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Structural Competence and Equity-Minded Interprofessional Education: A Common Reading Approach to Learning
Get PDFAs a result of the COVID-19 pandemic and the Black Lives Matter movement, leaders in the field of interprofessional (IP) education have encouraged faculty to explore online adaptations to curriculum and examine strategies that enhance students' structural competence. Structural competence is broadly defined as the ability to understand how oppression, governmental policies, and environmental inputs impact the health and well-being of an individual. With these changes in mind, a team of IP health science faculty developed two online curricular activities guided by the "common reading" book, Five Days at Memorial: Life and Death in a Storm-Ravaged Hospital by Sheri Fink. This article describes the development and findings of a mixed-methods evaluation of the two IP learning activities: (a) The Interprofessional Common Reading Experience (IPCRE) and (b) The IPCRE follow-up. The activities engaged over 250 students across multiple health professions (i.e., social work, nursing, athletic training, speech-language pathology, nutrition, and public health) attending three different universities. Our findings contribute to a greater understanding of how to develop online IP activities and curricular innovations that help to train equity-minded and anti-racist practitioners.This research received no external funding
Targeted Induction of Respiratory Immunity Increases Protection Against Lung Metastasis From An Extra-Pulmonary Primary Tumor
Get PDFLung cancer is the leading cause of cancer deaths worldwide. Despite advances made in early diagnosis of extra-pulmonary tumor malignancies, as well as in aggressive surgical and radio-chemo preventive treatments, the incidence of metastasis leading to a greater risk of cancer death is significant. The lung remains one of the most common organs of cancer metastasis and represents one of the leading causes of morbidity and mortality among cancer patients with metastatic disease. The high incidence of deaths recorded among patients with primary lung cancer and those with secondary lung metastasis from extra-pulmonary tumors is because of the difficulty in treating lung-occurring tumors. Despite challenges in treatment, immunotherapy is now considered a cornerstone of first-line therapy for lung tumors. Therefore, strategies aimed at priming and boosting antitumor immunity in the lung have become promising at preventing/treating lung-occurring tumors. To this end, the goal of the dissertation project was to prevent secondary lung metastasis from an extra-pulmonary tumor utilizing targeted nano- vaccine delivery. In the present study, we engineered CpG surface conjugated tumor antigen (Tag) encapsulating PLGA nanoparticulate cancer vaccine (CpG-NP-Tag) capable of intranasal administration (nasal nano-cancer vaccine) to target the lung's microenvironement. The main aim of our study was to test the efficacy of the nasal-nano vaccine at preventing secondary lung metastasis from an extra-pulmonary tumor. Considering that breast tumor is one of the leading extra-pulmonary tumors with a high propensity to metastasize to the lung, using the syngeneic female Balb/c mice and the murine mammary adenocarcinoma (4T1) tumor model, we demonstrated the utility of intranasal delivery of CpG-NP-Tag (nasal nano vaccine) as a prophylactic approach to prevent secondary lung metastasis from a primary breast tumor. We found that CpG-NP-Tag intranasal immunization prevented lung colonization by 4T1 tumor cells after challenge through lateral tail vein injection in female Balb/C mice (a mouse model of experimental lung metastasis). Decreased lung colonization by 4T1 tumor was linked to induction of protective mucosal immune responses mediated by tumor specific CD4+ and CD8+ T cell responses. Vaccine efficacy was diminished when tested in the presence of an existing primary tumor (a mouse model of spontaneous lung metastasis). The reduced vaccine efficacy was associated with an increased infiltration of primary breast tumor-induced CD11b+ myeloid-derived suppressor cells (MDSCs) to the lung's microenvironment. Concordantly, when the primary tumor was surgically removed, vaccine efficacy at preventing lung metastasis was enhanced despite primary tumor resection aggravating lung metastasis in control groups. In summary, this dissertation project presents targeting the lung with cancer vaccines as an attractive approach to prevent/treat lung tumors and provides new considerations for increasing vaccine efficacy
The Success Rate of Cryoablation vs. Radiofrequency Ablation for the Treatment of Atrial Fibrillation
No full textAtrial fibrillation (AF) is a heart rhythm disorder of the atrium caused by impulses that attack the Atrioventricular (AV) node and block signals to the ventricles. There are two types of catheter ablations that attempt to cure AF: radiofrequency (RF) ablation and cryoablation. RF ablations use an irrigated open-tip catheter to burn lesions in a point-by-point fashion around the pulmonary veins to stop the irregular electrical signals. Cryoablations use a balloon catheter that inflates in the pulmonary vein to freeze the tissue, which stops the irregular electrical signals. While both methods are adequate, the more effective procedure is a topic of debate. This study was performed at Baylor Scott and White Hillcrest hospital in the Cardiology Department. The data was obtained from 45 patients who suffered from AF from January 2017- June 2018. The purpose of this study was to evaluate the success rates of RF ablations and cryoablations within the Baylor Scott and White Hillcrest hospitals by measuring the readmission rates of patients who repeated an ablation. The initial success rates of RF ablation and cryoablation were calculated to be 88% and 95%, respectively. Even though this study aligns with other studies performed by Frankel Cardiovascular Center and CarolinaEast Medical Center, it was noted that the sample pool is small and limited to Baylor Scott and White Hillcrest
Association of multimorbidity with the use of health information technology
Get PDFOBJECTIVE: To examine the association of multimorbidity with health information technology use among adults in the USA. METHODS: We used cross-sectional study design and data from the Health Information National Trends Survey 5 Cycle 4. Health information technology use was measured with ten variables comprising access, recent use, and healthcare management. Unadjusted and adjusted logistic and multinomial logistic regressions were used to model the associations of multimorbidity with health information technology use. RESULTS: Among adults with multimorbidity, health information technology use for specific purposes ranged from 37.8% for helping make medical decisions to 51.7% for communicating with healthcare providers. In multivariable regressions, individuals with multimorbidity were more likely to report general use of health information technology (adjusted odds ratios = 1.48, 95% confidence intervals = 1.01-2.15) and more likely to use health information technology to check test results (adjusted odds ratios = 1.85, 95% confidence intervals = 1.33-2.58) compared to adults with only one chronic condition, however, there were no significant differences in other forms of health information technology use. We also observed interactive associations of multimorbidity and age on various components of health information technology use. Compared to younger adults with multimorbidity, older adults (>/= 65 years of age) with multimorbidity were less likely to use almost all aspects of health information technology. CONCLUSION: Health information technology use disparities by age and multimorbidity were observed. Education and interventions are needed to promote health information technology use among older adults in general and specifically among older adults with multimorbidity.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute on Minority Health and Health Disparities, National Institute of General Medical Sciences, National Institute of Health Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD), (grant number 5S21MD012472-05, 5U54GM104942-04, 1OT2OD032581-01
Effect of Monocarboxylate Transporter 2 Loss on Retinal Ganglion Cell Survival and Function
No full textResearch Appreciation Day Award Winner - HSC College of Pharmacy, 2023 Pharmaceutical Science Research Award - 3rd PlacePurpose: There is currently no cure for the vision loss in glaucoma that is characterized by retinal ganglion cell (RGC) loss and irreversible optic neuropathy. Monocarboxylate transporter 2 (MCT2s) that transport pyruvate, lactate, and ketone bodies, are exclusively found in neurons such as the RGCs. We have previously shown that MCT2 is lost during glaucoma, in advance of RGC loss, and MCT2 overexpression protects RGC number and function. This study was undertaken to test whether MCT2s are necessary for RGC survival and function.
Methods: To test this hypothesis, we used tamoxifen injection into Thy1-ERT2-cre: MCT2fl/fl mice to conditionally knock out MCT2 from Thy1-positive RGCs. Control mice carried the MCT2 flox’d allele but were Thy1-ERT2-cre-negative. Control and experimental mice were subjected to ocular hypertension using the magnetic microbead model; separate naïve controls from each genotype were also evaluated. Intraocular pressure (IOP) was measured using the TonoLab rebound tonometer. Pattern electroretinogram (PERG) was used to analyze RGC function. We used unbiased stereology (Stereo Investigator, Micro Brightfield) to count the number of retinal ganglion cells in wholemount retina, and ATP levels in retina were also measured.
Results: IOP was higher in the ocular hypertension (OHT) groups. MCT2 knockout alone did not impact IOP, nor did it alter baseline PERG amplitude or latency. After OHT, PERG amplitude was significantly lower in the MCT2-knockout mice (p=0.0013). MCT2 knockout alone did not change RGC density. After OHT, RGC density decreased, though in this preliminary analysis, RGC density among the groups was not significantly different. ATP production in the OHT+ Tamoxifen group was significantly higher (1.81 +/- 0.89 ug/ul) than in the naïve control group (0.68 +/- 0.42 ug/ul).
Conclusions: MCT2 knockout from RGCs did not change IOP or PERG, suggesting that MCT2 is not necessary for RGC survival. Ocular hypertension decreased PERG amplitude and RGC density, though the magnitude of the decrease may not have been increased by MCT2 knockout. These preliminary data suggest that RGCs are capable of meeting their immediate metabolic needs through means beyond MCT2.NIH: EY 02666
The Neuroprotective Effects of Hybrid SA-10 Nanoparticles in a Glaucoma Mouse Model of Retinal Ischemia/Reperfusion Injury
No full textResearch Appreciation Day Award Winner - School of Biomedical Sciences, 2023 North Texas Eye Research Institute Graduate Student Award - 1st PlacePurpose:
The progression of glaucoma is largely dependent on the gross functionality of retinal ganglion cells (RGCs), which transmit visual signals to the brain. Current treatments for glaucoma focus on lowering intraocular pressure (IOP), yet other risk factors such as oxidative stress and poor blood perfusion also contribute to RGC damage. Furthermore, no treatments exist which revitalize dysfunctional RGCs. One promising neuroprotective agent is SA-10, a hybrid compound with reactive oxygen species (ROS) scavenging sulfone moiety and perfusion-enhancing nitric oxide (NO) donor moiety. This study aims to investigate the in vivoneuroprotective effects of the nanoparticle (NP) formulation of SA-10 (SA-10-NPs) on RGCs in an acute rodent model of ischemia/reperfusion (I/R).
Methods:
C57BL/6J mice were separated into 3 groups (n= 5-8 per group): Sham control, 1% Blank NPs-treated, and 1% SA-10-NPs. Aside from sham, all groups received 4 μL of different blinded topical pre-treatments: poly(lactic-co-glycolic-acid) (PLGA) nanoparticles suspended PBS for the Blank-NPs group, and 1% SA-10 loaded in PLGA for the SA-10-NPs group. Besides the sham, all groups had their anterior chambers cannulated with normal saline to achieve an elevated IOP of 120 mmHg for 60 minutes. After I/R all groups received 4 μL of their respective treatments 3 times a week over 14 days. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) tests were independently performed both prior to I/R insult (baseline) and after completing the treatment regimen. Mouse eyes were then enucleated. Their retinas were stained with an RNA binding protein with multiple splicing (RBPMS) RGC-specific marker for quantification of cell survival. Parametric Analysis of Variance (ANOVA) and its non-parametric equivalent, the Kruskal-Wallis test, were performed for statistical analysis.
Results:
I/R injury (Blank-NPs-treated) produced a 52.1% decline (p<0.01) in PERG and a 17.9% decreasing trend in PVEP amplitudes as compared to sham. SA-10-NPs prevented this decline by a trend of 33.5% and 14%, respectively. I/R injury (Blank NPs-treated) caused a 33% decrease (p<0.01) in RGC survival in the inner retina in comparison with sham control, which was alleviated with the SA-10-NPs treatment by 33.4% (p<0.001).
Conclusions:
SA-10-NPs enhanced RGC survival and function following ischemia-induced damage in the mice I/R model and have the potential to be used as a neuroprotective therapy for glaucoma.NEI Grant EY02982
Clinical significance of Annexin A2 overexpression in kidney renal clear cell carcinoma
No full textPurpose: Invasion and metastasis led to poor prognosis and death of kidney renal clear cell carcinoma (KIRC) patients. In this study, we focus on the characterization of Annexin A2 (AnxA2), which plays an essential role in cell growth, angiogenesis, migration, invasion, and metastasis. Although the role of Annexin A2 (AnxA2) has been studied in many cancers, its function in KIRC is still unexplored. Therefore, in this study, we investigated the AnxA2 expression in tumor tissues of KIRC patients to determine its association with disease characteristics.
Methods: We utilized data from The Cancer Genome Atlas (TCGA) to observe AnxA2 gene expression in KIRC and its association with survival. Additionally, immunohistochemical (IHC) analysis was performed to examine the AnxA2 expression in tumor tissues of KIRC patients.
Results: In our analysis of TCGA data, AnxA2 mRNA expression was found significantly higher in KIRC tumor tissues compared to the adjacent noncancerous tissues. In addition, AnxA2 expression was significantly associated with higher tumor stage and grade. The high expression of AnxA2 in KIRC patients was significantly correlated to decreased survival [hazard ratio (HR), 1.75; 95% confidence interval (CI), 1.29 - 2.36; p = 0.00023] as compared to low expression. In addition, our IHC staining suggests that AnxA2 was overexpressed in tumor tissues of KIRC patients compared with adjacent noncancerous tissues.
Conclusion: AnxA2 is overexpressed in KIRC tumor tissues, and has a direct relationship to the advanced clinicopathological variables and adverse prognosis associated to patients with KIRC
Examining Familiarity with Location and People in Association with Protective Behavioral Strategy Use Among Adolescents and Young Adults at the Daily-Level
No full textResearch Appreciation Day Award Winner - School of Public Health, 2023 Research Award - 1st PlacePurpose: Despite protective behavioral strategies (PBS) often being a central component to alcohol prevention programs, many adolescents and young adults who drink alcohol use few to no PBS. Therefore, it is important to determine factors associated with PBS use. Situational factors such as social and physical environments have shown to influence drinking behavior. In addition, many PBS are often related to peers and location and thus may influence PBS use or nonuse. The study aimed to investigate the associations between situational familiarity (i.e., familiarity with locations and people) and PBS use at the daily level among adolescents and young adults.
Method: Participants were recruited in Texas for a longitudinal ecological momentary assessment (EMA) study that involved a 3-week EMA burst design (8 surveys per week; up to 2x/day) with bursts occurring quarterly over 12-months. Participants who reported drinking days and answered PBS items were included in the current analyses.
Data: The analytical sample consisted of 3,921 drinking days from 579 participants (55.44% females; 45.12% White, Non-Hispanic; ages 15 to 25 (mean = 21.04)). Data were analyzed with mixed effects zero-inflated Poisson models for each PBS outcome (i.e., serious harm reduction, limiting/stopping, manner of drinking).
Results: Within-person results indicated when participants had elevated (i.e., higher than their own average) familiarity with location (e.g., How familiar are you with the locations you were at yesterday?), they were less likely to use harm reduction PBS (RR) = 0.94, p < 0.001) and limiting/stopping PBS (RR = 0.96, p = 0.001). Results showed that on drinking days with elevated familiarity with people (e.g., How familiar are you with the people you were with yesterday?), individuals were more likely to use limiting/stopping PBS (RR = 1.04, p = 0.01). There were no significant daily-level associations between familiarity with people or location and manner of drinking PBS.
Conclusion: Results suggest that adolescent and young adult PBS use, particularly serious harm reduction and limiting/stopping PBS, can vary based on familiarity with people and location on a daily level. Alcohol prevention approaches, such as just-in-time intervention strategies, should consider how to increase PBS use even when drinking in more familiar situations or with less familiar people
Ligand Identification for the Orthosteric site of Sigma 1 Receptor using Computational Molecular Docking and Virtual Screening Methods
No full textPurpose:
The 1 Receptor (Sig-1R) is a ligand operated membrane protein resides in the mitochondria-associated-membranes of the endoplasmic reticulum (ER). At the molecular level, Sig-1R has several important roles in cellular homeostasis, including Ca2+ regulation, and helping chaperone the unfolded protein response. This ER stress has been found to be one of the factors leading to cytokine storm and clinical deterioration in patients with a coronavirus infection, leading to an interest in drugs which modulate the response of the Sig-1R for treatment of COVID-19.
These receptors are found throughout the CNS as well as the periphery, explaining its wide range of effects throughout the body. At the organ level, studies conducted on the Sig-1R have implicated its involvement in neurodegenerative diseases such as Parkinson’s and Alzheimer’s Disease, cardiac diseases such as heart failure and cardiovascular disease (CVD), and major depressive disorder. This implication in a wide variety of disease states means it has a large potential as a drug target. Our study's purpose is to identify novel potential drug candidates at the orthosteric binding site of Sig-1R with high binding affinity, specificity, and favorable PK parameters using a structure-based drug design approach.
Method:
Prior work in this lab found a list of the top 1000 orthosteric ligands by docking Sig-1R against libraries containing 9,270 small drug-like molecules using the TACC drug discovery tool. These libraries were extracted from the ZINC database. From this list of 1000 compounds, we selected the top 130 compounds (binding affinity cut-off ≥ -11.0 kcal/mol) and re-docked against the Sig-1R using the efficient docking suite Glide in Maestro. Also, we analyzed the pharmacokinetic/ADME parameters of these compounds using SwissADME, identifying possible candidates to use as our scaffold to try and design a ligand with even stronger binding affinity to the orthosteric site of Sig1R. Furthermore, we docked 130 compounds with the Dopamine Receptor D2 (D2R) to analyze their specificity for the Sig-1R.
Results:
Using an extra precision molecular docking in Glide, we found that our molecule 106 (-12.88 kcal/mol), molecule 105 (-12.83 kcal/mol), and molecule 100 (-12.29 kcal/mol) all had very high binding affinity for the Sig-1R. Both Molecules 105 and 100 had favorable PK parameters, as both were estimated to be BBB permeable, as well as not breaking any aspects of Lipinski’s Rule of Five. Molecule 100 was also found to have relatively low binding affinity (-7.6 kcal/mol) for the D2R.
Conclusion:
Using our computational molecular docking methods, we have identified molecule 100 as a ligand with strong affinity and specificity for the Sig1R, as well as favorable PK parameters. This could be a strong candidate to use as a chemical scaffold to develop a ligand with even stronger binding affinity for Sig-1R, which can eventually go on to in-vitro assays to confirm activity.Summerfield G. Roberts Foundatio