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Depression Screening in Type 2 Diabetes in Adolescent 12-18 Year Olds
Full text linkBackground
Although more commonly diagnosed in adults, type 2 diabetes is increasingly diagnosed in pediatric populations in the United States. Research suggests a correlation between depression and type 2 diabetes, however, a gap in research exists regarding depression and type 2 diabetes among pediatrics, specifically adolescents. This scoping review aims to address this gap by assessing the impact of depression screening on glycemic control in this specific population.
Purpose
The goal of the review is to contribute to the development of effective strategies for depressing screening in adolescents with type 2 diabetes, with the expectation this may positively impact glycemic control.
Methods
Between August 2022 and November 2023, a journal review was conducted to identify studies that examined adolescent depression in those with a type 2 diabetes mellitus diagnosis. Individual searches were conducted across various sources such as PubMed, Medline, and CINAHL. The following keywords were used to identify articles: adolescent, youth, depression, type 2 diabetes, depression screening, standardized screening, glycemic control, and HbA1c.
Results
Thirteen articles were identified following rapid critical appraisal, which yielded a final selection of eleven articles used in this review. Prior studies have primarily been limited to either type 1 diabetes or adults without fully exploring the relationship of depression in adolescents with type 2 diabetes. Thirteen articles were identified, yielding a final selection of 11 articles after rapid critical analysis used in this review. These consisted of five cohort studies, two descriptive studies, and four quality-improvement studies. All studies completed baseline depression screenings while most obtained HbA1c, but less than half examined any relationship between the two, yielding inconsistent findings.
Implication for Nursing Practice
The outcomes in this scoping review identified that more research is needed to establish any correlation between depression screening and type 2 diabetes. The articles used in this scoping review evaluated HbA1c measurement, glycemic control, and mood regulation in the adolescent population but not how they co-relate. These findings support the idea that incorporating depression screenings at regular intervals into the care of adolescents with type 2 diabetes may help providers prioritize both the physical and mental health of at-risk patients
Regulation of PIEZO Channels by Membrane Lipids
Full text linkIn cellular physiology, the transformation of energy from mechanical cues into electrical and/or chemical signals is called mechanotransduction. This ability to sense and react to external and internal mechanical forces is essential for the survival of single cell to multicellular organisms. As such, it is no surprise that mechanotransduction appeared early in the evolutionary history of life on our planet. At the cellular level, mechanotransduction is mediated by proteins and/or protein complexes that respond to mechanical stimuli in different timescales, including but not limited to changes in membrane electric potential, Ca2+ signaling, and gene expression. Among such protein complexes, mechanosensitive ion channels stand out as the quickest mechanotransductors, as they can generate physiologically relevant responses to mechanical cues, on a millisecond timescale. Mechanosensitive ion channels are transmembrane proteins that mediate the flow of ions across the cell membrane in response to mechanical stimuli. Mechanical forces can reach, and induce a response of, mechanosensitive ion channels by propagating through the membrane and/or from extra- and intracellular tethers. The mammalian PIEZO ion channel family is comprised of two mechanosensitive non-selective cation channels, PIEZO1 and PIEZO2. These ion channels have a fundamental role in multiple normal and pathophysiological mechanisms in mammals. Loss- and gain-of-function mutations of both proteins cause disease, yet there are no pharmacological tools available to modulate their function in vivo. As a collective, the chemically diverse lipid species that comprise membranes can endow them with distinct characteristics also known as the physical properties of the bulk plasma membrane. This dissertation focuses on how lipid composition and the physical properties of the bulk plasma membrane can shape physiological responses by modulating the function of PIEZO1 and PIEZO2. Here, we use lipid profile analysis, electrophysiology, and behavioral assays to demonstrate that PIEZO1 and PIEZO2 are modulated by membrane lipids. We found that the saturated fatty acid margaric acid inhibits PIEZO2 currents by increasing its mechanical threshold for activation, whereas polyunsaturated fatty acids such as eicosapentaenoic, arachidonic, docosahexaenoic, and linoleic acids modify channel inactivation. We show that topical lotions enriched in margaric acid can be used to alter touch responses of wild-type mice in vivo. Moreover, we found that dietary interventions improve PIEZO2-associated behaviors in mouse models of neurogenetic diseases where PIEZO2 function is either up- (distal arthrogryposis type 5) or down- (Angelman syndrome) regulated. Finally, we demonstrate that PIEZO1 function is upregulated in sickle cell disease, and that fatty acids can be used to rescue this increase ex vivo. Overall, our findings demonstrate that saturated and polyunsaturated fatty acids enriched in the plasma membrane modulate mechanical responses mediated by PIEZO channels in vitro, ex vivo, and in vivo
Leveraging Genomic Information for Safer Gene Therapy
Full text linkGene therapy holds enormous potential for the treatment of genetic disorders, which are caused by mutations in DNA disrupting normal gene function. These mutations can be monogenic, affecting a single gene, or polygenic, involving multiple genes. Since, the first gene therapy treatment for SCID in 1990, there have been quite progress in development of gene therapy treatments, and currently we have 38 FDA approved gene and cell therapy treatments. Although the field is moving in positive direction, there are still concerns regarding the safety and efficacy of the treatment. One of the examples being development of leukemia after treatment with SCID gene therapy. To mitigate these risks, our study focuses on identifying novel genomic safe harbor (GSH) sites and insulator elements to ensure safe and stable transgene integration without disrupting the host transcriptome. Here we developed a knowledge-based approach using common polymorphic mobile element insertions (pMEIs) along with epigenetic and 3D chromatin information to identify new genomic safe harbor (GSH) sites. Out of 19 blood specific and 5 brain specific GSH sites, we experimentally validated 3 GSH sites from blood which showed stable transgene expression without disruption of neighboring genes in the host erythroid cells. In parallel we also developed a high-throughput screening system to identify novel insulator sequences using two expression protein marker system, cyan fluorescent protein (CFP) for validation of sequence integration and green fluorescent protein (GFP) for measurement of strength of insulator sequence. Our findings showed that CTCF and RAD21 occupancy as the major but not the sole contributor for insulator activity. We also identified the influence of sequence specific features such as downstream motif to regulate the insulator function. Furthermore, we discovered that insulators could regulate gene expression by reducing nascent transcription from enhancers, underscoring their broader role in transcriptional control. In summary, our study provides significant advancements in gene therapy, offering new methods for enhancing the safety and efficacy of transgene integration. By integration of genomic and epigenomic information, we were able to understand the critical factors governing both GSH and insulator element. Thus, these discoveries not only improve our understanding but also paves way for precise and safer gene therapy strategies
WNT5B as a Therapeutic Target for Osteosarcoma Stemness, Metastasis, and Chemoresistance
Full text linkOsteosarcoma is a pediatric bone cancer that has no targeted therapy and has had no treatment advances for the last three decades. Osteosarcoma frequently metastasizes to the lungs and is highly chemotherapy resistant, reducing patient survival with metastatic disease to 20% after 5 years. New therapies targeted to metastasis and drug resistance in osteosarcoma are essential to improving patient outcomes.
Osteosarcoma is a pediatric bone cancer that has no targeted therapy and has had no treatment advances for the last three decades. Osteosarcoma frequently metastasizes to the lungs and is highly chemotherapy resistant, reducing patient survival with metastatic disease to 20% after 5 years. New therapies targeted to metastasis and drug resistance in osteosarcoma are essential to improving patient outcomes. We found that WNT5B is the most expressed WNT in osteosarcoma patients and correlates with both metastasis and survival. In osteosarcoma spheroids, both protein and mRNA levels of WNT5B are enhanced in the stem cell population compared to adherent cells. Further, WNT5B upregulates the expression of the stemness gene SOX2 and directs stemness phenotypes, such as sphere size, migration, and sphere forming efficiency.
Additionally, WNT5B enhances osteosarcoma chemoresistance to methotrexate. In vivo, WNT5B significantly increases osteosarcoma metastasis to the lungs, and these metastases are morphologically different between control and WNT5B knockout. We revealed that this morphologic difference is due to enhanced degradation of the glycosaminoglycan hyaluronic acid mediated by WNT5B. Further, ROR1 was identified as the receptor through which WNT5B signals, and we determined the effects of D10, a monoclonal antibody which targets ROR1. Next, we characterized the signaling pathway changes between adherent cells and stem cells, identifying FZD2 as the co-receptor which WNT5B signals through in stem cells. WNT5B signals through the WNT/PCP pathway in adherent cells, but switches to a non-conventional signaling pathway in osteosarcoma stem cells. Finally, RNA-sequencing was performed on 143B osteosarcoma adherent cells versus stem cells, comparing control and WNT5B knockout cells. The RNA-sequencing data provided validation of the results presented in this dissertation, as well as providing future directions for studying WNT5B in osteosarcoma.
Through revealing a novel role for WNT5B in osteosarcoma cancer stem cells, therapy resistance and metastasis, we present the WNT5B pathway as a candidate for therapeutically targeting osteosarcoma stem cells in patients
Effect of Certified Diabetes Clinical Education Specialists on Adults with Type 2 Diabetes
Full text linkPurpose/Background
Type 2 diabetes mellitus affects 13.1% of adults living in Shelby County and over 30 million adults in the United States. This chronic disease creates a higher risk of macrovascular and microvascular complications for this population resulting in poor outcomes if not properly managed. Improving glycemic control can help to improve the quality of life for people living with diabetes and reduce healthcare costs. Currently 20% of funds spent in the United States on healthcare is utilized for diabetic care. Certified Diabetes Care and Education Specialists (CDCES) primarily educate patients about managing their diabetes, including health promotion that can improve healthcare outcomes. Data shows that referrals to a CDCES by a primary healthcare provider can help improve A1c levels and diabetes management for people with poorly controlled diabetes. The purpose of this quality improvement project is to show the value of CDCES visits in patients with poorly controlled type 2 diabetes in a metropolitan underserved primary care clinic and implement a successful CDCES referral program to improve the quality of care for these patients.
Methods
A retrospective chart review was conducted in a metropolitan underserved primary care clinic in the Midsouth region for patients with type 2 diabetes mellitus over 21 years of age who received at least one diabetes education session.
Inclusion Criteria:
Speaks the English language
All races and ethnicities
Male or female
Age 21 and over
Diagnosis of type 2 diabetes mellitus
Hemoglobin A1c level greater than or equal to 8%
Demographic data, baseline HbA1c, and post-education HbA1c were extracted from 29 random charts. All patients were deidentified to only include gender (21 females, 8 males) along with HbA1c results. A two-tailed paired samples t-test was conducted to determine the mean difference in pre- and post-intervention HbA1c at baseline, 3, and 6 months.
Results
A two-tailed paired samples t-test was performed to evaluate whether the mean difference of HbA1c pre- and post-intervention by CDCES was significantly different. The observations for baseline HbA1c had an average of 9.16 (SD = 2.84). The observations for the 3-month follow-up HbA1c after CDCES visit had an average of 8.32 (SD = 2.36). The results of the two-tailed paired samples t-test was not significant based on an alpha value of .05, t(28) = 1.64, p = .113. While the results were not statistically significant (p = .113), there was a detectable decrease of the mean HbA1c after CDCES visit.
Implications for Nursing Practice
The data analysis points to the effectiveness of CDCES intervention for adults living with poorly controlled type 2 diabetes. A team-based approach to managing diabetes can be helpful to people with poorly controlled diabetes. A referral to a CDCES should be offered to any patient struggling to manage diabetes to help improve health outcomes, reduce the total cost of care, and increase the health span of these individuals. Further studies could be conducted to follow patients for an extended duration to assess the effects of CDCES intervention on long-term control of diabetes
Comparing the Effects of the Induction of Anesthesia with Etomidate to the Induction of Anesthesia with Midazolam on the Incidence of In-Hospital Mortality: A Scoping Review
Full text linkPurpose/Background
The induction of anesthesia using hypnotic sedatives, such as etomidate and midazolam, is common practice. Etomidate and midazolam are commonly employed in the induction of anesthesia in the septic patient population, each with its unique advantages and drawbacks. This scoping review aims to synthesize evidence on the effects of anesthetic induction with etomidate versus midazolam in adult septic patients, focusing on the incidence of mortality and associated adverse effects during hospitalization. The purpose is to establish a standard of care for anesthetic induction in this population.
Methods
A literature review was conducted from September 2022 to March 2023 utilizing CINAHL Complete, SCOPUS, Access Medicine, Cochrane Library, and PubMed databases. Over 100 articles were found utilizing our keywords, which included induction agent, etomidate, midazolam, critical illness, sepsis, septic shock, severe sepsis, mortality, and hospital length of stay. Of these, 25 articles met the author’s inclusion criteria and underwent Rapid Critical Appraisal (RCA) to assess the quality and validity of the studies. This appraisal yielded ten articles that were further synthesized and classified by their level of evidence table.
Results
Ten studies were examined to assess the effects of etomidate and midazolam on septic patients. The results showed that when etomidate is used to induce anesthesia in septic patients, it can lead to increased in-hospital mortality rates and longer ICU and hospital lengths of stay. Additionally, six studies found that etomidate can cause adrenal gland suppression. On the other hand, midazolam was associated with lower mortality rates when used to induce anesthesia in septic patients. However, there is insufficient data concerning its ability to produce profound anesthesia in septic patients without causing undesirable hemodynamic changes. Based on the available data, midazolam is considered to be the safer option for inducing anesthesia in septic patients.
Implications for Nursing Practice
The results of the scoping review support that etomidate usage is linked to longer stays in the ICU and hospital and higher hospital-wide mortality compared to midazolam. These findings indicate that the use of midazolam to induce anesthesia in septic patients is preferred but not without risks to patients. Anesthesia personnel should be educated when utilizing midazolam, blood pressure should be monitored closely, and timely intervention should be conducted to prevent hemodynamic changes. The results of this scoping review highlight the need for a standard of care to be established on what medications to use during the induction of anesthesia in septic patients. Further research is needed to guide nurse anesthesia practice for improved septic patient outcomes
Utilization of Depression Screening in Patients with Type 2 Diabetes Mellitus
Full text linkPurpose/Background
Type 2 diabetes is a chronic metabolic disorder affecting millions of individuals worldwide. Research has shown that individuals with diabetes are at a higher risk of developing depression in comparison to those of the general population. Depression affects the individual\u27s emotional well-being and has a significant impact on the management and outcomes of diabetes (Mather, 2022). This research study aims to investigate the feasibility and effectiveness of implementing the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 is one the most effective assessment tools available to identify symptoms of depression (Celik, 2020).
Methods
In this retrospective chart review, at least 50 charts of patients that ranged ages 30 to 78 with a diagnosis of type 2 diabetes were screened for depression from September 18, 2023 to November 29, 2023. The reviewers were assessing whether or not the PHQ-9 was administered to assess for comorbid depression in patients with Type II Diabetes diagnosis.
Results
This protocol was approved by the University of Tennessee Health Sciences Center (UTHSC) internal board review. Data was collected from the University Clinical Health/UT Family medicine in Memphis, TN with the assistance of Laura Reed, DNP-FNP. Of the 29 charts reviewed, 16 of the patients that met the criteria were assessed with the PHQ-9, and 13 were not. The data revealed there was a possible decrease in the likelihood of administering the PHQ9 to patients as they get older. On average, women were screened higher in comparison to men.
Implications
This research study will contribute to understanding the prevalence and impact of depression in individuals with type 2 diabetes. The findings may inform healthcare providers about the importance of routine depression screens and its potential benefits of early intervention. Implementing the PHQ-9 as a screening tool within the diabetes population can facilitate the identification and management of depression which can potentially lead to improved overall health outcomes for patients with type 2 diabetes
The Changing Landscape of Adolescent and Young Adult Substance Use
No full textSubstance use (SU) has long been a significant cause of morbidity and mortality in adolescents and young adults (AYA) worldwide, with the United States (US) accounting for more than half of drug overdoses internationally prior to the COVID-19 pandemic (hereafter, “COVID”).1 In the wake of COVID, however, SU epidemiology has shifted dramatically. Driven by the ubiquity of illicitly-manufactured fentanyl, a high-potency opioid, throughout the illicit drug supply in the US,2 drug-related poisonings and overdoses have become the third leading cause of death among American children and adolescents under 20 and the single leading cause of death in adults under 45.3 SU contributes to over one million emergency department visits per year among AYA,4 and to the other top causes of death in Americans under 20 (i.e., firearm-related injuries and motor vehicle crashes).5 Morbidity and mortality have risen despite adolescent SU declining to among the lowest rates observed in nearly 50 years.6,7 Overall, SU is less common but more hazardous, and clinicians caring for AYA—including physicians, nurses, social workers, clinical psychologists, and other professionals—must be prepared for this shifting landscape in the US and beyond. As fentanyl and its associated overdose burden spread to more and more countries across the globe, clinicians in other countries may also benefit from proactively incorporating SU-related skills into their practice.
Here, we briefly review the evolving epidemiology of AYA SU in the US; review US policy changes impacting SU disorder treatment since COVID’s onset; and provide guidance for clinicians worldwide around having nonjudgmental, meaningful, well-informed SU-related discussions with AYA
Targeting TRPC3: A Promising Therapeutic Strategy for Alzheimer\u27s Disease
Full text linkAlzheimer\u27s disease (AD) is a progressive neurological disorder characterized by extracellular β-amyloid (Aβ) plaques and intracellular tau tangles. The calcium (Ca2+) hypothesis of AD proposes that disrupted intracellular Ca2+ regulation underlies AD pathology, contributing to inflammation, oxidative stress, impaired autophagy, neurodegeneration, and cognitive dysfunction. Store-operated Ca2+ entry (SOCE) maintains ER Ca2+ stores, involving transient receptor potential canonical (TRPC) and Orai channels. Specifically, we speculated that dysregulated functions of TRPC3 contribute to the pathogenesis of AD. We believe that targeting TRPC3 with a pharmacologically feasible agent could prove beneficial in halting cognitive decline. We previously reported compound JW-65, a novel, metabolically stable, brain-penetrative, selective, and safe TRPC3 inhibitor that can directly bind to the TRPC3 protein. We utilized JW-65 as a tool molecule and identified TRPC3 as a unique member of the TRPC family that contributes to the development of AD via the Aβ cascade, in contrast to the predominantly protective role of TRPC6. Preliminary animal studies performed on PS19 mice, a widely studied mouse model of tau pathology, also demonstrated the therapeutic efficacy of JW-65. This finding highlights TRPC3 as a promising therapeutic target for AD. Considering the promising efficacy of JW-65 and the potential for TRPC3-targeted therapy, a panel of JW-65 analogs were synthesized, and their potency and selectivity were characterized. This approach aims to enhance the therapeutic options available for AD treatment
Evidenced-Based Strategies to Increase Cervical Cancer Screening Rates
Full text linkPurpose/Background
Cervical cancer is the fourth leading cause of cancer affecting women worldwide (Staley et al., 2021). With cervical cancer being a preventable disease, an effective method of reducing healthcare costs and mortality is primary prevention, such as screenings. Financial burdens and barriers to accessing medical care may result due to the lack of proper cervical cancer screenings. Detecting cervical cancer includes screening women 21 to 65 years old with a Papanicolaou (PAP) test every three years. Women aged 30 to 65 years old can extend the screening of cervical cancer by having a Human Papillomavirus (HPV) test along with a PAP test conducted every five years, according to the United States Preventative Service Task Force (USPSTF) (National Cancer Institute, 2022). The cessation of cervical cancer screening can occur for women aged 65 years or older who have had three sequential negative PAP tests or two sequential negative HPV results within ten years (U.S Preventive Services Task Force [USPSTF], 2008). Patient education emphasizing the benefits of cervical cancer screenings has been shown to improve compliance with screening recommendations.
Methods
A retrospective chart review at a metropolitan underserved primary clinic in the Midsouth was conducted consisting of 29 charts from women ages 18 and above with visit dates between January 1, 2023 and August 31, 2023. Descriptive statistics were generated and analyzed of the women’s age, race, visit date, insurance type, and their presence of an up-to-date pap smear per USPSTF guidelines.
Results
Between January 4, 2023 and August 15, 2023, 29 women (N=29) met eligibility criteria. Women’s ages ranged from 24 to 66 (M=46.97, SD 10.39). Findings indicate that 16 women (55.2%) had up-to-date PAP smear testing per USPSTF guidelines. Women who received up-to-date PAP smear testing had a mean age of 45.1 compared to the mean age of 49.3 in women without up-to-date screening.
Implications for Nursing Practice
The results of this retrospective chart review provide valuable insight into how many women prioritize having an up-to-date PAP smear in a primary care clinic. While the data indicates that 55.2% of women had up-to-date PAP smear testing, the mean age of women without up-to-date screening was only 4 years older (49.3) than the mean age of those who did have up-to-date PAP smear testing (45.1). At the same time, only slightly more than half of women had up-to-date PAP smear testing, leaving a significant portion of women still requiring valuable education. While further study is required to better understand the prevalence of cervical cancer screening, it is evident that further education on proper cervical cancer screening is recommended