Validation d'un questionnaire mesurant la consommation de boissons sucrées, jus et eau auprès d'adolescents francophones.

Purpose: To examine the temporal stability and relative validity of the adapted French version of an English self-reported questionnaire measuring the beverage intake (BEVQ) of adolescents.Methods: The French adaptation of the BEVQ (AF-BEVQ) included conversion from the imperial to the metric system and the adjustment of some formats to those available in Canada. Next, 60 adolescents from two regions in Quebec completed the AF-BEVQ and two web-based 24-hour dietary recalls (R24W) (one for a weekday and one for a weekend day) on two occasions, two weeks apart.Results: The AF-BEVQ had moderate intraclass correlation coefficients (ICC) for amounts of sugar-sweetened beverages (ICC: 0.68; 95% confidence interval [CI]: 0.46-0.81), fruit juice (ICC: 0.54; 95% CI: 0.23-0.72) and water (ICC: 0.66; 95% CI: 0.38-0.81) consumed. The amounts of sugar-sweetened beverages (rs = 0.49; p < 0.0001), fruit juice (rs = 0.38; p = 0.0024) and water (rs = 0.65; p < 0.0001) reported in the AF-BEVQ were significantly correlated with those of both R24Ws.Conclusions: For the most part, the AF-BEVQ had adequate metrological properties. It is an interesting tool to quickly measure the sugar-sweetened beverage, fruit juice and water intake of French-speaking adolescents.

Objectif : Vérifier la stabilité temporelle et validité relative de la version française adaptée d'un questionnaire auto-déclaré en anglais mesurant la consommation de diverses boissons (BEVQ) chez les adolescents.Méthodes : L'adaptation française du BEVQ (AF-BEVQ) comprenait notamment la conversion des unités impériales en unités métriques et l'ajustement de certains formats selon ceux disponibles au Canada. Ensuite, 60 adolescents provenant de deux régions du Québec ont complété l'AF-BEVQ et deux rappels de 24 heures Web (R24W) (un jour de semaine et un de fin de semaine) à deux reprises à deux semaines d'intervalle.Résultats : L'AF-BEVQ avait des coefficients intra-classe (ICC) modérés pour les quantités de boissons sucrées (ICC : 0,68; intervalle de confiance [IC] 95 % : 0,46­0,81), de jus de fruits (ICC : 0,54; IC 95 % : 0,23­0,72) et d'eau (ICC : 0,66; IC 95 % : 0,38­0,81) consommées. Les quantités de boissons sucrées (rs = 0,49; p < 0,0001), de jus de fruits (rs = 0,38; p = 0,0024) et d'eau (rs = 0,65; p < 0,0001) rapportées dans l'AF-BEVQ étaient significativement corrélées à celles des deux R24W.Conclusions : L'AF-BEVQ présentait majoritairement des propriétés métrologiques adéquates. Il est un outil d'intérêt pour mesurer rapidement la consommation de boissons sucrées, de jus de fruits et d'eau d'adolescents francophones.

Parental uveitis causes elevated hair loss in offspring of C57BL/6J mice.

Our previous study demonstrated that parental uveitis in a susceptible population can cause hair loss and increase the susceptibility to experimental autoimmune uveitis (EAU) in offspring. However, it is unclear whether parental uveitis affects the development of offspring in an EAU-moderate-susceptible population. Herein, moderate-susceptible C57BL/6J mice were immunized with inter-photoreceptor retinoid binding protein (IRBP) 651-670 to develop EAU and were kept together for mating. Gross examination and histopathological changes of the offspring gestated with parental uveitis were observed to evaluate the impact of parental uveitis on the development of the offspring. Differentially expressed genes (DEGs) were screened by RNA sequencing in the affected skin and eyeball of the offspring on postnatal day 27. Adult offspring were injected 75 µg IRBP651-670 to evaluate their susceptibility to EAU. Gross examination in the offspring revealed hair loss on postnatal days 11-31. Histopathological observation showed increased melanin granules and hair follicles of skin in the affected offspring with hair loss. Gene Ontology (GO) analysis in the skin revealed differential expression of genes involved in the mitotic cell cycle, response to endogenous stimulus, hair follicle development, and hair cycle. The DEGs in the skin were predominately associated with the cell cycle and peroxisome proliferator-activated receptor (PPAR) signaling pathway. The GO enrichment analysis in the eyeball showed differential expression of genes involved in the nervous system development, camera-type eye photoreceptor cell differentiation, neuron projection morphogenesis, axon development, and calcium-induced calcium release activity; enriched pathways included the circadian entrainment and glutamatergic synapses. No increased susceptibility to EAU in offspring gestated from parental remitting EAU was observed at a low-dose 75 µg IRBP induction. These results suggested that parental uveitis in a moderate-susceptible population could affect the skin development and DEG profiles of skin and eyeball related to the response to endogenous stimulus, the PPAR signaling pathway, and glutamatergic synapse, which provides the molecular evidence to explain the influence of parental uveitis on offspring development.

Do men with bladder stones benefit from treatment of benign prostatic obstruction?

OBJECTIVE: To identify whether men aged ≥40 years with bladder stones (BS) benefit from treatment of benign prostatic obstruction (BPO). PATIENTS AND METHODS: A regional, retrospective study of patients undergoing BS surgery between January 2011 and December 2018 was performed using a prospectively collected database. The primary outcome was BS recurrence after successful removal. Kruskal-Wallis and chi-squared statistical tests were used. RESULTS: A total of 174 patients underwent BS removal and 71 (40.8%) were excluded due to BS formation secondary to causes other than BPO. Hence, 103 men aged ≥40 years had BS successfully removed, of which 40% had a history of upper tract urolithiasis. These men were divided into three groups: those undergoing contemporaneous medical, surgical, or no BPO treatment. Age, diabetes, previous urolithiasis and previous BPO surgery were well matched between the BPO treatment groups. In all, 18 of these men (17%) had BS recurrence after 46 months follow-up. Recurrences were significantly lower following BPO surgery; one of 34 (3%) men versus five of 28 (18%) with no BPO treatment (P = 0.048) and 12 of 41 (29%) with medical BPO treatment (P = 0.003). Recurrences after medical and no BPO treatment were similar (P = 0.280). In all, 34 men (33%) had BPO complications that were similar between groups (P = 0.378). CONCLUSION: This is the largest reported cohort of men, with the longest follow-up after BS removal. Most men aged ≥40 years with BS benefit from BPO surgery. However, the study findings also support a multifactorial aetiology for BS, which questions the dogma that BS are an 'absolute indication' for BPO surgery, as is stated in the Non-neurogenic Male Lower Urinary Tract Symptoms European Association of Urology Guideline. Assessment and management of all causative factors is likely to enable selection of which men will benefit from BPO surgery and to reduce BS recurrence rates.

Cardiovascular Morbidity and Mortality in Men - Findings From a Meta-analysis on the Time-related Measure of Risk of Exogenous Testosterone.

BACKGROUND: In the context of established male hypogonadism, testosterone therapy (TTh) has been employed to regain physiologic levels of circulating testosterone and improve sexual function and overall quality of life. AIM: To assess the risk of cardiovascular disease and mortality as time-dependent outcomes in treated vs TTh untreated hypogonadal men. METHODS: A meta-analysis using weighted time-related measure of risk (hazard ratios (HRs)) for each of the outcome for all included studies was performed. Studies investigating male adults (≥18 years old) diagnosed with hypogonadism and divided into 2 arms (a treatment arm [any TTh] and a control arm [observation or placebo]) and assessing the risk of death and/or cardiovascular events were included. Single arm, non-comparative studies were excluded as well as studies that did not report the HRs for the chosen outcomes. This systemic review was registered on PROSPERO (CRD42022301592) and performed according to MOOSE and PRISMA guidelines. OUTCOMES: Overall mortality and cardiovascular events of any type. RESULTS: Overall, 10 studies were included in the meta-analysis, involving 179,631 hypogonadal men. Hypogonadal men treated with TTh were found to be at lower mortality risk from all causes relative to the control (observation or palcebo) arm (HR: 0.70; 95% Confidence Interval [CI]: 0.54-0.90; P < .01), whilst any unfavorable effect of TTh in hypogonadal men in terms of cardiovascular events compared to untreated/observed hypogonadal men was found (HR: 0.98; 95% CI 0.73-1.33; P = .89). CLINICAL IMPLICATIONS: TTh in hypogonadal men might play a role in reducing the overall risk of death without increasing cardiovascular events risk. STRENGTHS & LIMITATION: Main limitations are represented by the high heterogeneity among the studies in terms of included population, definition for hypogonadism, type of TTh, definition of cardio-vascular event used, and the length of follow-up. CONCLUSION: According to time-related measures of risk only, an increased risk of long-term morbidity and early mortality for untreated hypogonadal men was depicted, further outlining the clinical importance and safety of TTh in true hypogonadal men, with the urgent need of collecting long-term follow-up data. Fallara G, Pozzi E, Belladelli F, et al. Cardiovascular Morbidity and Mortality in Men - Findings From a Meta-analysis on the Time-related Measure of Risk of Exogenous Testosterone. J Sex Med 2022;19:1243-1254.

Photoreceptor Cells Constitutively Express IL-35 and Promote Ocular Immune Privilege.

Interleukin-27 is constitutively secreted by microglia in the retina or brain, and upregulation of IL-27 during neuroinflammation suppresses encephalomyelitis and autoimmune uveitis. However, while IL-35 is structurally and functionally similar to IL-27, the intrinsic roles of IL-35 in CNS tissues are unknown. Thus, we generated IL-35/YFP-knock-in reporter mice (p35-KI) and demonstrated that photoreceptor neurons constitutively secrete IL-35, which might protect the retina from persistent low-grade inflammation that can impair photoreceptor functions. Furthermore, the p35-KI mouse, which is hemizygous at the il12a locus, develops more severe uveitis because of reduced IL-35 expression. Interestingly, onset and exacerbation of uveitis in p35-KI mice caused by extravasation of proinflammatory Th1/Th17 lymphocytes into the retina were preceded by a dramatic decrease of IL-35, attributable to massive death of photoreceptor cells. Thus, while inflammation-induced death of photoreceptors and loss of protective effects of IL-35 exacerbated uveitis, our data also suggest that constitutive production of IL-35 in the retina might have housekeeping functions that promote sterilization immunity in the neuroretina and maintain ocular immune privilege.

Impact of Barrel Toasting on Ellagitannin Composition of Aged Cognac Eaux-de-Vie.

It is well established that C-glucosidic ellagitannins contribute to wine quality, and new forms of ellagitannins have been found recently in cognac eaux-de-vie. The contribution of some ellagitannin-derived spirit compounds to eaux-de-vie taste has been demonstrated recently. However, there is a gap in our knowledge of the content, composition, and evolution of C-glucosidic ellagitannins in this matrix. Indeed, the quantification of these compounds and their evolutionary compounds have never before been researched in cognac eaux-de-vie. Thus, the aim of this study was not only to quantify these compounds, but also to study their kinetics and to observe how they are impacted by barrel toasting. For this purpose, barrels representing eight different toasting levels were used to age the same eau-de-vie during the first 18 months. Ellagitannin quantification was carried out by HPLC-Triple quadrupole. The results showed that the evolutionary trend of the eight ellagitannins is the same for all eight types of barrel toasting. The maximum concentrations of C-glucosidic ellagitannins were found after 3 months of aging (up to 23 mg/L) before decreasing to 18 months (9.7 mg/L), whereas ellagitannin-derived spirit compound concentrations increased throughout aging (up to 130.9 mg/L). In addition, barrel toasting had such an impact on ellagitannin content that barrels could be differentiated according to their levels. Eaux-de-vie in barrels with high toasting were lower in ellagitannins concentrations.

Holmium laser enucleation and water vapor thermal therapy for the treatment of symptomatic benign prostatic hyperplasia: A cost analysis.

PURPOSE: To perform a cost analysis of the current gold standard operation of Holmium Laser Enucleation of the prostate (HoLEP) compared to the new technique of water vapor thermal therapy with the Rezum™ system for the treatment of symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Between October 2017 and January 2020, consecutive patients with invalidating lower urinary tract symptoms due to BPH who underwent Rezum™ and HoLEP procedures from the Aix regional hospital were identified. The outcome of each technique was assessed in terms of cost from the institutional perspective. Detailed expense reports based were provided by the accounts department of the hospital. These were used to compare in-hospital costs for each procedure. RESULTS: A total of 53 and 94 consecutive patients underwent respectively water vapor thermal therapy and HoLEP. The median costs for the surgical procedure were €1344 (IQR 1331-1361) and €669 (IQR 584-824), respectively for Rezum™ and HoLEP (median difference €675; P<0.001). The median costs of the hospital stay were €869 (IQR 869-869) for Rezum™ and €1295 (IQR 1295-1330) for HoLEP (median difference €426; P<0.001). Finally, the median total costs per patient were lower for HoLEP (€2005 [IQR 1902-2150]) than for Rezum™ (€2228 [IQR 2209-2243]) procedure, and the median difference of €233 was significant (P<0.001). CONCLUSIONS: One of the anticipated benefits of Rezum™, reduced length of hospital stay with an associated reduction in cost, did not materialize within this study. The patient's clinical condition and expectations should also be taken into account when deciding between Rezum™ and standard therapies. LEVEL OF PROOF: 3.

Comparison of water vapor thermal therapy and prostate artery embolization for fragile patients with indwelling urinary catheters: Preliminary results from a multi-institutional study.

PURPOSE: To report our preliminary experience with water vapor thermal therapy with the Rezum™ System and Prostate Artery Embolization (PAE) for treatment of medically refractory, complete urinary retention to achieve successful cessation of catheter dependency in frail-patients. PATIENTS AND METHODS: A multi-institutional study was conducted including all patients who underwent Rezum™ procedure and PAE between October 2017 and June 2020. The included population focused on frail-patients unsuitable for conventional surgery with complete urinary retention. Rezum™ patients were identified and matched (1:1) with patients who underwent PAE. The matching criteria were age, Charlson score, prostate volume and duration of follow-up. The primary outcome was catheter-free survival, defined as spontaneous voiding and release from catheter dependence. RESULTS: Eleven patients from the Rezum™ group were matched to 11 embolized patients. PAE and Rezum™ patients were comparable in age (median: 77 vs. 75 years), Charlson score (median: 6 vs. 6) and prostate volume (74 vs. 60 cc). Procedures were significantly longer in the PAE group compared to the Rezum™ procedures (median: 148 vs. 8min, P<0.001). After a median follow-up of 12 months, spontaneous voiding was conserved in all cases (100%) after the Rezum™ procedure and in 5 cases (45.4%) after PAE (P=0.01). In catheter-free patients, the rate of benign prostatic hyperplasia medication use after procedure was 40% for PAE and 18.2% for Rezum™ patients (P=0.54). CONCLUSIONS: Our preliminary experience for treatment of complete urinary retention in frail-patients shows the feasibility of PAE and Rezum™ to restore spontaneous urination without being associated with the occurrence of major complications. Early data suggests that Rezum™ may provide superior results in terms of cessation of catheter dependence. Future studies are needed to definitively assess which treatment would be best suited for each patient. LEVEL OF EVIDENCE: 3.

The protective function of invariant natural killer T cells in the relapse of experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU) in mice provides a useful platform to study the pathogenesis and experimental therapeutics of human uveitis. One often used EAU model employs C57BL/6 (B6) mice sensitized with a peptide residue having 1 to 20 amino acids of human interphotoreceptor retinoid binding protein (hIRBP1-20). The model using the B6 background has permitted a liberal use of genetically engineered strains and has provided insights for understanding uveoretinitis. However, this is usually acute/monophasic and does not represent human uveoretinitis that is characterized as a chronic/recurrent disease. Several chronic/recurrent EAU models have been developed; of these, we employed administration of staphylococcal enterotoxin B (SEB) for relapse in the present study, and found that recurrence was induced at day 24 after primary immunization, which is thought to be the convalescent phase. We reported the activation of invariant natural killer T (iNKT)-cells upon primary immunization of the EAU model mice with the ligand RCAI-56, which was found to mitigate the disease in our previous study. Here, we first attempted to ameliorate EAU in the relapse model using a preventive regimen by activating iNKT cells at the same time relapse induction (day 24) or in a regimen after 3 days of relapse induction (day 27). The preventive as well as post-inductive regimens were successful in reducing histopathological scores by inhibiting the Ag-specific Th17-biased response. Collectively, activation of iNKT cells may be useful to mitigate the relapse response of EAU induced with SEB.

Assessing in-hospital morbidity after urethroplasty using the European Association of Urology Quality Criteria for standardized reporting.

PURPOSE: To conduct a rigorous assessment of in-hospital morbidity after urethroplasty according with the European Association of Urology (EAU) guidelines for complication reporting. METHODS: We retrospectively (2015-2019) identified 469 consecutive patients receiving urethroplasty (e.g. bulbar urethroplasty with grafts, penile urethroplasty with/without grafts/flaps, Johanson, de novo or revision perineostomy, end-to-end anastomosis, meatoplasty and/or meatotomy) at our tertiary care institution. Complications were graded with Clavien-Dindo score and Comprehensive Complication Index (CCI). Complications were classified in: bleeding no gastrointestinal, cardiac, gastrointestinal, genitourinary, infectious, neurological, oral, wound, miscellaneous, and pulmonary. Logistic regression tested for predictors of in-hospital complications and prolonged hospitalization (> 75th percentile). Kaplan-Meier and Cox regression investigated the effect of complications on failure after urethroplasty. RESULTS: Overall, 161 (34.3%) patients experienced at least one complication. Of those, 47 (10%) experienced two or more complications and 59 (12.6%) experienced at least one Clavien-Dindo ≥ II complication. Only two patients had Clavien-Dindo III complications. Infectious was the most frequent complication, and de novo or revision perineostomy was associated with the highest rate of complications. The occurrence of any complications, as well as complication with Clavien-Dindo ≥ II were associated with prolonged hospitalizations, but not with higher rates of post-urethroplasty failure. CONCLUSIONS: Complications after urethroplasty were common events, but rarely with severe sequelae. Infectious were the most common complications and perineostomy was the type of urethroplasty with the highest rate of complications. The application of the EAU recommendations allowed the identifications of a higher number of complications after urethroplasty if compared with previous reports based on unsupervised chart review.

Guideline adherence for radical cystectomy significantly affects survival outcomes in non-muscle-invasive bladder cancer patients.

BACKGROUND: The relationship between guideline adherence for radical cystectomy of non-muscle-invasive bladder cancer and patient prognoses currently remains unclear. We investigated whether guideline adherence at the time of non-muscle-invasive bladder cancer affects the oncological outcomes of bladder cancer patients who underwent radical cystectomy. METHODS: Among 267 cTa-4N0-2M0 bladder cancer patients, 70 who underwent radical cystectomy under the non-muscle-invasive bladder cancer or muscle-invasive bladder cancer status that progressed from non-muscle-invasive bladder cancer were identified. Patients who followed the guidelines from initial transurethral resection of bladder tumors to radical cystectomy were defined as the guideline adherent group (n = 52), while those who did not were the guideline non-adherent group (n = 18). RESULTS: In the guideline non-adherent group, 8 (44.4%) out of 18 were diagnosed with highest risk non-muscle-invasive bladder cancer for Bacillus Calmette Guérin-naïve patients and 7 (38.9%) had a Bacillus Calmette Guérin unresponsive tumor status. Five-year recurrence-free survival and cancer-specific survival rates for the guideline non-adherent group vs guideline adherent group were 38.9% vs 69.8% (P = 0.018) and 52.7% vs 80.1% (P = 0.006), respectively. A multivariate analysis identified guideline non-adherence as one of independent indicators for disease recurrence (hazard ratio = 2.81, P = 0.008) and cancer-specific death (hazard ratio = 4.04, P = 0.003). In a subgroup analysis of 49 patients with cT1 or less non-muscle-invasive bladder cancer at the time of radical cystectomy, guideline non-adherence remained an independent prognostic factor for cancer-specific survival (hazard ratio = 3.46, P = 0.027). CONCLUSIONS: Guideline adherence during the time course of the non-muscle-invasive bladder cancer stage may result in a favorable prognosis of patients who receive radical cystectomy. Even under non-muscle-invasive bladder cancer status, radical cystectomy needs to be performed with adequate timing under guideline recommendations.

Renal expression and urinary excretion of aquaporin-2 in postobstructive uropathy in rats.

This work assessed the time course of water renal management together with aquaporin-2 (AQP2) kidney expression and urinary AQP2 levels (AQP2u) in obstructive nephropathy. Adult male Wistar rats were monitored after 1, 2, and 7 days of bilateral ureteral release (bilateral ureteral obstruction (BUO); BUO-1, BUO-2 and BUO-7). Renal water handling was evaluated using conventional clearance techniques. AQP2 levels were assessed by immunoblotting and immunohistochemical techniques. AQP2 expression in apical membranes was downregulated in BUO-1 rats and upregulated both in BUO-2 and BUO-7 animals. AQP2 protein expression in whole cell lysate fraction from kidney cortex and medulla were significantly decreased in all the experimental groups. Concomitantly, mRNA levels of AQP2 decreased in renal medulla of all groups and in renal cortex from BUO-1; however, in renal cortex from BUO-2 and BUO-7 a recovery and an increase in the level of AQP2 mRNA were, respectively, observed. BUO-7 group showed a significant increase in AQP2u. The alterations observed in apical membranes AQP2 expression could explain, at least in part, the evolution time of water kidney management in the postobstructive phase of BUO. Additionally, the AQP2u increase after 7 days of ureteral release may be postulated as a biomarker of improvement in the kidney function.

Comparative prevalence and diversity of Campylobacter jejuni strains in water and human beings over a 1-year period in southwestern Alberta, Canada.

Campylobacter jejuni was isolated from diarrheic people, river water (Oldman River watershed), wastewater, and drinking water over a 1-year period in southwestern Alberta (2008-2009). High rates of campylobacteriosis were observed during the study period (≥115 cases/100 K). Infections occurred throughout the year, with peaks in late summer and early autumn. Most infections occurred in people living in Lethbridge. Campylobacter jejuni was not isolated from municipal drinking water. In contrast, the bacterium was isolated from untreated and treated wastewater and river water (all sites). There were no correlations between C. jejuni recovery/detection from water and river flow rates, water turbidity, or fecal coliforms. Campylobacter jejuni recovery from water did not correspond to the peak periods of campylobacteriosis. The bacterium was most commonly isolated downstream of wastewater outfalls; waterfowl congregated at these sites, particularly during the winter months. A comparison of C. jejuni isolates from people and water revealed that most subtypes in water did not correspond to subtypes recovered from diarrheic people and were linked to waterfowl and other non-human animal sources. We conclude that waterborne C. jejuni did not contribute significantly to the high rates of campylobacteriosis observed in diarrheic people during the study period.

Deficiency of IL-27 Signaling Exacerbates Experimental Autoimmune Uveitis with Elevated Uveitogenic Th1 and Th17 Responses.

Human uveitis is an autoimmune disease of the central nervous system that is characterized by ocular inflammation with the involvement of uveitogenic Th1 and Th17 responses. In experimental autoimmune uveitis (EAU), the animal model for human uveitis, both responses are proven to be critical in disease development. Therefore, targeting both Th1 and Th17 cells has therapeutic implication for disease resolution. IL-27 is a multifunctional cytokine that can either promote or inhibit T cell responses and is implicated in both autoimmune and infectious diseases. The aim of this study is to characterize the role of IL-27/IL-27R signaling in regulating uveitogenic Th1/Th17 responses in EAU. By immunizing IL-27Rα-/- mice and their wild-type (WT) littermates for EAU, we demonstrated that IL-27 signaling deficiency exacerbated EAU with severe ocular inflammation and impairment of visual function. Furthermore, there was a significant increase in the eye-infiltrating Th1 and Th17 cells in IL-27Rα-/- EAU mice compared to WT. Their retinal antigen-specific Th1 and Th17 responses were also significantly increased, as represented by the elevation of their signature cytokines, IFN-γ and IL-17A, respectively. We also observed the upregulation of another pathogenic cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), from effector T cells in IL-27Rα-/- EAU mice. Mechanistic studies confirmed that IL-27 inhibited GM-CSF production from Th17 cells. In addition, the induction of IL-10 producing type 1 regulatory T (Tr1) cells was impaired in IL-27Rα-/- EAU mice. These results identified that IL-27 signaling plays a suppressive role in EAU by regulating multiple CD4+ cell subsets, including the effector Th1 and Th17 cells and the regulatory Tr1 cells. Our findings provide new insights for therapeutic potential in controlling uveitis by enhancing IL-27 signaling.

Assessment of the physicochemical water quality of the Moulouya River, Morocco, using the SEQ-Eau index.

Surface water is subject to strong anthropogenic pressures caused by the development and extension of agricultural activities and also by industrial and domestic activities. As a result, rational and sustainable management of water resources is necessary in order to protect them. The objective of this work is the use of geographic information system GIS and the application of the weighted index of the water quality evaluation system SEQ-Eau for the overall assessment of the physicochemical quality of surface waters of the Moulouya River. First, a cartographic representation of the study area was produced with the development of quality maps for the various alterations relating to acidification, temperature, mineralization, phosphorus materials, and organic and oxidizable materials. The overall quality map is generated from the lowest index of all the alterations considered. The results generally show surface water of excellent quality in the Upper Moulouya and of average to poor quality in the Middle and Lower Moulouya. The alteration of water, linked mainly to mineralization and phosphorus nutrients, organic and oxidizable matter, reveals a domestic type pollution in relation to urban wastewater and agricultural discharges in addition to the impact of the geological substratum of the watershed. The seasonal impact is influenced by the increase in the degree of deterioration of water quality due to the increase in the concentration of pollutants and the decrease in precipitation during the summer season.

Attenuation of experimental autoimmune uveoretinitis in mice by IKKß inhibitor IMD-0354.

Uveitis is a sight-threatening intraocular inflammatory disease that accounts for almost 10% of blindness worldwide. NF-κB signaling plays pivotal roles in inflammatory diseases. We have reported that IMD-0354, which inhibits NF-κB signaling via selective blockade of IKK-ß, suppresses inflammation in several ocular disease models. Here, we examined the therapeutic effect of IMD-0354 in an experimental autoimmune uveoretinitis (EAU) model, a well-established animal model for endogenous uveitis in humans. Systemic administration of IMD-0354 significantly suppressed the clinical and histological severity, inflammatory edema, and the translocation of NF-κB p65 into the nucleus of retinas in EAU mice. Furthermore, IMD-0354 treatment significantly inhibited the levels of several Th1/Th17-mediated pro-inflammatory cytokines in vitro. Our current data demonstrate that inhibition of IKKß with IMD-0354 ameliorates inflammatory responses in the mouse EAU model, suggesting that IMD-0354 may be a promising therapeutic agent for human endogenous uveitis.

miR-182-5p inhibits the pathogenic Th17 response in experimental autoimmune uveitis mice via suppressing TAF15.

BACKGROUND: CD4+ T helper 17 (Th17) cells play a contributory role in uveitis and other autoimmune disorders. However, less is understood about the contribution of microRNAs (miRNAs) in regulating the pathogenic Th17 response in uveitis. METHODS: The in vivo experimental autoimmune uveitis (EAU) model was constructed in female C57BL/6 mice. Primary EAU mouse CD4+ T-cells and the murine T-cell line EL4 were used for in vitro experiments. miRNA mimic/inhibitor, lentiviral overexpression plasmids, and small interfering RNAs (siRNAs) were used to modulate miR-182-5p and TAF15 expression. CD4+ T-cells from healthy controls (HC, n = 15), active Behçet's disease with uveitis (BD, n = 15), or active sympathetic ophthalmia with uveitis (SO, n = 15) were analyzed for miR-182-5p, TAF15, and Th17 marker gene expression. RESULTS: miR-182-5p was downregulated in EAU mouse-derived Th17 cells. miR-182-5p negatively regulated Th17 cell development in vitro. miR-182-5p mimic therapy in transplanted Th17 cells ameliorated EAU severity in vivo. Mechanistically, miR-182-5p directly inhibited the transcriptional initiator TATA-binding protein-associated factor 15 (TAF15, TAFII68). miR-182-5p's inhibition of TAF15 negatively regulated Th17 cell development by suppressing STAT3 phosphorylation. TAF15 and Th17 marker expression were positively correlated in CD4+ T-cells from BD and SO patients. CONCLUSION: miR-182-5p mimic therapy inhibits the pathogenic Th17 response in EAU mice. miR-182-5p's inhibition of TAF15 negatively regulates Th17 cell development by suppressing STAT3 phosphorylation. As TAF15 shows a positive relationship with Th17 cell markers in uveitis patients, the miR-182-5p/TAF15 axis shows promise as a therapeutic target for uveitis.

A cell-permeable peptide inhibitor of p55PIK signaling alleviates ocular inflammation in mouse models of uveitis.

PURPOSE: Previously we developed TAT-N24 as a synthetic cell-permeable peptide inhibitor of p55PIK signaling and demonstrated its anti-inflammatory effects. This study aimed to evaluate the potential of TAT-N24 as a new agent for the treatment of ocular inflammatory diseases. METHODS: The endotoxin-induced uveitis (EIU) model was established by intravitreal injection of lipopolysaccharide (LPS) in BALB/c mice and experimental autoimmune uveitis (EAU) model was established by subcutaneous injection of a peptide spanning amino acid residues 161-180 of interphotoreceptor retinoid binding protein (IRBP161-180) with complete Freund's adjuvant (CFA) in B10.RIII mice. TAT-N24 was topically administered in EIU model and intraperitoneally administered in EAU model. The severity levels of uveitis were assessed by clinical and histopathological scores. The mRNA levels of inflammatory cytokines in iris-ciliary body (ICB) and retina were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The protein levels of inflammatory factors were determined by ELISA or Western blotting. RESULTS: The results showed that TAT-N24 alleviated clinical signs, decreased inflammatory cell infiltration and the expression of inflammatory cytokines in both EIU and EAU models. Furthermore, protein levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in aqueous humor and mRNA and protein levels of NF-κB p65 in the ICB significantly decreased in EIU model. In EAU model, TAT-N24 application induced a significant decrease of IFN-gamma (IFN-γ) and interleukin-17 (IL-17) in the retina, which were secreted by Th1 and Th17 cells, respectively. CONCLUSION: In conclusion, TAT-N24 suppressed intraocular inflammation in both EIU and EAU models, and the anti-inflammatory effects were mediated by suppressing the expression of inflammatory cytokines by PI3K/NF-κB signaling pathway. TAT-N24 could be potential candidate for the treatment of ocular inflammatory diseases.

Household flooring associated with reduced infant diarrhoeal illness in Zimbabwe in households with and without WASH interventions.

OBJECTIVES: Diarrhoeal illness is a leading cause of childhood morbidity and mortality and has long-term negative impacts on child development. Although flooring, water and sanitation have been identified as important routes of transmission of diarrhoeal pathogens, research examining variability in the association between flooring and diarrhoeal illness by water and sanitation is limited. METHODS: We utilised cross-sectional data collected for the evaluation of Zimbabwe's Prevention of Mother-to-Child HIV transmission programme in 2014 and 2017-18. Mothers of infants 9-18 months of age self-reported the household's source of drinking water and type of sanitation facility, as well as infant diarrhoeal illness in the four weeks prior to the survey. Household flooring was assessed using interviewer observation, and households in which the main material of flooring was dirt/earthen were classified as having unimproved flooring, and those with solid flooring (e.g. cement) were classified as having improved flooring. RESULTS: Mothers of infants living in households with improved flooring were less likely to report diarrhoeal illness in the last four weeks (PDa  = -4.8%, 95% CI: -8.6, -1.0). The association between flooring and diarrhoeal illness did not vary by the presence of improved/unimproved water (pRERI  = 0.91) or sanitation (pRERI  = 0.76). CONCLUSIONS: Our findings support the hypothesis that household flooring is an important pathway for the transmission of diarrhoeal pathogens, even in settings where other aspects of sanitation are sub-optimal. Improvements to household flooring do not require behaviour change and may be an effective and expeditious strategy for reducing childhood diarrhoeal illness irrespective of household access to improved water and sanitation.

OBJECTIFS: Les maladies diarrhéiques sont l'une des principales causes de morbidité et de mortalité infantiles et ont des effets négatifs à long terme sur le développement de l'enfant. Bien que le revêtement de sol, l'eau et l'assainissement aient été identifiés comme des voies de transmission importantes des agents pathogènes diarrhéiques, la recherche examinant la variabilité de l'association entre le revêtement de sol et les maladies diarrhéiques par l'eau et les sanitaires est rare. MÉTHODES: Nous avons utilisé des données transversales collectées pour l'évaluation du programme de prévention de la transmission du VIH de la mère à l'enfant au Zimbabwe en 2014 et 2017-18. Les mères de nourrissons âgés de 9 à 18 mois ont déclaré la source d'eau potable du ménage et le type d'installation sanitaire, ainsi que les maladies diarrhéiques de l'enfant au cours des quatre semaines précédant l'enquête. Le revêtement de sol des ménages a été évalué en utilisant l'observation de l'intervieweur. Les ménages dont le principal matériau de revêtement de sol était de la terre étaient classés comme ayant un revêtement de sol non amélioré et les ménages dont le revêtement de sol était en ciment étaient classés comme ayant un revêtement de sol amélioré. RÉSULTATS: Les mères de nourrissons vivant dans des ménages avec un revêtement de sol amélioré étaient moins susceptibles de déclarer une maladie diarrhéique au cours des quatre semaines précédentes (PDa = --9%, IC95%: -8,6 à -1,0). L'association entre les revêtements de sol et les maladies diarrhéiques ne variait pas selon la présence d'eau améliorée/non améliorée (p RERI = 0,91) ou de sanitaires (p RERI = 0,76). CONCLUSIONS: Nos résultats corroborent l'hypothèse selon laquelle le revêtement de sol domestique est une voie importante pour la transmission d'agents pathogènes diarrhéiques, même dans des contextes où d'autres aspects des sanitaires ne sont pas optimaux. L'amélioration du revêtement de sol domestique ne nécessite pas de changement de comportement et peut être une stratégie efficace et rapide pour réduire les maladies diarrhéiques infantiles, indépendamment de l'accès des ménages à une eau et à des sanitaires améliorés.

Guideline adherence for the surgical treatment of T1 renal tumours correlates with hospital volume: an analysis from the British Association of Urological Surgeons Nephrectomy Audit.

OBJECTIVE: To assess European Association of Urology guideline adherence on the surgical management of patients with T1 renal tumours and the effects of centralisation of care. PATIENTS AND METHODS: Retrospective data from all kidney tumours that underwent radical nephrectomy (RN) or partial nephrectomy (PN) in the period 2012-2016 from the British Association of Urological Surgeons Nephrectomy Audit were retrieved and analysed. We assessed total surgical hospital volume (HV; RN and PN performed) per centre, PN rates, complication rates, and completeness of data. Descriptive analyses were performed, and confidence intervals were used to illustrate the association between hospital volume and proportion of PN. Chi- squared and Cochran-Armitage trend tests were used to evaluate differences and trends. RESULTS: In total, 13 045 surgically treated T1 tumours were included in the analyses. Over time, there was an increase in PN use (39.7% in 2012 to 44.9% in 2016). Registration of the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) complexity score was included in March 2016 and documented in 39% of cases. Missing information on postoperative complications appeared constant over the years (8.5-9%).  A clear association was found between annual HV and the proportion of T1 tumours treated with PN rather than RN (from 18.1% in centres performing <25 cases/year [lowest volume] to 61.8% in centres performing ≥100 cases/year [high volume]), which persisted after adjustment for PADUA complexity. Overall and major (Clavien-Dindo grade ≥III) complication rate decreased with increasing HV (from 12.2% and 2.9% in low-volume centres to 10.7% and 2.2% in high-volume centres, respectively), for all patients including those treated with PN. CONCLUSION: Closer guideline adherence was exhibited by higher surgical volume centres. Treatment of T1 tumours using PN increased with increasing HV, and was accompanied by an inverse association of HV with complication rate. These results support the centralisation of kidney cancer specialist cancer surgical services to improve patient outcomes.