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Preeclampsia is a life-threatening multiorgan systemic disease with manifestations including gestational hypertension, oxidative stress, and vascular dysfunction. We aimed to evaluate the therapeutic effects of melatonin on an L-NAME (NLG-nitro-l-arginine methyl ester)-induced rat preeclampsia model. During gestation, L-NAME was added to drinking water at 50 mg/kg/day from gestation day (GD) 8. Rats received the combination of L-NAME with melatonin (10 mg/kg/day), or aspirin (1.5 mg/kg/day), and rats that received only L-NAME or no treatments were used as controls. Aspirin was mixed with rodent chow and melatonin was administered intraperitoneally. Blood pressure and urine protein content were monitored every 3 days. On GD19, blood samples were collected for biochemical analysis. Compared to untreated L-NAME rats, melatonin led to markedly lowered blood pressure and urine protein content, and recovery in the fetus alive ratio, fetal weight, and the fetal weight/placental weight ratio. Compared to untreated L-NAME rats, plasma antioxidant capacity and plasma malondialdehyde were increased and decreased by melatonin, respectively, in L-NAME rats. Melatonin treatment also reduced sFlt-1, increased PlGF, and decreased the sFlt-1/PlGF ratio. In the placenta, melatonin also reduced sFlt-1 levels and increased Nrf2, PlGF, and HO-1 levels. We have demonstrated in a rat model of preeclampsia that melatonin exerts significant protective effects through lowering blood pressure and reducing oxidative stress.Background Mowat-Wilson syndrome (MWS) is a multiorgan system disorder caused by ZEB2 (zinc finger E-box-binding homeobox 2) mutations or deletions. One common manifestation is constipation, and approximately half of the patients have Hirschsprung disease (HSCR). In addition to classic histologic features of HSCR, an unusual supernumerary intestinal muscle coat was recently reported in a patient of MWS with HSCR. A similar smooth muscle alteration, segmental additional circular muscle coat, had been described in the specimens from patients with intestinal pseudo-obstruction without MWS or HSCR. Method Rectal biopsies and rectosigmoidectomy specimens from MWS patients were identified by retrospective reviews of surgical pathology records. Routinely prepared glass slides were examined to determine whether any smooth muscle structural alteration was present. Clinical information was obtained by chart review. Results Six MWS patients were identified. A supernumerary smooth muscle coat in the submucosa was present in 3 of them, including 2 of the 4 patients with HSCR. Conclusion The structural anomaly, termed submucosal supernumerary smooth muscle coat, is not a syndrome-specific pathological feature. However, it appears to be more common than expected in MWS and is consistent with contemporary models for the roles of ZEB2 and related cell signaling pathways in the patterning of intestinal musculature during embryonic development.Purpose We assessed the effect of ERAS protocol-related fluid restriction on kidney function and the incidence of postoperative acute kidney injury and 3-month kidney function. Material & methods In a retrospectively collected, single-institution cohort we studied 296 consecutive patients (146 pre-ERAS patients vs. 150 ERAS patients) who underwent radical cystectomy from 2010 to 2018. The primary outcome was the incidence of postoperative acute kidney injury. Secondary outcomes were the length of hospital stay, time to bowel movements, time to tolerate regular diet, postoperative complications, and 30-day readmission rate. Study limitations include its retrospective design and relatively modest sample size. Results We observed an increased rate of postoperative acute kidney injury in patients on the ERAS protocol (42.7 % vs. 30.1 % OR = 1.725, p=0.025). On multivariate analysis, ERAS protocol remained a significant predictor of acute kidney injury even when controlling for other covariates including baseline kidney functions (OR 1.8, 95% CI 1.04-3.30, p=0.036). Patients with postoperative acute kidney injury demonstrated a significantly higher odds of stage 3 chronic kidney disease at 3 months even after controlling for baseline renal function (OR 2.5, 95% CI 1.3-4.9, p=0.016). Conclusion Use of an ERAS protocol following radical cystectomy was associated with a higher risk of postoperative acute kidney injury, in patients who had baseline chronic kidney disease which could be related to the restricted perioperative fluid management mandated by ERAS. Use of the ERAS protocol did not impact the length of hospital stay or readmission rates.Purpose To establish severity banding ranges, bother assessment and key item content in principal patient reported outcomes measures (PROMs) in men seeking therapy for lower urinary tract symptoms (LUTS). Materials and methods Data for International Prostate Symptom Score (IPSS) and International Consultation on Incontinence Questionnaire Male LUTS (ICIQ-MLUTS) were derived from a study evaluating 820 men at 26 UK hospitals. Receiver operating characteristic (ROC) curves were used to establish severity bandings. selleck Results Classification tree showed that thresholds between mild-moderate and moderate-severe severity bands were 15 and 27 respectively for IPSS, 16 and 26 for ICIQ-MLUTS/severity, and 22 and 81 for ICIQ-MLUTS/bother. Highest area under ROC and lowest Akaike's information criteria of univariate logistic regression indicated that ICIQ-MLUTS/bother was more related to global quality of life (QoL) than were IPSS and ICIQ-MLUTS/severity. The symptoms affecting IPSS-QoL were only fully identified by ICIQ-MLUTS, because two key symptoms (urinary incontinence and post-micturition dribble) are not measured by IPSS. ICIQ-MLUTS demonstrated that bother of some LUTS is disproportionate to severity, and that persisting high bother levels following surgery are more likely due to storage (18-25%) and post-voiding (18-28%) LUTS than voiding LUTS (5-13%). Symptom improvement after surgery is uncertain if baseline IPSS-QoL score was less then 3. Conclusions The severity threshold scores were measured for the two key LUTS PROMs, and the results indicate suitable categories of symptom severity for use in men referred for urological care. The ICIQ-MLUTS measures all the LUTS affecting QoL, and includes individual symptom bother scores.

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