Medicine and Health Sciences Commons^™

Intrinsic Disorder-Based Design Of Stable Globular Proteins, Galina S. Nagibina, Bogdan S. Melnik, Vladimir N. Uversky, Tatiana N. Melnik, Bogdan S. Melnik

Molecular Medicine Faculty Publications

Directed stabilization of globular proteins via substitution of a minimal number of amino acid residues is one of the most complicated experimental tasks. This work summarizes our research on the effect of amino acid substitutions on the protein stability utilizing the outputs of the analysis of intrinsic disorder predisposition of target proteins. This allowed us to formulate the basis of one of the possible approaches to the stabilization of globular proteins. The idea is quite simple. To stabilize a protein as a whole, one needs to find its "weakest spot" and stabilize it, but the question is how this weak …

Hsp22 With An N-Terminal Domain Truncation Mediates A Reduction In Tau Protein Levels, Jack M. Webster, April L. Darling, Taylor A. Sanders, Danielle M. Blazier, Yamile Vidal-Aguiar, David Beaulieu-Abdelahad, Drew G. Plemmons, Shannon E. Hill, Vladimir N. Uversky, Paula C. Bickford, Chad Anthony Dickey, Laura J. Blair

Molecular Medicine Faculty Publications

Misfolding, aggregation and accumulation of proteins are toxic elements in the progression of a broad range of neurodegenerative diseases. Molecular chaperones enable a cellular defense by reducing or compartmentalizing these insults. Small heat shock proteins (sHsps) engage proteins early in the process of misfolding and can facilitate their proper folding or refolding, sequestration, or clearance. Here, we evaluate the effects of the sHsp Hsp22, as well as a pseudophosphorylated mutant and an N-terminal domain deletion (NTDΔ) variant on tau aggregation in vitro and tau accumulation and aggregation in cultured cells. Hsp22 wild-type (WT) protein had a significant inhibitory effect on …

Rigidity Of The Outer Shell Predicted By A Protein Intrinsic Disorder Model Sheds Light On The Covid-19 (Wuhan-2019-Ncov) Infectivity, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, …

Why Covid-19 Transmission Is More Efficient And Aggressive Than Viral Transmission In Previous Coronavirus Epidemics?, Fatma Elrashdy, Elrashdy M. Redwan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face a microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (severe acute respiratory syndrome (SARS-CoV) and middle east respiratory syndrome (MERS-CoV)) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans …

Why Covid-19 Transmission Is More Efficient And Aggressive Than Viral Transmission In Previous Coronavirus Epidemics?, Fatma Elrashdy, Elrashdy M. Redwan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face a microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (severe acute respiratory syndrome (SARS-CoV) and middle east respiratory syndrome (MERS-CoV)) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans …

Granulins Modulate Liquid–Liquid Phase Separation And Aggregation Of The Prion-Like C-Terminal Domain Of The Neurodegeneration-Associated Protein Tdp-43, Anukool A. Bhopatkar, Vladimir N. Uversky, Vijayaraghavan Rangachari

Molecular Medicine Faculty Publications

TAR DNA-binding protein 43 (TDP-43) has emerged as a key player in many neurodegenerative pathologies, including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Hallmarks of both FTLD and ALS are the toxic cytoplasmic inclusions of the prion-like C-terminal fragments of TDP-43 CTD (TDP-43 C-terminal domain), formed upon proteolytic cleavage of full-length TDP-43 in the nucleus and subsequent transport to the cytoplasm. Both full-length TDP-43 and its CTD are also known to form stress granules by coacervating with RNA in the cytoplasm during stress and may be involved in these pathologies. Furthermore, mutations in the PGRN gene, leading to …

New Technologies To Analyse Protein Function: An Intrinsic Disorder Perspective, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Functions of intrinsically disordered proteins do not require structure. Such structure-independent functionality has melted away the classic rigid “lock and key” representation of structure–function relationships in proteins, opening a new page in protein science, where molten keys operate on melted locks and where conformational flexibility and intrinsic disorder, structural plasticity and extreme malleability, multifunctionality and binding promiscuity represent a new-fangled reality. Analysis and understanding of this new reality require novel tools, and some of the techniques elaborated for the examination of intrinsically disordered protein functions are outlined in this review.

Lung Cancer Cells Survive Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Exposure Through Upregulation Of Cholesterol Synthesis, Mark C. Howell, Ryan Green, Roukiah Khalil, Elspeth Foran, Waise Quarni, Rajesh Nair, Stanley Stevens, Aleksandr Grinchuk, Andrew Hanna, Shyam Mohapatra, Subhra Mohapatra

Molecular Medicine Faculty Publications

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide clinical benefits over chemotherapy for lung cancer patients with EGFR activating mutations. Despite initial clinical responses, long-term efficacy is not possible because of acquired resistance to these therapies. We have developed EGFR TKI drug-tolerant (DT) human lung cancer cell lines as a model for de novo resistance. Mass spectroscopic analysis revealed that the cytochrome P450 protein, CYP51A1 (Lanosterol 14α-demethylase), which is directly involved with cholesterol synthesis, was significantly upregulated in the DT cells. Total cellular cholesterol, and more specifically, mitochondrial cholesterol, were found to be upregulated in DT cells. We …

The Dual Pi3kδ/Ck1Ε Inhibitor Umbralisib Exhibits Unique Immunomodulatory Effects On Cll T Cells, Kamira Maharaj, John J. Powers, Alex Achille, Melanie Mediavilla-Varela, Wael Gamal, Karen L. Burger, Renee Fonseca, Kun Jiang, Hari P. Miskin, Dave Maryanski, Andrii Monastyrskyi, Derek R. Duckett, William R. Roush, John L. Cleveland, Eva Sahakian, Javier Pinilla-Ibarz

Molecular Medicine Faculty Publications

The in-clinic phosphatidylinositol 3-kinase (PI3K) inhibitors idelalisib (CAL-101) and duvelisib (IPI-145) have demonstrated high rates of response and progression-free survival in clinical trials of B-cell malignancies, such as chronic lymphocytic leukemia (CLL). However, a high incidence of adverse events has led to frequent discontinuations, limiting the clinical development of these inhibitors. By contrast, the dual PI3Kδ/casein kinase-1-ε (CK1ε) inhibitor umbralisib (TGR-1202) also shows high rates of response in clinical trials but has an improved safety profile with fewer severe adverse events. Toxicities typical of this class of PI3K inhibitors are largely thought to be immune mediated, but they are poorly …

The Substantiality Of The Neuroplasticity Hypothesis Of Major Depressive Disorder: The Prospective Use Of Ketamine-Like Drugs As Antidepressants, Roma Kankaria

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Abstract

Major depressive disorder (MDD) affects approximately 17.3 million adults in the United States each year. For more than 50 years, the serotonin hypothesis of MDD, which hypothesizes that a deficiency of monoaminergic neurotransmitters results in depression, has been the foundation for neuropsychological research. However, studies reveal that only an estimated 50% of MDD patients respond to traditional, biogenic-amine-based antidepressants (ADs), like selective serotonin reuptake inhibitors (SSRIs). Research has noted that the neuroplasticity hypothesis, which posits that weakened excitatory synaptic transmission results in depression, offers an alternative mechanism by which ketamine-like drugs lacking the abuse liability and psychoactive effects of …

Ada Practice Transitions Announces National Expansion In October, American Dental Association

News Releases

This collection includes standard news releases, information kits and other documents distributed for publicity, information, announcements of events, etc. as issued from the ADA. Items included in this collection are archival and any costs, links, contact information, or other figures may be out of date. Please contact the ADA to verify information.

Applications Of Cloud-Based Quantum Computers With Cognitive Computing Algorithms In Automated, Evidence-Based Virginia Geriatric Healthcare, Henry Childs

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Quantum computers have recently headlined IBM’s next generation of products promoting computational evolution. After the successful release of the cloud-streaming quantum computer IBM Watson Q, the company has released projections for future development of quantum devices. Because of the incredible processing power of these machines and the expected integration into everyday life in the near future, what implications can this have in the healthcare field?

I am studying cloud-based quantum computers with natural language processing (NLP) algorithms and patient health record data because I want to understand automated, evidenced-based co-optimized treatment of home-bound geriatric patients in order to help my …

The Freshair Wristband: Comparison Of Personal Exposure Measured Using Different Wearable Form Factors, Elizabeth Ziying Lin

Public Health Theses

Organic air pollutants are widely used in building materials, personal care and household products. Studies have been linking the exposure to these organic air pollutants with adverse health outcomes, including respiratory, cardiovascular, neurobehavioral outcomes, and cancer. Techniques to measure personal exposure to organic air pollutants include backpacks containing filters/pumps, and a set of single pollutant monitors. These techniques usually involve solvent extraction of filters. They are expensive, time-consuming, and inefficient which are not suitable for large scale, longitudinal exposome studies. The FreshAir samplers were developed to capture a wide range of compounds simultaneously throughout the exposure, its high degree of …

A Feel For The Space: Engagement With The Built Environment Of Treatment Spaces Among Individuals In Recovery, James Richey

Public Health Theses

Background

Treatment spaces for substance use disorders (SUD) are diverse with respect to treatment modality and population served. However, there is a lack of literature describing the design of treatment spaces and treatment engagement. This project aims to identify how the built environment of SUD treatment spaces play a role in treatment acceptability, retention, and outcomes.

Methods

We conducted 15 semi-structured interviews with individuals in outpatient SUD treatment in southern Connecticut. These interviews explored individuals’ experience with the built environment of treatment spaces and facilities, including architectural and design-related features (e.g., functionality, spatial arrangement), and how space influences adherence to …

2020 Supplement Vol. 1, American Dental Association

ADA Transactions

This item is part of the Supplements subtitle of The ADA Transactions, a serial publication of the annual activities of the ADA House of Delegates (HOD)/Board of Trustees (BOT) made up of three separate subtitles: Annual Reports and Resolutions, Supplements, and the Transactions. Generally, The ADA Transactions are published in multiple volumes throughout the year. The Supplements function like an appendix and are, in more recent editions, numbered separately with page numbers determined by HOD reference committee assignation. Items are described variously as "Supplement #", "Volume #", etc. throughout the series but have been labeled here as Vol. # for …

Mapping Occupational Therapy Practice With Postsecondary Students: A Scoping Review, Karen Keptner, Karen Mccarthy

Occupational Therapy | Faculty Scholarship

Background: Legislation supports a role for occupational therapy in postsecondary settings, but this area is not a common practice area and the practice area is not well understood. This scoping review maps current literature of occupational therapists working with students in postsecondary settings in order to inform future research and practice.

Method: After identifying included articles, a narrative description of the quantitative studies along with a concept map were completed. A qualitative thematic analysis of the articles was also conducted.

Results: Twenty-five articles met the inclusion criteria. Quantitative results describe occupational therapy services as both a direct and indirect service …

Cybersecurity Risk-Responsibility Taxonomy: The Role Of Cybersecurity Social Responsibility In Small Enterprises On Risk Of Data Breach, Keiona Davis

CCAC Theses and Dissertations

With much effort being placed on the physical, procedural, and technological solutions for Information Systems (IS) cybersecurity, research studies tend to focus their efforts on large organizations while overlooking very smaller organizations (below 50 employees). This study addressed the failure to prevent data breaches in Very Small Enterprises (VSEs). VSEs contribute significantly to the economy, however, are more prone to cyber-attacks due to the limited risk mitigations on their systems and low cybersecurity skills of their employees. VSEs utilize Point-of-Sale (POS) systems that are exposed to cyberspace, however, they are often not equipped to prevent complex cybersecurity issues that can …

School-Based Speech-Language Pathologist Collaborative Practice: A Literature Review, Kaija R. Elenko

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Background: School-based speech language pathologists (SLPs) are increasing collaborative engagement with educators and other professionals in school settings. Collaborative practice in the general education classroom increased student’s awareness of literacy concepts. The push-in model of service delivery reached students with varied levels of literacy understanding. There is insufficient empirical evidence regarding school-based interprofessional practice (IPP) available to clinicians. Systemic reviews provide a model for educators and SLPs to follow; many professionals hesitate to engage in IPP because there is a deficiency in evidence of success.

Aims: Investigation of the necessary components for successful IPP and the impacts of collaboration on …

The Psychological Undertones For Delayed And Non-Treatment Seeking Behavior After Concussion, Nicholas G. Debellis

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Title: Psychological Undertones for Delayed or Non-responding After Concussion.

The topic of my research project focuses on mild traumatic brain injury (concussion) and the reason that people delay or simply never seek treatment after sustaining an injury.

Purpose: The goal of this project is to gain a general understanding for why individuals don’t seek or delay seeking help after sustaining a concussion. We believe that this project is important for helping us to identify why people don't seek treatment while shedding light on the dark figure that exists within mental health and sports culture. We hold that the data gathered …

Aging Induces B Cell Defects And Decreased Antibody Responses To Influenza Infection And Vaccination, Daniela Frasca, Bonnie B. Blomberg

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function.

Results: Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure …

Characteristics And Outcomes Of Patients Directly Discharged To Home From The Intensive Care Unit, Ann Zheng, Preeyal M. Patel, Michele Fiorella, Lauren Mcdonnell, Mina Yasuoka, Erika J. Yoo, Md

Phase 1

Introduction: Given the current era of decreasing hospital bed availability, there has been a rise in the practice of direct discharge to home (DDH) from ICUs. We evaluated the demographics, clinical characteristics, outcomes and readmission patterns among DDH patients.

Methods: Retrospective review of patients from 2 MICUs from June 2017 to June 2019 at Thomas Jefferson University hospital, an urban tertiary care center. Primary outcome of interest was 30-day hospital readmission. Patients were dichotomized into two groups based on time between ward transfer order and hospital discharge (<24 or ≥24 hours). Risk adjustment performed with Mortality Probability Model (MPM0 -III). ICU workload at admission and discharge was estimated with nine equivalents of nursing manpower use score (NEMS). Patient characteristics compared using t-test and Fisher exact or χ² test.

Results: 331 DDH patients were analyzed, with the majority …

Continuous-Flow Left Ventricular Assist Device Outflow Graft Stenting: Indications And Outcomes, Chelsey T. Wood, Mfa, Elizabeth J. Maynes, Md, Thomas J. O'Malley, Md, Rohinton J. Morris, Md, Louis E. Samuels, Md, H. Todd Massey, Md, Vakhtang Tchantchaleishvili

Phase 1

Introduction: Stenosis in the continuous-flow left ventricular assist device (CF-LVAD) outflow graft can be caused by various mechanical and anatomical factors. Increasingly, percutaneous management has been utilized to re-establish adequate CF-LVAD flow. We sought to evaluate indications for such interventions and their outcomes.

Methods: An electronic search was performed to identify all studies in the English literature reporting CF-LVAD outflow graft stenting for various etiologies. Twenty-one studies consisting of 26 patients were included in the analysis.

Results: Median patient age was 59 years [45.8-67.0] and 65.4% (17/26) were male. 58.3% (14/24) of patients had HeartWare HVAD, 37.5% (9/24) had HeartMate …

Development Of A Hert Trained Interprofessional Student Decontamination Team For Hospital Mass Casualty Response, Ashley Wong, Claire Zurlo, Edward Jasper

Phase 1

Introduction: FEMA’s Hospital Emergency Response Training (HERT) prepares healthcare workers to decontaminate patients during a mass casualty incident. This depletes the emergency department (ED) staff when they are needed most though. Developing an interprofessional student composed HERT team to screen and decontaminate affected populations will allow ED staff to handle more medically complex situations during a mass casualty event.

Methods: Likert scale surveys were conducted among ED physicians and nurses at Jefferson Hospital and HERT trained medical and nursing students at Jefferson University. These were to evaluate the training program and ED staff opinions of utilizing a student HERT …

Conversion Total Knee Arthroplasty Needs Its Own Diagnosis Related Group Facility Reimbursement Code, Jonah Stein, Michael Yayac, Md, Gregory K. Deirmengian, Md, Javad Parvizi, Md, P. Maxwell Courtney, Md

Phase 1

Introduction: Conversion from a prior surgery to a total knee arthroplasty (TKA) is a more technically difficult procedure than primary TKA and is associated with worse short-term outcomes and increased complication and readmission rates, despite being undifferentiated under the current bundled payment model. The aim of this study was to determine differences in facility costs between primary TKA and conversion TKA, which we hypothesize are significant, to ensure providers are not penalized for treatment and high-risk patients have the same access to care.

Methods: We retrospectively reviewed a consecutive series of patients undergoing primary TKA at two hospitals within …

Cardiac Risk Factors Predicting 30/90-Day Readmission Rates In Lumbar Decompression Surgeries, Kevin Xiao, Blake Nourie, Joseph Bechay, Dhruv K.C. Goyal

Phase 1

Preoperative cardiopulmonary disease is known to be a risk factor for perioperative complications in deformity surgery and lumbar fusion procedures, however there is a lack of literature evaluating cardiac risk factors and their influence on readmission rates following lumbar decompression surgery. We want to determine whether preoperative cardiac risk factors influenced the 30 and 90-day readmission rates in patients undergoing lumbar decompression surgery. Patient charts from Rothman Institute between were reviewed for history of preoperative cardiac risk factors such as coronary artery disease, congestive heart failure, myocardial infarction, stroke, cardiac catheterization, stent placement, coronary artery bypass graft, aspirin and/or clopidogrel …

Phenotype-Genotype Correlations In Patients With Epidermolysis Bullosa With Plec Mutations, Elizabeth Zhang, Masoomeh Faghankani, Hassan Vahidnezhad, Jouni Uitto

Phase 1

Epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders characterized by blistering skin and mucous membranes. Mutations of the protein plectin, encoded by PLEC, cause autosomal recessive EB simplex with muscular dystrophy (EBS-MD) and EB simplex with pyloric atresia (EBS-PA). Until now, no clear genotype-phenotype correlation has been identified from the positions of mutations in the PLEC gene. How do ten distinct families with PLEC mutations manifesting as various EB disorders compare with regard to gene mutations? The hypothesis is that clinical manifestations of EB will be more extreme in patients with more severe gene mutations.

The design of …

Surgical Resection Of Convexity Meningiomas: A Single Center Retrospective Analysis, Haley Wendt, Michael Baldassari, Donald Ye, Kevin Judy

Phase 1

Introduction: Dural convexity meningiomas (CMs) are the most common primary intracranial tumors. Although surgical resection carries relatively low risk, it is necessary to quantify perioperative risks from a large patient cohort and identify factors contributing to short-term and long-term outcomes.

Methods: Patients who underwent craniotomy for resection of CMs between January 2012-December 2018 at a single large academic center were reviewed for pre-operative demographics, radiographic characteristics, and post-operative outcomes.

Results: 122 cases of CMs were identified. Common presenting symptoms included headache (39.3%), seizure (27.0%) and weakness/paralysis (18%). CMs were located over frontal, parietal, temporal, and occipital lobes in 57.4%, …

Prevalence Of Asymptomatic Gonorrhea And Chlamydia Infections Among Ryan White Hiv Population Visiting A Center City Hiv Clinic, Sarah Stuccio, Rakhshanda Akram, Lisa A. Spacek

Phase 1

Introduction: Sexually transmitted infections (STIs) are a major public health problem. Two factors make their diagnosis challenging: frequent asymptomatic presentation and lack of screening, especially at extragenital sites. Additionally, STIs including gonorrhea (GC) and chlamydia (CT) have been shown to increase the risk of sexual HIV transmission. Information about the prevalence, as well as predictors of test positivity, of GC and CT infections can stress the importance of universal screening.

Methods: We carried out a retrospective analysis of the STI screening of patients who attended the Ryan White HIV clinic at Jefferson between 2016 and 2018. The primary …

Zero Tolerance – Mitigating The Opioid Epidemic Amongst Minimally Invasive Urologic Patients, Daniella Wong, Thenappan Chandrasekar, Md, Costas Lallas, Md

Phase 1

Introduction: Opioids are routinely prescribed following minimally invasive surgery (MIS), yet the majority of medication remains unused. However, the literature is lacking evidence for non-narcotic analgesia in MIS urologic procedures. The purpose of this study is to evaluate the efficacy of a non-narcotic postoperative pain management regimen in reducing opioid use following MIS urologic procedures.

Methods: In this prospective study, 51 MIS urologic patients were recruited over two months. Patients in the first month cohort (P1) were managed with the established pain management standard-of-care, while patients in the second month (P2) followed a non-narcotic postoperative pain management protocol that …

Development Of Vaccine Preferences In Parents Of Newborns, Ramon Ruiz, Neera Goyal

Phase 1

Introduction: The resurgence in cases of vaccine-preventable childhood diseases in the U.S. may be associated with increasing rates of vaccine hesitancy. Although previous research has sought to identify attributes of non-vaccinating parents, the timing in which parents make such vaccination decisions has yet to be explored. Our goal is to identify when first-time parents develop their vaccination preferences: before, after, or during pregnancy.

Methods: A cross sectional survey was conducted using a convenience sample of 73 first time parents at Thomas Jefferson University Hospital. Survey questions addressed timing of vaccination decisions and projected compliance with vaccine schedules. Eligibility for …