84 results on '"Levy SA"'
Search Results
2. Investigation of the Anti-Inflammatory and Analgesic Effects of the Aqueous Extract Obtained from the Bark of Guiacum Officinale (Lignum Vitae)
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Williams, K, primary, Jacob, AS, additional, and Levy, SA, additional
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- 2015
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3. Improving Data Security with Blockchain and Internet of Things in the Gourmet Cocoa Bean Fermentation Process
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Jauberth Abijaude, Péricles Sobreira, Levy Santiago, and Fabíola Greve
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smart agriculture ,Internet of Things ,blockchain ,smart contracts ,DApp ,middleware ,Chemical technology ,TP1-1185 - Abstract
Brazil was one of the largest cocoa producers in the world, mainly supported by the South of Bahia region. After the 1980s, the witch-broom disease demolished plantations, and farmers were forced into bankruptcy. The worldwide search for gourmet cocoa has rekindled interest in this production, whose fermentation process is a key step in obtaining fine cocoa, thanks to the fact that many processing properties and sensory attributes are developed in this phase. This article presents a blockchain-IoT-based system for the control and monitoring of these events, aiming to catalog in smart contracts valuable information for improvement of the cocoa fermentation process, and future research. Blockchain is used as a distributed database that implements an application-level security layer. A proof of concept was modeled and the performance of the emulated system was evaluated in the OMNet simulator, where a technique based on the SNMP protocol was applied to reduce the amount of data exchanged and resources served/consumed in this representation. Then, a physical platform was developed and preliminary experiments were performed on a real farm, as a way to verify the improvement of the cocoa fermentation process when using a technological approach.
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- 2022
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4. Simulation models for implementation of lean production concepts in earthmoving and paving
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Levy Sarmento de Matos, Bruno de Athayde Prata, Ernesto Ferreira Nobre Júnior, and Francisco Heber Lacerda de Oliveira
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Lean construction ,Decision support systems ,Earthmoving ,Paving. ,Transportation engineering ,TA1001-1280 - Abstract
Studies show that, despite the resistance of professionals to new modes of production, the application of Lean Construction philosophy improves the operations productivity, reducing costs and improving the quality of the final product. However, methodologies which evaluate the impacts of the implementation of this philosophy to road construction operations are scarce. This study aims to verify the improvements that the application of the Lean Construction Philosophy can bring to earthwork and paving operations in a matter of execution time and overall cost by developing a computational model and simulating different application scenarios and checking their benefits through a comparison of activity durations and equipment costs. After model development and data analysis, it was found that the models that incorporated the guidelines of the Lean philosophy got faster (up to 30% reduction in runtime) and cheaper (reduction of up to 28% on cost) results in terms of use of equipment’s.
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- 2018
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5. Isoniazid Hepatitis
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Alonso K, Levy Sa, Stead Ww, Starke Wr, and Badger Tl
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Hepatitis ,business.industry ,Isoniazid ,Internal Medicine ,Medicine ,General Medicine ,business ,medicine.disease ,Virology ,medicine.drug - Published
- 1973
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6. Strengthening preventive care programs: a permanent challenge for healthcare systems; lessons from PREVENIMSS México
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Cantón Sonia, Acosta Benjamín, Reyes Hortensia, Levy Santiago, Pérez-Cuevas Ricardo, Gutiérrez Gonzalo, and Muñoz Onofre
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Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background In 2001, the Instituto Mexicano del Seguro Social (IMSS) carried out a major reorganization to provide comprehensive preventive care to reinforce primary care services through the PREVENIMSS program. This program divides the population into programmatic age groups that receive specific preventive services: children (0-9 years), adolescents (10-19 years), men (20-59 years), women (20-59 years) and older adults (> = 60 years). The objective of this paper is to describe the improvement of the PREVENIMSS program in terms of the increase of coverage of preventive actions and the identification of unmet needs of unsolved and emergent health problems. Methods From 2003 to 2006, four nation-wide cross-sectional probabilistic population based surveys were conducted using a four stage sampling design. Thirty thousand households were visited in each survey. The number of IMSS members interviewed ranged from 79,797 respondents in 2003 to 117,036 respondents in 2006. Results The four surveys showed a substantial increase in coverage indicators for each age group: children, completed schemes of vaccination (> 90%), iron supplementation (17.8% to 65.5%), newborn screening for metabolic disorders (60.3% to 81.6%). Adolescents, measles - rubella vaccine (52.4% to 71.4%), hepatitis vaccine (9.3% to 46.2%), use of condoms (17.9% to 59.9%). Women, measles-rubella vaccine (28.5% to 59-2%), cervical cancer screening (66.7% to 75%), breast cancer screening (> 2.1%). Men, type 2 diabetes screening (38.6% to 57.8%) hypertension screening (48-4% to 64.0%). Older adults, pneumococcal vaccine (13.2% to 24.9%), influenza vaccine (12.6% to 52.9) Regarding the unmet needs, the prevalence of anemia in children was 30% and a growing prevalence of overweight and obesity, type 2 diabetes, and hypertension was found in men, women and older adults. Conclusion PREVENIMSS showed an important increase in the coverage of preventive services and stressed the magnitude of the old and new challenges that this healthcare system faces. The unsolved problems such as anemia, and the emerging ones such as overweight, obesity, among others, point out the need to strength preventive care through designing and implementing innovative programs aimed to attain effective coverage for those conditions in which prevention obtains substandard results.
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- 2010
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7. A general modeling and visualization tool for comparing different members of a group: application to studying tau-mediated regulation of microtubule dynamics
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Wilson Leslie, Gaylord Michelle, LeBoeuf Adria, Levy Sasha, Bhattacharya Arnab, Singh Ambuj K, and Feinstein Stuart C
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Innumerable biological investigations require comparing collections of molecules, cells or organisms to one another with respect to one or more of their properties. Almost all of these comparisons are performed manually, which can be susceptible to inadvertent bias as well as miss subtle effects. The development and application of computer-assisted analytical and interpretive tools could help address these issues and thereby dramatically improve these investigations. Results We have developed novel computer-assisted analytical and interpretive tools and applied them to recent studies examining the ability of 3-repeat and 4-repeat tau to regulate the dynamic behavior of microtubules in vitro. More specifically, we have developed an automated and objective method to define growth, shortening and attenuation events from real time videos of dynamic microtubules, and demonstrated its validity by comparing it to manually assessed data. Additionally, we have used the same data to develop a general strategy of building different models of interest, computing appropriate dissimilarity functions to compare them, and embedding them on a two-dimensional plot for visualization and easy comparison. Application of these methods to assess microtubule growth rates and growth rate distributions established the validity of the embedding procedure and revealed non-linearity in the relationship between the tau:tubulin molar ratio and growth rate distribution. Conclusion This work addresses the need of the biological community for rigorously quantitative and generally applicable computational tools for comparative studies. The two-dimensional embedding method retains the inherent structure of the data, and yet markedly simplifies comparison between models and parameters of different samples. Most notably, even in cases where numerous parameters exist by which to compare the different samples, our embedding procedure provides a generally applicable computational strategy to detect subtle relationships between different molecules or conditions that might otherwise escape manual analyses.
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- 2008
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8. Novel computational methods for increasing PCR primer design effectiveness in directed sequencing
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Busam Dana, McIntosh Tina C, Beeson Karen, Stockwell Timothy B, Brownley Anushka, Li Kelvin, Ferriera Steve, Murphy Sean, and Levy Samuel
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Polymerase chain reaction (PCR) is used in directed sequencing for the discovery of novel polymorphisms. As the first step in PCR directed sequencing, effective PCR primer design is crucial for obtaining high-quality sequence data for target regions. Since current computational primer design tools are not fully tuned with stable underlying laboratory protocols, researchers may still be forced to iteratively optimize protocols for failed amplifications after the primers have been ordered. Furthermore, potentially identifiable factors which contribute to PCR failures have yet to be elucidated. This inefficient approach to primer design is further intensified in a high-throughput laboratory, where hundreds of genes may be targeted in one experiment. Results We have developed a fully integrated computational PCR primer design pipeline that plays a key role in our high-throughput directed sequencing pipeline. Investigators may specify target regions defined through a rich set of descriptors, such as Ensembl accessions and arbitrary genomic coordinates. Primer pairs are then selected computationally to produce a minimal amplicon set capable of tiling across the specified target regions. As part of the tiling process, primer pairs are computationally screened to meet the criteria for success with one of two PCR amplification protocols. In the process of improving our sequencing success rate, which currently exceeds 95% for exons, we have discovered novel and accurate computational methods capable of identifying primers that may lead to PCR failures. We reveal the laboratory protocols and their associated, empirically determined computational parameters, as well as describe the novel computational methods which may benefit others in future primer design research. Conclusion The high-throughput PCR primer design pipeline has been very successful in providing the basis for high-quality directed sequencing results and for minimizing costs associated with labor and reprocessing. The modular architecture of the primer design software has made it possible to readily integrate additional primer critique tests based on iterative feedback from the laboratory. As a result, the primer design software, coupled with the laboratory protocols, serves as a powerful tool for low and high-throughput primer design to enable successful directed sequencing.
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- 2008
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9. Providers' experiences with identification, management and referral of adolescents with depression.
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Stevens SL, Kinsman SB, Pailler ME, Latif S, Levy SA, and Diamond GS
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- 2007
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10. A systematic comparison of deforestation drivers and policy effectiveness across the Amazon biome
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Aline Hänggli, Samuel Levy, Dolors Armenteras Pascual, Isabella Bovolo, Joyce Brandao, Ximena Rueda, Rachael D. Garrett, Levy, SA [0000-0003-0189-0036], Armenteras, D [0000-0003-0922-7298], Bovolo, CI [0000-0001-5750-5040], Rueda, X [0000-0002-5991-4048], Garrett, RD [0000-0002-6171-263X], and Apollo - University of Cambridge Repository
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land systems science ,sustainable development ,Renewable Energy, Sustainability and the Environment ,Public Health, Environmental and Occupational Health ,South America ,policy ,General Environmental Science - Abstract
The Amazon biome, spanning nine countries, has one of the highest rates of deforestation worldwide. This deforestation contributes to biodiversity loss, climate change, the spread of infectious diseases, and damage to rural and indigenous livelihoods. Hundreds of articles have been published on the topic of deforestation across Amazonia, yet there has been no recent synthesis of deforestation drivers and deforestation-control policy effectiveness in the region. Here we undertook the first systematic review of papers published between 2000 and 2021 that have causally linked proximate and underlying drivers and policies to deforestation outcomes in Amazonia. In the 155 articles that met our inclusion criteria, we find that causal research is concentrated in Brazil, and to a lesser degree Peru, Ecuador, and Bolivia. There has been little study of the Guianas, Venezuela or Colombia. Large- and small-scale agriculture linked to improved market access and high agricultural prices are frequently researched underlying drivers of deforestation across the heavily researched regions. In the Guianas research focuses on mining with little focus on underlying causes. Research on infrastructure expansion, mining, and oil extraction and on technological, sociocultural, and institutional factors remains sparse. Many public and private policies have been found to be effective in controlling deforestation across the biome, with protected areas and public policies standing out as particularly successful in slowing deforestation vis-a-vis supply chain approaches. Frontier age, land tenure, and policy interactions are key moderating factors affecting the outcomes of different underlying causes and policies. Our findings indicate a greater need for research on (i) additional deforestation drivers beyond agriculture and economic factors, (ii) the complex interactions between different drivers and deforestation control policies, (iii) causes underlying deforestation in low or new deforestation areas, and (iv) the dynamics between Amazonian subregions and countries. Understanding the extent and diversity of deforestation drivers and effectiveness of existing deforestation mitigation policies across Amazonia is a necessary first step toward designing policies to further reduce deforestation in the biome., Environmental Research Letters, 18 (7), ISSN:1748-9326, ISSN:1748-9318
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- 2023
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11. Neuroimaging and biofluid biomarkers across race and ethnicity in older adults across the spectrum of cognition.
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Wang WE, Asken BM, DeSimone JC, Levy SA, Barker W, Fiala JA, Velez-Uribe I, Curiel Cid RE, Rósselli M, Marsiske M, Adjouadi M, Loewenstein DA, Duara R, Smith GE, Armstrong MJ, Barnes LL, Vaillancourt DE, and Coombes SA
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- Humans, Cognition physiology, Aged, Ethnicity, Alzheimer Disease ethnology, Alzheimer Disease diagnosis, Cognitive Dysfunction ethnology, Cognitive Dysfunction diagnosis, Cognitive Dysfunction blood, Racial Groups, Biomarkers blood, Neuroimaging methods
- Abstract
Neuroimaging and biofluid biomarkers provide a proxy of pathological changes for Alzheimer's disease (AD) and are useful in improving diagnosis and assessing disease progression. However, it is not clear how race/ethnicity and different prevalence of AD risks impact biomarker levels. In this narrative review, we survey studies focusing on comparing biomarker differences between non-Hispanic White American(s) (NHW), African American(s) (AA), Hispanic/Latino American(s) (HLA), and Asian American(s) with normal cognition, mild cognitive impairment, and dementia. We found no strong evidence of racial and ethnic differences in imaging biomarkers after controlling for cognitive status and cardiovascular risks. For biofluid biomarkers, in AA, higher levels of plasma Aβ42/Aβ40, and lower levels of CSF total tau and p-tau 181, were observed after controlling for APOE status and comorbidities compared to NHW. Examining the impact of AD risks and comorbidities on biomarkers and their contributions to racial/ethnic differences in cognitive impairment are critical to interpreting biomarkers, understanding their generalizability, and eliminating racial/ethnic health disparities., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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12. Plasma p-tau217 concordance with amyloid PET among ethnically diverse older adults.
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Asken BM, DeSimone JC, Wang WE, McFarland KN, Arias F, Levy SA, Fiala J, Velez-Uribe I, Mayrand RP, Sawada LO, Freytes C, Adeyosoye M, Barker WW, Crocco EA, DeKosky ST, Adjouadi M, Rosselli M, Marsiske M, Armstrong MJ, Smith GE, Cid RC, Loewenstein DA, Vaillancourt DE, and Duara R
- Abstract
Introduction: Commercially available plasma p-tau217 biomarker tests are not well studied in ethnically diverse samples., Methods: We evaluated associations between ALZPath plasma p-tau217 and amyloid-beta positron emission tomography (Aβ-PET) in Hispanic/Latino (88% of Cuban or South American ancestry) and non-Hispanic/Latino older adults. One- and two-cutoff ranges were derived and evaluated to assess agreement with Aβ-PET., Results: A total of 239 participants underwent blood draw and Aβ-PET (age 70.8 ± 7.8, 55.2% female, education 15.6 ± 3.4 years, 48.9% Hispanic/Latino, 94.9% white). Plasma p-tau217 showed excellent discrimination of Aβ-PET positive and negative participants (visual read: AUC = 0.91 [0.87-0.95], p < 0.001; Centiloids quantification: AUC = 0.90 [0.86-0.94]). There was a greater percent agreement between low p-tau217 and negative Aβ-PET (95.8%) than high p-tau217 and positive Aβ-PET (86.3%). Analyses within ethnicity-specific subgroups suggested similar p-tau217 performance., Discussion: Plasma p-tau217 (ALZPath) relates to brain Aβ in Hispanic/Latino and non-Hispanic/Latino older adults. Independent validation and replication are necessary to establish reference ranges and inform appropriate contexts of use across ethno-racially diverse populations., Highlights: Plasma p-tau217 (ALZPath) and Aβ-PET were measured in Hispanic/Latino and non-Hispanic/Latino older adults.Plasma p-tau217 accurately discriminated Aβ-PET positive and negative participants.Applying a two-cutoff "intermediate" plasma p-tau217 approach could reduce need for more invasive and costly testing.Plasma p-tau217 associations with Aβ-PET were strong within both Hispanic/Latino and non-Hispanic/Latino groups., Competing Interests: The authors report no disclosures relevant to the content of this work. STDeK reports being a consultant with Biogen, Prevail, Vaccinex, and Acumen Dementia. DEV reports consulting for Neuroimaging Solutions. All other authors report no disclosures. Author disclosures are available in the Supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2024
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13. Multimodal cognitive and behavioral interventions for patients with MCI: a systematic review and meta-analysis on cognition and mood.
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Ying G, Perez-Lao A, Marsiske M, Levy SA, and Smith GE
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Background: Research has increasingly suggested a benefit to combining multiple cognitive or behavioral strategies in a single treatment program for cognitively impaired older adults. Therefore, this systematic review and meta-analysis aimed to summarize results on the effects of multimodal cognitive and behavioral interventions versus control conditions on changes in cognition and mood in patients with mild cognitive impairment (pwMCI)., Methods: The review followed a general PRISMA guideline for systematic literature review with a format consisting of participants, interventions, comparators, and outcomes (PICO). Multilevel meta-analyses of aggregated efficacy were performed to assess the pooled effect sizes for cognitive and mood outcomes. Risk-of-bias, heterogeneity across studies, and publication bias were assessed for each outcome., Results: After primary and reference searches, 18 studies with low or some concerns of risk of bias were included. Low heterogeneity was found for mood and cognition. Funnel plots did not indicate publication bias. All the studies assessed changes in cognition ( n = 1,555) while seven studies with mood outcomes ( n = 343) were included. Multilevel meta-analyses demonstrated moderate effect (Hedge's g = 0.44, 95% CI = [0.21-0.67]) in cognitive outcomes and large effect in mood ( g = 0.65, 95% CI = [0.37-0.93]). Subdomain analyses found low-moderate effects in global cognition, verbal and non-verbal memory, executive function, visuospatial abilities, and semantic fluency (0.20 < g < 0.50)., Conclusion: These findings showed comparable to larger effects of multimodal cognitive and behavioral interventions on cognition than pharmacological treatment. Future studies should focus on the longitudinal effects of multimodal interventions in delaying dementia. Systematic review registration : PROSEPRO, CRD42022349297., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ying, Perez-Lao, Marsiske, Levy and Smith.)
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- 2024
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14. Depression, Vascular Burden, and Dementia Prevalence in Late Middle-Aged and Older Black Adults.
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Levy SA, Misiura MB, Grant JG, Adrien TV, Taiwo Z, Armstrong R, and Dotson VM
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- Humans, Middle Aged, Aged, Prevalence, Magnetic Resonance Imaging, Brain, Vascular Depression, Dementia epidemiology
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Objectives: Late-life depression and white matter hyperintensities (WMH) have been linked to increased dementia risk. However, there is a dearth of literature examining these relationships in Black adults. We investigated whether depression or WMH volume are associated with a higher likelihood of dementia diagnosis in a sample of late middle-aged to older Black adults, and whether dementia prevalence is highest in individuals with both depression and higher WMH volume., Methods: Secondary data analysis involved 443 Black participants aged 55+ with brain imaging within 1 year of baseline visit in the National Alzheimer's Coordinating Center Uniform Data Set. Chi-square analyses and logistic regression models controlling for demographic variables examined whether active depression in the past 2 years, WMH volume, or their combination were associated with higher odds of all-cause dementia., Results: Depression and higher WMH volume were associated with a higher prevalence of dementia. These associations remained after controlling for demographic factors, as well as vascular disease burden. Dementia risk was highest in the depression/high WMH volume group compared to the depression-only group, high WMH volume-only group, and the no depression/low WMH volume group. Post hoc analyses comparing the Black sample to a demographically matched non-Hispanic White sample showed associations of depression and the combination of depression and higher WMH burden with dementia were greater in Black compared to non-Hispanic White individuals., Discussion: Results suggest late-life depression and WMH have independent and joint relationships with dementia and that Black individuals may be particularly at risk due to these factors., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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15. Procedural learning, declarative learning, and working memory as predictors of learning the use of a memory compensation tool in persons with amnestic mild cognitive impairment.
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De Wit L, Levy SA, Kurasz AM, Amofa P Sr, DeFeis B, O'Shea D, Chandler MJ, and Smith GE
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- Humans, Cross-Sectional Studies, Learning, Memory Disorders, Neuropsychological Tests, Memory, Short-Term, Cognitive Dysfunction
- Abstract
Persons with amnestic Mild Cognitive Impairment (aMCI) are at risk for experiencing changes in their daily functioning due to their memory impairment. The Memory Support System (MSS), a compensatory calendaring system, was developed to support functional independence in persons with aMCI (pwaMCI). This cross-sectional study examined procedural learning, declarative learning, and working memory as predictors of MSS learning efficiency in pwaMCI. Sixty pwaMCI participated in MSS training. The Serial Reaction Time Test and Mirror Tracing Test were used to assess procedural learning. The Rey Auditory Verbal Learning Test and CogState One Card Learning were used to assess declarative learning and the CogState One Back task was used to assess working memory. Multiple regression analyses were conducted to assess if procedural learning, declarative learning, and working memory predicted MSS learning efficiency. This study showed that declarative learning predicted MSS learning efficiency in pwaMCI, with less consistent results for procedural learning and non-significant results for working memory. Findings suggest that success in teaching compensatory tools is greater when training is offered in early aMCI before declarative learning skill is fully lost. Future studies should assess additional strategies to facilitate MSS learning in advanced aMCI.
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- 2023
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16. Health concerns and attitudes towards research participation in a community of rural Black Americans.
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Amofa PA, Kurasz AM, Smith GE, and Levy SA
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- Humans, Attitude to Health, Health Knowledge, Attitudes, Practice, Focus Groups, Black or African American, Dementia
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Objectives: Describe health concerns of Black Americans as they age and what influences their participation in aging and clinical research., Methods: Fifty participants attended focus groups and completed questionnaires to identify barriers to research participation and attitudes toward dementia screening. Bivariate correlations explored associations between barriers to research participation and attitudes toward dementia screening., Results: Cancer, hereditary conditions, vascular conditions, memory disorders, and psychological disorders were the greatest health concerns. Time demands, mistrust, lack of knowledge about potential research, and stigma were identified as barriers for research participation. Incentives, better understanding of how proposed research will benefit the community, lifestyle modification studies, active presence of principal researchers/clinicians, and community investment were identified as factors to improve participation. Questionnaires revealed mistrust and religious beliefs to be among the primary barriers. Attitudes toward dementia screening reflected perceived stigma, suffering, and subsequent loss of independence. Higher barriers to participation were associated with perceived stigma and loss of independence related to dementia screening., Conclusions: Successfully recruiting Black Americans for aging and clinical research remains a challenge. This study identifies barriers to participation and offers suggestions for planning and recruitment.
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- 2023
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17. An investigation of SMART Recovery: protocol for a longitudinal cohort study of individuals making a new recovery attempt from alcohol use disorder.
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Kelly JF, Levy SA, and Hoeppner BB
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- Humans, Longitudinal Studies, Cohort Studies, Quality of Life, Alcoholism therapy, Alcoholism psychology, Self-Management
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Introduction: Alcohol use disorder (AUD) remains one of the most pervasive of all psychiatric illnesses conferring a massive health and economic burden. In addition to professional treatments to address AUD, mutual-help organisations such as Alcoholics Anonymous (AA) and newer entities like Self-Management and Recovery Training (SMART Recovery) play increasingly important roles in many societies. While much is known about the positive effects of AA, very little is known about SMART. Hence, this study seeks to estimate real-world patterns of utilisation and benefit from SMART Recovery as well as explore for whom (moderators) and how (mechanisms) SMART confers recovery benefits., Methods and Analysis: Naturalistic, longitudinal, cohort study (n=368) of individuals with AUD recruited between February 2019 and February 2022, initiating a new recovery attempt who self-select into one of four groups at study entry: (1) SMART Recovery; (2) AA; (3) SMART+AA; (4) Neither SMART nor AA; (stratified by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) severity markers), with assessments conducted at intake, and 3 months, 6 months, 9 months, 12 months, 18 months and 24 months. Primary outcomes are: frequency of SMART and AA meetings attendance; per cent days abstinent and per cent days heavy drinking. Secondary outcomes include psychiatric distress; quality of life and functioning. Moderator variables include sex/gender; race/ethnicity; spirituality. Mediational variables include social networks; coping skills; self-efficacy; impulsivity. Multivariable regression with propensity score matching will test for patterns of attendance and effects of participation over time on outcomes and test for mechanisms and moderators., Ethics and Dissemination: This study involves human participants and was approved by the Massachusetts General Hospital Institutional Review Board (Protocol #: 2017P002029/PHS). Results will be published in peer-reviewed journals and presented at conferences., Registration: This is a non-randomised, naturalistic, longitudinal, cohort study, and thus was not registered in advance. Results, therefore, should be considered exploratory., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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18. Exploration and analysis of R-loop mapping data with RLBase.
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Miller HE, Montemayor D, Li J, Levy SA, Pawar R, Hartono S, Sharma K, Frost B, Chedin F, and Bishop AJR
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- DNA genetics, DNA chemistry, Hybridization, Genetic, Nucleic Acid Hybridization, RNA genetics, RNA chemistry, R-Loop Structures, Databases, Genetic
- Abstract
R-loops are three-stranded nucleic acid structures formed from the hybridization of RNA and DNA. In 2012, Ginno et al. introduced the first R-loop mapping method. Since that time, dozens of R-loop mapping studies have been conducted, yielding hundreds of publicly available datasets. Current R-loop databases provide only limited access to these data. Moreover, no web tools for analyzing user-supplied R-loop datasets have yet been described. In our recent work, we reprocessed 810 R-loop mapping samples, building the largest R-loop data resource to date. We also defined R-loop consensus regions and developed a framework for R-loop data analysis. Now, we introduce RLBase, a user-friendly database that provides the capability to (i) explore hundreds of public R-loop mapping datasets, (ii) explore R-loop consensus regions, (iii) analyze user-supplied data and (iv) download standardized and reprocessed datasets. RLBase is directly accessible via the following URL: https://gccri.bishop-lab.uthscsa.edu/shiny/rlbase/., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2023
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19. Hippocampal Subfields in Mild Cognitive Impairment: Associations with Objective and Informant-Report of Memory Function.
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O'Shea DM, de Wit L, Tanner J, Mejia Kurasz A, Amofa P, Perez Lao A, Levy SA, Chandler M, and Smith G
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- Humans, Aged, Neuropsychological Tests, Magnetic Resonance Imaging, Hippocampus diagnostic imaging, Cognitive Dysfunction diagnosis, Alzheimer Disease
- Abstract
Background: Evidence suggests that select hippocampal subfields are implicated in the initial stages of Alzheimer's disease (AD) and are selectively involved in objective memory. Less is known whether subfields are associated with informant-reported memory difficulties of individuals with a diagnosis of mild cognitive impairment (MCI)., Method: Data from 56 participants with a diagnosis of amnestic MCI were included in the present study. To test whether FreeSurfer derived hippocampal subfields (CA1-4, subiculum, presubiculum, and dentate gyrus) were associated with objective (learning and delayed recall) and informant-reports of memory difficulties, we used multiple linear regression analysis. Subfields were adjusted for total intracranial volume, and age, sex, and years of education were included as covariates in all models., Results: Larger presubiculum, subiculum, and CA4/dentate gyrus volumes were associated with higher delayed recall scores, and larger subiculum and CA4/dentate gyrus volumes were associated with fewer informant-reports of memory difficulties. There were no statistically significant associations between subfields and learning scores., Discussion: Findings from the present study support the idea that difficulties with memory-dependent everyday tasks in older adults with MCI may signal a neurodegenerative process while increasing understanding of subfields correlates of these memory-specific functional difficulties. Continued investigations into identifying patterns of subfield atrophy in AD may aid early identification of those at higher risk of dementia conversion while advancing precision medicine., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)
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- 2022
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20. Tau LUM , an in vivo Drosophila sensor of tau multimerization, identifies neuroprotective interventions in tauopathy.
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Levy SA, Zuniga G, Gonzalez EM, Butler D, Temple S, and Frost B
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- Animals, Drosophila metabolism, tau Proteins genetics, Animals, Genetically Modified, Cell Death, Tauopathies drug therapy, Alzheimer Disease genetics
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Tau protein aggregates are a defining neuropathological feature of "tauopathies," a group of neurodegenerative disorders that include Alzheimer's disease. In the current study, we develop a Drosophila split-luciferase-based sensor of tau-tau interaction. This model, which we term "tau
LUM ," allows investigators to quantify tau multimerization at individual time points or longitudinally in adult, living animals housed in a 96-well plate. TauLUM causes cell death in the adult Drosophila brain and responds to both pharmacological and genetic interventions. We find that transgenic expression of an anti-tau intrabody or pharmacological inhibition of HSP90 reduces tau multimerization and cell death in tauLUM flies, establishing the suitability of this system for future drug and genetic modifier screening. Overall, our studies position tauLUM as a powerful in vivo discovery platform that leverages the advantages of the Drosophila model organism to better understand tau multimerization., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)- Published
- 2022
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21. Quality-controlled R-loop meta-analysis reveals the characteristics of R-loop consensus regions.
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Miller HE, Montemayor D, Abdul J, Vines A, Levy SA, Hartono SR, Sharma K, Frost B, Chédin F, and Bishop AJR
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- Consensus, DNA chemistry, Nucleic Acid Hybridization, R-Loop Structures, RNA chemistry, RNA genetics
- Abstract
R-loops are three-stranded nucleic acid structures formed from the hybridization of RNA and DNA. While the pathological consequences of R-loops have been well-studied to date, the locations, classes, and dynamics of physiological R-loops remain poorly understood. R-loop mapping studies provide insight into R-loop dynamics, but their findings are challenging to generalize. This is due to the narrow biological scope of individual studies, the limitations of each mapping modality, and, in some cases, poor data quality. In this study, we reprocessed 810 R-loop mapping datasets from a wide array of biological conditions and mapping modalities. From this data resource, we developed an accurate R-loop data quality control method, and we reveal the extent of poor-quality data within previously published studies. We then identified a set of high-confidence R-loop mapping samples and used them to define consensus R-loop sites called 'R-loop regions' (RL regions). In the process, we identified a stark divergence between RL regions detected by S9.6 and dRNH-based mapping methods, particularly with respect to R-loop size, location, and colocalization with RNA binding factors. Taken together, this work provides a much-needed method to assess R-loop data quality and offers novel context regarding the differences between dRNH- and S9.6-based R-loop mapping approaches., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2022
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22. Factors in the neurodevelopment of negative urgency: Findings from a community-dwelling sample.
- Author
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Evans CL, Sawyer KS, Levy SA, Conklin JP, McDonough E, and Gansler DA
- Abstract
This study investigated neuroanatomic, genetic, cognitive, sociodemographic and emotional underpinnings of the Negative Urgency subscale of the Urgency, Premeditation, Perseverance, Sensation-Seeking and Positive Urgency Impulsive Behavior Scale in a healthy developmental sample. The goal of the investigation is to contribute to the harmonisation of behavioural, brain and neurogenetic aspects of behavioural self-control. Three domains - (1) Demographic, developmental, psychiatric and cognitive ability; (2) Regional brain volumes (neurobiological); and (3) Genetic variability (single nucleotide polymorphisms) - were examined, and models with relevant predictor variables were selected. Least absolute shrinkage and selection operator and best subset regressions were used to identify sparse models predicting negative urgency scores, which revealed that variables related to emotional regulation and right cingulate volume, as well as single nucleotide polymorphisms in CADM2 and SLC6A4 , were associated with negative urgency. Our results contribute to the construct and criterion validity of negative urgency and support the hypothesis that negative urgency is a result of a complex array of influences across domains whose integration furthers developmental psychopathology research., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)
- Published
- 2022
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23. Behavioral Interventions in Mild Cognitive Impairment (MCI): Lessons from a Multicomponent Program.
- Author
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Levy SA, Smith G, De Wit L, DeFeis B, Ying G, Amofa P, Locke D, Shandera-Ochsner A, McAlister C, Phatak V, and Chandler M
- Subjects
- Behavior Therapy, Caregivers psychology, Cognition, Humans, Randomized Controlled Trials as Topic, Cognitive Dysfunction psychology, Cognitive Dysfunction therapy, Quality of Life
- Abstract
Comparative effectiveness of behavioral interventions to mitigate the impacts of degeneration-based cognitive decline is not well understood. To better address this gap, we summarize the studies from the Healthy Action to Benefit Independence & Thinking (HABIT®) program, developed for persons with mild cognitive impairment (pwMCI) and their partners. HABIT® includes memory compensation training, computerized cognitive training (CCT), yoga, patient and partner support groups, and wellness education. Studies cited include (i) a survey of clinical program completers to establish outcome priorities; (ii) a five-arm, multi-site cluster randomized, comparative effectiveness trial; (iii) and a three-arm ancillary study. PwMCI quality of life (QoL) was considered a high-priority outcome. Across datasets, findings suggest that quality of life was most affected in groups where wellness education was included and CCT withheld. Wellness education also had greater impact on mood than CCT. Yoga had a greater impact on memory-dependent functional status than support groups. Yoga was associated with better functional status and improved caregiver burden relative to wellness education. CCT had the greatest impact on cognition compared to yoga. Taken together, comparisons of groups of program components suggest that knowledge-based interventions like wellness education benefit patient well-being (e.g., QoL and mood). Skill-based interventions like yoga and memory compensation training aid the maintenance of functional status. Notably, better adherence produced better outcomes. Future personalized intervention approaches for pwMCI may include different combinations of behavioral strategies selected to optimize outcomes prioritized by patient values and preferences., (© 2022. The American Society for Experimental NeuroTherapeutics, Inc.)
- Published
- 2022
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24. Healthcare Utilization for Stroke Patients at the End of Life: Nationally Representative Data.
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Levy SA, Pedowitz E, Stein LK, and Dhamoon MS
- Subjects
- Aged, Databases, Factual, Emergency Service, Hospital trends, Female, Health Services Needs and Demand trends, Hospital Mortality trends, Humans, Ischemic Stroke diagnosis, Ischemic Stroke mortality, Ischemic Stroke physiopathology, Male, Medicare, Patient Readmission trends, Retrospective Studies, Skilled Nursing Facilities trends, Time Factors, United States, Health Resources trends, Hospice Care trends, Ischemic Stroke therapy, Palliative Care trends, Terminal Care trends
- Abstract
Objectives Stroke and post-stroke complications are associated with high morbidity, mortality, and cost. Our objective was to examine healthcare utilization and hospice enrollment for stroke patients at the end of life. Materials and methods The 2014 Nationwide Readmissions Database is a national database of > 14 million admissions. We used validated ICD-9 codes to identify fatal ischemic stroke, summarized demographics and hospitalization characteristics, and examined healthcare use within 30 days before fatal stroke admission. We used de-identified 2014 Medicare hospice data to identify stroke and non-stroke patients admitted to hospice. Results Among IS admissions in 2014 (n = 472,969), 22652 (4.8%) had in-hospital death. 28.2% with fatal IS had two or more hospitalizations in 2014. Among those with fatal IS admission, 13.0% were admitted with cerebrovascular disease within 30 days of fatal IS admission. Half of stroke patients discharged to hospice from the Medicare dataset were hospitalized with cerebrovascular disease within the thirty days prior to hospice enrollment. Within the study year, 6.9% of hospice enrollees had one or more emergency room visits, 31.7% had one or more inpatient encounters, and 5.2% had one or more nursing facility encounters (compared to 21.4%, 70.6%, and 27.2% respectively in the 30-day period prior to enrollment). Conclusions High rates of readmission prior to fatal stroke may indicate opportunity for improvement in acute stroke management, secondary prevention, and palliative care involvement as encouraged by AHA/ASA guidelines. For patients who are expected to survive 6 months or less, hospice may offer goal-concordant services for patients and caregivers who desire comfort-focused care., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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25. Education differentially contributes to cognitive reserve across racial/ethnic groups.
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Avila JF, Rentería MA, Jones RN, Vonk JMJ, Turney I, Sol K, Seblova D, Arias F, Hill-Jarrett T, Levy SA, Meyer O, Racine AM, Tom SE, Melrose RJ, Deters K, Medina LD, Carrión CI, Díaz-Santos M, Byrd DR, Chesebro A, Colon J, Igwe KC, Maas B, Brickman AM, Schupf N, Mayeux R, and Manly JJ
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Male, Aging psychology, Black or African American, Brain diagnostic imaging, Cognitive Aging, Hispanic or Latino, Language, Magnetic Resonance Imaging, Memory physiology, Neuropsychological Tests, White Matter diagnostic imaging, White, Cognitive Reserve physiology, Educational Status, Ethnicity, Racial Groups
- Abstract
Introduction: We examined whether educational attainment differentially contributes to cognitive reserve (CR) across race/ethnicity., Methods: A total of 1553 non-Hispanic Whites (Whites), non-Hispanic Blacks (Blacks), and Hispanics in the Washington Heights-Inwood Columbia Aging Project (WHICAP) completed structural magnetic resonance imaging. Mixture growth curve modeling was used to examine whether the effect of brain integrity indicators (hippocampal volume, cortical thickness, and white matter hyperintensity [WMH] volumes) on memory and language trajectories was modified by education across racial/ethnic groups., Results: Higher educational attainment attenuated the negative impact of WMH burden on memory (β = -0.03; 99% CI: -0.071, -0.002) and language decline (β = -0.024; 99% CI:- 0.044, -0.004), as well as the impact of cortical thinning on level of language performance for Whites, but not for Blacks or Hispanics., Discussion: Educational attainment does not contribute to CR similarly across racial/ethnic groups., (© 2020 the Alzheimer's Association.)
- Published
- 2021
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26. Differential Expression of miRNAs in Hypoxia ("HypoxamiRs") in Three Canine High-Grade Glioma Cell Lines.
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Koehler J, Sandey M, Prasad N, Levy SA, Wang X, and Wang X
- Abstract
Dogs with spontaneous high-grade gliomas increasingly are being proposed as useful large animal pre-clinical models for the human disease. Hypoxia is a critical microenvironmental condition that is common in both canine and human high-grade gliomas and drives increased angiogenesis, chemo- and radioresistance, and acquisition of a stem-like phenotype. Some of this effect is mediated by the hypoxia-induced expression of microRNAs, small (~22 nucleotides long), non-coding RNAs that can modulate gene expression through interference with mRNA translation. Using an in vitro model with three canine high-grade glioma cell lines (J3T, SDT3G, and G06A) exposed to 72 h of 1.5% oxygen vs. standard 20% oxygen, we examined the global "hypoxamiR" profile using small RNA-Seq and performed pathway analysis for targeted genes using both Panther and NetworkAnalyst. Important pathways include many that are well-established as being important in glioma biology, general cancer biology, hypoxia, angiogenesis, immunology, and stem-ness, among others. This work provides the first examination of the effect of hypoxia on miRNA expression in the context of canine glioma, and highlights important similarities with the human disease., (Copyright © 2020 Koehler, Sandey, Prasad, Levy, Wang and Wang.)
- Published
- 2020
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27. Mitochondrial clearance and maturation of autophagosomes are compromised in LRRK2 G2019S familial Parkinson's disease patient fibroblasts.
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Korecka JA, Thomas R, Christensen DP, Hinrich AJ, Ferrari EJ, Levy SA, Hastings ML, Hallett PJ, and Isacson O
- Subjects
- Adult, Aged, Autophagosomes drug effects, Female, Fibroblasts metabolism, Gene Expression Regulation, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 antagonists & inhibitors, Male, Middle Aged, Mitochondria drug effects, Mitochondria metabolism, Oligonucleotides, Antisense pharmacology, Parkinson Disease metabolism, Autophagosomes metabolism, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 metabolism, Mutation, Parkinson Disease genetics
- Abstract
This study utilized human fibroblasts as a preclinical discovery and diagnostic platform for identification of cell biological signatures specific for the LRRK2 G2019S mutation producing Parkinson's disease (PD). Using live cell imaging with a pH-sensitive Rosella biosensor probe reflecting lysosomal breakdown of mitochondria, mitophagy rates were found to be decreased in fibroblasts carrying the LRRK2 G2019S mutation compared to cells isolated from healthy subject (HS) controls. The mutant LRRK2 increased kinase activity was reduced by pharmacological inhibition and targeted antisense oligonucleotide treatment, which normalized mitophagy rates in the G2019S cells and also increased mitophagy levels in HS cells. Detailed mechanistic analysis showed a reduction of mature autophagosomes in LRRK2 G2019S fibroblasts, which was rescued by LRRK2 specific kinase inhibition. These findings demonstrate an important role for LRRK2 protein in regulation of mitochondrial clearance by the lysosomes, which is hampered in PD with the G2019S mutation. The current results are relevant for cell phenotypic diagnostic approaches and potentially for stratification of PD patients for targeted therapy., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2019
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28. Pilot Study: Neurocognitive Disorders and Colonoscopy in Older Adults.
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Arias F, Riverso M, Levy SA, Armstrong R, Estores DS, Tighe P, and Price CC
- Subjects
- Aged, Aged, 80 and over, Cathartics administration & dosage, Female, Humans, Male, Pilot Projects, Colonoscopy methods, Colonoscopy psychology, Neurocognitive Disorders diagnosis, Neurocognitive Disorders psychology
- Abstract
In a preoperative anesthesia setting with integrated neuropsychology for individuals >64 years of age, we completed a pilot study examining the association between neurocognitive disorders with frequency of missed colonoscopies and quality of bowel preparation (prep). Gastroenterologists completed the Boston Bowel Preparation Scale (BBPS) for each patient. Of 47 older adults seen in our service, 68% met criteria for neurocognitive disorders. All individuals failing to attend the colonoscopy procedure had met criteria for major neurocognitive disorder. Poor bowel prep was also identified in 100% of individuals with major neurocognitive disorder and 28% of individuals with mild neurocognitive disorder. Our pilot data suggest that, in high-risk individuals, the presence of neurocognitive disorders is risk factors for missed appointments and inadequate bowel prep. These pilot data provide reference statistics for future intervention protocols.
- Published
- 2019
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29. A Randomized Controlled Trial: Attachment-Based Family and Nondirective Supportive Treatments for Youth Who Are Suicidal.
- Author
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Diamond GS, Kobak RR, Krauthamer Ewing ES, Levy SA, Herres JL, Russon JM, and Gallop RJ
- Subjects
- Adolescent, Child, Depression psychology, Depression therapy, Female, Humans, Male, Pennsylvania, Reactive Attachment Disorder psychology, Self Report, Suicide, Attempted psychology, Family Therapy, Object Attachment, Reactive Attachment Disorder therapy, Suicidal Ideation, Suicide, Attempted prevention & control
- Abstract
Objective: To evaluate the efficacy of attachment-based family therapy (ABFT) compared with a family-enhanced nondirective supportive therapy (FE-NST) for decreasing adolescents' suicide ideation and depressive symptoms., Method: A randomized controlled trial of 129 adolescents who are suicidal ages 12- to 18-years-old (49% were African American) were randomized to ABFT (n = 66) or FE-NST (n = 63) for 16 weeks of treatment. Assessments occurred at baseline and 4, 8, 12, and 16 weeks. Trajectory of change and clinical recovery were calculated for suicidal ideation and depressive symptoms., Results: There was no significant between-group difference in the rate of change in self-reported ideation (Suicidal Ideation Questionnaire-Jr; F
1,127 = 181, p = .18). Similar results were found for depressive symptoms. However, adolescents receiving ABFT showed a significant decrease in suicide ideation (t127 = 12.61, p < .0001; effect size, d = 2.24). Adolescents receiving FE-NST showed a similar significant decrease (t127 = 10.88, p < .0001; effect size, d = 1.93). Response rates (ie, ≥50% decrease in suicide ideation symptoms from baseline) at post-treatment were 69.1% for ABFT versus 62.3% for FE-NST., Conclusion: Contrary to expectations, ABFT did not perform better than FE-NST. The 2 treatments produced substantial decreases in suicidal ideation and depressive symptoms that were comparable to or better than those reported in other more intensive, multicomponent treatments. The equivalent outcomes could be attributed to common treatment elements, different active mechanisms, or regression to the mean. Future studies will explore long-term follow up, secondary outcomes, and potential moderators and mediators., Clinical Trial Registration Information: Attachment-Based Family Therapy for Suicidal Adolescents; http://clinicaltrials.gov; NCT01537419., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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30. Influence of Spirituality on Depression-Induced Inflammation and Executive Functioning in a Community Sample of African Americans.
- Author
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Herren OM, Burris SE, Levy SA, Kirk K, Banks KS, Jones VL, Beard B, Mwendwa DT, Callender CO, and Campbell AL
- Subjects
- Adult, Aged, Biomarkers blood, Cognition, Depression prevention & control, Depression psychology, Female, Humans, Inflammation prevention & control, Inflammation psychology, Male, Middle Aged, Risk Factors, Black or African American psychology, Depression blood, Executive Function physiology, Inflammation blood, Inflammation Mediators blood, Spirituality
- Abstract
African Americans (AAs) are disproportionately affected by cerebrovascular pathology and more likely to suffer from premature cognitive decline. Depression is a risk factor for poorer cognitive functioning, and research is needed to identify factors that serve to mitigate its negative effects. Studies have demonstrated positive influences of spirituality within the AA community. Determining whether spirituality attenuates the effects of depressive symptoms on cognitive functioning and the pathophysiological mechanisms that explain these relationships in AAs is paramount. This study examines the influence of daily spiritual experiences on the relationship between depressive symptoms and cognitive functioning, and how inflammatory markers may partially explain these associations. A sample of 212 (mean age= 45.6) participants completed the Daily Spiritual Experience Scale (DSES), Beck Depression Inventory-II (BDI-II), Trail Making Test A and B (TMT) and Stroop Color and Word Test (Stroop). Blood samples were collected to measure inflammatory mediators (IL-6, IL-1a, TNF-a). Linear regression analyses were used to evaluate associations. Higher BDI-II scores were associated with poorer psychomotor speed and visual scanning, measured by TMT A (B=1.49, P=.01). IL-6 explained a significant amount of variance in this relationship (B=.24, CI 95% [.00, .64]). IL-6 also significantly mediated the relationship between depressive symptoms and psychomotor speed and mental flexibility, measured by TMT B performance (B=.03, CI 95% [.003, .095]). Frequent spiritual experiences among AAs may ameliorate the negative influence of depressive symptoms on cognitive functioning., Competing Interests: Competing Interests: None declared.
- Published
- 2019
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31. Tau-induced nuclear envelope invagination causes a toxic accumulation of mRNA in Drosophila.
- Author
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Cornelison GL, Levy SA, Jenson T, and Frost B
- Subjects
- Animals, Animals, Genetically Modified, Polyadenylation, RNA Transport, Drosophila Proteins metabolism, Drosophila melanogaster metabolism, Nuclear Envelope metabolism, RNA, Messenger metabolism, tau Proteins metabolism
- Abstract
The nucleus is a spherical dual-membrane bound organelle that encapsulates genomic DNA. In eukaryotes, messenger RNAs (mRNA) are transcribed in the nucleus and transported through nuclear pores into the cytoplasm for translation into protein. In certain cell types and pathological conditions, nuclei harbor tubular invaginations of the nuclear envelope known as the "nucleoplasmic reticulum." Nucleoplasmic reticulum expansion has recently been established as a mediator of neurodegeneration in tauopathies, including Alzheimer's disease. While the presence of pore-lined, cytoplasm-filled, nuclear envelope invaginations has been proposed to facilitate the rapid export of RNAs from the nucleus to the cytoplasm, the functional significance of nuclear envelope invaginations in regard to RNA export in any disorder is currently unknown. Here, we report that polyadenylated RNAs accumulate within and adjacent to tau-induced nuclear envelope invaginations in a Drosophila model of tauopathy. Genetic or pharmacologic inhibition of RNA export machinery reduces accumulation of polyadenylated RNA within and adjacent to nuclear envelope invaginations and reduces tau-induced neuronal death. These data are the first to point toward a possible role for RNA export through nuclear envelope invaginations in the pathogenesis of a neurodegenerative disorder and suggest that nucleocytoplasmic transport machinery may serve as a possible novel class of therapeutic targets for the treatment of tauopathies., (© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
- Published
- 2019
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32. Neurite Collapse and Altered ER Ca 2+ Control in Human Parkinson Disease Patient iPSC-Derived Neurons with LRRK2 G2019S Mutation.
- Author
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Korecka JA, Talbot S, Osborn TM, de Leeuw SM, Levy SA, Ferrari EJ, Moskites A, Atkinson E, Jodelka FM, Hinrich AJ, Hastings ML, Woolf CJ, Hallett PJ, and Isacson O
- Subjects
- Cells, Cultured, Endoplasmic Reticulum metabolism, Humans, Mutation, Missense, Neurites drug effects, Neurites pathology, Parkinson Disease genetics, Thapsigargin pharmacology, Calcium Signaling, Induced Pluripotent Stem Cells metabolism, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Neurites metabolism, Parkinson Disease metabolism
- Abstract
The Parkinson disease (PD) genetic LRRK2 gain-of-function mutations may relate to the ER pathological changes seen in PD patients at postmortem. Human induced pluripotent stem cell (iPSC)-derived neurons with the PD pathogenic LRRK2 G2019S mutation exhibited neurite collapse when challenged with the ER Ca
2+ influx sarco/ER Ca2+ -ATPase inhibitor thapsigargin (THP). Baseline ER Ca2+ levels measured with the ER Ca2+ indicator CEPIA-ER were lower in LRRK2 G2019S human neurons, including in differentiated midbrain dopamine neurons in vitro. After THP challenge, PD patient-derived neurons displayed increased Ca2+ influx and decreased intracellular Ca2+ buffering upon membrane depolarization. These effects were reversed following LRRK2 mutation correction by antisense oligonucleotides and gene editing. Gene expression analysis in LRRK2 G2019S neurons identified modified levels of key store-operated Ca2+ entry regulators, with no alterations in ER Ca2+ efflux. These results demonstrate PD gene mutation LRRK2 G2019S ER calcium-dependent pathogenic effects in human neurons., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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33. Structural brain correlates of fatigue in older adults with and without Parkinson's disease.
- Author
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Kluger BM, Zhao Q, Tanner JJ, Schwab NA, Levy SA, Burke SE, Huang H, Ding M, and Price C
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Brain diagnostic imaging, Fatigue diagnostic imaging, Fatigue epidemiology, Magnetic Resonance Imaging trends, Parkinson Disease diagnostic imaging, Parkinson Disease epidemiology
- Abstract
Fatigue is one of the most common and disabling nonmotor symptoms seen in Parkinson's disease (PD) and is also commonly seen in healthy older adults. Our understanding of the etiology of fatigue in older adults with or without PD is limited and it remains unclear whether fatigue in PD is specifically related to PD pathology. The objective of this study was thus to determine whether fatigue in PD was associated with structural changes in gray or white matter and explore whether these changes were similar in older adults without PD. Magnetic resonance imaging (T
1 weighted) and diffusion tensor imaging were performed in 60 patients with PD (17 females; age = 67.58 ± 5.51; disease duration = 5.67 ± 5.83 years) and 41 age- and sex- matched healthy controls. FSL image processing was used to measure gray matter volume, fractional anisotropy, and leukoariosis differences. Voxel-based morphometry confirmed gray matter loss across the dorsal striatum and insula in the PD patient cohort. PD patients with fatigue had reduced gray matter volume in dorsal striatum relative to PD patients without fatigue (P < 0.05 False Discovery Rate corrected). No significant fatigue-related structural atrophy was found in controls. There were no areas of significant fractional anisotropy differences between high and low fatigue subjects in either the PD or non-PD groups. Control participants with high fatigue, but not PD, showed significantly greater total leukoariosis volumes (p = 0.03). Fatigue in PD is associated with unique structural changes in the caudate and putamen suggesting fatigue in PD is primarily related to PD pathology, particularly in the dorsal striatum, and not simply a consequence of aging., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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34. Nicotine as a discriminative stimulus for ethanol use.
- Author
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Ginsburg BC, Levy SA, and Lamb RJ
- Subjects
- Animals, Conditioning, Operant drug effects, Conditioning, Operant physiology, Discrimination Learning drug effects, Dose-Response Relationship, Drug, Male, Rats, Rats, Inbred Lew, Reaction Time drug effects, Reaction Time physiology, Varenicline administration & dosage, Alcohol Drinking psychology, Discrimination Learning physiology, Ethanol administration & dosage, Nicotine administration & dosage, Reinforcement, Psychology
- Abstract
Abused drugs reinforce behavior; i.e., they increase the probability of the behavior preceding their administration. Abused drugs can also act as discriminative stimuli; i.e., they can set the occasion for responding reinforced by another event. Thus, one abused drug could come to set the occasion for the use of another and this functional relationship may play a role in polysubstance abuse, where common patterns of use could result in this relationship. Here we establish nicotine (0.4mg/kg, ip 5-min pre-session) as a discriminative stimulus for behavior reinforced by ethanol (0.1ml 8% w/v po, versus food) and determine the ability of nicotine (0.02-0.4mg/kg), varenicline (0.1-3.0mg/kg), and ethanol (250 and 500mg/kg) to control responding for ethanol. We compare these results to those from rats where nicotine signaled food was available (and ethanol was not). Nicotine came to function as a discriminative stimulus. Nicotine and varenicline produced dose-dependent increases in responding on the nicotine-appropriate lever while ethanol produced responding on the vehicle-appropriate lever. Whether this responding occurred on the lever that produced ethanol or food access depended on the training condition. These results demonstrate that a drug can come to set the occasion for use of another and suggest that this behavioral mechanism could play an important role in the maintenance of and recovery from polysubstance abuse, depending on the pattern of use., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2018
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35. Exploring Acceptability and Feasibility of Evidence-Based Practice in Child Welfare Settings: A Pilot Study with Attachment-Based Family Therapy.
- Author
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Santens T, Levy SA, Diamond GS, Braet C, Vyvey M, Heylboeck E, and Bosmans G
- Abstract
The Flemish Child Welfare System (CWS) is in great need of a shared empirically informed clinical strategy for working with depressed adolescents and their families. Many evidence-based practices (EBP) exist, but little is known as to whether they can be successfully imported in the CWS. Therefore, the current study explores the implementation of a particular EBP, Attachment-Based Family Therapy (ABFT), in home-based services of the Flemish CWS in Belgium. Specifically, the study focused on (1) the acceptability of ABFT by counselors and whether negative attitudes about EBP can be changed ( n = 73 counselors), and (2) the feasibility of implementing ABFT ( n = 43 adolescents, 11-17 years old, 72% female) by exploring initial effectiveness. The results suggest that (1) initial negative attitudes of counselors towards ABFT were significantly more positive after attending training and discussions about ABFT, and that (2) ABFT could be used by counselors to successfully reduce adolescent depressive symptoms. Future research should include a control group to draw stronger causal conclusions. Strengths and limitations of the study's design and implications for further dissemination are discussed., Competing Interests: The authors have no competing interests to declare.
- Published
- 2017
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36. Marked brain asymmetry with intact cognitive functioning in idiopathic Parkinson's disease: a longitudinal analysis.
- Author
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Tanner JJ, Levy SA, Schwab NA, Hizel LP, Nguyen PT, Okun MS, and Price CC
- Subjects
- Aged, Aged, 80 and over, Anisotropy, Disease Progression, Female, Frontal Lobe diagnostic imaging, Gray Matter diagnostic imaging, Humans, Language Tests, Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory, Memory, Short-Term, Mental Processes, Middle Aged, Neostriatum diagnostic imaging, Parkinson Disease diagnostic imaging, Psychomotor Performance, Space Perception, White Matter diagnostic imaging, Cognition, Functional Laterality, Parkinson Disease physiopathology, Parkinson Disease psychology
- Abstract
Objective: A 71-year-old (MN) with an 11-year history of left onset tremor diagnosed as Parkinson's disease (PD) completed longitudinal brain magnetic resonance imaging (MRI) and neuropsychological testing. MRI scans showed an asymmetric caudate nucleus (right < left volume). We describe this asymmetry at baseline and the progression over time relative to other subcortical gray, frontal white matter, and cortical gray matter regions of interest. Isolated structural changes are compared to MN's cognitive profiles., Method: MN completed yearly MRIs and neuropsychological assessments. For comparison, left onset PD (n = 15) and non-PD (n = 43) peers completed the same baseline protocol. All MRI scans were processed with FreeSurfer and the FMRIB Software Library to analyze gray matter structures and frontal fractional anisotropy (FA) metrics. Processing speed, working memory, language, verbal memory, abstract reasoning, visuospatial, and motor functions were examined using reliable change methods., Results: At baseline, MN had striatal volume and frontal lobe thickness asymmetry relative to peers with mild prefrontal white matter FA asymmetry. Over time only MN's right caudate nucleus showed accelerated atrophy. Cognitively, MN had slowed psychomotor speed and visuospatial-linked deficits with mild visuospatial working memory declines longitudinally., Conclusions: This is a unique report using normative neuroimaging and neuropsychology to describe an individual diagnosed with PD who had striking striatal asymmetry followed secondarily by cortical thickness asymmetry and possible frontal white matter asymmetry. His decline and variability in visual working memory could be linked to ongoing atrophy of his right caudate nucleus.
- Published
- 2017
- Full Text
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37. Attachment-Based Family Therapy With a 13-Year-Old Girl Presenting With High Risk for Suicide.
- Author
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Krauthamer Ewing ES, Levy SA, Boamah-Wiafe L, Kobak R, and Diamond G
- Subjects
- Adolescent, Female, Humans, Suicidal Ideation, Depression psychology, Family Therapy methods, Object Attachment, Suicide Prevention
- Abstract
This article describes the application of Attachment-Based Family Therapy (ABFT) to the treatment of a 13-year-old female adolescent presenting with high risk of suicide, complicated by a history of depression and sexual trauma. The article begins with an overview of ABFT, including (a) how attachment theory guides treatment; (b) the structure of the clinical model; and (c) the data that provide empirical support. A case example is then presented that exemplifies the primary clinical procedures used to reach therapeutic goals in ABFT, including attachment repair and autonomy/competence promotion. Weekly changes in suicide ideation and depression scores are presented. The article concludes with a discussion about implications for family-based treatment of suicidal youth., (© 2015 American Association for Marriage and Family Therapy.)
- Published
- 2016
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38. In sickness and in health: context matters when considering potential benefits and risks of genome-wide sequencing.
- Author
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Strong KA, May T, and Levy SA
- Subjects
- Genome-Wide Association Study ethics, Humans, Risk Assessment, Sequence Analysis, DNA, Genome-Wide Association Study methods, Genome-Wide Association Study statistics & numerical data
- Published
- 2015
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39. Orthopedic Surgery and Post-Operative Cognitive Decline in Idiopathic Parkinson's Disease: Considerations from a Pilot Study.
- Author
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Price CC, Levy SA, Tanner J, Garvan C, Ward J, Akbar F, Bowers D, Rice M, and Okun M
- Subjects
- Aged, Feasibility Studies, Female, Humans, Male, Middle Aged, Pilot Projects, Arthroplasty, Replacement, Knee adverse effects, Cognition Disorders etiology, Parkinson Disease complications, Postoperative Complications physiopathology
- Abstract
Background: Post-operative cognitive dysfunction (POCD) demarks cognitive decline after major surgery but has been studied to date in "healthy" adults. Although individuals with neurodegenerative disorders such as Parkinson's disease (PD) commonly undergo elective surgery, these individuals have yet to be prospectively followed despite hypotheses of increased POCD risk., Objective: To conduct a pilot study examining cognitive change pre-post elective orthopedic surgery for PD relative to surgery and non-surgery peers., Methods: A prospective one-year longitudinal design. No-dementia idiopathic PD individuals were actively recruited along with non-PD "healthy" controls (HC) undergoing knee replacement surgery. Non-surgical PD and HC controls were also recruited. Attention/processing speed, inhibitory function, memory recall, animal (semantic) fluency, and motor speed were assessed at baseline (pre-surgery), 3 weeks, 3 months, and 1 year post- orthopedic surgery. Reliable change methods examined individual changes for PD individuals relative to control surgery and control non-surgery peers., Results: Over two years we screened 152 older adult surgery or non-surgery candidates with 19 of these individuals having a diagnosis of PD. Final participants included 8 PD (5 surgery, 3 non-surgery), 47 Control Surgery, and 21 Control Non-Surgery. Eighty percent (4 of the 5) PD surgery declined greater than 1.645 standard deviations from their baseline performance on measures assessing processing speed and inhibitory function. This was not observed for the non-surgery PD individuals., Conclusion: This prospective pilot study demonstrated rationale and feasibility for examining cognitive decline in at-risk neurodegenerative populations. We discuss recruitment and design challenges for examining post-operative cognitive decline in neurodegenerative samples.
- Published
- 2015
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40. Fasting glucose and glucose tolerance as potential predictors of neurocognitive function among nondiabetic older adults.
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Sims Wright R, Levy SA, Katzel LI, Rosenberger WF, Manukyan Z, Whitfield KE, and Waldstein SR
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- Adult, Aged, Cross-Sectional Studies, Female, Glucose Tolerance Test, Humans, Linear Models, Male, Middle Aged, Neuropsychological Tests, Predictive Value of Tests, Blood Glucose metabolism, Cognition physiology, Fasting blood
- Abstract
Introduction: Significant evidence has demonstrated that Type 2 diabetes mellitus and related precursors are associated with diminished neurocognitive function and risk of dementia among older adults. However, very little research has examined relations of glucose regulation to neurocognitive function among older adults free of these conditions. The primary aim of this investigation was to examine associations among fasting glucose, glucose tolerance, and neurocognitive function among nondiabetic older adults. The secondary aim was to examine age, gender, and education as potential effect modifiers., Method: The study employed a cross-sectional, correlational study design. Participants were 172 older adults with a mean age of 64.43 years (SD = 13.09). The sample was 58% male and 87% White. Participants completed an oral glucose tolerance test as part of a larger study. Trained psychometricians administered neuropsychological tests that assessed performance in the domains of response inhibition, nonverbal memory, verbal memory, attention and working memory, visuoconstructional abilities, visuospatial abilities, psychomotor speed and executive function, and motor speed and manual dexterity. Linear multiple regressions were run to test study aims., Results: No significant main effects of fasting glucose and 2-hour glucose emerged for performance on any neurocognitive test; however, significant interactions were present. Higher fasting glucose was associated with poorer short-term verbal memory performance among men, but unexpectedly better response inhibition and long-term verbal memory performance for participants over age 70. Higher 2-hour glucose values were associated with reduced divided attention performance among participants with less than a high school education., Conclusions: Mixed findings suggest that glucose levels may be both beneficial and deleterious to neurocognition among nondiabetic older adults. Additional studies with healthy older adults are needed to confirm this unexpected pattern of associations; however, findings have implications for the importance of maintaining healthy glucose levels in older adulthood.
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- 2015
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41. Executive function and negative eating behaviors in severely obese African Americans.
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Sims RC, Bennett NK, Mwendwa DT, Ali MK, Levy SA, Callender CO, and Campbell AL
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- Adult, Cross-Sectional Studies, Female, Humans, Inhibition, Psychological, Male, Middle Aged, Set, Psychology, Socioeconomic Factors, Black or African American psychology, Executive Function physiology, Feeding Behavior ethnology, Obesity, Morbid ethnology, Obesity, Morbid psychology
- Abstract
Objective: African Americans are disparately impacted by severe obesity. Low socioeconomic status and psychosocial risk factors help to explain this disparity; however, few studies have examined the role of negative eating behaviors or the influence of executive function on negative eating behaviors in this population. The objective was to examine the association between executive function (ie, inhibition and set shifting) and negative eating behaviors in severely obese African Americans., Participants: Forty-seven African Americans who met criteria for severe obesity participated., Design and Setting: Data were analyzed from a cross-sectional study entitled Stress and Psychoneuroimmunological Factors in Renal Health and Disease. The mean age of participants was 45.7 years (SD = 10.8) and the mean educational attainment was 13 years (SD = 2.1)., Main Outcome Measures: Participants completed the Wisconsin Card Sorting Task, the Stroop Color-Word Test, and the Eating Behavior Patterns Questionnaire., Results: Correlation results suggested poorer inhibition was associated with greater self-reported emotional eating and snacking on sweets. Subsequent hierarchical regression analyses confirmed the inverse relations between inhibition, emotional eating, and snacking on sweets, after controlling for age, sex, years of education, and depression., Conclusions: Reduced inhibition may be an important risk factor for negative eating behaviors and subsequent obesity in this population. Interventions aimed at increasing inhibition and self-regulation in this at-risk group are warranted.
- Published
- 2014
42. Distinct functions of social support and cognitive function among older adults.
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Sims RC, Hosey M, Levy SA, Whitfield KE, Katzel LI, and Waldstein SR
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- Aged, Aged, 80 and over, Female, Humans, Male, Memory, Middle Aged, Neuropsychological Tests, Self Concept, Aging psychology, Cognition, Social Support
- Abstract
Unlabelled: BACKGROUND/STUDY CONTEXT: Social support has been shown to buffer cognitive decline in older adults; however, few studies have examined the association of distinct functions of perceived social support and cognitive function. The current study examined the relations between distinct functions of social support and numerous cognitive domains in older adults., Methods: Data were derived from a cross-sectional, correlational study of cardiovascular risk factors, cognitive function, and neuroimaging. The participants were 175 older adults with a mean age of 66.32. A number of neuropsychological tests and the Interpersonal Support Evaluation List were administered. Multiple linear regression analyses were conducted to determine cross-sectional relations of social support to cognitive function after controlling for age, gender, education, depressive symptomatology, systolic blood pressure, body mass index, total cholesterol, and fasting glucose., Results: No significant positive relations were found between distinct functions of social support and cognitive function in any domain; however, inverse relations emerged such that greater social support across several functions was associated with poorer nonverbal memory and response inhibition., Conclusion: Results suggest that the receipt of social support may be a burden for some older adults. Within the current study, fluid cognitive abilities reflected this phenomenon. The mechanism through which social support is associated with poorer cognitive function in some domains deserves further exploration.
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- 2014
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43. Dispositional depression and hostility are associated with inflammatory markers of cardiovascular disease in African Americans.
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Mwendwa DT, Ali MK, Sims RC, Cole AP, Lipscomb MW, Levy SA, Callender CO, and Campbell AL
- Subjects
- Adult, C-Reactive Protein physiology, Cardiovascular Diseases etiology, Cardiovascular Diseases immunology, Cardiovascular Diseases psychology, Depression immunology, Depression physiopathology, Educational Status, Female, Humans, Interleukin-6 physiology, Male, Middle Aged, Personality Inventory, Psychiatric Status Rating Scales, Regression Analysis, Risk Factors, Sex Factors, Socioeconomic Factors, Black or African American, C-Reactive Protein analysis, Cardiovascular Diseases blood, Depression blood, Hostility, Interleukin-6 blood
- Abstract
Prior research has demonstrated that state depressive symptoms and hostility can modulate inflammatory immune responses and directly contribute to cardiovascular disease (CVD) onset and development. Previous studies have not considered the contribution of dispositional depressive symptoms to the inflammatory process. They have also largely excluded African Americans, despite their disproportionate risk for CVD. The first aim of the study was to examine the impact of state and dispositional depression and hostility on CVD-associated inflammatory biomarkers interleukin-6 (IL-6) and C-reactive protein (CRP) in an African American sample. The second aim was to examine synergistic influences of hostility and state and dispositional depression on IL-6 and CRP. The final aim was to examine whether the relations between state and dispositional depression, hostility, IL-6, and CRP varied as a function of gender and education. Anthropometric measures, blood serum samples, and psychosocial data were collected from 198 African Americans from the Washington, DC metropolitan area. Hierarchical and stepwise regression analyses indicated that (1) increased levels of hostility were associated with increased levels of CRP; (2) hostility and IL-6 were more strongly associated among participants with lower educational attainment; and (3) dispositional depression and CRP were more strongly associated among participants with greater hostility and lower educational attainment. Findings suggest that enduring personality dispositions, such as dispositional depression and hostility, are critical to a thorough assessment of cardiovascular profiles in African Americans. Future studies should investigate causal pathways that link depressive and hostile personality styles to inflammatory activity for African American men and women., (Published by Elsevier Inc.)
- Published
- 2013
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44. Psychometric properties of the Cook Medley hostility scale and its association with inflammatory markers in African Americans.
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Mwendwa DT, Ali MK, Sims RC, Madhere S, Levy SA, Callender CO, and Campbell AL
- Subjects
- Adolescent, Adult, Aged, Anxiety Disorders immunology, Biomarkers, Cardiovascular Diseases ethnology, Cardiovascular Diseases immunology, Disease Susceptibility, Enzyme-Linked Immunosorbent Assay, Factor Analysis, Statistical, Female, Humans, Inflammation, Male, Middle Aged, Neuroticism, Psychometrics instrumentation, Risk Factors, Young Adult, Black or African American psychology, C-Reactive Protein immunology, Hostility, Interleukin-6 immunology, Personality physiology, Personality Inventory
- Abstract
Dispositional hostility as measured by the Cook Medley Hostility (Ho) Scale has been associated with inflammation and cardiovascular disease (CVD) risk. There is evidence that suggests that factors of hostility are more useful in predicting poor cardiovascular health outcomes than a single hostility construct. The purpose of this study was to investigate the latent factors of hostility and their association with inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) in an African-American community sample. This racial/ethnic group has been largely excluded from this line of research despite their disproportionate burden of CVD and its risk factors. Blood samples for plasma IL-6 and CRP were collected on the same day the Ho Scale was administered. Plasma IL-6 and CRP levels were determined using enzymatic-linked immunosorbent assay. Confirmatory factor analysis revealed three latent main factors of hostility: Neuroticism, Manichaeism and Moral Primitiveness, and seven intermediary subfactors. Of the subfactors, hostile affect was significantly associated with greater CRP levels and predatory self interest was significantly associated with greater IL-6 levels. Findings suggest that African Americans have a unique pattern of hostility and two latent subfactors are associated with a marker of CVD. Based on the findings, future studies should aim to further delineate how hostility influences health outcomes in African Americans.
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- 2013
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45. Atopy patch test (APT) in the diagnosis of food allergy in children with atopic dermatitis.
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Levy SA, Dortas Junior SD, Pires AH, Abe AT, Valle SO, Coelho VP, Hahnstadt LR, and França AT
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- Case-Control Studies, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Female, Food Hypersensitivity complications, Humans, Hypersensitivity, Delayed diagnosis, Hypersensitivity, Immediate diagnosis, Immunoglobulin E analysis, Male, Sensitivity and Specificity, Allergens immunology, Dermatitis, Atopic etiology, Food Hypersensitivity diagnosis, Immunoglobulin E blood, Patch Tests methods
- Abstract
Background: Atopic Dermatitis is a chronic inflammatory skin disease. Food allergens are important in the pathogenesis in 1/3 of the cases. Several mechanisms are involved in the pathogenesis of Atopic Dermatitis. Immediate reactions are identified by both measurement of specific IgE and skin prick test. Atopy Patch Test seems to be relevant in the investigation of patients with suspected delayed-type reactions., Objectives: To evaluate the standardization of this method concerning allergen concentration, occlusion time and interpretation, and determine the specificity and sensitivity of the Atopy Patch Test according to the skin prick test and specific IgE levels in food allergy diagnosis in children with Atopic Dermatitis., Methods: Seventy-two children, aged 2-12 years were selected and followed at the allergy clinic of the Hospital São Zacharias. Skin prick test, specific IgE and food Atopy Patch Test (cow's milk, egg, soy and wheat) were carried out. Three groups were submitted to the Atopy Patch Test: (1) Atopic Dermatitis with or without Rhinitis and Asthma; (2) Rhinitis and or Asthma without AD; (3) Healthy individuals., Results: In group 1, 40% of the patients presented positive reactions. The longer the exposure time (48h and 72h), the higher the sensitivity. In group 2, the test was more specific than sensitive for all the extracts, with increased sensitivity the longer the time of exposure (72h). In group 3, 8.3% presented positive tests., Conclusion: APT evidenced a great diagnostic value in late-phase reactions to food, with high specificity. It showed to be a specific and reliable tool in comparison with the healthy group's results.
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- 2012
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46. Prevalence of autoantibodies in a group of hereditary angioedema patients.
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Dortas Junior SD, Valle SO, Levy SA, Tortora RP, Abe AT, Pires GV, Papi JA, and França AT
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- Adult, Female, Humans, Male, Prevalence, Angioedemas, Hereditary immunology, Autoantibodies blood
- Abstract
Hereditary Angioedema is a dominantly inherited disease. Routine screening of autoantibodies (AAB) is not recommended for individuals with Hereditary Angioedema; however, prevalence of these antibodies in Hereditary Angioedema patients is not well documented. We aim to determine the prevalence of AAB so that individuals at risk of developing autoimmune diseases can be identified. Fifteen patients with Hereditary Angioedema attended at Clementino Fraga Filho University Hospital accepted to participate in this study. Prevalence of AAB was 40%. Our data indicate high prevalence of AAB in patients with Hereditary Angioedema. Large-scale studies should be considered to determine the significance of these AAB in the follow-up care of patients with Hereditary Angioedema.
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- 2012
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47. Cross-cultural adaptation of the Brazilian-Portuguese version of the chronic urticaria quality-of-life questionnaire - CU-Q2oL.
- Author
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Dias GA, Pires GV, Valle SO, França AT, Papi JA, Dortas SD Jr, Levy SA, Baiardini I, and Canonica GW
- Subjects
- Adult, Brazil, Chronic Disease, Female, Humans, Male, Middle Aged, Portugal, Urticaria physiopathology, Cross-Cultural Comparison, Quality of Life psychology, Surveys and Questionnaires, Urticaria psychology
- Abstract
Background: Chronic urticaria (CU) is a debilitating skin disorder that affects patients' health related quality of life and the only questionnaire prepared specifically to CU is the Chronic Urticaria Quality of Life Questionnaire (CU-Q(2)oL)., Objective: The purpose of this study was to cross-culturally adapt and validate the CU-Q(2)oL Brazilian-Portuguese version., Methods: Forward and back translation by three bilingual translators followed by pre-test was used to adapt the questionnaire. The CU-Q(2)oL was self-administered along with the Dermatology Life Quality Index (DLQI) in 112 patients with CU. Disease activity was assessed using the Urticaria Activity Score. Factor analysis was used to identify scales of the Brazilian portuguese CU-Q(2)oL. Internal consistency, convergent validity and known-group validity was determined. Reproducibility was evaluated by interclass correlation coefficient (ICC). Multiple linear regression was used to determine the predicting factors of CU-Q(2)oL results., Results: Factor analysis revealed a three-dimensional structure: sleep/mental status/eating (I), pruritus/impact on life activities (II) and swelling/limits/look (III), which explained 52.49% of the total variance. All scales showed excellent internal consistency. External construct validity was supported by correlations between the CU-Q(2)oL and DLQI. The tool was found to be able to differentiate between patients with high and low levels of urticaria activity. Test-retest reliability was good to excellent (ICC = 0.69-0.86). Disease severity and urticaria type were the only factors predicting results., Conclusions: The CU-Q(2)oL Brazilian portuguese version was easily filled out, well accepted by the patients, demonstrated an acceptable validity and reliability and might be used to evaluate treatment outcomes and in clinical research., (© 2011 John Wiley & Sons A/S.)
- Published
- 2011
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48. The influence of functional social support on executive functioning in middle-aged African Americans.
- Author
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Sims RC, Levy SA, Mwendwa DT, Callender CO, and Campbell AL Jr
- Subjects
- Female, Humans, Inhibition, Psychological, Interpersonal Relations, Male, Middle Aged, Neuropsychological Tests, Regression Analysis, Residence Characteristics, Black or African American psychology, Executive Function physiology, Social Support
- Abstract
Social support has a positive influence on cognitive functioning and buffers cognitive decline in older adults. This study examined the relations between social support and executive functioning in middle-aged adults. A community-based sample of African Americans completed the Interpersonal Support Evaluation List, a measure of functions of social support, and two measures of executive functioning, the Stroop Color and Word Test and the Wisconsin Card Sorting Test (WCST). Hierarchical regression analyses were used to explore the hypothesis that different facets of perceived social support influence performance on measures of executive functioning. After controlling for age, gender, and education, social support facets including belonging support, self-esteem support, appraisal support, and tangible support were significant predictors of Stroop performance. In addition, tangible support significantly predicted WCST performance. These findings add to previous literature on social support and cognition; however, findings for middle-aged adults are unique and suggest that social support has a positive influence on some executive functions in African Americans prior to old age.
- Published
- 2011
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49. Coping with perceived racism: a significant factor in the development of obesity in African American women?
- Author
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Mwendwa DT, Gholson G, Sims RC, Levy SA, Ali M, Harrell CJ, Callender CO, and Campbell AL Jr
- Subjects
- Adolescent, Adult, Aged, Body Mass Index, Female, Humans, Middle Aged, Obesity epidemiology, United States, Young Adult, Adaptation, Psychological, Obesity psychology, Prejudice
- Abstract
Background: African American women have the highest rates of obesity in the United States. The prevalence of obesity in this group calls for the identification of psychosocial factors that increase risk. Psychological stress has been associated with obesity in women; however, there is scant literature that has explored the impact of racism on body mass index (BMI) in African American women., Objective: The current study aimed to determine whether emotional responses and behavioral coping responses to perceived racism were associated with BMI in African American women., Methods: A sample of 110 African American women participated in a community-based study. Height and weight measurements were taken to calculate BMI and participants completed the Perceived Racism Scale and the Perceived Stress Scale., Results: Hierarchical regression analyses demonstrated a significant relationship between BMI and behavioral coping responses to perceived racism. Findings for emotional responses to perceived racism and appraisal of one's daily life as stressful were nonsignificant. Mean comparisons of BMI groups showed that obese African American women used more behavioral coping responses to perceived racism as compared to normal-weight and overweight women in the sample., Conclusion: Findings suggest that behavioral coping responses better explained increased risk for obesity in African American women. A biobehavioral pathway may explain this finding with a stress-response process that includes cortisol reactivity. Maladaptive behavioral coping responses may also provide insight into obesity risk. Future research is needed to determine which behavioral coping responses place African American women at greater risk for obesity.
- Published
- 2011
- Full Text
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50. Communication about smoking between depressed adolescents and their parents.
- Author
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Levy SA, Westin AM, Reamy AM, Reyner JC, Syed T, and Diamond GS
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- Adolescent, Adult, Female, Humans, Male, Young Adult, Communication, Depression, Parent-Child Relations, Smoking
- Abstract
Introduction: Better understanding of effective parent-adolescent communication regarding tobacco use could inform smoking cessation intervention., Methods: Semistructured interviews related to communication about smoking were conducted with 15 depressed adolescent smokers and their parents, primarily from urban areas. This study, conducted in 2006-2008, was funded by the Pennsylvania Department of Health. Interview transcripts (N = 30) were coded in QSR N6., Results: Quality of communication, rather than content, seemed to determine whether parental communication was effective. Parents reactivity to, or avoidance of, adolescent smoking presented a barrier to effective communication. In this sample, parents and adolescents were more concerned about problems, such as depression, than smoking., Discussion: Involving parents in adolescent smoking cessation programs may be promising. Parental involvement may include teaching parent-child communication skills, building stronger relational bonds, or helping parents quit simultaneously. Further research is needed to explore whether coupling smoking cessation with depression treatment increases parent and adolescent treatment engagement and effectiveness.
- Published
- 2010
- Full Text
- View/download PDF
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