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Disfavor By means of National Lens: A Pilot Qualitative Investigation of Pain-Related Disfavor Evaluations Amid Arab-Americans Along with Persistent Mid back pain.
re research is needed to see if the observed trends also apply to a broader and more diverse population. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail [email protected] is an inflammatory disease that primarily affects women during their reproductive years and since current hormonal therapies are of concern new hormone-independent treatment regimens are needed. The orphan nuclear receptor 4A1 (NR4A1, Nur77) is expressed in patient-derived (stromal) endometriotic cells and also epithelial cell lines, and we observed that knockdown of NR4A1 in patient-derived ESECT-7 and ESECT-40 cells decreased cell proliferation and induced apoptosis. Moreover, the treatment of these cells with bis-indole derived NR4A1 ligands 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) and its buttressed 3-chloro-5-methoxy analog (DIM-C-pPhOH-3-Cl-5-OCH3) inhibited cell growth and induced apoptosis and related genes. The compounds exhibit NR4A1 antagonist activities in both functional and transactivation assays whereas these effects were not observed in normal (NEM) endometrial cells. We also observed that NR4A1 knockdown and treatment with NR4A1 antagonists decreased fibrosis, α-smooth muscle actin (α-SMA), and related pro-fibrotic genes in ESECT-7 and ESECT-40 cells, and similar results were observed in epithelial-derived endometriotic cell lines. Moreover, in an endometriosis mouse model with auto-transplantation and also in SCID mice transplanted with human endometriotic cells treatment with 25 mg/kg/day DIM-C-pPhOH-3-Cl-5-OCH3 significantly inhibited growth and expansion of endometriotic lesions. Thus, bis-indole derived NR4A1 ligands represent a novel class of drugs as non-hormonal therapy for endometriosis. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail [email protected] the 5 taste qualities, salt is the least understood. The receptors, their expression pattern in taste cells, and the transduction mechanisms for salt taste are still unclear. Previous studies have suggested that low concentrations of NaCl are detected by the amiloride-sensitive epithelial Na+ channel (ENaC), which in other systems requires assembly of 3 homologous subunits (α, β, and γ) to form a functional channel. However, a new study from Lossow and colleagues, published in this issue of Chemical Senses, challenges that hypothesis by examining expression levels of the three ENaC subunits in individual taste cells using gene-targeted mice in combination with immunohistochemistry and in-situ hybridization. Selleckchem RXC004 Results show a lack of co-localization of ENaC subunits in taste cells as well as expression of subunits in taste cells that show no amiloride sensitivity. These new results question the molecular identity of the amiloride-sensitive Na+ conductance in taste cells. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail [email protected] QUESTION Is it cost-effective to use in vitro fertilisation and preimplantation genetic testing of monogenic defects (IVT/PGT-M) to prevent transmission of BRCA1/2 mutations to second-generation new births in comparison with naturally conceived births? SUMMARY ANSWER In this cost-effectiveness analysis, we found that IVF/PGT-M is cost-effective for BRCA1 and BRCA2 mutation carriers if using a willingness to pay of $50 000 per quality-adjusted life-year (QALY). WHAT IS KNOWN ALREADY Carriers of a BRCA1 or BRCA2 mutation have a significantly increased risk of several types of cancer throughout their lifetime. The cost of risk reduction, screening and treatment of cancer in this population is high. In addition, there is a 50% chance of passing on this genetic mutation to each child. One option to avoid transmission of an inherited deleterious gene to one's offspring involves in vitro fertilisation with preimplantation genetic testing. STUDY DESIGN, SIZE, DURATION We implemented a state transition model com Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail [email protected] Glutamate has been considered as neurotransmitter that is critical in triggering relapse to drugs of abuse, including ethanol and cocaine. Extracellular glutamate concentrations are tightly regulated by several mechanisms, including reuptake through glutamate transporters. Glutamate transporter type 1 (GLT-1) is responsible for clearing the majority of extracellular glutamate. The astrocytic cystine/glutamate antiporter (xCT) regulates also glutamate homeostasis. In this study, we investigated the effects of cocaine exposure and ampicillin/sulbactam (AMP/SUL), a β-lactam antibiotic known to upregulate GLT-1 and xCT, on relapse-like ethanol intake and the expression of astrocytic glutamate transporters in mesocorticolimbic brain regions. METHODS Male alcohol-preferring (P) rats had free access to ethanol for 5 weeks. On Week 6, rats were exposed to either cocaine (20 mg/kg, i.p.) or saline for 12 consecutive days. Ethanol bottles were then removed for 7 days; during the last 5 days, either AMP/SUL (100 or 200 mg/kg, i.p.) or saline was administered to the P rats. Ethanol bottles were reintroduced, and ethanol intake was measured for 4 days. RESULTS Cocaine exposure induced an alcohol deprivation effect (ADE), which was associated in part by a decrease in the expression of GLT-1 and xCT in the nucleus accumbens (NAc) core. AMP/SUL (100 mg/kg, i.p.) attenuated the ADE, while AMP/SUL (200 mg/kg, i.p.) reduced ethanol intake during 4 days of ethanol re-exposure and upregulated GLT-1 and xCT expression in the NAc core, NAc shell and dorsomedial prefrontal cortex (dmPFC). CONCLUSION This study suggests that these astrocytic glutamate transporters might be considered as potential targets for the treatment of polysubstance abuse. © The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.
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