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Yeboah J, Carr JJ, Terry JG, Ding J, Zeb I, Liu S, Nasir K, Post W, Blumenthal RS, Budoff MJ.
Eur J Prev Cardiol. 2013 May 20. [Epub ahead of print]
PMID: 23689526
AIM: We assess the improvement in discrimination afforded by the addition of the computed tomography risk markers thoracic aorta calcium (TAC), aortic valve calcification (AVC), mitral annular calcification (MAC), pericardial adipose tissue volume (PAT), and liver attenuation (LA) to the Framingham risk score (FRS) + coronary artery calcium (CAC) for incident coronary heart disease (CHD) and incident cerebrovascular disease (CVD) in a multiethnic cohort. METHODS AND RESULTS: A total of 5745 participants were enrolled, with 2710 at intermediate Framingham risk, 210 CVD events, and 155 CHD events). Over 9 years of follow up, 251 had adjudicated CHD, 346 had CVD events, and 321 died. The data were analysed using Cox proportional hazard, receiver operator curve (ROC), and net reclassification improvement (NRI) analyses. In the whole cohort and also when the analysis was restricted to only the intermediate-risk participants, CAC, TAC, AVC, and MAC were all significantly associated with incident CVD, incident CHD, and mortality, and CAC had the strongest association. When added to the FRS, CAC had the highest area under the curve (AUC) for the prediction of incident CVD and incident CHD; LA had the least. The addition of TAC, AVC, MAC, PAT, and LA to FRS + CAC all resulted in a significant reduction in AUC for incident CHD (0.712 vs. 0.646, 0.655, 0.652, 0.648, and 0.569; all p < 0.01, respectively) in participants with intermediate FRS. The addition of CAC to FRS resulted in an NRI of 0.547 for incident CHD in the intermediate-risk group. The NRI when TAC, AVC, MAC, PAT, and LA were added to FRS + CAC were 0.024, 0.026, 0.019, 0.012, and 0.012, respectively, for incident CHD in the intermediate-risk group. Similar results were obtained for incident CVD in the intermediate-risk group and also when the whole cohort was used instead of the intermediate FRS group. CONCLUSIONS: The addition of CAC to the FRS provides superior discrimination especially in intermediate-risk individuals compared with the addition of TAC, AVC, MAC, PAT, or LA for incident CVD and incident CHD. Compared with FRS + CAC, the addition of TAC, AVC, MAC, PAT, or LA individually to FRS + CAC worsens the discrimination for incident CVD and incident CHD. These risk markers are unlikely to be useful for improving cardiovascular risk prediction.
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Taheri A, Mansoori P, Al-Dabagh A, Feldman S.
J Dermatolog Treat. 2013 May 20. [Epub ahead of print]
PMID: 23688200
Abstract Background: Superficial second degree skin burns only need re-epithelialization to heal without a scar. After re-epithelialization, inflammation in the dermis contributes to changes in skin architecture and scarring. Suppression of inflammation and fibroblast activation immediately after re-epithelialization may prevent scar formation. Corticosteroids are the mainstay of treatment for keloids and hypertrophic scars. Objective: To assess the available data on use of corticosteroids for prevention of scars. Methods: A review of literature was performed seeking clinical trials using corticosteroids for prevention of scars. Results: Corticosteroids have been used to prevent recurrence after keloid or hypertrophic scar excision with variable success. We did not find any report involving the clinical use of corticosteroids for the prevention of scar formation in other settings, including after skin burns. Conclusion: Theoretically, topical corticosteroids can suppress inflammation and fibroblast activation after skin burn, decreasing the incidence of scar formation. However, there is no study evaluating this hypothesis.
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Luersen K, Dabade TS, West C, Davis SA, Feldman S.
J Dermatolog Treat. 2013 May 20. [Epub ahead of print]
PMID: 23688185
Abstract Background: Use of phototherapy in the United States declined during the 1990s, largely due to unfavorable economic incentives. The trends in phototherapy since then are not well characterized. Methods: We analyzed the National Ambulatory Medical Care Survey (NAMCS) data on quantity of phototherapy visits and associated diagnoses and payment sources. Trends were assessed by linear regression. Results: There were an estimated 230,000 outpatient phototherapy visits per year, with an increasing trend over time (P=0.03). Dermatologists managed 87% of the visits. Leading diagnoses associated with phototherapy included psoriasis (25%), dermatitis NOS (6%), vitiligo (6%), other dyschromia (6%), and actinic keratosis (5%). Conclusions: Use of phototherapy for psoriasis has remained relatively low up to 2010. However, phototherapy may be becoming more frequent for conditions other than psoriasis.
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Del Gaizo A, Silva AC, Lam-Himlin DM, Allen BC, Leyendecker J, Kawashima A.
Insights Imaging. 2013 May 19. [Epub ahead of print]
PMID: 23686749
Solid urethral and peri-urethral lesions are rare and encompass benign and malignant aetiologies. A diagnosis without imaging is often challenging secondary to non-specific clinical symptoms and overlapping findings at the time of physical examination. Magnetic resonance (MR) imaging may be helpful in confirming a diagnosis while providing anatomical detail and delineating disease extent. This article reviews the normal MR anatomy of the male and female urethra, the MR appearance of solid primary and secondary urethral lesions, and the MR appearance of solid urethral lesion mimics. Teaching points • MRI is an important imaging technique in the evaluation of the spectrum of solid urethral lesions.• With excellent soft tissue resolution, MR is accurate in staging primary urethral carcinoma.• Disruption of the zonal anatomy of the female urethral wall indicates peri-urethral extension.• Be aware of benign urethral lesions, particularly those that may mimic solid urethral masses.
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Marcus S, Whitlow CT, Koonce J, Zapadka ME, Chen MY, Williams DW, Lewis M, Evans AK.
Int J Pediatr Otorhinolaryngol. 2013 May 17. [Epub ahead of print]
PMID: 23688380
OBJECTIVE: To investigate whether the effects of sex (male/female) that have been demonstrated in the pathology literature using 0.1mm histopathologic slices are measurable and statistically significant using high-resolution (0.625mm slice) computed tomography (CT). METHODS: IRB-approved retrospective analysis of high-resolution "normal" CT temporal bone images in pediatric subjects (0-18 years) using comparative anatomic measurements between males and females obtained from the semicircular canals, cochlea and vestibule as follows: (1) lateral semicircular canal (LSCC) bony island width, (2) superior semicircular canal (SSCC) bony island width, (3) central lucency of the LSCC bony island, (4) coronal cochlear height, (5) axial cochlear height, (6) cochlear length, (7) cochlea basal turn lumen width, (8) cochlear aperture width, (9) cochlear aperture height, (10) vestibular length, (11) vestibular width, and (12) coronal vestibule oblique diameter. RESULTS: Eighteen females (36 ears) and twenty males (36 ears) were included in the study. Independent-samples t-tests revealed statistically significant differences in measurements for females and males as follows (differences reported as a percentage and as an absolute difference (AD) in mm): (1) vestibular width was 4.2% (0.13mm AD) smaller in females (mean±SD; 3.0±0.27) compared to males (mean±SD; 3.2±0.25) [t(70)=2.083, p=0.041]; (2) cochlear length was 3.9% (.23mm AD) smaller in females (mean±SD; 5.8±0.32) compared to males (mean±SD; 6.0±0.40) [t(70)=2.660, p=0.010]; (3) cochlear aperture height was 11.6% (0.13mm AD) smaller in females (mean±SD; 1.0±0.18) compared to males (mean±SD; 1.2±0.22) [t(70)=2.549, p=0.013]; and (4) coronal cochlear height was 11.4% (0.55mm AD) smaller in females (mean±SD; 4.8±0.58) compared to males (mean±SD; 5.4±0.48) [t(68)=4.270, p<0.005]. CONCLUSION: Sexual dimorphism of inner ear structures may contribute to variability in reported normative and pathologic measurements of inner ear structures. This variability must be taken into consideration when designing future research studies to investigate inner ear structures and for drawing accurate conclusions about possible inner ear morphologic abnormalities associated with SNHL compared to controls.
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Rejeski WJ, Marsh AP, Anton S, Chen SH, Church T, Gill TM, Guralnik JM, Glynn NW, King AC, Rushing J, Ip EH.
J Gerontol A Biol Sci Med Sci. 2013 May 17. [Epub ahead of print]
PMID: 23685766
BACKGROUND: The measurement of mobility is essential to both aging research and clinical practice. A newly developed self-report measure of mobility, the mobility assessment tool-short form (MAT-sf), uses video animations to improve measurement accuracy/precision. Using a large baseline data set, we recalibrated the items, evaluated the extent to which older patients' self-efficacy (i.e., confidence) for walking was related to MAT-sf scores beyond their actual 400-m walk time, and assessed the relationship of the MAT-sf with body mass index and other clinical variables. METHODS: The analyses employed baseline data from the Lifestyle Interventions and Independence for Elders Study. RESULTS: Item recalibration demonstrated that the MAT-sf scoring algorithm was robust. In an analysis with 400-m walk time and self-efficacy regressed on the MAT-sf, both variables shared unique variance with the MAT-sf (p < .001). The MAT-sf was inversely related to several comorbidities, most notably hypertension and arthritis (p < .001), and scores were lowest when body mass index ≥ 35kg/m(2). Finally, MAT-sf scores were directly related to Short Physical Performance Battery scores, inversely related to difficulty with activities of daily living (p < .001) and higher for men than for women (p < .001). CONCLUSIONS: The findings extend the validity and clinical utility of this innovative tool for assessing self-reported mobility in older adults. Longitudinal data on the MAT-sf from the Lifestyle Interventions and Independence for Elders Study will enable us to evaluate the relative contributions of self-report and performance-based measures of mobility on important health outcomes.
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Shah SA, Kambur T, Chan C, Herrington DM, Liu K, Shah SJ.
Am J Cardiol. 2013 May 16. [Epub ahead of print]
PMID: 23683953
Whether autonomic dysfunction predates the development of symptomatic heart failure (HF) or is simply a consequence of severe HF is unknown. We hypothesized that reduced heart rate variability (a marker of abnormal autonomic function) at baseline is associated with incident HF in subjects free of clinically recognized cardiovascular disease. In the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of subclinical cardiovascular disease in adults aged 45 to 84 years, we measured the heart rate variability using a standard 30-second, 12-lead electrocardiogram to measure the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). During a median follow-up of 7.6 years, 95 participants developed HF (incidence rate 2.7/1,000 person-years). After adjusting for age, gender, and ethnicity, the hazard ratio for incident HF stratified by the RMSSD tertile was 2.4 (95% confidence interval 1.4 to 4.2) for the lowest tertile and 1.7 (95% confidence interval 1.0 to 3.2) for the middle tertile (highest tertile was the referent group; p for trend <0.001). The inverse association between the RMSSD and incident HF persisted after adjustment for additional covariates, including diabetes, systolic blood pressure, heart rate, subclinical atherosclerosis, left ventricular end-systolic volume, interim myocardial infarction, and high-sensitivity C-reactive protein (p for trend = 0.009). A similarly significant inverse association was also observed for SDNN. In conclusion, baseline autonomic dysfunction was a risk factor for the development of HF in a multiethnic cohort. These population-based findings implicate autonomic dysfunction in the pathogenesis of HF, and decreased short-term heart rate variability might be a novel form of stage B (asymptomatic) HF.
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Palmer NR, Geiger AM, Felder TM, Lu L, Case LD, Weaver KE.
Am J Public Health. 2013 May 16. [Epub ahead of print]
PMID: 23678936
Objectives. We examined racial/ethnic disparities in health care receipt among a nationally representative sample of male cancer survivors. Methods. We identified men aged 18 years and older from the 2006-2010 National Health Interview Survey who reported a history of cancer. We assessed health care receipt in 4 self-reported measures: primary care visit, specialist visit, flu vaccination, and pneumococcal vaccination. We used hierarchical logistic regression modeling, stratified by age (< 65 years vs ≥ 65 years). Results. In adjusted models, older African American and Hispanic survivors were approximately twice as likely as were non-Hispanic Whites to not see a specialist (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.19, 2.68 and OR = 2.09; 95% CI = 1.18, 3.70, respectively), not receive the flu vaccine (OR = 2.21; 95% CI = 1.45, 3.37 and OR = 2.20; 95% CI = 1.21, 4.01, respectively), and not receive the pneumococcal vaccine (OR = 2.24; 95% CI = 1.54, 3.24 and OR = 3.10; 95% CI = 1.75, 5.51, respectively). Conclusions. Racial/ethnic disparities in health care receipt are evident among older, but not younger, cancer survivors, despite access to Medicare. These survivors may be less likely to see specialists, including oncologists, and receive basic preventive care. (Am J Public Health. Published online ahead of print May 16, 2013: e1-e8. doi:10.2105/AJPH.2012.301096).
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Weaver KE, Palmer N, Lu L, Case LD, Geiger AM.
Cancer Causes Control. 2013 May 16. [Epub ahead of print]
PMID: 23677333
PURPOSE: Rural US adults have increased risk of poor outcomes after cancer, including increased cancer mortality. Rural-urban differences in health behaviors have been identified in the general population and may contribute to cancer health disparities, but have not yet been examined among US survivors. We examined rural-urban differences in health behaviors among cancer survivors and associations with self-reported health and health-related unemployment. METHODS: We identified rural (n = 1,642) and urban (n = 6,162) survivors from the cross-sectional National Health Interview Survey (2006-2010) and calculated the prevalence of smoking, physical activity, overweight/obesity, and alcohol consumption. Multivariable models were used to examine the associations of fair/poor health and health-related unemployment with health behaviors and rural-urban residence. RESULTS: The prevalence of fair/poor health (rural 36.7 %, urban 26.6 %), health-related unemployment (rural 18.5 %, urban 10.6 %), smoking (rural 25.3 %, urban 15.8 %), and physical inactivity (rural 50.7 %, urban 38.7 %) was significantly higher in rural survivors (all p < .05); alcohol consumption was lower (rural 46.3 %, urban 58.6 %), and there were no significant differences in overweight/obesity (rural 65.4 %, urban 62.6 %). All health behaviors were significantly associated with fair/poor health and health-related unemployment in both univariate and multivariable models. After adjustment for behaviors, rural survivors remained more likely than urban survivors to report fair/poor health (OR = 1.21, 95 % CI 1.03-1.43) and health-related unemployment (OR = 1.49, 95 % CI 1.18-1.88). CONCLUSIONS: Rural survivors may need tailored, accessible health promotion interventions to address health-compromising behaviors and improve outcomes after cancer.
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Andersson KE.
Curr Urol Rep. 2013 May 16. [Epub ahead of print]
PMID: 23677692
The new information generated over the last decade on the physiology/pharmacology of the normal bladder and on the pathophysiology of the overactive bladder has resulted in the introduction of a new therapeutic principle, β3-adrenoceptor (AR) agonism, and the approval of mirabegron, a selective agonist at β3-ARs. It may be asked in what respects the β3-AR agonists as a group, and mirabegron in particular, differ from the antimuscarinics, and what can clinically be gained by the β3-AR agonists. In this short review, the mechanisms of action, clinical efficacy, and adverse effect profiles of the two groups of drugs are compared and discussed.
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Cartwright MS, Walker FO.
Muscle Nerve. 2013 May 16. [Epub ahead of print]
PMID: 23681885
Neuromuscular ultrasound involves the use of high-resolution ultrasound to image the peripheral nervous system of patients with suspected neuromuscular diseases. It complements electrodiagnostic studies well by providing anatomic information regarding nerves, muscles, vessels, tendons, ligaments, bones, and other structures that cannot be obtained with nerve conduction studies and electromyography. Neuromuscular ultrasound has been studied closely over the past 10 years and has been used most often in the assessment of entrapment neuropathies. This review focuses on the use of neuromuscular ultrasound in 4 of the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow and wrist, and fibular neuropathy at the knee. © 2013 Wiley Periodicals, Inc.
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Gustafson CJ, Feldman SR, Quandt SA, Isom S, Chen H, Spears CR, Arcury TA.
Int J Dermatol. 2013 May 15. [Epub ahead of print]
PMID: 23675774
BACKGROUND: Skin conditions are common among Latino migrant farm workers. Although many skin conditions are related to occupational exposures, poor housing conditions may also contribute to skin ailments in migrant farm workers. OBJECTIVES: To evaluate the association between housing conditions and skin conditions among Latino migrant farm workers. MATERIALS AND METHODS: A cross-sectional study design using interview questionnaires, home inspections, and environmental sampling was implemented to document housing quality of farm worker camps/homes and the prevalence of self-reported skin conditions in Latino migrant farm workers. Interviews were completed with 371 farm workers residing in 186 of the 226 camps (camp response rate 82.3%). RESULTS: Self-reported pruritus (31%), rash (25%), scaling (12%), blisters (11%), and ingrown nails (10%) were common among the participants. Pruritus was more likely to be reported by farm workers living in dwellings without air-conditioning (P < 0.05). Rash was associated with dwellings reported to have a low humidity (P < 0.05). Scaling was more likely to be reported by farm workers living in dwellings with indoor temperatures in the thermal discomfort range (P < 0.05). No statistically significant associations were detected for indoor allergens and self-reported skin ailments among migrant farm workers. CONCLUSIONS: Skin conditions are common among migrant farm workers in North Carolina. The quality of housing conditions, particularly hot, dry indoor thermal environment, demonstrated significant associations with pruritus, rash, and scaling. The impact of housing characteristics on pruritus and blisters was greatest in new migrant farm workers. Further research is needed to delineate additional housing factors that could cause or exacerbate skin diseases in farm workers.
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Amoah S, Holbrook BC, Yammani RD, Alexander-Miller MA.
J Immunol. 2013 May 15;190(10):5020-9.
PMID: 23589620
Generating and maintaining a robust CD8(+) T cell response in the face of high viral burden is vital for host survival. Further, balancing the differentiation of effectors along the memory precursor effector cell pathway versus the short-lived effector cell (SLEC) pathway may be critical in controlling the outcome of virus infection with regard to clearance and establishing protection. Although recent studies have identified several factors that have the capacity to regulate effector CD8(+) T cell differentiation-for example, inflammatory cytokines-we are far from a complete understanding of how cells choose the memory precursor effector cell versus SLEC fate following infection. In this study, we have modulated the infectious dose of the poxvirus vaccinia virus as an approach to modulate the environment present during activation and expansion of virus-specific effector cells. Surprisingly, in the face of a high virus burden, the number of SLECs was decreased. This decrease was the result of increased natural regulatory T cells (Tregs) generated by high viral burden, as depletion of these cells restored SLECs. Our data suggest Treg modulation of differentiation occurs via competition for IL-2 during the late expansion period, as opposed to the time of T cell priming. These findings support a novel model wherein modulation of the Treg response as a result of high viral burden regulates late-stage SLEC number.
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Divers J, Núñez M, High KP, Murea M, Rocco MV, Ma L, Bowden DW, Hicks PJ, Spainhour M, Ornelles DA, Kleiboeker SB, Duncan K, Langefeld CD, Turner J, Freedman BI.
Kidney Int. 2013 May 15. [Epub ahead of print]
PMID: 23677244
Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30 mg/g), and kidney disease defined as an eGFR under 60 ml/min per 1.73 m(2) and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.Kidney International advance online publication, 15 May 2013; doi:10.1038/ki.2013.173.
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Sukumar P, Maloney G, Muday GK.
Plant Physiol. 2013 May 15. [Epub ahead of print]
PMID: 23677937
Adventitious roots emerge from aerial plant tissues and the induction of these roots is essential for clonal propagation of agriculturally important plant species. This process has received extensive study in horticultural species, but much less focus in genetically tractable model species. We have explored the role of auxin transport in this process in Arabidopsis thaliana seedlings in which adventitious root initiation was induced by excising roots from low light grown hypocotyls. Inhibition of auxin transport from the shoot apex abolishes adventitious root formation under these conditions. Root excision was accompanied by a rapid increase in radioactive IAA transport and its accumulation in the hypocotyl above the point of excision where adventitious roots emerge. Local increases in auxin-responsive gene expression were also observed above the site of excision, using auxin responsive reporters, pIAA2:GUS, pGH3:GUS, and pDR5:GUS. These changes in auxin accumulation preceded cell division events, monitored by pCYCB1:GUS, and adventitious root initiation. We examined excision-induced adventitious root formation in auxin influx and efflux mutants, including aux1, pin1, pin2, pin3, and pin7, with the most profound reductions observed in abcb19. An ABCB19 overexpression line forms more adventitious roots than wild-type in intact seedlings. Examination of transcriptional and translational fusions between ABCB19 and GFP indicates that excision locally induced the accumulation of ABCB19 transcript and protein that is temporally and spatially linked to local IAA accumulation leading to adventitious root formation. These experiments are consistent with localized synthesis of ABCB19 protein leading to enhanced IAA transport and local IAA accumulation driving adventitious root formation.
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O'Neal WT, Efird JT, Anderson CA, Kindell LC, O'Neal JB, Bruce Ferguson T, Randolph Chitwood W, Kypson AP.
Heart Lung Circ. 2013 May 14. [Epub ahead of print]
PMID: 23683716
BACKGROUND: Previous studies examining the influence of prior percutaneous coronary intervention (PCI) on long-term survival after coronary artery bypass grafting (CABG) have reported conflicting results. The purpose of this study was to further examine the influence of prior PCI on long-term survival after CABG at a large tertiary referral heart institute. METHODS: Long-term survival between 1992 and 2011 was compared in non-emergent CABG cases with and without prior PCI. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: A total of 2532 (19%) patients had prior PCI before CABG (n=13,354). The median follow-up for study participants was 8.1 years. The median survival for patients with and without prior PCI was 15 years and 14 years, respectively (p<0.0001). Long-term survival was similar between patients with and without prior PCI after adjusting for age, sex, race, hypertension, coronary artery disease severity, congestive heart failure, and prior stroke (adjusted HR=0.99, 95%CI=0.91-1.06). CONCLUSION: Findings from outcomes research are important in the planning of appropriate postoperative patient care. Our study provides additional evidence that prior PCI is not a significant predictor of long-term survival after CABG.
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Mondal AK, Sharma NK, Elbein SC, Das SK.
Physiol Genomics. 2013 May 14. [Epub ahead of print]
PMID: 23673729
Type-2 diabetes (T2D)-associated SNPs are more likely to be eQTLs. The allelic expression imbalance (AEI) analysis is the measure of relative expression between two allelic transcripts and is the most sensitive measurement to detect cis-regulatory effects. We performed AEI screening to detect cis-regulators for genes expressed in transformed lymphocytes of 190 Caucasian (CA) and African American (AA) subjects to identify functional variants for T2D susceptibility in the chromosome1q21-24 region of linkage. Among transcribed SNPs studied in 115 genes, significant AEI (p<0.001) occurred in 28 and 30 genes in CA and AA subjects, respectively. Analysis of the effect of selected AEI-SNPs (≥10% mean AEI) on total gene expression further established the cis-eQTLs in THEM4 (rs13320, p=0.027), and IGSF8 (rs1131891, p=0.02). Examination of published genome-wide association data identified significant associations (p<0.01) of three AEI-SNPs with T2D in the DIAGRAM-v3 dataset. Six AEI-SNPs, including rs13320 (p=1.35E-04) in THEM4, were associated with glucose homeostasis traits in the MAGIC dataset. Evaluation of AEI-SNPs for association with glucose homeostasis traits in 611 nondiabetic subjects showed lower AIRG (p=0.005) in those with TT/TC-genotype for rs13320. THEM4 expression in adipose was higher (p=0.005) in subjects carrying the T-allele; in vitro analysis with luciferase construct confirmed the higher expression of the T-allele. Resequencing of THEM4 exons in 192 CA subjects revealed four coding non-synonymous variants, but did not explain transmission of T2D in 718 subjects from 67 Caucasian pedigrees. Our study indicates the role of a cis-regulatory SNP in THEM4 that may influence T2D predisposition by modulating glucose homeostasis.
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Espeland MA, Rejeski WJ, West DS, Bray GA, Clark JM, Peters AL, Chen H, Johnson KC, Horton ES, Hazuda HP, .
J Am Geriatr Soc. 2013 May 13. [Epub ahead of print]
PMID: 23668423
OBJECTIVES: To compare the effects of 4 years of intensive lifestyle intervention on weight, fitness, and cardiovascular disease risk factors in older and younger individuals. DESIGN: Randomized controlled clinical trial. SETTING: Sixteen U.S. clinical sites. PARTICIPANTS: Individuals with type 2 diabetes mellitus: 1,053 aged 65 to 76 and 4,092 aged 45 to 64. INTERVENTIONS: An intensive behavioral intervention designed to promote and maintain weight loss through caloric restriction and increased physical activity was compared with diabetes mellitus support and education. MEASUREMENTS: Standardized assessments of weight, fitness (based on graded exercise testing), and cardiovascular disease risk factors. RESULTS: Over 4 years, older individuals had greater intervention-related mean weight losses (6.2%) than younger participants (5.1%; interaction P = .006) and comparable relative mean increases in fitness (0.56 vs 0.53 metabolic equivalents; interaction P = .72). These benefits were seen consistently across subgroups of older adults formed according to many demographic and health factors. Of a panel of age-related health conditions, only self-reported worsening vision was associated with poorer intervention-related weight loss in older individuals. The intensive lifestyle intervention produced mean increases in high-density lipoprotein cholesterol (2.03 mg/dL; P < .001) and decreases in glycated hemoglobin (0.21%; P < .001) and waist circumference (3.52 cm; P < .001) over 4 years that were at least as large in older as in younger individuals. CONCLUSION: Intensive lifestyle intervention targeting weight loss and increased physical activity is effective in overweight and obese older individuals to produce sustained weight loss and improvements in fitness and cardiovascular risk factors.
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Clarkson TB, Ethun KF, Pajewski NM, Golden D, Floyd E, Appt SE.
Menopause. 2013 May 13. [Epub ahead of print]
PMID: 23676638
OBJECTIVE: This study aims to evaluate the effects of a new selective estrogen receptor modulator (bazedoxifene acetate [BZA]) and a tissue-specific estrogen complex (BZA combined with conjugated equine estrogens [CEE]) on the extent and severity of cerebral artery atherosclerosis. METHODS: Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and randomized to receive no treatment or women's equivalent doses of BZA (20 mg/d), CEE (0.45 mg/d), or BZA + CEE. After an experimental period of 20 months (approximately equivalent to 5 years of participant experience), the extent and severity of atherosclerosis in the common carotid artery, carotid bifurcation, internal carotid artery, and basilar artery were determined. Lesion severity was determined using the American Heart Association grading system (grades 0-V). RESULTS: BZA had no consistent adverse effects on the extent and severity of atherosclerosis in the cerebral arteries and did not attenuate the beneficial effects of CEE on the severity of common carotid artery atherosclerosis. Although CEE had only modest beneficial effects on the extent of carotid bifurcation atherosclerosis, the severity of lesions and the number of affected cases in the common carotid artery were reduced with CEE treatment. As reported previously, plasma lipid profiles did not differ among the treatment groups. CONCLUSIONS: In this long-term (equivalent to 5 human patient-years) nonhuman primate trial, BZA shows no consistent adverse effect on cerebral artery atherosclerosis and does not attenuate the modest beneficial effect of CEE on the common carotid artery. Furthermore, CEE inhibits the development of complicated plaques in the common carotid artery.
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Iwano H, Little WC.
J Cardiol. 2013 May 11. [Epub ahead of print]
PMID: 23672790
Heart failure (HF) occurs across the entire range of left ventricular (LV) ejection fractions (EF), not just reduced EF. Nearly half or more patients presenting with HF have a preserved EF>0.50 (HFpEF). Diastolic dysfunction is apparent in all patients with HF, regardless of EF. A preserved EF indicates that the end-diastolic volume is appropriate for the stroke volume, and a reduced EF indicates that the end-diastolic volume is enlarged relative to stroke volume (i.e. the LV is dilated). Most therapies proven to be effective in HF with a reduced EF (ACE-inhibitors, angiotensin receptor blockers, beta-blockers, and cardiac resynchronization) reverse LV dilation. These therapies have not been proven to be effective in HFpEF. Increasing c-GMP may be a treatment target in HFpEF, and potential ways of increasing c-GMP are being studied. Finally, comorbidities are important in HFpEF and are additional targets for therapy.
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