Dale W.,Section of Geriatrics and Palliative Medicine |
Mohile S.G.,University of Rochester |
Eldadah B.A.,U.S. National Institute on Aging |
Trimble E.L.,U.S. National Cancer Institute |
And 8 more authors.
Journal of the National Cancer Institute | Year: 2012
In September 2010, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging, conducted the first of three planned conferences to discuss research methodology to generate the highest quality research in older adults with cancer and then disseminate these findings among those working in the fields of cancer and aging. Conference speakers discussed the current level of research evidence in geriatric oncology, outlined the current knowledge gaps, and put forth principles for research designs and strategies that would address these gaps within the next 10 years. It was agreed that future oncology research trials that enroll older adults should include: 1) improved standardized geriatric assessment of older oncology patients, 2) substantially enhanced biological assessment of older oncology patients, 3) specific trials for the most vulnerable and/or those older than 75 years, and 4) research infrastructure that specifically targets older adults and substantially strengthened geriatrics and oncology research collaborations. This initial conference laid the foundation for the next two meetings, which will address the research designs and collaborations needed to enhance therapeutic and intervention trials in older adults with cancer. © 2012 The Author.
Kalayjian R.C.,MetroHealth Medical Center |
Kalayjian R.C.,Washington University in St. Louis |
Wu K.,Geriatric Research Education and Clinical Centers |
Evans S.,Geriatric Research Education and Clinical Centers |
And 5 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2014
Background: Proteinuria is a marker of vascular dysfunction that predicted increased cardiovascular mortality and is associated with neurocognitive impairment (NCI) in population-based studies. We examined associations between proteinuria and HIV-Associated NCI. Methods: Multivariable logistic regression was used to examine associations between NCI at the first neurocognitive assessment (baseline) and simultaneous, clinically significant proteinuria [as random spot urine protein-to-creatinine ratios (UP/Cr) 200 mg/g] in a prospective multicenter observational cohort study. Generalized estimating equations were used to examine associations between baseline proteinuria and subsequent NCI among subjects without NCI at baseline. NCI was defined as a Z-score, derived from the combination of normalized scores from the Trailmaking A and B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol tests. Results: A total of 1972 subjects were included in this analysis. Baseline proteinuria was associated with increased odds of NCI [odds ratio (OR): 1.41, 95% confidence interval (CI): 1.08 to 1.85; P = 0.01] and with subsequent NCI among subjects without NCI at baseline (OR: 1.39, 95% CI: 1.01 to 1.93; P = 0.046) in multivariable models adjusted for risk factors and potential confounders. Similar associations were evident when these analyses were limited to visits at which time study subjects maintained plasma HIV RNA levels <200 copies per milliliter. Conclusions: The association between proteinuria and NCI observed in this study adds to a growing body of evidence implicating contributions by vascular disease to NCI in antiretroviral treated individuals. Studies examining interventions that improve vascular function are warranted. © 2014 by Lippincott Williams & Wilkins.
Itty S.,Duke Eye Center |
Day S.,Stanford University |
Lyles K.W.,Duke University |
Lyles K.W.,Geriatric Research Education and Clinical Centers |
And 4 more authors.
Retina | Year: 2014
PURPOSE:: To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. METHODS:: Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. RESULTS:: Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non-age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (<30 ng/mL 25OHD), deficiency (<20 ng/mL), and severe deficiency (<10 ng/mL) were highest in the NVAMD group. The highest quintile of 25OHD was associated with a 0.35 (95% confidence interval, 0.18-0.68) odds ratio for NVAMD. CONCLUSION:: This is the largest study to compare 25OHD levels in patients with the different clinical forms of age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD. Copyright © by Ophthalmic Communications Society, Inc.
Slentz C.A.,Duke University |
Bateman L.A.,Duke University |
Willis L.H.,Duke University |
Shields A.T.,Geriatric Research Education and Clinical Centers |
And 11 more authors.
American Journal of Physiology - Endocrinology and Metabolism | Year: 2011
While the benefits of exercise are clear, many unresolved issues surround the optimal exercise prescription. Many organizations recommend aerobic training (AT) and resistance training (RT), yet few studies have compared their effects alone or in combination. The purpose of this study, part of Studies Targeting Risk Reduction Interventions Through Defined Exercise-Aerobic Training and/or Resistance Training (STRRIDE/ AT/RT), was to compare the effects of AT, RT, and the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting insulin resistance [homeostatic model assessment (HOMA)]. In a randomized trial, 249 subjects [18-70 yr old, overweight, sedentary, with moderate dyslipidemia (LDL cholesterol 130-190 mg/dl or HDL cholesterol ≤ 40 mg/dl for men or ≤ 45 mg/dl for women)] performed an initial 4-mo run-in period. Of these, 196 finished the run-in and were randomized into one of the following 8-mo exercise-training groups: 1) RT, which comprised 3 days/wk, 8 exercises, 3 sets/ exercise, 8-12 repetitions/set, 2) AT, which was equivalent to ~ 19.2 km/wk (12 miles/wk) at 75% peak O2 uptake, and 3) full AT + full RT (AT/RT), with 155 subjects completing the intervention. The primary outcome variables were as follows: visceral and liver fat via CT, plasma liver enzymes, and HOMA. AT led to significant reductions in liver fat, visceral fat, alanine aminotransferase, HOMA, and total and subcutaneous abdominal fat (all P < 0.05). RT resulted in a decrease in subcutaneous abdominal fat (P < 0.05) but did not significantly improve the other variables. AT was more effective than RT at improving visceral fat, liver-to-spleen ratio, and total abdominal fat (all P < 0.05) and trended toward a greater reduction in liver fat score (P < 0.10). The effects of AT/RT were statistically indistinguishable from the effects of AT. These data show that, for overweight and obese individuals who want to reduce measures of visceral fat and fatty liver infiltration and improve HOMA and alanine aminotransferase, a moderate amount of aerobic exercise is the most time-efficient and effective exercise mode.
Otzel D.M.,University of Florida |
Otzel D.M.,Geriatric Research Education and Clinical Centers |
Chow J.W.,University of Florida |
Chow J.W.,Center for Neuroscience and Neurological Recovery |
And 2 more authors.
Physical Therapy in Sport | Year: 2015
Objective: Even some time after a ruptured ACL has been reconstructed thigh musculature atrophy, voluntary activation, and knee-extensor strength deficits may be encountered. The purpose of this study was to evaluate bilateral knee-extension strength, voluntary activation of the quadriceps, and thigh circumference in males and females with ACL reconstruction (ACLR). Design and participants: Within-subject and between-subject designs were used to evaluate 24 unilateral ACLR individuals and 23 controls. Main outcome measures: Isokinetic knee-extension strength was assessed in ACLR participants while central activation ratio (CAR) and thigh circumference measures were obtained from both groups. Results: Knee-extensor strength deficits (p<.039) and lower CAR of the quadriceps were found in the ACLR limb compared to the uninvolved limb (p=047). Extensor strength was greater in males (p<.001), however, CAR was not different between sexes (p=086). No difference in voluntary activation was revealed among the ACLR limb, uninvolved limb, and control limb when compared as independent groups (p=460). The strength deficits found in the ACLR limb are partly attributable to lower voluntary activation compared to the uninvolved leg, given that no difference was found in thigh circumference between legs. Conclusion: Clinicians should consider the deficits in muscle function when returning patients to pre-injury activity levels. © 2014.
Liu P.,University of Minnesota |
Paulson J.B.,University of Minnesota |
Forster C.L.,University of Minnesota |
Shapiro S.L.,University of Minnesota |
And 3 more authors.
PLoS ONE | Year: 2015
Amyloid plaques composed of β-amyloid (Aβ) protein are a pathological hallmark of Alzheimer's disease. We here report the generation and characterization of a novel transgenic mouse model of Aβ toxicity. The rTg9191 mice harbor a transgene encoding the 695 aminoacid isoform of human amyloid precursor protein (APP) with the Swedish and London mutations (APPNLI) linked to familial Alzheimer's disease, under the control of a tetracycline-response element, as well as a transgene encoding the tetracycline transactivator, under the control of the promoter for calcium-calmodulin kinase IIα. In these mice, APPNLI is expressed at a level four-fold that of endogenous mouse APP and its expression is restricted to forebrain regions. Transgene expression was suppressed by 87% after two months of doxycycline administration. Histologically, we showed that (1) Aβ plaques emerged in cerebral cortex and hippocampus as early as 8 and 10.5-12.5 months of age, respectively; (2) plaque deposition progressed in an age-dependent manner, occupying up to 19% of cortex at ∼25 months of age; and (3) neuropathology - such as abnormal neuronal architecture, tau hyperphosphorylation and misfolding, and neuroinflammation - was observed in the vicinity of neuritic plaques. Biochemically, we determined total Aβ production at varied ages of mice, and we showed that mice produced primarily fibrillar Aβ assemblies recognized by conformation-selective OC antibodies, but few non-fibrillar oligomers (e.g., Aβ∗56) detectable by A11 antibodies. Finally, we showed that expression of the tetracycline transactivator resulted in reduced brain weight and smaller dentate-gyrus size. Collectively, these data indicate that rTg9191 mice may serve as a model for studying the neurological effects of the fibrillar Aβ assemblies in situ. © 2015, Public Library of Science. All rights reserved.
Wang X.,Texas A&M University |
Wang S.,Texas A&M University |
Li C.,Texas A&M University |
Li C.,Harbin Medical University |
And 12 more authors.
PLoS Genetics | Year: 2012
Family with sequence similarity 20,-member C (FAM20C) is highly expressed in the mineralized tissues of mammals. Genetic studies showed that the loss-of-function mutations in FAM20C were associated with human lethal osteosclerotic bone dysplasia (Raine Syndrome), implying an inhibitory role of this molecule in bone formation. However, in vitro gain- and loss-of-function studies suggested that FAM20C promotes the differentiation and mineralization of mouse mesenchymal cells and odontoblasts. Recently, we generated Fam20c conditional knockout (cKO) mice in which Fam20c was globally inactivated (by crossbreeding with Sox2-Cre mice) or inactivated specifically in the mineralized tissues (by crossbreeding with 3.6 kb Col 1a1-Cre mice). Fam20c transgenic mice were also generated and crossbred with Fam20c cKO mice to introduce the transgene in the knockout background. In vitro gain- and loss-of-function were examined by adding recombinant FAM20C to MC3T3-E1 cells and by lentiviral shRNA-mediated knockdown of FAM20C in human and mouse osteogenic cell lines. Surprisingly, both the global and mineralized tissue-specific cKO mice developed hypophosphatemic rickets (but not osteosclerosis), along with a significant downregulation of osteoblast differentiation markers and a dramatic elevation of fibroblast growth factor 23 (FGF23) in the serum and bone. The mice expressing the Fam20c transgene in the wild-type background showed no abnormalities, while the expression of the Fam20c transgene fully rescued the skeletal defects in the cKO mice. Recombinant FAM20C promoted the differentiation and mineralization of MC3T3-E1 cells. Knockdown of FAM20C led to a remarkable downregulation of DMP1, along with a significant upregulation of FGF23 in both human and mouse osteogenic cell lines. These results indicate that FAM20C is a bone formation "promoter" but not an "inhibitor" in mouse osteogenesis. We conclude that FAM20C may regulate osteogenesis through its direct role in facilitating osteoblast differentiation and its systemic regulation of phosphate homeostasis via the mediation of FGF23. © 2012 Wang et al.
Davila E.P.,University of Miami |
Florez H.,Geriatric Research Education and Clinical Centers |
Fleming L.E.,University of Miami |
Lee D.J.,University of Miami |
And 8 more authors.
Diabetes Care | Year: 2010
OBJECTIVE - Differences in the prevalence of cardiovascular disease (CVD) and its risk factors among occupational groups have been found in several studies. Certain types of workers (such as shift workers) may have a greater risk for metabolic syndrome, a precursor of CVD. The objective of this study was to assess the differences in prevalence and risk of metabolic syndrome among occupational groups using nationally representative data of U.S. workers. RESEARCH DESIGN AND METHODS - Data from 8,457 employed participants (representing 131 million U.S. adults) of the 1999-2004 National Health and Nutrition Examination Survey were used. Unadjusted and age-adjusted prevalence and simple and multiple logistic regression analyses were conducted, adjusting for several potential confounders (BMI, alcohol drinking, smoking, physical activity, and sociodemographic characteristics) and survey design. RESULTS - Of the workers, 20% met the criteria for the metabolic syndrome, with "miscellaneous food preparation and food service workers" and "farm operators, managers, and supervisors" having the greatest age-adjusted prevalence (29.6-31.1%) and "writers, artists, entertainers, and athletes," and "engineers, architects, scientists" the lowest (8.5-9.2%). In logistic regression analyses "transportation/material moving" workers had significantly greater odds of meeting the criteria for metabolic syndrome relative to "executive, administrative, managerial" professionals (odds ratio 1.70 [95% CI 1.49-2.52]). CONCLUSIONS - There is variability in the prevalence of metabolic syndrome by occupational status, with "transportation/material moving" workers at greatest risk for metabolic syndrome. Workplace health promotion programs addressing risk factors for metabolic syndrome that target workers in occupations with the greatest odds may be an efficient way to reach at-risk populations. © 2010 by the American Diabetes Association.
Kale M.S.,Mount Sinai School of Medicine |
Ornstein K.A.,Mount Sinai School of Medicine |
Smith C.B.,Mount Sinai School of Medicine |
Kelley A.S.,Mount Sinai School of Medicine |
Kelley A.S.,Geriatric Research Education and Clinical Centers
Journal of the American Geriatrics Society | Year: 2016
Objectives: To determine the prevalence of end-of-life (EOL) conversations with older adults. Design: National Health and Aging Trends Study (NHATS), a prospective, longitudinal survey of Medicare beneficiaries. Setting: Nationally representative. Participants: A sample drawn from Wave 2 of the NHATS. Measurements: The main outcome was the report of an EOL planning discussion, based upon the participant's response to the question “Have you talked to anyone about the types of medical treatment you would want or not want if you became seriously ill in the future?”. Results: Sixty-one percent of the sample (n = 1,993 individuals, weighted n = 11,123,910) responded that they had discussed EOL treatment preferences with someone. In multivariate regression, factors associated with reporting an EOL discussion included being younger (adjusted odds ratio (AOR) = 1.70, 95% confidence interval (CI) = 1.17–2.47), having more education (high school degree: AOR = 1.45, 95% CI = 1.02–2.07; some college: AOR = 2.03, 95% CI = 1.40–2.95), and having multiple chronic conditions (AOR = 1.25, 95% CI = 1.01–1.55). Black race was associated with lower odds of reporting a discussion (AOR = 0.46, 95% CI = 0.33–0.65). Conclusion: Forty percent of a nationally representative sample of Medicare beneficiaries had not discussed their preferences regarding EOL medical treatment. Promoting these conversations in clinical and nonclinical settings will be important to ensure that health care is delivered to individuals in a person-centered manner. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society
Phosphodiesterase Type 5 Inhibitors as Adjunctive Therapy in the Management of Systolic Heart Failure [Inhibidores de la Fosfodiesterasa tipo 5 Como Tratamiento Adjunto en el Manejo de Fallo Cardiaco Sistólico]
Cvelich R.G.,Geriatric Research Education and Clinical Centers |
Roberts S.C.,Campbell University |
Brown J.N.,Durham Veterans Affairs Medical Center
Annals of Pharmacotherapy | Year: 2011
Objective: To review the efficacy and safety of phosphodiesterase-5 (PDE5) inhibitors in the treatment of patients with chronic systolic heart failure (HF). Data Sources: Literature was retrieved through MEDLINE (1966-September 2011) and EMBASE (1980-September 2011), using the medical subject heading terms heart failure and phosphodiesterase-5 inhibitors, sildenafil, tadalafil, and vardenafil. Focus was placed on multidose trials of patients with systolic HF, because of these trials' greater strength of clinical evidence. Study Selection And Data Extraction: All English-language, peer-reviewed publications were analyzed for relevance. Studies appropriate to the objective were evaluated, including 4 multidose trials investigating the effect of sildenafil on cardiovascular function. Data Synthesis: In patients with New York Heart Association class II or III HF, treatment with sildenafil was associated with improvements in cardiac index, right ventricular ejection fraction, and other markers of cardiovascular function, as well as reduced pulmonary arterial pressure. Study durations ranged from 4 weeks to 1 year, and the studies used varying doses of sildenafil, ranging from 75 to 225 mg/day, in divided doses. The most common adverse effects associated with sildenafil therapy were headache and flushing. Conclusions: Based on current studies, sildenafil appears to be well tolerated and can improve markers of cardiovascular and pulmonary function in patients with HF. PDE5 inhibitors may be a therapeutic option for patients who cannot tolerate standard therapy for HF or who remain symptomatic with standard therapy. Larger long-term trials are necessary to better understand the role of PDE5 inhibitors in HF.