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A Case Study Analyzing PALYNZIQ (pegvvaliase) Use in Phenylketonuria Patients During Pregnancy
No full textThe purpose of this case study is to determine the efficacy and safety of pegvaliase therapy for PKU patients during pregnancy. For my thesis, I hypothesized that PALYNZIQ® (pegvaliase) would be safe for use in maternal PKU cases and facilitate Phe level control to decrease the risk of congenital abnormalities in maternal PKU cases. This retrospective case study collected de-identified data from UT Southwestern Medical Center patient medical records who had a diagnosis of PKU and remained on pegvaliase therapy throughout their pregnancy. Fetal outcomes of the cases included in this study were compared with those of uncontrolled maternal PKU cases. Additionally, the correlation between Phe levels and pegvaliase dose changes throughout the pregnancies was assessed. Finally, the trimester Phe and Tyr level averages of this study were compared to population averages in healthy pregnancies. Results showed decreased frequencies of spontaneous abortion, microcephaly, and CHD. No statistical correlation was identified between Phe level and pegvaliase dose. Trimester averages of Phe and Tyr levels were comparable to healthy populations. In conclusion, pegvaliase proved an effective and safe treatment for managing PKU patients during pregnancy in the cases treated at UT Southwestern Medical Center
Factors associated with COVID-19-related mental health among Asian Indians in the United States
No full textBACKGROUND: In the United States, the COVID-19 pandemic has caused increased mental health symptoms and mental illness. Specific subgroups such as Asian Indians in the US have also been subject to additional stressors due to unprecedented loss of lives in their home country and increased Asian hate due to the misperception that Asians are to be blamed for the spread of the SARS-CoV-2. OBJECTIVE: We examined the various factors including discrimination associated with COVID-19-related mental health symptoms among Asian Indians. METHODS: We administered an online survey between May 2021 and July 2021 using convenient and snowball sampling methods to recruit Asian Indian adults (age > 18 years, N = 289). The survey included questions on mental health and the experience with unfair treatment in day-to-day life. Descriptive analysis and logistic regressions were performed. RESULTS: Overall, 46.0% reported feeling down, depressed, or lonely and feeling nervous, tense, or worried due to the COVID-19 pandemic; 90.0% had received at least one dose of vaccination and 74.7% reported some form of discrimination. In the fully-adjusted logistic regression, age (AOR = 0.95; 95%CI- 0.92, 0.97;p < 0.01) and general health (AOR=0.84; 95%CI- 0.73, 0.97; p < 0.015) were negatively associated with mental health symptoms. Participants who experienced discrimination were more likely (AOR=1.26; 95%CI- 1.08, 1.46; p < 0.01) to report mental health symptoms. CONCLUSION: In this highly vaccinated group of Asian Indians discriminatory behaviors were associated with mental health symptoms suggesting the need for novel institutional level policy responses to reduce anti-Asian racism.This research was, in part, funded by the National Institutes of Health NIH/1OT2HL158258- Texas CEAL Alliance (Usha Sambamoorthi, Jamboor K Vishwanatha), and the National Institute on Minority Health and Health Disparities through the Texas Center for Health Disparities (NIMHD), 5U54MD006882 (Usha Sambamoorthi, Jamboor K Vishwanatha). The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the NIH
Combination of Small Extracellular Vesicle-Derived Annexin A2 Protein and mRNA as a Potential Predictive Biomarker for Chemotherapy Responsiveness in Aggressive Triple-Negative Breast Cancer
No full textSmall extracellular vesicles (sEVs), mainly exosomes, are nanovesicles that shed from the membrane as intraluminal vesicles of the multivesicular bodies, serve as vehicles that carry cargo influential in modulating the tumor microenvironment for the multi-step process of cancer metastasis. Annexin A2 (AnxA2), a calcium(Ca(2+))-dependent phospholipid-binding protein, is among sEV cargoes. sEV-derived AnxA2 (sEV-AnxA2) protein is involved in the process of metastasis in triple-negative breast cancer (TNBC). The objective of the current study is to determine whether sEV-AnxA2 protein and/or mRNA could be a useful biomarkers to predict the responsiveness of chemotherapy in TNBC. Removal of Immunoglobulin G (IgG) from the serum as well as using the System Bioscience's ExoQuick Ultra kit resulted in efficient sEV isolation and detection of sEV-AnxA2 protein and mRNA compared to the ultracentrifugation method. The standardized method was applied to the twenty TNBC patient sera for sEV isolation. High levels of sEV-AnxA2 protein and/or mRNA were associated with stage 3 and above in TNBC. Four patients who responded to neoadjuvant chemotherapy had high expression of AnxA2 protein and/or mRNA in sEVs, while other four who did not respond to chemotherapy had low levels of AnxA2 protein and mRNA in sEVs. Our data suggest that the sEV-AnxA2 protein and mRNA could be a combined predictive biomarker for responsiveness to chemotherapy in aggressive TNBC.This work was supported by awards from the National Institute of Health under awards R01CA220273 and S21MD012472 to Dr. Jamboor K. Vishwanatha. The Cryo-EM study was performed in collaboration with the Structural Biology Laboratory and the Cryo-Electron Microscopy Facility at UT Southwestern Medical Center, partially supported by grant RP170644 from the Cancer Prevention & Research Institute of Texas (CPRIT) for Cryo-EM studies
An Analysis of Student Satisfaction with Active Learning Techniques in an Online Graduate Anatomy Course: Consideration of Demographics and Previous Course Enrollment
No full textPurpose: Online learning has become an essential part of mainstream higher education, allowing greater access for students. With the increase in online course enrollment, specifically that of anatomy, understanding online teaching best practices is critical. Active learning has previously shown many benefits in face-to-face anatomy courses, including increases in student satisfaction. Currently, no research has measured the satisfaction of several active learning techniques implemented in an asynchronous, online graduate anatomy course. Methods: This study compared the student satisfaction achieved by four active learning techniques with consideration of demographics and previous course enrollment. Survey questions consisted of multiple-choice and Likert-style that asked students to indicate their level of satisfaction with the active learning techniques. One hundred seventy (170) students completed the online anatomy course and surveys. Results: Students were more satisfied with question constructing and jigsaw than with concept mapping and team-learning module. Additionally, historically excluded student groups (underrepresented racial minorities) were more satisfied with active learning than White students. Age, gender, previous anatomy experience and/or online course experience did not influence the satisfaction of the active learning techniques. However, students with higher GPAs and those who had no graduate degree were more satisfied with the active learning techniques than students who had lower GPAs and those with a graduate degree. Conclusion: These findings provide evidence that students enrolled in an online graduate anatomy course were satisfied with the active learning techniques, dependent on the specific technique, demographics, and previous course enrollment. Results provide anatomy educators with a better understanding of which techniques work best in an online anatomy course. Currently, there is a lack of research comparing active learning techniques in an online learning environment. These findings provide online anatomy educators with evidence that active learning techniques improve satisfaction, with consideration of student demographics and previous course enrollment.American Association for Anatomist
ystematic Review of Focus Group Discussions & Mixed Method Surveys Regarding Colorectal Cancer Screening
No full textBackground:
Colorectal cancer (CRC) screening has a significant potential to decrease mortality from CRC. Many published studies have used either focus groups or structured interviews to identify barriers and facilitators of CRC. However, a systematic review of methods and findings from focus groups is lacking.
Objective:
The objective of this study was to conduct a systematic literature review that describes the characteristics of focus group participants and synthesize major themes of CRC screening barriers and facilitators. A secondary objective was to identify the impact of barriers related to social determinants of health (SDoH) factors.
Methods:
A systematic review of qualitative studies was conducted on CRC screening focus groups following ENTREQ guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). Our inclusion criteria were as follows: (1) empirical scientific studies with a qualitative focus group or mixed methods study design; (2) that have been published in a peer-reviewed journal; (3) from January 1, 2012, and August 12, 2022; (4) in English; (5) exploring the attitudes, beliefs and behaviors related to adults and colon cancer screening; (6) face-to-face and online format. Keyword searches were conducted in the electronic databases PubMed and SCOPUS. After review, 31 studies contributing to our research questions were found eligible for inclusion.
Results:
Findings revealed that the number of participants per focus group (where reported) ranged from 2 to 23 participants with a median of 6 participants. There was a range of 20 to 232 total focus group participants per study while the mixed method studies ranged from 25 to 492. Most of the studies utilized education, income level, and access to healthcare as social determinants of health factors. The most commonly reported SDoH variable noted as a barrier to CRC screening was the lack of recommendation or education of a screening by their healthcare provider (15 of 31, 48%) with embarrassment or disgust regarding the procedure as a secondary barrier (11 of 31, 35%).
Conclusions:
Main themes for barriers and facilitators that emerged from the review were insurance status and awareness of the benefits of screening. Commonly reported concerns for barriers were embarrassment or disgust regarding the procedure and lack of trust in their provider relationship. Previous awareness of this disease through family history was a common facilitator. Opportunities to increase CRC screening arise in ensuring education and access to alternatives that provoke less embarrassment, such as FIT or FOBT tests.
Sponsorship:
Non
Machine Learning Based Classification of CRISPR-Cas Proteins Using Complete Protein Spectrum
No full textPurpose: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and its associated (Cas) proteins together form the CRISPR-Cas system. The CRISPR-Cas system typically forms the machinery for innate defense mechanism in prokaryotes against foreign genetic elements such as phages and plasmids. The recent development of this mechanism into a gene editing technology holds a promise to correct gene level defects for several genetic diseases. The key element of CRISPR-Cas system is the Cas protein that are nucleases and possess the ability to edit gene of interest. Different types of Cas proteins are involved in different CRISPR-Cas systems. Cas proteins however suffer from inherent limitations like specificity and off-target effects which limits its widespread application as a gene editing tool. In the current study, a novel method has been developed for classifying the Cas9 and Cas12 families. Existing classification tools have a low overall accuracy and are usually built using only a few types of protein features. We also attempt to understand the different protein features governing the Cas9 and Cas12 classes using a multitude of protein features. Method: We built Random Forest (RF) binary classifiers to classify Cas12 and Cas9 proteins respectively using the complete spectrum of protein features (13,495 features) encoding the physiochemical, constitutional, and evolutionary information. Additionally, we also built multiclass RF classifiers that differentiates between Cas9, Cas12 and non-Cas proteins. The performance of all models was evaluated using a 5-fold cross validation and six evaluation metrices like accuracy, precision, recall, F1-score, AUC score and specificity. We also tested our models on the respective independent datasets that were developed in-house from various public domain databases. Results: The Cas12 and Cas9 models achieved a high overall accuracy of 0.97 and 0.96 on their independent datasets respectively while the multiclass classifier achieved a high F1 score of 1.0. We observed that amino acid composition, Qasi-sequence-order and Composition-based protein features are particularly important for the Cas12 and Cas9 family of proteins. Conclusions: We successfully built the classification models for Cas12 and Cas9 protein families and identified the protein features that are unique to each family, which enhance the understanding of the structure and functions of Cas9 and Cas12 proteins and also provide valuable insights into plausible structural modifications in these proteins to achieve enhanced specificity and reduced off-target effects
Analysis of Key Cellular Changes of Triple Negative Breast Cancer Cells in Response to Kinase-Inhibiting BI2536 and Associated Derivatives
No full textPurpose: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer that grows quickly and has higher rates of metastasis and reoccurrence relative to other Breast Cancer subtypes that make it, in general, a much more dangerous subtype of breast cancer. The Kinase Chemogenomic Set (KCGS) is a collection of 187 kinase-inhibiting compounds with broad activity across 215 different kinases. We hypothesize that this plate contains compounds with the potential to inhibit TNBC and that exploring the transcriptomic and proteomic changes in TNBC cells may give insights into novel treatment targets. Methods: To test this hypothesis, we have utilized two main cell lines, the MDA-MB-231 line and a patient-derived xenograft line, the TuX-BxC-4IC cell line. Measurements have been taken at various time points up until 72 hours at various concentrations of a compound of interest, BI2536, between 1nM and 1uM. Primarily, data will be collected using qRT-PCR to gain insight into the transcriptomic changes during the potential EMT changes. Additionally, various other experiments related to migration, staining, and other essential markers will be conducted on the compound of interest and derivatives of the compound. Results: Initial results and prior work indicate that the compound of interest has moderate success in slowing cancer cell growth. Additionally, initial findings indicate that the compound may succeed in halting and potentially even reversing the EMT process. Conclusion: With this primary data set, we believe that the kinases targeted by the compound may hold potential key targets for the treatment of TNBC
Interactive Influence of Climate and Energetics on Human Nasal Morphology
No full textFor more than a century, studies have demonstrated strong statistical associations between climate and modern human nasal morphology, showing that populations indigenous to colder-drier environments exhibit relatively narrower nasal apertures, more projecting nasal bones, and taller/longer/narrower nasal cavities than those from warmer-humid environments. This ecogeographic patterning of nasal morphology has historically been attributed to pressures for intranasal air-conditioning (i.e., heat and moisture transfer) in different climatic conditions. However, recent studies suggest that energetic requirements also represent an important selection pressure on nasal morphology, with greater metabolic demands for oxygen intake necessitating larger nasal passages in order to respire more air with each breath. This theoretical precept has consequently been deemed the "respiratory-energetics hypothesis." Yet, despite substantial evidence that both climatic pressures and metabolic demands likely influence nasal anatomy, virtually no research has investigated the interaction and possible trade-offs of both factors on nasal size and shape. Thus, this dissertation has three objectives, 1) test the respiratory-energetics hypothesis in a mixed-sex sample from a circumscribed geographic locale (i.e., holding climate constant), 2) test the applicability of the respiratory-energetics hypothesis across ecogeographically diverse populations, and 3) investigate the influence of metabolic demands on ecogeographic variation in the nasal index. A total of 232 cranial computed tomography (CT) scans of modern human skeletons from a wide range of climatic regimes were employed in this study. Linear measurements and three-dimensional coordinate landmarks were collected from the nasal skeletons of each individual along with basal metabolic rate (BMR, kcal/day) estimates derived from associated postcranial elements. Multivariate analyses were then performed to complete each of the three objectives. This study found the basic tenets of the respiratory-energetics hypothesis to be supported both across and within modern human populations, with higher BMRs associated with larger nasal passages. Further, this study found that metabolically-mediated variation in passage size is predominantly driven by nasal passage heights and lengths, while breadths appear differentially constrained by climatic pressures
Hemodynamic Responses to Oscillatory Thigh Cuff Inflations
No full textBackground. In the clinical setting, individuals have varying tolerance to hypovolemia induced by blood loss. Experimental generation of 0.1 Hz oscillations (~10-s cycle) in arterial pressure and cerebral blood flow via oscillatory lower body negative pressure (OLBNP) increases tolerance to this simulated hemorrhage, and protects cerebral tissue oxygenation. However, use of OLBNP as a method of inducing hemodynamic oscillations in the clinical setting is limited as: 1) it is a large and cumbersome technique, and; 2) it induces central hypovolemia, which would only worsen the magnitude of hemorrhage. In this study we evaluated a more clinically applicable method of inducing 0.1 Hz oscillations in arterial pressure and cerebral blood flow, using intermittent inflation of bilateral thigh cuffs. We hypothesized that the amplitude of arterial pressure and cerebral blood flow oscillations at 0.1 Hz would increase in response to repeated thigh cuff inflations at 0.1 Hz when compared with a baseline control condition. Methods. Ten healthy human subjects were tested (6 male, 4 female; 26.8 ± 4.1 y). Middle cerebral artery velocity (MCAv) was measured via transcranial doppler ultrasound, arterial pressure was measured via finger photoplethysmography, and end tidal CO2 (etCO2) was measured via capnography. Following a 10-min baseline period, intermittent thigh cuff inflations at 0.1 Hz and 230 mmHg (5-s inflation, 5-s deflation) were performed for 10-min ("oscillations”). 0.1 Hz oscillatory amplitude of mean arterial pressure and mean MCAv were quantified using Fast Fourier transformation during the last 5-min of baseline and the oscillatory period, and compared via two-tailed paired t-tests. Results. The amplitude of 0.1 Hz oscillations increased during the oscillatory period vs. baseline for mean arterial pressure (baseline: 1.7 ± 1.0 mmHg2 vs. oscillations: 9.0 ± 6.2 mmHg2; P = 0.004) and mean MCAv (baseline: 1.1 ± 0.6 (cm/s)2 vs. oscillations: 3.4 ± 3.1 (cm/s)2; P = 0.04). Absolute mean arterial pressure was similar between baseline and the oscillatory period (baseline: 97.2 ± 8.1 mmHg vs. oscillations: 99.1 ± 15.0 mmHg; P = 0.54), but absolute mean MCAv was lower during the oscillatory period (baseline: 61.7 ± 14.6 cm/s vs. oscillations: 53.2 ± 13.1 cm/s; P = 0.02). This reduction in mean MCAv was most likely due to hypocapnia (indexed by etCO2) induced by pacing the breathing of all subjects at ≥10 breaths/min (baseline: 33.2 ± 4.8 mmHg vs. oscillations 27.2 ± 4.5 mmHg; P = 0.005). Conclusions. Intermittent thigh cuff inflations at 0.1 Hz induced 0.1 Hz oscillations in both arterial pressure and cerebral blood flow when compared to baseline. These findings indicate that intermittent thigh cuff inflations could be developed as a method to induce pulsatile perfusion as a potential new therapy for individuals experiencing major blood loss.American Heart Association #19TPA34910073; UNTHSC 2021 Physiology and Anatomy Seed Gran
Inadequate Administration of Post-Intubation Sedation and Analgesia in the Pediatric Emergency Department (PED)
No full textPurpose:
Previous adult studies demonstrate patients in emergency departments (ED) often do not receive subsequent sedative or analgesic medications within the intubation medication’s duration of action (DOA). These patients can experience pain or remember events while still being under the effects of the paralytic medication. Inadequate sedation following intubation increases rates of adverse events. The purpose of this project was to evaluate if pediatric patients intubated in the Cook Children’s Medical Center ED (CCMC ED) are administered timely post-intubation sedation and analgesia.
Methods:
Chart review was performed for patients intubated in the CCMC ED between June and December 2021. Exclusion criteria included intubation at another facility and charts with incomplete data. Data were collected for medications administered, time of medication administration, and intubation time.
Results:
There were 106 patients intubated in the CCMC ED meeting inclusion criteria. Following intubation, 17 (16%) patients were provided with a sedative or analgesic within the DOA of the sedative or analgesic used for induction, while the remaining 89 (84%) were inadequately medicated. Thirty-one patients (29%) did receive a sedative or analgesic following intubation but not within the DOA of the initial agent. The remaining 58 (55%) patients were inadequately medicated due to a lack of medication administration before intubation, following intubation, or both.
Conclusions:
The majority of intubations in the CCMC ED were not adequately medicated with sedatives and/or analgesics after intubation. Thus, these patients were at risk of suboptimal levels of sedation while paralyzed following intubation. Given the adverse effects of inadequate sedation seen in previous studies, timely administration of further sedation and analgesia after intubation may lead to decreased adverse events. Quality improvement interventions are being implemented in the CCMC ED to improve post-intubation sedation and analgesia administration