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The uniqueness of the NACE-ESI-MS/MS method lies in its simplicity and reliability for proving the phosphorylation isomerism (C1 or C4') and acylation pattern of native lipid A species or those designed for therapeutic applications. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Singular use of activity assays or staining dyes to assess pathogen agrochemical tolerance can underestimate tolerance if pesticides cause sublethal effects. We exposed Schistosoma mansoni cercariae, the aquatic life stage of this trematode that infects humans, to four insecticides at five concentrations using a 24-hr time-to-death assay. We used Trypan blue dye, which stains dead tissue, and activity assays simultaneously to discriminate dead from live, but paralyzed individuals. Whereas cypermethrin, deltamethrin, and dimethoate exposure did not affect cercariae at any ecologically relevant concentrations, methamidophos exposure increased survival of cercariae compared to those in the controls. This was because methamidophos induced paralysis reduced cercarial activity and thus energy expenditures, extending the lifespan of this short-lived parasite that causes human schistosomiasis. These findings highlight that sublethal effects should be considered when investigating pesticide effects on disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND AND OBJECTIVES Postoperative complications (POCs) after hepatic resection for colorectal liver metastases (CRLM) adversely affect long-term survival. The aim of this study was to analyze the effect of POC etiology and severity on overall survival (OS) and disease-free survival (DFS). METHODS A retrospective study of 254 consecutive hepatectomies for CRLM was performed. Univariate and multivariate analyses were performed to determine the effects of demographic, tumor-related and perioperative variables on OS and DFS. A 11 propensity score matching (PSM) was then used to compare patients with different POC etiology infective (Inf-POC), noninfective (Non-inf POC), and no-complications (No-POC). RESULTS Inf-POC, Non-inf POC, and No-POC patients represented 18.8%, 19.2%, and 62% of the sample, respectively. In univariate and multivariate analyses infectious POC were independent risk factors for decreased OS and DFS. After PSM, Inf-POC group presented decreased OS and DFS when compared with Non-inf POC (5-year OS 31.8% vs 51.6%; P = .05 and 5-year DFS 13.6% vs 31.9%; P = .04) and with No-POC (5-year OS 29.4% vs 58.7%; P = .03 and 5-year DFS 11.8% vs 39.7%; P = .03). There were no differences between Non-inf POC and No-POC patients. POC severity calculated using the Comprehensive Complications Index did not influence OS and DFS before and after PSM. CONCLUSION The negative oncological impact of POCs after CRLM resection is determined by infective etiology not by severity. © 2020 Wiley Periodicals, Inc.High temperature (HT) has an adverse effect on rice grain filling by inhibiting the accumulation of storage materials. However, the regulatory mechanism of this inhibition remains unknown. Here, we report that Opaque2 like transcription factor OsbZIP58 is a key factor regulating storage material accumulation under HT. The OsbZIP58 gene promotes expression of many seed storage protein genes and starch synthesis genes while inhibits expression of some starch hydrolyzing α-amylase genes under HT. The loss of OsbZIP58 function leads to floury and shrunken endosperms and dramatically reduced storage materials in the seeds under HT. HT is found to affect alternative splicing of OsbZIP58, promoting the formation of the truncated OsbZIP58β protein form over the full-length OsbZIP58α protein form. The OsbZIP58β form has a lower transcriptional activity than the OsbZIP58α form, especially under HT condition. Interestingly, rice varieties with less heat sensitivity have reduced alternative splicing of OsbZIP58. Therefore, OsbZIP58 is a crucial gene in regulating storage material accumulation under HT and lower alternative splicing of OsbZIP58 may contribute to heat tolerance during grain filling. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The target of this study is the synthesis of a new diester derivative and radiolabeling with one of the most effective diagnostic radioisotopes to be investigated as a novel targeting radiotracer for tumor imaging. selleckchem 10-[2-(9-carboxynonanoyloxy)propoxy]-10-oxodecanoic acid was synthesized in excellent yield and characterized by FT-IR, mass, 1 HNMR and 13 C-NMR spectra. The diester was technetium-99m radiolabeled by direct technique using sodium dithionite as a reducing agent. The labeling parameters such as diester amount, reducing agent amount, pH of the medium and reaction time were optimized. High radiochemical yield of 95.10 ± 0.41% and in-vitro stability in serum up to 12h have been obtained on complexation of the synthesized diester with Tc-99m. Evaluation of the diester anticancer activity against breast cancer cell line (MCF-7) showed high percent of inhibition about 61.5 % at 100 μg/ml. The rhenium complex of the diester was synthesized and characterized by LC-MS (ESI) and elemental analysis depending on the strong chemical resemblance between Tc and Re. Biodistribution studies of 99m Tc-diester complex showed high target to non-target ratio (T/NT) equals 6.24 ± 0.09 in tumor bearing mice at 30 min post injection, suggesting this complex could be used as hopeful solid tumor imaging agent. This article is protected by copyright. All rights reserved.Our study investigated the differences in pharmacokinetics of three major components of crude Cimicifuga foetida L.and its fried product, honey- and liquor-prepared products. A rapid and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry approach was established for determing caffeic acid, isoferulic acid and ferulic acid in rat plasma. The approach has good linearity, precision, accuracy, recovery and stability. Phenolic acid were rapidly absorbed. The Tmax were shorter in processed group than that of the crude product, with their values of less than 30 min. The Cmax values of caffeic acid and isoferulic acid were higher in crude group than that of the processed groups (p less then 0.05). AUC values of the three phenolics in the crude group were significantly higher than that of the processed groups (p less then 0.05). This article is protected by copyright. All rights reserved.After a cluster of human pneumonia cases in Wuhan City (China) on 7 January 2020 a novel coronavirus, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified as the causative agent of the disease COVID-19 (World Health Organization (WHO). 2020). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Drug entry into the adult brain is controlled by efflux mechanisms situated in various brain barrier interfaces. The effectiveness of these protective mechanisms in the embryo, fetus and newborn brain is less clear. The longstanding belief that "the" blood brain barrier is absent or immature in the fetus and newborn has led to many misleading statements with potential clinical implications. Here we review the properties of brain barrier mechanisms in the context of drug entry into the developing brain and discuss the limited number of studies published on the subject. We noticed that most of available literature suffers from some experimental limitations, notably that drug levels in fetal blood and cerebrospinal fluid have not been measured. This means that the relative contribution to the overall brain protection provided by individual barriers such as the placenta (which contains similar efflux mechanisms) and the brain barriers cannot be separately ascertained. Finally, we propose that systematic studies in appropriate animal models of drug entry into the brain at different stages of development would provide a rational basis for use of medications in pregnancy and in newborns, especially prematurely born, where protection usually provided by the placenta is no longer present. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.It is hypothesized that prenatal vitamin D deficiency may contribute to the development of childhood wheezing and asthma. Beyond its known functions in bone development and health, vitamin D is emerging as a pleiotropic hormone exerting several extraskeletal effects, some of which could reduce the risk of asthma. Experimental evidence shows that vitamin D is an important regulator of foetal and neonatal lung growth. It can also modulate innate and adaptive immune responses, enhancing antiviral and antimicrobial defences on epithelial surfaces and inhibiting some pro-inflammatory responses associated with asthma and allergic diseases. This article is protected by copyright. All rights reserved.AIM The goal of this study is to present the utility of quantitative modeling for extrapolation of drug safety and efficacy to underrepresented populations in controlled clinical trials. To illustrate this, the stepwise development of an integrated disease/pharmacokinetics/pharmacodynamics model of antipyretic efficacy of ibuprofen in children with cystic fibrosis (CF) is presented along with therapy optimization suggestions. METHOD Published clinical trials, in vitro data and drug physiochemical properties were used to develop an ibuprofen-mediated antipyresis model for febrile children also having CF. Workflow included first developing a mechanistic absorption model using in vitro-in vivo extrapolation followed by physiologically-based pharmacokinetic (PBPK) modeling. The verified PBPK model was then scaled to pediatric patients with CF. Once verified, the PBPK model was linked to an indirect response model of antipyresis for simulation of the overall antipyretic efficacy of ibuprofen in CF children. RESULTS Model simulations showed therapeutic inequivalence between healthy children and pediatric patients with CF; Cmax and AUC decreased by 39% (32-46%) and 44% (36-52%), respectively, in patients. Further and in agreement with literature reports, predicted pharmacodynamics time courses suggest a slower onset and faster offset of action in patients compared to healthy children, 30 and 60 minutes, respectively. Exploratory simulations suggest an increase in dosing frequency for CF children as a better therapeutic strategy. CONCLUSION Model-informed approaches to leveraging knowledge obtained throughout the life cycle of drug development may play a key role in extrapolating drug efficacy and safety to underrepresented populations. This article is protected by copyright. All rights reserved.The impact of recent outbreak of novel coronavirus disease, COVID-19, to the global healthcare systems is unprecedently enormous. Like many other clinical disciplines, medical physics has encountered unique challenges during this special period in wider aspects from clinical practice, research, administration to education. As hospitals implement various preventive and control measures to contain the virus, medical physicists are asked to perform non-essential activities by telecommuting or work-from-home (WFH) in many places. This article is protected by copyright. All rights reserved.