Claude D. Pepper Older Americans Independence Center

Marco Pahor, M.D.
Principal Investigator
Connie Caudle
Program Administrator

The mission of the University of Florida Older Americans Independence Center (OAIC) is twofold: 1) to optimize older persons’ physical performance and mobility through interdisciplinary approaches; and 2) to train new investigators in aging and disability research while developing their leadership qualities. Our goal is to enhance late-life health and independence, with a special focus on mobility. To accomplish our mission, our strategy is to attract studies and inventive investigators from diverse behavioral, clinical, basic, and technological science disciplines with a common research focus: “mobility and prevention of disability.” Traversing the entire spectrum of biomedical investigation, including molecular biology, animal studies, clinical research, behavioral sciences, epidemiology, and engineering, our research effort addresses the OAIC’s general goal: to increase scientific knowledge that leads to better ways to maintain or restore independence of older people. Our research objectives are to: 1) assess, using translational research (among diverse disciplines), the biological, co-morbid, psychosocial, behavioral, and other factors that contribute to physical function decline, loss of mobility, and progression toward disability; and 2) develop and reliably test, in clinical and preclinical studies, interventions that target mobility to prevent, delay, or recover the age-related declines in physical function. Our educational objective is to train future leaders in clinical translational research on aging. To meet these objectives the proposed OAIC trains Junior Scholars and supports investigators, resources, services, external studies, development projects, and pilot/exploratory studies through seven integrated cores: Leadership and Administrative Core; Research Education Core; Pilot/Exploratory Studies Core; Clinical Research Core; Metabolism and Translational Science Core; Biostatistics Core; and Data Science and Applied Technology Core. A relevant strength of the proposed OAIC is the concerted action of the interdisciplinary cores, projects, and investigators who address one common research focus spanning the entire spectrum of biomedical investigation.

Research hypotheses:
  • Multiple biological, co-morbid, psychosocial, cognitive, and behavioral factors contribute to agerelated physical function decline, loss of mobility, and progression to disability.
  • Interventions that target individual or multiple biological, co-morbid, psychosocial, cognitive, and behavioral risk factors of physical function decline avert the loss of mobility and prevent disability.
Research objectives:
  • Assess, by taking advantage of a bidirectional translation between basic and clinical research, the multiple factors that contribute to physical function decline, loss of mobility, and progression to disability.
  • Develop and test pharmacological, nutritional, and behavioral interventions for preventing decline in physical function, loss of mobility, and progression to disability.
Educational objectives:
  • Educate and train new investigators in research on aging and disability in older adults.
  • Develop leadership qualities and roles in Junior Scholars supported by the OAIC.
  • Develop skills for translating findings between basic and clinical research.
Operational objectives:
  • To provide outstanding investigators and state-of-the-art resources, environment, and services to support the above-mentioned research and educational objectives.

Leadership and Administrative Core (LAC)
Leader 1:    Marco Pahor, MD
The Leadership and Administrative Core (LAC) is responsible for strategic planning, organization, administrative operations, and evaluation of the Older Americans Independence Center (OAIC) research and training program. A special effort is devoted to ensure the cohesion of the Center and maintain an interdisciplinary and translational research focus on the common research theme, which is “mobility and prevention of disability.” The Core Leader and three committees achieve the key LAC tasks. The Executive Committee, which is composed of the OAIC core leaders, administers, governs, provides scientific guidance, and sets productivity benchmarks for the OAIC. The External Advisory Board, which is composed of experts external to the institution, reviews all OAIC activities and provides overall scientific guidance to the OAIC. The Independent Review Panel, which is composed of ad hoc experts (at least one third external to the institution), reviews proposed support for development projects, and pilot/exploratory studies. Taken together, the LAC provides support for planning, organizational, evaluation, and administrative activities relating to the other cores and to the OAIC as a whole. The LAC monitors, stimulates, sustains, evaluates, and reports progress toward the overall goals of the OAIC.

Research Education Component (REC)
Leader 1:    Christiaan Leeuwenburgh, PhD
Leader 2:    Roger Fillingim, PhD
The REC promotes the development of independent investigators in interdisciplinary research on aging relevant to the independence of older Americans. One of our major goals is to identify the most promising Junior Scholars with research relevant to the OAIC theme at UF & VA and to provide them with mentorship, training activities, access to OAIC Core resources and funding and enable them to become independent investigators in interdisciplinary aging research. Furthermore, this core emphasizes the development of leadership, and research skills for translating basic findings into clinical research and clinical findings into basic research. The REC supports the research training of OAIC Junior Scholars that span the spectrum from beginning trainees who are not yet funded to advanced trainees who already have competed successfully for career development grants that provide substantial salary support.

Pilot and Exploratory Studies Core (PESC)
Leader 1:    Yenisel Cruz-Almeida, Ph.D.
Leader 2:    Marco Pahor, MD
The Pilot/Exploratory Studies Core serves to develop key information needed to select and design future, original and independently funded studies that can advance our insight into sarcopenia and prevention of disability in older Americans. Specifically, the core fosters the Pilot and Exploratory studies by ensuring the availability of optimal infrastructure, environment, funding, expertise, and instrumentation. Pilot and Exploratory studies foster Junior Scholars in their efforts to develop research careers in aging by providing opportunities for meaningful participation in well-designed research studies and by collecting the needed preliminary data for independent research applications. Furthermore, these studies will allow investigators already accomplished in aging research to gather data that will extend and broaden their focus of research. Finally, these studies will also be a vehicle to encourage and facilitate experienced investigators traditionally working in other research fields to focus on aging.

Clinical Research Core (RC1)
Leader 1:    Stephen Anton, PhD
Leader 2:    Marco Pahor, MD
The Clinical Research Core (RC 1) is a key resource for the UF OAIC in providing the infrastructure and investigators for conducting clinical research -- randomized controlled trials and observational studies. The clinical research core has four primary goals: 1) optimal selection and utilization of measures for clinical trials and observational studies 2) understanding the physiological and biomechanical mechanisms contributing to changes in walking speed, 3) in collaboration with the Biostatistics Core, conduct secondary analyses of randomized clinical trials and observational studies to provide preliminary data to support the rationale for future clinical trials, and 4) development of behavioral and pharmacological interventions to improve physical function and quality of life of older adults. The RC 1 offers state-of the art infrastructure and experienced personnel to support the conduction of observational studies, and Phase 2 and 3 randomized controlled trials that involve behavioral and pharmacological interventions. Senior researchers with NIH and/or VA funding, who also have established track records as mentors for career development, lead each one of these goals.

Biostatistics Core (RC 3) (Biostats)
Leader 1:    Peihua Qiu, PhD
The Biostatistics Core is one of four research cores in the OAIC at UF. The mission of the OAIC at UF is to assess risk factors of physical disability in older adults, to develop and test effective prevention and rehabilitation therapies, and to train new investigators in research on aging and disability. The Biostatistics Core is a key cog in the interaction among scientists from many disciplines to accomplish this mission. The core provides data coordination including: developing data collection forms, designing web based capture systems, and managing the data (including quality control) for studies conducted within the OAIC. The core also is involved in all phases of these studies including initial study design and sample size calculations pre-proposal, randomization, and state-of-the-art statistical analyses once the data are completed. For study designs and data for which current methodology is lacking, the core has the expertise to develop new state of the art methodology to perform correct and appropriate analyses of data collected in the Center. The Biostatistics Core will also be involved in preparation of manuscripts for dissemination within the research community. The Core also conducts research using The UF & Shands Academic Health Center’s new electronic medical record system (EPIC), which has gone live with new modules planned through the next few years. This includes the implementation of a clinical data warehouse (CDW). The CDW is the foundation for the development of a research data repository whereby researchers and junior scholars and faculty may have unfettered access to anonymized data for clinic research.

Circadian Rhythms Core (RC5)
Leader 1:    Karyn Esser, PhD
The new Circadian Rhythms research core within the UF OAIC will provide the specialized resources and expertise to support scientists that want to incorporate circadian and sleep concepts into their aging research program. This includes new investigators, early-stage investigators and current investigators in aging. The core will support research through; 1) in vivo rodent circadian phenotyping across age; 2) resources to implement time restricted feeding with unique automated cages; 3) methods to test the robustness and resilience of the circadian system across ages; 4) non-invasive analysis of rodent sleep parameters; 5) statistical support for analysis of circadian data from rodents and humans. 6) Ongoing development of an in vitro assay to analyze human circadian clock function using primary cells from subjects of different ages and health status. 7) Work with RC4, the Biostatistics core to leverage UF machine learning strengths to define a blood marker assay as a biomarker of human circadian health.

Data Science and Applied Technology Core (RC 4) (Data Science)
Leader 1:    Todd Manini, PhD
Leader 2:    Sanjay Ranka, PhD
The Data Science and Applied Technology (DSAT) Core (RC4) provides an interactive data and technology ecosystem for preserving mobility and preventing disability. Big data initiatives, applied technologies, and new methodological approaches for data science have exploded in many various environments, and the world is moving toward a connected system of computing and sensing components. Additionally, mobile health (mHealth, smartphones and smartwatches) technologies are changing the landscape for how patients and research participants communicate about their health in real time. DSAT investigators provide OAIC leadership to assure that researchers in Geriatrics in general, mobility and disability are prepared for the rapid advances in these expanding technologies. The RC4 provides many unique attributes, such as developing software for interactive mobile technology (e.g., wearable sensors that are programmable in real time); validating new sensing technology; warehousing data; repurposing data; and applying machine learning techniques to domain problems. DSAT provides a central hub of expertise in computer science, biomedical engineering, biomedical informatics, data science, applied technology, epidemiology, and content expertise in the assessment of mobility. There is a growing demand for data science and applied technology for meeting the challenge of preserving mobility and preventing disability. The DSAT Core adds a highly innovative aspect to this challenge that will lead it into the future of connected systems of computing, sensing and biomedical informatics.

Metabolism and Translational Science (RC2) (Metabolism and Translational Science)
Leader 1:    Christiaan Leeuwenburgh, PhD
The Metabolism and Translational Science Core provides the infrastructure, laboratory space, trained personnel, consultative and collaborative scientific expertise and a wide spectrum of established and novel methodologies of biochemistry and molecular biology ( Western blot and Quantitative-PCR, quantitative-Real-Time PCR, enzyme-linked immunosorbent assays, multiplex immunoassays), high resolution respirometry, and selected measures of metabolism (i.e., ATP measures and enzymes activities of metabolism) that will address a set of genetic and biological themes focused on causes for aging and disability. The Core utilizes this state-of-the-art technology to determine specific mechanisms of aging and sarcopenia and the cause of reduced physical function present in elderly populations. The Core provides support for numerous independently funded studies, development projects, pilot studies and exploratory studies. Analyses of levels of biomarkers or cell signaling molecules will help to identify specific biological pathways of aging implicated in the development of sarcopenia. If the precise mechanisms underlying age-associated cellular deterioration can be identified, it will explain the loss of muscle mass and function with age and provide us with potential targets for intervention. In this context, we will also test if specific rehabilitation, physical activity and dietary interventions can attenuate biological pathways leading to aging and functional impairment. In addition, the Core supports preclinical phenotyping of various domains of function include Cognition, Physical, Motor, and Sensory/Hearing. Each of these sophisticated measures currently in use in our laboratories require expert oversight and the use of highly trained technicians. These assessment methodologies are conceptually similar to those used in humans and highly translatable.

REC Scholar, Research & Grants Funded During Pepper Supported Time Years /
Lakeshia Cousin, PhD, APRN, AGPCNP-BC
Assistant Professor / College of Nursing
A Pilot Feasibility Study of a Gratitude Journaling Intervention to enhance Well-being and Exercise Readiness in Older African American Female Breast Cancer Survivors
2022-2024 /
0 (total)
0 (1st/Sr)
Feng Yue, PhD
Assistant Professor / Department of Animal Sciences
Mechanisms of sepsis-induced myopathy in aging: insights from a new modified surgical sepsis model by single cell analysis
2022-2024 /
0 (total)
0 (1st/Sr)
Clayton Swanson, PhD, MS
Assistant Professor / Department of Aging & Geriatric Research
Development of a Home-based Self-delivered Prehabilitation Intervention to Proactively Reduce Fall Risk in Older Adults
2022-2024 /
0 (total)
0 (1st/Sr)

Past Scholars
Dr. Rui Xiao, Department of Aging & Geriatric Research (2015-2017)
Hyochol "Brian" Ahn PhD, ARNP, ANP BC, College of Nursing, Department of Family, Community and Health System Science (2015-2017)
Scott Brakenridge, MD, College of Medicine, Department of Surgery (2015-2017)
Andrew Bryant, MD, College of Medicine, Department of Internal Medicine Pulmonary, Critical Care and Sleep Medicine (2015-2016)
Sara Burke, PhD, College of Medicine, Department of Neuroscience (2015-2017)
Huaihou Chen, PhD, Department of Biostatistics (2015-2017)
Sooyeon Lee, PhD, College of Medicine, Department of Surgery (2015-2016)
Joshua Brown, PhD, MS, Department of Pharmaceutical Outcomes & Policy (2017-2019)
Robert Mankowski, PhD, Department of Aging & Geriatric Research (2017-2019)
Yu-Jung “Jenny” Wei, PhD, MS , Department of Pharmaceutical Outcomes and Policy (2017-2019)
Dr. Joseph McQuail, PhD , Department of Neuroscience (2018-2019)
Dr. Terence Ryan, PhD, Department of Applied Physiology & Kinesiology (2018-2020)
Sung Min Han, PhD , College of Medicine Department of Aging and Geriatric Research (2019-2021)
Carolina Maciel, MD, Department of Neurology, Division of Neurocritical Care (2019-2021)
Scott Vouri, PharmD, MSCI, PhD, Department of Pharmaceutical Outcomes and Policy (2019-2021)
Matthew R. Burns, MD, PhD, Department of Neurology (2020-2022)
Sudeshina A. Chatterjee, BPTh, MS, PhD, Department of Aging & Geriatric Research (2020-2022)
Mamoun Al Mardini, PhD, Health Outcomes and Biomedical Informatics (2020-2022)
Samir K. Shah, MD, MPH, Department of Surgery (2020-2022)

1. Project Title: Time Course Adaptations using Deuterated Creatine (D3Cr) method
  Leader: Anoop Balachandran, PhD (Todd Manini, PhD)
  This pilot study is focused on assessing the time course adaptions in functional muscle mass and performance outcomes in response to a high-intensity resistance training intervention in low functioning older adults. It will provide critical clinical preliminary data for a successful extra-mural application for a future larger study. Specifically, the proposed future study will examine the impact of a high intensity resistance training intervention to increase skeletal muscle mass compared to an education control on physical performance outcomes, such as 400 m walk, lower body strength, balance, SPPB Short Physical Performance Battery (SPPB) in low functioning older adults.
2. Project Title: Circadian dysfunction in aging and chronic kidney disease
  Leader: Michelle Gumz, PhD (Karyn Esser, PhD)
  The goal of this pilot study is to provide feasibility and supporting data for an R01 application. This new line of investigation is aimed at discerning mechanisms of and novel therapeutic interventions for chronic kidney disease. Chronic kidney disease is increasing in large part due to our aging population and it is associated with muscle wasting, decreased mobility, and increased disability. Our preliminary data for this pilot proposal strongly suggest that Dr. Esser’s unique mouse model of circadian disruption and accelerated aging has a renal defect. The funds requested in this application are necessary to test our hypothesis that circadian disruption and accelerated aging lead to kidney damage and reduced renal function. These funds are needed to provide supporting data for a larger, long-term project in which we will further test the hypothesis that circadian disruption and accelerated aging lead to chronic kidney disease with consequences for cardiovascular mortality.
3. Project Title: Exosomal Mediation of Exercise induced benefits in aging
  Leader: Brittney Yegla, PhD
  The goal of this pilot study is to examine intercellular signaling, specifically exosomes and their miRNA content, in aging with exercised and non-exercised Fischer-344 rats. The study proposes to investigate age- and sex-related differences in exercise-induced exosome release following either an acute or sustained exercise regimen and how this relates to the changes in musculature, cognition, metabolism, inflammation, and redox state in multiple organs with exercise. Young and aged male and female rats will undergo treadmill running for a single bout of exercise (acute; Aim 1) or for two months on a progressive workload schedule (sustained; Aim 2) to produce a 70% VO2max. Following exercise rats will be evaluated for physical and cognitive capacity changes compared to sedentary controls. After final bout of exercise, rats will be euthanized, and the blood, muscle, liver, kidney, brain, and fat tissue will be collected to examine the impact of age, sex, and exercise on exosome-derived miRNA expression and metabolic and inflammatory marker levels. Regular sustained exercise is expected to produce quantitative and qualitative changes in exosome-derived miRNA expression, correlating with cellular, cognitive, and physical changes. It is predicted that continued exercise will shift the aging secretome to resemble a younger profile. The findings from this study will not only establish the foundation for future NIH-funded experiments but also provide critical insight into age-related shifts in intercellular signaling and its sensitivity and responsiveness to exercise.
4. Project Title: Identification of novel circulating factors affecting skeletal muscle mass & function in advanced age
  Leader: Russell T. Hepple, PhD
  This pilot study aims to identify novel circulating (blood-borne) factors that can promote physical function and maintenance of skeletal muscle mass and function in advanced age. We will capitalize on substantial pre-existing data, banked blood serum and banked myoblast cultures that we collected in recent studies examining world-class octogenarian track & field athletes as a model of very healthy aging. We will complement this with study of pre-frail/frail elderly individuals with the objective of identifying both positive circulating factors (e.g., those found in serum of world class octogenarian athletes) and negative circulating factors (e.g., those found in serum of pre-frail/frail elderly) by doing advanced proteomics screening of serum from these subjects. Additionally, we will conduct preliminary evaluation of promising candidate proteins enriched in high functioning (octogenarian athletes) versus low functioning (pre-frail/frail elderly) individuals by screening for muscle and neuromuscular junction impact using human myoblast cultures. These highly novel and exciting studies will directly address factors that likely contribute to mobility and disability with aging.
5. Project Title: Estrogen and Prevention of Hearing Loss
  Leader: Shinichi Someya, PhD
  Numerous studies have reported gender differences in human auditory function. In general, the results of these studies show that women of virtually all ages demonstrate better hearing than men5-13. Considerable evidence also suggests that auditory function is diminished following menopause14-15, whereas estrogen therapy prevents decline of auditory function in postmenopausal women16-20. Estrogen also has neuroprotective and glutathione antioxidant defense actions21-24. However, the molecular mechanisms underlying these beneficial effects are largely unknown and prescribing estrogen therapy to women experiencing hearing problems remains controversial25-27. The central hypothesis of our research proposal is that estrogen protects hearing by enhancing glutathione transferase detoxification in the auditory system of females over the lifespan. The results of our proposed work will provide women, suffering from post-menopausal hearing loss, practical approaches to prevent decline of auditory function and disability associated with hearing loss.
6. Project Title: Probing metabolomics of pancreatic cancer and skeletal muscle in elderly patients
  Leader: Ashwin S. Akki, MD, PhD
  The overall goal of this research project is to increase the understanding of metabolic alterations in the skeletal muscle of elderly patients with cachexia and accelerated sarcopenia in pancreatic ductal adenocarcinoma (PDAC). Since skeletal muscle metabolism and strength are intricately linked to tumor metabolism, simultaneously probing PDAC metabolism is crucial. This knowledge will enable us to decipher the impact of a rapidly proliferating tumor on aggressive cachexia, accelerated sarcopenia and impaired mobility in elderly PDAC patients and help identify novel metabolic targets that could potentially be modulated to curb tumor growth, preserve skeletal muscle mass/strength, and prevent disability in the aging population. Consequently, the proposed project is highly relevant to the OAIC theme of “Mobility and Prevention of Disability”. This proposal is extremely relevant to the interests of the “Clinical and Translational Research of Aging Review Committee (NIAT)” and/or the “Aging Systems and Geriatrics Study Section”
7. Project Title: Pain Resilience and Inflammatory Marker Expression (PRIME)
  Leader: Emily J. Bartley, PhD
  The overarching goal of this study is to elucidate the immunological and resilience mechanisms underlying self-reported and functional disability in older adults with cLBP. This project expands an existing community-based study (Adaptability and Resilience in Aging Adults [ARIAA]) whereby 60 adults (ages 60+ years) with cLBP completed clinical (psychological and pain measures), functional (tests of mobility), and somatosensory pain assessments. The study supplements the parent project through the inclusion of biomarker assays to assess pro- and anti-inflammatory function. These findings will provide novel and important information regarding the mechanisms underpinning pain and disability and will be a step toward the development of therapeutic modalities aimed at mobility preservation in older adults with cLBP.
8. Project Title: Impact of Pain and Exercise on Mobility in Older Adults with Opioid Use Disorder
  Leader: Meredith S. Berry, PhD and Danielle E. Jake-Schoffman, PhD
  This study aims to determine the effects of the exercise intervention versus control on (i) self-reported pain and pain catastrophizing, (ii) objective and self-reported mobility ratings (iii) biologically verified urinalysis results of illicit drug-use, and (iv) craving, withdrawal, and behavioral economic demand for opioids. The study directly aligns with the central OAIC themes of enhancing mobility, and reducing pain through an exercise intervention. This project has tremendous potential for public health impact with possibility for wide deployment for those in need. Our multidisciplinary team is uniquely suited to advance understanding of shared mechanisms underlying pain, mobility, craving and withdrawal, and to complete the proposed project with expertise in (i) OUD (ii) PA promotion (iii) pain (iv) exercise physiology (v) cardiology and (vi) biostatistics.
9. Project Title: Prevention of Cancer-Induced Immobility and Dysfunction
  Leader: Daria Neyroud, PhD and Andrew D'Lugos, PhD
  This study aims to 1. Quantify the extent to which cancer impacts mobility and skeletal muscle dysfuction; and 2. Determine the efficacy of exercise training for preventing cancerinduced disability and cachexia. The project is therefore highly aligned with the mission of the National Institute on Aging (NIA), in particular with goal C of the current NIA Strategic Direction for Research, “to develop effective interventions to maintain health, well-being, and function and prevent or reduce the burden of age-related diseases, disorders, and disabilities”.
10. Project Title: Role of skeletal muscle Bmal1 on healthspan and survival
  Leader: Miguel Gutierrez-Monreal, PhD (Karyn Esser, PhD)
  The goal of this pilot study is to provide feasibility and supporting data for a NIH grant application. This pilot is aimed to examine the effect of skeletal muscle molecular clock on systemic metabolism and inflammation during aging. We have recently identified there is a progressive age-related decline in circadian function in skeletal muscle. Disruptions in circadian rhythms have profound negative consequences on several pathways that comprise the hallmarks of aging including metabolism and inflammation.
11. Project Title: Sleep, pain and aging: potential underlying mechanisms
  Leader: Soamy Montesino Goicolea, MD (Yenisel Cruz-Almeida, PhD)
  This study will quantify the levels of the GABA neurotransmitter after oral administration, regardless of the direct or indirect route that mediates its function in the brain. This constitutes the starting point in the development of cost-effective over-the-counter GABA treatments aiming at improving the currently costly and often co-morbid problems of sleep dysfunction and chronic pain in the aging population. The project addresses an existing knowledge gap and may potentially identify GABA.
12. Project Title: Design of Printable Gelatin Microgel and Stem Cell-based Composite Bioink for Repairing Degenerated Intervertebral Discs
  Leader: Yong Huang, PhD, Christiaan Leeuwenburgh, PhD, Brian Harfe, PhD, Kyle Allen, PhD
  The overarching goal of this pilot study is to design and evaluate a gelatin microgel and stem cellbased printable bioink as a delivery system for the repair and regeneration of age-related degenerative intervertebral discs (IVDs) for personal mobility and independence. Intervertebral disc degeneration (IDD) is an age-related condition that happens when one or more of the discs between the vertebrae of the spinal column deteriorate or even break down. As a natural occurrence that comes with aging, it may lead to lower back pain and even immobility due to weakness, numbness, and pain that radiates down the leg, resulting in disability. As a minimally invasive approach, the cell-therapy approach aims to address disc inflammation by inhibiting aberrant cytokine production as well as disc rehydration and height restoration by initiating matrix anabolism and repopulating native cells. While the cell-therapy approach needs a unified understanding of the disease mechanism of degeneration and useful interpretation of clinical evaluations, clinical trials also call for effective delivery systems of therapeutic cells, which is the subject of the study. Accordingly, two specific aims are proposed: Aim 1: Repair of degenerative IVD using a gelatin microgel and mesenchymal stem cell-based printable composite bioink. Aim 2: Evaluation of the mechanical properties and formation of fibrocartilage-like intervertebral disc tissue of IVDs repaired using the proposed cell delivery system. This pilot study provides a novel gelatin microgel-based self-supported cell delivery system to repair degenerated IVDs for their better regeneration by integrating engineering and biology to create a costeffective and safe cell therapy for IVD regeneration. Such a printable stem-cell therapy will help improve the mobility and independence of seniors who are disabled due to IDD-induced weakness, numbness, and back pain that radiates down the leg. We further envision that the delivery system using the proposed printable self-supporting cellular bioink can be explored as a much-needed reliable and costefficient stem-cell therapy to facilitate in situ tissue repair and wound healing applications, to name a few.
13. Project Title: Fear of falling as an underlying mechanism of age-related altered walking mechanics
  Leader: Francesca Wade, PhD, David Clark, PhD, Christopher Hass, PhD
  As we age, our ability to independently move outside of the home environment wanes. Limiting out of home activity is often due to reduced confidence in walking, especially in situations where environment- and task-demands are heightened. Older adults also adopt slower walking speeds; a cautious walking strategy due to fear of falling (FoF). Walking speed is determined by forward propulsion; appropriately timed muscular forces and joint actions produce forces on the ground that efficiently move the person forward. Although older adults maintain the ability to generate the requisite ankle force for walking, they typically rely less on contributions from the ankle and more on contributions from the hip. Increased hip contributions to propulsion may lead to more stable gait; thus propulsive force generation at the ankle may be underutilized to adapt gait patterns to compensate for FoF. The proposed research will take a novel and interdisciplinary approach to understand how FoF may play a role in age-related changes in walking function. This is an important area to study, as the changes in walking function reduce independent mobility outside of the home. The relationship between FoF and walking biomechanics will be investigated in older adults, who have either high- or low- fear of falling. The proposal also includes an experiment to artificially increase fear of falling to obtain direct measures of its effects on walking function. Findings from the proposed research will be used as pilot data in part of a larger grant proposal investigating walking mechanics, fear of falling, when in the lifespan these changes occur, and eventually, to develop interventions to promote independence and mobility in the aging population.
DEVELOPMENT PROJECTS (2 Development Projects Listed)
1. Project Title: Development of Novel Measures to Assess Fuel Utilization and Circadian Rhythms in Overweight, Older Adults
  Leader: Stephen Anton, PhD, Karyn Esser, PhD, Christiaan Leeuwenburgh, PhD, Todd Manini, PhD, Marco Pahor, MD, Bhanuprasad Sandesara, MD, William Donahoo, MD, Peihua Qiu, PhD
  Core(s): Clinical Research Core (RC1)
Data Science and Applied Technology Core (RC 4) (Data Science)
Metabolism and Translational Science (RC2) (Metabolism and Translational Science)
  The purpose of this development project is to develop and test the feasibility of relatively non-invasive new measures of fuel utilization and circadian health that can provide an index of both cellular and mitochondrial health. Hence, with this development project, we propose to investigate the feasibility of obtaining relatively non-invasive measures of fuel utilization and circadian health biomarkers in older adults. If these measures are found to be feasible, they may become useful measurement tools to be included in future clinical trials conducted within the University of Florida’s Pepper Center. In specific aim 1, we will test the feasibility of measuring fuel utilization within white blood cells through Seahorse XF Technology, a new measure that could detect shifts in fuel utilization at a cellular level. We will also measure 24-hour fluctuations in plasma glucose levels using a continuous glucose monitor. In specific aim 2, we will develop a new measure to detect the expression of circadian clock genes in whole blood. We will also test the feasibility of measuring systemic measure of circadian health using Wearable Technology (i.e., the Oura ring) that continuously tracks heart rate, body temperature, activity levels, as well as sleep patterns. The reliability and variability in the new measures of fuel utilization and circadian health markers will be compared to that of our standard Clinical Research Core measures of cognitive and physical function.
2. Project Title: Time restricted feeding to improve aging circadian clocks and healthspan in rodents
  Leader: Karyn Esser, PhD, Thomas Foster, PhD, Andrew Liu, PhD, Christiaan Leeuwenburgh, PhD
  Aging is associated with changes in circadian rhythms including patterns of locomotor activity and sleep/wake states (114-120). Underlying circadian rhythms is a molecular clock mechanism that is found in virtually all cells throughout the body. Research has demonstrated that disruption of circadian timekeeping leads to increases in pathology, morbidity, and mortality (121-129). The purpose of this project is to implement a circadian-based intervention, time-restricted feeding, for its potential to enhance circadian function across organs and improve healthspan in aging mice. This preclinical study will complement the clinical DP-1 (described in RC1) with the ability to carefully control the times of feeding the mice, and to assess the health impact on organs such as brain, heart, and skeletal muscle.
RESEARCH (25 Projects Listed)
  Leader(s): CLARK, DAVID J
    VA I01RX003115 / ( 2019 - 2023 )
  Aging often leads to substantial declines in walking function, especially for walking tasks that are more complex such as obstacle crossing. This is due in part to a lack of continued practice of complex walking (sedentary lifestyle) combined with age-related deficits of brain structure and the integrity of brain networks. Neurorehabilitation can contribute to recovery of lost walking function in older adults, but major and persistent improvements are elusive. A cornerstone of neurorehabilitation is motor learning, defined as an enduring change in the ability to perform a motor task due to practice or experience. Unfortunately, in most clinical settings, the time and cost demands of delivering a sufficiently intensive motor learning intervention is not feasible. There is a need for research to develop strategies for enhancing motor learning of walking ( locomotor learning ) in order to improve the effectiveness of neurorehabilitation. The objective of this study is to use non-invasive brain stimulation to augment locomotor learning and to investigate brain networks that are responsible for locomotor learning in mobility-compromised older adults. We have shown that frontal brain regions, particularly prefrontal cortex, are crucial to control of complex walking tasks. Our neuroimaging and neuromodulation studies also show that prefrontal cortex structure and network connectivity are important for acquisition and consolidation of new motor skills. However, a major gap exists regarding learning of walking tasks. The proposed study is designed to address this gap. Our pilot data from older adults shows that prefrontal transcranial direct current stimulation (tDCS) administered during learning of a complex obstacle walking task contributes to multi-day retention of task performance. In the proposed study we will build upon this pilot work by conducting a full scale trial that also investigates mechanisms related to brain structure, functional activity, and network connectivity. We will address the following specific aims: Specific Aim 1: Determine the extent to which prefrontal tDCS augments the effect of task practice for retention of performance on a complex obstacle walking task. Specific Aim 2: Determine the extent to which retention of performance is associated with individual differences in baseline and practice-induced changes in brain measures (working memory, gray matter volume, task- based prefrontal activity, and brain network segregation). Specific Aim 3: Investigate the extent to which tDCS modifies resting state network segregation. We anticipate that prefrontal tDCS will augment retention of locomotor learning, and that our data will provide the first evidence of specific brain mechanisms responsible for locomotor learning/retention in older adults with mobility deficits. This new knowledge will provide a clinically feasible intervention approach as well as reveal mechanistic targets for future interventions to enhance locomotor learning and rehabilitation.
  Leader(s): BOOKER, STAJA
    NIH K23AR076463 / ( 2020 - 2023 )
  Knee osteoarthritis (OA) is one the most problematic sources of persistent musculoskeletal pain, impaired function and mobility, and reduced quality of life in older adults. Although these are common outcomes associated with OA, they are disproportionately worse in older African Americans. These threats to healthy aging demand further investigation into the most significant driver of OA pain and disability, which is movement. The experience of pain due to movement, known as movement-evoked pain (MEP), often prohibits full participation in daily living activities and self-management actions such as physical activity/exercise. MEP is consequently a substantial contributor to high-impact chronic pain and disability in people with OA; yet, our understanding of the mechanisms contributing to MEP and its management in older African Americans is severely limited. Therefore, the overall goals for this two-phased Mentored Patient-Oriented Research Career Development Award (K23) is to fill this knowledge gap by (1) characterizing the biopsychosocial-behavioral mechanisms of MEP and function and (2) develop a mechanism-based self-management intervention (Pain Relief for OsteoArthritis using Culturally-Tailored InterVentions for Black Elders [PROACTIVE]). This intervention will address the most pivotal and culturally-relevant predictors of MEP and impaired function in older African Americans. Our methods represent a new and substantive departure from current static pain assessments in chronic musculoskeletal disorders by measuring pain with movement. This K23 proposes training and research activities that will launch a program of research which advances the science of pain and disability in African American older adults. To this end, I have assembled an interdisciplinary team of senior scientists representing nursing, psychology/pain science, aging, and epidemiology/community engagement who will provide mentorship to help me achieve proposed training goals and facilitate my transition to an independent research career. Primary training goals essential to my research program include: (1) advance understanding of biopsychosocial and behavioral- environmental mechanisms of OA pain, (2) develop a comprehensive knowledge base in the application of community-engaged participatory research within experimental designs, and (3) enhance translational research skills to function as an independent investigator capable of conducting rigorous clinical trials testing the effectiveness of non-pharmacological, behavioral chronic pain self-management interventions within a cultured community (e.g., southern African Americans). Phase 2 of the K23 will apply community-based participatory mixed-methods to collaboratively create the PROACTIVE intervention. The University of Florida and University of Connecticut are strong incubators for pain research and provide ideal environments to extend the PI s prior work and forge a path towards understanding multiple biopsychosocial and behavioral mechanisms uniquely involved in the intra-ethnic experience of chronic pain, which are key to the discovery of better therapeutic interventions and self-management behaviors.
3. Project Title: Natural language processing (NLP) to connect social determinants and clinical factors for outcomes research
  Leader(s): WU, YONGHUI
    PCORI ME-2018C3-14754 / ( 2020 - 2024 )
  People interact with the environment at different levels in a large social system. Individuals health outcomes are determined through a complex interplay of multilevel factors, including both social determinants of health (e.g., education, employment, social cohesion) and behavioral determinants of health (e.g., smoking). For example, cancer, the second leading cause of death in the U.S., presents multiple causation and outcomes related to its biological, clinical, behavioral, and social influences. Nonetheless, these important variables are scarcely documented in structured medical codes but are often available in narrative clinical text. Clinical natural language processing (NLP) is the key technology to extract information from unstructured clinical text to support downstream applications that depend on structured data. However, NLP methods to extract social determinants of health have been understudied. Existing NLP systems for behavioral determinants and adverse events are suboptimal. Current clinical outcomes studies in PCORI communities are often limited to only structured medical codes due to a lack of NLP systems to identify and extract the necessary information and populate it into the national Patient-Centered Clinical Research Network (PCORnet) Common Data Model (CDM). This proposal seeks to develop NLP methods and systems to extract and connect social/behavioral information and adverse events with clinical factors (medical concepts that are directly generated by clinical practice, e.g., diseases, medications) for clinical outcomes research. The proposed NLP system will unlock mentions of social determinants, behavioral determinants, and adverse events from narrative clinical notes and populate them into structured PCORnet CDM databases. The NLP methods proposed in this project will also advance the extraction of general medical concepts from clinical narratives. This project will leverage the informatics infrastructure and clinical data at two PCORnet Clinical Data Research Network (CDRN) sites--the University of Florida affiliated with OneFlorida Clinical Research Consortium (OneFlorida CRC) and Weill Cornell Medicine affiliated with the New York City CDRN (NYC-CDRN). If successful, this project will provide an easy-to-use package to bridge the gap of using clinical narratives for PCORI and other communities. To develop a successful NLP tool for extracting social determinants (SDoH), behavioral determinants (BDoH), and adverse events (AEs) from clinical narratives, the involving of clinicians, patients, researchers, and data managers is very important. The clinician and patient representatives will provide suggestions on how the information was mentioned and documented in electronic health record systems (EHR) during patient-provider communications. This information can help us determine where different social and behavioral variables are documented to guide the development of methods and systems. The researchers will provide suggestions on identifying and categorizing the SDoH, BDoH, AEs, and other clinical factors that are priorities for their own studies. The representatives of data managers and analysts will provide feedback on pipelines to populate information to structured databases (e.g., PCORnet CDM) and how to use NLP extracted information to form queries that were not available before. We will form an advisory panel of all stakeholders and evaluate the system using cancer patients as cancer outcomes are known to relate with various social and behavioral influences and adverse events.
    NIH P30AG059297 / ( 2018 - 2023 )
  PROJECT SUMMARYChronic pain conditions represent arguably the most prevalent and costly public health problem in the UnitedStates, and they are the leading cause of disability worldwide. While pain affects individuals throughout thelifespan, older adults are disproportionately impacted and are at particularly increased risk for chronic pain andpain-related disability. Surprisingly, knowledge regarding the biopsychosocial mechanisms underlying age-related increases in pain remains quite limited, therefore, increased research is needed to elucidate social andbehavioral contributions to pain and disability among older adults. A critical barrier to progress in this area ofresearch is the limited availability of investigators with appropriate interdisciplinary training in addressing laterlife pain and disability. With strong institutional support, the University of Florida (UF) Resource Center forMinority Aging Research (RCMAR) will be established to address these scientific and workforce developmentneeds. The UF RCMAR has an educational objective to provide outstanding training and career developmentopportunities to promising investigators from underrepresented backgrounds. The UF RCMAR's researchobjective is to conduct innovative and impactful transdisciplinary social and behavioral research addressing painand disability among older adults, including health disparities in later life pain and disability (e.g. racial and ethnicdifferences, sex and gender differences, and socioeconomic influences). The UF RCMAR will accomplish theseobjectives through the synergistic efforts of four Cores: an Administrative Core (AC), a Research EducationComponent (REC), an Analysis Core (AnC), and a Community Liaison and Recruitment Core (CLRC). Inaddition, the UF RCMAR will benefit from extensive collaborations with other UF entities, including The UF PainResearch & Intervention Center of Excellence (PRICE), the UF Institute on Aging (IOA), and the UF Clinical andTranslational Science Institute (CTSI). The UF RCMAR boasts an outstanding interdisciplinary group of CoreFaculty with expertise spanning the spectrum of clinical and translational research related to our theme ofbiopsychosocial contributions to pain and disability among older adults. In order to accomplish its objectives, theUF RCMAR will recruit and retain outstanding early stage investigators from unrepresented backgrounds andprovide them with excellent mentoring and career development support. Through its research activities, the UFRCMAR will produce novel and important information regarding social and behavioral contributors to pain anddisability in older adults, and will develop and test innovative interventions to reduce later life pain and disability.
    NIH R01AG037984 / ( 2010 - 2023 )
  AbstractSex differences are evident in vulnerability to age-related cognitive decline and diseases of aging. Estradiol(E2) is protective against neurodegenerative diseases, including Alzheimer s disease, implicating sexhormone effects on sex differences in vulnerability. However, obstacles to sex steroid treatments includeclosing of the therapeutic window observed as decreased effectiveness of E2 treatment with advanced age.The goal of the proposed research is to provide an understanding of the mechanisms for E2 effects onmemory and the closing of the therapeutic window. Closing of the therapeutic window is marked by a decreasein E2-responseive transcription and an inability of E2 treatment to enhance N-methyl-D-aspartate receptor(NMDAR)-mediated synaptic transmission examined several days after treatment. Aim 1 will test thehypothesis that E2 treatment, several days prior to testing, specifically influences NMDAR-dependentepisodic memory, such that it can rescue an age-related decline in episodic memory examined on the watermaze and novel object recognition tasks. Aim 2 will test the hypothesis that E2 effects on memory andNMDAR function are mediated by reversal of NMDAR hypofunction, mediated by redox regulation ofphosphatase/kinase activity, similar to that previously described in aging males. Thus, it is predicted that priorto closing of the therapeutic window (i.e. in animals in which E2 treatment improves cognition and increasesNMDAR function), E2 treatment will promote antioxidant enzyme activity, reduce oxidative stress, andminimize redox-mediated decrease in CaMKII activity and NMDAR function. Further, following closing of thetherapeutic window (i.e. for animals in which E2 does not rescue cognition and NMDAR function), E2treatment will not promote antioxidant enzyme activity or reduce oxidative stress, and the NMDAR responseand CaMKII activity will be decreased due to an oxidized redox state. Aim 3 will test the hypothesis that age-related changes in transcriptional responsiveness to E2 are due, at least in part, to epigenetic regulationthrough DNA methylation. It is predicted that decreased responsiveness of E2-sensitive genes will beassociated with DNA hypermethylation, particularly in gene body regions (introns), and specific to CpG,relative to non-CpG methylation sites. The proposed studies will employ a powerful combination of behavioraltests that are sensitive to NMDAR function, patch-clamp recording of NMDAR synaptic responses, measuresof oxidative stress and enzyme activity, transcription, and DNA methylation.
    NIH R01AG055529 / ( 2018 - 2023 )
  PROJECT SUMMARY/ABSTRACTAging is the primary risk factor for the majority of chronic diseases. Studies in mice have implicated specificgrowth and differentiation factors (GDFs) and proteins secreted by senescent cells as potential modifiers ofaging. The objective of this proposal is to establish the rationale and provide robust clinical evidence for GDF8,GDF11, and senescence-related proteins eotaxin (CCL11), intracellular adhesion molecule 1 (ICAM1), activinA (AA), and plasminogen activator inhibitor 2 (PAI2), as indicators of biological age and age-related conditionsin humans. The central hypothesis is that circulating concentrations of GDFs and senescence-related proteinsare associated with, and predictive of, clinically important health outcomes and can be altered by physicalactivity. Samples from the Lifestyle Interventions and Independence for Elders (LIFE) Study; the largest andlongest randomized trial of a physical activity intervention in older adults, will be used to test this hypothesis,and samples from the Health, Aging, and Body Composition (HABC) Study will be used to validate studyfindings. A novel multiplexed liquid chromatography-tandem mass spectrometry assay will be leveraged toaccurately quantify GDFs, and an advanced multiplexing platform will be used to measure senescence-relatedproteins in LIFE and HABC biospecimens. In Specific Aim 1, a multidisciplinary team will first determine theextent to which baseline concentrations of GDF8, GDF11, CCL11, ICAM1, AA and PAI2 are associated withbaseline measures of physical (i.e., gait speed, Short Physical Performance Battery (SPPB) score),cardiopulmonary (i.e., blood pressure, forced expiratory volume), and cognitive (i.e., processing speed,memory) function, inflammation, and prevalence of multimorbidity (based on the ICD-9 codes for 20 chronicconditions). In Specific Aim 2, the degree to which baseline concentrations of GDFs and senescence-relatedproteins predict longitudinal changes in a) gait speed and SPPB score, b) major mobility disability (i.e., theinability to walk 400m), c) combined cardiovascular events (e.g., myocardial infarction, heart failure, stroke); d)adjudicated falls and injurious falls, e) cognitive function (as Aim 1), and f) the number of chronic conditions (asin Aim 1), at 1 and 2 years in LIFE and at 2 and 4 years in HABC will be determined. Finally, Specific Aim 3 willaddress whether a structured physical activity intervention impacts longitudinal changes in GDF8, GDF11,CCL11, ICAM1, AA, and PAI2, compared to a health education control intervention, and the degree to whichchange in the concentrations of these proteins parallel change in the health outcomes described in Aim 2. Thesuccessful completion of the proposed research will fill an important translational gap in our understanding ofhow GDFs and senescence-related proteins predict and, therefore, potentially mediate aging related disabilityand disease in older women and men. Ultimately, these proteins may be viable targets for innovative therapiesto extend human healthspan.
    NIH R01AG057693 / ( 2018 - 2023 )
  PROJECT SUMMARY Our work and that of others has established that people with lower extremity peripheral artery disease(PAD) have greater functional impairment and faster rates of functional decline than people without PAD.However, few therapies improve functioning or prevent functional decline in people with PAD. Intermittent pneumatic compression (IPC) is a non-invasive intervention, consisting of an air pumpinside inflatable cuffs that are wrapped around the feet, ankles, and calves and worn for two hours daily. Every20 second, the cuffs rapidly inflate, followed by rapid deflation. During deflation, arterial blood return into thearteriovenous pressure gradient generates shear stress and stimulates nitric oxide production. Preliminaryevidence suggests that IPC improves lower extremity blood flow and walking endurance in people with PADand that benefits persist for up to 12 months after intervention completion. However, evidence is limited bysmall sample sizes, high loss to follow-up, lack of blinding, and lack of sham controls. Clinical practiceguidelines do not mention IPC as a therapeutic option in PAD. A definitive randomized trial is needed. Walking exercise is first-line therapy for PAD. However, many PAD patients are unable or unwilling toexercise. Therefore, in people with PAD, we will determine whether IPC augments the benefits of exercise onwalking endurance and whether IPC alone improves walking endurance compared to sham control. We willconduct a randomized trial (2 x 2 factorial design) of 230 PAD participants randomized to one of four groups:Group A: IPC + exercise; Group B: IPC + no exercise control; Group C: sham control + exercise; and GroupD: sham control + no exercise control. The IPC and sham interventions will be delivered for six months. Inour primary specific aims, we will determine whether IPC combined with exercise improves the 6-minute walkat 6-month follow-up compared to exercise alone and whether IPC alone improves the 6-minute walk at 6-month follow-up, compared to sham control. In secondary aims, we will determine whether benefits of IPCpersist by re-measuring study outcomes at twelve-month follow-up, six months after the IPC intervention iscompleted. We will also delineate mechanisms by which IPC affects walking performance, by measuringchanges in MRI-measured calf muscle perfusion, physical activity (measured with ActiGraph), and calf musclebiopsy measures of angiogenesis, muscle regeneration, mitochondrial biogenesis, mitochondrial activity, andautophagy. Based on preclinical evidence that IPC increases nitric oxide abundance and promotesvasodilation in skeletal muscle distant from the lower extremities, we will determine whether IPC improvessystemic endothelial function, by measuring changes in brachial artery flow-mediated dilation. If the IPC intervention with and without exercise improves functional performance and preventsfunctional decline in PAD, this non-invasive and well tolerated intervention will have a major impact onpreventing mobility loss and improving quality of life in the large and growing number of people with PAD.
    NIH R01AG059809 / ( 2018 - 2023 )
  ABSTRACTOsteoarthritis (OA) represents a significant cause of disability worldwide in individuals aged 65 and older, arapidly growing segment of our population. The knee is the most commonly affected joint with pain being theprimary symptom, negatively impacting physical, cognitive, and emotional functioning. Symptomatic knee OAhas been traditionally attributed to peripheral mechanisms, but measures of joint damage only modestly accountfor the presence or severity of OA-related pain. The neuropeptide oxytocin (OT) has been recognized as amediator of endogenous analgesia in animal and human studies. However, little is known about theneurobiological mechanisms underlying OT's pain-relieving properties. This proposal is based on a mechanisticmodel of OT's analgesic effects leveraging pilot data supporting efficacy and safety of self-administeredintranasal OT over 4-weeks in older individuals. Relative to placebo (P), daily administration of intranasal OTdiminished self-reported pain intensity, reduced experimental pain sensitivity, and increased self-reportedphysical and emotional functioning. Further, participants treated with OT, compared to P, showed decreases inbrain metabolite concentrations associated with inflammation. Thus, our overarching goal is to evaluate theeffects of intranasal OT on pain and function in aging and to determine the extent to which central and peripheralinflammatory mechanisms contribute to these analgesic responses. We aim to 1) determine the effect ofintranasal OT administration on clinical and experimental pain sensitivity in older adults with symptomatic kneeOA and 2) characterize inflammatory mechanisms contributing to the inter-individual variability in analgesicresponses to OT. Older adults with symptomatic knee OA will self-administer intranasal OT or P over 4 weeksusing a double-blinded, parallel study design. With strong support from the University of Florida and the McKnightBrain Institute, our interdisciplinary project, using a comprehensive multi-methods approach, will be the first todetermine the potential benefit of OT as a novel analgesic therapy for knee OA pain in aging. OT is currentlyused in obstetrics and may be an inexpensive, effective method for pain management in older adults with littlepotential for addiction. Embedded in a biopsychosocial framework, our proposal will help pave the way for futureinvestigations using a mechanism-based treatment optimization strategy for individuals suffering from chronicpain.
  Leader(s): XIAO, RUI
    NIH R01AG063766 / ( 2019 - 2024 )
  Project SummaryAge-dependent olfactory decline (presbyosmia) is widely present in many species, including humans. At leastfifteen million Americans over 55 years old suffer from presbyosmia. By affecting the well-being, quality of life,and overall health, presbyosmia presents a significant challenge to public health. Patients with presbyosmiaoften show a decreased interest in food, can withdraw socially, and exhibit higher rates of depression.Furthermore, many age-related neurological diseases, including Parkinson's disease and Alzheimer's disease,are commonly associated with olfactory dysfunction. In fact, olfactory loss often precedes various motoricsymptoms in these deadly neurological diseases. Despite the importance of olfaction to human physiology andhealth, the cellular and molecular mechanisms underlying presbyosmia are poorly understood (knowledgegap).As a major cell type in the nervous system, glial cells are typically considered as passive modulators duringneural development and synaptic transmission. Whether glial cells play active roles in sensory transductionand brain aging is not well understood. C. elegans is a well-established model organism for neuroscience andaging research due to its simple nervous system, short lifespan, and powerful genetic tools. Very importantly,genetic studies from multiple model organisms have shown that the evolutionarily conserved genetic programsand signaling pathways play pivotal roles in regulating sensory transduction and aging process across species.This proposal will bring together in vivo calcium imaging, optogenetics, molecular genetics, and behavioralanalysis to investigate and discover the molecular mechanisms through which the olfactory glial cells playactive roles in odorant detection and age-dependent olfactory decline. Since both olfaction and aging areregulated by the evolutionarily conserved genes and signaling pathways, our innovative studies on C. elegansglial cells in olfaction and age-associated olfactory decline will provide mechanistic insights into similarprocesses in other species.
    NIH R01AG067757 / ( 2020 - 2025 )
  Discovery and validation of strong candidate biomarkers and clinical endpoints for pain is urgently needed that can be used to facilitate the development of non-opioid pain therapeutics from discovery through Phase II clinical trials. Emerging research using a combination of biomarkers deliver individualized predictions about future brain and body health. Our own findings suggest that behavioral chronic pain characteristics are associated with multiple biological biomarkers where a greater pain burden is associated with accelerated detrimental biological processes. However, prospective research is urgently needed to determine pain s impact on the heterogeneity of these biological processes within an individual to elucidate the underlying patterns of biological changes using a biobehavioral perspective which is needed for predicting future health and to be able to use as clinical endpoints for interventions. The proposed study will prospectively address biobehavioral factors (i.e., cognitive, psychological, social and cultural) affecting the experience and interpretation of knee pain and physical function across racial/ethnic groups over time. We will prospectively assess pain along with multiple biomarkers as predictors of cognitive, psychological and physical functional progression among middle-aged and older non- Hispanic Blacks and non-Hispanic Whites with knee pain and controls over a four-year study period. With strong support from the University of Florida, our interdisciplinary project, using a comprehensive biobehavioral multi- methods approach, we will be the first to prospectively determine the trajectory and interactions among pain, biological biomarkers and multiple domains of function within race/ethnic groups in OA pain. Findings will contribute towards increased understanding of pain and its biobehavioral basis, with the potential to reduce race/ethnic group disparities and improve pain-related health and functional outcomes.
  Leader(s): BIAN, JIANG; GUO, YI ;
    NIH R01CA246418 / ( 2020 - 2023 )
  Lung cancer is the leading cause of cancer related death in both men and women in the United States. Currently, approximately 70% of lung cancer patients are diagnosed at advanced stages, and the 5-year survival rate of advanced stage lung cancer is very low, at only 16%. Investigators have been searching for effective screening modalities for the early detection of lung cancer so that patients can receive curative treatments at an early stage. When the National Lung Screening Trial (NLST) demonstrated the effectiveness of using low-dose computed tomography (LDCT) scan for lung cancer screening (LCS), researchers and physicians hope to save lives from lung cancer by screening high-risk population who aged 55 to 77 years and have a 30 pack years making history or former smokes who have quitted within the past 15 years. Since the release of the landmark NLST results, many medical associations published guidelines to recommend LDCT-based screening for individuals at high risk for lung cancer and the Centers for Medicare and Medicaid Services (CMS) also decided to cover the LCS for Medicare beneficiaries who are at high risk for lung cancer. While many efforts have been made to accelerate the dissemination the beneficial LCS, the concerns over the high false positive rates (96.4% of the positive results), invasive diagnostic procedures, postprocedural complications and health care costs may hinder the utilization of lung cancer screening. This concern was magnified as researchers and policy makers started questioning whether the complication rate and false positives in real-world settings would be even higher than the rates reported in the NLST, which was conducted in a setting with well-established facilities and proficiency in cancer care. Therefore, we propose to understand the contemporary use of lung cancer screening and associated health care outcomes and costs using data from a real-world setting. Our study has three goals: 1) to develop an innovative computable phenotype algorithm to identify high-risk and low-risk individuals for LCS from both structured and unstructured (i.e., clinical notes) electronic health record (EHR) data and to develop advanced natural language processing (NLP) methods to extract LCS related clinical information from clinical notes such as radiology reports; 2) to determine the appropriate and inappropriate use of LDCT among high-risk and low-risk individuals in Florida and to examine the test results of LDCT, the rates of invasive diagnostic procedures, postprocedural complications, and incidental findings in real-world settings; and 3) to develop and validate a microsimulation model of the clinical courses of LCS incorporating the real-world data in LCS to estimate the long-term benefits and the cost-effectiveness of LCS. Our proposed study has the potential to reduce lung cancer incidence and mortality by informing policymakers and practitioners on the appropriateness of contemporary use of LCS. This knowledge will help both patients and physicians better understand the harm- benefit tradeoff of lung cancer screening and transform such knowledge into practice to prevent avoidable postprocedural complications.
12. Project Title: Evaluation of an Adaptive Intervention for Weight Loss Maintenance
    NIH R01DK119244 / ( 2019 - 2024 )
  Obesity remains a substantial public health challenge in the United States. Behavioral weight management programs have demonstrated effectiveness for weight loss, but long-term maintenance of these weight losses after the end of treatment tends to be poor. Evidence has demonstrated that individuals who can maintain their changes in eating and activity can successfully maintain their weight loss; thus, attempts to improve weight loss maintenance have often involved provision of continued support through monthly extended-care intervention sessions. While these interventions have demonstrated significant improvements in weight loss maintenance, effects have been modest. A key challenge is continued participant engagement (often assessed as attendance at intervention sessions). Attendance has been closely tied to weight outcomes, but rates tend to be poor and decline over time. The once-per-month, static treatment schedules of existing programs may contribute to these suboptimal outcomes; a participant experiencing a small lapse in weight-related behaviors may not receive support for several weeks, by which point they may be experiencing a larger lapse or weight regain. This can lead to feelings of frustration, shame, or embarrassment and disengagement from intervention. In contrast, tailoring intervention delivery such that sessions are provided when individuals are at high risk for weight regain offers potential to disrupt this cycle and significantly improve program engagement, adherence to program goals, and long-term weight maintenance outcomes. We propose to evaluate an innovative method of providing phone-based extended-care adaptive to participant needs. We have built a smartphone application that can be used by participants to track weight, dietary intake, and physical activity (key self-monitoring behaviors in traditional behavioral weight management programs) and can further query participants throughout the week regarding self-report factors (e.g., ratings of hunger and the importance of staying on track with weight management goals) that indicate high risk for weight regain. We have also developed a predictive algorithm that uses this data to identify when individuals are at high risk of weight regain. We propose to conduct a randomized controlled trial evaluating the impact of ADAPTIVE (delivered only when indicated by our algorithm or when initiated by participants via an in-app support request) versus STATIC (the monthly, pre-scheduled format used in existing extended-care programs) treatment provision on weight regain at 24 Months in 258 adults who successfully lose = 5% of initial weight during a gold-standard 16-week behavioral weight management program. Results of this study have clear treatment implications for the timing/frequency of sessions within extended-care weight maintenance programs, and this study will result in an innovative, low-cost, and easily scalable intervention for weight loss maintenance. Further, the proposed research will fill a critical gap in the weight management literature by building a foundational evidence base of proximal predictors of weight-related behaviors for future adaptive intervention development.
  Leader(s): GUIRGIS, FAHEEM W
    NIH R01GM133815 / ( 2020 - 2025 )
  Sepsis is a dysregulated response to infection that has both fatal and non-fatal morbid consequences. Unfortunately, initial survival does not provide relief from morbidity for most sepsis survivors. Initial clinical trajectories include rapid recovery, early in-hospital death, and progression to chronic critical illness (ICU stay = 14 days with organ dysfunction). Late complications include sepsis readmission and late death, both of which have rates of approximately 40% at 90 days and 6 months, respectively. Circulating lipids play an important role in sepsis and cholesterol levels of both high density lipoproteins (HDL-C) and low density lipoproteins (LDL-C) are dynamically regulated in sepsis. HDL and LDL are both thought to play protective roles in sepsis via several mechanisms (antioxidant/anti-inflammatory function, bacterial toxin clearance, steroid synthesis), but the exact mechanisms by which HDL and LDL protects against sepsis are not known. Lipid and lipoprotein dysregulation occurs in early sepsis, leading to failure to protect against sepsis. We have shown that: 1) HDL becomes dysfunctional (pro-oxidant and pro-inflammatory) in early sepsis (Dys-HDL); 2) elevated Dys-HDL levels positively correlate with and predict organ failure severity and are associated with poor outcomes including 28-day mortality; 3) HDL from older septic patients exhibits impaired cholesterol efflux capacity (required for toxin clearance and steroidogenesis); 4) HDL and LDL levels drop precipitously during sepsis, and the severity of the drop is predictive of death; and 5) low baseline LDL levels are associated with increased long-term community-acquired sepsis risk. Highly biologically active lipid metabolites are also present in the circulation during sepsis that may propagate and promote inflammation resolution and contribute to cholesterol dysfunction. Our data strongly suggest that lipid and lipoprotein dysregulation occurs in sepsis and leads to altered function, oxidation, and reduced levels that may influence clinical outcomes. We hypothesize that specific functional, lipidomic, and genomic changes in lipid and lipoprotein metabolism occur in early sepsis and relate to relevant clinical trajectories (rapid recovery, early death, and chronic critical illness and sepsis recidivism). To test our hypothesis, we will capitalize on an established and experienced sepsis research team and the opportunity provided by an existing bank of samples from a diverse cohort of 80 community-acquired (CA) and 85 hospital-acquired (HA) sepsis patients from two-centers. This approach has several advantages: 1) cost-savings from use of existing samples with isolated mRNA, 2) a recent cohort of sepsis patients (2016-2018) consistently treated with institutional evidence-based management bundles, 3) availability of serial samples over time (enrollment, 48h, 28d, and 90d), sepsis readmission samples, and mRNA for the CA cohort, 4) age/gender matched control samples, 5) available clinical and outcomes data. We also propose two-site prospective enrollment of a small cohort of sepsis readmission patients to study this novel and important outcome. This project satisfies the NIGMS mission of researching biological mechanisms that underlay the foundation for advances in treatment of diseases such as sepsis.
  Leader(s): DELISLE, BRIAN P
    NIH R01HL141343 / ( 2019 - 2023 )
  SummaryCircadian rhythms help to match the optimal function of the cardiovascular system to the daily changes in theenvironment. Normal cardiovascular rhythms provide a physiological advantage to people. Unfortunately,normal circadian signaling can also unmask a time-of-day pattern in adverse events like heart attack, stroke,and sudden death in patients with underlying cardiovascular disease.Emerging data now show that abnormal or unhealthy daily rhythms can create a negative impact on normalhealth too. For example shiftwork, which repeatedly causes shifts in endogenous circadian rhythms, is anindependent risk factor for cardiovascular disease.In mammals the suprachiasmatic nucleus (SCN) in the brain is the primary circadian pacemaker that helps toentrain endogenous rhythms to the environment. SCN rhythms are synchronized to the environment via light,and its signaling helps to coordinate the molecular rhythms in cells throughout the body. What is new aboutthis application is we determine how repeated changes in light cycle will impact molecular circadian signaling inthe heart.Most cells have a molecular clock signaling mechanism that cycles with a periodicity of ~24 hours. We foundgenetic disruptions in the molecular clock mechanism of heart cells (cardiomyocytes) primarily causesabnormal changes in cardiac electrophysiology by disrupting the regulation of ion channel function.The goal of this application is to determine how repeated shifts in the light cycle impact molecular clocksignaling in the mouse heart and its regulation on ion channel function.Aim 1. To identify new mechanisms with which the cardiac molecular clock regulates different ion channels.Aim 2. To determine how repeated changes in light impact molecular clock signaling in the heart and ionchannel regulation.This project creates new knowledge at the interface between chronobiology and cardiac electrophysiology.
  Leader(s): SCALI, SALVATORE T.
    NIH R01HL148597 / ( 2019 - 2024 )
  PROJECT SUMMARYCurrently, in the United States, there are ~425,000 patients receiving hemodialysis (HD) and it is estimated that30-60% of this population have some element of hand dysfunction after hemoaccess surgery. The underlyingpathophysiologic mechanisms responsible for this devastating problem are poorly understood. The renaldysfunction (RD) milieu causes a variety of physiologic derangements in HD patients including increasedoxidative stress (OS) and chronic inflammation that have been implicated as major contributors to acceleratedatherosclerosis and elevated mortality. Profound changes in OS contribute to skeletal muscle and neuromuscularjunction dysfunction associated with muscle atrophy and frailty in this population. AVF surgery causes significanthemodynamic changes in the extremity which presents an adaptive challenge to the skeletal muscle andneuromotor end-plate. Supported by our previous work, as well as preliminary data on RD associated skeletalmuscle mitochondrial phenotypic changes, we propose that RD driven mitochondrial dysfunction alters skeletalmuscle and neuromuscular junction responses to AVF induced ischemia leading to clinically apparent handdysfunction. Further, these pathways can be modified either prior to AVF creation or at first evidence of handdysfunction to reverse/prevent the functional impairment. Our hypothesis is that the RD milieu disruptsmitochondrial and cellular energetics resulting in elevated OS predisposing patients undergoing AVF surgery todeveloping skeletal muscle and neuromuscular junction perturbations causing clinically significant handdysfunction. RD mediated mitochondrial impairments are further exacerbated by local hemodynamic changesfollowing AVF creation through maladaptive OS metabolic responses that drives the diversity of clinicallyapparent hand dysfunction. Aim 1 will establish how RD impacts mitochondrial and cellular energetics that areexacerbated by AVF-induced limb ischemia. Using a series of in vitro experiments, we will uncover thebiochemical mechanisms by which RD impacts mitochondrial energetics leading to impaired oxidativephosphorylation and increased OS. Aim 2 will determine the efficacy of global or mitochondrial-targetedantioxidant therapies delivered prior to- and following AVF surgery in mice. Using a novel RD murine AVF model,we will determine whether global (N-acetylcysteine) or mitochondrial-targeted (AAV delivery of mitochondrialtargeted catalase) antioxidant therapy have therapeutic potential for AVF-induced muscle dysfunction. Aim 3will evaluate the association between mitochondrial health and AVF-induced hand dysfunction in humanpatients. Mitochondrial health will be examined in-situ using permeabilized myofibers prepared from RD patientsbefore and after AVF surgery: mitochondrial phenotypic changes will be evaluated and their association withchanges in serial hemodynamic, neurophysiological and biomechanical outcomes modulating the spectrum ofhand function will be determined.
  Leader(s): RYAN, TERENCE E
    NIH R01HL149704 / ( 2019 - 2024 )
  Peripheral artery disease (PAD) is caused by atherosclerosis in the lower extremities which leads to a spectrum of life-altering symptomatology, including claudication, ischemic rest pain, and gangrene requiring limb amputation. Complicating the etiology of PAD, patients typically present with comorbid conditions or risk factors that accelerate disease evolution and substantially worsen pathology contributing to increased mortality risk. Among these, chronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases functional capacity, and increases risk of amputation or death, however the underlying biologic mechanism(s) are poorly understood and vastly understudied compared with other comorbidities (i.e. smoking and diabetes). We have uncovered a novel molecular pathway that may link CKD and PAD pathobiology. We find that many uremic metabolites, which accumulate in CKD, cause chronic activation of the aryl hydrocarbon receptor (AHR) which leads to disruption of the mitochondrial electron transport system that exacerbates ischemic muscle injury and impairs angiogenesis. Preliminary experiments demonstrate that genetic knockdown of the AHR is protective against uremic toxicity, whereas expression of a constitutively active AHR causes mitochondrial dysfunction. Thus, we propose to test the novel hypothesis that the chronic activation of the AHR pathway results in ischemic muscle injury and impaired angiogenesis, thereby linking CKD and PAD pathobiology. This hypothesis will be tested using muscle- and vascular-specific inducible knockout of the AHR as well as adeno- associated virus-mediated expression of the a constitutively active AHR in pre-clinical models of CKD/PAD. Finally, our recent human data indicate elevated AHR signaling in PAD patients with CKD. We propose to extend these findings to establish a clinical link between muscle health/function, mitochondrial energetics, and AHR signaling in human PAD patients. Success in these studies will provide mechanistic insight into the impact of CKD on PAD pathobiology, and would provide a novel target for therapeutic development aimed to treat a patient population that currently has few available options.
    NIH R01HL153042 / ( 2020 - 2024 )
  The overall objectives of this proposal are to 1) define the genomic and transcriptomic mechanisms by which the cardiomyocyte clock regulates ion channels that contribute to cardiac excitability; and 2) disrupt the cardiomyocyte clock to link changes in circadian-ordered gene expression with electrophysiological properties of atrial and ventricular cardiomyocytes. The outcomes will address significant gaps in our understanding for how the myocardial circadian clock regulates the expression of key cardiac ion channels and how abnormal cardiac clock function contributes to arrhythmia vulnerability. The mechanism regulating circadian timing, the molecular clock, exists in virtually all cell types in the body. A critical function of the molecular clock is to link time of day with a large-scale transcriptional program to support cellular homeostasis To date, our labs have used an inducible cardiomyocyte specific mouse model to knock out the core clock gene, Bmal1 (iCSBmal1). These studies showed that disruption of the myocardial clock is sufficient to decrease ventricular K+ and Na+ channel gene expression, disrupt current levels, disrupt cardiac excitability, and increase arrhythmia susceptibility. These studies establish a critical role for the cardiomyocyte clock, independent of the central clock, in regulating the expression of different families of ion channel genes that impact the ionic balance needed for normal excitability. One goal of this project is to utilize large scale genomic and transcriptomic approaches with our mouse model system to define the circadian clock dependent control of temporal gene expression in both atrial and ventricular tissues. To address abnormal circadian clock function, our lab has used different models of circadian disruption, such as chronic phase advance or time restricted feeding to test links between circadian disruption and arrhythmia vulnerability in mouse models. We have found that disrupting either light or feeding time cues is sufficient to induce pathological changes in cardiac rhythms in normal mice and to accelerate sudden cardiac death in a genetic mouse model of arrhythmia susceptibility. These studies support our premise that disruption of day- night rhythms through environmental factors leads to altered myocardial clock function with outcomes that include modified ion channel expression, cardiac excitability and arrhythmia vulnerability. The aims of this proposal are designed to test the following hypotheses: 1) The molecular clocks in both atrial and ventricular cardiomyocytes are necessary to direct daily chromatin accessibility and transcriptional output including expression of key ion channel and ion channel regulatory genes. 2) Chronic disruption of the cardiomyocyte clock using altered time of feeding is sufficient to cause dysregulation of the cardiac clock resulting in an imbalance in cardiac ion channel expression and currents leading to altered excitability and increased arrhythmia vulnerability.
    NIH R01NR016986 / ( 2018 - 2023 )
  ABSTRACT Our long-term goal is to elucidate the complex biobehavioral mechanisms responsible for symptoms andhealing outcomes for older adults with venous leg ulcers (VLUs) for the development of targeted therapies thataddress both the patient-oriented outcomes and healing outcomes in this growing group of affected individuals.VLUs, which account for 70 90% of ulcers found in the lower leg, affect 2 million persons annually, includingnearly 4% of people over age 65 years. To date, the basic biology underlying the development and persistenceof VLUs and the influence of aging and multiple disease conditions on wound healing are generally not wellunderstood. Individuals living with chronic VLU (CVLU) have a high symptom burden of both wound-relatedsymptoms and symptoms of pain, depression, anxiety, fatigue and cognitive dysfunction, collectively labeled as psychoneurologic symptoms (PNS). Guided by the National Institutes of Health Symptom Science Model(NIH-SSM) framework, the central hypothesis of this application is that there are interrelated molecularmechanisms by which the immune activation that contributes to the development and persistence of CVLUalso leads to the development, persistence and severity of PNS. The specific aims of the proposed study areto: (1) Characterize the strength of the associations at baseline among patient-host factors, systemicinflammation, and wound microenvironment with wound area and symptoms (PNS and wound-related); and,(2) Test associations and models over time for: (a) Patient-host factors and systemic inflammation with woundmicroenvironment; (b) Patient-host factors and wound microenvironment with systemic inflammation; (c)Patient-host factors, systemic inflammation, and wound microenvironment with wound healing; (d) Patient-hostfactors, systemic inflammation, and wound microenvironment with symptoms (PNS and wound-related) and (e)Patient-host factors, systemic inflammation, wound microenvironment and wound healing with symptoms (PNSand wound-related). To achieve the specific aims, we will longitudinally examine 200 older adults (age >60)who are receiving state of the art, standardized wound treatment biweekly across eight weeks time. We willfully characterize patient-host characteristics (age, comorbidities, sex, race/ethnicity, BMI, nutritional status,lifestyle habits, and wound treatment [pressure therapy, debridement, antibiotics]); systemic inflammatoryactivation (C-reactive protein and cytokines); wound microenvironment factors (local inflammation [Matrixmetalloproteinase (MMP) enzymes C-reactive protein, cytokines], biofilm, and micro RNAs); symptoms (PNS[cognitive dysfunction, pain, fatigue, and depressive/anxiety symptoms] and wound-related); and woundcharacteristics and healing trajectory at the five timepoints. This knowledge is critical to provide a foundationfor developing targeted interventions to address this critical health problem from a holistic perspective and toprovide a basis for preventing or reversing the adverse health outcomes of CVLUs, a condition thatdifferentially affects older and minority individuals.
    NIH R37AG033906 / ( 2009 - 2024 )
  No abstract provided
    NIH T32AG049673 / ( 2015 - 2025 )
  DESCRIPTION (provided by applicant): As detailed in a recent Institute of Medicine (IOM) report, chronic pain represents a major public health concern, affecting 100 million U.S. adults and costing more than $500 billion annually. Aging confers increased risk for chronic pain, with half of older adults reporting persistent or recurring pain, and aging is associated with greater pain-related loss of physical and psychosocial function. Current knowledge regarding pain and aging is surprisingly limited, and future progress in the field hinges on the availability of well-trained scientists who have an appreciation for preclinical and clinical research approaches to the study of both aging and pain. At present, there are no existing NIH-funded T32 programs devoted to training in pain and aging. To address this unmet need, we propose to develop a new postdoctoral training program: the Integrative and Multidisciplinary Pain and Aging Research Training (IMPART) Program. The overall goal of the IMPART program is to develop outstanding independent investigators capable of sustaining productive clinical and translational research careers addressing the biopsychosocial mechanisms underlying age-related changes in the experience of pain and/or designing clinical interventions to ameliorate acute and chronic pain among older adults. In order to accomplish this overarching goal, the specific aims of this new postdoctoral training program in pain and aging research are to: 1) Recruit and train promising junior investigators to conduct mechanistically-based and clinically relevant translational research in pain and aging; 2) Implement an integrated didactic and experiential training program, which will equip trainees with new research skills and the knowledge and expertise to apply these skills to address important and unanswered questions regarding pain and aging; and 3) Create a culture of research excellence in order to ensure that trainees aspire to the high standards of scientific integrity and quality, which will set the tone for their futurecareers in pain and aging research. IMPART leverages two excellent and collaborative research programs at the University of Florida - the aging research community represented by the Institute on Aging (IOA), and the pain research community, organized under the Pain Research and Intervention Center of Excellence (PRICE). Each member of the training faculty boasts an excellent track record of both research funding and mentoring experience. The proposed program requests support for four postdoctoral trainees from a variety of training backgrounds, each of whom will work with their multidisciplinary mentoring team to create and implement a tailored independent development plan as the blueprint for their training. Trainees will achieve their research and career development objectives through a combination of didactic, research, and professional development activities, and program evaluation will be ongoing and multimodal. The IMPART Program is committed to promoting diversity among our trainees, and the program will provide a training experience that emphasizes excellence in research integrity and ethics.
  Leader(s): MANINI, TODD
    NIH T32AG062728 / ( 2020 - 2025 )
  Preserved mobility is one of hallmarks of geriatric care, gerontology and geroscience. The loss of mobility with aging is progressive, caused by multiple factors and does not have a simple cure. Unfortunately, mobility loss continues to lack clinical attention, robust biomedical targets, objectively-measured surveillance systems, and effective treatments. As a result, mobility difficulties have remained persistently high and stagnant since it was systematically measured in the late 1980's. Currently, 30% of Americans aged 60-69, 40% of individuals aged 70-79, and 55% of individuals age 80 or older report difficulties with their mobility (e.g. walking and climbing stairs). To address this unmet need, we propose the Translational Research training on Aging and Mobility (TRAM) postdoctoral training program to train 4 post-doctoral fellows per year (2 in year one). The overall goal of the TRAM program is to develop outstanding independent investigators capable of sustaining productive multi-disciplinary and translational research careers addressing the multi-factorial causes and consequences of age-related changes in mobility and/or designing multi-modal interventions to prevent and rehabilitate mobility impairments in older adults. The goals are to: 1) Provide a 2-3 year integrated training program for PhD/MD fellows to create a career pathway for conducting mechanistic and clinically relevant translational research in mobility and aging; 2) Implement a cross-fertilized training program based on the Experiential Learning Theory; 3) To equip trainees with new research skills along with the knowledge and expertise to address impactful and unanswered questions regarding mobility and aging; 4) Closely monitor and track trainee-related experiences and outcomes for making continuous quality improvements; 5) Create a culture for professional excellence and development based on enhancing rigor, reproducibility and transparency in trainee-related research and; 6) To attract, recruit and enroll minorities, and those with disabilities and disadvantaged backgrounds. TRAM program faculty are collaborators on each other's projects, bring strong mentorship experience and successful commitment to research related to mobility and/or aging. Program faculty are grouped into either Aging or Mobility Research Clusters based on research focus and expertise. TRAM will use a mosaic mentoring approach that will employ dual primary mentors one from aging and another from mobility expertise a third mentor will serve as an advocate/sponsor. Mentees will also receive support from other archetypes like coaches, connectors and senior peer mentors. This unified mentoring team will guide trainees through an individual development plan, didactic coursework (e.g. mechanistic and clinical-based research on aging and/or mobility, ethics, responsible conduct of research), directed research training, and professional development activities (e.g. strategic planning, innovative leadership) that will be tailored according to the educational needs and research interests of the trainee. At completion, TRAM fellows will fulfill the scientific needs and grow the research workforce for meeting the growing population of mobility impaired older adults.
  Leader(s): MOLDAWER, LYLE L
    NIH T32GM008721 / ( 1999 - 2024 )
  This Ruth Kirschstein NRSA training Program proposes to take primarily surgeons and other critical caremedicine physicians during the second or third year of their general residency programs, and expose them totwo, three and even four years of mentored research in inflammation biology with highly productive basic sciencementors focused on inflammation-related topics. Four training positions are requested. The overall researchprogram will focus on mastery of molecular biology, functional genomics and gene regulation, as it appliesbroadly to inflammation research. Although the bulk of the training program will be in the laboratory of anexperienced research mentor, trainees will be expected to participate in didactic experiences that complementtheir research experience. Select trainees will have the opportunity to complete a Ph.D. program in the GraduateSchool in three to four years. Other trainees can participate in graduate certificate programs which are formalcollections of courses that together form a coherent program of study offered through an academic unit. Thistraining program takes advantage of the unique strengths of the College of Medicine in the expanding field offunctional genomics and molecular biology, as well as the existing collaborations between basic scientists andclinicians committed to the training of future clinical academicians. The interface between molecular biology andinflammation research will be targeted to trauma, sepsis syndromes, ischemia/reperfusion injury, vascular injury,delayed wound healing and the burn wound. The faculty will be drawn from funded basic and clinical scientistsin the Surgery, Medicine, Pathology, Aging and Geriatric Research and Molecular Genetics and MicrobiologyDepartments, who will serve as research mentors to the trainees. Clinical mentors from the Surgery, Medicineand Pathology Departments will interact with the trainees and the research faculty to assure that the traineesare being exposed to clinically-important issues in inflammation research. Overall direction of the program willrest with the Program Director and an Executive Committee. Candidates for the fellowship are recruitednationally and from the University of Florida College of Medicine (Gainesville, Jacksonville). Successfulapplicants with the Executive Committee will identify a research and clinical mentor who will help formulate aformal training program and periodic review of the trainee s progress. Furthermore, trainees are expected toparticipate in basic science seminars in the Institute on Aging, Emerging Pathogens Institute and GeneticsInstitute, and in their own basic science departments, as well as laboratory research meetings. They will also beexpected to attend clinical seminars, including Surgery and Critical Care Medicine Grand Rounds and theDepartment of Surgery Academic Research Conference. Based on our past experiences, it is anticipated thatsuccessful graduates of this training program will possess sufficient research skills to successfully compete fortransitional funding in inflammation research and become leaders in academic surgery.
    NIH U01AG061389 / ( 2018 - 2023 )
  Project Description: Mobility impairments in older adults decrease quality of life and are associated with highsocietal and economic burden. NIH RFA-AG-18-019 solicits applications to investigate the central neuralcontrol of mobility in older adults using innovative and cutting-edge methods. Current approaches to studythe neural control of walking are limited by either the inability to measure people during walking (functionalmagnetic resonance imaging, fMRI) or the inability to measure activity below the cortex (functional near-infrared spectroscopy, fNIRS). We assert that a full and accurate understanding of the neural control of walkingin older adults requires real time measurement of active regions throughout the brain during actual walking. Wewill achieve this by using innovative mobile brain imaging with high-density electroencephalography (EEG).This approach relies upon innovative hardware and software to deliver three-dimensional localization of activecortical and subcortical brain regions with high spatial and temporal resolution during walking. The result isunprecedented insight into the neural control of walking. Here, our overarching objective is to determine thecentral neural control of mobility in older adults by collecting EEG during walking and correlating these findingswith a comprehensive set of diverse mobility outcomes (clinic-based walking, complex walking and communitymobility measures). Our first aim is to evaluate the extent to which brain activity during actual walking explainsmobility decline. In both cross sectional and longitudinal designs, we will determine whether poorer walkingperformance and steeper trajectories of decline are associated with the Compensation Related Utilization ofNeural Circuits Hypothesis (CRUNCH). CRUNCH is a well-supported model of brain activity patterns that areseen when older individuals perform tasks of increasing complexity. CRUNCH describes the over-recruitmentof frontoparietal brain networks that older adults exhibit in comparison to young adults, even at low levels oftask complexity. CRUNCH also describes the limited reserve resources available in the older brain. Thesefactors cause older adults to quickly reach a ceiling in brain resources when performing tasks of increasingcomplexity. When the ceiling is reached, performance suffers. The RFA also calls for proposals to Operationalize and harmonize imaging protocols and techniques for quantifying dynamic gait and motorfunctions . In accordance with this call, our second aim is to characterize and harmonize high-density EEGduring walking with fNIRS (during actual and imaged walking) and fMRI (during imagined walking). This willallow us to identify the most robust CRUNCH-related hallmarks of brain activity across neuroimagingmodalities, which will strengthen our conclusions and allow for widespread application of our findings. Ourthird aim is to study the mechanisms related to CRUNCH during walking. Thus, our project will address amajority of the objectives in NIH RFA-AG-18-019 and will identify the neural correlates of walking in olderadults, leading to unprecedented insight into mobility declines and dysfunction.
24. Project Title: PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr Adults (PREVENTABLE)
    NIH U19AG065188 / ( 2019 - 2026 )
  There is an urgent need for evidence to guide clinical care of older adults due to demographic shifts, including longer life expectancy and a recent doubling of the older adult population. Statins reduce recurrent CVD events and prevent initial events in patients younger than 75 years. However, clinical research has often excluded persons older than 75 years due to a higher prevalence of comorbidity and frailty so little to no evidence is available to guide care in this population. For older adults living longer, the promise of preventing cognitive impairment is as compelling as preventing a CVD event, but some evidence suggests statins may contribute to memory difficulty or muscle symptoms. There is equipoise regarding the usefulness of statins for primary CVD, dementia, and disability prevention in adults older than 75 years, especially in the setting of multiple chronic conditions, advanced age, or frailty. Evidence to improve cognitive and functional outcomes in older populations with diverse race/ethnicity and health status will require new clinical trial approaches with sustainable methodology and infrastructure. We propose PREVENTABLE (PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr adults), the first statin trial with a non-CVD primary outcome survival free of dementia or persisting disability. Using a placebo-controlled pragmatic clinical trial (PCT) design across PCORnet and VA network, the trial will be under the leadership of Dr. Karen Alexander at DCRI, Dr. Jeff Williamson at WFSM, Dr. Adrian Hernandez at DCRI, and Dr. Walter Ambrosius at WFSM. This team has established experience and track-record of accomplishment in the design and conduct of PCTs, trial expertise in ascertaining cognitive and disability outcomes in older adults, and is supported by a robust administrative infrastructure for coordinating these shared responsibilities for success. The overarching goal of PREVENTABLE is to generate knowledge about the role of statins in older adults, a population in which risk/benefit for primary prevention has been under studied. The hypothesis is that a large trial conducted in an older adult population will demonstrate the benefit of statins for reducing dementia, disability, and CV events. We further hypothesize that extensive genomic, biochemical and imaging ancillary studies will offer unique insights into these key outcomes. PREVENTABLE has the following specific aims: AIM 1: Determine the role of a moderate-intensity statin in preventing dementia and prolonging disability-free survival in patients 75 years and older without clinically evident coronary heart disease, including those with frailty, impaired physical function, mild cognitive impairment, polypharmacy, and multi-morbidity. AIM 2: Determine the role of moderate- intensity statin in preventing hospitalization for myocardial infarction/acute coronary syndrome, stroke, heart failure, revascularization or cardiovascular-related death, and preventing either mild cognitive impairment or dementia. AIM 3: Test the safety and tolerability of statins in older adults and collect 17,000 bio-specimens to advance precision health.
  Leader(s): MITCHELL, DUANE A.
    NIH UL1TR001427 / ( 2015 - 2024 )
  Florida is a demographically and geographically diverse state. The University of Florida (UF) and Florida StateUniversity (FSU) CTSA hub will work within this environment to further the mission to improve human health byaccelerating the translation of scientific discoveries and the implementation of evidence-based best practicesfor the diagnosis, treatment, prevention and cure of human diseases across the lifespan. The UF-FSU hubvision is think globally, act locally , offering research opportunities to underserved participants in North andNorth Central Florida, creating innovative career development and training opportunities, as well ascollaborating across the country with the Accelerated Clinical Trials Network and PCORnet. Researchstrengths include precision medicine, team science, community engagement, implementation science andinformatics which are conducted in diverse settings through the OneFlorida Clinical Research Consortium. The2019-2024 period represents the next phase of evolution from creating a clinical and translational scienceinfrastructure to enhancing the local, state and national impact of CTSI-led science. During this period, FSUwill be integrated across all components and will engage six additional colleges. Hub activities will be centeredaround four strategic goals: (1) chart new pathways for developing the translational workforce by taking UF ssuccess in career development and translating this success to the FSU and historically black colleges anduniversities; (2) strengthen the capacity of the learning health system environment and develop transferablemodels for embedding translational science into the clinical enterprise by further integrating data and software,developing multi-site pilots in healthcare institutions serving unique patient populations and building on thesuccess of the personalized medicine program to use genomics data to improve patient outcomes; (3) expandstatewide collaborations and opportunities to advance a participant-centered research agenda that reflects thehealth priorities and diversity of the catchment area by continuing to strengthen stakeholder engagement andtrust in research through the HealthStreet Program and enhance collaboration with policy stakeholders fromFlorida Medicaid, Florida surgeon general and others; and (4) strengthen regional and national collaborationsto accelerate the collective impact of the CTSA network through continued work with ACT, PCORnet, genomicmedicine, aging and metabolomics. Throughout this important work, the UF-FSU hub will remain dedicated tosupporting the recruitment, retention and career development of underrepresented minority and disabledtrainees and faculty. Integral to the success of the proposed work, the UF-FSU hub will further integrate healthcare and research in Florida guided by four keys to success: (1) organizational alignment, (2) clinicalinformatics, (3) clinician and stakeholder engagement, and (4) strong support from implementation andimprovement science expertise.
  1. Genetic Testing for Cancer Risk and Perceived Importance of Genetic Information Among US Population by Race and Ethnicity: a Cross-sectional Study.
    Hong YR, Yadav S, Wang R, Vadaparampil S, Bian J, George TJ, Braithwaite D
    J Racial Ethn Health Disparities, 2023 Jan 23 1-13 | PMID: 36689121 | PMCID: PMC9870197
    Citations: 42 | AltScore: 1.5
  2. Sex differences in body composition, voluntary wheel running activity, balance performance, and auditory function in CBA/CaJ mice across the lifespan.
    Kim MJ, Carmichael PB, Bose U, Honkura Y, Suzuki J, Ding D, Erfe SL, Simms SS, Avaiya KA, Milani MN, Rymer EJ, Fragnito DT, Strom N, Salvi R, Someya S
    Hear Res, 2023 Feb, 428: 108684 | PMID: 36599258
    Citations: | AltScore: NA
  3. The role of mitochondria in the recovery of neurons after injury.
    McElroy T, Zeidan RS, Rathor L, Han SM, Xiao R
    Neural Regen Res, 2023 Feb, 18(2): 317-318 | PMID: 35900413 | PMCID: PMC9396508
    Citations: 12 | AltScore: 0.5
  4. Relationship between Mitochondrial Quality Control Markers, Lower Extremity Tissue Composition, and Physical Performance in Physically Inactive Older Adults.
    Picca A, Triolo M, Wohlgemuth SE, Martenson MS, Mankowski RT, Anton SD, Marzetti E, Leeuwenburgh C, Hood DA
    Cells, 2023 Jan 2, 12(1): | PMID: 36611976 | PMCID: PMC9818256
    Citations: 57 | AltScore: NA
  5. Conscious connected breathing with breath retention intervention in adults with chronic low back pain: protocol for a randomized controlled pilot study.
    Pratscher SD, Sibille KT, Fillingim RB
    Pilot Feasibility Stud, 2023 Jan 24, 9(1): 15 | PMID: 36694217 | PMCID: PMC9872326
    Citations: 185 | AltScore: 1
  6. Disease correction in mucopolysaccharidosis type IIIB mice by intraparenchymal or cisternal delivery of a capsid modified AAV8 codon-optimized NAGLU vector.
    Rouse CJ, Hawkins K, Kabbej N, Dalugdug J, Kunta A, Kim MJ, Someya S, Herbst Z, Gelb M, Dinelli I, Butterworth E, Falk DJ, Rosenkrantz E, Elmohd H, Khaledi H, Mowafy S, Ashby F, Heldermon CD
    Hum Mol Genet, 2023 Jan 13, 32(3): 417-430 | PMID: 35997776 | PMCID: PMC9851742
    Citations: 36 | AltScore: 0.75
  7. Feasibility of a Smartwatch Platform to Assess Ecological Mobility: Real-Time Online Assessment and Mobility?Monitor.
    Smail EJ, Alpert JM, Mardini MT, Kaufmann CN, Bai C, Gill TM, Fillingim RB, Cenko E, Zapata R, Karnati Y, Marsiske M, Ranka S, Manini TM
    J Gerontol A Biol Sci Med Sci, 2023 May 11, 78(5): 821-830 | PMID: 36744611 | PMCID: PMC10172974
    Citations: 49 | AltScore: NA
  8. Defining the age-dependent and tissue-specific circadian transcriptome in male mice.
    Wolff CA, Gutierrez-Monreal MA, Meng L, Zhang X, Douma LG, Costello HM, Douglas CM, Ebrahimi E, Pham A, Oliveira AC, Fu C, Nguyen A, Alava BR, Hesketh SJ, Morris AR, Endale MM, Crislip GR, Cheng KY, Schroder EA, Delisle BP, Bryant AJ, Gumz ML, Huo Z, Liu AC, Esser KA
    Cell Rep, 2023 Jan 31, 42(1): 111982 | PMID: 36640301 | PMCID: PMC9929559
    Citations: 63 | AltScore: 50.1
  9. Reducing tobacco-associated lung cancer risk: a study protocol for a randomized clinical trial of AB-free kava.
    Xing C, Malaty J, Malham MB, Nehme AMA, Freeman B, Huo Z, Firpi-Morrel R, Salloum RG
    Trials, 2023 Jan 18, 24(1): 36 | PMID: 36653872 | PMCID: PMC9847434
    Citations: 37 | AltScore: 2
  1. A Socio-Ecological Framework for Cancer Prevention in Low and Middle-Income Countries.
    Akinyemiju T, Ogunsina K, Gupta A, Liu I, Braithwaite D, Hiatt RA
    Front Public Health, 2022, 10: 884678 | PMID: 35719678 | PMCID: PMC9204349
    Citations: 104 | AltScore: 0.5
  2. Using Machine Learning To Define the Impact of Beta-Lactam Early and Cumulative Target Attainment on Outcomes in Intensive Care Unit Patients with Hospital-Acquired and Ventilator-Associated Pneumonia.
    Alshaer MH, Maranchick N, Bai C, Maguigan KL, Shoulders B, Felton TW, Mathew SK, Mardini MT, Peloquin CA
    Antimicrob Agents Chemother, 2022 Jul 19, 66(7): e0056322 | PMID: 35699444 | PMCID: PMC9295596
    Citations: 32 | AltScore: NA
  3. Ineffective Erythropoietin Response to Anemia in Sepsis.
    Apple CG, Kelly LS, Kannan KB, Ungaro RF, Moore FA, Brakenridge SC, Moldawer LL, Efron PA, Mohr AM
    Surg Infect (Larchmt), 2022 Mar, 23(2): 142-149 | PMID: 34958257 | PMCID: PMC8892986
    Citations: 40 | AltScore: NA
  4. Differential DNA methylation in Black and White individuals with chronic low back pain enrich different genomic pathways.
    Aroke EN, Jackson P, Meng L, Huo Z, Overstreet DS, Penn TM, Quinn TL, Cruz-Almeida Y, Goodin BR
    Neurobiol Pain, 2022 Jan-Jul, 11: 100086 | PMID: 35243180 | PMCID: PMC8885563
    Citations: 83 | AltScore: 13.3
  5. Are Machine Learning Models on Wrist Accelerometry Robust against Differences in Physical Performance among Older Adults?
    Bai C, Wanigatunga AA, Saldana S, Casanova R, Manini TM, Mardini MT
    Sensors (Basel), 2022 Apr 15, 22(8):
    pii: 3061. | PMID: 35459045 | PMCID: PMC9032589
    Citations: 50 | AltScore: 1.75
  6. Characterizing Expiratory Respiratory Muscle Degeneration in Duchenne Muscular Dystrophy Using MRI.
    Barnard AM, Lott DJ, Batra A, Triplett WT, Willcocks RJ, Forbes SC, Rooney WD, Daniels MJ, Smith BK, Vandenborne K, Walter GA
    Chest, 2022 Mar, 161(3): 753-763 | PMID: 34536384 | PMCID: PMC9160975
    Citations: 34 | AltScore: 13.45
  7. Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging.
    Batra A, Barnard AM, Lott DJ, Willcocks RJ, Forbes SC, Chakraborty S, Daniels MJ, Arbogast J, Triplett W, Henricson EK, Dayan JG, Schmalfuss C, Sweeney L, Byrne BJ, McDonald CM, Vandenborne K, Walter GA
    BMC Cardiovasc Disord, 2022 Jun 9, 22(1): 260 | PMID: 35681116 | PMCID: PMC9185987
    Citations: 68 | AltScore: 1.5
  8. Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project).
    Bernabei R, Landi F, Calvani R, Cesari M, Del Signore S, Anker SD, Bejuit R, Bordes P, Cherubini A, Cruz-Jentoft AJ, Di Bari M, Friede T, Gorostiaga Ayestar?n C, Goyeau H, J?nsson PV, Kashiwa M, Lattanzio F, Maggio M, Mariotti L, Miller RR, Rodriguez-Ma?as L, Roller-Wirnsberger R, R?znarov? I, Scholpp J, Schols AMWJ, Sieber CC, Sinclair AJ, Skalska A, Strandberg T, Tchalla A, Topinkov? E, Tosato M, Vellas B, von Haehling S, Pahor M, Roubenoff R, Marzetti E, SPRINTT consortium.
    BMJ, 2022 May 11, 377: e068788 | PMID: 35545258 | PMCID: PMC9092831
    Citations: 44 | AltScore: 644.23
  9. Cancer and aging: A call to action.
    Braithwaite D, Anton S, Mohile S, DeGregori J, Gillis N, Zhou D, Bloodworth S, Pahor M, Licht J
    Aging Cancer, 2022 Jun, 3(2): 87-94 | PMID: 36188489 | PMCID: PMC9521708
    Citations: 73 | AltScore: 13
  10. Personalised Lung Cancer Screening (PLuS) study to assess the importance of coexisting chronic conditions to clinical practice and policy: protocol for a multicentre observational study.
    Braithwaite D, Karanth SD, Slatore CG, Zhang D, Bian J, Meza R, Jeon J, Tammemagi M, Schabath M, Wheeler M, Guo Y, Hochhegger B, Kaye FJ, Silvestri GA, Gould MK
    BMJ Open, 2022 Jun 22, 12(6): e064142 | PMID: 35732383 | PMCID: PMC9226937
    Citations: 62 | AltScore: 0.25
  11. Evaluation of a Multivalent Transcriptomic Metric for Diagnosing Surgical Sepsis and Estimating Mortality Among Critically Ill Patients.
    Brakenridge SC, Chen UI, Loftus T, Ungaro R, Dirain M, Kerr A, Zhong L, Bacher R, Starostik P, Ghita G, Midic U, Darden D, Fenner B, Wacker J, Efron PA, Liesenfeld O, Sweeney TE, Moldawer LL
    JAMA Netw Open, 2022 Jul 1, 5(7): e2221520 | PMID: 35819783 | PMCID: PMC9277492
    Citations: 25 | AltScore: 17.8
  12. A wrinkle in time: circadian biology in pulmonary vascular health and disease.
    Bryant AJ, Ebrahimi E, Nguyen A, Wolff CA, Gumz ML, Liu AC, Esser KA
    Am J Physiol Lung Cell Mol Physiol, 2022 Jan 1, 322(1): L84-L101 | PMID: 34850650 | PMCID: PMC8759967
    Citations: 237 | AltScore: 15.35
  13. Objective and subjective sleep measures are associated with neurocognition in aging adults with and without HIV.
    Campbell LM, Kohli M, Lee EE, Kaufmann CN, Higgins M, Delgadillo JD, Heaton RK, Cherner M, Ellis RJ, Moore DJ, Moore RC
    Clin Neuropsychol, 2022 Aug, 36(6): 1352-1371 | PMID: 32993422 | PMCID: PMC8007669
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  14. Chronic Critical Illness in Patients With Sepsis is Associated With Persistent Anemia, Inflammation, and Impaired Functional Outcomes.
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  15. Post-meeting report of the 2022 On-site Padua Days on Muscle and Mobility Medicine, March 30 - April 3, 2022, Padua, Italy.
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    Eur J Transl Myol, 2022 Apr 13, 32(2): | PMID: 35421919 | PMCID: PMC9295170
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  16. Simulating Colorectal Cancer Trials Using Real-World Data.
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  17. Relationships Between Cognitive Screening Composite Scores and Pain Intensity and Pain Disability in Adults With/At Risk for Knee Osteoarthritis.
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  18. Uneven terrain treadmill walking in younger and older adults.
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  19. Exosomes in Age-Related Cognitive Decline: Mechanistic Insights and Improving Outcomes.
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    Front Aging Neurosci, 2022, 14: 834775 | PMID: 35299946 | PMCID: PMC8921862
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    J Trauma Acute Care Surg, 2022 Mar 24, 93(2): 137-146 | PMID: 35324554 | PMCID: PMC9323556
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  21. Associations between biomarkers of cellular senescence and physical function in humans: observations from the lifestyle interventions for elders (LIFE) study.
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  22. Animal Models for Studies of Alcohol effects on the Trajectory of Age-Related Cognitive Decline.
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  25. Biopsychosocial influence on shoulder pain: results from a randomized pre-clinical trial of exercise-induced muscle injury.
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  26. Unexplained anemia of aging: Etiology, health consequences, and diagnostic criteria.
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  27. Effects of Walking Exercise at a Pace With Versus Without Ischemic Leg Symptoms on Functional Performance Measures in People With Lower Extremity Peripheral Artery Disease: The LITE Randomized Clinical Trial.
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    J Am Heart Assoc, 2022 Aug 2, 11(15): e025063 | PMID: 35894088 | PMCID: PMC9375509
    Citations: 20 | AltScore: 559.96
  28. Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma.
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  29. In vivo Structure-Activity Relationship of Dihydromethysticin in Reducing Nicotine-Derived Nitrosamine Ketone (NNK)-Induced Lung DNA Damage against Lung Carcinogenesis in A/J Mice.
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    ChemMedChem, 2022 Apr 5, 17(7): e202100727 | PMID: 35064644 | PMCID: PMC9399735
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  30. Reuniting the Body \Neck Up and Neck Down\ to Understand Cognitive Aging: The Nexus of Geroscience and Neuroscience.
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    J Gerontol A Biol Sci Med Sci, 2022 Jan 7, 77(1): e1-e9 | PMID: 34309630 | PMCID: PMC8751793
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  31. Analysis of US Household Catastrophic Health Care Expenditures Associated With Chronic Disease, 2008-2018.
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  32. Gradient and Acceleration of Decline in Physical and Cognitive Functions in Older Adults: A Disparity Analysis.
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  33. Cross-Sectional Brain-Predicted Age Differences in Community-Dwelling Middle-Aged and Older Adults with High Impact Knee Pain.
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    J Pain Res, 2022, 15: 3575-3587 | PMID: 36415658 | PMCID: PMC9676000
    Citations: 64 | AltScore: 2.25
  34. Persistent Non-pharmacological Pain Management and Brain-Predicted Age Differences in Middle-Aged and Older Adults With Chronic Knee Pain.
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  35. Advancing our understanding of neuropathic pain in diabetes mellitus using conditioned pain modulation: further considerations for age and testing site.
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  36. Sociodemographic and Clinical Characteristics Associated With Worst Pain Intensity Among Cancer Patients.
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  37. Cancer diagnosis is associated with a lower burden of dementia and less Alzheimer's-type neuropathology.
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    Brain, 2022 Jul 29, 145(7): 2518-2527 | PMID: 35094057 | PMCID: PMC9612796
    Citations: 66 | AltScore: 33.8
  38. Patterns of Medical Cannabis Use Among Older Adults from a Cannabis Dispensary in New York State.
    Kaufmann CN, Kim A, Miyoshi M, Han BH
    Cannabis Cannabinoid Res, 2022 Apr, 7(2): 224-230 | PMID: 33998868 | PMCID: PMC9070740
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  39. Declining trend in use of medications for sleep disturbance in the United States from 2013 to 2018.
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    J Clin Sleep Med, 2022 Oct 1, 18(10): 2459-2465 | PMID: 35818727 | PMCID: PMC9516584
    Citations: 33 | AltScore: 632.53
  40. The prevalence of comorbid chronic pain conditions among patients with temporomandibular disorders: A systematic review.
    Kleykamp BA, Ferguson MC, McNicol E, Bixho I, Arnold LM, Edwards RR, Fillingim R, Grol-Prokopczyk H, Ohrbach R, Turk DC, Dworkin RH
    J Am Dent Assoc, 2022 Mar, 153(3): 241-250.e10 | PMID: 34952681
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  41. Methods for Phenotyping Adult Patients in Sepsis and Septic Shock: A Scoping Review.
    Li H, Markal A, Balch JA, Loftus TJ, Efron PA, Ozrazgat-Baslanti T, Bihorac A
    Crit Care Explor, 2022 Apr, 4(4): e0672 | PMID: 35372844 | PMCID: PMC8970078
    Citations: 33 | AltScore: 4.6
  42. The circadian E3 ligase FBXL21 regulates myoblast differentiation and sarcomere architecture via MYOZ1 ubiquitination and NFAT signaling.
    Lim JY, Kim E, Douglas CM, Wirianto M, Han C, Ono K, Kim SY, Ji JH, Tran CK, Chen Z, Esser KA, Yoo SH
    PLoS Genet, 2022 Dec, 18(12): e1010574 | PMID: 36574402 | PMCID: PMC9829178
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  43. Gait subgroups among older adults with chronic pain differ in cerebellum and basal ganglia gray matter volumes.
    Lipat AL, Clark DJ, Hass CJ, Cruz-Almeida Y
    Exp Gerontol, 2022 Jun 15, 163: 111773 | PMID: 35341939 | PMCID: PMC9948689
    Citations: 47 | AltScore: 0.75
  44. Decreased cognitive function is associated with impaired spatiotemporal gait performance in community dwelling older adults with chronic musculoskeletal pain.
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    Brain Cogn, 2022 Jun, 159: 105862 | PMID: 35358922
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  45. Aligning Patient Acuity With Resource Intensity After Major Surgery: A Scoping Review.
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  46. Postoperative Overtriage to an Intensive Care Unit Is Associated With Low Value of Care.
    Loftus TJ, Ruppert MM, Ozrazgat-Baslanti T, Balch JA, Shickel B, Hu D, Efron PA, Tighe PJ, Hogan WR, Rashidi P, Upchurch GR Jr, Bihorac A
    Ann Surg, 2022 Jul 6, 277(2): 179-185 | PMID: 35797553 | PMCID: PMC9817331
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  47. Interventions for Informal Caregivers of Stroke Survivors: Is There Racial and Ethnic Representation in Stroke Caregiver Studies?
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    Rehabil Nurs, 2022 Jan-Feb 01, 47(1): 3-11 | PMID: 33560779
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  48. Early Biomarker Signatures in Surgical Sepsis.
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    J Surg Res, 2022 Sep, 277: 372-383 | PMID: 35569215 | PMCID: PMC9827429
    Citations: 32 | AltScore: 5.2
  49. Sepsis-Induced Myopathy and Gut Microbiome Dysbiosis: Mechanistic Links and Therapeutic Targets.
    Mankowski RT, Laitano O, Darden D, Kelly L, Munley J, Loftus TJ, Mohr AM, Efron PA, Thomas RM
    Shock, 2022 Jan 1, 57(1): 15-23 | PMID: 34726875 | PMCID: PMC9373856
    Citations: 108 | AltScore: 8.3
  50. Time for Exercise? Exercise and Its Influence on the Skeletal Muscle Clock.
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    J Biol Rhythms, 2022 Dec, 37(6): 579-592 | PMID: 36129164 | PMCID: PMC9729417
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  51. Care coordination needs for deprescribing benzodiazepines and benzodiazepine receptor agonists.
    McCarthy M, Mak S, Kaufmann CN, Lum HD, Fung CH
    Res Social Adm Pharm, 2022 Apr, 18(4): 2691-2694 | PMID: 34229951 | PMCID: PMC8720104
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  52. Effect of Telmisartan on Walking Performance in Patients With Lower Extremity Peripheral Artery Disease: The TELEX Randomized Clinical Trial.
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    JAMA, 2022 Oct 4, 328(13): 1315-1325 | PMID: 36194220 | PMCID: PMC9533188
    Citations: 30 | AltScore: 44.116
  53. Enrichment of genomic pathways based on differential DNA methylation profiles associated with knee osteoarthritis pain.
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    Neurobiol Pain, 2022 Aug-Dec, 12: 100107 | PMID: 36531611 | PMCID: PMC9755025
    Citations: 66 | AltScore: 3
  54. Chronic Musculoskeletal Pain Moderates the Association between Sleep Quality and Dorsostriatal-Sensorimotor Resting State Functional Connectivity in Community-Dwelling Older Adults.
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    Pain Res Manag, 2022, 2022: 4347759 | PMID: 35432664 | PMCID: PMC9010216
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  56. The Associations between Depression, Acculturation, and Cardiovascular Health among African Immigrants in the United States.
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    J Behav Med, 2022 Aug, 45(4): 580-588 | PMID: 35124742 | PMCID: PMC9344470
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    J Psychiatr Res, 2022 Jun, 150: 257-263 | PMID: 35405410 | PMCID: PMC9107496
    Citations: 48 | AltScore: 1.5
  59. Applying the NIA Health Disparities Research Framework to Identify Needs and Opportunities in Chronic Musculoskeletal Pain Research.
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    J Pain, 2022 Jan, 23(1): 25-44 | PMID: 34280570 | PMCID: PMC8890583
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    Peterson JA, Meng L, Rani A, Sinha P, Johnson AJ, Huo Z, Foster TC, Fillingim RB, Cruz-Almeida Y
    Exp Gerontol, 2022 May 29, 166: 111861 | PMID: 35640781 | PMCID: PMC9887947
    Citations: 63 | AltScore: 1.75
  61. Epigenetic Aging Mediates the Association between Pain Impact and Brain Aging in Middle to Older Age Individuals with Knee Pain.
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    Epigenetics, 2022 Dec, 17(13): 2178-2187 | PMID: 35950599 | PMCID: PMC9665126
    Citations: 49 | AltScore: 4.6
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    Semin Cell Dev Biol, 2022 Mar 30, 143: 37-45
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    Philos Trans R Soc Lond B Biol Sci, 2022 Aug 29, 377(1858): 20210048 | PMID: 35858076 | PMCID: PMC9274329
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  64. HUMAN STUDY COMT and DRD3 haplotype-associated pain intensity and acute care utilization in adult sickle cell disease.
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  65. Influence of age and sex on microRNA response and recovery in the hippocampus following sepsis.
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    Citations: 142 | AltScore: 2
  66. The skeletal muscle circadian clock regulates titin splicing through RBM20.
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    Elife, 2022 Sep 1, 11: | PMID: 36047761 | PMCID: PMC9473687
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  67. Immunopathology of chronic critical illness in sepsis survivors: Role of abnormal myelopoiesis.
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    Handb Exp Pharmacol, 2022, 274: 331-348 | PMID: 35624229
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    Ross KM, Carpenter CA, Arroyo KM, Shankar MN, Yi F, Qiu P, Anthony L, Ruiz J, Perri MG
    Obesity (Silver Spring), 2022 Apr, 30(4): 858-863 | PMID: 35037410 | PMCID: PMC8957501
    Citations: 20 | AltScore: 41.4
  70. Interventional- and amputation-stage muscle proteomes in the chronically threatened ischemic limb.
    Ryan TE, Kim K, Scali ST, Berceli SA, Thome T, Salyers ZR, O'Malley KA, Green TD, Karnekar R, Fisher-Wellman KH, Yamaguchi DJ, McClung JM
    Clin Transl Med, 2022 Jan, 12(1): e658 | PMID: 35073463 | PMCID: PMC8785983
    Citations: 59 | AltScore: 4
  71. Dysregulated Genes, MicroRNAs, Biological Pathways, and Gastrocnemius Muscle Fiber Types Associated With Progression of Peripheral Artery Disease: A Preliminary Analysis.
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    J Am Heart Assoc, 2022 Nov, 11(21): e023085 | PMID: 36300658 | PMCID: PMC9673627
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  72. Time-Restricted Eating Regimen Differentially Affects Circulatory miRNA Expression in Older Overweight Adults.
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  73. Vulnerable Dispositional Traits and Chronic Pain: Predisposing but not Predetermining.
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  74. Circulating Omega-6 and Omega-3 Polyunsaturated Fatty Acids in Painful Temporomandibular Disorder and Low Back Pain.
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    J Pain, 2022 Jun 10, 23(10): 1724-1736
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  75. Timing of food intake in mice unmasks a role for the cardiomyocyte circadian clock mechanism in limiting QT-interval prolongation.
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    Chronobiol Int, 2022 Apr, 39(4): 525-534 | PMID: 34875962 | PMCID: PMC8989643
    Citations: 46 | AltScore: 9.7
  76. The role of the cardiomyocyte circadian clocks in ion channel regulation and cardiac electrophysiology.
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    J Physiol, 2022 May, 600(9): 2037-2048 | PMID: 35301719 | PMCID: PMC9980729
    Citations: 66 | AltScore: 6.05
  77. Characterizing OPRM1 DNA methylation in prescription opioid users with chronic musculoskeletal pain.
    Sheikh S, Smotherman C, Patel M, Langaee T, Wang D, Swaray E, Velasquez E, Schmidt SOF, Hendry P, Cavallari LH, Fillingim RB
    Pain Rep, 2022 Nov-Dec, 7(6): e1046 | PMID: 36447952 | PMCID: PMC9699511
    Citations: 38 | AltScore: 0.5
  78. Worsening sleep predicts lower life space mobility during the onset of the COVID-19 pandemic.
    Smail EJ, Kaufmann CN, Riehm KE, Mardini MT, Cenko E, Bai C, Manini TM
    J Am Geriatr Soc, 2022 May 24, 70(7): 1931-1938 | PMID: 35608359 | PMCID: PMC9283282
    Citations: 22 | AltScore: 10.1
  79. Clinical vitamin D levels are associated with insular volume and inferior temporal gyrus white matter surface area in community-dwelling individuals with knee pain.
    Strath LJ, Hernandez PV, Nodarse CL, Johnson AJ, Edberg JD, Fillingim RB, Cruz-Almeida Y
    Front Neurosci, 2022, 16: 882322 | PMID: 36117614 | PMCID: PMC9470941
    Citations: 43 | AltScore: NA
  80. The language of sleepiness in obstructive sleep apnea beyond the Epworth.
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    Sleep Breath, 2022 Sep 13 1-9 | PMID: 36098927 | PMCID: PMC9469060
    Citations: 30 | AltScore: NA
  81. MicroRNA panels as diagnostic biomarkers for colorectal cancer: A systematic review and meta-analysis.
    Sur D, Advani S, Braithwaite D
    Front Med (Lausanne), 2022, 9: 915226 | PMID: 36419785 | PMCID: PMC9676370
    Citations: 58 | AltScore: NA
  82. Chronic Pain Severity and Sociodemographics: An Evaluation of the Neurobiological Interface.
    Tanner JJ, Cardoso J, Terry EL, Booker SQ, Glover TL, Garvan C, Deshpande H, Deutsch G, Lai S, Staud R, Addison A, Redden D, Goodin BR, Price CC, Fillingim RB, Sibille KT
    J Pain, 2022 Feb, 23(2): 248-262 | PMID: 34425249 | PMCID: PMC8828699
    Citations: 2 | AltScore: 7.6
  83. Associations between pain catastrophizing and resting-state functional brain connectivity: Ethnic/race group differences in persons with chronic knee pain.
    Terry EL, Tanner JJ, Cardoso JS, Sibille KT, Lai S, Deshpande H, Deutsch G, Price CC, Staud R, Goodin BR, Redden DT, Fillingim RB
    J Neurosci Res, 2022 Apr, 100(4): 1047-1062 | PMID: 35187703 | PMCID: PMC8940639
    Citations: 130 | AltScore: 1.5
  84. Promoting weight-loss maintenance among Black women primary care patients: A cluster RCT of a culturally sensitive versus standard behavioural approach.
    Tucker CM, Anton SD, Wippold GM, Marsiske M, Bilello LA, Henry MA, Shah NR, Gautam SP, Klein KG, Mathews A, Webb F, Desmond F
    Clin Obes, 2022 Dec, 12(6): e12553 | PMID: 36151609 | PMCID: PMC9786626
    Citations: 35 | AltScore: 5.08
  85. Evaluation of the key prescription sequence symmetry analysis assumption using the calcium channel blocker: Loop diuretic prescribing cascade.
    Vouri SM, Morris EJ, Usmani SA, Reise R, Jiang X, Pepine CJ, Manini TM, Malone DC, Winterstein AG
    Pharmacoepidemiol Drug Saf, 2022 Jan, 31(1): 72-81 | PMID: 34553438 | PMCID: PMC8688319
    Citations: 23 | AltScore: 7
  86. Kinematic analysis of speed transitions within walking in younger and older adults.
    Wade FE, Kellaher GK, Pesquera S, Baudendistel ST, Roy A, Clark DJ, Seidler RD, Ferris DP, Manini TM, Hass CJ
    J Biomech, 2022 Jun, 138: 111130 | PMID: 35569430 | PMCID: PMC9284670
    Citations: 40 | AltScore: 15.15
  87. Reducing Chemotherapy-Induced DNA Damage via nAChR-Mediated Redox Reprograming-A New Mechanism for SCLC Chemoresistance Boosted by Nicotine.
    Wang Y, Bian T, Song L, Jiang Y, Huo Z, Salloum RG, Warren GW, Kaye FJ, Fujioka N, Jin L, Xing C
    Cancers (Basel), 2022 May 2, 14(9): | PMID: 35565402 | PMCID: PMC9100082
    Citations: 61 | AltScore: 1
  88. Combined impact of Medicare's hospital pay for performance programs on quality and safety outcomes is mixed.
    Waters TM, Burns N, Kaplan CM, Graetz I, Benitez J, Cardarelli R, Daniels MJ
    BMC Health Serv Res, 2022 Jul 28, 22(1): 958 | PMID: 35902910 | PMCID: PMC9330620
    Citations: 26 | AltScore: 3.75
  89. Gestational weight change and childhood body composition trajectories from pregnancy to early adolescence.
    Widen EM, Burns N, Daniels M, Backlund G, Rickman R, Foster S, Nichols AR, Hoepner LA, Kinsey EW, Ramirez-Carvey J, Hassoun A, Perera FP, Bukowski R, Rundle AG
    Obesity (Silver Spring), 2022 Mar, 30(3): 707-717 | PMID: 35137558 | PMCID: PMC8957403
    Citations: 45 | AltScore: 255.3
  90. Associations between Vitamin D, Omega 6:Omega 3 Ratio, and Biomarkers of Aging in Individuals Living with and without Chronic Pain.
    Wijayabahu AT, Mickle AM, Mai V, Garvan C, Glover TL, Cook RL, Zhao J, Baum MK, Fillingim RB, Sibille KT
    Nutrients, 2022 Jan 9, 14(2):
    pii: 266. | PMID: 35057447 | PMCID: PMC8779718
    Citations: 85 | AltScore: 1.25
  91. Experimental Pain Phenotype Profiles in Community-dwelling Older Adults.
    Wilson AT, Johnson AJ, Laffitte Nodarse C, Hoyos L, Lysne P, Peraza JA, Montesino-Goicolea S, Valdes-Hernandez PA, Somerville J, Bialosky JE, Cruz-Almeida Y
    Clin J Pain, 2022 Jul 1, 38(7): 451-458 | PMID: 35656805 | PMCID: PMC9202441
    Citations: 49 | AltScore: 1.25
  92. A Preliminary Study of Extracting Pulmonary Nodules and Nodule Characteristics from Radiology Reports Using Natural Language Processing.
    Yang S, Yang X, Lyu T, He X, Braithwaite D, Mehta HJ, Guo Y, Wu Y, Bian J
    IEEE Int Conf Healthc Inform, 2022 Jun, 2022: 618-619 | PMID: 36168559 | PMCID: PMC9511964
    Citations: 13 | AltScore: 1.5
  93. Autonomic Nervous System Dysregulation and Osteoarthritis Pain: Mechanisms, Measurement, and Future Outlook.
    Yeater TD, Cruz CJ, Cruz-Almeida Y, Allen KD
    Curr Rheumatol Rep, 2022 Jun, 24(6): 175-183 | PMID: 35420372 | PMCID: PMC9189055
    Citations: 88 | AltScore: 52.75
  94. Operationally defining cognitive reserve genes.
    Yegla B, Foster TC
    Neurobiol Aging, 2022 Feb, 110: 96-105 | PMID: 34565615
    Citations: 2 | AltScore: NA
  95. Analysis of Biological Aging and Risks of All-Cause and Cardiovascular Disease-Specific Death in Cancer Survivors.
    Zhang D, Leeuwenburgh C, Zhou D, Gong Y, Pahor M, Licht JD, Braithwaite D
    JAMA Netw Open, 2022 Jun 1, 5(6): e2218183 | PMID: 35731518 | PMCID: PMC9218849
    Citations: 6 | AltScore: 13.75
  96. Frailty and risk of mortality in older cancer survivors and adults without a cancer history: Evidence from the National Health and Nutrition Examination Survey, 1999-2014.
    Zhang D, Mobley EM, Manini TM, Leeuwenburgh C, Anton SD, Washington CJ, Zhou D, Parker AS, Okunieff PG, Bian J, Guo Y, Pahor M, Hiatt RA, Braithwaite D
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    Citations: 59 | AltScore: 12.85


George Kuchel, MD
University of Connecticut
Serving since 2022 (1 years)

Joseph Takahashi, PhD
University of Texas Southwestern
Serving since 2022 (1 years)

Laura Niedernhofer, MD, PhD
University of Minnesota
Serving since 2022 (1 years)

Monty Montano, PhD
Harvard University
Serving since 2022 (1 years)


Recognition and Awards not specified.


General Brief Description of Minority Activities:

Steve Anton, PhD

·         Co-PI R33 AG056540: “The University of Florida Jacksonville Aging Studies Center (JAXASCENT)

·         Mentor for minority junior faculty member, Latoya O’Neal, Ph.D. (2017)


Yenisel Cruz-Almeida, MSPH, PhD

·         Pedro Valdes Hernandez, PhD- T32 Mentor

·         Soamy Montesino Goicolea, MD- Mentor

·         Carolina Maciel, MD- Junior Pepper Scholar Mentor

·         Desiree Lussier, PhD- Mentor

·         Keesha Roach, BSN, PhD- T32 Mentor

·         Sophia McCray- Honors Thesis Mentor

·         Vanessa Davila- Honors Thesis Mentor

·         Lorraine Hoyos- Medical Student, UCF, Research Mentor


Roger Fillingim, PhD

P30AG059297: “University of Florida Resource Center for Minority Aging Research


Todd Manini, PhD, Mentor 

·         Dottington Fullwood, PhD


Marco Pahor, MD

·         Co-PI R33 AG056540: “The University of Florida Jacksonville Aging Studies Center (JAXASCENT)


Carolyn Tucker, PhD

·         Human Foundation: “Health-Smart, Holistic Health and Wellness Centers Program to Promote Social Connection and Food Security among Minority, Underserved, and/or Low- Income Jacksonville Seniors”


·         PCORI: “Culturally Sensitive Primary Care Clinic-Based Interventions”

Minority Trainee(s):
  • M. Dottington Fullwood, PhD, Postdoctoral Fellow
    Dr. Fullwood is a rising scientist who is enthusiastic to expand his research focus to include aging, specifically understanding the connection between multidimensional impacts of chronic low back pain and mobility decline using mobile health technology in older minority adults. His research plan to assess the extent to assessment of behavioral interventions delivered to underserved older adult populations explains low back pain and mobility decline that leads to better ways to maintain and restore physical function to older adults. These objectives are directly aligned with the objective of the our JAX-ASCENT, which will provide excellent resources for him to pursue and achieve his research and training goals. Most importantly, he will work closely with JAX-ASCENT investigators who are invested in promoting an interdisciplinary academic environment by building lasting collaborations with clinical, behavioral and epidemiology scientists. His primary mentor—Dr. Anton—exemplifies this characteristic through his many collaborative research initiatives (see Biosketch). Moreover, Dr. Fullwood has assembled a mentoring team that contains experts in behavioral interventions to promote healthy aging, mobile health technology and multidimensional aspects of pain. His advisement from each mentor will vary in activities ranging from one-on-one individual meetings to directed readings and group discussion with his dream team of expert mentors. Dr. Fullwood will also participate in the many activities offered through the Claude D. Pepper Older Americans Independence Center (OAIC: P30AG028740) and Research Career Development Core (RCDC). He will follow specific training plans outlined by the RCDC co-leaders that will provide him clear benchmarks for meeting his career and research goals. He will attend weekly seminars focused on pain and aging and round table meetings with other more senior scholars.
  • Pedro Valdes Hernandez , PhD, Postdoctoral Fellow
    Over the 22-months of the supplement, the research and career development plan for Pedro is designed to promote his transition to independence as a researcher at the intersection of the fields of pain and aging. Results from a recent paper submitted by Dr. Valdes Hernandez revealed that chronic musculoskeletal pain in older adults may negatively impact specific cerebral circuits related to memory, language, motor planning, mobility and physical function (see Figure 1). These findings fueled Pedro’s avidity to delve into the fields of pain and aging, specifically investigating the mechanisms mediating the impact of pain on mobility and physical function in older adults. This critical gap in knowledge aligns quite well with the scientific theme of the UF OAIC. Pedro came to UF 18 months ago with no previous background in pain or aging research. His preliminary research training experiences have provided a foundation of knowledge and skills in these areas, enabling him to develop and implement innovative mechanism-based research protocols investigating pain in older adults. This Administrative Supplement would provide the opportunity for Pedro to pursue advanced training in pain, aging and mobility research in a more structured manner, allowing him the time to develop research interests and expertise, expediting his transition to research independence. His mid-term goal is to submit a K01 award by February 2021. His long-term goals are to: 1) excel in an academic institution as an independent translational neuroscientist with expertise in the fields of pain and aging; and 2) to contribute to the biomedical research community through scholarship and education with the ultimate goal of improving the life of older populations. The proposed research and career development plan is designed to help him achieve these career goals. Specifically, we propose a combination of experiential, training, pain and aging dedicated research and grant-writing activities. This will provide Pedro with hands-on research experience and increased knowledge in aging and pain. As a result of this training program, Pedro will be prepared to continue pain and geriatric research as a faculty member to greatly enhance his ability to pursue his long-term goal of an independent academic research career.

Minority Grant(s):