Characterization of YB1 in Hepatocellular Carcinoma Cells

Background: The Rio Grande Valley’s demographics show that the Hispanic population demographics exceeds more than 92% in The Rio Grande Valley. Being the most prominent ethnicity. Hepatocellular carcinoma (HCC) affects the Hispanic community greatly, and many factors impact the suceptibility. In 2022, liver cancer was predicted to be the fifth and seventh major cause for mortality in both males and females, respectively. Given its fast-growing rate and its aggressiveness, it is important to study the social, cultural, and most importantly the biogenetic factors that affect the prevalence of the disease. Unfortunately, in Texas, and specifically in the RGV, its prevalence rate has increased by 36% in recent years. One of the reasons for the high mortality of HCC, is drug resistance to first line drug treatment for the disease. According to TCGA data, YBox Binding Protein 1 (YBX1) is upregulated in HCC and is part of a super family of proteins that regulates mRNA translation. Further investigation of this protein could lead to a mechanism of drug resistance in HCC. Methods: Hepatocellular carcinoma cell line Skhep-1 will be obtained from ATCC and cultured as recommended. Stable overexpressing and knock-down cell lines of YB1 will be generated via plasmid transfection, puromycin selection, and FACS sorting. RT-PCR and western blot will be utilized to verify the overexpression of YBX1 at the mRNA and protein level in the recombinant cell lines. The resulting cell lines will be tested for oncogenicity though phenotypic assays, such as migration, invasion, proliferation, and colony formation. Results: Prior bioinformatic work done by the lab investigated YBX1 expression levels in the TCGA database, the structure and domain were also analysed. This protein has been reported to be linked to a worse survival rate and according to TCGA data it is overexpressed in HCC patients. The recombinant YBX1 overexpressed cells are sorted for GFP enrichment and validated via RT-PCRs and Western Blots. Preliminary data elucidates YBX1 protein overexpression has an increased proliferation, migration, invasion, and colony formation. Conclusions: The identification of this protein is important as it is linked with a lower survival rate. Further comprehensive research has revealed that oncogenic proteins, such as YBX1, can also play roles in drug resistance. Since one of the many hurdles of treating HCC is an unfavorable interaction with first-line drugs currently utilized to treat HCC, the future direction of this research will include further investigation of YBX1 overexpression and its relation to drug resistance

Adipose Stem Cells as an Adjunct to Peripheral Nerve Surgery

Background: Currently, many different techniques exist for the surgical repair of peripheral nerves. The degree of injury dictates the repair and, depending on the defect or injury of the peripheral nerve, plastic surgeons can perform nerve repairs, grafts, and transfers. All the previously listed techniques are routinely performed in human patients, but a novel addition to these peripheral nerve surgeries involves concomitant fat grafting to the repair site at the time of surgery. Fat grafting provides adipose-derived stem cells (ADSCs) to the injury site. Though fat grafting is performed as an adjunct to some peripheral nerve surgeries, there is no clear evidence as to which procedures have improved outcomes resultant from concomitant fat grafting. This review explores the evidence presented in various animal studies regarding outcomes of fat grafting at the time of various types of peripheral nerve surgery. Methods: A literature search was performed with key words including “fat grafting,” “adipose derived stem cells,” “animal research,” and “peripheral nerve surgery.” An additional requirement for the studies was that they evaluated functional outcomes. Participant number and outcome evaluation of animal nerve repair surgeries, nerve grafting studies, tissue engineered nerve graft studies, and nerve transfer studies were inserted into tables for study comparison. Results: Animal experiments demonstrate that various types of peripheral nerve surgeries have the potential to benefit from the addition of ADSCs during surgery. ADSCs have proven beneficial for nerve regeneration on multiple levels, including by secreting growth factors and by morphing into Schwann-like cells, which can modulate genes in a way that facilitates peripheral nerve healing. Current literature on animal peripheral nerve surgery with an addition of fat grafting includes studies on nerve repair. nerve grafting, nerve grafting with tissue engineered nerve grafts, and nerve transfers. Conclusion: Very few of the existing studies evaluate the functional outcomes of adipose derived stem cell addition to peripheral nerve studies, as seen in this review. One of the reasons that animal studies are so useful is due to their ability to correlate histological and functional outcomes, which is not ethical in many cases in human studies. Future studies should consider evaluating functional outcomes so that meaningful applications could be more easily extracted in relation to physiological effects

Comatose Deception, Benzodiazepine masquerade of Myxedema Coma

Introduction: Myxedema coma is a life:-threatening condition due to severe hypothyroidism or long-standing untreated hypothyroidism. This condition can be triggered by factors such as infection, exposure to certain medications, or other stressors on the body. Symptoms of myxedema coma include hypothermia, altered mental status, and fluid accumulation. This condition can be life threatening and requires immediate medical attention. Benzodiazepines are often prescribed to address various conditions such as anxiety, sedation, and seizures. However, they have significant side effects including drowsiness, sedation, low blood pressure, and slow heart rate. These side effects can mimic symptoms of other conditions such as myxedema coma. In this case we describe a patient who initially appeared to have overdosed on benzodiazepines but was later diagnosed with myxedema coma. Case Presentation: A 49-year-old lady presented to the emergency department in an obtunded state and decreased respiratory drive. Earlier that day, she accidentally ingested a fish burger despite having a fish allergy, and experienced wheezing, facial swelling, and vomiting. She self-administered an epinephrine pen to manage the allergic symptoms. She was found unconscious by her daughter, who promptly called emergency medical services (EMS). Although no signs of an allergic reaction observed, EMS noted bradycardia and a reduced respiratory drive and administered naloxone and flumazenil which mildly improved her symptoms. The patient\u27s medical history included post-traumatic stress disorder, generalized anxiety disorder, bipolar type one, fibromyalgia, and hypothyroidism with inconsistent medication (levothyroxine) adherence. Her medication regimen included clonazepam (2mg twice daily), trazodone (100mg twice daily), tizanidine (4mg twice daily), fluoxetine (20mg daily), and temazepam (50mg twice daily). She was not taking levothyroxine at that time daily. Her daughter reported a progressive decline in strength, fatigue, weight gain, hoarse voice, dyspnea on exertion, and cold intolerance over the recent months. During assessment, vital signs indicated a temperature of 97 degrees Fahrenheit, bradycardia (56), respiratory rate (10), blood pressure 93/38, oxygen saturation of 85% on room air, and body mass index of 55. Physical examination revealed obesity, acute distress, constricted pupils (2-3), a short supple neck, audible inspiratory stridor, tenderness in the left upper quadrant of the abdomen, and 2+ pitting edema in bilateral lower extremities. Laboratory findings revealed hypercarbia (31.7 mmol/L), reduced glomerular filtration rate (39.4 ml/min/1.73 mm2), elevated thyroid-stimulating hormone (179 uIU/ml), and low free thyroxine (0.1 ng/dl) levels. With a Popoveniuc score of 80, she met the diagnostic criteria for myxedema coma and was promptly started on levothyroxine. Conclusion: Initial diagnosis of benzodiazepine overdose was questioned due to consistent use, confirmed by pharmacy refill dates, and most importantly lack of typical symptoms of overdose and response to treatment. Later it was proved that noncompliance with levothyroxine led to myxedema coma triggered by benzodiazepines which worsened her condition. This case emphasizes the need for vigilance in distinguishing between benzodiazepine side effects and other conditions. Timely recognition and appropriate treatment, such as levothyroxine initiation, are crucial in managing myxedema coma and preventing life-threatening complications

Correlation Between Lecture Engagement and Academic Performance in the UTRGV School of Medicine

Introduction: The landscape of medical education has witnessed significant changes in recent years, marked by a decline in both in-person lecture attendance and online lecture viewership. This trend is particularly notable in the post-COVID-19 era and raises important questions about the relationship between lecture engagement and academic performance among medical students. Our study seeks to investigate the correlation between lecture viewership and course performance, with a specific focus on the unique context of the UTRGV School of Medicine. Our primary objectives were to (1) evaluate the correlation between lecture viewership and academic performance and (2) examine the relationship between lecture engagement and academic outcomes based on the medical school year (MS1 and MS2). We hypothesized that performance would be related to lecture engagement in a discipline-related manner. Our findings aim to provide insights into the effectiveness of lecture engagement as a learning method and its potential influence on academic success in the unique context of the UTRGV School of Medicine. The results may serve as valuable guidance for administrative decisions regarding the optimization of lecture formats to better meet the needs of medical students. Methodology: Lecture engagement was evaluated by analyzing viewing data from Panopto, the UTRGV learning management system capture system. The study focused on the class of 2026 in the 2023 Renal and Male Reproduction (RMR) module. De-identified viewing data from the module was systematically categorized by discipline and week. We evaluated relationships with viewing data to corresponding performance overall and by discipline. Statistical analysis was conducted using SPSS. Results: Preliminary data from the Renal and Male Reproduction module suggests that total minutes of lecture viewing had a negative trend in relation to end of module performance (R=0.0135; slope = -0.2874). Notably, students performing above 90% were identified in both students who watched a substantial amount of lectures and those with minimal viewership. However, a positive trend was observed between online lecture engagement and performance on the quizzes, particularly in quiz 4 (R=0.0585, slope=87.575). Conclusions: In summary, our findings suggest that online lecture engagement correlates to a trend in increased quiz grades but decreased performance on the end-of-module exam. We attribute this pattern to the nature of assessments, with quizzes being professor-written and end-of-module exam questions sourced from an NBME standardized question bank. Also, it is worth noting that the higher scores associated with decreased lecture watching may point to active, in-class participation. Therefore, this negative trend may indicate a potential benefit of in-person lecture attendance and engagement. Moreover, reduced lecture engagement may suggest that those students could be utilizing self-study and alternative means of learning to fulfill course outcomes

Evaluation of ergosterol and its metabolites as LXR agonists and their anticancer potential in colon cancer

Purpose: Aberrant cholesterol homeostasis is a well-recognized hallmark of cancer and implicated in metastasis and chemotherapeutic resistance, the two major causes of cancer associated mortality. Liver X receptors (LXRs) are the key transcription factors that induce cholesterol efflux via enhancing the expression of ABCA1 and ABCG1. Methods: Molecular docking and dynamic simulation studies were done to assess the binding affinity and stability of the receptor ligand complexes. Activation of LXRs was evaluated using the luciferase reporter assay. qRT-PCR and western blotting was done to analyse the mRNA and protein expression of cholesterol homeostasis genes. Flow cytometric analysis was carried out to evaluate the surface expression of ABCA1. The effect of selected sterols on viability of three cancer cell lines and one normal epithelial cell line was assessed using MTT assay. Results: Ergosterol (Erg), ergosta-7,22,24(28)-trien-3β-ol (Erg1), ergosta-5,22,25-trien-3-ol (Erg2), ergosta-5,7,22,24(28)-tetraen-3β-ol (Erg3), and ergosta-7,22-dien-3β-ol (Erg4) displayed good binding affinities and formed stable complexes with both isoforms of LXRs. Treatment with Erg led to 2.5 fold while Erg2 and Erg4 led to 1.7 fold increase in LXR activation. Furthermore, a significant increase in mRNA expression of NR1H2, ABCA1, ABCG1 and ApoE was observed upon Erg treatment and it also led to a 25 fold increase in cell surface expression of ABCA1. All of the sterol were selectively toxicity toxic towards colorectal cancer cells but not towards normal epithelial cells. Conclusion: Our findings suggests that ergosterol activates LXRβ and have significant anticancer activity and thus it could be a likely candidate to manage aberrant cholesterol homeostasis associated with colorectal cancer

Contribution of 24-h Blood Pressure Variability to Dementia-Related Disorders in Hispanics

Introduction: As the number of people living with dementia is increasing at alarming rates worldwide, there is an urgent need to understand the physiopathology of dementia syndromes. Among the most important preventable risk factors, treatment of vascular risk factors such as high blood pressure (BP) decreases the risk of Alzheimer’s disease and related dementias (ADRD). Recent evidence suggests that examining BP variability provides additional physiopathological and predictive information above the mean BP level. However, studies examining the relationship between 24-h BP variability and ADRD are limited, and evidence of the association with dementia has not been documented yet. Therefore, we aimed in this study to assess the association of 24-h ambulatory BP variability with brain imaging and cognitive markers of ADRD. Methods: A cross-sectional observational study was conducted using a subset of 420 individuals from the Maracaibo Aging Study aged ≥40 years. Study participants underwent brain MRI scanning and 24-h ambulatory BP monitoring assessments. Markers of ADRD included 1) cerebral small vessel disease (CSVD, defined as white matter hyperintensities, presence of lacunes, cerebral microbleeds, and enlarged perivascular spaces, and hippocampal volume), 2) cognitive functioning addressed with the mini-mental state exam (EMEMS), and 3) diagnose of dementia at baseline. 24-h ambulatory BP variability was studied as the average real variability index. Adjusted linear and logistic regression models were used to analyze the association between 24-h BP and ADRD and accounted for age, sex, education level, body mass index (BMI), current smoking, alcohol intake, hypertension treatment, diabetes mellitus, serum total cholesterol, previous cardiovascular diseases, and cephalic circumference and 24-h mean BP level. Results: The mean age was 57.1±11.8 years old and 73.2% were women (n=303). In adjusted analysis, each unit increase in the 24-h systolic BP variability was significantly associated with lower hippocampus volume (β, -0.036; 95% confidence interval [CI], -0.064, -0.008, P=0.011), greater white matter hyper intensities volume (β, 0.026; 95% CI, 0.008, 0.044; P=0.006), lower cognitive scores (β, -0.370; 95% CI, -0.729, -0.011; P=0.044), greater presence of lacunes (Odds ratios [OR], 1.38; 95% CI, 1.10, 1.71; P=0.004), enlarged perivascular spaces (OR,1.34; 95% CI, 1.08, 1.67; P=0.007), and dementia prevalence (OR, 1.41; 95% CI, 1.07, 1.85; P=0.014). 24-hour diastolic blood pressure variability was only significantly associated with lacunes (OR, 1.42; 95% CI, 1.06, 1.90; P=0.017). In exploratory analysis, we found that neither daytime nor nighttime variability in BP significantly relate with ADRD. Conclusions: Excessive 24-h BP variability associates with ADRD independently of the mean BP level. Understanding the physiological mechanisms explaining the relationship between excessive 24-h BP variability and ADRD may be clinically relevant in the prevention of ADRDs

Investigation of the efficacy local anesthetics for perioperative peripheral nerve blocks in patients with diabetes: A Retrospective Chart Review

Background: Peripheral nerve neuralgia is a common manifestation of diabetes and can cause patients to have severe episodes of pain. Although pharmacologic treatment with antineuropathic drugs are first line, they often are not effective and can warrant further treatment with peripheral nerve blocks. Further studies support that peripheral nerve blocks should be considered as the first option for anesthesia for lower limb surgery in diabetic patients. The goal of this study is to evaluate local anesthetic agent regimens in the Rio Grande Valley for peripheral nerve blocks in diabetic patients and determine post operative effectiveness and complications. Methods: Here, we conducted a retrospective chart review at UTHealth RGV. We evaluated medical charts with ICD-10 codes for Diabetes (E109, E1100) that also had current procedural terminology (CPT) codes for perioperative peripheral nerve blocks. For all referenced medical charts we evaluated sex, age, time of diagnosis, ethnicity, pre-operative notes, post-operative notes, past medical history, current medical history, duration of block and number of blocks. Medical charts were excluded from the analysis that were duplicative, incomplete, or misclassified. Data was analyzed in SPSS to determine if there were significant advantages for certain anesthetic agents or certain complications that arose more frequently with certain anesthetic agents. Results/Discussion: We evaluated over 2000 medical charts from UTHealth RGV that were coded with a diagnosis of diabetes. We observed a high variation in the types of peripheral nerve blocks utilized perioperatively. Our preliminary data suggests that peripheral nerve blocks in patients with diabetes show varying efficacy and in some cases, substantial complications. Conclusion: Our data and project highlights that post-operative effectiveness and complications can be altered in patients with diabetes. Future work will evaluate how differing types of neuropathy may influence peripheral nerve block outcomes

Characterization of Anti-Cancer properties of Fungal Metabolite Ophiobolin A

Background: Ophiobolin A (Oph A) is a secondary metabolite and a phytotoxin produced by the pathogenic fungi Cochliobolus heterostrophus that causes “southern corn leaf blight” disease in maize via modulation of the calcium binding protein calmodulin. Numerous studies have found antiproliferative effects of Ophiobolin A against a variety of cells including bacteria and various cancers including melanoma, glioma and leukemia. Recent studies have shown that OphA induces paraptosis-like cell death in glioblastoma multiforme (GBM) cells via vacuolization of the cytoplasm and enlargement of the mitochondria and endoplasmic reticulum. Notably, unlike apoptosis, paraptosis cell death lacks DNA fragmentation and activation of caspases, creating a possible mechanism for targeted treatment of malignant brain tissue of GBM patients who have GBM cells that are highly resistant to pro-apoptotic treatments. This study aimed to further characterize the effects of this promising anti-cancer agent on glioblastoma (U118 and U87), breast cancer (MCF7 and T47D), neuroblastoma cells (SH-SY5Y) and rat pheochromocytoma cells (PC12). SH-SY5Y and rat PC12 commonly serve as two popular neuron models to test drug toxicity and viability. Methods: The effects of Ophiobolin A were studied in six cancer cell lines from various tissue types including glioblastoma, breast cancer and rat pheochromocytoma cells: U87, MCF-7, T47D, U118, SH-SY5Y and PC12. Over 4 weeks, cell lines were recovered and cultured until adequate confluence was reached with subculturing and medium refreshing. Once adequate growth and attachment was confirmed with microscopy, cells were seeded in 6-well plates from 100k to 600k and treated with either DMSO or 1 µM of Ophiobolin A. Cell morphology was monitored using inverted microscope at 1 hour, 3 hours, and 6 hours following Ophiobolin A application. Cell survivability was measured using Countess at 6 hours post drug treatment. Results: Similar to previous studies, OphA was found to induce cell apoptosis and decrease cell numbers in glioblastoma cell lines, U87 and U118. As expected, similar results were observed in the breast cancer line MCF7. The impact of Oph A on cell morphology changes demonstrated a time-dependent manner in both glioblastoma cell lines, showing elongated neuronal bodies and cell processes. In MCF7 cells, we observed increased vacuolization after drug treatment at 1 hour, 3 hours, and 6 hours. Cell survival rates were significantly reduced in all tested cancer cells in compared to the control groups. Conclusions: Ophiobolin A has been shown to induce cell apoptosis in glioblastoma cells and breast cancer cells. The effect of OphA on healthy cells and the mechanisms underlying the OphA-induced cell apoptosis will be studied

Addressing Educational Disparities to Improve Health in the Rio Grande Valley

Background: The Rio Grande Valley (RGV) has emerged as a region in the United States grappling with profound health challenges, prominently characterized by elevated rates of diabetes and obesity among its diverse residents. (11) In this comprehensive public health research endeavor, our objective is to delve deeply into the intricate relationship between educational disparities and health outcomes of the multifaceted RGV population. This connection can then be utilized as a focal point for breaking down the health disparities in the RGV. Methods: Employing a rigorous methodology, we conduct an exhaustive literature review to illuminate the connection between educational disparities and healthcare disparities in the Rio Grande Valley. Our exploration aims to find the extent to which disparities in education contribute to the emergence and perpetuation of healthcare disparities within the region. Drawing on valuable insights garnered from over nine-hundred hours of active participation in the “College 1st” educational outreach program, we underscore the pivotal role that education plays in proactively addressing and mitigating health disparities. (17,21) 300 surveys were collected after each event. These surveys contained questions assessing the effectiveness of the camp in changing the students cognitions about college, homework, and school. Results and Discussion: The findings underscore an urgent and compelling need to address prevailing educational gaps within the RGV, emphasizing that rectifying these gaps is not only crucial but also a fundamental step toward improving the overall health and well-being of its diverse residents. Despite the region’s enduring reputation as a focal point for health disparities, acknowledging the connection between educational disparities and health disparities is paramount in designing effective intervention strategies such as College 1st. Survey analysis is still underway, but the preliminary data showcases that the implementation of College 1st program helps to improve the students cognitions surrounding homework, school, and attending college. Conclusion: This research contributes to the broader discourse on health disparities by providing an examination of the relationship between educational disparities and health outcomes in the Rio Grande Valley. It is imperative to address educational gaps in order to find a solution for the healthcare disparities in the Rio Grande Valley. Through these efforts we can pave the way for a healthier and more equitable future for the Rio Grande Valley, which can serve as a model for the world

Perceptions of dengue risk and acceptability of a dengue vaccine in residents of Puerto Rico

Dengvaxia is the first dengue vaccine recommended in the United States (U.S.). It is recommended for children aged 9–16 y with laboratory-confirmed previous dengue infection and living in areas where dengue is endemic. We conducted focus groups with parents and in-depth interviews with key informants (i.e. practicing pediatricians, physicians from immunization clinics, university researchers, and school officials) in Puerto Rico (P.R.) to examine acceptability, barriers, and motivators to vaccinate with Dengvaxia. We also carried out informal meetings and semi-structured interviews to evaluate key messages and educational materials with pediatricians and parents. Barriers to vaccination included lack of information, distrust toward new vaccines, vaccine side effects and risks, and high cost of/lack of insurance coverage for laboratory tests and vaccines. Motivators included clear information about the vaccine, a desire to prevent future dengue infections, the experience of a previous dengue infection or awareness of dengue fatality, vaccine and laboratory tests covered by health insurance, availability of rapid test results and vaccine appointments. School officials and parents agreed parents would pay a deductible of $5–20 for Dengvaxia. For vaccine information dissemination, parents preferred an educational campaign through traditional media and social media, and one-on-one counseling of parents by healthcare providers. Education about this vaccine to healthcare providers will help them answer parents’ questions. Dengvaxia acceptability in P.R. will increase by addressing motivators and barriers to vaccination and by disseminating vaccine information in plain language through spokespersons from health institutions in P.R