Circulating monocytes expressing senescence-associated features are enriched in COVID-19 patients with severe disease.

Accurate biomarkers for predicting COVID-19 severity have remained an unmet need due to an incomplete understanding of virus pathogenesis and heterogeneity among patients. Cellular senescence and its pro-inflammatory phenotype are suggested to be a consequence of SARS-CoV-2 infection and potentially drive infection-dependent pathological sequelae. Senescence-associated markers in infected individuals have been identified primarily in the lower respiratory tract, while little is known about their presence in more easily accessible bio-specimens. Here, we measured the abundance of senescence-associated signatures in whole blood, plasma and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients and patients without an infection. Bulk transcriptomic and targeted proteomic assays revealed that the level of senescence-associated markers, including the senescence-associated secretory phenotype (SASP), is predictive of SARS-CoV-2 infection. Single-cell RNA-sequencing data demonstrated that a senescence signature is particularly enriched in monocytes of COVID-19 patients, partially correlating with disease severity. Our findings suggest that monocytes are prematurely induced to senescence by SARS-CoV-2 infection, might contribute to exacerbating a SASP-like inflammatory response and can serve as markers and predictors for COVID-19 and its sequelae.

Emotional and behavioral problems in children and adolescents with lower urinary tract dysfunction: a population-based study.

BACKGROUND: An association has been found between lower urinary tract dysfunction (LUTD) and emotional and behavioral problems, particularly in cases of urinary incontinence. Other associated symptoms and the coexistence of functional constipation require further investigation. OBJECTIVE: To assess whether emotional and behavioral problems are more common in children and adolescents with LUTD. STUDY DESIGN: A multicenter, cross-sectional, population-based study conducted in public places. Parents answered questions on urinary and psychological symptoms in their children aged 5-14 years. Children/adolescents with neurological problems or anatomical urinary tract abnormalities were excluded. The Dysfunctional Voiding Scoring System was used for assessing urinary symptoms, the Rome III Diagnostic Criteria for evaluating bowel symptoms, and the Strengths and Difficulties Questionnaire (SDQ) for evaluating emotional and behavioral problems. RESULTS: Of the 806 children/adolescents included, 53% were female. The mean age was 9.1 ± 2.7 years. The prevalence of LUTD was 16.4%. Overall, 26.2% had abnormal scores in the overall SDQ scale, 29.2% in the emotional problems subscale, and 30% in the conduct problems subscale. Of the children with LUTD, 40.5% screened positive for emotional/behavioral problems, with a significant association being found for the overall SDQ scale (P < 0.001) and for the emotional problems (P < 0.001), conduct problems (P < 0.001), and hyperactivity (P = 0.037) subscales. Urinary urgency, urinary incontinence, and voiding postponement were significantly associated with a greater prevalence of abnormalities in the overall SDQ score (P = 0.05; P = 0.004, and P = 0.012, respectively). Bladder and bowel dysfunction was an aggravator of emotional and behavioral problems, with more intense symptoms, both in the overall SDQ scale and in the subscales. In the multivariate analysis, the factors independently associated with the presence of emotional and behavioral problems were LUTD (odds ratio [OR] = 1.91), constipation (OR = 1.7), studying in a government-funded school (OR = 2.2), and poor education of the head of the family (OR = 1.9). CONCLUSIONS: Children and adolescents with LUTD have more emotional and behavioral problems, with bladder and bowel dysfunction being an aggravating factor for this association.

Topical estradiol increases epidermal thickness and dermal collagen of foreskin prior to hypospadia surgery - Randomized double blinded controlled trial.

INTRODUCTION: The use of preoperative topical testosterone stimulation prior to hypospadias correction aims to increase penile size and achieve better surgical results. Topical estradiol has been shown to improve the quality of skin in other sites, but its use in boys with hypospadia has not yet been elucidated. OBJECTIVE: This study aims to evaluate the primary effects in epidermal thickness and collagen distribution of estradiol compared to testosterone and placebo in skin of prepuce before hypospadia surgery. MATHERIALS AND METHODS: Patients were randomized into three groups according to the topical hormone used: TG: Testosterone ointment; EG: Estradiol ointment; CG: Neutral base ointment. Fragments of foreskin were excised, fixed and then sectioned for histology. For each sample, epidermal thickness and dermal collagen expression was measured by specific computer analysis, P-values of <0.05. RESULTS: Thirty-three patients with a mean age of 4.01 ± 2.92 years were included. Hypospadia classification was similar in all three groups. Mean epidermal thickness and collagen type I expression in EG were greater than those of the other groups. Collagen type III expression was similar in all groups. DISCUSSION: Foreskin has a fundamental role in many techniques of hypospadias surgery and can be used either as a graft or a flap in the correction of the penile defect. Increase of epidermal thickness and dermal collagen observed in the present study has already been related to use of estradiol in other skin sites, but not yet in foreskin. Further studies are needed to evaluate the real significance of these findings in boys with hypospadias. CONCLUSION: Use of topical estradiol before hypospadias surgery lead to greater epidermal thickness and increases dermal collagen expression in foreskin.

Erectile dysfunction association with physical activity level and physical fitness in men aged 40-75 years.

The aim of this study is to evaluate the association between physical activity level and physical fitness with erectile dysfunction in men aged 40-75 years. We examined 180 men aged 40-75 years. The individuals were evaluated for age, presence of dyslipidemia and smoking and for anthropometric parameters for the characterization of body mass index. For assessing the level of physical fitness, a test was performed to measure the indirect maximum oxygen consumption. The evaluation of erectile function was made by the International Index of Erectile Function questionnaire and assessment of physical activity level by the International Physical Activity questionnaire in its short version. This study showed that younger men with higher physical activity and better physical fitness are less likely to suffer from erectile dysfunction. Multivariable analysis through logistic regression showed that age (odds ratio (OD)=1.15; 95% confidence interval (95% CI)=1.07-1.23), physical activity (OD=10.38; 95% CI=3.94-27.39) and physical fitness (OD=4.62; 95% CI=1.75-12.25) were independent variables associated with erectile dysfunction. This study reinforces the concept that healthy habits have a direct effect on erectile function.

Clorpromazina e funçäo mitocondrial na isquemia-reperfusäo renal / Chlorpromazine and mitochondrial function in kidney ischemia-reperfusion

Introduçäo e objetivo - em transplante renal com doador cadáver, a funçäo do enxerto depende da manutençäo da integridade celular e subcelular, principalmente mitocondrial. Neste estudo o objetivo foi analisar a funçäo mitocondrial do rins submetidos a período prolongado de isquemia fria, seguido de reperfusäo por uma hora, empregando-se, ou näo, a clorpromazina previamente à isquemia. Métodos - utilizando autotransplante renal em cäes, subdivididos em dois grupos, foram extraidas mitocôndrias de rins submetidos à isquemia fria de 48 horas, seguida de 1 hora de reperfusäo pós-transplante. Um grupo recebeu clorpromazina antes da nefrectomia. A análise da fosforilaçäo oxidativa e do intumescimento osmótico ("swelling") mitocôndrial foi comparada com dados obtidos de rins normais, sem isquemia. Resultados - Os dados obtidos para o estado III e IV da respiraçäo näo mostraram diferença significativa entre os grupos experimentais. A primeira fase do "swelling" ocorreu em tempo semelhante em todos os grupos experimentais. Durante a reversäo, os grupos I e II se comportaram de maneira estatisticamente semelhante, com fraçöes de reversäo de 57 por cento, e 68 por cento, respectivamente, valores significativamente menores que os obtidos para o grupo normal (99 por cento) (grupo I: p = 0,0374 e grupo II: p = 0,0221). Discussäo - é conhecida a açäo protetora da clorpromazina na isquemia renal normotérmica. Entretanto, os dados aqui obtidos mostram que após 48 horas de isquemia fria, o grupo II (clorpromazina) comportou-se de maneira semelhante ao grupo I (hipotermia isolada) tanto no estudo da fosforilaçäo oxidativa, quanto no "swelling", embora os valores apresentem tendência a serem maiores no grupo II. Isto pode ser devido a alguns fatores, como: 1) a clorpromazina possui efeito protetor mínimo quando o tempo de isquemia é prolongado; 2) seu efeito pode ser afetado ou sua açäo protetora sobreposta àquela imposta pela hipotermia; 3) tempo de reperfusäo curto para manifestaçäo de seus efeitos.

Successful management of a large xanthine calculus by percutaneous nephrolithotomy after failed SWL in a 5-year-old boy.

A 5-year-old child with a xanthine calculus resistant to SWL was made stone free by percutaneous ultrasonic lithotripsy.

Pediatric inflammatory bladder tumors: myofibroblastic and eosinophilic subtypes.

PURPOSE: Benign bladder tumors are rare in children. A number of descriptive terms have previously been used to describe inflammatory tumors with myofibroblastic proliferation or eosinophilic infiltration. We present our experience with these tumors and review the literature. MATERIALS AND METHODS: We retrospectively reviewed the records of all children presenting with a benign focal bladder mass during the last 5 years, including 2 girls and 3 boys 2 to 12 years old (mean age 7). RESULTS: Presenting symptomatology included irritative voiding symptoms, suprapubic pain and hematuria. All bladder masses were diagnosed by ultrasonography and all patients underwent transurethral resection. Three children who had an inflammatory bladder tumor with myofibroblastic features required open tumor excision with preservation of the bladder. In the 2 remaining children urine culture was positive preoperatively and the diagnosis was an inflammatory bladder tumor with eosinophilic infiltration. Transurethral resection of the mass was performed without partial cystectomy. CONCLUSIONS: Inflammatory myofibroblastic and eosinophilic tumors represent forms of focal cystitis with a tumefactive component. Differentiation from the malignant bladder neoplasms of childhood has important consequences for therapy. Management of these benign but aggressive inflammatory lesions involves local control by endoscopic or open surgery with bladder preservation. We encourage refined use of the terminology for inflammatory myofibroblastic and eosinophilic tumors.

Xanthogranulomatous pyelonephritis in an infant with an obstructed upper pole renal moiety.

We report a case of xanthogranulomatous pyelonephritis in an infant involving the upper renal pole moiety of a duplicated system associated with an obstructed ectopic ureter. It was successfully managed by an upper pole heminephroureterectomy. We also review the published reports of xanthogranulomatous pyelonephritis in pediatric patients.