Digital Commons Network^™

Practical Considerations Of Dissolved Oxygen Levels For Platelet Function Under Hypoxia., Branden Kusanto, Andrew Gordon, Leigh Naylor-Adamson, Lloyd Atkinson, Charlie Coupland, Zoe Booth, Yusra Ahmed, Isabel M Pires, Graeme J Stasiuk, Roger Sturmey, Simon D J Calaminus, Mònica Arman

Student and Faculty Publications

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the …

Lgr5 Regulation Of Stat3 Signaling And Drug Resistance In Colorectal Cancer, Tressie Posey, Tressie Alexandra Posey

Dissertations & Theses (Open Access)

LGR5 Regulation of STAT3 Signaling and Drug Resistance in Colorectal Cancer

Tressie Alexandra Capri Posey B.S.

Advisory Professor: Kendra Carmon, Ph.D.

The greatest difficulty in treating colorectal cancer (CRC) is the development of drug resistance which leads to relapse after treatment and progression to metastasis. Cancer stem cells (CSCs) are believed to drive relapse because of their capacity to self-renew, acquire resistance mechanisms, and differentiate promoting tumor growth and heterogeneity. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is a bona-fide marker of CSCs and has been considered a viable target for CSC specific therapeutic development. While we showed targeting LGR5 …

4d Ex Vivo Crispr/Cas9 Whole-Genome Screen To Identify Genes Regulating Lung Cancer Metastasis, Alexandria Plumer

Dissertations & Theses (Open Access)

Metastatic lung cancer has a 5-year survival rate of 5%. Lung cancers tend to be asymptomatic until late stages, and almost 90% are not diagnosed until they are advanced. Metastases are very rare events, often initiated by a single cell from a primary tumor into a new niche at a distant location. Investigation of the early metastatic process is of urgent need for the development of early diagnostics and targeted therapeutics. We performed a proof-of-concept CRISPR/Cas9 whole genome knockout screen in the A549 lung adenocarcinoma cell line and utilized a novel ex vivo 4D lung metastasis model to find gene …

Deciphering The Role Of Hsp110 Chaperones In Diseases Of Protein Misfolding, Unekwu M. Yakubu

Dissertations & Theses (Open Access)

Molecular chaperones maintain protein homeostasis (proteostasis) by ensuring the proper folding of polypeptides. Loss of proteostasis has been linked to the onset of numerous neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s disease. Hsp110 is a member of the Hsp70 class of molecular chaperones and acts as a nucleotide exchange factor (NEF) for Hsp70, the preeminent Hsp70-family protein folding chaperone. Hsp110 promotes rapid cycling of ADP for ATP, allowing Hsp70 to properly fold nascent or unfolded polypeptides in iterative cycles. In addition to its NEF activity, Hsp110 possesses an Hsp70-like substrate binding domain (SBD) whose biological roles are undefined. Previous work …

Evaluating The Efficacy Of Automated Smoking Treatment For People With Hiv: Protocol For A Randomized Controlled Trial, Damon J Vidrine, Thanh C Bui, Michael S Businelle, Ya-Chen Tina Shih, Steven K Sutton, Lokesh Shahani, Diana Stewart Hoover, Kristina Bowles, Jennifer I Vidrine

Student and Faculty Publications

BACKGROUND: Smoking prevalence rates among people with HIV are nearly 3 times higher than those in the general population. Nevertheless, few smoking cessation trials targeting smokers with HIV have been reported in the literature. Efforts to develop and evaluate sustainable, low-cost, and evidence-based cessation interventions for people with HIV are needed. Given the widespread proliferation of mobile phones, the potential of using mobile health apps to improve the reach and efficacy of cessation interventions is promising, but evidence of efficacy is lacking, particularly among people with HIV.

OBJECTIVE: This study will consist of a 2-group randomized controlled trial to evaluate …

Candida Albicans Elicits Protective Allergic Responses Via Platelet Mediated T Helper 2 And T Helper 17 Cell Polarization, Yifan Wu, Zhimin Zeng, Yubiao Guo, Lizhen Song, Jill E Weatherhead, Xinyan Huang, Yuying Zeng, Lynn Bimler, Cheng-Yen Chang, John M Knight, Christian Valladolid, Hua Sun, Miguel A Cruz, Bernhard Hube, Julian R Naglik, Amber U Luong, Farrah Kheradmand, David B Corry

Student and Faculty Publications

Fungal airway infection (airway mycosis) is an important cause of allergic airway diseases such as asthma, but the mechanisms by which fungi trigger asthmatic reactions are poorly understood. Here, we leverage wild-type and mutant Candida albicans to determine how this common fungus elicits characteristic Th2 and Th17 cell-dependent allergic airway disease in mice. We demonstrate that rather than proteinases that are essential virulence factors for molds, C. albicans instead promoted allergic airway disease through the peptide toxin candidalysin. Candidalysin activated platelets through the Von Willebrand factor (VWF) receptor GP1bα to release the Wnt antagonist Dickkopf-1 (Dkk-1) to drive Th2 and …

Apathy Is Not Associated With A Panel Of Biomarkers In Older Adults With Hiv Disease, Steven Paul Woods, Jennifer L Thompson, Michelle A Babicz, Lokesh Shahani, Gabriela Delevati Colpo, Natalia P Rocha, Erin E Morgan, Antonio L Teixeira

Student and Faculty Publications

OBJECTIVE: Apathy is prevalent in HIV disease and can significantly impact personal well-being; however, little is known about its neurobiological substrates in persons with HIV (PWH) disease.

METHODS: This cross-sectional, correlational study examined the association between apathy and several plasma biomarkers (tumor necrosis factor alpha, kynurenine, tryptophan, quinolinic acid, brain-derived neurotrophic factor, glial fibrillary acidic protein, neurofilament light chain, and phosphorylated tau at position threonine 181) in 109 PWH and 30 seronegative participants ages 50 and older. Apathy was measured with a composite score derived from subscales of the Frontal Systems Behavior Scale and the Profile of Mood States.

RESULTS: …

Identification Of An Atp/P2x7/Mast Cell Pathway Mediating Ozone-Induced Bronchial Hyperresponsiveness, Xiaomei Kong, William C Bennett, Corey M Jania, Kelly D Chason, Zachary German, Jennifer Adouli, Samuel D Budney, Brandon T Oby, Catharina Van Heusden, Eduardo R Lazarowski, Ilona Jaspers, Scott H Randell, Barry A Hedgespeth, Glenn Cruse, Xiaoyang Hua, Stephen A Schworer, Gregory J Smith, Samir Np Kelada, Stephen L Tilley

Student and Faculty Publications

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast …

Atypical St-Segment-Elevation Myocardial Infarction Presentation In Patients With Covid-19 At A High-Volume Center In New York City, Miguel A Alvarez Villela, Ahmad Alkhalil, Michael A Weinreich, Jonathan Koslowsky, Shunsuke Aoi, M Azeem Latib

The Texas Heart Institute Journal

Atypical presentations of ST-segment-elevation myocardial infarction (STEMI) have been reported in patients who have COVID-19. We have seen this occurrence in our center in Bronx, New York, where multitudes of patients sought treatment for the coronavirus. We studied the prevalence of atypical STEMI findings among patients with COVID-19 who presented during the first 2 months of the pandemic.

Consistent with previous reports, 4 of our 10 patients with COVID-19 and STEMI had no identifiable culprit coronary lesion; rather, they often had diffuse ST-segment elevations on surface electrocardiograms along with higher levels of D-dimer and inflammatory markers. In contrast, 32 of …

Left Ventricular Ballooning Patterns In Recurrent Takotsubo Cardiomyopathy: A Systematic Review And Meta-Analysis Of Reported Cases, Ravi Korabathina, Jamie Porcadas, Kevin E Kip, Puja R Korabathina, Andrew D Rosenthal, Peter Wassmer

The Texas Heart Institute Journal

Recurrent takotsubo cardiomyopathy (TTC) and the clinical profiles and outcomes of patients have not been fully evaluated, nor has the effect of left ventricular ballooning pattern. After searching the medical literature for reports of patients with recurrent TTC, we identified 84 articles with 101 case descriptions. We divided the cases into those with only apical left ventricular ballooning patterns at recurrence (typical, n=60), and those with at least one midventricular or basal ballooning pattern (atypical, n=41). We then compared their clinical profiles and outcomes.

The groups were similar in terms of baseline demographic characteristics, presence and types of triggers, use …

Novel Pharmacomechanical Thrombolysis For Treating Intermediate-Risk Acute Pulmonary Embolism: The Bashir Endovascular Catheter, Maninder Singh, Austin Quimby, Vladimir Lakhter, Mohamad Al-Otaibi, Parth M Rali, Riyaz Bashir

The Texas Heart Institute Journal

No abstract provided.

Large-Bore Aspiration Thrombectomy: Catalyst For A Revolution In Treating Pulmonary Embolism, Thomas M Tu

The Texas Heart Institute Journal

No abstract provided.

Surgical Treatment Of Valvular Heart Disease In Nigeria: A 6-Year Experience, Ikechukwu A Nwafor, John C Eze, Maureen N Nwafor

The Texas Heart Institute Journal

Surgical treatment of valvular heart disease in Nigeria, the most populous country in sub-Saharan Africa, is adversely affected by socioeconomic factors such as poverty and ignorance. To evaluate our experience in this context, we identified all patients who underwent surgery for acquired or congenital valvular heart disease at our Nigerian center from February 2013 through January 2019. We collected data from their medical records, including patient age and sex, pathophysiologic causes and types of valvular disease, surgical treatment, and outcomes. Ninety-three patients (43 males [46.2%]; mean age, 38.9 ± 10.0 yr [range, 11–80 yr]) underwent surgical treatment of a total …

Endovascular Treatment Of Acquired Atheromatous Postsubclavian Aortic Coarctation, Bhushan S Sonawane, Sreeja Pavithran, Kothandam Sivakumar

The Texas Heart Institute Journal

Coral reef aorta is a rare calcifying obstructive disease that involves the thoracoabdominal aorta. Similar presentations in the postsubclavian aorta may result in acquired atheromatous aortic coarctation leading to systemic hypertension and heart failure. The associated calcification makes surgical anatomic or extraanatomic bypass and thromboendarterectomy challenging. Extensive circumferential calcification often precludes endovascular intervention. We present the case of a 25-year-old man with an acquired atheromatous coarctation of the postsubclavian aorta who underwent successful endovascular treatment with use of a balloon-expandable covered stent.

Mitophagy In Depression: Pathophysiology And Treatment Targets, Ashutosh Tripathi, Giselli Scaini, Tatiana Barichello, João Quevedo, Anilkumar Pillai

Student and Faculty Publications

Mitochondria, the 'powerhouse' of eukaryotic cells, play a key role in cellular homeostasis. However, defective mitochondria increase mitochondrial ROS (mtROS) production and cell-free mitochondrial DNA (mtDNA) release, leading to increased inflammation. Mitophagy is a vital pathway, which selectively removes defective mitochondria through the process of autophagy. Thus, an impairment in the mitophagy pathway might trigger the gradual accumulation of defective mitochondria. Accumulating evidence suggest that inflammation and mitochondrial dysfunction are linked to the pathogenesis of depression. In this article, we have reviewed the role of impaired mitophagy as a contributing factor in depression pathophysiology. Further, we have discussed the potential …

Revisiting The Controversy: The Role Of Fungi In Chronic Rhinosinusitis, Matthew A Tyler, Kent Lam, Michael J Marino, William C Yao, Isaac Schmale, Martin J Citardi, Amber U Luong

Student and Faculty Publications

In the last two decades, the development of culture-independent genomic techniques has facilitated an increased appreciation of the microbiota-immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial.

Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a Type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have …

Glycogen Storage Disease Type Ia: Current Management Options, Burden And Unmet Needs, Terry G J Derks, David F Rodriguez-Buritica, Ayesha Ahmad, Foekje De Boer, María L Couce, Sarah C Grünert, Philippe Labrune, Nerea López Maldonado, Carolina Fischinger Moura De Souza, Rebecca Riba-Wolman, Alessandro Rossi, Heather Saavedra, Rupal Naik Gupta, Vassili Valayannopoulos, John Mitchell

Student and Faculty Publications

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists …

Computer-Assisted Analysis Of Oral Antifungal Therapy In Chronic Rhinosinusitis With Airway Mycosis: A Retrospective Cohort Analysis, Evan Li, Michael Scheurer, Farrah Kheradmand, Amber U Luong, David B Corry

Student and Faculty Publications

Environmental fungi are etiologically related to chronic rhinosinusitis (CRS) with airway mycosis, but their infectious role remains uncertain, in part because of potentially inadequate methods of disease quantitation. Our objective was to determine objective radiographic and symptomatic outcomes of oral antifungal therapy in adult patients with CRS and airway mycosis by using computer-assisted analysis. We conducted a retrospective study of 65 patients with CRS and culture-proven airway mycosis in a single-center referral-based academic practice, comparing paired sinus computed tomography (CT) scans and symptom scores prior to and during chronic oral antifungal therapy using computer-assisted analysis of sino-mucosal area (CAASMA). A …

Ucp3 (Uncoupling Protein 3) Insufficiency Exacerbates Left Ventricular Diastolic Dysfunction During Angiotensin Ii-Induced Hypertension, Xu Chen, Sadia Ashraf, Nadia Ashraf, Romain Harmancey

Student and Faculty Publications

Background Left ventricular diastolic dysfunction, an early stage in the pathogenesis of heart failure with preserved ejection fraction, is exacerbated by joint exposure to hypertension and obesity; however, the molecular mechanisms involved remain uncertain. The mitochondrial UCP3 (uncoupling protein 3) is downregulated in the heart with obesity. Here, we used a rat model of UCP3 haploinsufficiency (ucp3

Avoidance Of St-Segment-Elevation Myocardial Infarction Treatment For >1 Week Due To Covid-19 Fears, Rahul V Annabathula, Gregory J Sinner, Talal S Alnabelsi, Rachel P Goodwin, Vincent L Sorrell

The Texas Heart Institute Journal

During the coronavirus disease 2019 (COVID-19) pandemic, social distancing guidelines have negatively affected the care-seeking behavior of patients with chronic medical conditions, including those with cardiovascular disease. We report the case of a 60-year-old man with vague gastrointestinal symptoms who waited more than 1 week to seek treatment for fear of COVID-19 infection. On presentation at another hospital, he was found to have had an anterior myocardial infarction, and he underwent percutaneous coronary intervention to stent an occluded proximal left anterior descending coronary artery. Subsequently, the patient experienced refractory cardiogenic shock and, during his transfer to our hospital, refractory ventricular …

Cheyne-Stokes Respiration In A 17-Year-Old Boy Awaiting Heart Transplantation, Nooralam A Rai, Aliva De, Carin Lamm

The Texas Heart Institute Journal

Cheyne-Stokes respiration is a pattern of alternating central apnea and hyperpnea. It is well described in adults with congestive heart failure, but not in children.

We report the case of a 17-year-old boy whose systolic heart failure was complicated by Cheyne-Stokes respiration. He was given supportive therapy until heart transplant, after which his Cheyne-Stokes respiration clinically resolved. Clinicians should be aware of this uncommon condition in pediatric and adolescent patients who have advanced heart failure and irregular breathing.

Sudden Cardiac Death In Athletes, Darren C Tsang, Mark S Link

The Texas Heart Institute Journal

No abstract provided.

Medical And Device Therapy For Stroke Prevention In Patients With Atrial Fibrillation, Sophia Huang, Payam Safavi-Naeini, Abdi Rasekh

The Texas Heart Institute Journal

No abstract provided.

Extracorporeal Membrane Oxygenation Rescue For Severe Aspiration Pneumonitis In Two Patients After Roux-En-Y Gastric Bypass Procedure, Melissa M Felinski, Daniyal Abbas, Peter A Walker, John A Primomo, Tanyaradzwa M Kajese, Biswajit Kar, Igor D Gregoric, Igor Banjac, Lisa Janowiak, Sriram Nathan, Rahat Hussain, Sheilendra S Mehta, Kulvinder S Bajwa, Shinil K Shah, Bindu Akkanti

Student and Faculty Publications

Roux-en-y gastric bypass (RYGB) is one of the most common weight loss surgical procedures performed in the United States. Early post-operative small bowel obstruction is a rare but potentially morbid, complication of RYGB. We report two patients who underwent RYGB and required subsequent treatment for a post-operative small bowel obstruction. Their post-operative course was complicated by severe aspiration pneumonitis leading to hypoxemic respiratory failure requiring rescue with femoral veno-venous extracorporeal membrane oxygenation (V-V ECMO). Both patients were successfully extubated, weaned off V-V ECMO support, and discharged to home. These cases highlight the potential role of V-V ECMO for patients who …

Diabetes Detection And Prevention In Dermatology, Alexandra Ngo, Luise Froessl, John Wesley Mcwhorter, William Brett Perkison, Rajani Katta

Student and Faculty Publications

We are currently in the midst of an international epidemic of diabetes mellitus (DM) and prediabetes. The prevalence of DM in the United States is estimated at 9.4% of the population across all ages, while an estimated 1 in 3 Americans (33.9%) has prediabetes. According to the WHO, about 60 million people suffer from diabetes in the European Region. Dermatologists may play an important role in tackling this epidemic via efforts to improve early detection of both diabetes and prediabetes. Dermatologists often treat patients with, or at risk of, diabetes. This includes patients who present with cutaneous manifestations such as …

Primary Ciliary Dyskinesia: Ancestral Haplotypes Analysis Of The Rsph4a Founder Mutation In Puerto Rico, Wilfredo De Jesús-Rojas, Dalilah Reyes De Jesús, Angélica M Nieves, Ricardo A Mosquera, Juan C Martinez-Cruzado

Student and Faculty Publications

Genetic mutations in >50 genes, including RSPH4A, can lead to primary ciliary dyskinesia (PCD). RSPH4A mutations affect radial spokes, which alter the configuration of the ciliary ultrastructure and lead to chronic oto-sinopulmonary disease. The RSPH4A [c.921+3_6delAAGT] founder mutation was described as one cause of PCD without laterality defects in Puerto Rico. The average Puerto Rican genetic composition includes 64% European, 21% African ancestral, and 15% Native-American or Taino, a native tribe in the Caribbean at the start of the European colonization, genes. Due to the relatively elevated Taino ancestry on the island, it might have contributed to the endemicity of …

Delirium In Frail Older Adults, Min Ji Kwak

Student and Faculty Publications

Delirium and frailty are prevalent geriatric syndromes and important public health issues among older adults. The prevalence of delirium among hospitalized older adults ranges from 15% to 75%, while that of frailty ranges from 12% to 24%. The exact pathophysiology of these two conditions has not been clearly identified, although several hypotheses have been proposed. However, these conditions are considered to be multifactorial in etiology and are associated with inflammation related to aging, alterations in vascular systems, genetics, and nutritional deficiency. Furthermore, clinically, they are significantly associated with frailty, which increases the risk of delirium by almost two- to three-fold …

Primary Osteoarthritis Early Joint Degeneration Induced By Endoplasmic Reticulum Stress Is Mitigated By Resveratrol, Jacqueline T Hecht, Alka C Veerisetty, Juliana Wu, Francoise Coustry, Mohammad G Hossain, Frankie Chiu, Francis H Gannon, Karen L Posey

Student and Faculty Publications

Increasing numbers of people are living with osteoarthritis (OA) due to aging and obesity, creating an urgent need for effective treatment and preventions. Two top risk factors for OA, age and obesity, are associated with endoplasmic reticulum (ER) stress. The I-ERS mouse, an ER stress-driven model of primary OA, was developed to study the role of ER stress in primary OA susceptibility. The I-ERS mouse has the unique ability to induce ER stress in healthy adult articular chondrocytes and cartilage, driving joint degeneration that mimics early primary OA. In this study, ER stress-induced damage occurred gradually and stimulated joint degeneration …

Atypical Idiopathic Intracranial Hypertension Presenting As Cyclic Vomiting Syndrome: A Case Report, Nafee T Talukder, Amanda H Clorfeine, Moira K Black, Shade B Moody

Student and Faculty Publications

BACKGROUND: Idiopathic intracranial hypertension is a disorder of increased intracranial pressure in the absence of cerebrospinal outflow obstruction, mass lesion, or other underlying cause. It is a rare phenomenon in prepubertal children and is most typically found in women of childbearing age. The classic presentation consists of headaches, nausea, vomiting, and visual changes; however, children present more atypically. We report a case of idiopathic intracranial hypertension in an otherwise healthy, 4-year-old child with atypical symptoms resembling those of cyclic vomiting syndrome.

CASE PRESENTATION: A 4-year-old Caucasian, otherwise healthy, male child presented to our emergency department with episodic intermittent early-morning vomiting …

Occlusive Pulmonary Artery Thrombosis In A Healthy Neonate With No Identifiable Risk Factors, Cynthia Laviolette, Jason Turner, Latasha Lewis, Song-Gui Yang, Tim Pettitt, Kurt D Piggott

Student and Faculty Publications

Pulmonary artery thrombosis is reported in neonates with risk factors for hypercoagulability. No consensus exists regarding standard therapy for this condition. We present a neonate, with no risk factors for thrombosis, who was admitted after birth to the Pediatric Cardiac Intensive Care Unit with an occlusive left pulmonary artery thrombus.