Francklu4753

BACKGROUND Hyperfiltration (HF) occurs early in diabetes or obesity (OB)-associated renal disease. Alterations of glomerular filtration rate (GFR) in childhood OB remain unclear. OBJECTIVES To compare the prevalence of GFR alterations and its association with uric acid in children and adolescents with type 1 diabetes (T1D) vs overweight (OW)/OB. METHODS Cross-sectional study of 29 youths (aged 13 ± 2 years) with T1D (disease duration 7 ± 3 years) and 165 with OW/OB (aged 11 ± 3 years). Patients with an albumin-creatinine ratio >3.39 mg/mmol were excluded. GFR was estimated with creatinine-cystatin C Zappitelli equation. HF and low GFR were defined by a GFR > 135 and less then 90 mL/min.1.73 m2 , respectively. RESULTS HF was higher in children with T1D vs OW/OB (28% vs 10%, P less then  .005). Children with OW/OB also showed a 10% of low GFR. In patients with T1D, HbA1c (β = .8, P less then  .001), and systolic blood pressure (β = 11.4, P less then  .005) were independent predictors of GFR (R2 = .65). In OW/OB, HF cases were almost limited to prepubertal children and low GFR to pubertal ones. GFR in OW/OB was associated with age (β = -2.2, P less then  .001), male sex (β = -11.6, P less then  .001), and uric acid (β = -.05, P less then  .001) in adjusted models (R2 = .33). CONCLUSIONS GFR alterations were different between youths with T1D and with OW/OB. Higher uric acid, older age, and puberty were related to lower GFR values in OW/OB children. Longitudinal studies will determine if low GFR is consequence of a rapid GFR decline in pediatric patients with OW/OB. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.The design and synthesis of achiral organic functional molecules which can assemble into a chiral with selective handedness in the absence of chiral substances is an important in understanding the role chirality plays within these systems. In this review, we described general approaches towards supramolecular chiral molecules the synthesis and self-assembly of achiral molecule to active chiral molecules to investigate controlled supramolecular chiral nanostructures with their photoluminescent properties for rapid, sensitive and selective detection of analytes of choice. Various small molecules have been discussed for achiral to chiral along with induction of chirality and controlled chiral helical structures in detail. We discussed few examples where stimuli used to control the chirality such as temperature, pH etc. Finally, we will also explore on the photo responsive helicity properties of the aggregation induced emission active molecule such as tetraphenylethene conjugates. © 2020 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Since December 2019, world healthcare community faced with Coronavirus Disease 2019 (COVID-19) outbreak caused by SARS-CoV-2. Due to the high viral contagiousness and the possible transmission during the pre-symptomatic phase, COVID-19 progressively spread to several countries. Currently, Italy is the third Country for number of confirmed cases after mainland China and South Chorea, and the first western nation with a well-established deceased transplant program to tackle a COVID-19 outbreak1 . This article is protected by copyright. All rights reserved.BACKGROUND Preclinical evidence has demonstrated that common intratumor bacteria metabolize the chemotherapeutic drug gemcitabine. The significance of this bacterial metabolism pathway, relative to the known metabolic pathways by host enzymes, is not known. We hypothesized that bacterial metabolism is clinically significant and that "knockdown" by antibacterial therapy has the unintended effect of increasing the effective dose of gemcitabine, thereby increasing the risk for gemcitabine-associated toxicities. MATERIALS AND METHODS We reanalyzed the comparator arm of the MPACT trial (NCT01442974), made available through Project Data Sphere, LLC (CEO Roundtable on Cancer's Life Sciences Consortium, Cary, NC; www.projectdatasphere.org). In this arm, 430 patients with metastatic pancreatic adenocarcinoma were treated with gemcitabine. We used the Anderson-Gill survival model to compare the risk of developing an adverse event after antibacterial prescription with time unexposed to antibacterials. Adverse events of hematologic and gastrointestinal events, as well as four specific hematologic adverse events, suggesting that intratumor bacteria may be responsible for a clinically significant portion of gemcitabine metabolism. Alternative avenues of evidence will be necessary to confirm this preliminary finding and assess its generalizability. There is plentiful opportunity for similar analyses on other clinical trial data sets, where gemcitabine or other biomimetic small molecules were used. IMPLICATIONS FOR PRACTICE Patients treated with gemcitabine for metastatic pancreatic ductal adenocarcinoma have an increased rate of gemcitabine-associated toxicity during and after antibiotic therapy. This observation is consistent with preclinical evidence that intratumor bacteria metabolize gemcitabine to an inactive form. see more Further research is needed to determine whether this observation merits any changes in clinical practice. © AlphaMed Press 2020.Mechanically induced biological responses in bone cells involve a complex biophysical process. Although various mechanosensors have been identified, the precise mechanotransduction pathway remains poorly understood. PIEZO1 is a newly discovered mechanically activated ion channel in bone cells. This study aimed to explore the involvement of PIEZO1 in mechanical loading (fluid shear stress)-induced signaling cascades that control osteogenesis. The results showed that fluid shear stress increased PIEZO1 expression in MC3T3-E1 cells. The fluid shear stress elicited the key osteoblastic gene Runx-2 expression; however, PIEZO1 silencing using small interference RNA blocked these effects. The AKT/GSK-3β/β-catenin pathway was activated in this process. PIEZO1 silencing impaired mechanically induced activation of the AKT/GSK-3β/β-catenin pathway. Therefore, the results demonstrated that MC3T3-E1 osteoblasts required PIEZO1 to adapt to the external mechanical fluid shear stress, thereby inducing osteoblastic Runx-2 gene expression, partly through the AKT/GSK-3β/β-catenin pathway.