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How Barriers to Using the Electronic Health Record Effects Behavioral Healthcare
Get PDFThe healthcare scene is rapidly changing due to the introduction of the electronic health record (EHR) and advances in technology. This means more patient data is readily available for use and gives physicians and patients’ faster access to that data. With the passing of recent legislature such as the Health Information Technology for Economic and Clinical Health Act and the American Recovery and Reinvestment Act of 2009, resulting in the rapid adoption of electronic health records due to incentive payment programs. With this comes the push for use of the electronic health record to prepare for Meaningful Use and improved quality of patient care. One field however, seems to be behind the times in regards to the use of the electronic health records, and it is the field of behavioral health. The simple reason being that behavioral health has barriers that other health fields do not. The challenge is how behavioral health can overcome these barriers in order to move forward with using the electronic health record
The Roles of Nuclear Receptor NR4A1 in Cancer Cell Proliferation and Skeletal Muscle Differentiation
Get PDFNuclear receptors (NRs) constitute a major class of drug targets in the treatment of various cancer types. NRs respond to cellular signals and become activated upon ligand binding to transcriptionally modulate expression of target genes. NR4A1 (Nur77) is a member of the NR4A family of nuclear receptors and displays an oncogenic profile in many cancer models. It is often upregulated in adult solid malignancies and is known to promote cell proliferation and survival. Knockdown studies of NR4A1 in cancer cell lines results in decreased cell growth and angiogenesis and increased apoptosis, suggesting NR4A1 is an oncogenic protein. Due to the elevated levels of NR4A1 in cancer, it is important to determine the regulatory mechanisms behind this expression pattern.
One such mechanism is through microRNAs (miRNAs), which regulate gene expression by binding to the 3ʹUTR of target mRNA and effectively inhibit translation into protein. Prior to
this study, no miRNAs had been identified to directly target NR4A1. By using luciferase reporter assays, we identified miR-124, miR-15a, and miR-224 as potential NR4A1 regulators. The direct binding of these miRNAs to their potential seed regions within the 3ʹUTR of NR4A1 was confirmed by mutagenesis of their respective seed sequences. This abrogated the binding and thereby confirmed the direct targeting of these miRNAs to these particular sequences. To further study the relationship between NR4A1 and these miRNAs, we analyzed endogenous expression levels in several pediatric cancer cell lines. NR4A1 was upregulated in RD, Rh41, and Rh30 rhabdomyosarcoma cells and D341 and Daoy medulloblastoma cells as well as NB3 neuroblastoma cells. All three miRNAs were downregulated in Daoy cells. Considering that miR-124 is highly expressed in the brain and is a tumor suppressor, we decided to investigate the functional significance between NR4A1 and miR-124 in Daoy cells. We found that miR-124 could decrease NR4A1 mRNA and protein levels as well as the expression of several NR4A1 target genes. Overexpression of NR4A1 led to enhanced cell viability and proliferation while knockdown resulted in the opposite phenotype. Furthermore, stable expression of miR-124 in Daoy cells resulted in decreased proliferation and smaller spheroid formation. Lastly, we examined expression levels in granule neuron precursors (GNPs), which are the most common cell type in the cerebellum where medulloblastoma arises. Interestingly, there was an inverse expression pattern in which miR-124 was increased while Nr4a1 was decreased in the differentiated GNPs, suggesting a potential role for NR4A1 in neuronal development.
In addition to cancer cell proliferation, the role of NR4A1 in skeletal muscle differentiation was also explored. We found that NR4A1 increased during the differentiation of human LHCN myoblasts, and that knockdown of NR4A1 impairs differentiation and reduces expression of myogenic markers in LHCN as well as SkMC, and HSMM primary human skeletal muscle cells. This data agrees with previous studies performed in mouse models and mouse C2C12 cells showing increased Nr4a1 expression during differentiation as well as the ability of NR4A1 to enhance muscle mass and myofiber size.
Together, these two studies highlight two different and opposing functional roles of NR4A1 in medulloblastoma and skeletal muscle. The first study identified three miRNAs capable of directly targeting and suppressing NR4A1 and also provides a rationale for the use of miRNA mimics as a potential therapeutic in cancers with high NR4A1 expression. In the second study, we provided evidence that further confirms the pro-myogenic function of NR4A1 during skeletal muscle differentiation. It is important to understand this basic biology as it can help further understand and treat diseases related to muscle such as rhabdomyosarcoma and muscular dystrophy
Modulation of the Magnetic Properties of Aqueous Metal Ions and the Bioelectrodynamic Effects on Cancerous and Noncancerous Cells
Get PDFBioelectrodynamics is the study of how electromagnetism affects the biophysical functions of living organisms by examining the effects on biochemical processing at the cellular level. The Cellular Energy Transfer Science (CETS) system modulates the magnetic behavior of aqueous metal ions by applying direct current (DC) with a Lorenz force to a hypotonic saline solution. This treated solution was then used to make growth media for cancerous and noncancerous cell lines in vitro. Exposure of cancerous and noncancerous cells to this media showed significant growth inhibition, cell cycle arrest, hyperpolarization of transmembrane potential and apoptosis of cancerous cells while not causing a growth inhibition, cell cycle arrest or apoptosis of the noncancerous cell lines. Microarray and RT-qPCR show the cancerous cells headed to apoptosis by the unfolded protein response (UPR), TNF/TRAIL, and p53 oncogene activation. Alternatively, the noncancerous cells show a significant increase in cell migration/wound healing after exposure to the treated media with no activation of apoptosis pathways
Super-Utilization: The New Perfect Storm of Health Reform
Get PDFThis three-essay dissertation was focused on geographic variation of super-utilization, or the disproportionately high healthcare utilization and costs attributed to a small sub-set of the inpatient population. For purposes of this research, super-utilization was operationalized as high repeat utilization (HRU) and referred to inpatient utilization and inpatient readmission expenditures attributed to beneficiaries with four or more 30-day readmissions per year. The overall purpose of the research was to identify geographic areas at increased risk for HRU. These areas corresponded to where beneficiaries live and were aligned with the geographically-bound healthcare delivery systems. Each essay employed an observational study design using 100% Medicare Part A claims data on beneficiaries ages 65 and older residing in Tennessee hospital referral regions during the 2012 study period. The first essay focused on the impact of super-utilization on population-based rates of readmission across healthcare delivery systems. Specific aims of the first essay were: 1) to assess geographic variation in a population-based overall rate of readmissions across local healthcare delivery systems by conducting one sample means testing use the Z statistic to determine whether rates were lower, higher, or no different from the state average; 2) to contrast the number of beneficiaries, readmission events, and inpatient readmission expenditures attributed to beneficiaries with one compared to four or more readmissions per year between local delivery systems in the 10th and 90th percentiles of readmission rates using descriptive statistics; and 3) to assess the effect of the number of readmissions by beneficiaries with one, two, three, and four or more readmissions per year on overall readmission rates using a quasi-experimental approach to linear regression. The second essay focused on identifying clusters of super-utilization across healthcare delivery systems. Specific aims of the second essay were: 1) to detect statistically significant clusters of concentrated readmission events attributed specifically to HRU by using the SatScanTM method for spatial scan statistics; 2) to explore overlap of identified clusters with population-based rates of readmission using chloropleth mapping to visually depict the relationship; and 3) to assess differences in the geographic distribution of readmission events attributed to HRU between urban and rural locations within cross-border areas using the Mann-Whitney U test to determine statistical significance. The third essay focused on predicting risk of super-utilization across healthcare delivery systems using community demographic variables. Specific aims of the third essay were: 1) to assess the effect of rurality, income, and race on the presence of HRU using a logistic regression model; 2) to determine whether differences in model effects existed among regional healthcare delivery systems by including region as a class variable within the model; and 3) to evaluate whether differences in model effects existed at various concentrations of low-income households by performing decomposition analysis using contrasts based on percentiles of the distribution of low-income households. Findings on the whole suggest that local healthcare delivery systems with high population-based rates of overall readmissions are also more likely to have underlying issues related to super-utilization. In fact, half of all inpatient readmission expenditures attributed to super-utilization across the study area were concentrated in local healthcare delivery systems in the 90th percentile of readmission rates. Unsurprisingly, clusters of super-utilization overlapped these local healthcare delivery systems with high rates. However, clusters of super-utilization were identified in all regions including some local healthcare delivery systems with rates no different or lower than the statewide per capita rate of readmissions. Furthermore, the highest risk of super-utilization occurred in areas with the highest concentration of low-income households, regardless of rural-urban designation, household race, or region
The Nucleolar Protein Nucleophosmin Undergoes Liquid-Liquid Phase Separation with Arginine-Rich Nucleolar Proteins through Weak, Multivalent Electrostatic Interactions
Get PDFNucleoli are nuclear membrane-less organelles that are the sites for ribosome biogenesis and serve as sensors of cellular stress. Weak, multivalent protein-protein interactions and interactions between disordered, low complexity domains (LCDs) and rRNA have been shown to promote liquid-liquid phase separation (LLPS) in vitro, suggesting a basis for the liquid-like behavior of nucleoli. Nucleophosmin (NPM1), a multifunctional and highly abundant nucleolar protein, exhibits structural features associated with LLPS suggesting a role in nucleolar organization. Specifically, NPM1 forms a pentamer through its N-terminal oligomerization domain and can bind to rRNA through its C-terminal nucleic acid binding domain. Multiple acidic tracts throughout NPM1, two within an intrinsically disordered region (IDR), confer additional multivalency and mediate interactions with proteins that contain multiple arginine-rich motifs (R-proteins). Using a variety of techniques, we have identified several nucleolar R-proteins which bind to and phase separate with NPM1. Here we show that the liquid-like properties of NPM1 droplets can be tuned by modulating the extent of electrostatic interactions within the droplet. We propose that a hierarchy of R-motifs, varying in valency and affinity, within nucleolar R-proteins exists which leads to a heterogeneous network of interactions between proteins and rRNA within nucleoli, thus promoting formation of a dynamic liquid-like phase conducive to ribosome biogenesis and other nucleolar functions
Does the Electronic Health Record Improve the Timeliness Review and Notification of Medical Laboratory and X-ray Test Results?
Get PDFThe medical community struggles with timeliness issues throughout the different healthcare environments in many areas of patient care. The demands of meeting patient care needs is great everywhere. One area that can lead to extreme adverse outcomes and affects patient safety is failure to review and follow-up on medical test results timely. In addition the lack of timely follow-up and treatment can lead to medico-legal implications for all healthcare professionals involved in the patients care. Some timeliness issues have been attributed to understaffed healthcare institutions, lack of trained staff, and in many instances inefficient and insufficient processes. This is an important issue to improve and is very complex in nature. This study will examine the timeliness review of diagnostic test results and if the electronic health record has improved the process. Procedures will be reviewed and any adjustments will be made depending on the outcome of the analysis
EHR Quality Documentation Research Thesis
Get PDFThis research proposal contains and introduction to my proposed research, background of the issue at hand, purpose of the research, significance of the research, research questions that I will be asking, definition of terms, limitations that I may be facing, literature review, SWOT Analysis, and Work Flow diagram on literature review. Also discussed are my proposed research methodology, research design, population sample, data collection procedures, as well as a table of survey variables that I propose to include. This proposal will go over why documentation quality and quantity is so important and the history behind why we are facing a documentation crisis. I am proposing to be able to conduct my research to see how the documentation quality and quantity has improved, or declined since the implementation of EHRs and voice recognition systems across the North Eastern Pennsylvania Region
Is Cloud Computing in Healthcare Providing a Safe Environment for Storing Protected Health Information? A Systematic Review and Meta-Analysis
Get PDFOver the past several years, cloud computing has become increasingly more popular for the use of storing, accessing, and maintaining electronic health records (EHRs). In comparison to conventional EHR management tools, such as installed software, cloud computing offers more capabilities for medical facilities and their patients. Experts claim that in addition to changing the face of health information technology, it will also advance healthcare services, and benefit medical research. As the use of cloud computing has increased, so has the amount of healthcare data breaches. This study is proposing that there is a correlation between the increase in cloud computing protected health information (PHI), and healthcare data breaches. This study researches the top five largest healthcare data breaches in 2015 what the organizations’ could have done differently. This study also proposes that current privacy and security laws do not clearly defined cloud computing regulations. Suggestions are also made for organizations to employ a multilevel security framework for cloud-based applications. This information will be valuable to all health information management (HIM) professionals that are involved in migrating and maintaining PHI stored in the cloud
Discoveries of Targets and Novel Agents for the Treatment of Ischemic Retinopathy and Neovascular Disease
Get PDFDiabetic retinopathy (DR) and age-related macular degeneration (AMD) are among the most common causes of blindness in adults. Vision loss can occur during the advanced stages of DR and AMD as a consequence of unregulated and dysfunctional growth of new blood vessels, or neovascularization (NV) in the retina or choroid. NV can also be triggered by numerous other ocular insults and diseases including radiation retinopathy (RR) and retinal vein occlusion. These latter cases are generally less common but, like DR and AMD, they are characterized by an initial injury, chronic inflammation, and ischemia which perpetuates episodes of retinal neovascularization (RNV).
Current targets for RNV include vascular endothelial growth factor, VEGF which is achieved through anti-VEGF protein therapeutics aimed at sequestering the growth factor and preventing the activation of its receptor. However, prospective studies show that anti-VEGF resistance has become a major clinical concern in patients receiving long-term therapy. Thus, targeting downstream signaling proteins linked to pathological RNV represents an alternative or adjunctive approach to approved anti-VEGF treatments, which may provide better patient outcomes through enhanced efficacy of antiangiogenic therapy.
Our first goal was to understand how RNV progresses from early stage injury to proliferative ischemic retinopathy, in order to justify protein targets for drug discovery. We first began with an investigation into the causality of radiation injury itself to identify mechanisms of radiation sensitivity and/or resistance in the genetically diverse, murine BXD strains using a total-body irradiation (TBI) model. Our studies suggested mean survival time (MST) over 30 days may in fact be related to genetic variation in genes associated with endothelial progenitor cells (EPC) localization, wound healing, and focal adhesion (FA) dynamics involving both the hematopoietic and gastrointestinal systems. We targeted these mechanisms of tissue repair by blocking the homing of hematopoietic-derived cells to sites of irradiation (IR) injury which proved fatal to mice treated with an integrin-paxillin inhibitor, 6-B345TTQ. In a physiological flow-based assay, we inhibited circulating leukocytes from interacting with an inflamed endothelium, in vitro. These results suggested that the reparative/inflammatory angiogenic response triggered by radiation could be blocked by targeting FA signaling, a central process of RNV progression in ischemic retinopathies.
Findings in BXD studies linked tissue reparative processes involving ischemia- induced angiogenesis with mortality. We hypothesized that by targeting early injury in retinal endothelial cells (REC), we could prevent late-stage RNV. Thus, we first explored how RECs respond to radiation injury at levels high enough to cause significant vision impairments in RR. Previously identified radioprotectant, KZ-41, was used in these studies to ameliorate IR-induced injury to RECs through decreased inflammatory stress kinase activation, cell death, and subsequent IR-induced proliferation, in vitro. FA activation through paxillin was found to be a crucial mechanism by which KZ-41 inhibited ischemia-induced RNV in the murine oxygen-induced retinopathy (OIR) model.
Targeting stress kinase activation of FA signaling post-IR injury served as a way to prevent the pathological progression of RNV, in vivo. However, it is difficult to predict when or how to treat the inflammation early in ischemic retinopathy, especially in chronic conditions such as diabetes, when the injury has already occurred. Therefore, we sought to target the common focal point of ischemic disease by focusing on drivers of late stage RNV, the focal adhesion signaling complex. Using VEGF as the driver of in vitro angiogenesis, we explored growth factor-induced FA signaling in RECs to validate target proteins Src, focal adhesion kinase (FAK), and paxillin as crucial to RNV progression. Our work helped to identify a novel paxillin modulator, JP-153 which afforded excellent antiangiogenic activity, in vitro. JP-153 achieved potent inhibition of RNV in the OIR model through topical application by disrupting paxillin activation. Together, these data suggested paxillin is a key driver of RNV and may serve as a viable target for the treatment of neovascular eye disease.
In Chapter 6, we characterized the pharmacokinetic profile of JP-153 with regard to its absorption, distribution, metabolism, and elimination (ADME) after both oral and intravenous administration. We found that JP-153 exhibited rapid metabolism in rats with an oral bioavailability of approximately 30%. During these studies, we successfully developed a sensitive and selective analytical method using mass spectrometry in order to detect JP-153 concentrations in rat plasma. JP-153 possessed a relatively rapid clearance profile, which is an ideal characteristic for ocular therapeutics. Lower systemic exposures decrease the risk of cardiovascular side effects, a common concern with antiangiogenic therapies. Though, further work to characterize its ocular pharmacokinetic profile is needed to identify the proper dosing regimen in future studies. Thus, these data herein have served as a basis for further development of JP-153 series analogs, used either as a topical or systemic therapeutic for in vivo efficacy studies and pre-clinical work.
In conclusion, our work has successfully provided rationales for new drug targets and clinically relevant pharmacological agents to halt RNV. The following chapters describe and discuss novel ways in which we target inflammatory signaling and protein-protein interactions related to FA protein paxillin to effectively stop angiogenesis in the retina. Importantly, targeting paxillin has much broader implications in treating angiogenesis in general, and work studying paxillin modulation in cancer cells represents interesting hypotheses for future work in our laboratory
Examining the Associations between Depressive Symptoms, Body Mass Index, and Physical Activity Self-Efficacy in African American Mother-Child Dyads
Get PDFIn recent decades the prevalence of childhood and adult depression and obesity has increased worldwide. Multiple factors influence the onset of both depression and obesity. Individual manifestations of depressive symptomatology and health-related problems associated with obesity vary; however, genetics and environmental and psychological factors have been implicated as correlates. Consequently, both disorders can ultimately interfere with individuals’ activities of daily living and decrease their quality of life. African American women are known to have a higher prevalence of obesity and more severe depressive symptoms in comparison to Caucasian women. Likewise, African American children are more obese and experience many factors that influence the onset of depressive symptoms. With increases in the prevalence of childhood obesity and diagnoses of mood disorders in youth, analyzing the family’s influence on these outcomes has become increasingly important. The purpose of this correlational study was to examine the associations among child depressive symptoms, body mass index (BMI) Z-scores, and physical activity self-efficacy and maternal depressive symptoms and BMI in African American mother-child dyads. A community sample of 65 African American mother-child dyads was recruited. Data were collected on height and weight to estimate BMI and self-report questionnaires were used to assess depressive symptoms among participating mothers and their children. Additional information on physical activity self-efficacy was collected from each child. Pearson product moment correlation coefficients were estimated to determine associations between variables that were sampled from underlying normal distributions. Spearman correlation coefficients were estimated to assess correlates of maternal BMI because data from this variable did not reflect sampling from a normal distribution. Results indicated positive correlations between children’s depressive symptoms and their BMI Z-scores and their mothers’ depressive symptoms. More depressive symptoms in children were related to having a higher BMI Z-score and a mother with more depressive symptoms. Results also indicated important correlations for the children’s physical activity self-efficacy with their depressive symptoms, their BMI Z-scores, and maternal depressive symptoms. Although several associations were found between the children’s physical activity self-efficacy and their depressive symptoms, BMI Z-scores, and maternal depressive symptoms, researchers should cautiously rely on self-reports of physical activity self-efficacy from younger children given that some children had difficulty understanding the self-efficacy measure. Findings suggest that the associations between depressive symptoms, BMI, and physical activity self-efficacy in African American mother-child dyads merit additional examination as such research studies may inform future approaches to prevent and treat obesity and depression in this population