Epigenetic Regulation of Drug Metabolizing Enzymes in Normal Aging

Geriatric populations are at a higher risk for adverse drug reactions (ADRs). This may be partly due to changes in drug metabolism in old age, but the underlying mechanisms are poorly understood. Prior research in humans and mice has shown age-associated changes to the expression of several genes involved in drug metabolism. Furthermore, studies of human blood showed that epigenetic regulation of genes encoding drug metabolizing enzymes change with age. However, it is unknown if genes in the liver are similarly affected. Therefore, we hypothesize that genes encoding drug metabolizing enzymes may show differential epigenetic regulation in the liver with age, and that this will affect rates of drug metabolism. We selected genes encoding phase I and II drug metabolizing enzymes showing the strongest evidence of age-related epigenetic changes in prior genome-wide studies of human blood DNA. We mapped the homologues of these genes in mice and analyzed DNA methylation and histone acetylation levels in liver samples from aged mice (4, 18, 24 and 32 months) coupled with functional investigations at those genes. We successfully demonstrated a strong relationship between DNA methylation and histone acetylation (H3K9ac) levels at cytochrome P450 2E1 (Cyp2e1) and sulfotransferase family 1A member 1 (Sult1a1) and their expression levels in liver. Moreover, intrinsic clearance of the CYP2E1 probe drug chlorzoxazone was strongly associated with DNA methylation and histone acetylation at two regulatory regions of Cyp2e1. Next, we investigated DNA methylation levels at these genes in peripheral blood and organs like the liver and the brain. We show that DNA methylation levels of Cyp2e1 and Sult1a1 are substantially different between blood, liver, and the brain and are correlated to various extents and directions of effects. Finally, we report an optimized method for genome-wide investigation, Reduced Representation Bisulfite Sequencing (RRBS), of methylation levels using the innovative Adaptase technology for utilization in larger aging studies of epigenetics and drug metabolism by our group in the future. Our successful demonstration of epigenetic control of drug metabolism in an aged mouse model could pave the way for future clinical studies to develop epigenetic biomarkers of pharmacokinetic pathways in geriatric patients

利用公司税收优惠政策吸引外国直接投资：设计和实施注意事项

Countries are increasingly relying on corporate tax incentives to attract FDI. However, governments often overestimate the role of these instruments in swaying investors, translating to lost tax revenue, market distortions, and other unintended consequences. This Perspective provides good practice guidelines for policymakers to adopt incentives in a strategic, cost-effective manner

Leveraging corporate tax incentives to attract FDI: design and implementation considerations

Countries are increasingly relying on corporate tax incentives to attract FDI. However, governments often overestimate the role of these instruments in swaying investors, translating to lost tax revenue, market distortions, and other unintended consequences. This Perspective provides good practice guidelines for policymakers to adopt incentives in a strategic, cost-effective manner

Medical tourism: a fad or an opportunity Comment on “Patient mobility in the global marketplace: a multidisciplinary perspective”

This article is a commentary of an overview on “medical tourism” submitted by Lunt and Marrion, which describes a framework for the study of the issues related to medical tourism. The commentary attempts to differentiate between the current interest in medical tourism and the time-honored and well-established treatment abroad from countries with underdeveloped health systems. The commentary also calls for efforts to strengthen medical services and quality of care through the inflow of patients to countries that attract “medical tourists

Electroconvulsive Therapy Increases Plasma Levels of Interleukin-6 a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74956/1/j.1749-6632.1990.tb40529.x.pd

Bipolar disorders in the Arab world: a critical review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111799/1/nyas12652.pd

Immune function in mania

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27250/1/0000258.pd

Eliciting policymakers' and stakeholders' opinions to help shape health system research priorities in the Middle East and North Africa region

Evidence-informed decisions can strengthen health systems. Literature suggests that engaging policymakers and other stakeholders in research priority-setting exercises increases the likelihood of the utilization of research evidence by policymakers. To our knowledge, there has been no previous priority-setting exercise in health policy and systems research in countries of the Middle East and North Africa (MENA) region. This paper presents the results of a recent research priority-setting exercise that identified regional policy concerns and research priorities related to health financing, human resources and the non-state sector, based on stakeholders in nine low and middle income countries (LMICs) of the MENA region. The countries included in this study were Algeria, Egypt, Jordan, Lebanon, Morocco, Palestine, Syria, Tunisia and Yemen. This multi-phased study used a combination of qualitative and quantitative research techniques. The overall approach was guided by the listening priority-setting approach, adapted slightly to accommodate the context of the nine countries. The study was conducted in four key phases: preparatory work, country-specific work, data analysis and synthesis, and validation and ranking. The study identified the top five policy-relevant health systems research priorities for each of the three thematic areas for the next 3-5 years. Study findings can help inform and direct future plans to generate, disseminate and use research evidence for LMICs in the MENA region. Our study process and results could help reduce the great chasm between the policy and research worlds in the MENA region. It is hoped that funding agencies and countries will support and align financial and human resources towards addressing the research priorities that have been identifie

Selected psychiatric problems among college students in two Arab countries: Comparison with the USA

Background: Psychiatric problems among college students on USA campuses are common. Little is known about similar problems in developing countries, particularly the Arab region. The goal of this study was to assess the frequency of selected psychiatric problems among college students in two Arab countries: Qatar and Lebanon, and to compare them to the USA. Methods: The Healthy Minds Study, an online confidential survey of common psychiatric symptoms designed for college campuses was used. We used the Patient Health Questionnaire-9 (PHQ-9) to screen for major depression, the Generalized Anxiety Disorder-7 (GAD-7) to screen for generalized anxiety and the SCOFF questionnaire to screen for eating disorders. Comparisons were made using ANOVA, Chi-Square tests and logistic regressions. Results: A total of 1841 students participated in the study. The rates of depression (PHQ-9 ? 12), generalized anxiety (GAD-7 ? 10) and eating disorders (SCOFF?3) at the combined Arab universities were 34.6, 36.1 and 20.4% respectively. The corresponding rates in the USA were: 12.8, 15.9 and 6.8% (p < 0.001 for all measures). The impact of psychiatric problems on functioning in general and academic performance in particular was more severe in the Arab countries compared to the USA (p < 0.001). Independent predictors of psychiatric problems in general included location, female gender, financial difficulties and poor grades. Being religious had a protective association with mental health. Conclusion: The rates of depression, anxiety and eating disorders were significantly higher among college students in Qatar and Lebanon compared to the USA. Additional research is needed to determine whether these results reflect methodological limitations or true differences in psychopathology across these populations. If replicated, the results indicate that the psychiatric problems on college campuses in the USA are a microcosm of a global problem that needs global solutions. 2018 The Author(s).This study was made possible by NPRP Grant 5–618–5-087 from the Qatar National Research Fund (a member of Qatar Foundation). The findings achieved herein are solely the responsibility of the authors.Scopu

Suppression of Tumor Necrosis Factor Production by Alcohol in Lipopolysaccharide-Stimulated Culture

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66388/1/j.1530-0277.1994.tb00917.x.pd