Medicine and Health Sciences Commons^™

How The Commonwealth Of The Northern Mariana Islands Stalled Covid-19 For 22 Months And Managed Its First Significant Community Transmission, Dwayne Davis, Stephanie Kern-Allely, Lily Muldoon, John M. Tudela, Jesse Tudela, Renea Raho, Heather S. Pangelinan, Halina Palacios, John Tabaguel, Alan Hinson, Guillermo Lifoifoi, Warren Villagomez, Joseph R. Fauver, Haley L. Cash, Esther Muña, Sean T. Casey, Ali S. Khan

Journal Articles: Epidemiology

OBJECTIVE: The Commonwealth of the Northern Mariana Islands (CNMI) is a remote Pacific island territory with a population of 47 329 that successfully prevented the significant introduction of coronavirus disease (COVID-19) until late 2021. This study documents how the response to the introduction of COVID-19 in CNMI in 2021 was conducted with limited resources without overwhelming local clinical capacity or compromising health service delivery for the population.

METHODS: Data from COVID-19 case investigations, contact tracing, the Commonwealth's immunization registry and whole genome sequencing were collated and analysed as part of this study.

RESULTS: Between 26 March 2020 and 31 December …

Overlooked Sex And Gender Aspects Of Emerging Infectious Disease Outbreaks: Lessons Learned From Covid-19 To Move Towards Health Equity In Pandemic Response, Lynn Lieberman Lawry, Roberta Lugo-Robles, Vicki Mciver

Journal Articles: Epidemiology

Sex and gender issues are especially important in emerging infectious diseases (EIDs) but are routinely overlooked despite data and practice. Each of these have an effect either directly, via the effects on vulnerability to infectious diseases, exposures to infectious pathogens, and responses to illness, and indirectly through effects on disease prevention and control programs. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the viral agent of coronavirus disease 2019 (COVID-19) has underscored the importance of understanding the sex and gender impacts on pandemics. This review takes a broader looks at how sex and gender impact vulnerability, exposure risk, and treatment and …

Accelerated Sars-Cov-2 Intrahost Evolution Leading To Distinct Genotypes During Chronic Infection, Chrispin Chaguza, Anne M. Hahn, Mary E. Petrone, Shuntai Zhou, David Ferguson, Mallery I. Breban, Kien Pham, Mario A. Peña-Hernández, Christopher Castaldi, Verity Hill, Yale Sars-Cov-2 Genomic Surveillance Initiative, Wade Schulz, Ronald I. Swanstrom, Scott C. Roberts, Nathan D. Grubaugh, Kendall Billig, Rebecca Earnest, Joseph R. Fauver, Chaney C. Kalinch, Nicholas Kerantzas, Tobias R. Koch, Bony De Kumar, Marie L. Landry, Isabel M. Ott, David Peaper, Irina R. Tikhonova, Chantal B. F. Vogels

Journal Articles: Epidemiology

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting …

Rural–Urban Otolaryngologic Observational Workforce Analysis: The State Of Nebraska, Frantzlee Lacrete, Kendra Ratnapradipa, Kristy Carlson, Elizabeth Lyden, Jayme Dowdall

Journal Articles: Epidemiology

Objective

To analyze the rural–urban access to otolaryngology (OHNS) care within the state of Nebraska.

Design

Cross-sectional study.

Methods

Counties in Nebraska were categorized into rural versus urban status based upon the 2013 National Center for Health Statistics urban–rural classification scheme with I indicating most urban and VI indicating most rural. The information on otolaryngologists was gathered utilizing the Health Professions Tracking System. Otolaryngologists were categorized based on the county of their primary and outreach clinic location(s). Travel burden was estimated using census tract centroid distance to the nearest clinic location, aggregated to county using weighted population means to determine …

Nasal Host Response-Based Screening For Undiagnosed Respiratory Viruses: A Pathogen Surveillance And Detection Study, Nagarjuna R. Cheemarla, Amelia Hanron, Joseph R. Fauver, Jason Bishai, Timothy A. Watkins, Anderson F. Brito, Dejian Zhao, Tara Alpert, Chantal B. F. Vogels, Albert I. Ko, Wade L. Schulz, Marie L. Landry, Nathan D. Grubaugh, David Van Dijk, Ellen F. Foxman

Journal Articles: Epidemiology

BACKGROUND: Symptomatic patients who test negative for common viruses are an important possible source of unrecognised or emerging pathogens, but metagenomic sequencing of all samples is inefficient because of the low likelihood of finding a pathogen in any given sample. We aimed to determine whether nasopharyngeal CXCL10 screening could be used as a strategy to enrich for samples containing undiagnosed viruses.

METHODS: In this pathogen surveillance and detection study, we measured CXCL10 concentrations from nasopharyngeal swabs from patients in the Yale New Haven health-care system, which had been tested at the Yale New Haven Hospital Clinical Virology Laboratory (New Haven, …

Viral Kinetics Of Sequential Sars-Cov-2 Infections, Stephen M. Kissler, James A. Hay, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Deverick J. Anderson, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad

Journal Articles: Epidemiology

The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we identified 71 individuals with two well-sampled SARS-CoV-2 infections between March 11^th, 2020, and July 28^th, 2022. We compared the SARS-CoV-2 viral kinetics of first vs. second infections in this group, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a faster clearance time. Furthermore, a person's relative (rank-order) viral clearance time, compared to others infected with the …

The Association Between Mediated Deprivation And Ovarian Cancer Survival Among African American Women, Andrew B. Lawson, Joanne Kim, Courtney Johnson, Kendra Ratnapradipa, Anthony J. Alberg, Maxwell Akonde, Theresa Hastert, Elisa V. Bandera, Paul Terry, Hannah Mandle, Michele L. Cote, Melissa Bondy, Jeffrey Marks, Lauren C. Peres, Joellen Schildkraut, Edward S. Peters

Journal Articles: Epidemiology

BACKGROUND: Deprivation indices are often used to adjust for socio-economic disparities in health studies. Their role has been partially evaluated for certain population-level cancer outcomes, but examination of their role in ovarian cancer is limited. In this study, we evaluated a range of well-recognized deprivation indices in relation to cancer survival in a cohort of self-identified Black women diagnosed with ovarian cancer. This study aimed to determine if clinical or diagnostic characteristics lie on a mediating pathway between socioeconomic status (SES) and deprivation and ovarian cancer survival in a minority population that experiences worse survival from ovarian cancer.

METHODS: We …

An Epidemiological Synthesis Of Emerging And Re-Emerging Zoonotic Disease Threats In Cameroon, 2000-2022: A Systematic Review, Nancy B. Tahmo, Frankline Sevidzem Wirsiy, Dum-Buo Nnamdi, Marcel Tongo, James V. Lawler, M. Jana Broadhurst, Charles S. Wondji, David Brett-Major

Journal Articles: Epidemiology

INTRODUCTION: Population factors such as urbanization, socio-economic, and environmental factors are driving forces for emerging/re-emerging zoonotic diseases in Cameroon. To inform preparedness and prioritization efforts, this study mapped out epidemiological data (including prevalence) of zoonotic diseases occurring in Cameroon between 2000 and 2022 by demographic factors.

METHODS: Following the PRISMA guidelines, a protocol was registered in the PROSPERO database (CRD42022333059). Independent reviewers searched the PubMed, Embase, CINAHL, Cochrane, and Scopus databases on May 30, 2022 for relevant articles; duplicates were removed, and the titles, abstracts, and full texts were screened to identify eligible articles.

RESULTS: Out of 4142 articles identified, …

Nonsystematic Reporting Biases Of The Sars-Cov-2 Variant Mu Could Impact Our Understanding Of The Epidemiological Dynamics Of Emerging Variants, Mary E. Petrone, Carolina Lucas, Bridget Menasche, Mallery I. Breban, Inci Yildirim, Melissa Campbell, Saad B. Omer, Edward C. Holmes, Albert I. Ko, Nathan D. Grubaugh, Akiko Iwasaki, Craig B. Wilen, Chantal B. F. Vogels, Joseph R. Fauver

Journal Articles: Epidemiology

Developing a timely and effective response to emerging SARS-CoV-2 variants of concern (VOCs) is of paramount public health importance. Global health surveillance does not rely on genomic data alone to identify concerning variants when they emerge. Instead, methods that utilize genomic data to estimate the epidemiological dynamics of emerging lineages have the potential to serve as an early warning system. However, these methods assume that genomic data are uniformly reported across circulating lineages. In this study, we analyze differences in reporting delays among SARS-CoV-2 VOCs as a plausible explanation for the timing of the global response to the former VOC …

Evaluation Of Theoretical Frameworks To Detect Correlates Of Hpv Vaccination In The Midwest, Us, Using Structural Equation Modeling, Abraham Degarege, Shinobu Watanabe-Galloway, Kristyne Mansilla, Rahel M. Sileshi, Edward S. Peters

Journal Articles: Epidemiology

Knowledge of a valid, well-designed, and targeted theory-based framework helps better characterize reasons for HPV vaccine hesitancy and identify promising approaches to increase vaccination rates for eligible individuals. This study evaluated health theories in explaining factors affecting HPV vaccination and used a theoretical framework to identify direct and indirect predictors and mediators of HPV vaccination. A cross-sectional survey regarding HPV vaccine uptake and related factors was conducted among 1306 teenagers and young adults in the Midwest, US, in March and April 2023. Structural equation modeling confirmed fit of the framework based on the Integrated Health Theory (IHT) to the HPV …

Omega-3 Polyunsaturated Fatty Acid Levels In Maternal And Cord Plasma Are Associated With Maternal Socioeconomic Status, Alexandra Hergenrader, Matthew Van Ormer, Rebecca Slotkowski, Maranda Thompson, Alyssa Freeman, Olivia Paetz, Sarah Sweeney, Lauren Wegner, Khadijjta Ali, Nicole S. Bender, Ridhi Chaudhary, Melissa K. Thoene, Corrine K. Hanson, Ann Anderson-Berry

Journal Articles: Pediatrics

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) play a crucial role in fetal growth and neurodevelopment, while omega-6 (n-6) PUFAs have been associated with adverse pregnancy outcomes. Previous studies have demonstrated that socioeconomic status (SES) influences dietary intake of n-3 and n-6 PUFAs, but few studies have evaluated the association between maternal and cord plasma biomarkers of PUFAs and socioeconomic markers. An IRB-approved study enrolled mother-infant pairs (n = 55) at the time of delivery. Maternal and cord plasma PUFA concentrations were analyzed using gas chromatography. Markers of SES were obtained from validated surveys …

Repeated Social Defeat Stress Induces An Inflammatory Gut Milieu By Altering The Mucosal Barrier Integrity And Gut Microbiota Homeostasis, Santosh K. Yadav, Rizwan Ahmad, Cassandra M. Moshfegh, Jagadesan Sankarasubramanian, Vineet A. Joshi, Safwan K. Elkhatib, Yashpal S. Chhonker, Goeffrey A. Talmon, Chittibabu Guda, Adam Case, Amar B. Singh

Journal Articles: Cellular & Integrative Physiology

Background

Posttraumatic stress disorder (PTSD) is a mental health condition triggered by exposure to traumatic events in an individual’s life. Patients with PTSD are also at a higher risk for comorbidities. However, it is not well understood how PTSD affects human health and/or promotes the risk for comorbidities. Nevertheless, patients with PTSD harbor a proinflammatory milieu and dysbiotic gut microbiota. Gut barrier integrity helps to maintain normal gut homeostasis and its dysregulation promotes gut dysbiosis and inflammation.

Methods

We used a mouse model of repeated social defeat stress (RSDS), a preclinical model of PTSD. Behavioral studies, metagenomics analysis of the …

A Critical Role For Staphylococcal Nitric Oxide Synthase In Controlling Flavohemoglobin Toxicity, Ryan M. Singh, Sujata S. Chaudhari, Sasmita Panda, Elizabeth H. Hutfless, Cortney E. Heim, Dhananjay Shinde, Abdulelah A. Alqarzaee, Margaret F. Sladek, Vineet Kumar, Matthew C. Zimmerman, Paul D. Fey, Tammy Kielian, Vinai Chittezham Thomas

Journal Articles: Cellular & Integrative Physiology

Most coagulase-negative staphylococcal species, including the opportunistic pathogen Staphylococcus epidermidis, struggle to maintain redox homeostasis and grow under nitrosative stress. Under these conditions, growth can only resume once nitric oxide (NO) is detoxified by the flavohemoglobin Hmp. Paradoxically, S. epidermidis produces endogenous NO through its genetically encoded nitric oxide synthase (seNOS) and heavily relies on its activity for growth. In this study, we investigate the basis of the growth advantage attributed to seNOS activity. Our findings reveal that seNOS supports growth by countering Hmp toxicity. S. epidermidis relies on Hmp activity for its survival in the host under NO stress. …

Potential Of Synthetic And Natural Compounds As Novel Histone Deacetylase Inhibitors For The Treatment Of Hematological Malignancies, Dilipkumar Pal, Khushboo Raj, Shyam Sundar Nandi, Surajit Sinha, Abhishek Mishra, Arijit Mondal, Ricardo Lagoa, Jack T. Burcher, Anupam Bishayee

Journal Articles: Cellular & Integrative Physiology

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor …

Elevated Crp And Tnf-Α Levels Are Associated With Blunted Neural Oscillations Serving Fluid Intelligence, Sarah M. Dietz, Mikki Schantell, Rachel K. Spooner, Megan E. Sandal, Amirsalar Mansouri, Yasra Arif, Hannah J. Okelberry, Jason A. John, Ryan Glesinger, Pamela E. May, Elizabeth Heinrichs-Graham, Adam J. Case, Matthew C. Zimmerman, Tony W. Wilson

Journal Articles: Cellular & Integrative Physiology

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf.

METHODS: Seventy adults between the ages of 20-66 years …

Commonalities And Differences In Carotid Body Dysfunction In Hypertension And Heart Failure, Igor S. A. Felippe, Rodrigo Del Río, Harold D. Schultz, Benedito H. Machado, Julian F R Paton

Journal Articles: Cellular & Integrative Physiology

Carotid body pathophysiology is associated with many cardiovascular-respiratory-metabolic diseases. This pathophysiology reflects both hyper-sensitivity and hyper-tonicity. From both animal models and human patients, evidence indicates that amelioration of this pathophysiological signalling improves disease states such as a lowering of blood pressure in hypertension, a reduction of breathing disturbances with improved cardiac function in heart failure (HF) and a re-balancing of autonomic activity with lowered sympathetic discharge. Given this, we have reviewed the mechanisms of carotid body hyper-sensitivity and hyper-tonicity across disease models asking whether there is uniqueness related to specific disease states. Our analysis indicates some commonalities and some potential …

Exploring Barriers And Promoters Of Crc Screening Use Among Agricultural Operators: A Pilot Study Of An Application Of Concept Mapping, Cheryl Beseler, Jungyoon Kim, Roma Subramanian, Susan Harris, Karen Funkenbusch, Aaron Yoder, Tamara Robinson, Jason M. Foster, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

INTRODUCTION: The purpose of the study was to identify barriers and facilitators of colorectal cancer (CRC) screening use among agricultural operators in Nebraska, US.

METHODS: The concept mapping approach was used to engage participants and enhance the generation of ideas and opinions regarding CRC screening. Two focus groups (seven women and seven men) were conducted.

RESULTS: Among women, the cost domain was most agreed upon as important, followed by experiencing symptoms, awareness, and family. Among men, the important concepts related to CRC screening were family and friend support, feeling too young to get CRC, family or personal history of CRC, …

Biomarkers Of Toxic Exposure And Oxidative Stress Among U.S. Adult Users Of Premium Cigar Versus Other Cigar Subtypes: 2013-2019, Hongying Dai, Neal L. Benowitz, Eleanor Rogan, Abraham Degarege, James Buckley, Ali S. Khan

Journal Articles: Epidemiology

INTRODUCTION: Cigars are currently the second-highest-used combustible tobacco product among U.S. adults, but knowledge about health effects of premium cigars versus other cigar subtype use is limited.

AIMS AND METHODS: This study analyzed the biospecimen data (n = 31 875) from Waves 1-5 of the Population Assessment of Tobacco and Health Study, collected during 2013-2019. Multivariable generalized estimation equations, accounting for within-person clustering, were conducted to examine differences in urine biomarkers of exposure (BOE) from five classes of harmful and potentially harmful constituents along with a biomarker of oxidative stress (urine 8-isoprostane) among exclusive users of premium cigars versus other …

Development And Validation Of A Questionnaire To Assess Awareness And Knowledge Of Nonalcoholic Fatty Liver Disease, A Liver Cancer Etiological Factor, Among Chinese Young Adults, Yi Du, Fedja A. Rochling, Dejun Su, Kendra Ratnapradipa, Jianghu James Dong, Evi A. Farazi

Journal Articles: Epidemiology

PURPOSE: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of valid, reliable, ready-to-use survey instruments for assessing awareness and knowledge of NAFLD in this population. The aims of this study were to develop, validate, and assess the reliability of a web-based, self-administered questionnaire evaluating awareness and knowledge of NAFLD among CYA.

METHODS: Based on review of relevant literature, a draft questionnaire was initially developed. Face and content validity of the questionnaire was evaluated by an expert panel of seven gastroenterologists. The construct validity was …

Exploring First Responders' Use And Perceptions On Continuous Health And Environmental Monitoring, Jacob Grothe, Sarah Tucker, Anthony Blake, Chandran Achutan, Sharon J. Medcalf, Troy Suwondo, Ann Fruhling, Aaron Yoder

Journal Articles: Epidemiology

First responders lose their lives in the line of duty each year, and many of these deaths result from strenuous physical exertion and exposure to harmful environmental agents. Continuous health monitoring may detect diseases and alert the first responder when vital signs are reaching critical levels. However, continuous monitoring must be acceptable to first responders. The purpose of this study was to discover first responders' current use of wearable technology, their perceptions of what health and environmental indicators should be monitored, and who should be permitted to monitor them. The survey was sent to 645 first responders employed by 24 …

Occupational Therapy Intervention For Survivors Of Sex Trafficking: A Systematic Review, Alexis Spicer, Jensen Antilla, Madeleine Hubka, Sheridan Widhelm

Student Systematic Reviews: Occupational Therapy

PURPOSE: There are an estimated 15,000 to 50,000 women and children are forced into sex trafficking every year in the United States (Heinze, 2021). Sex trafficking leaves a lasting impact on survivors’ mental health and quality of life and presents these individuals with a complex set of barriers to occupational performance including various psychological challenges as well as cognitive impairments (Boyanapalli, 2020). Exposure to sex trafficking affects all aspects of a person’s life including work, community and social participation, self-care, and leisure (United Nations Office on Drugs and Crime, 2019). Occupational therapists are equipped to address these domains. The purpose …

Assessing The Agreement Of Light Microscopic Evaluation Of Oral Lichen Planus Lesions With Associated Direct Immunofluorescence Evaluation, Blake T. Hansen, Jeffrey B. Payne, Kaeli Samson, Peter J. Giannini

Journal Articles: College of Dentistry

AIM/OBJECTIVE: Assess agreement between light microscopy and direct immunofluorescence (DIF) for histopathologic evaluation of oral lichen planus (OLP).

METHODS: Records evaluated included 60 OLP, 16 lichenoid mucositis (LM), and 56 non-OLP/non-LM cases. Cases had both light microscopic and DIF evaluations. Histopathologic parameters of OLP included: (1) hydropic degeneration of the basal cell layer, (2) band-like lymphocytic infiltrate immediately subjacent to the epithelium, and (3) presence of Civatte bodies. Two calibrated examiners independently assessed light microscopic features. Examiners reviewed cases with discordant diagnoses to determine a consensus diagnosis. Intra-rater reliability (IRR), sensitivity, specificity, positive, and negative predictive values (PPV and NPV) …

High-Grade B-Cell Lymphoma, Not Otherwise Specified: A Multi-Institutional Retrospective Study, Adam S. Zayac, Daniel J. Landsburg, Mitchell E. Hughes, Allison M. Bock, Grzegorz S. Nowakowski, Emily C. Ayers, Mark Girton, Marie Hu, Amy K. Beckman, Shaoying Li, L Jeffrey Medeiros, Julie E. Chang, Adam Stepanovic, Habibe Kurt, Jose Sandoval-Sus, M Ali Ansari-Lari, Shalin K. Kothari, Anna Kress, Mina L. Xu, Pallawi Torka, Suchitra Sundaram, Stephen D. Smith, Kikkeri N. Naresh, Yasmin H. Karimi, Narendranath Epperla, David A. Bond, Umar Farooq, Mahak Saad, Andrew M. Evens, Karan Pandya, Seema G. Naik, Manali Kamdar, Bradley Haverkos, Reem Karmali, Timothy S. Oh, Julie M. Vose, Heather Nutsch, Paul G. Rubinstein, Amina Chaudhry, Adam J. Olszewski

Journal Articles: Oncology and Hematology

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, …

Angiopoietin-Like4 Is A Novel Marker Of Covid-19 Severity, Pavan K. Bhatraju, Eric D. Morrell, Ian B. Stanaway, Neha A. Sathe, Avantika Srivastava, Radu Postelnicu, Richard Green, Adair Andrews, Martin Gonzalez, Christopher J. Kratochvil, Vishakha K. Kumar, Tien-Ying Hsiang, Michael Gale, George L. Anesi, David Wyles, M. Jana Broadhurst, David Brett-Major, Vikramjit Mukherjee, Jonathan E. Sevransky, Douglas Landsittel, Chi Hung, William A Altemeier, Sina A. Gharib, Timothy M. Uyeki, J. Perren Cobb, Janice M. Liebler, David R. Crosslin, Gail P. Jarvik, Leopoldo N. Segal, Laura Evans, Carmen Mikacenic, Mark M. Wurfel

Journal Articles: Epidemiology

IMPORTANCE: Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.

OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes.

DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New …

Amyloid Cascade Hypothesis For Alzheimer’S Disease. Does It Work Under Physiological Conditions?, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Plaques in the brain consisting of proteins are a hallmark of diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such aggregates can be assembled spontaneously by specialized proteins such as amyloid beta (Ab) proteins in the case of AD. Numerous in vitro studies made a foundation for the Amyloid Cascade Hypothesis (ACH), according to which the misfolding of proteins leads to their self-assembly into toxic oligomers along with the formation of amyloid fibrils assembled as plaques in the brain. Notably physiological concentration of Ab proteins in the brain is in the low nanomolar concentration, so no spontaneous aggregation of …

Molecular Subtyping And Survival Analysis Of Osteosarcoma Reveals Prognostic Biomarkers And Key Canonical Pathways, Siddesh Southekal, Sushil Kumar Shakyawar, Prachi Bajpai, Amr Elkholy, Upender Manne, Nitish Kumar Mishra, Chittibabu Guda

Journal Articles: Genetics, Cell Biology & Anatomy

Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, a lack of understanding of the molecular subtypes remains a challenge to characterize its genetic heterogeneity and subsequently to identify diagnostic and prognostic biomarkers for developing effective treatments. In the present study, global analysis of DNA methylation, and mRNA and miRNA gene expression in OS patient samples were correlated with their clinical characteristics. The mucin family of genes, MUC6, MUC12, and MUC4, were found to be highly mutated in the OS patients. …

Rescue Of Auditory Function By A Single Administration Of Aav-Tmprss3 Gene Therapy In Aged Mice Of Human Recessive Deafness Dfnb8, Wan Du, Volkan Ergin, Corena Loeb, Mingqian Huang, Stewart Silver, Ariel Miura Armstrong, Zaohua Huang, Channabasavaiah B. Gurumurthy, Hinrich Staecker, Xuezhong Liu, Zheng-Yi Chen

Journal Articles: Genetics, Cell Biology & Anatomy

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3^A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. …

Bacteria Commonly Associated With Central Nervous System Catheter Infections Elicit Distinct Csf Proteome Signatures, Matthew K. Beaver, Dragana Noe, Ishwor Thapa, Hesham Ali, Jessica Snowden, Tammy Kielian, Gwenn Skar

Journal Articles: Pathology and Microbiology

Background: Cerebrospinal fluid (CSF) shunt infection is a common and devastating complication of the treatment of hydrocephalus. Timely and accurate diagnosis is essential as these infections can lead to long-term neurologic consequences including seizures, decreased intelligence quotient (IQ) and impaired school performance in children. Currently the diagnosis of shunt infection relies on bacterial culture; however, culture is not always accurate since these infections are frequently caused by bacteria capable of forming biofilms, such as Staphylococcus epidermidis, Cutibacterium acnes, and Pseudomonas aeruginosa resulting in few planktonic bacteria detectable in the CSF. Therefore, there is a critical need to identify a …

Investigating Novel Ispe Inhibitors Of The Mep Pathway In Mycobacterium, Seoung Ryoung Choi, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

In a recent effort to mitigate harm from human pathogens, many biosynthetic pathways have been extensively evaluated for their ability to inhibit pathogen growth and to determine drug targets. One of the important products/targets of such pathways is isopentenyl diphosphate. Isopentenyl diphosphate is the universal precursor of isoprenoids, which are essential for the normal functioning of microorganisms. In general, two biosynthetic pathways lead to the formation of isopentenyl diphosphate: (1) the mevalonate pathway in animals; and (2) the non-mevalonate or methylerythritol phosphate (MEP) in many bacteria, and some protozoa and plants. Because the MEP pathway is not found in mammalian …

An Intravenous Pancreatic Cancer Therapeutic: Characterization Of Crispr/Cas9n-Modified Clostridium Novyi-Non Toxic, Kaitlin M. Dailey, James M. Small, Jessica E. Pullan, Seth Winfree, Krysten E. Vance, Megan Orr, Sanku Mallik, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E Brooks

Journal Articles: Pathology and Microbiology

Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic-impeding the penetration of current therapeutics. C. novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C. novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C. novyi-NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C. novyi-NT could be designed …