RESUMEN
Visceral leishmaniasis (VL) is a neglected tropical disease transmitted by Lutzomyia longipalpis, a sand fly widely distributed in Brazil. Despite efforts to strengthen national control programs reduction in incidence and geographical distribution of VL in Brazil has not yet been successful; VL is in fact expanding its range in newly urbanized areas. Ecological niche models (ENM) for use in surveillance and response systems may enable more effective operational VL control by mapping risk areas and elucidation of eco-epidemiologic risk factors. ENMs for VL and Lu. longipalpis were generated using monthly WorldClim 2.0 data (30-year climate normal, 1-km spatial resolution) and monthly soil moisture active passive (SMAP) satellite L4 soil moisture data. SMAP L4 Global 3-hourly 9-km EASE-Grid Surface and Root Zone Soil Moisture Geophysical Data V004 were obtained for the first image of day 1 and day 15 (0:00-3:00 hour) of each month. ENM were developed using MaxEnt software to generate risk maps based on an algorithm for maximum entropy. The jack-knife procedure was used to identify the contribution of each variable to model performance. The three most meaningful components were used to generate ENM distribution maps by ArcGIS 10.6. Similar patterns of VL and vector distribution were observed using SMAP as compared to WorldClim 2.0 models based on temperature and precipitation data or water budget. Results indicate that direct Earth-observing satellite measurement of soil moisture by SMAP can be used in lieu of models calculated from classical temperature and precipitation climate station data to assess VL risk.
Asunto(s)
Leishmaniasis Visceral , Psychodidae , Animales , Brasil/epidemiología , Insectos Vectores/fisiología , Leishmaniasis Visceral/epidemiología , Enfermedades Desatendidas , SueloRESUMEN
BACKGROUND: The failing right ventricle (RV) does not respond like the left ventricle (LV) to guideline-directed medical therapy of heart failure, perhaps due to interventricular differences in their molecular pathophysiology. METHODS: Using the canine tachypacing-induced biventricular heart failure (HF) model, we tested the hypothesis that interventricular differences in microRNAs (miRs) expression distinguish failing RV from failing LV. RESULTS: Severe RV dysfunction was indicated by elevated end-diastolic pressure (11.3±2.5 versus 5.7±2.0 mm Hg; P<0.0001) and diminished fractional area change (24.9±7.1 versus 48.0±3.6%; P<0.0001) relative to prepacing baselines. Microarray analysis of ventricular tissue revealed that miR-21 and miR-221, 2 activators of profibrotic and proliferative processes, increased the most, at 4- and 2-fold, respectively, in RV-HF versus RV-Control. Neither miR-21 or miR-221 was statistically significantly different in LV-HF versus LV-Control. These changes were accompanied by more extensive fibrosis in RV-HF than LV-HF. To test whether miR-21 and miR-221 upregulation is specific to RV cellular response to mechanical and hormonal stimuli associated with HF, we subjected fibroblasts and cardiomyocytes isolated from normal canine RV and LV to cyclic overstretch and aldosterone. These 2 stressors markedly upregulated miR-21 and miR-221 in RV fibroblasts but not in LV fibroblasts nor cardiomyocytes of either ventricle. Furthermore, miR-21/221 knockdown significantly attenuated RV but not LV fibroblast proliferation. CONCLUSIONS: We identified a novel, biological difference between RV and LV fibroblasts that might underlie distinctions in pathological remodeling of the RV in biventricular HF.
Asunto(s)
Fibroblastos/metabolismo , Insuficiencia Cardíaca/metabolismo , Ventrículos Cardíacos/metabolismo , MicroARNs/metabolismo , Disfunción Ventricular Derecha/metabolismo , Animales , Perros , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Miocitos Cardíacos/metabolismo , Regulación hacia Arriba , Disfunción Ventricular Derecha/fisiopatología , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Prognostic factors after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) are inconclusive, because most data in the literature have been obtained from small series. OBJECTIVE: To assess the association of tumour necrosis with cancer recurrence and survival in a large international series of patients treated with RNU. DESIGN, SETTING, AND PARTICIPANTS: Data were collected from 1425 patients treated with RNU at 13 centres and combined into a relational database. Pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria. Extensive tumour necrosis was scored as >10% of the tumour area. INTERVENTION: Patients underwent either open or laparoscopic RNU. Lymph node dissection was performed in the presence of enlarged nodes. MEASUREMENTS: Recurrence was defined as tumour relapse in the operative field, lymph node (LN) metastasis, and/or distant metastases. Bladder recurrences were not considered. Associations of extensive tumour necrosis with recurrence-free survival and cancer-specific survival were evaluated by univariate and multivariate analyses. RESULTS AND LIMITATIONS: Extensive tumour necrosis was observed in 364 patients (25.5%) and was associated with advanced tumour stage, high tumour grade, sessile architecture, lymphovascular invasion (LVI), concomitant carcinoma in situ, and LN metastasis (p<0.0001 each). Extensive tumour necrosis was independently associated with disease recurrence and survival (p=0.037 and p=0.046, respectively) after adjusting for the effects of pathologic stage, grade, LVI, and LN status. The addition of extensive tumour necrosis to a base model comprising standard pathologic predictors marginally improved its predictive accuracy for both cancer-specific recurrence (1.5%) and survival (1.4%). CONCLUSIONS: Extensive tumour necrosis is an independent predictor of clinical outcomes in patients who undergo RNU for UTUC. Assessment of tumour necrosis may help to identify patients who could benefit from multimodal therapy after RNU in the future. Evaluation of extensive tumour necrosis should be part of standard pathologic reporting.