Lucaswhittaker0860

INTRODUCTION To combine numerical simulations, in vitro and in vivo experiments to evaluate the feasibility of measuring diffusion exchange across the cell membrane with diffusion exchange spectroscopy (DEXSY). METHODS DEXSY acquisitions were simulated over a range of permeabilities in nerve tissue and yeast substrates. In vitro measurements were performed in a yeast substrate and in vivo measurements in mouse tumor xenograft models, all at 9.4 T. RESULTS Diffusion exchange was observed in simulations over a physiologically relevant range of cell permeability values. In vitro and in vivo measures also provided evidence of diffusion exchange, which was quantified with the Diffusion Exchange Index (DEI). CONCLUSIONS Our findings provide preliminary evidence that DEXSY can be used to make in vivo measurements of diffusion exchange and cell membrane permeability. © 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.BACKGROUND In dogs with protein-losing enteropathy (PLE), data on the clinical characteristics of food-responsive PLE (FR-PLE) remain scarce. OBJECTIVE To determine the clinical characteristics of FR-PLE in dogs responsive to ultralow-fat diet (ULFD) management. ANIMALS Thirty-three dogs diagnosed with PLE based on standard diagnostic criteria. METHODS Retrospective review of medical records. Clinical findings were compared between dogs with FR-PLE (FR-PLE group) and those with immunosuppressant-responsive PLE (IR-PLE) or nonresponsive PLE (NR-PLE) (IR/NR-PLE group). The area under the curve (AUC) of a receiver operating characteristic curve was used to evaluate the ability of factors to differentiate the FR-PLE and IR/NR-PLE groups. Survival time was compared between the FR-PLE and IR/NR-PLE groups. learn more RESULTS Twenty-three dogs responded to ULFD management and were diagnosed with FR-PLE. The canine chronic enteropathy clinical activity index (CCECAI) was significantly lower in the FR-PLE group than in the IR/NR-PLE group (P  less then  .001). The AUC of CCECAI for differentiating the FR-PLE group was 0.935 (95% confidence interval [CI], 0.845-1.000) with an optimal cutoff value of 8 (sensitivity, 0.826; specificity, 0.889). Survival times were significantly longer in the FR-PLE group (median, not reached) than in the IR/NR-PLE group (median, 432 days; P  less then  .001). CONCLUSIONS AND CLINICAL IMPORTANCE Dogs that respond to ULFD management and are diagnosed with FR-PLE are expected to have a favorable prognosis. Clinical scores, specifically the CCECAI, could be useful for differentiating FR-PLE from IR-PLE or NR-PLE. © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.Cancer associated fibroblasts (CAFs) are 'activated' fibroblasts in the tumor microenvironment (TME), and play a vital role in all steps of cancer development. Increasing evidence focusing on the function of CAFs suggests that CAFs are candidate therapeutic targets, and that drugs targeting the modification of CAFs would suppress tumor progression and be beneficial to tumor treatment and prevention. In the present study, we found that curcumin reversed the phenotype of CAFs to that of peri-tumor fibroblasts (PTFs)-like cells by downregulating the expression of α-SMA (a special marker for CAFs) and inhibiting the secretion of pro-carcinogenic cytokines, including transforming growth factor-β1 (TGF-β1), matrix metalloproteinases 2 (MMP2), and stromal cell-derived factor-1 (SDF-1). We further demonstrated that the conditioned medium (CM) derived from CAFs promoted the proliferation of Cal27, and this effect was confirmed by the xenograft model. More importantly, we found that curcumin blocked the CAFs-mediated enhancement of Cal27 proliferation in vitro and in vivo. In conclusion, our data suggest that curcumin reverses cell phenotype from CAF to PTF-like cells, and suppresses the CAF-mediated proliferation and tumorigenicity of Cal27 by inhibiting TSCC CAFs. This article is protected by copyright. All rights reserved.BACKGROUND Pain in people with advanced cancer is prevalent. When a stable dose of opioids is established, people still experience episodic breakthrough pain for which dosing of an immediate release opioid is usually a proportion of the total daily dose. METHODS This multi-site, double blind, randomized trial tested three dose proportions (1/6, 1/8, 1/12 of total daily dose) in two blocks, each block with three dose proportions in random order (6 numbered bottles in total). When participants required opioid breakthrough doses and it was their first breakthrough dose for that study day, they took the next numbered bottle rather than their usual breakthrough dose. (Subsequent doses on that day reverted to their usual dose.) RESULTS Eighty-five people were randomized in this study of whom 81 took at least one dose and 73 (90%) took at least block one (one of each dose proportion). No dose was found to be optimal at 30 min with approximately one-third of participants showing maximal reduction with each dose propo Federation - EFIC®.BACKGROUND AND OBJECTIVE Having to deal on a daily routine with prescriptions in adults with intellectual disability (ID), we systematically reviewed the literature on the specificities of pain interventions in that population, focusing on medication and trying to gather practical information on appropriate pain treatments. Given the scarcity of the literature on the topic, we also discussed the pharmacological considerations to be taken into account when prescribing analgesic drugs in that vulnerable population. DATABASES AND DATA TREATMENT Articles on pain and ID were searched in the Medline and Google scholar electronic databases using the key words "Intellectual Disability," "Developmental Disability" and specific keywords for pharmacological and non-pharmacological pain interventions. Preset outcomes about pharmacological treatment specificity, efficacy and safety were then collected. RESULTS One hundred and fifty-two articles were found and 16 were retained based on our inclusion and exclusion criteria.gesic prescriptions in this population. © 2020 European Pain Federation - EFIC®.Perinatal hypoxic-ischemic (HI)-related brain injury is an important cause of morbidity and long-standing disability in newborns. The only currently approved therapeutic strategy available to reduce brain injury in the newborn is hypothermia. Therapeutic hypothermia can only be used to treat HI encephalopathy in full-term infants and survivors remain at high risk for a wide spectrum of neurodevelopmental abnormalities as a result of residual brain injury. Therefore, there is an urgent need for adjunctive therapeutic strategies. Inflammation and neurovascular damage are important factors that contribute to the pathophysiology of HI-related brain injury and represent exciting potential targets for therapeutic intervention. In this review, we address the role of each component of the neurovascular unit (NVU) in the pathophysiology of HI-related injury in the neonatal brain. Disruption of the blood-brain barrier (BBB) observed in the early hours after an HI-related event is associated with a response at the basal lamina level, which comprises astrocytes, pericytes, and immune cells, all of which could affect BBB function to further exacerbate parenchymal injury. Future research is required to determine potential drugs that could prevent or attenuate neurovascular damage and/or augment repair. However, some studies have reported beneficial effects of hypothermia, erythropoietin, stem cell therapy, anti-cytokine therapy and metformin in ameliorating several different facets of damage to the NVU after HI-related brain injury in the perinatal period. © 2020 Wiley Periodicals, Inc.BACKGROUND Growing evidence suggested that B- and T-lymphocyte attenuator (BTLA) polymorphisms raised the susceptibility to a wide range of cancers. This study aimed to evaluate whether BTLA variants were related to the risk of esophageal squamous cell carcinoma (ESCC). METHODS A total of 721 ESCC patients and 1208 matched non-cancer controls were included in this research, and four tagging BTLA polymorphisms (rs2171513 G > A, rs3112270 A > G, rs1982809 G > A, and rs16859629 T > C) were selected and genotyped using SNPscan™ Assays. RESULTS In the present study, no significant relationship between BTLA polymorphisms and ESCC was observed. However, stratified analyses suggested that the variant of BTLA rs3112270 A > G reduced the risk of ESCC in the male subgroup (AG vs AA adjusted OR = 0.78, 95% CI = 0.61-0.99, P = .042), BMI  A variants in the BTLA gene are candidates for the risk of ESCC, which might be helpful for the early diagnosis and treatment of ESCC. © 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.We have developed efficient procedure for isolation of horseradish peroxidase (HRP) using aminobenzohydrazide based affinity chromatography. Sepharose 4B-bounded aminobenzohydrazides are suitable for long term use and large scale purification. In this study, 26 aminobenzohydrazide derivatives were synthesized, characterized and defined as new HRP inhibitors. In addition, detailed inhibition effect of these molecules on HRP enzyme were investigated. Affinity matrix was formed by bonding aminobenzohydrazides which exhibited inhibitory activity to Sepharose-4B-L-tyrosine. HRP was isolated from crude homogenate in single-step and purification factors were recorded as 1151 fold (recovery of 8.5 %) with 4-amino 3-bromo benzohydrazide, and purification factors were recorded as 166.16 fold (recovery of 16.67 %) with 3-amino 4-chloro benzohydrazide. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Succinate dehydrogenase (SDH) deficiency is associated with gastrointestinal stromal tumor (GIST) oncogenesis, but the underlying molecular mechanism remains to be further investigated. Here, we show that succinate accumulation induced by SDHB loss of function increased the expression of zinc finger protein 148 (ZNF148, also named ZBP-89) in GIST cells. Meanwhile, ZNF148 is found to be phosphorylated by ERK at Ser306, and this phosphorylation results in ZNF148 binding to Forkhead box M1 (FOXM1). Through the complex formation at the promoter, ZNF148 facilitates Histone H3 acetylation and FOXM1-mediated Snail transcription, which eventually promotes cell invasion and tumor growth. The clinical analysis indicates that SDHB deficiency is associated with elevated ZNF148 levels, and ZNF148-S306 phosphorylation level displays a positive correlation with poor prognosis in GIST patients. These findings illustrate an unidentified molecular mechanism underlying FOXM1-regulated gene transcription related to GIST cell invasion, which highlights the physiological effects of SDHB deficiency on the invasiveness of GIST. © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.In this study, we investigated the design and construct of a chitosan-based targeted gene delivery system and evaluated its function. To this end, chitosan-folic acid/pDNA (CA-FA/pDNA) nanoparticles were prepared in different formulations using the ion gelation method. All the synthesized nanoparticles were characterized using FTIR, TEM, SEM and DLS analysis. Moreover, the effects of molecular weight (MW) of chitosan (CA), DNA and CA concentration were inspected on encapsulation efficiency (EE). The results showed that the EE of pDNA was directly proportional with MW of CA and CA concentration but was in an inverse proportion with DNA concentration. In addition, HMwC and LMwC nanoparticles showed lower and higher pDNA release in all pH ranges, respectively. It is concluded that the N/P ratio increase can cause controlled pDNA release. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.