Wake Forest University

About: Wake Forest University is a education organization based out in Winston-Salem, North Carolina, United States. It is known for research contribution in the topics: Population & Diabetes mellitus. The organization has 21499 authors who have published 48731 publications receiving 2246027 citations. The organization is also known as: Wake Forest College.

Epigenetic Signatures of Cigarette Smoking

Abstract: Background —DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results —To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15,907 blood derived DNA samples from participants in 16 cohorts (including 2,433 current, 6,518 former, and 6,956 never smokers). Comparing current versus never smokers, 2,623 CpG sites (CpGs), annotated to 1,405 genes, were statistically significantly differentially methylated at Bonferroni threshold of p<1×10-7 (18,760 CpGs at False Discovery Rate (FDR)<0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant p<1×10-7 (2,623 CpGs at FDR<0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Conclusions —Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biologic effects of smoking, and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.

CT Angiography for Safe Discharge of Patients with Possible Acute Coronary Syndromes

Abstract: A b s t r ac t Background Admission rates among patients presenting to emergency departments with possible acute coronary syndromes are high, although for most of these patients, the symptoms are ultimately found not to have a cardiac cause. Coronary computed tomographic angiography (CCTA) has a very high negative predictive value for the detection of coronary disease, but its usefulness in determining whether discharge of patients from the emergency department is safe is not well established. Methods We randomly assigned low-to-intermediate-risk patients presenting with possible acute coronary syndromes, in a 2:1 ratio, to undergo CCTA or to receive traditional care. Patients were enrolled at five centers in the United States. Patients older than 30 years of age with a Thrombolysis in Myocardial Infarction risk score of 0 to 2 and signs or symptoms warranting admission or testing were eligible. The primary outcome was safety, assessed in the subgroup of patients with a negative CCTA examination, with safety defined as the absence of myocardial infarction and cardiac death during the first 30 days after presentation. Results We enrolled 1370 subjects: 908 in the CCTA group and 462 in the group receiving traditional care. The baseline characteristics were similar in the two groups. Of 640 patients with a negative CCTA examination, none died or had a myocardial infarction within 30 days (0%; 95% confidence interval [CI], 0 to 0.57). As compared with patients receiving traditional care, patients in the CCTA group had a higher rate of discharge from the emergency department (49.6% vs. 22.7%; difference, 26.8 percentage points; 95% CI, 21.4 to 32.2), a shorter length of stay (median, 18.0 hours vs. 24.8 hours; P<0.001), and a higher rate of detection of coronary disease (9.0% vs. 3.5%; difference, 5.6 percentage points; 95% CI, 0 to 11.2). There was one serious adverse event in each group. Conclusions

Obesity, regional body fat distribution, and the metabolic syndrome in older men and women

Abstract: Background:Themetabolicsyndromeisadisorderthat includes dyslipidemia, insulin resistance, and hypertension and is associated with an increased risk of diabetes andcardiovasculardisease.Wedeterminedwhetherpatterns of regional fat deposition are associated with metabolic syndrome in older adults. Methods: A cross-sectional study was performed that included a random, population-based, volunteer sample of Medicare-eligible adults within the general communities of Pittsburgh, Pa, and Memphis, Tenn. The subjects consisted of 3035 men and women aged 70 to 79 years, of whom 41.7% were black. Metabolic syndrome was defined by Adult Treatment Panel III criteria, including serum triglyceride level, high-density lipoprotein cholesterol level, glucose level, blood pressure, and waist circumference. Visceral, subcutaneous abdominal, intermuscular, and subcutaneous thigh adipose tissue was measured by computed tomography. Results:Visceral adipose tissue was associated with the metabolic syndrome in men who were of normal weight (odds ratio, 95% confidence interval: 2.1, 1.6-2.9), overweight (1.8, 1.5-2.1), and obese (1.2, 1.0-1.5), and in women who were of normal weight (3.3, 2.4-4.6), overweight (2.4, 2.0-3.0), and obese (1.7, 1.4-2.1), adjustingforrace.Subcutaneousabdominaladiposetissuewas associated with the metabolic syndrome only in normalweight men (1.3, 1.1-1.7). Intermuscular adipose tissue was associated with the metabolic syndrome in normalweight (2.3, 1.6-3.5) and overweight (1.2, 1.1-1.4) men. In contrast, subcutaneous thigh adipose tissue was inversely associated with the metabolic syndrome in obese men (0.9, 0.8-1.0) and women (0.9, 0.9-1.0). Conclusion: In addition to general obesity, the distribution of body fat is independently associated with the metabolic syndrome in older men and women, particularly among those of normal body weight. Arch Intern Med. 2005;165:777-783

Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review) Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Abstract: Objective: To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of movement disorders. Methods: A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and selected movement disorders. Authors reviewed, abstracted, and classified articles based on American Academy of Neurology criteria (Class I–IV). Results: The highest quality literature available for the respective indications was as follows: blepharospasm (two Class II studies); hemifacial spasm (one Class II and one Class III study); cervical dystonia (seven Class I studies); focal upper extremity dystonia (one Class I and three Class II studies); focal lower extremity dystonia (one Class II study); laryngeal dystonia (one Class I study); motor tics (one Class II study); and upper extremity essential tremor (two Class II studies). Recommendations: Botulinum neurotoxin should be offered as a treatment option for the treatment of cervical dystonia (Level A), may be offered for blepharospasm, focal upper extremity dystonia, adductor laryngeal dystonia, and upper extremity essential tremor (Level B), and may be considered for hemifacial spasm, focal lower limb dystonia, and motor tics (Level C). While clinicians’ practice may suggest stronger recommendations in some of these indications, evidencebased conclusions are limited by the availability of data. Neurology ® 2008;70:1699–1706

A Phase III Trial of Surgery With or Without Adjunctive External Pelvic Radiation Therapy in Intermediate-Risk Endometrial Adenocarcinoma: A Gynecologic Oncology Group Study

Abstract: Between June 1987 and July 1995, 448 women with endometrial cancer were enrolled in a prospective, randomized trial comparing the use of postoperative radiation versus no postoperative treatment. Participants had stage IB, IC, II, or IIB endometrial adenocarcinoma with an intermediate risk of recurrence (that is, tumor with any degree of myometrial invasion, adenocarcinoma of any grade, and no evidence of lymph node involvement). In addition, an analysis was performed of 2 subgroups. High-risk patients had all of these risk factors: moderate to poorly differentiated tumor, presence of lymphvascular invasion, and myometrial invasion to the outer third; they were 50 years of age or older with 2 of the 3 risk factors; or they were 70 years of age or older and had one additional risk factor. Women who did not qualify for the high-risk subgroup were considered in the low-risk subgroup. Three hundred ninety-two participants met all eligibility requirements for inclusion in the analysis. Two hundred two women were randomized to the whole pelvic radiation group, and 190 received no additional postoperative treatment. Otherwise, both groups had similar clinical and demographic characteristics. In the radiation therapy (RT) group, 13 patients refused postoperative treatment and 5 received less than the prescribed dose. In the no-treatment group, 2 patients received fall-dose postoperative RT. Twenty-four participants were lost to follow up within a median of 50 months. Overall median follow up was 68 months. Forty-four patients, 31 in the unirradiated group and 13 in the radiation group, developed disease recurrence. After a median follow up of 80 months, 15 of the women who recurred were alive with disease. In all, 66 women in the study died, 32 from disease or treatment-related causes. Women who received postoperative radiation therapy were less likely to have a recurrence of disease than those who had no additional treatment Among the 202 patients who had no postoperative treatment, 13 recurred in the vagina, 4 in the pelvis, 1 in the vagina and pelvis, and 13 had distant recurrences. In the RT group, 2 women, both of whom refused treatment with radiation, had a recurrence in the vagina. One other patient recurred in the vagina and pelvis, and 10 had distant recurrences. Patients who were treated with postoperative radiation therapy had a 58% lower risk of ever having a recurrence of disease than women who did not. The overall risk of recurrence in the first 24 months after treatment was 3% (90% confidence interval [CI], 0.02-0.06) for women who received RT and 12% (90% CI, 0.09-0.17) for women who had no additional treatment. The estimated cumulative risk of recurring in the vagina or pelvis within the first 24 months was 1.6% (90% CI, 0.6-3.9) for those in the RT group compared with 7.4% (90% CI, 4.9-11.0) for the no additional treatment group. In the 132 women who were in the high-risk subgroup, 28 (28 of 44; 64%) had a recurrence of disease and 22 died from disease (22 of 32; 67%). The estimated risk of recurrence for high-risk women was 0.46 (90% CI, 0.19-1.11) compared with 0.42 (90% CI, 0.21-0.83) for low-risk women. There were 2 deaths from intestinal injury associated with radiation treatrnent. Overall, there were 6 instances of bowel obstruction in the RT group and 1 in the no additional treatment group.