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Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set. EVI5 showed the strongest association outside the major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06-1.43, P-value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A seems to be associated with disease progression. None of the tested variants showed results that were statistically inconsistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry.

Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set. EVI5 showed the strongest association outside the major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06-1.43, P-value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A seems to be associated with disease progression. None of the tested variants showed results that were statistically inconsistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry.

EXECUTIVE SUMMARY- Iowa was a tobacco control leader in the 19th Century. In 1897 the General Assembly completely prohibited the use, sale, and possession of tobacco products in the state. When the law was repealed in 1921, the General Assembly enacted strong measures to prevent tobacco use by minors. In 1921 Iowa passed the first state cigarette excise tax (2 cents).- Tobacco control reemerged in the 1970s, however a coalition of health groups were consistently outmaneuvered by tobacco industry lobbyists.- In 1990 health groups attempted to strengthen Iowa’s Clean Indoor Air Act (passed in 1987), however the tobacco industry, represented primarily by Charles Wasker, co-opted the bill, stripping meaningful tobacco control provisions and using it to include ambiguous language to preempt localities from passing clean indoor air laws, which chilled local clean indoor air action for a decade.- In 1993 the voluntary health organizations founded Tobacco Free Iowa (TFI), a dedicated statewide tobacco control coalition to advocate for tobacco control policy change. In 1995 TFI hired Serge Garrison, a former R.J. Reynolds (RJR) lobbyist, to lobby to repeal clean indoor air preemption. Garrison, who helped draft the preemption clause when working for RJR, questioned whether Iowa’s ambiguously worded clause actually preempted local clean indoor air action.- Iowa, represented by Attorney General Tom Miller (D), was a party in the 1998 Master Settlement Agreement. Miller and the Iowa Attorney General’s Office, have been strong allies to tobacco control in Iowa.- After the MSA, in 2000, Iowa created the Division of Tobacco Use Prevention and Control within the Iowa Department of Public Health to implement a state tobacco control program funded with MSA revenue.- In 2001 the General Assembly passed legislation to securitize the MSA revenue stream to receive an upfront lump sum in lieu of most future MSA payments. Politicians framed MSA securitization as a way to create stable fund

EXECUTIVE SUMMARY- Iowa was a tobacco control leader in the 19th Century. In 1897 the General Assembly completely prohibited the use, sale, and possession of tobacco products in the state. When the law was repealed in 1921, the General Assembly enacted strong measures to prevent tobacco use by minors. In 1921 Iowa passed the first state cigarette excise tax (2 cents).- Tobacco control reemerged in the 1970s, however a coalition of health groups were consistently outmaneuvered by tobacco industry lobbyists.- In 1990 health groups attempted to strengthen Iowa’s Clean Indoor Air Act (passed in 1987), however the tobacco industry, represented primarily by Charles Wasker, co-opted the bill, stripping meaningful tobacco control provisions and using it to include ambiguous language to preempt localities from passing clean indoor air laws, which chilled local clean indoor air action for a decade.- In 1993 the voluntary health organizations founded Tobacco Free Iowa (TFI), a dedicated statewide tobacco control coalition to advocate for tobacco control policy change. In 1995 TFI hired Serge Garrison, a former R.J. Reynolds (RJR) lobbyist, to lobby to repeal clean indoor air preemption. Garrison, who helped draft the preemption clause when working for RJR, questioned whether Iowa’s ambiguously worded clause actually preempted local clean indoor air action.- Iowa, represented by Attorney General Tom Miller (D), was a party in the 1998 Master Settlement Agreement. Miller and the Iowa Attorney General’s Office, have been strong allies to tobacco control in Iowa.- After the MSA, in 2000, Iowa created the Division of Tobacco Use Prevention and Control within the Iowa Department of Public Health to implement a state tobacco control program funded with MSA revenue.- In 2001 the General Assembly passed legislation to securitize the MSA revenue stream to receive an upfront lump sum in lieu of most future MSA payments. Politicians framed MSA securitization as a way to create stable fund

Background: Cerebral palsy (CP) is a group of nonprogressive disorders of movement and posture caused by abnormal development of, or damage to, motor control centers of the brain. A single nucleotide polymorphism (SNP), rs1800795, in the promoter region of

Background: Cerebral palsy (CP) is a group of nonprogressive disorders of movement and posture caused by abnormal development of, or damage to, motor control centers of the brain. A single nucleotide polymorphism (SNP), rs1800795, in the promoter region of

BackgroundPediatric onset multiple sclerosis (MS) accounts for 2-4% of all MS. It is unknown whether the disease shares the same underlying pathophysiology found in adult patients or an extreme early onset phenotype triggered by distinct biological mechanisms. It has been hypothesized that copy number variations (CNVs) may result in extreme early onset diseases because CNVs can have major effects on many genes in large genomic regions.Objectives and methodsThe objective of the current research was to identify CNVs, with a specific focus on de novo CNVs, potentially causing early onset MS by competitively hybridizing 30 white non-Hispanic pediatric MS patients with each of their parents via comparative genomic hybridization (CGH) analysis on the Agilent 1M CGH array.Results and discussionWe identified 10 CNVs not overlapping with any CNV regions currently reported in the Database of Genomic Variants (DGV). Fifty-five putatively de novo CNVs were also identified: all but one common in the DGV. We found the single rare CNV was a private variation harboring the SACS gene. SACS mutations cause autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease. Additional clinical review revealed that the patient with the SACS gene CNV shared some features of both MS and ARSACS.ConclusionsThis is the first reported study analyzing pediatric MS CNVs. While not yielding causal variation in our initial pediatric dataset, our approach confirmed diagnosis of an ARSACS-like disease in addition to MS in the affected individual, which led to a more complete understanding of the patient's disease course and prognosis.

BACKGROUND: Topiramate can improve drinking outcomes via a hypothesized mechanism of facilitating gamma-aminobutyric acid function and inhibiting glutaminergic pathways in the corticomesolimbic system. We sought to determine whether topiramate's antidrinking effects are bolstered by improvements in physical and psychosocial well-being. METHODS: In a 17-site, 14-week, double-blind, randomized controlled trial, we compared the effects of topiramate (up to 300 mg/d) vs placebo on physical health, obsessional thoughts and compulsions about using alcohol, and psychosocial well-being among 371 alcohol-dependent subjects who received weekly adherence enhancement therapy. RESULTS: Topiramate was more efficacious than placebo in reducing body mass index (calculated as weight in kilograms divided by height in meters squared) (mean difference, 1.08; 95% confidence interval [CI], 0.81-1.34; P < .001), all liver enzyme levels (P < .01 for all comparisons), plasma cholesterol level (mean difference, 13.30 mg/dL; 95% CI, 5.09-21.44 mg/dL; P = .002), and systolic (mean difference, 9.70 mm Hg; 95% CI, 6.81-12.60 mm Hg; P < .001) and diastolic (mean difference, 6.74 mm Hg; 95% CI, 4.57-8.90 mm Hg; P < .001) blood pressure to about prehypertension levels-effects that might lower the risk of fatty liver degeneration and cirrhosis as well as cardiovascular disease. Topiramate compared with placebo significantly (P < .05 for all comparisons) decreased obsessional thoughts and compulsions about using alcohol, increased subjects' psychosocial well-being, and improved some aspects of quality of life, thereby diminishing the risk of relapse and longer-term negative outcomes. Paresthesia, taste perversion, anorexia, and difficulty with concentration were reported more frequently for topiramate than for placebo. CONCLUSION: Topiramate appears to be generally effective at improving the drinking outcomes and physical and psychosocial well-being of alcoholic subjects.