Medicine and Health Sciences Commons^™

Gain-Of-Signal Assays For Probing Inhibition Of Sars-Cov-2 Mpro/3clpro In Living Cells, Seyed Arad Moghadasi, Morgan A Esler, Yuka Otsuka, Jordan T Becker, Sofia N Moraes, Constance B Anderson, Srinivas Chamakuri, Christopher Belica, Chloe Wick, Daniel A Harki, Damian W Young, Louis Scampavia, Timothy P Spicer, Ke Shi, Hideki Aihara, William L Brown, Reuben S Harris

Faculty, Staff and Students Publications

The main protease, Mpro, of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here, we report quantitative reporters for Mpro function in living cells in which protease inhibition by genetic or chemical methods results in robust signal readouts by fluorescence (enhanced green fluorescent protein [eGFP]) or bioluminescence (firefly luciferase). These gain-of-signal systems are scalable to high-throughput platforms for quantitative discrimination between Mpro mutants and/or inhibitor potencies as evidenced by validation of several reported inhibitors. Additional utility is shown by single Mpro amino acid variants and structural information combining to demonstrate that …

Expanding Anti-Cd38 Immunotherapy For Lymphoid Malignancies, Xu Wang, Xinfang Yu, Wei Li, Praveen Neeli, Ming Liu, Ling Li, Mingzhi Zhang, Xiaosheng Fang, Ken H Young, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Lymphoid neoplasms, including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and NK/T cell neoplasms, are a major cause of blood cancer morbidity and mortality. CD38 (cyclic ADP ribose hydrolase) is a transmembrane glycoprotein expressed on the surface of plasma cells and MM cells. The high expression of CD38 across MM and other lymphoid malignancies and its restricted expression in normal tissues make CD38 an attractive target for immunotherapy. CD38-targeting antibodies, like daratumumab, have been approved for the treatment of MM and tested against lymphoma and leukemia in multiple clinical trials.

METHODS: We generated chimeric antigen receptor (CAR) T cells targeting …

Efficacy And Outcomes Of Faecal Microbiota Transplantation For Recurrent Clostridioides Difficile Infection In Children With Inflammatory Bowel Disease, Maribeth R Nicholson, Erin Alexander, Sonia Ballal, Zev Davidovics, Michael Docktor, Michael Dole, Jonathan M Gisser, Alka Goyal, Suchitra K Hourigan, M Kyle Jensen, Jess L Kaplan, Richard Kellermayer, Judith R Kelsen, Melissa A Kennedy, Sahil Khanna, Elizabeth D Knackstedt, Jennifer Lentine, Jeffery D Lewis, Sonia Michail, Paul D Mitchell, Maria Oliva-Hemker, Tiffany Patton, Karen Queliza, Sarah Sidhu, Aliza B Solomon, David L Suskind, Madison Weatherly, Steven Werlin, Edwin F De Zoeten, Stacy A Kahn, North American Society Of Pediatric Gastroenterology And Nutrition Faecal Microbiota Transplantation Special Interest Group

Faculty, Staff and Students Publications

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD.

METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data …

Fecal Microbiota Transplantation In Decompensated Cirrhosis: A Systematic Review On Safety And Efficacy, Annie S. Hong, Kyaw Min Tun, Jenny M. Hong, Kavita Batra, Gordon Ohning

Department of Internal Medicine Faculty Research

Background and Aims: Due to increasing knowledge of the “gut–liver axis”, there has been growing interest regarding the use of fecal microbiota transplant in the management of chronic liver disease. There are limited data available and current guidelines are mostly based on expert opinions. We aim to perform the first systematic review investigating safety and efficacy of fecal microbiota transplant particularly among high-risk decompensated cirrhosis patient populations. Methods: Literature search was performed using variations of the keywords “fecal microbiota transplant” and “cirrhosis” on PubMed/Medline from inception to 3 October 2021. The resulting 116 articles were independently screened by two authors. …

Assessing The Reidentification Risks Posed By Deep Learning Algorithms Applied To Ecg Data, Arin Ghazarian, Jianwei Zheng, Daniele Struppa, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

ECG (Electrocardiogram) data analysis is one of the most widely used and important tools in cardiology diagnostics. In recent years the development of advanced deep learning techniques and GPU hardware have made it possible to train neural network models that attain exceptionally high levels of accuracy in complex tasks such as heart disease diagnoses and treatments. We investigate the use of ECGs as biometrics in human identification systems by implementing state-of-the-art deep learning models. We train convolutional neural network models on approximately 81k patients from the US, Germany and China. Currently, this is the largest research project on ECG identification. …

Thyrotoxic Periodic Paralysis: A Case Report And Discussion Of Clinical And Imaging Features, Kristian Quevada, Kishan Patel, Pauline Germaine

Cooper Rowan Medical Journal

Thyrotoxic Periodic Paralysis (TPP) is a rare manifestation of thyrotoxicosis, resulting in periodic episodes of acute onset muscle weakness in the setting of hypokalemia. The thyrotoxic form of Hypokalemic Periodic Paralysis (HPP) is less studied than the more well-known familial form due to fewer reported cases and smaller prevalence. This case study presents a 30-year-old African American male with multiple episodes of acute lower extremity muscle weakness, tachycardia, and a history of heat intolerance. Abnormal findings on thyroid ultrasound coupled with increased thyroid related immunoglobulins led to a diagnosis of TPP related to exacerbation of newly-found Graves’ disease. The case …

Treating Cytokine Storm In Patients With Covid-19, Ahmed Abdelhaleem, Deekshitha Turaka, Shameera Shaik Masthan, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Covid-19 Newsletter (Vol. 124), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.

Does Individualized Guided Selection Of Antiplatelet Therapy Improve Outcomes After Percutaneous Coronary Intervention? A Systematic Review And Meta-Analysis, Naser Yamani, Samuel Unzek, Muhammad Hasnain Mankani, Talal Almas, Adeena Musheer, Humera Qamar, Shausha Farooq, Waqas Shahnawaz, Kaneez Fatima, Vincent Figueredo

Department of Medicine

Background: The potential benefits of individualized guided selection of antiplatelet therapy over standard antiplatelet therapy in improving outcomes in patients undergoing percutaneous coronary intervention (PCI) have not been established. Therefore, we pooled evidence from available clinical trials to assess the effectiveness by comparing the two regimens in patients undergoing PCI.
Methods: We queried two electronic databases, MEDLINE and Cochrane CENTRAL, from their inception to April 20, 2021 for published randomized controlled trials in any language that compared guided antiplatelet therapy, using either genetic testing or platelet function testing, versus standard antiplatelet therapy in patients undergoing PCI. The results from trials …

Pneumococcal Carriage In Infants Post-Pcv10 Introduction In Pakistan: Results From Serial Cross-Sectional Surveys, Shahira Shahid, Amala Khan, Muhammad Imran Nisar, Farah Khalid, Muhammad Farrukh Qazi, Sheraz Ahmed, Furqan Kabir, Aneeta Hotwani, Sahrish Muneer, Syed Asad Ali, Anita K. M. Zaidi, Fyezah Jehan

Department of Paediatrics and Child Health

The 10-valent pneumococcal vaccine was introduced in Pakistan's Expanded Program on Immunization (EPI) in 2013 as a 3 + 0 schedule without catchup. We conducted three annual cross-sectional surveys from 2014-2016 to measure vaccine-type (VT) carriage in infants from a rural part of Pakistan. Nasopharyngeal specimens were collected by random sampling of infants from two union councils of Matiari. Samples were then transported to the Infectious Disease Research Laboratory (IDRL) at the Aga Khan University within 6-8 h of collection. Serotypes were established using sequential multiplex PCR. Of the 665 children enrolled across three surveys, 547 were culture-positive for pneumococcus. …

Rural-Urban And Within-Rural Differences In Covid-19 Mortality Rates, Yue Sun, Kent Jason G. Cheng, Shannon M. Monnat

Journal of Rural Social Sciences

Since late-2020, COVID-19 mortality rates have been higher in rural than in urban America, but there has also been substantial within-rural heterogeneity. Using CDC data, we compare COVID-19 mortality rates across the rural-urban continuum as well as within rural counties across different types of labor markets and by metropolitan adjacency. As of October 1, 2021, the cumulative COVID-19 mortality rate was 247.0 per 100,000 population in rural counties compared to 200.7 in urban counties. Higher COVID-19 mortality rates in rural counties are explained by lower average educational attainment and lower median household income. Within rural counties, mortality rates have been …

Sars-Cov-2 Neuroinvasion, Inflammatory Neurodegeneration And Alzheimer's Disease, Yuhai Zhao, Walter J. Lukiw

School of Medicine Faculty Publications

No abstract provided.

Fusobacterium Necrophorum Septicemia Secondary To An Ovarian Abscess: A Case Report., Amanda Morrall, Uwe Schmidt

Ambulatory and Primary Care Articles

Fusobacterium necrophorum is part of the normal oropharyngeal flora and can result in a life-threatening systemic infection known as Lemierre's syndrome. A rare presentation of F. necrophorum infection is seen in the female genital tract and is typically due to obstetric infections. Here we present a unique case of F. necrophorum without traditional features of Lemierre's syndrome with the female genital tract as a primary site. A 50-year-old female presents with a two-month history of nausea, vomiting, abdominal pain, and weight loss. She ultimately developed bilateral lower extremity necrotizing fasciitis, colonic perforation, and a left chest wall abscess. Blood and …

Evaluation Of Long-Chain Fatty Acid Respiration In Neonatal Mouse Cardiomyocytes Using Seahorse Instrument, Aude Angelini, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

Metabolic switches play a critical role in the pathophysiology of cardiac diseases, including heart failure. Here, we describe an assay for long-chain fatty acid oxidation in neonatal mouse cardiomyocytes by using a SeaHorse Flux Analyzer (Agilent). This protocol is a simplified but robust adaptation of the standard protocol that enables metabolic measurements in cells isolated from transgenic mouse models, which can be timesaving and informative. Cell isolation and culture represent a critical point that may require bench optimization.

For complete details on the use and execution of this protocol, please refer to Angelini et al. (2021).

Microrna, The Innate-Immune System And Sars-Cov-2, James M. Hill, Walter J. Lukiw

School of Medicine Faculty Publications

The single-stranded viral RNA (ssvRNA) known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19 can be effectively inactivated by a number of natural ribonucleic acid-based host cell defenses. One of the most important of these defenses includes the actions of a class of small non-coding RNAs (sncRNAs) known as microRNAs (miRNAs). Via base-pair complementarity miRNAs are capable of specifically targeting ssvRNA sequences such as SARS-CoV-2 promoting its inactivation and neutralization. RNA-sequencing and bioinformatics analysis indicate that multiple naturally-occurring human miRNAs have extensive complementarity to the SARS-CoV-2 ssvRNA genome. Since miRNA abundance, speciation, and complexity vary significantly …

Effect Of Sub-Inhibitory Concentrations Of Nitrofurantoin, Ciprofloxacin And Trimethoprim On In-Vitro Biofilm Formation In Uropathogenic Escherichia Coli, Shane Whelan

ORBioM (Open Research BioSciences Meeting)

The purpose of the current study was to determine the effect of sublethal concentrations of nitrofurantoin, ciprofloxacin and trimethoprim on biofilm formation in 57 uropathogenic Escherichia coli strains (UPEC).

The MIC of nitrofurantoin, ciprofloxacin and trimethoprim was determined for 57 UPEC isolates. Biofilm formation for each isolate with and without sub-lethal concentrations of each antibiotic was then quantified, and the statistical significance of changes in biofilm formation was ascertained by way of a Dunnett's test.

The effects of sub-MIC antibiotics on biofilm formation of UPEC were variable. A total of 22.8% of strains were induced to form biofilm by nitrofurantoin, …

Covid-19 Newsletter (Vol. 123), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.

Genetically Encoded Atp Biosensors For Direct Monitoring Of Cellular Atp Dynamics, Donnell White, Qinglin Yang

School of Medicine Faculty Publications

Adenosine 5′-triphosphate, or ATP, is the primary molecule for storing and transferring energy in cells. ATP is mainly produced via oxidative phosphorylation in mitochondria, and to a lesser extent, via glycolysis in the cytosol. In general, cytosolic glycolysis is the primary ATP producer in proliferative cells or cells subjected to hypoxia. On the other hand, mitochondria produce over 90% of cellular ATP in differentiated cells under normoxic conditions. Under pathological conditions, ATP demand rises to meet the needs of biosynthesis for cellular repair, signaling transduction for stress responses, and biochemical processes. These changes affect how mitochondria and cytosolic glycolysis function …

Mortality From Aspiration Pneumonia: Incidence, Trends, And Risk Factors, Trisha Gupte, John D. Cramer M.D., Arthur Knack Phd, Ccc-Slp

Medical Student Research Symposium

Aspiration pneumonia is a potentially preventable, aggressive type of pneumonia. Little is understood on the burden in mortality from aspiration pneumonia. Our objectives were to first examine the burden of mortality from aspiration pneumonia in the United States and second investigate comorbidities associated with aspiration pneumonia to understand risk factors. We conducted a case-control study of individuals who died of aspiration pneumonia matched to those who died of other causes. We analyzed all deaths in the United States using the Multiple Cause of Death Dataset from 1999-2017. Cases were matched with controls based on age, sex, and race. We calculated …

Meta-Analysis Of 175 Patients With Covid-19 And Seizures, Status Epilepticus, Or Cortical Myoclonus: An Individual Patient Data Analysis, Aditi Kappagantu Bs, Helena A. Brantz Ms, Amman Bhasin Ba, Cristina Jageka Bs, Rooqash Ali Md, Izzy Saef Md, Brittany M. Stopa Mph, Ayaz Khawaja Md

Medical Student Research Symposium

Objective

To characterize management and outcomes of seizures, status epilepticus, and cortical myoclonus in COVID-19, with individual patient data analysis of published literature.

Methods

Systematic literature review was conducted in accordance with PRISMA guidelines. Criteria included new-onset seizures, status epilepticus, and/or cortical myoclonus with concomitant COVID-19. COVID-19 severity was dichotomized into mild and severe cases. Good outcome was defined as discharge without severe deficits, and/or return to baseline.

Results

A total of 105 studies reporting 176 patients (male 56.3%;mean age 47.8,SD 25.6) were included. Status epilepticus occurred in 47 patients (26.7%) and myoclonus in 41 (23.3%). Severe COVID-19 occurred in …

Lysosomal Zn 2+ Release Triggers Rapid, Mitochondria-Mediated, Non-Apoptotic Cell Death In Metastatic Melanoma, Wanlu Du, Mingxue Gu, Meiqin Hu, Timothy Nold, Prateeksunder Pinchi, Wei Chen, Michael Ryan, Ahmed Bannaga, Haoxing Xu

Medical Student Research Symposium

During tumor progression, lysosome function is often maladaptively upregulated to match the high energy demand required for cancer cell hyper-proliferation and invasion. Here, we report that mucolipin TRP channel 1 (TRPML1), a lysosomal Ca2+ and Zn2+ release channel that regulates multiple aspects of lysosome function, is dramatically upregulated in metastatic melanoma cells compared with normal cells. TRPML-specific synthetic agonists (ML-SAs) are sufficient to induce rapid (within hours) lysosomal Zn2+-dependent necrotic cell death in metastatic melanoma cells while completely sparing normal cells. ML-SA-caused mitochondria swelling and dysfunction lead to cellular ATP depletion. While pharmacological inhibition or genetic silencing of TRPML1 in …

Attitudes And Barriers Toward Covid-19 Vaccination Among People Experiencing Homelessness In Detroit, Mi, Sanjna Ghanshani, Sophie Wittenberg, Richard Bryce

Medical Student Research Symposium

Introduction: People experiencing homelessness (PEH) have a high risk of exposure to communicable diseases and limited access to health care services and treatment in their communities. Despite the availability of highly effective vaccines against COVID-19, the infection prevention practices and level of COVID-19 vaccine hesitancy among PEH in Detroit have not been well studied.

Methods: Medical students administered an electronic Qualtrics survey to consented participants during outreach visits to local homeless shelters and encampments organized by Street Medicine Detroit. The questionnaire comprised six topics, including hygiene and masking practices, experience with COVID-19 testing and vaccination, and attitudes toward …

Identifying Predictors For Inflammation-Induced Preterm Birth: A Murine Study, Tzu Ning Liu Bs, Jose Galaz Md, Nardhy Gomez-Lopez Phd

Medical Student Research Symposium

Introduction: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. A large proportion of preterm deliveries is affected by intra-amniotic inflammation, which can occur in the presence (intra-amniotic infection) or absence (sterile intra-amniotic inflammation) of microbes. Studies have shown an association between intra-amniotic inflammation, cervical shortening, and changes in the cervicovaginal microbiome. However, their causal relationships are unknown. This study aims to determine the causality of intra-amniotic inflammation, cervical shortening, and cervicovaginal microbiome alterations.

Methods: Pregnant C57BL/6 dams received an ultrasound-guided intra-amniotic injection of an endotoxin lipopolysaccharide (LPS) or the alarmin interleukin-1 alpha (IL-1 alpha) on 16.5 …

Complications Of Pediatric Cochlear Implant Surgery, Andrew Stefan, Sabrina Bernardo, William Azkoul Ii, Bianca Siegel

Medical Student Research Symposium

Background:

Cochlear implantation (CI) surgery is the standard of care treatment for pediatric patients diagnosed with severe to profound sensorineural hearing loss. While considered a relatively safe operation, any invasive procedure involving the cranium has risks. However, there are few recent studies in the United States that have analyzed complication rates among children who have received CI. Furthermore, existing studies fail to discuss specific risk factors that led to post-operative complications, nor offer solutions to reduce their incidence. This study aims to 1) determine the incidence of specific complications in pediatric CI patients and 2) identify evidence-based risk factors for …

Thromboelastography Profiles Of Hemophilia A Patients On Emicizumab, Daniel J. Vanzweden, Meera Chitlur, Charity J. Stadler

Medical Student Research Symposium

Emicizumab is a new monoclonal antibody developed to dtreat people with Hemophilia A, especially those with antibodies. However, breakthrough bleeding can still occur in patients taking Emicizumab. TEG is a global coagulation assay which measures coagulability through viscosity. This study describes the use of tissue factor activated TEG in measuring bleeding profiles in patients taking Emicizumab. The goal of this prospective study is to determine if TEG can be used, which variables of TEG might be useful, and how much more useful it is than the current standard, aPtt. Findings include a 25% increased R time and 24% increased K …

Corticosteroid Injection Exhibits Symptomatic Improvement In Cts Patients With Negative Emgs, Brooke G. Garnica, Aaron R. Prater, Elizabeth A. Washnock-Schmid, Alaa Hazime, Dr. Charles S. Day

Medical Student Research Symposium

Introduction

While corticosteroid injections for carpal tunnel syndrome (CTS) are effective in patients with mild EMGs, no literature has examined the effectiveness of injections in patients with negative EMGs. We hypothesized that patients with negative EMGs will have minimal symptomatic and functional improvement.

Methods

The Boston Carpal Tunnel Questionnaire (BCTQ) was administered to patients clinically diagnosed with CTS and a negative or mild EMG prior to corticosteroid injection. The BCTQ comprises functional (FSS) and symptom status (SSS) questions. The patient was re-evaluated at 2-weeks, 1-, 3-, and 6-months post-injection. Data were analyzed via one-way ANOVA tests. A post-hoc Benjamini-Hochberg FDR …

Differential And Shared Genetic Effects On Kidney Function Between Diabetic And Non-Diabetic Individuals, Thomas W. Winkler, Humaira Rasheed, Alexander Teumer, Mathias Gorski, Bryce X. Rowan, Kira J. Stanzick, Laurent F. Thomas, Adrienne Tin, Anselm Hoppmann, Mikko Kuokkanen

School of Medicine Publications

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic …

Estimating Circadian Phase In Elementary School Children: Leveraging Advances In Physiologically Informed Models Of Circadian Entrainment And Wearable Devices, Jennette P Moreno, Kevin M Hannay, Olivia Walch, Hafza Dadabhoy, Jessica Christian, Maurice Puyau, Abeer El-Mubasher, Fida Bacha, Sarah R Grant, Rebekah Julie Park, Philip Cheng

Faculty, Staff and Students Publications

STUDY OBJECTIVES: Examine the ability of a physiologically based mathematical model of human circadian rhythms to predict circadian phase, as measured by salivary dim light melatonin onset (DLMO), in children compared to other proxy measurements of circadian phase (bedtime, sleep midpoint, and wake time).

METHODS: As part of an ongoing clinical trial, a sample of 29 elementary school children (mean age: 7.4 ± .97 years) completed 7 days of wrist actigraphy before a lab visit to assess DLMO. Hourly salivary melatonin samples were collected under dim light conditions (<5 >lx). Data from actigraphy were used to generate predictions of circadian …

An Updated Patient-Centered Sialadenitis Instrument: The Obstructive Salivary Problem Impact Test (Spit), Arushi Gulati, David M. Cognetti, David S. Cohen, M. Allison Ogden, Barry M. Schaitkin, Rohan R. Walvekar, William R. Ryan, Jolie L. Chang

School of Medicine Faculty Publications

Objective: The Chronic Obstructive Sialadenitis Symptoms questionnaire (COSS) was created to assess chronic sialadenitis symptoms and treatment response, but its development lacked patient input and validation. We analyzed COSS responses and feedback from sialadenitis patients and physician experts to create the novel obstructive Salivary Problem Impact Test (SPIT), a new standardized measure of sialadenitis-associated symptoms. Methods: We analyzed COSS responses via exploratory factor analysis (EFA) to identify essential symptom domains and reduce overlap in questions. Sialadenitis patients evaluated the significance of index symptoms identified from the literature review. Expert physicians rated symptom relevance in clinical assessment. An updated questionnaire (SPIT) …

Impact Of The Covid-19 Pandemic On The Care Continuum Of Youth Living With Hiv: Qualitative Study Of The Scale It Up Program Clinical Sites, Tyra Dark, Sitaji Gurung, Mary Dooley, Kit N. Simpson, Seyram A. Butame, Sylvie Naar

Publications and Research

The study objective was to explore the impact of COVID-19 pandemic restrictions on the clinics’ ability to provide continuous healthcare services to youth (15–24 years) living with HIV (YLWH). One focused semi-structured interview was conducted with each HIV clinic site—resulting in ten interviews. Data were analyzed using thematic analysis techniques assisted by NVIVO coding software and themes indicating barriers and facilitators to providing uninterrupted healthcare were elicited. Six themes were identified that affected the care continuum of YLWH: Timeframe of clinic preparation to address COVID-19 restrictions; impact on treatment cascade monitoring data; impact on patient care; impact on staff and …