MEDICA@MUSC (Medical University of South Carolina)
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The Impact of Using Community Health Workers in Collaboration with Nurse Case Managers in Effecting Change in the Quality of Life for Diabetes Patients
Get PDFThis project was designed to evaluate the effectiveness of improving the quality of life among type 2 diabetes patients with the addition of the role of Community Health Worker (CHW) to a current continuum case management model. The study also addressed the increased need for more appropriate and cost-effective chronic care management for diabetic patients. Hospitals and healthcare systems are being challenged to find innovative ways to decrease readmissions, decrease unnecessary emergency room visits, increase patient adherence, and manage chronic disease, all improving the patient’s overall quality of life. CHW services enhance the current Continuum Case Management (CCM) program by providing additional health education, health care system navigation, healthcare monitoring, and identification of potential barriers for patients to receive appropriate care. In addition to improving the overall quality of life, patients receiving interventions from the CHW also experienced decreased readmissions and Emergency Department (ED) visits
Librarians Without Borders®: Door to Sustainable Global Librarianship
No full textPoster presented at the joint International Congress of Medical Librarianship (ICML) and the Association for Health Information and Libraries in Africa (AHILA)Congress in Pretoria, South Africa March 2022.https://medica-musc.researchcommons.org/posters/1015/thumbnail.jp
The Design and Synthesis of Tetrahydrophenylmethanones and Chromenephenylmethanones: Novel Classes of Biphenylpyrans as Broad-Spectrum Inhibitors of SARS and MERS Coronaviruses Targeting the 2’-OMTase (Nsp10-Nsp16) Viral Protein
No full textUnlike the vaccines for COVID-19, which depend on the highly mutable Spike (S) protein of SARS-CoV-2, antiviral therapeutics that directly inhibit nonstructural proteins (Nsps) can be designed to be specific and efficacious for all variants of related viruses. Nsps retain genetic homology throughout closely related viruses, such as SARS and MERS viruses from the Beta-coronavirus genus, allowing all variants of SARS-CoV-2, such as Delta (Δ) and Omicron (Ο), to be directly targeted. As a result, antiviral compounds with suspected activity against highly conserved Nsps were produced to inhibit a broad-spectrum of coronaviruses. Novel classes of biphenylpyrans (BPPs), specifically chromenephenylmethanones (CPMs) and tetrahydrophenylmethanones (TPMs), were selected from a unique pool of over 1000 naturally-derived or inspired compounds. Selection of the novel BPPs was based on compelling in silico docking scores to Nsps of coronaviruses, but with high specificity to the 2’-O-methyltransferase (2’-OMTase, Nsp10-Nsp16) responsible for viral mRNA maturation and host innate immune response evasion. In silico experiments were conducted to predict the compounds’ binding affinities to Nsps, the compounds’ physicochemical parameters, and the compounds’binding interactions to the S-adenosylmethionine (SAM) binding pocket in 2’-O-MTase. BPP regioisomers with a tetrahydrodibenzopyran (TBP) or benzochromenepyran (BCP) core motif, which are found in cannabinoids and other natural products, were chemically synthesized, purified via chromatography, and structurally analyzed using nuclear magnetic resonance (NMR) and DP4+ calculations. Molecular ion networking (MoIN) was conducted via tandem mass spectrometry (MS/MS) to molecularly compare synthesized BPPs to cannabinoids that share the core motif. In vitro assays for cytotoxicity, kinetic replication, and antiviral activity were conducted using Vero (African Green Monkey Kidney), Calu-3 (Human Lung Carcinoma), and Caco-2 (Human Colorectal Adenocarcinoma) cell lines. The BPPs displayed similarly high viral inhibitory percentages (BPP 2-A: 99.3% at 10 μM) as the FDA-approved remdesivir antiviral (99.9% at 10 μM) used as a control. The BPPs also had significantly greater CC50 concentrations in PBM cells (BPP 2-A: \u3e100 μM) in comparison to the control (2.0 μM), which indicated their potential safety as broad-spectrum coronavirus inhibitors. Future experiments have been planned to biochemically assay the BPPs predicted role as ligands for 2’-O-MTase inhibition. Further in vitro Tox/ADME studies will be conducted to screen candidate compounds prior to in vivo research
Client-Centered Outcome Measurement for Goal Setting, Treatment Planning, and Documentation in Home and Community Health Utilizing PROMIS Rasch Model Outputs
No full textInvestigating Needs and Concerns of Working AgeInformal Caregivers of Stroke Survivors
Get PDFPurpose: The purpose of this dissertation was to explore the unmet needs of working age (18-64) caregivers of stroke survivors and their quality of Life (QoL). First, a scoping review of peer support interventions for caregivers of individuals with cognitive impairment, including stroke, was conducted through the lens of the Social Ecological Model (SEM) Next, an integrative review was conducted to examine stroke caregiver’s QoL utilizing the model of QoL for family caregivers of stroke survivors. Finally, the needs and concerns of working age caregivers of stroke survivors and the factors affecting their QoL were explored through a cross-sectional descriptive study framed with the model of QoL for family caregivers of stroke survivors. Problem: Informal caregivers are an integral part of maintaining quality of life (QoL) for stroke survivors. However, this often comes at the expense of their own QoL. Working age (18-64) caregivers are at an increased risk for decreased QoL due to the many other responsibilities they have in addition to the role of caregiver. Peer support interventions could be one strategy to increase QoL in informal caregivers of stroke survivors, though research on the needs and concerns of working age caregivers of stroke survivors, their QoL, and peer support interventions for this population is limited. The specific aims of this dissertation were: Aim 1: To investigate peer support interventions for informal caregivers via a scoping review Aim 2: To examine the QoL of informal caregivers of stroke survivors through an integrative review Aim 3: To characterize unmet needs and concerns, caregiver self-efficacy, social support, and quality of life of working age caregivers of stroke survivors through a cross-sectional descriptive online survey using validated measures Design: A cross-sectional descriptive study design, informed by the model of QoL for informal caregivers of stroke survivors, guided quantitative data collection. Findings: In the scoping review, twenty-nine articles representing twenty-five studies were included in the analysis. Twenty-four of the studies noted statistically significant improvements in outcomes including an increase in caregiver self-efficacy, health, and QoL as well as knowledge, social support, and community integration. The integrative review examined sixty-one articles representing fifty-one studies. The review confirmed the stability of the model of QoL for informal caregivers of stroke survivors and identified additional factors that influence caregiver QoL including stroke survivor characteristics, time spent in daily care, duration of care, coping styles, and training. In the cross-sectional descriptive study, there were many needs and concerns identified in working age caregivers of stroke survivors. There were also statistically significant relationships found between these needs and concerns and stroke survivor functional status, caregiver strain, caregiver self-efficacy, and caregiver QoL. Relationships were also statistically significant between caregiver QoL and several factors identified in the model of QoL for family caregivers of stroke survivors. Conclusion: Working age caregivers of stroke survivors had unmet needs and concerns as well as many factors that put them at risk for decreased QoL. Peer support interventions have shown benefit for informal caregivers of persons with cognitive impairment (CI) and future studies could evaluate the effectiveness of peer support for working age caregivers of stroke survivors. Future studies with a strong theoretical framework such as that provided by the updated model of QoL for informal caregivers of stroke survivors should be conducted to further explore how unmet needs can be met and how they predict working age caregiver QoL. Caregiver needs and concerns should also be explored through the lens of sociodemographic factors such as duration of care, gender, and race
Understanding the Role of Brain Insulin Levels and Signaling in Post Stroke Cognitive Impairment
Get PDFStroke is the leading cause of long term disability and has the potential to impact a person’s activities of daily life on a physical and cognitive level. Insulin resistance has been linked to increased risk of stroke recurrence, death, and poor outcome following stroke. Insulin resistance leads to decreased insulin transport into the brain. Insulin was thought to be primarily important for peripheral bodily function, however brain insulin has proven to improve memory and cognition as well as having neuroprotective properties. Brain insulin levels and increasing insulin in the brain has not been examined as a therapeutic model for improving stroke recovery. This dissertation introduced a way to bypass the blood brain barrier and administered insulin as a therapeutic directly to the brain, through intranasal administration. The first dissertation chapter provided background of stroke, populations that experience worse stroke outcome, importance of insulin, and a potential therapeutic avenue, the second chapter detailed the experimental methods used to answer the questions. The third chapter explored the impact diet-induced brain insulin deficiency had on cognition. Brain insulin deficiency mimicked by inducing hyperinsulinemia though a high fat diet (HFD) in male and female mice. Brain insulin was demonstrated by observing brain insulin levels, signaling, and cognition was observed by having the mice perform cognitive tasks. HFD males had reduced brain insulin, and impaired performance on cognitive tasks. To account for the impact of diet on cognition chapter four focused on the impact pharmacologically induced brain insulin deficiency had on cognition in male and female mice on a standard diet (STD). Insulin signaling, and cognition were assessed. Male mice demonstrated reduced downstream insulin signaling in the brain and impaired performance on cognitive tasks. The fifth chapter explored the impact increasing brain insulin had on stroke recovery in a STD and HFD mouse model. Following stroke, male and female mice received intranasal insulin treatment then survival, neurological deficits, cognitive and motor deficits were assessed. Intranasal insulin improved functional stroke recovery in male mice. These studies provide insight into the impact brain insulin deficiency has on cognition and the importance of brain insulin on stroke recovery
The Intersection of Research and Community Health: Using Evidence to Inform Population Health Strategy
Get PDFBackground: Social determinants of health (SDoH) are the conditions in which people are born, grow, live, and work, and they significantly impact an individual’s health and wellbeing. With robust connections to community partners, access to data, and touch points with patients, healthcare systems are ideally positioned to address SDoH, yet systems struggle to identify how best to capture and manage SDoH needs. The hospital within our academic medical center leveraged a partnership with our medical library to create an evidence review program, specifically aimed at informing the health system’s population health strategy and implementation tactics using best research evidence. Description: When tasked with developing a comprehensive population health strategy, the hospital within our academic medical center partnered with our medical library to create an evidence synthesis service aimed at infusing best research practices into strategy development and implementation. The hospital’s executive leadership team identified clinical and policy questions, and members of the hospital’s population health department worked closely with a medical librarian to complete literature searches, appraise evidence and summarize findings for leaders. These findings were used to inform strategy and implementation decisions. Examples of topics searched included the following: the most effective way to screen for SDoH needs, the best clinical data to use for predictive risk assessments, approaches to outreaching high-risk patients, and the effectiveness of integrating behavioral health resources into clinics for patients with complex medical conditions. Conclusion: This program led to the successful implementation of population health strategies for our healthcare system, and has benefited our community. The evidence synthesis service helped secure grant funding for two behavioral health resources for our adult and pediatric sickle cell disease clinics. This program also informed our enterprise-wide roll-out of SDoH screening and referral management. These are a few demonstrable ways the program has resulted in improvements in care delivery. Our population health strategy tactics each have metrics of success, which are monitored on our health system’s scorecard. Achievement of these measures will also serve as a way to monitor our program’s effectiveness going forward
Neuronal PAS Domain Protein 4 (NPAS4) Controls Cell Type-Specific Circuit Adaptations Underlying Drug Seeking Behavior and Chronic Stress-Induced Hypofrontality
No full textRe-exposure to diffuse and discrete cues associated with active drug use can trigger relapse in individuals recovering from substance use disorder (SUD). Relapse-like behavior is promoted in the nucleus accumbens (NAc) by the preponderant activation of D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs), while it is generally impeded by D2 dopamine receptor-expressing MSN (D2-MSN) stimulation. However, the molecular mechanisms controlling balance of activity between D1-MSNs and D2-MSNs during relapse-like drug seeking remain unknown. We show here that the activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), plays an essential role in this process. First, using a novel NPAS4-TRAP (Targeted Recombination in Active Populations) mouse combined with chemogenetics, we found that neurons expressing NPAS4 during cocaine conditioning are required for future drug seeking. In addition, using cell type-specific manipulations, we discovered that NPAS4 is required in D2-MSNs, but not D1-MSNs, for drug seeking in multiple behavioral models of SUD. Single-cell transcriptomic analyses of NAc tissues from drug-experienced mice revealed that that NPAS4 regulates numerous genes in D2-MSNs linked to synapse plasticity, SUD, and drug-related behavior. NPAS4 in NAc D2-MSNs also blocks cocaine experience-dependent strengthening of glutamatergic prefrontal cortical (PFC) inputs onto those neurons, which allows drug cues to activate D1-MSNs and trigger drug-seeking behavior. As such, our findings reveal a novel, cell type-specific function for NPAS4 to enable relapse-like behavior by selectively preventing drug experience-dependent potentiation of the PFC-\u3eNAc:D2-MSN circuit. Finally, there is high comorbidity between SUD and stress-induce neuropsychiatric disorders. Chronic stress can produce reward system deficits (e.g. anhedonia) and other common symptoms associated with depressive disorders, as well as neural circuit hypofunction in the medial prefrontal cortex (mPFC), though the molecular mechanisms remain unclear. We show that NPAS4 in the mPFC is regulated by chronic social defeat stress (CSDS) and that it’s required in this brain region for CSDS-induced changes in natural reward motivation. Additionally, mPFC NPAS4 is required for CSDS-induced reductions in pyramidal neuron dendritic spine density, and transcriptomic analysis from the mPFC revealed that NPAS4 influences expression of genes that are also dysregulated in common neuropsychiatric disorders. Together our findings reveal an essential role for the activity-regulated transcription factor, NPAS4, in both cocaine-conditioned behaviors and chronic stress-induced anhedonia, providing a novel mechanistic insight into potential pharmacotherapeutic treatments for comorbidity between SUDs and stress-related neuropsychiatric disorders
Disorder: The Impact of Structure and Function on Transcranial Magnetic Stimulation Treatment Response
Get PDFAlcohol Use Disorder (AUD) is the third leading cause of preventable death in the United States. While there are several treatment options available, none of these interventions specifically target the neural circuits known to contribute to alcohol use, abstinence, and relapse. In the following chapters, this dissertation will introduce transcranial magnetic stimulation (TMS) as a potential neural-circuit based therapeutic tool for AUD. Following a brief introduction to the neural circuitry involved in AUD (Chapter 1), Chapter 2 reviews the results of a multimodal randomized, double-blind, sham-controlled trial evaluating 10 sessions of TMS delivered to the frontal pole as a therapeutic tool for AUD. In this study, active TMS significantly reduced brain reactivity to alcohol cues and improved 3-month sobriety rates relative to sham, however there was high degree of individual variability in response to treatment. To explore neurobiological sources of variability that may influence TMS efficacy, Chapters 3 and 4 address three unique aspects of brain structure in AUD: grey and white matter integrity (Chapter 3) and scalp-to-cortex distance (Chapter 4). Chapter 3 demonstrates that individuals with AUD have lower cortical grey and white matter volume in areas frequently targeted with TMS, suggesting a greater dose of TMS may be needed to modulate cortical-striatal circuits. Chapter 4 demonstrates that while scalp-to-cortex distances (and TMS induced electric fields) are not significantly different between individuals with AUD and controls, overall, males have a longer scalp-to-cortex distance than females. This suggests that men may need a higher intensity of stimulation to achieve a comparable electric field strength at the cortex. Following the observations from Chapters 3 and 4, we conclude with a secondary analysis of Chapter 2. Additionally, we explore the influence of individual patterns of brain reactivity to alcohol cues as a factor associated with treatment response. The results demonstrated that individuals with overlapping electrical field and patterns of brain reactivity to alcohol cues were significantly more likely to remain sober at 3 months. Collectively, these findings provide strong evidence that TMS is an effective treatment for AUD and that integrating individual brain function and structure may robustly enhance treatment response