Medicine and Health Sciences Commons^™

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …

Inter-Organizational Network Effects On The Implementation Of Public Health Services, Glen P. Mays

Health Management and Policy Presentations

Background: The Affordable Care Act created new incentives for hospitals, insurers, public health agencies, and others to contribute to disease prevention and health promotion activities, potentially changing inter-organizational relationships and expanding implementation of strategies that improve population health. This study uses data from the 1998-2014 National Longitudinal Survey of Public Health Systems to examine: (1) the extent and nature of change in inter-organizational contributions to public health activities; (2) whether network changes attenuate or exacerbate disparities in public health implementation across communities; and (3) how network changes affect preventable mortality and resource use.

Methods: We follow a longitudinal cohort of …

Accounting For Indirect Costs In Public Health Cost Analyses, Melanie D. Whittington, Adam Atherly, Lisa Vanraemdonck

Frontiers in Public Health Services and Systems Research

Background. There is a gap in research regarding the resources needed to deliver public health activities, which inhibits informed decision making around investments in public health and the allocation of funds among activities. When conducting cost analyses in public health, it is important to include costs from all cost components, including personnel, non-personnel, and indirect costs. However, defining, identifying, and measuring indirect costs is challenging and can impede studies of this type. Purpose. The purpose of this pilot study is to create a catalog of the methodologies public health researchers have used to account for indirect costs. Methods. We surveyed …

Mice Deficient In Endothelial Α5 Integrin Are Profoundly Resistant To Experimental Ischemic Stroke, Jill Roberts, Leon De Hoog, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2–3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no …

Early Shifts Of Brain Metabolism By Caloric Restriction Preserve White Matter Integrity And Long-Term Memory In Aging Mice, Janet Guo, Vikas Bakshi, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals’ memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We …

Estimating Health & Economic Gains From Public Health Delivery System Transformation, Glen P. Mays

Health Management and Policy Presentations

Objectives: The Affordable Care Act created new resources and incentives for hospitals, insurers, public health agencies, and others to contribute to disease prevention and health promotion activities, potentially changing the structure of public health delivery systems and expanding the implementation of strategies that improve population health. This study uses data from the 1998-2014 National Longitudinal Survey of Public Health Systems to examine: (1) the extent and nature of change in inter-organizational contributions to public health activities, which we use as indicators of public health system change; and (2) the effects of these changes on preventable mortality and resource use. Methods: …

Residual Impact Of Previous Injury On Musculoskeletal Characteristics In Special Forces Operators, Jeffrey J. Parr, Nicholas C. Clark, John P. Abt, Julie Y. Kresta, Karen A. Keenan, Shawn F Kane, Scott M. Lephart

Physical Therapy Faculty Publications

Background: Musculoskeletal injuries are a significant burden to United States Army Special Operations Forces. The advanced tactical skill level and physical training required of Army Special Operators highlights the need to optimize musculoskeletal characteristics to reduce the likelihood of suffering a recurrent injury.

Purpose: To identify the residual impact of previous injury on musculoskeletal characteristics.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: Isokinetic strength of the knee, shoulder, and back and flexibility of the shoulder and hamstrings were assessed as part of a comprehensive human performance protocol, and self-reported musculoskeletal injury history was obtained. Subjects were stratified based …

Kentucky’S Public Health Strategic Plan: Strengthening Foundational Services & Improving Population Health, Glen P. Mays

Health Management and Policy Presentations

This session examines recent progress toward the 2012 Institute of Medicine recommendation to identify the components and costs of a "minimum package" of public health services and foundational capabilities to be available across the U.S. Research about the health and economic benefits of Foundational Public Health Services has begun to shape Kentucky's strategic plan for transforming the public health system.

Analytic Approaches For Causal Inference With Complex Multi-Component Interventions, Glen P. Mays, Arnold J. Stromberg, Jing Li, Mark V. Williams

Health Management and Policy Presentations

Estimating the causal effects of complex, multi-component health interventions is a task with many challenges in measurement and methodology. This presentation profiles the methods being used as part of the PCORI-funded Project Achieve, a national study to estimate the comparative effectiveness of heterogeneous care transition programs designed to help hospitalized patients and their caregivers navigate care delivery systems effectively and return back to the community with optimal health and wellbeing.

Misdiagnosis: Dysfunction Between Western Health Organizations And Developing Nations, Dannette Smith Cook

Ex-Patt Magazine

Improving the global public health system is no simple task. Find out how Indonesia can help explain a culture of distrust between developing nations and international health organizations.

Prevailing Against Polio: India's Holistic Development Strategy, Anonymous Submission

Ex-Patt Magazine

No abstract provided.

Trends In Health Care Delivery Systems: Implications For Cancer Prevention And Control, Glen P. Mays

Health Management and Policy Presentations

The Affordable Care Act and larger economic forces are leading both health care providers and public health agencies to renegotiate their roles and responsibilities within the U.S. health system. This session reviews major changes occurring in both health care and public health delivery systems, with a focus on the implications for cancer prevention and control. The information infrastructure created by cancer registries and other health information systems are increasingly important for enabling greater coordination, alignment and accountability within the nation's changing delivery systems.

Domestic Violence In The Workplace, Amanda Fallin

Kaleidoscope

Intimate partner violence (IPV) is a pervasive problem that follows victims from the home into the workplace. Many women who experience violence in their homes are also harassed at work and are abused in the workplace. For the current study, thirty women who reported a history of workplace violence were recruited from a homeless women’s shelter. Of the participants, thirteen experienced domestic violence in the workplace, and this paper focuses on the results obtained from those thirteen respondents. This paper also discusses the link between poverty and homelessness, intimate partner violence, and workplace violence.

The National Health Security Preparedness Index: Proposed Updates For 2015-16, Glen P. Mays

Health Management and Policy Presentations

The U.S. Centers for Disease Control and Prevention (CDC) initiated development of the National Health Security Preparedness Index in 2012 to create a platform for measuring the nation’s progress in preparing for, responding to, and recovering from disasters and other large-scale emergencies that pose risks to health and well-being in the United States. As a measurement tool, the Index is designed to summarize levels of preparedness achieved within individual states and for the nation as a whole. This session summarizes proposed updates to the Index for 2015-16 that are designed to improve the validity and reliability of Index measures and …

Time-Dependent Effects Of Cx3cr1 In A Mouse Model Of Mild Traumatic Brain Injury, Heidi Y. Febinger, Hannah E. Thomasy, Maria N. Pavlova, Kristyn M. Ringgold, Paulien R. Barf, Amrita M. George, Jenna N. Grillo, Adam D. Bachstetter, Jenny A. Garcia, Astrid E. Cardona, Mark R. Opp, Carmelina Gemma

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI). Microglia are highly plastic cells with dual roles in neuronal injury and recovery. Recent studies suggest that the chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, and depending upon the type and time of injury, either protects or exacerbates neurological diseases.

METHODS: In this study, mice deficient in CX3CR1 were subjected to mild controlled cortical impact injury (CCI), a model of TBI. We evaluated …

Albumin Administration In Acute Ischemic Stroke: Safety Analysis Of The Alias Part 2 Multicenter Trial, Michael D. Hill, Renee H. Martin, Yuko Y. Palesch, Claudias S. Moy, Diego Tamariz, Karla J. Ryckborst, Elizabeth B. Jones, David Weisman, L. Creed Pettigrew, Myron D. Ginsberg

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial.

METHODS: Ischemic stroke patients, aged 18-83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism.

RESULTS: …

Using Research And Roi To Drive Partnerships In Public Health Delivery Systems, Glen P. Mays

Health Management and Policy Presentations

Stimulating public-private partnerships (PPP) for health and economic development initiatives requires research that can answer key questions: (1) what are the health and economic returns likely to be realized; (2) over what time frames and with what certainty; (3) what investments are required to achieve results; and (4) what are the implementation strategies most likely to succeed. This presentation reviews ongoing research on the PPPs used to deliver public health services in the U.S., and explores the lessons this research offers PPPs in low and middle income countries. We examine how scientific evidence on public health delivery systems and their …

Estimating Patient-Centered And Community-Centered Treatment Effects: Examples From Medical Care And Public Health, Glen P. Mays

Health Management and Policy Presentations

Health services researchers face growing clinical and policy imperatives for estimating how the effectiveness of medical and public health interventions vary across patients, population groups, and community settings. Recent advances in local instrumental variables estimation techniques allow for the estimation of person-specific and community-specific treatment effects in the presence of unobserved heterogeneity. This presentation explores examples from both medicine and public health following the local IV methods developed by Basu et al. (2013).

Foundational Public Health Services And Health System Reform, Glen P. Mays

Health Management and Policy Presentations

The Institute of Medicine's 2012 report on public health financing recommended a national initiative to identify the components and costs of a "minimum package" of public health programs and infrastructure that should be available in every U.S. community. In response, efforts are now underway to reach consensus on a set of "Foundational Public Health Services" for the nation, and to identify resource requirements for implementing these services. This presentation reviews existing research on the current availability of Foundational Public Health Services across the U.S. and the health and economic effects attributable to these services. We also review progress on ongoing …

Fundamentals Of Economic Evaluation For Public Health, Glen P. Mays, Cezar Mamaril

Health Management and Policy Presentations

This workshop provides an overview of the design and implementation of economic evaluation studies of public health programs and policies. Strategies for integrating economic evaluation principles, measurement strategies, analytic approaches, and results into the routine operations of public health agencies are examined.

Economic Evaluation Of Fungal Meningitis Outbreak Response In New River Valley: Local Health Department Perspective, Kaja M. Abbas, Nargesalsadat Dorratoltaj, Margaret L. O’Dell, Paige Bordwine, Thomas M. Kerkering, Kerry J. Redican

Frontiers in Public Health Services and Systems Research

Background: The multi-state fungal meningitis outbreak started in September 2012 in Tennessee. The cause of the outbreak was injection of contaminated lots of methylprednisolone acetate used in epidural spinal injections. Roanoke and New River Valley were the epicenter of this outbreak in Virginia, with two clinical centers having administered the contaminated injections to their patients. New River Health District, in coordination with hospitals, and state and federal agencies, deployed its resources to control the local impact of the outbreak.

Purpose: The objective of this study was to conduct an economic evaluation of the fungal meningitis outbreak response in New River …

Measuring Changes In Local Surveillance And Investigation Capacity, Christine A. Bevc, Mary V. Davis, Anna P. Schenck

Frontiers in Public Health Services and Systems Research

Background: The outbreak of Ebola virus disease in West Africa and confirmation of the first cases in the United States highlight the need for robust and responsive public health surveillance system. With a 25% decline in funding since 2007, the impact on local surveillance capacities has not previously been described.

Purpose: The Surveillance & Investigation domain of the Local Health Department Preparedness Capacities Survey (PCAS) was reweighted to reflect the national profile of LHDs. Changes in subdomain performance of capacities and the effect of population size on subdomain capacity performance were examined over time.

Methods: Participating LHDs (n=208) …

Medicaid Crowd-Out Of Other Public Health Spending: Modeling Economic & Health Effects, Glen P. Mays

Health Management and Policy Presentations

MOTIVATION: Thirty states are expanding Medicaid eligibility under the Affordable Care Act (ACA) as of 2015, and while federal funds cover most costs for newly eligible recipients, states must share the additional costs of covering previously-eligible state residents who enroll in Medicaid. States, together with their local government counterparts, also provide the vast majority (87%) of public sector funds for public health programs designed to promote health and prevent disease and injury on a population-wide basis. Fiscal constraints and generous federal matching funds create strong budgetary incentives for states to channel their health-related spending to Medicaid rather than to other …

Altered Lysosomal Proteins In Neural-Derived Plasma Exosomes In Preclinical Alzheimer Disease, Edward J. Goetzl, Adam Boxer, Janice B. Schwartz, Erin L. Abner, Ronald C. Petersen, Bruce L. Miller, Dimitrios Kapogiannis

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy.

METHODS: Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker.

RESULTS: Mean exosomal levels of cathepsin D, lysosome-associated membrane …

Low Neural Exosomal Levels Of Cellular Survival Factors In Alzheimer's Disease, Edward J. Goetzl, Adam Boxer, Janice B. Schwartz, Erin Abner, Ronald C. Petersen, Bruce L. Miller, Olga D. Carlson, Maja Mustapic, Dimitrios Kapogiannis

Sanders-Brown Center on Aging Faculty Publications

Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer's disease patients than controls (P < 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1-silencing transcription factor than in controls. Exosomal transcription factors were diminished 2-10 years before clinical diagnosis of Alzheimer's disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer's disease neurotoxic proteins.

Using Network Analysis To Understand Public Health Delivery Systems & Community Health Initiatives, Glen P. Mays

Health Management and Policy Presentations

The increasingly connected world of health care delivery relies on an expanding frontier of multi-stakeholder structures and processes, from interdisciplinary patient-centered care teams, to virtual accountable care organizations (ACOs), to complex community-level interventions. This session highlights recent advances in applying social network analysis (SNA) methods to study the implementation and impact of these types of innovations. This methods workshop examines the benefits and limits of novel SNA applications based on the expanding availability of large, linkable electronic clinical and administrative data sources with dependent data structures. This paper profiles examples of using SNA principles and methods to study the implementation …

Learning From Network Analysis: Care Transitions, Market Competition, & Community Interventions, Glen P. Mays

Health Management and Policy Presentations

The increasingly connected world of health care delivery relies on an expanding frontier of multi-stakeholder structures and processes, from interdisciplinary patient-centered care teams, to virtual accountable care organizations (ACOs), to complex community-level interventions. This methods workshop highlights recent advances in applying social network analysis (SNA) methods to study the implementation and impact of these types of innovations. This session will examine the benefits and limits of novel SNA applications based on the expanding availability of large, linkable electronic clinical and administrative data sources with dependent data structures.

Learning From Delivery System Behavior, Dynamics & Interactions To Advance A Culture Of Health, Glen P. Mays

Health Management and Policy Presentations

A new "Systems for Action" national research program flows directly from the Robert Wood Johnson Foundation's Culture of Health action framework. This program will build evidence on how best to align the delivery and financing systems for medical care, public health, and community services & supports so as to promote wellbeing and resiliency, realize efficiencies in resource use, and reduce inequities in health.

Changes In Public Health System Capital And Long-Run Health And Economic Outcomes: 1998 To 2014, Glen P. Mays, Cezar B. Mamaril

Health Management and Policy Presentations

Research Objective: The Affordable Care Act created new resources and incentives for hospitals, insurers, public health agencies, and others to contribute to disease prevention and health promotion activities, potentially changing the structure of public health delivery systems and expanding the implementation of strategies that improve population health. This study uses data from the 1998-2014 National Longitudinal Survey of Public Health Systems to examine: (1) the extent and nature of change in inter-organizational contributions to public health activities, which we use as indicators of public health “system capital”; and (2) the effects of these changes on preventable mortality and resource use. …

Apoε2 And Education In Cognitively Normal Older Subjects With High Levels Of Ad Pathology At Autopsy: Findings From The Nun Study, Diego Iacono, Peter Zandi, Myron Gross, William R. Markesbery, Olga Pletnikova, Gay Rudow, Juan C. Troncoso

Sanders-Brown Center on Aging Faculty Publications

Asymptomatic Alzheimer's disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE …