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investigated. © 2020 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.AIM To identify associations between opioid-related mortality and neighborhood-level risk factors. DESIGN Cross-sectional study. SETTING Massachusetts, USA. PARTICIPANTS Using 2011-2014 Massachusetts death certificate data, we identified opioid-related (n=3,089) and non-opioid-related premature deaths (n=8,729). MEASUREMENTS The independent variables consisted of four sets of neighborhood-level factors (1) psychosocial, (2) economic, (3) built environment, and (4) health related. At the individual level we included the following compositional factors age at death, sex, race/ethnicity, marital status, education, veteran status, and nativity. The primary outcome of interest was opioid-related mortality. FINDINGS Multilevel models identified number of social associations per 10,000 (OR=0.84, p=0.002, 95% CI=0.75-0.94) and number of hospital beds per 10,000 (OR=0.78, p less then 0.001, 95%CI=0.68-0.88) to be inversely associated with opioid-related mortality, whereas percent living in poverty (OR=1.01, p=0.008, 95% CI=1.00-1.01), food insecurity rate (OR=1.21, p=0.002, 95%CI=1.07-1.37), number of federally qualified health centers (OR= 1.02, p=0.028, 95%CI=1.02-1.08), and per capita morphine milligram equivalents of hydromorphone (OR=1.05, p=0.003, 95%CI=1.01-1.08) were positively associated with opioid-related mortality. CONCLUSIONS Opioid-related deaths between 2011-2014 in the state of Massachusetts appear to be positively associated with percent living in poverty, food insecurity rate, number of federally qualified health centers, and per capita morphine milligram equivalents of hydromorphone, but inversely associated with number of social associations per 10,000 and number of hospital beds per 10,000. This article is protected by copyright. All rights reserved.Cereblon (CRBN) is a target for immunomodulatory drugs. This study investigated the prognostic value of the expression of CRBN-pathway genes on the clinical relevance of lenalidomide (Len) treatment and evaluated the levels of CRBN-binding proteins and mutations in these genes after Len treatment. Forty-eight primary multiple myeloma cells were collected prior to treatment with Len and dexamethasone (Ld) and 25 paired samples were obtained post-Ld therapy. These tumor cells were used to determine the expression and mutated forms of the CRBN-pathway genes. Following normalization with CRBN levels, there was a significantly reduced IKZF1/CRBN ratio in samples that responded poorly to Ld therapy. Moreover, patients with low ratios of IKZF1/CRBN showed a significantly shorter progression-free survival (PFS) and overall survival (OS) than those with higher ratios. However, patients with high ratios of KPNA2/CRBN showed a significantly shorter PFS and OS than patients with lower ratios. Of the 25 paired samples analyzed, most samples showed a reduction in the expression of CRBN and an increase in IKZF1 gene expression. No mutations were observed in CRBN, IKZF1, or CUL4A genes in the post-Ld samples. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of Ld therapy. © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.This paper introduces an 1 H NMR method to identify individual divalent metal cations Be2+ , Mg2+ , Ca2+ , Sr2+ , Zn2+ , Cd2+ , Hg2+ , Sn2+ , and Pb2+ in aqueous salt solutions through their unique signal shift and coupling after complexation with the salt of ethylenediaminetetraacetic acid (EDTA). Furthermore, quantitative determination applied for the divalent metal cations Ca2+ , Mg2+ , Hg2+ , Sn2+ , Pb2+ , and Zn2+ (limit of quantification 5-22 μg/ml) can be achieved using an excess of EDTA with aqueous model salt solutions. An internal standard is not required because a known excess of EDTA is added and the remaining free EDTA can be used to recalculate the quantity of chelated metal cations. The utility of the method is demonstrated for the analysis of divalent cations in some food supplements and in pharmaceutical products. © 2020 John Wiley & Sons, Ltd.PROBLEM Epigenetic age indices are markers of biological aging determined from DNA methylation patterns. Accelerated epigenetic age predicts morbidity and mortality. Women tend to demonstrate slower blood epigenetic aging compared to men, possibly due to female-specific hormones and reproductive milestones. Pregnancy and the post-partum period are critical reproductive periods that have not been studied yet with respect to epigenetic aging. The purpose of this paper was to examine whether pregnancy itself and an important pregnancy-related variable, changes in body mass index (BMI) between pregnancy and the post-partum period, are associated with epigenetic aging. METHOD OF STUDY A pilot sample of 35 women was recruited as part of the Healthy Babies Before Birth (HB3) project. Whole blood samples were collected at mid-pregnancy and 1 year post-partum. this website DNA methylation at both time points was assayed using Infinium 450K and EPIC chips. Epigenetic age indices were calculated using an online calculator. RESULTS Paired-sample t-tests were used to test differences in epigenetic age indices from pregnancy to 1 year after birth. Over this critical time span, women became younger with respect to phenotypic epigenetic age, GrimAge, DNAm PAI-1, and epigenetic age indices linked to aging-related shifts in immune cell populations, known as extrinsic epigenetic age. Post-partum BMI retention, but not prenatal BMI increases, predicted accelerated epigenetic aging. CONCLUSION Women appear to become younger from pregnancy to the post-partum period based on specific epigenetic age indices. Further, BMI at 1 year after birth that reflects weight retention predicted greater epigenetic aging during this period. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Skin hyperpigmentary disorders, commonly including melasma and post-inflammatory hyperpigmentation, are frequent dermatologic problems with higher prevalence in people with darker Fitzpatrick skin type.1,2 The current gold standard treatment is triple combination cream containing hydroquinone, retinoid and topical steroids3 but concerns over its long-term use including exogenous ochronosis, along with the lack of guidelines on the management of hyperpigmentary disorders, have contributed to the inconsistent practice amongst dermatologists. This article is protected by copyright. All rights reserved.