In summary, our study revealed that LPS-induced IUI leads to increased activation of microglia cells, neuronal damage, and dynamic alterations in mTOR signaling in the mouse fetal brain. Our findings indicate that abnormal changes in mTOR signaling may underlie the development of future neurological complications in offspring exposed to prenatal IUI. This article is protected by copyright. All rights reserved.BACKGROUND Thorough assessment of obstructed defecation syndrome (ODS) is imperative for the selection of treatment options. The present study aimed to examine the utility of Mansoura Numeroalphabetic Constipation Score (MNCS) in distinguishing patients with ODS from healthy control subjects and in predicting the outcome of treatment of ODS. METHODS Patients with ODS associated with anterior rectocele and/or rectoanal intussusception were assessed with MNCS at the first visit to the clinic. All patients were offered conservative treatment for three months and patients who improved were continued on conservative treatment for 6 more months while patients who failed were treated surgically. The MNCS was reassessed at the end of follow-up in both groups. A cohort of healthy controls was compared to ODS patients with regards to age, sex, and baseline MNCS. RESULTS 124 ODS patients and 53 healthy controls were included. The ODS patients had a significantly higher baseline MNCS than controls (9.5± 1.5 Vs 0.76± 0.71, p less then 0.0001). Forty out of 124 patients improved after conservative management and showed a significant decrease in MNCS (6.9± 1.08 to 3.1± 1.2, p less then 0.0001). 84 (67.8%) patients failed to respond to conservative measures and were surgically treated, 77 (91.6%) of whom showed significant improvement in symptoms postoperatively while 7 (8.4%) failed to improve, the difference in postoperative MNCS between the two groups was significant. CONCLUSION The MNCS successfully distinguished ODS patients from controls and was able to predict the outcome of ODS treatment. This article is protected by copyright. All rights reserved.PURPOSE To evaluate the capacity of retinal nerve fibre layer (RNFL) thickness measured by SD-OCT to discriminate glaucoma patients from controls in an elderly population. METHODS The MONTRACHET (Maculopathy, Optic Nerve, nuTRition, neurovAsCular and HEarT diseases) Study is a population-based study including participants aged 75 years and over. All participants underwent a complete eye examination with optic nerve photographs, visual field testing and OCT peripapillary RNFL thickness measurement. Glaucoma was defined according to the ISGEO (International Society for Epidemiologic and Geographical Ophthalmology) classification. Performance indicators were calculated including area under the receiver operating characteristics curves (AUC), likelihood ratios (LR) and diagnostic odds ratios (DOR). RESULTS In total, 1061 participants were included in the study, of whom 89 were classified as having glaucoma and 972 were classified as normal. The mean (SD) age of the population was 82.3 (3.7) years. The average RNFL thickness was significantly lower in the glaucoma group than in controls 64.0 (14.9) µm versus 88.9 (12.4) µm, respectively, p  less then  0.001) and in all sectors compared with controls. The average RNFL thickness had the highest AUC (0.901) followed by the temporal-inferior (0.879) and temporal-superior sectors (0.862). When RNFL thickness was classified as abnormal by SD-OCT, the average RNFL thickness had the best sensitivity (83.75%) followed by the temporal-inferior sector (75.64%). The specificity for these two parameters was 87.34% and 91.08%, respectively. The highest DOR was 28.70 for average RNFL thickness and reached 34.84 when using the reference database of the OCT manufacturer. CONCLUSION This study confirms that SD-OCT could be useful as an additional test to discriminate glaucoma patients from controls in an elderly population. © 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.Prostate cancer (PCa) is one of the most frequent tumor types in the male Western population. Early- and late-stage PCa are dependent on androgen signaling, and inhibitors of the androgen receptor (AR) axis represent the standard therapy. Here, we studied in detail the global impact of darolutamide, a newly approved AR antagonist, on the transcriptome and AR-bound cistrome in two PCa cell models. Darolutamide strongly depleted the AR from gene regulatory regions and abolished AR-driven transcriptional signaling. Enhancer activation was blocked at the chromatin level as evaluated by H3K27 acetylation (H3K27ac), H3K4 monomethylation (H3K4me1), and FOXA1, MED1 and BRD4 binding. We identified genomic regions with high affinities for the AR in androgen-stimulated, but also in androgen-depleted conditions. A similar AR affinity pattern was observed in healthy and PCa tissue samples. https://www.selleckchem.com/products/blu-945.html High FOXA1, BRD4, H3K27ac and H3K4me1 levels were found to mark regions showing AR binding in the hormone-depleted setting. Conversely, low FOXA1, BRD4 and H3K27ac levels were observed at regulatory sites that responded strongly to androgen stimulation, and AR interactions at these sites was blocked by darolutamide. Beside marked loss of AR occupancy, FOXA1 recruitment to chromatin was also clearly reduced after darolutamide treatment. We furthermore identified numerous androgen-regulated super-enhancers (SEs) that were associated with hallmark androgen and cell proliferation-associated gene sets. Importantly, these SEs are also active in PCa tissues and sensitive to darolutamide treatment in our models. Our findings demonstrate that darolutamide is a potent AR antagonist blocking genome-wide AR enhancer and SE activation, and downstream transcription. We also show the existence of a dynamic AR cistrome that depends on the androgen levels and on high AR affinity regions present in PCa cell lines and also in tissue samples. This article is protected by copyright. All rights reserved.A systematic and structured ultrasound scan (USS) evaluation of the entire small bowel is feasible intraoperatively during ileocolic Crohn's disease (CD) surgery as we have previously reported [1]. Our video demonstrates the ultrasound assessment performed via a 4 cm midline laparotomy used for specimen extraction, extracorporeal control of the mesentery and fashioning of the anastomosis. The right colon and terminal ileum have been fully mobilised laparoscopically with a medial approach and the main steps of the laparoscopic procedure are also demonstrated in the video, with focus on anatomical landmarks and take down of the hepatic flexure. This article is protected by copyright. All rights reserved.Lumbar disc herniation (LDH) is a relatively common spinal disease, but its pathogenesis is still unknown. Numerous studies have shown that LDH is closely correlated with inflammation, and it has been found to be related to some single nucleotide polymorphisms (SNPs). Our purpose is to explore the correlation between gene polymorphisms of GSDMC and LDH risk, which is of great significance for the study of the pathogenesis of LDH. DNA was extracted from 508 LDH patients and 508 controls. We select SNPs with minor allele frequency >5% in GSDMC gene from 1,000 genome project (http//www.internationalgenome.org/). Then, genotyping was performed using Agena MassARRAY. We used unconditional logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The haplotype construction and analysis in GSDMC were applied to detect the association. We identified that rs77681114 in the GSDMC gene was significantly associated with a decreased risk of LDH in the alleles model (OR = 0.81, 95% CI = 0.66-0.99, p = .049) and the log-additive model (OR = 0.81, 95% CI = 0.65-0.99, p = .049) adjusted by age and gender. The haplotype "AG" constructed by rs77681114 and rs4285452 (OR = 1.24, 95% CI = 1.01-1.53, p = .039) was associated with increased risk of LDH. After age and gender stratification, rs77681114 protected LDH risk at age 49 or older in allelic model (p = .010), co-dominant model (p = .006), dominant model (p = .029), recessive model (p = .011) and log-additive model (p = .005). Rs77681114 had protective effect on female LDH risk in both co-dominant models (p = .033) and recessive models (p = .043). These studies indicated that genetic polymorphisms of GSDMC can relatively reduce the risk of LDH. © 2020 John Wiley & Sons Ltd.The aerial parts of Polygonum chinense L. var. hispidum. are one of the key herbs in Cantonese herbal tea, which is quite a common local beverage in LingNan area of China. Previous investigation has found that this herb possesses antioxidant activity and the ethyl acetate fraction of its ethanol extract shows the strongest antioxidant activity. However, little is known about its antioxidant chemical constituents. The aim of this research was to investigate the active constituents of this plant by identifying and characterizing the chemical profile in ethyl acetate fraction using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, which can provide characteristic ultraviolet absorption, accurate molecular weight and diagnostic MS/MS fragment ions. As a result, 85 compounds were identified including 22 flavonoids, 12 ellagic acids, 34 ellagitannins, 16 phenolic acids and one phenolic amide. All the phenolic compounds identified in this work, especially ethyl gallate, geraniin, chebulagic acid and quercitrin with the higher peak areas in UPLC-MS chemical profile of this plant, could be the bioactive principles responsible for the antioxidant activity. These findings in the present study could benefit further studies involving the functions and chemicals of this plant, and provide scientific evidence for usage of Cantonese herbal tea. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The short supply of donor corneas is exacerbated by the unsuitability of donors with insufficient endothelial cell density. Few studies have investigated promoting corneal endothelial cell proliferation to increase the endothelial cell density. We hypothesize that pre-transplantation treatment of proliferative tissue-cultivated corneas may increase corneal endothelial cell density. We observed that the airlift cultures were superior to immersion cultures with respect to both transparency and thickness. In this tissue culture system, we observed that lysophosphatidic acid increased the rabbit corneal endothelial cell density, number of BrdU-positive cells and improve wound healing. We also observed an indirect effect of lysophosphatidic acid on corneal endothelial cell proliferation mediated by the stimulation of interleukin-1β secretion from stromal cells. Human corneal tissues treated with lysophosphatidic acid or interleukin-1β contained significantly more Ki-67-positive cells than untreated group. The lysophosphatidic acid- or interleukin-1β-treated cultured tissue remained hexagon-shaped, with ZO-1 expression and no evidence of the endothelial-mesenchymal transition. Our novel protocol of tissue culture may be applicable for eye banks to optimize corneal grafting. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.