Mcfaddenwestergaard6204

Despite the ubiquity of organophosphate flame retardants (OPFRs) metabolites in the biota, the endocrine disrupting potency has not been well examined. Herein, we chose three primary metabolites of OPFRs (BCIPP, BDCIPP, and DPHP) to investigate their potential endocrine disrupting effects by in vitro, in vivo, and in silico assays. Three metabolites were agonistic to rat estrogenic receptor alpha (ERα) and antagonists to human mineralocorticoid receptor (MR). BCIPP exerted endocrine disrupting effect contrasting to the negative response of its parental compound. It also poses the strongest binding capacity to ERα among the tested compounds. Both BCIPP and BDCIPP upregulated the genes encoded for estrogenic synthesis enzymes in H295R cells, including 17βHSD and CYP19. All three compounds stimulated the transcription of CYP11B1, whereas BCIPP and DPHP also triggered CYP11B2, encoding for corticoid production. BDCIPP inhibits genes for progesterone synthesis including CYP11A1, STAR, and 3-βHSD. The induction of mortality and low hatchability of zebrafish embryo were ranked as BCIPP ≥ BDCIPP > DPHP. All compounds lead to malformation of zebrafish larvae. Both of the hypothalamic-pituitary-adrenocortical and hypothalamic-pituitary-gonadal axes were disrupted, with the highest impact by BCIPP. Altogether, the data clarified OPFRs metabolites may produce comparable or even higher endocrine disrupting effects than OPFRs.Background Nowadays, children get access to smartphones at an early age. However, their ability to use mobile apps has not yet been studied in detail. Purpose The purpose was to study the ability of children aged between two and eight years to perform touchscreen gestures and follow prompting techniques, i.e. ways used by apps to provide instructions on how to use them. Methods We developed a mobile app to test the ability of children to perform various touchscreen gestures and another mobile app to test their ability to follow various prompting techniques. We used these apps to perform our experiment with 90 children in a kindergarten and a primary school in New Delhi in July 2019. We noted the touchscreen gestures that the children could perform and the most sophisticated prompting technique that they could follow. Results Two and three year old children could not follow any prompting technique and only a minority (27%) of them could tap the touchscreen at an intended place. Four to six year old children could perform simple gestures like tap and slide (57%), and follow instructions provided through animation (63%). Seven and eight year old children could perform more sophisticated gestures like drag and drop (30%), and follow instructions provided in audio and video formats (34%). We observed a significant difference between the number of touchscreen gestures that the children could perform and the number of prompting techniques that they could follow (F=544.0407, P0.05). Conclusion Children gradually learn to use mobile apps beginning at two years of age. They become comfortable in performing single-finger gestures and following non-textual prompting techniques by eight years of age. We recommend that these results be taken into consideration while developing mobile apps for children.OBJECTIVS Cigarette smoking with its various phenotypes is an established, strong, and modifiable risk factor for coronary heart disease (CHD). Little research has been conducted on the effect of former smokers who have quitted smoking but are exposed to others' cigarette smoke (former & secondhand smokers) on CHD risk. Limitations of published data have left this important question. METHODS A prospective population-based cohort (TLGS) was conducted (n=20069) with median follow-up time of 14.6 years. A subset of 8050 participants ≥30 years old (first CHD events as study outcome) were considered. Participants were categorized as never, former, current, secondhand, and former & secondhand smokers. Data on smoking intensity (cigarettes/day) were also collected. Blasticidin S cell line Cox proportional hazards regression model was applied to estimate the risk of CHD taking into account the main potential confounders. RESULTS The mean (SD) age of individuals was 46.10 (11.38) years that experienced 1118 first CHD events (most CHD cases in former smokers) during follow-up. The risk of CHD was higher in current, former & secondhand, former, and secondhand smokers (HR 1.99, 95% CI 1.65-2.39; HR 1.55, 95% CI 1.15-2.08; HR 1.39, 95% CI 1.12-1.72; HR 1.27, 95% CI 1.07-1.51) respectively than never smokers. The risk of CHD increased with rising the smoking intensity (as a better proposed smoking phenotype) indicating a dose-response pattern. CONCLUSIONS The risk of CHD in former & secondhand smokers was an interesting and remarkable finding which need to further research to establish and approve in future studies to transfer to health policy makers.AIM To explore the effect of incremental positive end-expiratory pressure recruitment maneuver (iPEEPRM) in children with congenital heart diseases (CHDs) using lung ultrasound. METHODS Thirty-six children aged 3 months to 5 years scheduled for cardiac surgery participated. iPEEPRM was performed with PEEP stepwise increase (0-5-10-15 cmH2 O) and decrease at the same rate before and after surgery. Atelectatic areas, ultrasound scores, arterial oxygen pressure (PaO2 ), and respiratory system dynamic compliance per kilogram body weight (CDyn/kg) were analyzed before and after iPEEPRM. The primary outcome is the incidence of atelectasis. Secondary outcomes are oxygenation, ventilation, CDyn/kg, and atelectasis area. RESULTS iPEEPRM was successfully applied in 92% (33/36) children before surgery and 71% (24/34) children after surgery. The incidence of atelectasis was significantly reduced by iPEEPRM from 76% to 15% before surgery and from 92% to 38% after surgery, respectively (P  less then  .001). Before surgery, iPEEPRM significantly reduced atelectatic areas and ultrasound scores 32.5 (0-128.1) mm2 vs 0 (0-0) mm2 and 8 (3-12) vs 2 (0-4). PaO2 and CDyn/kg were significantly increased after iPEEPRM 243 (129-275) mm Hg vs 278 (207-323) mm Hg and 0.6 (0.4-0.7) mL/cmH2 O/kg vs 0.8 (0.6-1.0) mL/cmH2 O/kg. After surgery, iPEEPRM significantly reduced atelectatic areas and ultrasound scores 45.7 (13.1-115.8) mm2 vs 0 (0-34.7) mm2 , and 9 (6-12) vs 3 (0-5). PaO2 and CDyn/kg were also significantly increased after iPEEPRM. CONCLUSIONS iPEEPRM effectively reduced atelectasis, improved lung aeration, oxygenation, and CDyn/kg in children undergoing cardiac surgery. © 2020 Wiley Periodicals, Inc.It is critical to identify patients with stage II and III colorectal cancer (CRC) who will benefit from adjuvant chemotherapy (ACT) after curative surgery, while the only use of clinical factors is insufficient to predict this beneficial effect. In this study, we performed genetic algorithm (GA) to select ACT candidate genes, and built a predictive model of support vector machine (SVM) using gene expression profiles from the Gene Expression Omnibus database. The model contained four ACT candidate genes (EDEM1, MVD, SEMA5B, and WWP2) and TNM stage (stage II or III). After using Subpopulation Treatment Effect Pattern Plot to determine the optimal cutoff value of predictive scores, the validated patients from The Cancer Genome Atlas database can be divided into the predictive ACT-benefit/-futile groups. Patients in the predictive ACT-benefit group with 5-fluorouracil (5-Fu)-based ACT had significantly longer relapse-free survival (RFS) compared to those without ACT (P = .015); However, the difference in RFS in the predictive ACT-futile group was insignificant (P = .596). The multivariable analysis found that the predictive groups were significantly associated with the effect of ACT (Pinteraction  = .011). Consequently, we developed a predictive model based on the SVM and GA algorithm which was further validated to define patients who benefit from ACT on recurrence. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.A generally used chemotherapeutic drug for glioma, a frequently diagnosed brain tumour, is temozolomide (TMZ). Our study investigated the activity of FBXL7 and miR-152-5p in glioma. Levels of microRNA-152-5p (miR-152-5p) and the transcript and protein of FBXL7 were assessed by real-time PCR and Western blotting, respectively. The migratory and invasive properties of cells were measured by Transwell migration and invasion assay and their viability were examined using CCK-8 assay. Further, the putative interaction between FBXL7 and miR-152-5p were analysed bioinformatically and by luciferase assay. The activities of FBXL7, TMZ and miR-152-5p were analysed in vivo singly or in combination, on mouse xenografts, in glioma tumorigenesis. The expression of FBXL7 in glioma tissue is significantly up-regulated, which is related to the poor prognosis and the grade of glioma. TMZ-induced cytotoxicity, proliferation, migration and invasion in glioma cells were impeded by the knock-down of FBXL7 or overexpressed miR-152-5p. Furthermore, the expression of miR-152-5p reduced remarkably in glioma cells and it exerted its activity through targeted FBXL7. Overexpression of miR-152-5p and knock-down of FBXL7 in glioma xenograft models enhanced TMZ-mediated anti-tumour effect and impeded tumour growth. Thus, the miR-152-5p suppressed the progression of glioma and associated tumorigenesis, targeted FBXL7 and increased the effect of TMZ-induced cytotoxicity in glioma cells, further enhancing our knowledge of FBXL7 activity in glioma. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.BACKGROUND Pressure rise time (PRT), also known as slope time to the peak inflating pressure can be set on some modern neonatal ventilators. On other ventilators, PRT is determined by the set circuit flow. Changing slope time can affect mean airway pressure (MAP), oxygenation, and carbon dioxide elimination. Our aim was to investigate the effect of PRT on ventilator parameters and gas exchange during volume-guaranteed ventilation. METHODS In a crossover study, 12 infants weighing greater than 2 kg were ventilated using a Dräger Babylog VN500 ventilator with synchronized intermittent positive pressure ventilation with volume guarantee (SIPPV-VG) and pressure support ventilation with volume guarantee (PSV-VG). During both modes PRTs between 0.08 and 0.40 seconds were used in 15-minute epochs. Data from the ventilator and patient monitors were downloaded with 1- and 100-Hz sampling rate and analyzed using the Python computer language. RESULTS During PSV-VG, longer PRTs were associated with longer inspiratory time (P  less then  .0001) and with lower peak inflating pressure (PIP; P = .003), but the MAP was similar. During SIPPV-VG the PIP was not significantly different; however, MAP was lower with longer PRT (P = .001). With a short PRT (0.08 seconds), the PIP was higher during PSV-VG than during SIPPV-VG (19.8 vs 16.5 mbar; P = .042). There were no significant differences in tidal volume delivery, respiratory rate, minute volume, oxygen saturations, or end-tidal CO2 with different PRTs in either mode. CONCLUSIONS During SIPPV-VG or PSV-VG, using short or long PRTs affects some ventilation parameters but does not significantly change oxygenation or carbon dioxide elimination. © 2020 Wiley Periodicals, Inc.