73 results match your criteria: "Geriatric Research Educational and Clinical Center[Affiliation]"

Background: Shortly after Medicare implemented post-acute care payment reforms, the COVID-19 pandemic began, but little is known about how these reforms and the pandemic impacted admissions to the most common post-acute settings-skilled nursing facilities (SNF) and home health agencies (HHAs)-for the full Medicare fee-for-service population.

Methods: Using 100% of Medicare fee-for-service data, we conducted adjusted interrupted time series analyses of 31,730,994 hospital stays of all adult beneficiaries discharged alive from the hospital between 2018 and 2021 to examine whether payment reforms and the pandemic were associated with differences in admissions to SNFs and HHAs compared to pre-reform and pre-COVID (baseline) trends.

Results: At baseline, an average 18.

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Article Synopsis
  • Women currently lack a comprehensive tool to report their toileting decisions and bladder symptoms, which are influenced by real-world factors that may affect bladder health.
  • The PLUS research consortium developed and tested WhereIGo, a mobile app aimed at capturing various environmental and social influences on women's toileting choices, including unique features for reporting urge sensations.
  • The app underwent usability testing with community women to measure its effectiveness, employing a user-friendly design and gathering real-time data while adhering to a limit on screen taps.
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Systemic treatment with ubiquitin carboxy terminal hydrolase L1 TAT protein ameliorates axonal injury and reduces functional deficits after traumatic brain injury in mice.

Exp Neurol

March 2024

Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:

Traumatic brain injury (TBI) is often associated with axonal injury that leads to significant motor and cognitive deficits. Ubiquitin carboxy terminal hydrolase L1 (UCHL1) is highly expressed in neurons and loss of its activity plays an important role in the pathogenesis of TBI. Fusion protein was constructed containing wild type (WT) UCHL1 and the HIV trans-activator of transcription capsid protein transduction domain (TAT-UCHL1) that facilitates transport of the protein into neurons after systemic administration.

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The Potential of the Nose-to-Brain Delivery of PACAP for the Treatment of Neuronal Disease.

Pharmaceutics

July 2023

Univ Rouen Normandie, Inserm U1245, Medical Faculty, Normandie Univ, F-76000 Rouen, France.

Research on the neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) and its use as a therapeutic agent has grown over the past 30 years. Both in vitro and in vivo experiments have shown that PACAP exerts a strong neuroprotective effect in many central and peripheral neuronal diseases. Various delivery routes have been employed from intravenous (IV) injections to intracerebroventricular (ICV) administration, leading either to systemic or topical delivery of the peptide.

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Brain gray matter reduction and premature brain aging after breast cancer chemotherapy: a longitudinal multicenter data pooling analysis.

Brain Imaging Behav

October 2023

Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, and Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.

Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as deformation-based morphometry (DBM), machine-learning-based brain aging metrics, or the relationship of clinical and demographic risk factors to GM reduction. This international data pooling study begins to address these questions.

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High-mobility group box 1 (HMGB1) is a ubiquitous protein that regulates transcription in the nucleus, and is an endogenous damage-associated molecular pattern molecule that activates the innate immune system. HMGB1 activates the TLR4 and RAGE recepto, inducing downstream signals reminiscent of cytokines that have been found to cross the blood-brain barrier (BBB). Blood HMGB1 increases in stroke, sepsis, senescence, alcohol binge drinking and other conditions.

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The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity.

Cancers (Basel)

July 2022

Department of Neurology and Pittsburgh Institute for Neurodegenerative Disease, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Cancer cells possess a high metabolic demand for their rapid proliferation, survival, and progression and thus create an acidic and hypoxic tumor microenvironment (TME) deprived of nutrients. Moreover, acidity within the TME is the central regulator of tumor immunity that influences the metabolism of the immune cells and orchestrates the local and systemic immunity, thus, the TME has a major impact on tumor progression and resistance to anti-cancer therapy. Specifically, myeloid cells, which include myeloid-derived suppressor cells (MDSC), dendritic cells, and tumor-associated macrophages (TAMs), often reprogram their energy metabolism, resulting in stimulating the angiogenesis and immunosuppression of tumors.

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Background: There is a growing cohort of head and neck cancer (HNC) patients affected by late- and long-term posttreatment side effects. Our study evaluates the relationship between the demographics, clinical characteristics, and posttreatment symptom burden with the subjective sense of flourishing among HNC survivors.

Methods: A cross-sectional, single-center study of adult survivors of squamous cell cancer of the oral cavity, oropharynx, and larynx/hypopharynx who completed the Secure Flourishing Index (SFI) and patient-reported outcomes related to depression, anxiety, swallowing dysfunction, neck disability, and insomnia between November 2020 and April 2021.

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Applying VitalTalk Techniques to Best Case/Worst Case Training to Increase Scalability and Improve Surgeon Confidence in Shared Decision-making.

J Surg Educ

June 2022

Department of Surgery, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania; The Wolff Center at UPMC, Pittsburgh, Pennsylvania; Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Geriatric Research Educational and Clinical Center, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.

Objective: Best Case/Worst Case (BC/WC) is a communication tool designed to promote shared decision-making for high-risk procedures near the end of life. This study aimed to increase scalability of a BC/WC training program and measure its impact on surgeon confidence in and perceived importance of the methodology.

Design: A prospective cohort pre-post study; December 2018 to January 2019.

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Background: Frailty tools assess symptoms and comorbidities that may coincide with those of primary hyperparathyroidism. To test the hypothesis that parathyroidectomy improves frailty, we conducted a prospective cohort comparison of frailty after parathyroid or thyroid surgery.

Methods: The Risk Analysis Index measuring frailty was prospectively administered to patients undergoing curative parathyroid exploration or total thyroidectomy.

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Importance: Recent legislation facilitates veterans' ability to receive non-Veterans Affairs (VA) surgical care. However, contemporary data comparing the quality and safety of VA and non-VA surgical care are lacking.

Objective: To compare perioperative outcomes among veterans treated in VA hospitals with patients treated in private-sector hospitals.

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Mutation of a Ubiquitin Carboxy Terminal Hydrolase L1 Lipid Binding Site Alleviates Cell Death, Axonal Injury, and Behavioral Deficits After Traumatic Brain Injury in Mice.

Neuroscience

November 2021

Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, Pittsburgh, PA, 15240, USA; Department of Neurology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, 15213, USA. Electronic address:

Ubiquitin carboxy terminal hydrolase L1 (UCHL1) is a protein highly expressed in neurons that may play important roles in the ubiquitin proteasome pathway (UPP) in neurons, axonal integrity, and motor function after traumatic brain injury (TBI). Binding of reactive lipid species to cysteine 152 of UCHL1 results in unfolding, aggregation, and inactivation of the enzyme. To test the role of this mechanism in TBI, mice bearing a cysteine to alanine mutation at site 152 (C152A mice) that renders UCHL1 resistant to inactivation by reactive lipids were subjected to the controlled cortical impact model (CCI) of TBI and compared to wild type (WT) controls.

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Background: The Unified Medical Language System (UMLS) maps relationships between and within >100 biomedical vocabularies, including Current Procedural Terminology (CPT) codes, creating a powerful knowledge resource which can accelerate clinical research.

Methods: We used synonymy and concepts relating hierarchical structure of CPT codes within the UMLS, (1) guiding surgical experts in expanding the Operative Stress Score (OSS) from 565 originally rated CPT codes to additional, 1,853 related procedures; (2) establishing validity of the association between the added OSS ratings and 30-day outcomes in VASQIP (2015-2018).

Results: The UMLS Metathesaurus and Semantic Network was converted into an interactive graph database (https://github.

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Article Synopsis
  • Huntington's disease (HD) may impact not just motor function but also the autonomic nervous system, affecting bladder, bowel, and sexual functions.
  • A study with 48 HD patients revealed that 93.8% experienced symptoms in at least one of these areas, with over 39% reporting issues across all three.
  • Patients with concurrent symptoms tended to have a longer disease duration and lower overall functional capacity.
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Apolipoprotein E (APOE) ε4 moderates the relationship between c-reactive protein, cognitive functioning, and white matter integrity.

Brain Behav Immun

July 2021

National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Boston Attention and Learning Laboratory, VA Healthcare System, Boston, MA, USA.

Elevated serum C-reactive protein (CRP) and possessing an APOE ε4 allele are two of the most prominent risk factors for cognitive and neurological dysfunction in older adults, but little is known about the unique or cumulative effects of these risk factors in young-to-middle-aged adults. To further characterize these potential relationships, measures of cognition and microstructural white matter integrity were examined using data from a sample of 329 post-9/11 war veterans that was collected as part of a comprehensive evaluation that included assessment of neuropsychological functioning, MRI scanning, psychiatric diagnoses, health screening, markers of inflammation, and APOE genotypes. Hierarchical linear regression analyses revealed the CRP and APOE ε4 interaction was associated with global cognition (β = -0.

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Abolishing UCHL1's hydrolase activity exacerbates TBI-induced axonal injury and neuronal death in mice.

Exp Neurol

February 2021

Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, PA, USA. Electronic address:

Ubiquitin (Ub) C-terminal hydrolase L1 (UCHL1) is a multifunctional protein that is expressed in neurons throughout brain at high levels. UCHL1 deletion is associated with axonal degeneration, progressive sensory motor ataxia, and premature death in mice. UCHL1 has been hypothesized to play a role in the pathogenesis of neurodegenerative diseases and recovery after neuronal injury.

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PTSD is associated with increased DNA methylation across regions of HLA-DPB1 and SPATC1L.

Brain Behav Immun

January 2021

Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA; Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA. Electronic address:

Posttraumatic stress disorder (PTSD) is characterized by intrusive thoughts, avoidance, negative alterations in cognitions and mood, and arousal symptoms that adversely affect mental and physical health. Recent evidence links changes in DNA methylation of CpG cites to PTSD. Since clusters of proximal CpGs share similar methylation signatures, identification of PTSD-associated differentially methylated regions (DMRs) may elucidate the pathways defining differential risk and resilience of PTSD.

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PTSD and the klotho longevity gene: Evaluation of longitudinal effects on inflammation via DNA methylation.

Psychoneuroendocrinology

July 2020

National Center for PTSD at VA Boston Healthcare System, United States; Department of Psychiatry, Boston University School of Medicine, United States.

Background: Longevity gene klotho (KL) is associated with age-related phenotypes including lifespan, cardiometabolic disorders, cognition, and brain morphology, in part, by conferring protection against inflammation. We hypothesized that the KL/inflammation association might be altered in the presence of psychiatric stress and operate via epigenetic pathways. We examined KL polymorphisms, and their interaction with posttraumatic stress disorder (PTSD) symptoms, in association with KL DNA methylation in blood.

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Background: Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD).

Methods: In this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs.

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A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium).

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Epigenetic age estimations based on DNA methylation (DNAm) can predict human chronological age with a high level of accuracy. These DNAm age algorithms can also be used to index advanced cellular age, when estimated DNAm age exceeds chronological age. Advanced DNAm age has been associated with several diseases and metabolic and inflammatory pathology, but the causal direction of this association is unclear.

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The goddess who spins the thread of life: Klotho, psychiatric stress, and accelerated aging.

Brain Behav Immun

August 2019

National Center for PTSD at VA Boston Healthcare System, Boston, MA, USA; Boston University School of Medicine, Department of Psychiatry, Boston, MA, USA.

Background: Longevity gene klotho (KL) is associated with age-related phenotypes but has not been evaluated against a direct human biomarker of cellular aging. We examined KL and psychiatric stress, including posttraumatic stress disorder (PTSD), which is thought to potentiate accelerated aging, in association with biomarkers of cellular aging.

Methods: The sample comprised 309 white, non-Hispanic genotyped veterans with measures of epigenetic age (DNA methylation age), telomere length (n = 252), inflammation (C-reactive protein), psychiatric symptoms, metabolic function, and white matter neural integrity (diffusion tensor imaging; n = 185).

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Ubiquitin C-terminal hydrolase L1 (UCHL1) is a unique brain-specific deubiquitinating enzyme. Mutations in and aberrant function of UCHL1 have been linked to many neurological disorders. UCHL1 activity protects neurons from hypoxic injury, and binding of stroke-induced reactive lipid species to the cysteine 152 (C152) of UCHL1 unfolds the protein and disrupts its function.

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