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MicroRNAs and Their Immunotherapeutic Potential for Treatment and Detection of Triple Negative Breast Cancer
No full textPoster Highlight: College of Biomedical and Translational Science, RAD 2025 Award Winning Posters & Oral PresentationsPurpose: MicroRNAs are small, non-coding, single-stranded RNA molecules that regulate post-transcriptional gene expression. MicroRNAs are roughly 22 nucleotides in length and downregulate genetic expression by binding to messenger RNA transcripts resulting in inhibition of mRNA translation and prompting RNA degradation to modulate different cellular functions. In the context of cancer, various cellular functions are altered by miRNAs. These functions include evading immune destruction, evading tumor suppression, activation of invasion and metastasis, and many other important physiological roles. Previous studies have demonstrated the utility of selecting different miRNAs and their gene targets involved in cell proliferation, metastasis, and apoptosis, miRNAs can be used to modify the expressions of oncogenes and tumor suppressors for immunotherapeutic purposes. The purpose of this study is to interrogate optimal miRNAs and target genes for precise modulation of potential therapeutic use against triple-negative breast cancer (TNBC) alone/or given immune-based anticancer treatment. Methods: The lab conducted a murine miRNA panel assay of 84 miRNAs with known associations of TNBC on primary tumor surgically resected from tumor-bearing vaccinated mice. MiRNAs showed at least 2-fold increased or decreased expression from tumor-bearing non-immunized mice selected as putative targets for gene association studies using The University of Alabama at Birmingham Cancer Data Analysis Portal database. The University of Alabama at Birmingham Cancer Data Analysis Portal was a database used to determine potential gene targets of interest for the miRNAs from the panel. Results: Analysis of listed miRNAs revealed the most highly expressed downregulated and upregulated miRNAs for both categories were selected for analysis. The most highly expressed upregulated miRNA was hsa-miR-29c-3p which has displayed in previous studies that it can inhibit the proliferation, migration, and invasion of breast cancer cells. The most highly expressed downregulated was hsa-miR-200a-3p which has displayed in previous studies that it can act as either a tumor suppressor or an oncogene in breast cancer, depending on the cancer type and the target genes. It can regulate cell proliferation and metastasis
Bite force production and the origin of Homo
Get PDFThe divergence of Homo from gracile australopiths has been described as a trend of decreasing dentognathic size and robusticity, precipitated by stone tool use and/or a shift to softer foods, including meat. Yet, mechanical evidence supporting this narrative is sparse, and isotopic and archaeological data have led to the suggestion that a shift away from a gracile australopith-like diet would not have occurred in the most basal members of Homo but rather only with the appearance of Homo erectus, implying that the origin of our genus is not rooted in dietary change. Here, we provide mechanical evidence that Homo habilis exhibits an australopith-like pattern of facial strain during biting but, unlike most australopiths, was not suited for a diet that required forceful processing by the molar teeth. Homo habilis was at elevated risk of distractive jaw joint forces during those bites, constraining muscle recruitment so as to avoid generating uncomfortable/dangerous levels of tension in the joint. Modern humans have similar limitations. This suggests that selection on skeletal traits favouring forceful postcanine processing was relaxed by the earliest stages in the evolution of our genus, implying that dietary or food processing changes played an important role in the emergence of Homo.This research was funded by NSF BCS 0725219, 0725183, 0725147, 0725141, 0725136, 0725126, 0725122,0725078 and NSF DBI 0743460, the EU FP6 Marie Curie Actions MRTN-CT-2005- 019564 'EVAN,' The Leakey Foundation Research Grant 40463, and an OVPR Research Grant from East Tennessee State Uni
Changes in A1c and BP in Patients with Diabetes Managed by a Clinical Pharmacy Team in a Low-Income Ambulatory Clinic
No full textPurpose: This study aimed to assess the impact of a clinical pharmacy team's management on difficult-to-manage patients with diabetes mellitus (DM) by evaluating changes in A1c and blood pressure (BP) at Baylor Community Care – Fort Worth (BCC-FW). Methods: A retrospective chart review was conducted comparing pre- and post-intervention data for patients ≥18 years of age diagnosed with DM and actively enrolled in clinical pharmacy team medication management services at BCC-FW. Patients under 18 years and those with gestational diabetes were excluded. Results: The study included 186 patients. The average A1c decreased from 10.05% to 8.07%, representing a reduction of 1.98%. The number of patients achieving an A1c <7% increased from 14 (7.5%) to 60 (32.3%). For BP, the average systolic and diastolic BP both decreased by 2 mmHg. The number of patients with BP <130/80 mmHg increased from 89 (47.8%) to 112 (60.2%). Conclusion: The intervention by the BCC-FW clinical pharmacy team demonstrated significant improvements in both A1c and BP control for patients with difficult-to-manage DM. These results highlight the value of referring complex patients to clinical pharmacy teams for improved management of diabetes and associated cardiovascular risk factors
A Rare Case of Paraneoplastic Myasthenia Gravis in a Patient with Metastatic Colon Cancer
No full textBackground: Paraneoplastic myasthenia gravis is a neuromuscular junction disorder presentation commonly associated with the presence of thymoma. While some case reports have noted this condition in conjunction with some extrathymic malignancies, we present a case of paraneoplastic myasthenia gravis in a patient with metastatic colon cancer. Case Presentation: A 66-year-old man initially presented to his primary care physician with symptoms of generalized fatigue, worsening cervical and paraspinal muscle weakening, as well as intermittent diplopia. Laboratory evaluation at the time of work-up revealed positive acetylcholine receptor antibodies, and the patient was diagnosed with myasthenia gravis. Following limited symptom improvement with multiple therapies, efgartigimod was initiated. He began to experience acute left-sided flank pain following one cycle of efgartigimod which led to subsequent imaging. CT of the abdomen and pelvis led to an incidental finding of advanced, neuroendocrine colon cancer metastatic to the liver and retroperitoneal lymph nodes. The patient was referred to oncology and the diagnosis was confirmed with liver biopsy. Modified folfirinox was initiated as first-line therapy but discontinued after the first cycle due to disease progression and poor tolerance. Molecular testing revealed the presence of a BRAF V600E mutation. Metastatic, second-line therapy with Encorafenib + Panitumumab was planned based on the presence of this mutation. However, due to the patient’s poor clinical status with an ECOG PS of 4, the patient made the decision not to pursue active treatment and instead enter hospice care. Due to the aggressive nature of the disease and advanced stage at the time of diagnosis, the patient passed away two weeks after entering hospice. Conclusions: This case highlights a rare association between myasthenia gravis as a paraneoplastic process in a malignancy unrelated to thymoma. The association points to a likely colorectal-related immunogenic process leading to acetylcholine receptor autoantibody production. This case indicates a consideration of neuroendocrine and colonic malignancy in the initial workup of myasthenia gravis, especially with new onset of myasthenia gravis symptoms in a patient of older age, as in this case. As early detection of colon cancers leads to significantly improved prognosis, non-invasive testing like stool testing or cross-sectional abdominal imaging should be considered in cases with similar presentation to this patient. This is especially true in the setting of negative work-up for thymoma. This case presents an addition of neuroendocrine colon cancer as another extrathymic malignancy associated with paraneoplastic myasthenia gravis, which has not yet been reported
Leading Predictors of Depression among Working Age Adults with Cognitive Limitations: An Interpretable Machine Learning Approach
No full textObjectives: There are research knowledge gaps in depression in adults with cognitive disabilities. This study identified the leading predictors and their associations with depression working age adults with cognitive disabilities using machine learning methods. Methods: This cross-sectional study used data from the 2022 National Health Interview Survey and included working age adults (18-64 years) with cognitive disabilities (weighted N=464,453). We employed eXtreme Gradient Boosting (XGBoost) regression to determine key predictors. Global and local interpretations of associations were performed using SHapley Additive exPlanations (SHAP). Our predictive model used 20 features such as age, health status, and social determinants of health (SDoH) such as education, and poverty. The model building steps included 70% training and 30% testing split of the data, 10-fold cross-validations, and six rounds of optimization using Python 3.9.12. Model performance was evaluated using the test dataset. Results: Model performance metrics was: area under the curve (0.83,0.77) for training and test curves, respectively. The top 10 leading predictors of depression in working age adults with cognitive disabilities included less than high school, high income, employment, health insurance, marital status, and health status. SHAP plots suggested a complex relationship between age and depression as well as race and depression. Marital status and perceived physical health were associated with lower depression. Being a smoker was associated with higher depression. Conclusions: 1 in 2 adults with cognitive disabilities reported depression in 2022. SDoH were some of the leading predictors of depression. Our findings suggest developing policies that target SDoH to reduce the risk of depression and promote optimal treatment for mental health. The model performance was good with the AUC as 0.83
When Comfort Crosses the Line: A Case Report on the Biomechanical Hazards of “Foot Sitting”
No full textBackground: “Foot sitting”, where one foot is folded underneath the body, is a common yet underrecognized postural habit that may have significant biomechanical consequences. Despite the frequent occurrence of foot sitting, long-term effects on posture, alignment, and injury risk remain underexplored. Other postures like cross-legged sitting, however, have been well studied. Cross-legged sitting has shown significant changes in spinal and pelvic flexion, pelvic obliquity, and muscular elongation. Literature also details cross-legged sitting placing uneven pressure on the pelvis and spine and leading to changes in shoulder inclination, lateral pelvic tilt, and forward head posture. Given that foot sitting is a unilateral version of cross-legged sitting, amplification of these effects is likely. In addition to alterations in the body’s alignment, the foot sitting posture demonstrates significant alterations in sacral base alignment and ipsilateral lower extremity biomechanics. These changes may lead to compensatory stress, increasing the risk for both chronic pain and acute injuries, such as fractures or ligament damage. Case: A 51-year-old female presented to clinic for an evaluation of a nondisplaced spiral fracture of the left fifth metatarsal, which occurred after standing up from a seated position. The patient reported recurrent hip pain and gait disturbances. Given the abnormal mechanism of injury leading to the fracture, alternative etiologies were considered, including autoimmune, nutritional, degenerative, and neuropathic. After ruling these out, our focus shifted to the patient’s posture. The patient had a long-standing habit of foot sitting, which led to compensatory biomechanical changes of the lower extremity, as demonstrated on physical exam. It was hypothesized that years of accumulated stress contributed to the patient’s chronic pain, postural imbalance, and weakened structural integrity of the foot and ankle. Information: Chronic foot sitting causes the foot to adopt a supinated position, leading to tibial external rotation, subtalar inversion, and relative talocrural abduction and dorsiflexion. During normal gait, the foot quickly moves from supination to pronation, allowing it to come into full contact with the surface. As the foot then transitions back into supination for propulsion, the 5th metatarsal absorbs much of the force and weight. It can reasonably be assumed that in a chronic foot sitter, the hindfoot would remain supinated in mid-stance, rendering the midfoot hypomobile, and compromising the whole foot's ability to adjust to the terrain. This would increase the demand on surrounding structures to maintain postural stability and balance and could potentially lead to a fracture of the 5th metatarsal, as we observed in this case. Conclusions: To the best of our knowledge, this is the first case report to emphasize the potential long-term impact of foot sitting on lower extremity musculoskeletal health. Although our patient had multiple contributory issues that may have made her more vulnerable to ankle and foot injuries, this case illustrates the deleterious influence of foot sitting on biomechanics in the ipsilateral lower extremity. It also underscores the need for greater clinical recognition and further research into this common yet underrecognized sitting posture
Induced 0.1 Hz hemodynamic oscillations protect peripheral tissue oxygenation despite no effect on vascular conductance during simulated hemorrhage in humans
No full textBackground: High amplitude 0.1 Hz (~10-s cycle) oscillations in arterial pressure and blood flow are observed in humans with high tolerance to simulated blood loss. We have shown that experimentally induced hemodynamic oscillations (i.e., Pulsatile Perfusion Therapy, PPT) increases tolerance to simulated blood loss and protects tissue oxygenation. Increases in sympathetic activity are associated with a greater amplitude of spontaneous 0.1 Hz blood pressure and blood flow oscillations, but it is not known if induced arterial pressure oscillations at 0.1 Hz can lead to increases in sympathetic activity. Hypothesis: Induced 0.1 Hz oscillations in arterial pressure and blood flow during simulated blood loss increases sympathetic activity, indexed by a decrease in peripheral vascular conductance. Methods: Thirteen healthy humans (8M, 5F; aged 25.9 ± 4.8 y) completed two bouts of -60 mmHg lower body negative pressure (LBNP) for 10-min each, separated by at least 15-min of recovery. In the PPT condition, 0.1 Hz hemodynamic oscillations were induced by inflating and deflating bilateral thigh cuffs every 5-s (10-s cycle) between 0-230 mmHg. During the control condition (CON), the thigh cuffs were inactive throughout the LBNP protocol. The order of conditions was randomized and counterbalanced. Mean arterial pressure (MAP), brachial artery (BA) blood flow (via velocity and vessel cross-sectional area), and forearm muscle tissue oxygenation (SmO₂) were measured continuously. BA conductance was calculated by dividing BA blood flow by MAP. Results: During LBNP, the amplitude of 0.1 Hz oscillations in MAP (CON: 73.5 ± 66.2 mmHg² vs. PPT: 715.0 ± 519.8 mmHg²; p<0.01) and BA blood velocity (CON: 2.7 ± 2.3 (cm/s)² vs. PPT: 25.1 ± 18.4 (cm/s)², p<0.01) were greater with PPT compared with CON. Simulated hemorrhage via LBNP with and without PPT had similar effects on MAP (CON, baseline: 97.9 ± 7.5 mmHg vs. LBNP: 81.1 ± 8.4 mmHg, p<0.01; PPT, baseline: 99.0 ± 9.3 mmHg vs. LBNP: 84.9 ± 10.9 mmHg, p<0.01; Condition Effect: p=0.33), BA blood flow (CON, baseline: 39.2 ± 21.1 ml/min vs. LBNP: 23.0 ± 8.1 ml/min, p<0.01; PPT, baseline: 42.1 ± 23.7 ml/min vs. LBNP: 25.4 ± 12.3 ml/min, p<0.01; Condition Effect: p=0.29), and BA conductance (CON, baseline: 0.41 ± 0.20 ml/min/mmHg vs. LBNP: 0.28 ± 0.08 ml/min/mmHg, p=0.04; PPT, baseline: 0.42 ± 0.24 ml/min/mmHg vs. LBNP: 0.31 ± 0.14 ml/min/mmHg, p=0.04; Condition Effect: p=0.60). However, during LBNP, absolute SmO₂ was greater with PPT compared with CON (CON, baseline: 71.5 ± 6.3 % vs. LBNP: 63.1 ± 6.9%, p<0.01; PPT, baseline: 72.9 ± 7.1 % vs. LBNP: 65.4 ± 7.3%, p<0.01; Condition Effect: p=0.03). Conclusions: These data suggest that PPT does not alter peripheral blood flow or peripheral vascular conductance during simulated hemorrhage in humans, but does protect tissue oxygenation. Analysis of plasma catecholamines is planned from blood samples collected from these participants as a more direct measure of sympathetic activity. These findings add further support for the potential use of 0.1 Hz hemodynamic oscillations as a therapeutic intervention for conditions associated with vital organ ischemia such as hemorrhage, stroke, myocardial infarction, and sepsis
Skin Color Cannot Be Confined to Six Categories: Comparing the Fitzpatrick Scale and Colorimetric Measures
No full textPoster Highlight: Texas College of Osteopathic Medicine - Research, RAD 2025 Award Winning Posters & Oral PresentationsPurpose: The Fitzpatrick Scale (FS), originally developed to dose photochemotherapy in Caucasian skin, has been widely adopted to categorize skin color. It originally included types I-IV, with types V-VI added later for darker skin. Although the FS was designed to assess ultra-violet radiation reactivity, it has increasingly been used as a proxy for objective skin color classification. However, the FS is inherently flawed given its categories are based on a subjective questionnaire. Individual Typology Angle (ITA) is a validated measurement in color science, obtained through objective colorimetry measurements. It presents a promising potential alternative classification of skin color to the Fitzpatrick skin type (FST). Previous studies examining the relationship between these classification systems have been limited by small sample sizes and uneven distribution across skin tones with subjects predominantly having lighter skin tones. This study aims to explore these limitations by investigating the relationship between ITA measurements and Fitzpatrick Skin Types (FST) on a self-reported skin color survey in a cohort including the full spectrum of skin tones. Methods: This study enrolled 440 subjects to evaluate the relationship between subjective skin typing systems and objective colorimetric measurements. Subjects completed a standardized questionnaire encompassing two subjective classification methods: self-reported skin color descriptors (very fair, fair, olive, light brown, dark brown, and very dark) and self-assessed Fitzpatrick skin type (I-VI). Objective colorimetric measurements were obtained using a colorimeter, with measurements taken on the left inner arm to minimize the influence of sun exposure on skin color. Individual Typology Angle (ITA) values were calculated from the colorimetric measurements according to established protocols. Statistical analysis was performed using pairwise comparisons with t-tests and pooled standard deviations to evaluate the relationships between ITA values and both subjective classification systems (p<0.05). Results: Statistical analysis showed that ITA angle was not statistically significant at predicting Fitzpatrick skin type (p=0.3528). As well, ITA angle was not as consistent in its predictability of perceived color descriptions (p=0.615). However, ITA angle showed a stronger association with self-described skin color compared to Fitzpatrick type (p < 2.2e-16). Conclusion: Our results reveal that Individual Typology Angle (ITA) measurements and Fitzpatrick Skin Types (FST) represent distinct and non-equivalent systems for skin categorization. While ITA provided more precise differentiation than FST for self-reported skin color, it still showed limitations in capturing the full nuance of skin tone variation (p<2e-10). FST showed more distinct limitations with no significant differences between adjacent FST categories I-III (p=0.35286). These results may be explained by insufficient categorization options, evident in the limited descriptive terms (fair, olive, dark) commonly used for self-reporting. These categories may not resonate with how individuals perceive and identify their skin tone, as seen by the lack of statistical significance between adjacent self-reported categories (Olive vs. Fair, p=0.381; Very Dark vs. Dark Brown, p=0.615). Our findings show that the FP’s six choices inadequately represent skin color variation; future studies should investigate both objective measurements and a wider range of categories to better serve clinical applications
Predictive value and weight of factors associated with cognitive performance in Hispanics/Latinos enrolled in the Health and Aging Brain Study: Health Disparities
Get PDFINTRODUCTION: In this analysis of cognitively unimpaired (CU) Hispanic participants from the Health and Aging Brain Study: Health Disparities (HABS-HD), we aimed to identify the main predictor factors for cognitive performance and their relative importance (weight). METHODS: The HABS-HD is a community-based longitudinal cohort study. Data from 952 CU Hispanics, enrolled from 2017 to February 2024, were analyzed. Random forest, an assembly learning method based on decision trees, was used to cross-sectionally forecast the predictive value of 42 risk factors (4 demographic variables, 4 socioeconomic variables, 6 psychosocial variables, 17 health variables, and 11 plasma and magnetic resonance imaging biomarkers) together, and the weighting of each factor for different cognitive domains (global cognition, memory, language, executive function, attention, and processing speed). RESULTS: Participants included in the analyses had a mean age of 61.3 years (9.14), 69.4% were female, and had a mean of 10.52 (4.61) years of education. Income, glucose levels, plasma amyloid beta (Abeta)42, total tau, and neurofilament light chain were in the top 10 predictors in six cognitive domains. Age, education years, Penn State Worry Questionnaire, body mass index, and C-reactive protein were the main predictors in four cognitive domains, while plasma Abeta40 was in the top 10 list for five cognitive domains. DISCUSSION: Results support the notion that cognitive performance depends on interactions among social, economic, biological, and functional factors. The effects of factors together, and the weight of each factor in various cognitive domains may be different in Hispanics. More studies comparing different ethnic groups are necessary to help in the development of tailored interventions to prevent cognitive decline. HIGHLIGHTS: Numerous factors have been associated with cognitive decline and dementia.Research on these factors has relied on a meta-analysis of their individual association with cognition, consolidating data from different non-Hispanic White populations.Hispanics are the largest minority group in the United States, and only a few studies have analyzed the overall impact of these factors together, and their individual relative effect in different cognitive domains.We found that cognitive performance in Hispanics may be a result of interactions among social, economic, biological, and functional factors.National Institute on Aging, Grant/AwardNumbers: RO1AG054073, RO1AG058533,P41EB015922, U19AG0781
Orthopedic Surgery Environmental Sustainability Recommendations: A Literature Review
No full textPurpose: This review aims to examine waste management practices in orthopedic surgery, evaluate their environmental impacts, and explore evidence-based recommendations to reduce waste while maintaining high-quality healthcare services. Climate change has become an increasingly pressing issue in the healthcare field, with surgery being a significant contributor to the vast amount of waste produced. Orthopedic surgeries, in particular, generate considerable waste through the extensive use of single-use plastics and the substantial energy required for cleaning and sterilizing instruments. The primary challenge lies in reducing plastic waste and energy consumption without compromising patient care or safety. Identifying and implementing effective solutions could significantly benefit the environment while supporting sustainable healthcare practices. Methods: A literature review was conducted to identify and analyze studies that explore the environmental impacts of waste generated in orthopedic surgery. This review focused on evidence-based methods aimed at reducing waste in operating rooms and critical care settings, with an emphasis on maintaining healthcare quality. Results: The findings of the review highlighted that orthopedic surgery significantly contributes to environmental waste due to high material utilization and energy consumption. Operating rooms and critical care management were identified as major contributors to environmental pollutants, which lead to public health concerns through air contamination. Recent studies have tried various strategies to reduce waste, such as optimizing resource usage, implementing recycling programs, and adopting energy-efficient practices, all of which have shown promising outcomes for improving environmental sustainability in orthopedic care. Conclusion: In conclusion, orthopedic surgery has a substantial environmental footprint, which necessitates a critical review of waste management practices. Evidence-based recommendations to reduce waste, as identified in the literature, provide viable pathways to mitigate environmental impacts while maintaining healthcare quality. Implementing these strategies can address public health concerns and contribute to the global effort to combat climate change