Digital Commons Network^™

Opportunities And Challenges In Developing A Cryptosporidium Controlled Human Infection Model For Testing Antiparasitic Agents, Rajiv S Jumani, Johanne Blais, Hanns-Christian Tillmann, Florencia Segal, Dean Wetty, Christian Ostermeier, Natko Nuber, Jay Lakshman, Natasha Aziz, Richa Chandra, Wilbur H Chen, Cynthia L Chappell, Thierry T Diagana, Ujjini H Manjunatha

Faculty, Staff and Student Publications

Cryptosporidiosis is a leading cause of moderate-to-severe diarrhea in low- and middle-income countries, responsible for high mortality in children younger than two years of age, and it is also strongly associated with childhood malnutrition and growth stunting. There is no vaccine for cryptosporidiosis and existing therapeutic options are suboptimal to prevent morbidity and mortality in young children. Recently, novel therapeutic agents have been discovered through high-throughput phenotypic and target-based screening strategies, repurposing malaria hits, etc., and these agents have a promising preclinical in vitro and in vivo anti-

A Neural Basis For Brain Leptin Action On Reducing Type 1 Diabetic Hyperglycemia, Shengjie Fan, Yuanzhong Xu, Yungang Lu, Zhiying Jiang, Hongli Li, Jessie C Morrill, Jing Cai, Qi Wu, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Cheng Huang, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepRArc) are selectively activated in T1D. Activation of LepRArc neurons, Arc GABAergic (GABAArc) neurons, or arcuate AgRP neurons, is able to reverse the leptin’s rescuing effect. Conversely, inhibition of GABAArc neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin’s rescuing effects. Finally, T1D LepRArc neurons show defective nutrient sensing and signs of cellular energy deprivation, which are …

Consumption Of High-Fructose Corn Syrup Compared With Sucrose Promotes Adiposity And Increased Triglyceridemia But Comparable Nafld Severity In Juvenile Iberian Pigs, Magdalena Maj, Brooke Harbottle, Payton A Thomas, Gabriella V Hernandez, Victoria A Smith, Mark S Edwards, Rob K Fanter, Hunter S Glanz, Chad Immoos, Douglas G Burrin, Tasha M Santiago-Rodriguez, Michael R La Frano, Rodrigo Manjarín

Children’s Nutrition Research Center Staff Publications

Background: Fructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated.

Objectives: We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity.

Methods: Iberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = …

Associations Of Perceived Overall Health, Psychological Distress, Functional Impairment, And Alcohol Use Among Older Adults Of Sexual Minority Status And Heterosexual Peers, Carolyn Tran

Dissertations and Theses (Open Access)

Background: Lesbian, gay, and bisexual (LGB) adults, 50 and older, are likely to have experienced mistreatment and discrimination, contributing to poor physical and mental health and risky behaviors, such as alcohol misuse. Few studies have examined the relationships between perceived health, psychological distress, functional impairment, and alcohol use of older LGB adults and heterosexuals.

Specific Aims: The specific aims were: (1) to determine if perceived overall health status is associated with psychological distress and functional impairment in sexual minority older adults compared to heterosexual older adults, and (2) to determine if sexual minority status moderates the relationship between psychological distress …

Invasive Therapies For Acute Coronary Syndromes In The Covid-19 Era, Sanket Borgaonkar, Joshua Hahn, Marilyne Daher, Waleed Kayani, Hani Jneid

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: To identify and address the challenges associated with the care of ACS patients during the coronavirus 2019 pandemic.

RECENT FINDINGS: The COVID-19 pandemic has had a considerable global impact with over 2.0 million deaths worldwide so far. There has been considerable evidence suggesting that COVID-19 increases the risk of acute coronary syndromes (ACS). We propose characterizing ACS patients into 3 distinct categories to better assist in appropriate triage and management: critically ill patients, non-critically ill ST elevation myocardial infarction (STEMI) patients, and non-critically ill non-ST elevation myocardial infarction (NSTEMI)/unstable angina (UA) patients. We thoroughly review treatments strategies, …

The Contribution Of Age-Related Changes In The Gut-Brain Axis To Neurological Disorders, M Kareem Shaath, Stephen J Warner, James F Kellam, Timothy S Achor

Faculty, Staff and Student Publications

INTRODUCTION: In 2018, orthopaedic trauma had the lowest match rate among orthopaedic subspecialties. The purpose of this study was to determine the importance of factors evaluated by orthopaedic trauma fellowship directors when ranking applicants after the interview.

METHODS: An electronic survey was submitted to fellowship directors and consisted of 16 factors included in a fellowship application. Respondents were asked to rate the importance of these factors for applicants they interviewed on a 1 to 5 Likert scale, with 1 being not at all important and 5 being critical.

RESULTS: Thirty-seven fellowship directors responded (63.8%). The highest-rated factor was the applicant …

Identifying And Predicting Food Parenting Practice Profiles Among Canadian Parents, Claire N Tugault-Lafleur, Olivia De-Jongh González, Teresia M O'Connor, Sheryl O Hughes, Louise C Mâsse

Children’s Nutrition Research Center Staff Publications

Background: Food parenting practices (FPP) can affect children's eating behaviours, yet little is known about how various FPP co-occur. The primary aim was to identify profiles of FPPs use among Canadian parents. Secondary aims included examining sociodemographic correlates of FPP profiles and evaluating whether children's eating behaviours differed across FPP profiles.

Methods: Parents (n = 799) of 5-12-year-old children completed a validated FPP Item Bank and the Children's Eating Behaviour Questionnaire. Latent Class Analysis (LCA) was used to identify distinct FPP profiles. Regression analyses were used to explore associations between FPP profiles, sociodemographic variables (race, sex and education) and children's …

Feasibility Of The Use Of A Stereoscopic Camera In The Final Inclusion (Sci-Fi) Of Donor Organ Assessment Using Virtual Reality Technology, Ismael A. Salas De Armas, Juan E. Marcano, Jayeshkumar A. Patel, Mehmet H. Akay, Manish K. Patel, Bindu Akkanti, Marwan F. Jumean, Sachin Kumar, Rajko Radovancevic, Sriram Nathan, Biswajit Kar, Igor D. Gregoric

The VAD Journal

Objective: Donor organ assessment is challenging, particularly when physicians and surgeons have to make decisions remotely. To improve communication and preparation for the transplant process, we proposed that a versatile, secure, and transportable video presence would enable a detailed assessment of donor organs.

Methods: A virtual reality camera with a 360-degree visualization range was used with a smartphone receiver to enable integral assessment of the donor's heart in the operating room, with visualization of the organs in real time. Prospective, observational data was collected in two cases in this proof-of-concept study. An assessment physician evaluated the donor heart remotely, and …

Removal Of Impella In The Setting Of Left Ventricular Thrombus: A Potential Indication For Cerebral Embolic Protection Devices, Miro Asadourian, Avinash Sharma, Richard Kiel, Felice Lin, Manminder Bhullar

The VAD Journal

Successful percutaneous mechanical circulatory support (MCS) has been used for acute stabilization of cardiogenic shock (CS). Improved survival outcomes have been observed in patients with CS from an acute myocardial infarction (AMI) who undergo implantation of left ventricular (LV) to ascending aorta rotodynamic pumps, such as the Impella® device (Abiomed). However, thrombotic events are a known complication of such devices in poor flow states such as CS. There is limited evidence regarding the management of patients who develop an LV thrombus after Impella insertion. Currently, the Sentinel cerebral protection system (SCPS, Boston Scientific) is the only FDA-approved device for cerebral …

Protecting Sanitation Workers In Low-Middle Income Countries Amid Covid-19, Muhammad Mainuddin Patwary, Md Riad Hossain, Faysal Kabir Shuvo, Sadia Ashraf, Rabeya Sultana, Md Ashraful Alam

Faculty, Staff and Student Publications

No abstract provided.

Ms 202 Guide To The Richard E. Wainerdi, Ph.D Papers (1984-2013), Richard E. Wainerdi (1931-2021)

Manuscript Finding Aids

This collection consists of the administrative records and other materials of Dr. Richard Wainerdi who was president of the Texas Medical Center, 1984-2012. See more at MS 202.

Jove – Journal Of Visualized Experiments, Joanne Romano

TMC Library Newsletter (2015-)

JoVE – the Journal of Visualized Experiments – is a scientific video database that provides peer-reviewed, multidisciplinary protocols of laboratory experiments and techniques. Indexed in PubMed and Web of Science, JoVE also contains very basic and introductory education videos, suitable for students just learning their way around the lab, and graduates who need a refresher course in lab protocols.

A Novel Role For Dyrk1a In Kidney Development, Alexandria Blackburn

Dissertations and Theses (Open Access)

Congenital anomalies of the kidney and urinary tract (CAKUT) are a leading cause of pediatric kidney failure and encompass a wide range of structural malformations resulting from defects in morphogenesis. CAKUT occur in ∼1/500 live births and with an average wait time of 3-5 years for a kidney transplant, the need is high for the development of new strategies aimed at reducing the incidence of CAKUT and preserving renal function. Approximately 14% of CAKUT cases have a known genetic component. This low causality suggests that CAKUT is complex and that there are underlying genes and mechanisms which lead to CAKUT …

Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede

Dissertations and Theses (Open Access)

Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. Core essential genes are absolutely required for growth and proliferation in every cell type. On the other hand, context-dependent essential genes become essential in an environmental or genetic context. The concept of context-dependent gene essentiality is particularly important in cancer, since killing cancer cells selectively without harming surrounding healthy tissue remains a major challenge. The toxicity of …

Discovery Of Novel Ubiquitin- And Methylation-Dependent Interactions Using Protein Domain Microarrays, Jianji Chen

Dissertations and Theses (Open Access)

Post-translational modifications (PTMs) drive signal transduction by interacting with "reader" proteins. Protein domain microarray is a high throughput platform to identify novel readers for PTMs. In this dissertation, I applied two protein domain microarrays identifying novel readers for histone H2Aub1 and H2Bub1, and H3TM K4me3. Ubiquitinations of histone H2A at K119 (H2Aub1) and histone H2B at K120 (H2Bub1) function in distinct transcription regulation and DNA damage repair pathways, likely mediated by specific "reader" proteins. There are only two H2Aub1-specific readers identified and no known H2Bub1-specific readers. Using a ubiquitin-binding domain microarray, I discovered the phospholipase A2-activating protein (PLAA) PFU domain …

Breast Cancer Risk For Female Relatives Of Male Breast Cancer Patients With Negative Brca1/2 Testing, Emily Martin

Dissertations and Theses (Open Access)

Risk models exist to estimate a female’s lifetime risk of breast cancer in the absence of a hereditary predisposition to cancer, namely Hereditary Breast and Ovarian Cancer syndrome. These risk models consider various factors such as reproductive history and family history, but few models take a family history of male breast cancer into account. This study aims to evaluate if prevalence of breast cancer among female relatives is higher when there is a family history of male breast cancer in the context of uninformative BRCA1 and BRCA2 testing. This information may aid in the process of risk assessments for patients …

Assessing Genetic Counselors' Clinical Approach And Practices Regarding Pathogenic/Likely Pathogenic Variant Downgrades, Grant Bonesteele

Dissertations and Theses (Open Access)

Although rare, variant downgrades from a pathogenic/likely pathogenic (P/LP) variant to a variant of uncertain significance can have a significant impact on patients and their families in the clinical cancer setting. However, there is a lack of literature about how to approach these potentially challenging cases as a genetic counselor. Therefore, we aimed to characterize genetic counselors’ experiences, approach, and practices to variant downgrade cases using an online survey. The survey asked participants how they would approach variant downgrade scenarios involving the CDH1 or ATM genes with variable family histories. Genetic counselors appear to be united in whether they would …

Enabling Precision Medicine In Cancer Care Through A Molecular Data Warehouse: The Moffitt Experience, Steven A Eschrich, Jamie K Teer, Phillip Reisman, Erin Siegel, Chandan Challa, Patricia Lewis, Katherine Fellows, Everin Malpica, Rodrigo Carvajal, Guillermo Gonzalez, Scott Cukras, Miguel Betin-Montes, Garrick Aden-Buie, Melissa Avedon, Daniel Manning, Aik Choon Tan, Brooke L Fridley, Travis Gerke, Mattias Van Looveren, Amilcar Blake, Jennifer Greenman, Dana E Rollison

Faculty, Staff and Students Publications

PURPOSE: The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose. Effective storage, query, retrieval, and visualization of these data are essential to create an infrastructure to enable new discoveries in cancer research.

METHODS: Moffitt Cancer Center implemented a molecular data warehouse to complement the extensive enterprise clinical data warehouse …

Genetics Of Atrial Fibrillation, Jitae A Kim, Mihail G Chelu, Na Li

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Atrial fibrillation is the most common sustained cardiac arrhythmia. In addition to traditional risk factors, it is increasingly recognized that a genetic component underlies atrial fibrillation development. This review aims to provide an overview of the genetic cause of atrial fibrillation and clinical applications, with a focus on recent developments.

RECENT FINDINGS: Genome-wide association studies have now identified around 140 genetic loci associated with atrial fibrillation. Studies into the effects of several loci and their tentative gene targets have identified novel pathways associated with atrial fibrillation development. However, further validations of causality are still needed for many …

Genetic Pathway Analysis Of Abnormal Facial Development In Nonsyndromic Cleft Lip And Palate, Lorena Maili

Dissertations and Theses (Open Access)

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is the most common craniofacial birth defect resulting from incomplete fusion of the facial prominences during development, which leaves a gap in the lip, primary palate and/or the secondary palate. NSCLP affects 135,000 NSCLP newborns worldwide each year based on a birth prevalence of 1 per 700 live births. While surgical treatments have dramatically improved, many long-term health issues persist, imposing significant medical, psychosocial and economic burdens. Familial aggregation and segregation analyses suggest genetic contributions underlie NSCLP, but despite decades of study, only a small portion of the NSCLP genetic liability …

Investigating Mechanisms In Nociceptors Driving Ongoing Activity And Ongoing Pain, Elia Lopez

Dissertations and Theses (Open Access)

Ongoing (apparently spontaneous) pain at rest is a major complaint of patients suffering from many forms of acute and chronic pain, including acute and persistent postsurgical pain. Accumulating evidence suggests ongoing activity in nociceptors is a major driver of ongoing pain. Ongoing activity can be generated in sensory neurons in the absence of sensory generator potentials if one or more of three neurophysiological alterations occur – prolonged depolarization of resting membrane potential (RMP), hyperpolarization of action potential (AP) threshold, and/or increased amplitude of depolarizing spontaneous fluctuations of membrane potential (DSFs) to bridge the gap between RMP and AP threshold. Cellular …

N-3 Fatty Acid Biomarkers And Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project Of 20 Prospective Cohort Studies, Frank Qian, Andres V Ardisson Korat, Fumiaki Imamura, Matti Marklund, Nathan Tintle, Jyrki K Virtanen, Xia Zhou, Julie K Bassett, Heidi Lai, Yoichiro Hirakawa, Kuo-Liong Chien, Alexis C Wood, Maria Lankinen, Rachel A Murphy, Cecilia Samieri, Kamalita Pertiwi, Vanessa D De Mello, Weihua Guan, Nita G Forouhi, Nick Wareham, Interact Consortium Frank B Hu, Ulf Riserus, Lars Lind, William S Harris, Aladdin H Shadyab, Jennifer G Robinson, Lyn M Steffen, Allison Hodge, Graham G Giles, Toshiharu Ninomiya, Matti Uusitupa, Jaakko Tuomilehto, Jaana Lindström, Markku Laakso, David S Siscovick, Catherine Helmer, Johanna M Geleijnse, Jason H Y Wu, Amanda Fretts, Rozenn N Lemaitre, Renata Micha, Dariush Mozaffarian, Qi Sun

Children’s Nutrition Research Center Staff Publications

Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

Research design and methods: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed …

A Hindbrain Dopaminergic Neural Circuit Prevents Weight Gain By Reinforcing Food Satiation, Yong Han, Guobin Xia, Yanlin He, Yang He, Monica Farias, Yong Xu, Qi Wu

Children’s Nutrition Research Center Staff Publications

The neural circuitry mechanism that underlies dopaminergic (DA) control of innate feeding behavior is largely uncharacterized. Here, we identified a subpopulation of DA neurons situated in the caudal ventral tegmental area (cVTA) directly innervating DRD1-expressing neurons within the lateral parabrachial nucleus (LPBN). This neural circuit potently suppresses food intake via enhanced satiation response. Notably, this cohort of DAcVTA neurons is activated immediately before the cessation of each feeding bout. Acute inhibition of these DA neurons before bout termination substantially suppresses satiety and prolongs the consummatory feeding. Activation of postsynaptic DRD1LPBN neurons inhibits feeding, whereas genetic deletion of Drd1 within the …

Exploring Motivational Factors To Pursue Genetic Counseling And Testing In Adolescent And Young Adult Cancer Patients, Megan Morand

Dissertations and Theses (Open Access)

Adolescent and young adult (AYA) cancer patients face a unique set of challenges when navigating cancer treatment and survivorship. For many patient populations, motivational factors to pursue genetic counseling/testing have been described, but these motivational factors in AYA cancer patients have yet to be explored. The goal of this study was to describe AYA cancer patients’ decision-making process, including motivational factors and barriers as it relates to genetic counseling/testing. We conducted a qualitative study consisting of semi-structured interviews with 30 individuals from the AYA Program at MD Anderson Cancer Center who attended or were referred to a genetic counseling appointment. …

Isolated, Absent Cavum Septum Pellucidum: A Single Center’S Outcomes And Review Of The Literature, Renee Bardini

Dissertations and Theses (Open Access)

An absent cavum septum pellucidum (CSP) has traditionally been associated with a wide range of neuroanatomical anomalies. With recent advancements in prenatal imaging, however, an absent CSP that occurs in isolation of other anomalies is becoming a more frequent finding. Yet knowledge of clinical outcomes remain limited. Our study aims to describe ultrasound abnormalities associated with an absent CSP and the postnatal outcomes of an isolated, absent CSP. Additionally, we explore the accuracy of prenatal ultrasounds in evaluating for an absent CSP. This is a retrospective study of all cases diagnosed with an absent CSP between January 1, 2009 and …

Engineering B Cells For Use In Immunotherapy And Cancer, Emily Ensley

Dissertations and Theses (Open Access)

B cells can be divided into effector and regulatory immune cells. While effector B cells are key drivers of humoral immunity due to their ability to generate antibodies specific to pathogens, regulatory B cells (Bregs) have recently been shown to control inflammatory responses in multiple diseases through the production of anti-inflammatory cytokines, including interleukin (IL)-10, IL-35 and transforming growth factor-beta (TGF-b). Ex vivo expansion of B cells has been challenging due to their tendency to undergo apoptosis in culture. Thus, creating a successful expansion protocol with exceptional viability will open the door for B cells to be used directly for …

Increased Oxidative Phosphorylation In An Ipsc- Derived Model Of Rothmund-Thomson Syndrome Associated Osteosarcomagenesis, Brittany Jewell

Dissertations and Theses (Open Access)

Osteosarcoma is the most common bone malignancy in children and adolescents worldwide. Patients with Type II Rothmund-Thomson Syndrome (RTS) are highly predisposed to develop osteosarcoma, with 30% of patients in the largest cohort study developing osteosarcoma. Patients with Type II RTS have biallelic mutations in the DNA helicase RECQL4, which has been shown to have mitochondrial functions that include DNA replication and repair. We describe the generation of 12 induced pluripotent stem cell lines (iPSCs) from two paired RTS patient/ parental control (Family) sets. These iPSCs were validated, then differentiated to the bone precursor, mesenchymal stem cells (MSCs). After verification …

Evaluating Insurance Approval Rates Of Exome Sequencing And Its Effect On Minority Patients' Access To Genetic Care, Katlyn Frane

Dissertations and Theses (Open Access)

Exome sequencing (ES) is often a standard step in the genetic testing process for patients with rare or complex disease. Despite clinical implementation of ES, insurance companies (payers) continue to deny this test. We investigated if the payer barrier is influenced by payer type, and if other demographic or clinical information correlated to ES approval and obtainment. To do this, a retrospective chart and clinical database review was completed on patients seen at a tertiary care center and community-based clinic. Patient demographics, clinical indications, and testing recommendations and outcomes were used to assess ES approval and obtainment. We found that …

Endogenous Mechanisms Regulating Myeloid Cell Mediated Inflammation During Acute Lung Injuries, Nathaniel Berg

Dissertations and Theses (Open Access)

Acute lung injuries (ALI) can result from both direct insults (e.g. pneumonia or inhalation injury), or systemic conditions such as sepsis or trauma. Current treatment options for patients are limited to supportive care and novel approaches are urgently needed. Appreciating the role of excessive inflammation that underlies the pathophysiology of ALI, we sought to identify endogenous mechanisms that dampen inflammation. Here we investigated two pathways that worked to limit excessive pulmonary inflammation in myeloid cells using a mouse model of sepsis-associated ALI. In the first approach we screened for microRNAs during the recovery phase of ALI that could potentially regulate …

Assessing The Outcomes Of Blocking Ccl2-Ccr2 Signaling Axis On Breast Cancer Brain Metastasis, Yutao Qi

Dissertations and Theses (Open Access)

Breast cancer brain metastases have remained one of the most intense challenges for precision cancer therapeutics, but current treatment options are limited and not curative. Recently, our lab reported that adoptive PTEN downregulation in metastatic breast tumor cells activates PI3K/NF-ƙB signaling and increases the secretion of the chemokine CCL2, which enhances the chemotaxis of CCR2⁺ myeloid cells, a major subpopulation of bone marrow-derived myeloid cells (BMDMs), from peripheral blood into the brain tumor microenvironment (TME), eventually promoting brain metastasis outgrowth by driving immune suppression. Here, in this project we have been aiming to develop effective therapies by immune-modulating the …