Diseases Commons^™

Effects Of Tamoxifen Inducible Mercremer On Gene Expression In Cardiac Myocytes In Mice, Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Melis Olcum, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

The Cre-LoxP technology, including the tamoxifen (TAM) inducible MerCreMer (MCM), is increasingly used to delineate gene function, understand the disease mechanisms, and test therapeutic interventions. We set to determine the effects of TAM-MCM on cardiac myocyte transcriptome. Expression of the MCM was induced specifically in cardiac myocytes upon injection of TAM to myosin heavy chain 6-MCM (Myh6-Mcm) mice for 5 consecutive days. Cardiac function, myocardial histology, and gene expression (RNA-sequencing) were analyzed 2 weeks after TAM injection. A total of 346 protein coding genes (168 up- and 178 down-regulated) were differentially expressed. Transcript levels of 85 genes, analyzed …

The Wnt/Β-Catenin Pathway Regulates Expression Of The Genes Involved In Cell Cycle Progression And Mitochondrial Oxidative Phosphorylation In The Postmitotic Cardiac Myocytes, Melis Olcum, Sirisha M Cheedipudi, Leila Rouhi, Siyang Fan, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: Aging is associated with cardiac myocyte loss, sarcopenia, and cardiac dysfunction. Adult cardiac myocytes are postmitotic cells with an insufficient proliferative capacity to compensate for myocyte loss. The canonical WNT (cWNT) pathway is involved in the regulation of cell cycle reentry in various cell types. The effects of the cWNT pathway on the expression of genes involved in cell cycle reentry in the postmitotic cardiac myocytes are unknown.

AIM: The aim of the study was to identify genes whose expression is regulated by the β-catenin, the indispensable component to the cWNT signaling, in the postmitotic myocytes.

METHODS AND RESULTS: …

Engineered Cord Blood Megakaryocytes Evade Killing By Allogeneic T-Cells For Refractory Thrombocytopenia, Bijender Kumar, Vahid Afshar-Kharghan, Mayela Mendt, Robert Sackstein, Mark R Tanner, Uday Popat, Jeremy Ramdial, May Daher, Juan Jimenez, Rafet Basar, Luciana Melo Garcia, Mayra Shanley, Mecit Kaplan, Xinhai Wan, Vandana Nandivada, Francia Reyes Silva, Vernikka Woods, April Gilbert, Ricardo Gonzalez-Delgado, Sunil Acharya, Paul Lin, Hind Rafei, Pinaki Prosad Banerjee, Elizabeth J Shpall

Faculty, Staff and Student Publications

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, …

Human Papillomavirus 16 E2 Regulates Host Cell Pathways Important For Cancer Progression And Treatment Sensitivity Which May Contribute To Cancer Outcomes, Christian Fontan

Theses and Dissertations

Human papillomaviruses (HPVs) are causative agents in around 5% of all cancers, including cervical and oropharyngeal. A feature of HPV cancers is their better clinical outcome compared with non-HPV anatomical counterparts. In turn, the presence of E2 predicts a better clinical outcome in HPV-positive cancers; the reason(s) for the better outcome of E2-positive patients is not fully understood.

Previously, we demonstrated that HPV16 E2 regulates host gene transcription that is relevant to the HPV16 lifecycle in N/Tert-1 cells. One of the genes repressed by E2 and the entire HPV16 genome in N/Tert-1 cells is TWIST1. In these studies, we demonstrate …

Advancing The Standard: Venetoclax Combined With Intensive Induction And Consolidation Therapy For Acute Myeloid Leukemia, Curtis A Lachowiez, Himachandana Atluri, Courtney D Dinardo

Faculty, Staff and Student Publications

The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with lower-intensity therapy is an efficacious treatment for acute myeloid leukemia (AML). VEN in combination with the hypomethylating agent azacitidine improved rates of response and measurable residual disease (MRD)-negative remissions in addition to overall survival in the pivotal phase 3 VIALE-A trial compared with azacitidine monotherapy and has since emerged as the current standard of care in older or unfit patients with AML. In younger, fit patients with AML, intensive induction and consolidation chemotherapy (IC) is commonly employed as frontline therapy; however, relapse remains the principal cause of treatment failure …

Prediction Of Early (4-Week) Mortality In Acute Myeloid Leukemia With Intensive Chemotherapy, Koji Sasaki, Tapan Kadia, Kebede Begna, Courtney D Dinardo, Gautam Borthakur, Nicholas J Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Lucia Masarova, Sherry Pierce, Marina Konopleva, Farhad Ravandi, Ayalew Tefferi, Hagop Kantarjian

Faculty, Staff and Student Publications

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was …

Serum Gamma Glutamyltransferase (Ggt) In Coronary Artery Disease: Exploring The Asian Indian Connection, Kunal K Singh, Aditya Kapoor, Roopali Khanna, Ankit Sahu, Vishwas Kapoor, Sudeep Kumar, Naveen Garg, Satyendra Tewari, Pravin Goel

Faculty, Staff and Student Publications

BACKGROUND: There is a need to identify novel markers for CAD, independent of traditional CV risk factors. One of these is gamma-glutamyl transferase (GGT), a marker of increased oxidative stress. Given the high prevalence of CAD in Asian Indians, the link of GGT and CAD in them needs to be studied.

AIM: To assess GGT in patients with angiographically documented CAD.

METHODS AND RESULTS: Two hundred patients aged 58.1 ± 9.95 years, 73% males, hypertension 56%, diabetes 40% were included. Mean GGT was 63.6 ± 44.33 (10–269 U/L). The levels of GGT progressively increased in those with single/double or triple-vessel …

Farmers’ Knowledge, Perceptions, And Practices On Animal Trypanosomosis And The Tsetse Fly Vector: A Cross-Sectional Study Around Kenya’S Arabuko-Sokoke Forest Reserve At The Livestock-Wildlife Interface, Erick K. Serem, Joel L. Bargul, Moses M. Ngari, Osman A. Abdullahi, David M. Mburu

All Peer-Reviewed Publications

Background: Animal African trypanosomosis (AAT) is a veterinary disease caused by trypanosomes transmitted cyclically by tsetse flies. AAT causes huge agricultural losses in sub-Saharan Africa. Both tsetse flies and trypanosomosis (T&T) are endemic in the study area inhabited by smallholder livestock farmers at the livestock-wildlife interface around Arabuko-Sokoke Forest Reserve (ASFR) in Kilifi County on the Kenyan coast. We assessed farmers’ knowledge, perceptions and control practices towards T&T. Methods: A cross-sectional study was conducted during November and December 2017 to collect data from 404 randomly selected cattle-rearing households using a structured questionnaire. Descriptive statistics were used to determine farmers’ knowledge, …

Molecular Detection Of Novel Anaplasma Sp. And Zoonotic Hemopathogens In Livestock And Their Hematophagous Biting Keds (Genus Hippobosca) From Laisamis, Northern Kenya, Daniel M. Mwaki, Kevin O. Kidambasi, Johnson Kinyua, Kenneth Ogila, Collins Kigen, Dennis Getange, Jandouwe Villinger, Daniel K. Masiga, Mark Carrington, Joel L. Bargul

All Peer-Reviewed Publications

Background: Livestock are key sources of livelihood among pastoral communities. Livestock productivity is chiefly constrained by pests and diseases. Due to inadequate disease surveillance in northern Kenya, little is known about pathogens circulating within livestock and the role of livestock-associated biting keds (genus Hippobosca) in disease transmission. We aimed to identify the prevalence of selected hemopathogens in livestock and their associated blood-feeding keds. Methods: We randomly collected 389 blood samples from goats (245), sheep (108), and donkeys (36), as well as 235 keds from both goats and sheep (116), donkeys (11), and dogs (108) in Laisamis, Marsabit County, northern Kenya. …

The Combat Project: Controlling And Progressively Minimizing The Burden Of Vector-Borne Animal Trypanosomosis In Africa, Alain Boulangé, Veerle Lejon, David Berthier, Sophie Thévenon, Geoffrey Gimonneau, Marc Desquesnes, Samuel Abah, Prudenciène Agboho, Kalinga Chilongo, Tsegaye Gebre, Assane Gueye Fall, Dramane Kaba, Stefan Magez, Daniel Masiga, Enock Matovu, Aldjibert Moukhtar, Luis Neves, Pamela A. Olet, Soumaïla Pagabeleguem, William Shereni, Brice Sorli, Moeti O. Taioe, María Teresa Tejedor Junco, Rehab Yagi, Philippe Solano, Giuliano Cecchi

All Peer-Reviewed Publications

Vector-borne diseases affecting livestock have serious impacts in Africa. Trypanosomosis is caused by parasites transmitted by tsetse flies and other blood-sucking Diptera. The animal form of the disease is a scourge for African livestock keepers, is already present in Latin America and Asia, and has the potential to spread further. A human form of the disease also exists, known as human African trypanosomosis or sleeping sickness. Controlling and progressively minimizing the burden of animal trypanosomosis (COMBAT) is a four-year research and innovation project funded by the European Commission, whose ultimate goal is to reduce the burden of animal trypanosomosis (AT) …

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li

Faculty, Staff and Students Publications

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone …

The Effects Of Glucocorticoids And Immunosuppressants On Cancer Outcomes In Checkpoint Inhibitor Therapy, Sebastian Bruera, Maria E Suarez-Almazor

Faculty, Staff and Students Publications

The emergence of checkpoint inhibitors has created a paradigm shift for the treatment of various malignancies. However, although these therapies are associated with improved survival rates, they also carry the risk of immune-related adverse events (irAEs). Moderate to severe irAEs are typically treated with glucocorticoids, sometimes with the addition of immunosuppressants as steroid-sparing therapy. However, it is unclear how glucocorticoids and immunosuppressants may impact cancer survival and the efficacy of immune checkpoint therapy on cancer. In this narrative review, we discuss the effects of glucocorticoids and immunosuppressants including methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, tumor-necrosis factor (TNF)-inhibitors, interleukin-6 inhibitors, interleukin-1 inhibitors, …

Amelioration Of Mitochondrial Bioenergetic Dysfunction In Diabetes Mellitus: Delving Into Specialized And Non-Specific Therapeutics For The Ailing Heart, Andrya Jean Durr

Graduate Theses, Dissertations, and Problem Reports (ETD)

Morbidity and mortality of the diabetic population is influenced by many confounding factors, but cardiovascular disease (CVD), remains the leading cause of death. Mitochondrial dysfunction is central in the development of cardiac contractile dysfunction, with decreased mitochondrial bioenergetic function, increased dependence on free fatty acid utilization, and a decrease in glucose utilization having been shown to contribute to contractile dysfunction. Strategies targeting the amelioration of mitochondrial bioenergetic function are attractive for limiting diabetes-induced heart failure, and preserving health-span. The goals of this dissertation were to assess two mitochondrial-centric approaches for the amelioration of mitochondrial and cardiac contractile dysfunction in diabetes …

Mental Health And Access To Medical Care In Patients With Chronic Cardiovascular Conditions: An Analysis Of The Behavior Risk Factor Surveillance System, Riyad Y Kherallah, Mahmoud Al Rifai, Jing Liu, Sina Kianoush, Arunima Misra, Salim S Virani

Faculty, Staff and Students Publications

INTRODUCTION: Poor mental health is associated with worse outcomes for chronic diseases. It is unclear whether mental illness predisposes to difficulties with healthcare access.

METHODS: Using a combined dataset of the 2016-2019 Behavioral Risk Factor Surveillance System, this study focused on individuals who reported a chronic cardiovascular condition. Weighted multivariable logistic regression analyses were used to explore the association between domains of mental health and measures of healthcare access including delaying medical care, more than one year since last routine checkup, lack of a primary care physician, and cost-related medication nonadherence.

RESULTS: Among 1,747,397 participants, 27% had a chronic cardiovascular …

Utilizing The K18-Hace2 Mouse Model To Develop Protective Covid-19 Vaccines, Ting Y. Wong

Graduate Theses, Dissertations, and Problem Reports (ETD)

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the respiratory virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Similar to other respiratory viruses, SARS-CoV-2 is transmitted through inhalation of respiratory droplets and aerosols from infected individuals. Once inhaled, SARS-CoV-2 utilizes the receptor binding domain (RBD) on the spike protein to bind to human Angiotensin Converting Enzyme 2 (hACE2) receptor to gain entrance into host cells to begin viral replication. SARS-CoV-2 infection can result in mild to severe cases of COVID-19 ranging from asymptomatic infections, cold or flu like symptoms to respiratory failure. The onset of the pandemic in …

Metastatic Insulinoma Presenting With Postprandial Hypoglycemia, Monique Debrah Maher, Dimpi Nitin Desai, Mandeep Bajaj

Faculty, Staff and Students Publications

BACKGROUND/OBJECTIVE: Patients with an insulinoma, a type of pancreatic neuroendocrine tumor, typically present with fasting hypoglycemia but can rarely present exclusively with postprandial hypoglycemia.

CASE REPORT: A 69-year-old man presented with episodes of postprandial blurry vision, sweating, and confusion for the last 2 years that were becoming more frequent over the last several weeks. Home blood glucose measurements revealed postprandial hypoglycemia (glucose level, 45-70 mg/dL), and symptoms were consistent with the Whipple triad. Continuous glucose monitoring revealed only postprandial hypoglycemia within 2 hours following meals. An outpatient fast was conducted with detectable insulin (6 μIU/mL) and C-peptide (2.0 ng/mL) levels …

Widening Health Disparities: Increasing Cholangiocarcinoma Incidence In An Underserved Population, Disha Kumar, Varun Bansal, Syed A Raza, Aaron P Thrift, Hoda M Malaty, Robert J Sealock

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Cholangiocarcinoma is a relatively rare malignancy with high mortality. In the U.S., incidence rates of cholangiocarcinoma have increased, particularly affecting younger age groups and Hispanic and Asian individuals. We investigated the incidence of cholangiocarcinoma in a largely under-represented, minority population.

METHODS: We performed a retrospective cohort study from 2005 to 2017 among adults in a county-funded healthcare system in Harris County, Texas. Incidence rate ratios were computed to compare age-standardized rates using U.S. standard population between 2 time periods: 2005-2011 and 2012-2017.

RESULTS: We identified 139 cholangiocarcinoma cases (64% intrahepatic, 36% extrahepatic). The median age at diagnosis …

Endpoints In Heart Failure Drug Development, Aliza Hussain, Arunima Misra, Biykem Bozkurt

Faculty, Staff and Students Publications

Heart failure (HF) is a major health problem worldwide. The development of effective drug and/or device therapy is crucial to mitigate the significant morbidity, mortality and healthcare costs associated with HF. The choice of endpoint in clinical trials has important practical and clinical implications. Outcomes of interest including mortality and HF hospitalisations provide robust evidence for regulatory approval granted there is sufficiency of safety data. At the same time, it is important to recognise that HF patients experience significant impairments in functional capacity and quality of life, underscoring the need to incorporate parameters of symptoms and patient-reported outcomes in clinical …

Meta-Analysis Comparing Outcomes Of High-Power Short-Duration And Low-Power Long-Duration Radiofrequency Ablation For Atrial Fibrillation, Dibbendhu Khanra, Abdul Hamid, Saurabh Deshpande, Anindya Mukherjee, Sanjiv Petkar, Mohammad Saeed, Indranill Basu-Ray

Faculty, Staff and Students Publications

OBJECTIVE: High power short duration (HPSD) ablation strategy is proposed to be more effective than low power long duration (LPLD) for radiofrequency ablation of atrial fibrillation. Although small trials abound, data from a large cohort are lacking. This meta-analysis compares all the existing studies comparing these two approaches to evaluate perceived advantages of one over the other.

METHODS: A systematic search of PubMed, EMBASE, and Cochrane databases identified studies comparing HPSD to LPLD ablation. All the analyses used the random-effects model.

RESULTS: Ablation settings varied widely across 20 studies comprising 2,136 patients who underwent HPSD and 1,753 patients who underwent …

Adult Memory T Cell Responses To The Respiratory Syncytial Virus Fusion Protein During A Single Rsv Season (2018-2019), Brittani N Blunck, Laura S Angelo, David Henke, Vasanthi Avadhanula, Matthew Cusick, Laura Ferlic-Stark, Lynn Zechiedrich, Brian E Gilbert, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory Syncytial Virus (RSV) is ubiquitous and re-infection with both subtypes (RSV/A and RSV/B) is common. The fusion (F) protein of RSV is antigenically conserved, induces neutralizing antibodies, and is a primary target of vaccine development. Insight into the breadth and durability of RSV-specific adaptive immune response, particularly to the F protein, may shed light on susceptibility to re-infection. We prospectively enrolled healthy adult subjects (n = 19) and collected serum and peripheral blood mononuclear cells (PBMCs) during the 2018–2019 RSV season. Previously, we described their RSV-specific antibody responses and identified three distinct antibody kinetic profiles associated with infection …

Evaluation Of Virtual Screening Strategies For The Identification Of Γ-Secretase Inhibitors And Modulators, Alicia Ioppolo, Melissa Eccles, David Groth, Giuseppe Verdile, Mark Agostino

Research outputs 2022 to 2026

γ-Secretase is an intramembrane aspartyl protease that is important in regulating normal cell physiology via cleavage of over 100 transmembrane proteins, including Amyloid Precursor Protein (APP) and Notch family receptors. However, aberrant proteolysis of substrates has implications in the progression of disease pathologies, including Alzheimer’s disease (AD), cancers, and skin disorders. While several γ-secretase inhibitors have been identified, there has been toxicity observed in clinical trials associated with non-selective enzyme inhibition. To address this, γ-secretase modulators have been identified and pursued as more selective agents. Recent structural evidence has provided an insight into how γ-secretase inhibitors and modulators are recognized …

Gut Microbiota From Sjögren Syndrome Patients Causes Decreased T Regulatory Cells In The Lymphoid Organs And Desiccation-Induced Corneal Barrier Disruption In Mice, Laura Schaefer, Claudia M Trujillo-Vargas, Firas S Midani, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Sjögren syndrome (SS) is an autoimmune inflammatory disorder characterized by secretory dysfunction in the eye and mouth; in the eye, this results in tear film instability, reduced tear production, and corneal barrier disruption. A growing number of studies show that homeostasis of the ocular surface is impacted by the intestinal microbiome, and several 16S sequencing studies have demonstrated dysbiosis of the intestinal microbiota in SS patients. In this study, we utilized metagenomic sequencing to perform a deeper analysis of the intestinal microbiome using stools collected from sex- and age-matched healthy (n = 20), dry eye (n = 4) …

Clonal Hematopoiesis Analyses In Clinical, Epidemiologic, And Genetic Aging Studies To Unravel Underlying Mechanisms Of Age-Related Dysfunction In Humans, Kenneth Walsh, Nalini Raghavachari, Candace Kerr, Alexander G Bick, Steven R Cummings, Todd Druley, Cynthia E Dunbar, Giulio Genovese, Margaret A Goodell, Siddhartha Jaiswal, Jaroslaw Maciejewski, Pradeep Natarajan, Anastasia V Shindyapina, Alan R Shuldiner, Erik B Van Den Akker, Jan Vijg

Faculty, Staff and Students Publications

Aging is characterized by increased mortality, functional decline, and exponential increases in the incidence of diseases such as cancer, stroke, cardiovascular disease, neurological disease, respiratory disease, etc. Though the role of aging in these diseases is widely accepted and considered to be a common denominator, the underlying mechanisms are largely unknown. A significant age-related feature observed in many population cohorts is somatic mosaicism, the detectable accumulation of somatic mutations in multiple cell types and tissues, particularly those with high rates of cell turnover (e.g., skin, liver, and hematopoietic cells). Somatic mosaicism can lead to the development of cellular clones that …

Metabolic Targeting, Immunotherapy And Radiation In Locally Advanced Non-Small Cell Lung Cancer: Where Do We Go From Here?, Annika Dhawan, Phillip M Pifer, Vlad C Sandulache, Heath D Skinner

Faculty, Staff and Students Publications

In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with …

Esophageal Perforation Successfully Treated With Evt, Kavea Panneerselvam, Ronald Samuel, Robert J Sealock

Faculty, Staff and Students Publications

Esophageal perforation is rare and carries high morbidity and mortality. A high degree of suspicion is needed for timely diagnosis and treatment. A 54-year-old man presented with fever and confusion. Imaging revealed air in the hepatic inferior vena cava and concern for a fistula between the distal esophagus and the inferior vena cava. An upper endoscopic evaluation revealed a dental floss pick penetrating the distal esophagus. The foreign body was removed, and endoluminal vacuum therapy was used to close the perforation. Endoluminal vacuum therapy is an emerging therapy to treat full-thickness gastrointestinal injuries.

Management Of A Novel Autoimmune Disease, Copa Syndrome, In Pregnancy, Archana Ayyar, Rachel D Seaman, Kalpalatha Guntupalli, Mary C Tolcher

Faculty, Staff and Students Publications

BACKGROUND: COPA syndrome is a rare autoimmune disease, demonstrating an autosomal dominant inheritance pattern with variable penetration that occurs more frequently in females than males. This disease manifests in childhood as pulmonary hemorrhage, arthritis, and renal disease.

CASE: We present a case of obstetric management of a 20-year-old nulligravida patient with a diagnosis of COPA syndrome. Her case was further complicated by multiple antepartum admissions for hypoxemia and a complex psychosocial history of substance use. On her first antepartum admission, rheumatology recommended management with hydroxychloroquine, inhaled corticosteroids (budesonide), and bronchodilators (albuterol inhaler) as needed. On admission for induction of labor, …

Comparative Analytical Study Of Phytochemicals In Selected Antidiabetic Medicinal Plant Seeds In Sri Lanka, Gowri Rajkumar, Mihiri Rangika Jayasinghe, Vinotha Sanmugarajah

Pharmaceutical Sciences and Research

Medicinal plants are universally used in the management of various diseases in different medical practices. A varied diversity of compounds extracted from plants may show anticancer, antibacterial, and antidiabetic activities. Comparative laboratory studies and scientific approach of efficacy related to phytochemicals found in medicinal plants in Sri Lanka have not been reported yet. This study aims to evaluate the phytochemicals in selected four different plant seeds such as Syzygium cumini (L.) Skeels, Brassica alba (L.) Rabenh, Trigonella foenum-graecum L. and Nigella sativa L., which are used in the management of diabetes mellitus in Sri Lanka. The ethanol extracts of …

Biologic Tnf-Α Inhibitors Reduce Microgliosis, Neuronal Loss, And Tau Phosphorylation In A Transgenic Mouse Model Of Tauopathy, Weijun Ou, Joshua Yang, Juste Simanauskaite, Matthew Choi, Demi M. Castellanos, Rudy Chang, Jiahong Sun, Nataraj Jagadeesan, Karen D. Parfitt, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer’s disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported. Existing biologic TNFIs do not cross the blood–brain barrier (BBB), therefore we engineered a BBB-penetrating biologic TNFI by fusing the extracellular domain of the type-II human TNF-α receptor (TNFR) to a transferrin receptor antibody (TfRMAb) that ferries the TNFR into the brain via …

Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Ciliary extracellular vesicles (ciEVs), released from primary cilia, contain functional proteins that play an important role in cilia structure and functions. We have recently shown that ciEVs and cytosolic extracellular vesicles (cyEVs) have unique and distinct biomarkers. While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. These results support the growing evidence of the critical physiological roles …