Medicine and Health Sciences Commons^™

Peptide-Based Nanoparticles For Systemic Extrahepatic Delivery Of Therapeutic Nucleotides, Samuel A Wickline, Kirk K Hou, Hua Pan

2020-Current year OA Pubs

Peptide-based nanoparticles (PBN) for nucleotide complexation and targeting of extrahepatic diseases are gaining recognition as potent pharmaceutical vehicles for fine-tuned control of protein production (up- and/or down-regulation) and for gene delivery. Herein, we review the principles and mechanisms underpinning self-assembled formation of PBN, cellular uptake, endosomal release, and delivery to extrahepatic disease sites after systemic administration. Selected examples of PBN that have demonstrated recent proof of concept in disease models in vivo are summarized to offer the reader a comparative view of the field and the possibilities for clinical application.

Hyperhydration To Improve Kidney Outcomes In Children With Shiga Toxin-Producing E. Coli Infection: A Multinational Embedded Cluster Crossover Randomized Trial (The Hiko Stec Trial), Stephen B Freedman, David Schnadower, Myka Estes, T Charles Casper, Stuart L Goldstein, Silviu Grisaru, Andrew T Pavia, Benjamin S Wilfond, Melissa Metheney, Kadyn Kimball, Phillip I Tarr, Hyperhydration To Improve Kidney Outcomes In Children With Shiga Toxin-Producing E. Coli Infection (Hiko-Stec) Study Team

2020-Current year OA Pubs

BACKGROUND: Shiga toxin-producing E. coli (STEC) infections affect children and adults worldwide, and treatment remain solely supportive. Up to 15-20% of children infected by high-risk STEC (i.e., E. coli that produce Shiga toxin 2) develop hemolytic anemia, thrombocytopenia, and kidney failure (i.e., hemolytic uremic syndrome (HUS)), over half of whom require acute dialysis and 3% die. Although no therapy is widely accepted as being able to prevent the development of HUS and its complications, several observational studies suggest that intravascular volume expansion (hyperhydration) may prevent end organ damage. A randomized trial is needed to confirm or refute this hypothesis.

METHODS: …

Team-Focused Implementation Strategies To Improve Implementation Of Mental Health Screening And Referral In Rural Children's Advocacy Centers: Study Protocol For A Pilot Cluster Randomized Hybrid Type 2 Trial, Elizabeth A Mcguier, Gregory A Aarons, Jaely D Wright, John C Fortney, Byron J Powell, Scott D Rothenberger, Laurie R Weingart, Elizabeth Miller, David J Kolko

2020-Current year OA Pubs

BACKGROUND: Children's Advocacy Centers (CACs) use multidisciplinary teams to investigate and respond to maltreatment allegations. CACs play a critical role in connecting children with mental health needs to evidence-based mental health treatment, especially in low-resourced rural areas. Standardized mental health screening and referral protocols can improve CACs' capacity to identify children with mental health needs and encourage treatment engagement. In the team-based context of CACs, teamwork quality is likely to influence implementation processes and outcomes. Implementation strategies that target teams and apply the science of team effectiveness may enhance implementation outcomes in team-based settings.

METHODS: We will use Implementation Mapping …

Evaluation Of Pitting Corrosion By Dynamic Speckle Pattern Analysis, Omid Pedram, Ramin Jamali, Vahid Abbasian, Vahideh Farzam Rad, Arash Darafsheh, Ramin Khamedi, Esmaeil Poursaeidi, Ali-Reza Moradi

2020-Current year OA Pubs

There is an increasing interest in non-destructive and real-time high-resolution approaches for corrosion studies in metals. In this paper, we propose the dynamic speckle pattern method as a low-cost, easy-to-implement, and quasi in-situ optical technique for the quantitative evaluation of pitting corrosion. This type of corrosion occurs in a specific area of a metallic structure and causes holes formation leading to structural failure. A Custom 450 stainless steel sample, placed in 3.5 wt% NaCl solution and applied to a [Formula: see text] potential to initiate the corrosion, is used as the sample. The speckle patterns formed by the scattering of …

Tau Accumulation In Autosomal Dominant Alzheimer's Disease: A Longitudinal [18f]Flortaucipir Study, Antoinette O'Connor, Shaney Flores, Russ Hornbeck, Eric Mcdade, Brian A Gordon, Randall J Bateman, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

Cortical tau accumulation is a key pathological event that partly defines Alzheimer's disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir …

Induction Of A Torpor-Like Hypothermic And Hypometabolic State In Rodents By Ultrasound, Yaoheng Yang, Jinyun Yuan, Rachael L Field, Dezhuang Ye, Zhongtao Hu, Kevin Xu, Lu Xu, Yan Gong, Yimei Yue, Alexxai V Kravitz, Michael R Bruchas, Jianmin Cui, Jonathan R Brestoff, Hong Chen

2020-Current year OA Pubs

Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (>24 h) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic …

Targeted Neurostimulation Reverses A Spatiotemporal Biomarker Of Treatment-Resistant Depression, Anish Mitra, Marcus E Raichle, Andrew D Geoly, Ian H Kratter, Nolan R Williams

2020-Current year OA Pubs

Major depressive disorder (MDD) is widely hypothesized to result from disordered communication across brain-wide networks. Yet, prior resting-state-functional MRI (rs-fMRI) studies of MDD have studied zero-lag temporal synchrony (functional connectivity) in brain activity absent directional information. We utilize the recent discovery of stereotyped brain-wide directed signaling patterns in humans to investigate the relationship between directed rs-fMRI activity, MDD, and treatment response to FDA-approved neurostimulation paradigm termed Stanford neuromodulation therapy (SNT). We find that SNT over the left dorsolateral prefrontal cortex (DLPFC) induces directed signaling shifts in the left DLPFC and bilateral anterior cingulate cortex (ACC). Directional signaling shifts in the …

Mechanically Manipulating Glymphatic Transport By Ultrasound Combined With Microbubbles, Dezhuang Ye, Si Chen, Yajie Liu, Charlotte Weixel, Zhongtao Hu, Jinyun Yuan, Hong Chen

2020-Current year OA Pubs

The glymphatic system is a perivascular fluid transport system for waste clearance. Glymphatic transport is believed to be driven by the perivascular pumping effect created by the pulsation of the arterial wall caused by the cardiac cycle. Ultrasound sonication of circulating microbubbles (MBs) in the cerebral vasculature induces volumetric expansion and contraction of MBs that push and pull on the vessel wall to generate a MB pumping effect. The objective of this study was to evaluate whether glymphatic transport can be mechanically manipulated by focused ultrasound (FUS) sonication of MBs. The glymphatic pathway in intact mouse brains was studied using …

Pilot Study On The Influence Of Incentive Spirometry On Percutaneous Image-Guided Intra-Abdominal Drainage Catheter Pressure: A Potential Method To Enhance Drainage, Aravinda Ganapathy, David H. Ballard, Grace L. Bishop, Mark J. Hoegger, Nihil Abraham, Horacio B. D'Agostino

2020-Current year OA Pubs

No abstract provided.

Upregulation Of The Oct3/4 Network In Basal Breast Cancer Is Associated With Its Metastatic Potential And Shows Tissue Dependent Variability, Robin G Rajan, Raisa I Krutilina, Tatyana N Ignatova, Zoran S Pavicevich, Galina M Dulatova, Maria A Lane, Arindam R Chatterjee, Robert J Rooney, Mymoon Antony, Vivian R Hagerty, Nickolay V Kukekov, Khalid A Hanafy, Frank D Vrionis

2020-Current year OA Pubs

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the

Missense Vkor Mutants Exhibit Severe Warfarin Resistance But Lack Vkcfd Via Shifting To An Aberrantly Reduced State, Shuang Li, Jie Sun, Shixuan Liu, Fengbo Zhou, Michael L Gross, Weikai Li

2020-Current year OA Pubs

Missense vitamin K epoxide reductase (VKOR) mutations in patients cause resistance to warfarin treatment but not abnormal bleeding due to defective VKOR activity. The underlying mechanism of these phenotypes remains unknown. Here we show that the redox state of these mutants is essential to their activity and warfarin resistance. Using a mass spectrometry-based footprinting method, we found that severe warfarin-resistant mutations change the VKOR active site to an aberrantly reduced state in cells. Molecular dynamics simulation based on our recent crystal structures of VKOR reveals that these mutations induce an artificial opening of the protein conformation that increases access of …

Protocol To Isolate Rbp-Mrna Complexes Using Rna-Clip And Examine Target Mrnas, Valerie Blanc, Elizabeth A Molitor, Nicholas O Davidson

2020-Current year OA Pubs

RNA-binding proteins (RBPs) regulate diverse functions by interacting with target transcripts. Here we present a protocol to isolate RBP-mRNA complexes using RNA-CLIP and examine target mRNAs in association with ribosomal populations. We describe steps to identify specific RBPs and RNA targets reflecting a variety of developmental, physiological, and pathological states. This protocol enables RNP complex isolation from tissue sources (liver and small intestine) or populations of primary cells (hepatocytes), but not at a single-cell level. For complete details on the use and execution of this protocol, please refer to Blanc et al. (2014)

Smoking Status, Nicotine Medication, Vaccination, And Covid-19 Hospital Outcomes: Findings From The Covid Ehr Cohort At The University Of Wisconsin (Cec-Uw) Study, Thomas M Piasecki, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown.

METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission.

RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass …

Serum Metabolomic Signatures Of Fatty Acid Oxidation Defects Differentiate Host-Response Subphenotypes Of Acute Respiratory Distress Syndrome, Tomeka L Suber, Stacy G Wendell, Steven J Mullett, Benjamin Zuchelkowski, William Bain, Georgios D Kitsios, Bryan J Mcverry, Prabir Ray, Anuradha Ray, Rama K Mallampalli, Yingze Zhang, Faraaz Shah, Seyed Mehdi Nouraie, Janet S Lee

2020-Current year OA Pubs

BACKGROUND: Fatty acid oxidation (FAO) defects have been implicated in experimental models of acute lung injury and associated with poor outcomes in critical illness. In this study, we examined acylcarnitine profiles and 3-methylhistidine as markers of FAO defects and skeletal muscle catabolism, respectively, in patients with acute respiratory failure. We determined whether these metabolites were associated with host-response ARDS subphenotypes, inflammatory biomarkers, and clinical outcomes in acute respiratory failure.

METHODS: In a nested case-control cohort study, we performed targeted analysis of serum metabolites of patients intubated for airway protection (airway controls), Class 1 (hypoinflammatory), and Class 2 (hyperinflammatory) ARDS patients …

Integrating Tobacco Treatment Into Oncology Care: Reach And Effectiveness Of Evidence-Based Tobacco Treatment Across National Cancer Institute-Designated Cancer Centers, Sarah D Hohl, Alex T Ramsey, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

PURPOSE: Quitting smoking improves patients' clinical outcomes, yet smoking is not commonly addressed as part of cancer care. The Cancer Center Cessation Initiative (C3I) supports National Cancer Institute-designated cancer centers to integrate tobacco treatment programs (TTPs) into routine cancer care. C3I centers vary in size, implementation strategies used, and treatment approaches. We examined associations of these contextual factors with treatment reach and smoking cessation effectiveness.

METHODS: This cross-sectional study used survey data from 28 C3I centers that reported tobacco treatment data during the first 6 months of 2021. Primary outcomes of interest were treatment reach (reach)-the proportion of patients identified …

Multi-Stakeholder Perspectives Regarding Preferred Modalities For Mental Health Intervention Delivered In The Orthopedic Clinic: A Qualitative Analysis, Abby L Cheng, Ashwin J Leo, Ryan P Calfee, Christopher J Dy, Melissa A Armbrecht, Joanna Abraham

2020-Current year OA Pubs

BACKGROUND: Although depressive and anxious symptoms negatively impact musculoskeletal health and orthopedic outcomes, a gap remains in identifying modalities through which mental health intervention can realistically be delivered during orthopedic care. The purpose of this study was to understand orthopedic stakeholders' perceptions regarding the feasibility, acceptability, and usability of digital, printed, and in-person intervention modalities to address mental health as part of orthopedic care.

METHODS: This single-center, qualitative study was conducted within a tertiary care orthopedic department. Semi-structured interviews were conducted between January and May 2022. Two stakeholder groups were interviewed using a purposive sampling approach until thematic saturation was …

Conditional Deletion Of Lrrc8a In The Brain Reduces Stroke Damage Independently Of Swelling-Activated Glutamate Release, Mustafa Balkaya, Preeti Dohare, Sophie Chen, Alexandra L Schober, Antonio M Fidaleo, Julia W Nalwalk, Rajan Sah, Alexander A Mongin

2020-Current year OA Pubs

The ubiquitous volume-regulated anion channels (VRACs) facilitate cell volume control and contribute to many other physiological processes. Treatment with non-specific VRAC blockers or brain-specific deletion of the essential VRAC subunit LRRC8A is highly protective in rodent models of stroke. Here, we tested the widely accepted idea that the harmful effects of VRACs are mediated by release of the excitatory neurotransmitter glutamate. We produced conditional LRRC8A knockout either exclusively in astrocytes or in the majority of brain cells. Genetically modified mice were subjected to an experimental stroke (middle cerebral artery occlusion). The astrocytic LRRC8A knockout yielded no protection. Conversely, the brain-wide …

Using Mass Spectrometry Imaging To Map Fluxes Quantitatively In The Tumor Ecosystem, Michaela Schwaiger-Haber, Ethan Stancliffe, Dhanalakshmi S Anbukumar, Blake Sells, Jia Yi, Kevin Cho, Kayla Adkins-Travis, Milan G Chheda, Leah P Shriver, Gary J Patti

2020-Current year OA Pubs

Tumors are comprised of a multitude of cell types spanning different microenvironments. Mass spectrometry imaging (MSI) has the potential to identify metabolic patterns within the tumor ecosystem and surrounding tissues, but conventional workflows have not yet fully integrated the breadth of experimental techniques in metabolomics. Here, we combine MSI, stable isotope labeling, and a spatial variant of Isotopologue Spectral Analysis to map distributions of metabolite abundances, nutrient contributions, and metabolic turnover fluxes across the brains of mice harboring GL261 glioma, a widely used model for glioblastoma. When integrated with MSI, the combination of ion mobility, desorption electrospray ionization, and matrix …

Safety, Tolerability, And Effectiveness Of The Sodium-Glucose Cotransporter 2 Inhibitor (Sglt2i) Dapagliflozin In Combination With Standard Chemotherapy For Patients With Advanced, Inoperable Pancreatic Adenocarcinoma: A Phase 1b Observational Study, Lauren K Park, Kian-Huat Lim, Jonas Volkman, Mina Abdiannia, Hannah Johnston, Zack Nigogosyan, Marilyn J Siegel, Janet B Mcgill, Alexis M Mckee, Maamoun Salam, Rong M Zhang, Da Ma, Karteek Popuri, Vincent Tze Yang Chow, Mirza Faisal Beg, William G Hawkins, Linda R Peterson, Joseph E Ippolito

2020-Current year OA Pubs

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC's excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin is safe and efficacious in humans with PDAC is unclear.

METHODS: We performed a phase 1b observational study (ClinicalTrials.gov ID NCT04542291; registered 09/09/2020) to test the safety and tolerability of dapagliflozin (5 mg p.o./day × 2 weeks escalated to 10 mg p.o./day × …

Predicting Alcohol-Related Memory Problems In Older Adults: A Machine Learning Study With Multi-Domain Features, Chella Kamarajan, Andrey P Anokhin, Sarah Hartz, Laura J Bierut, Vivia V Mccutcheon, Kathleen K Bucholz, Et Al.

2020-Current year OA Pubs

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (the memory group) were compared with a matched control group who did not have memory problems. The random forests model identified specific features from each domain that contributed to the classification of the memory group vs. the control group (AUC = 88.29%). Specifically, individuals from the memory group manifested a …

Dual Targeting Of Cd19 And Cd22 With Bicistronic Car-T Cells In Patients With Relapsed/Refractory Large B-Cell Lymphoma, Claire Roddie, Nancy Bartlett, Et Al.

2020-Current year OA Pubs

Relapse after CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL) is commonly ascribed to antigen loss or CAR-T exhaustion. Multiantigen targeting and programmed cell death protein-1 blockade are rational approaches to prevent relapse. Here, we test CD19/22 dual-targeting CAR-T (AUTO3) plus pembrolizumab in relapsed/refractory LBCL (NCT03289455). End points include toxicity (primary) and response rates (secondary). Fifty-two patients received AUTO3 and 48/52 received pembrolizumab. Median age was 59 years (range, 27-83), 46/52 had stage III/ IV disease and median follow-up was 21.6 months. AUTO3 was safe; grade 1-2 and grade 3 cytokine release syndrome affected 18/52 (34.6%) …

Distress Related To Psychotic Experiences: Enhancing The World Health Organization Composite International Diagnostic Interview Psychosis Screen, Hans Oh, Nicole R Karcher, Nirit Soffer-Dudek, Ai Koyanagi, Megan Besecker, Jordan E Devylder

2020-Current year OA Pubs

BACKGROUND: The abbreviated version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) psychosis screen tends to yield high prevalence in online samples. Psychotic Experiences (PE) may not necessarily indicate current or imminent psychopathology; however, distressing PE appear to be more clinically informative.

METHODS: We analyzed data collected from an online survey administered to a Qualtrics panel (N = 2522 adults). Using multivariable logistic regression, we examined the association between PE (with and without associated distress) and several mental health outcomes, adjusting for age, gender, and race/ethnicity.

RESULTS: Individuals with distressing PE had greater odds of most mental …

The Evolution Of Primary Care Telehealth Disparities During Covid-19: Retrospective Cohort Study, Rachel D'Amico, Patrick M Schnell, Randi Foraker, J Nwando Olayiwola, Daniel E Jonas, Seuli Bose Brill

2020-Current year OA Pubs

BACKGROUND: Telehealth has become widely used as a novel way to provide outpatient care during the COVID-19 pandemic, but data about telehealth use in primary care remain limited. Studies in other specialties raise concerns that telehealth may be widening existing health care disparities, requiring further scrutiny of trends in telehealth use.

OBJECTIVE: Our study aims to further characterize sociodemographic differences in primary care via telehealth compared to in-person office visits before and during the COVID-19 pandemic and determine if these disparities changed throughout 2020.

METHODS: We conducted a retrospective cohort study in a large US academic center with 46 primary …

Choroid Plexus-Targeted Nkcc1 Overexpression To Treat Post-Hemorrhagic Hydrocephalus, Cameron Sadegh, Yong Zhang, Michael J Holtzman, Et Al.

2020-Current year OA Pubs

Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH. Mimicking IVH with intraventricular blood led to increased CSF [K

How Does Facilitation In Healthcare Work? Using Mechanism Mapping To Illuminate The Black Box Of A Meta-Implementation Strategy, Amy M Kilbourne, Elvin Geng, Ingrid Eshun-Wilson, Shannon Sweeney, Donna Shelley, Deborah J Cohen, Joann E Kirchner, Maria E Fernandez, Michael L Parchman

2020-Current year OA Pubs

BACKGROUND: Healthcare facilitation, an implementation strategy designed to improve the uptake of effective clinical innovations in routine practice, has produced promising yet mixed results in randomized implementation trials and has not been fully researched across different contexts.

OBJECTIVE: Using mechanism mapping, which applies directed acyclic graphs that decompose an effect of interest into hypothesized causal steps and mechanisms, we propose a more concrete description of how healthcare facilitation works to inform its further study as a meta-implementation strategy.

METHODS: Using a modified Delphi consensus process, co-authors developed the mechanistic map based on a three-step process. First, they developed an initial …

Genome-Wide Association Study Of Breast Density Among Women Of African Ancestry, Shefali Setia Verma, Lindsay Guare, Sarah Ehsan, Aimilia Gastounioti, Gabrielle Scales, Marylyn D Ritchie, Despina Kontos, Anne Marie Mccarthy, Penn Medicine Biobank

2020-Current year OA Pubs

Breast density, the amount of fibroglandular versus fatty tissue in the breast, is a strong breast cancer risk factor. Understanding genetic factors associated with breast density may help in clarifying mechanisms by which breast density increases cancer risk. To date, 50 genetic loci have been associated with breast density, however, these studies were performed among predominantly European ancestry populations. We utilized a cohort of women aged 40-85 years who underwent screening mammography and had genetic information available from the Penn Medicine BioBank to conduct a Genome-Wide Association Study (GWAS) of breast density among 1323 women of African ancestry. For each …

A Single-Cell Multiomic Analysis Of Kidney Organoid Differentiation, Yasuhiro Yoshimura, Yoshiharu Muto, Nicolas Ledru, Haojia Wu, Kohei Omachi, Jeffrey H Miner, Benjamin D Humphreys

2020-Current year OA Pubs

Kidney organoids differentiated from pluripotent stem cells are powerful models of kidney development and disease but are characterized by cell immaturity and off-target cell fates. Comparing the cell-specific gene regulatory landscape during organoid differentiation with human adult kidney can serve to benchmark progress in differentiation at the epigenome and transcriptome level for individual organoid cell types. Using single-cell multiome and histone modification analysis, we report more broadly open chromatin in organoid cell types compared to the human adult kidney. We infer enhancer dynamics by cis-coaccessibility analysis and validate an enhancer driving transcription of

Circadian Clock Protein Bmal1 Broadly Influences Autophagy And Endolysosomal Function In Astrocytes, Celia A Mckee, Alexander J Polino, Melvin W King, Erik S Musiek

2020-Current year OA Pubs

An emerging role for the circadian clock in autophagy and lysosome function has opened new avenues for exploration in the field of neurodegeneration. The daily rhythms of circadian clock proteins may coordinate gene expression programs involved not only in daily rhythms but in many cellular processes. In the brain, astrocytes are critical for sensing and responding to extracellular cues to support neurons. The core clock protein BMAL1 serves as the primary positive circadian transcriptional regulator and its depletion in astrocytes not only disrupts circadian function but also leads to a unique cell-autonomous activation phenotype. We report here that astrocyte-specific deletion …

Developing Tools For The Implementation And Evaluation Of Participatory Worker Health Promotion Interventions, Ryan J. Walsh

WUSM Theses and Dissertations – All Programs

The chronic disease burden among American workers leads to substantial expenditures on healthcare, lost productivity at work, and reduced quality of life. Workers from communities of lower socioeconomic status (SES) shoulder a disproportionate burden of chronic diseases and costs. A promising strategy for addressing this population health burden is to develop and implement participatory worker health promotion interventions in workplaces. Part of this effort to develop and implement these programs entails improving the quality of evaluation tools and approaches. Thus, we completed a series of secondary analyses of a large participatory worker health promotion program trial called Working For You. …

Goal Setting And Goal Management For Chronic Conditions: Intervention And Implementation Strategies, Eunyoung Kang

WUSM Theses and Dissertations – All Programs

Adults with chronic conditions experience limited participation in personally meaningful activities and roles. Chronic conditions can present challenges across personal factors such as cognitive, psychological, physiological, or neurobehavioral functions. These personal factors then dynamically interact with environmental factors, occupation, and performance, ultimately hindering adults with chronic conditions in achieving their goals to fully participate in meaningful activities and roles.

Goal setting and goal management has evolved from diverse theories including Social Cognitive Theory, Self-Determination Theory, and The Theory of Intentional Action Control. These theories emphasize the importance of addressing influential theoretical constructs such as self-efficacy and outcome expectancy but also …