding words translated from one language to another, and differences in comprehension in adolescents ages 10-19 years. There is a critical need to consider cultural adaptation of depression and anxiety tools for adolescents. CONCLUSION: Results informed a set of culturally adapted scales. The process was community-driven and adhered to the principles of cultural adaptation for assessment tools.

Abstract Background Urological complications are not uncommon among people living with HIV and are often the initial clinical manifestation of HIV and AIDS. These complications, when presenting with bothersome lower urinary tract symptoms (LUTS), can significantly impact the Quality of life (QoL) of affected individuals. We, therefore, conducted a study aiming at determining the prevalence of bothersome LUTS, identifying factors influencing the severity of these symptoms, and examining their influence on the QoL among people living with HIV on antiretroviral treatment (ART). Methods A cross-sectional study was conducted among randomly selected adult HIV-positive patients who attended the Care and Treatment Center at Muhimbili National Hospital, located in Dar es Salaam, Tanzania, from September 2021 to February 2022. Data was collected using a questionnaire that incorporated the American version of the International Prostate Symptom Score (IPSS). The IPSS was utilized to assess the severity of LUTS and their influence on the QoL. Descriptive statistics were used to summarize the results, and ordinal regression analysis was employed to assess the factors influencing the severity of LUTS. Results The prevalence of LUTS in the study population was 57.8%, with mild symptoms (mean IPSS 3.92 ± 1.92) being the most common manifestation. The mean age of the study participants who presented with LUTS was 47.89 ± 12.05 years, and the majority were females (55.6%). Factors that were significantly associated with increased severity of LUTS included male sex (OR 2.75; 95% CI 1.59–4.75; p

Abstract Introduction The first predominant clinical symptoms of dementia with Lewy bodies (DLB) are highly variable; however, the prognosis based on initial predominant symptoms remains poorly understood. Methods Multicenter retrospective study in 4 French expert neurological centers. Patients were categorized in 3 groups according to their first more predominant symptoms: cognitive, psychiatric, or motor. Results Analysis of 310 DLB patients. The mean age was 73.5 years old (SD 7.5) including 32.3% of women. The mean follow-up was 7.25 years (SD 3.6). We observed that the full clinical picture was more frequent in the motor group than in the cognitive group (p = 0.01); male gender and age at onset were associated with a significant excess risk of instantaneous mortality (p = 0.01). Conclusion Initial symptoms may affect the clinical course of patients, but no significant difference in mortality was observed.

Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction in cell height due to the increase in cell spreading and decrease in cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs, leading to their dramatic 5.4-fold larger widening. Consistent with the increase in TEM density and width in siCAV1 cells, we record a higher lethality in CAV1 KO mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity points toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis.