Medicine and Health Sciences Commons^™

Quantifying The Impact Of Immune History And Variant On Sars-Cov-2 Viral Kinetics And Infection Rebound: A Retrospective Cohort Study, James A. Hay, Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Radhika M. Samant, Sarah Connolly, Deverick J. Anderson, Gaurav Khullar, Matthew Mackay, Miral Patel, Shannan Kelly, April Manhertz, Isaac Eiter, Daisy Salgado, Tim Baker, Ben Howard, Joel T. Dudley, Christopher E. Mason, Manoj Nair, Yaoxing Huang, John Difiori, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad

Journal Articles: Epidemiology

BACKGROUND: The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.

METHODS: We characterized 1,280 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of age, variant, symptom status, infection history, vaccination status and antibody titer to the founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics. The frequency of viral rebounds was quantified under multiple cycle threshold (Ct) value-based definitions.

RESULTS: Among individuals detected …

Qualitative Analysis Of Cancer Care Experiences Among Rural Cancer Survivors And Caregivers, Kendra L. Ratnapradipa, Jordan Ranta, Krishtee Napit, Lady Beverly Luma, Tamara Robinson, Danae Dinkel, Laura Schabloske, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

PURPOSE: Rural (vs urban) patients experience poorer cancer outcomes and are less likely to be engaged in cancer prevention, such as screening. As part of a community needs assessment, we explored rural cancer survivors' and caregivers' experiences, perceptions, and attitudes toward cancer care services.

METHODS: We conducted 3 focus groups (N = 20) in Spring 2021 in rural Nebraska.

FINDINGS: Three patterns of cancer diagnosis were regular care/screening without noticeable symptoms, treatment for symptoms not initially identified as cancer related, and symptom self-identification. Most participants, regardless of how diagnosis was made, had positive experiences with timely referral for testing (imaging …

Intestinal Helminth Infection, Anemia, Undernutrition And Academic Performance Among School Children In Northwestern Ethiopia, Abraham Degarege, Berhanu Erko, Yohannes Negash, Abebe Animut

Journal Articles: Epidemiology

This study examined the prevalence and intensity of intestinal helminth infections and their association with anemia, undernutrition, and academic performance among school children in Maksegnit, northwestern Ethiopia. A total of 1205 school children, who attended Maksegnit Number Two Elementary School between May and July 2021, participated in this study. To determine helminth infection status, two thick Kato–Katz slides were examined for each child. Hemoglobin level was measured using a HemoCue machine. Academic performance was assessed using the mean score of all subjects children have taken for the Spring 2020/2021 academic term. Out of 1205 children examined, 45.4% were infected with …

Fielding Vaccines-Challenges And Opportunities In Outbreaks, Complex Emergencies, And Mass Gatherings, Laura J. Fischer, Robert C. Rains, Sherry M. Brett-Major, Mikiko Senga, Debra Holden, David Brett-Major

Journal Articles: Epidemiology

With the recent COVID-19 pandemic, the importance of vaccine development, distribution, and uptake has come to the forefront of the public eye. Effectively fielding vaccines during an emergency-whether that emergency is a result of an infectious disease or not-requires an understanding of usual vaccine-related processes; the impact of outbreak, complex emergencies, mass gatherings, and other events on patients, communities, and health systems; and ways in which diverse resources can be applied to successfully achieve needed vaccine uptake. In this review, both the emergency setting and briefly vaccine product design are discussed in these contexts in order to provide a concise …

Addressing And Evaluating Health Literacy In Mhealth: A Scoping Review, Margaret Emerson, Sydney Buckland, Maxwell A. Lawlor, Danae Dinkel, David J. Johnson, Maria S. Mickles, Louis Fok, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

BACKGROUND: Recent surveys have revealed many adults have basic or below basic health literacy, which is linked to medical errors, increased illness, and compromised public health. Health literacy as a concept is multi-faceted extending beyond the individual to include social structures and the context in which health information is being accessed. Delivering health information via mobile devices (mHealth) expands the amount of information available while presenting challenges to ensuring these materials are suitable for a variety of literacy needs. The aims of this study are to discover how health literacy is addressed and evaluated in mHealth app development.

METHODS: A …

Comparative Genomics, Evolutionary Epidemiology, And Rbd-Hace2 Receptor Binding Pattern In B.1.1.7 (Alpha) And B.1.617.2 (Delta) Related To Their Pandemic Response In Uk And India, Chiranjib Chakraborty, Ashish Ranjan Sharma, Manojit Bhattacharya, Bidyut Mallik, Shyam Sundar Nandi, Sang-Soo Lee

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: The massive increase in COVID-19 infection had generated a second wave in India during May-June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant.

METHODS: This study was performed in three directions to understand the pandemic response of the two emerging variants. First, …

T-Lymphocyte Tyrosine Hydroxylase Regulates T H 17 T-Lymphocytes During Repeated Social Defeat Stress, Safwan K. Elkhatib, Cassandra M. Moshfegh, Gabrielle F. Watson, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which results in deleterious changes to psychological and physical health. Patients with PTSD are especially susceptible to life-threatening co-morbid inflammation-driven pathologies, such as autoimmunity, while also demonstrating increased T-helper 17 (T_H17) lymphocyte-driven inflammation. While the exact mechanism of this increased inflammation is unknown, overactivity of the sympathetic nervous system is a hallmark of PTSD. Neurotransmitters of the sympathetic nervous system (i.e., catecholamines) can alter T-lymphocyte function, which we have previously demonstrated to be partially mitochondrial redox-mediated. Furthermore, we have previously elucidated that T-lymphocytes generate their own catecholamines, and strong …

Access, Socioeconomic Environment, And Death From Covid-19 In Nebraska, He Bai, Michelle M. Schwedhelm, John-Martin Lowe, Rachel Lookadoo, Daniel R. Anderson, Abigail Lowe, James V. Lawler, M. Jana Broadhurst, David Brett-Major

Journal Articles: Epidemiology

Our study assesses whether factors related to healthcare access in the first year of the pandemic affect mortality and length of stay (LOS). Our cohort study examined hospitalized patients at Nebraska Medicine between April and October 2020 who were tested for SARS-CoV-2 and had a charted sepsis related diagnostic code. Multivariate logistic was used to analyze the odds of mortality and linear regression was used to calculate the parameter estimates of LOS associated with COVID-19 status, age, gender, race/ethnicity, median household income, admission month, and residential distance from definitive care. Among 475 admissions, the odds of mortality is greater among …

Self-Care: An Occupational Therapy Student Perspective, Isabelle Laposha, Stacy Smallfield

Journal Articles: Occupational Therapy

Health professional students, including occupational therapy students, report increasing rates of stress, anxiety, depression, and burnout while completing their academic programs of study. Self-care is one potential solution to this crisis, as engagement in evidence-based self-care practices has been found to improve the health and well-being of various student populations; however, the self-care practices of occupational therapy students have not been well studied. Therefore, this study explored how occupational therapy students understand and practice self-care, and how self-care correlates to perceived stress. Twenty participants engaged in a focus group and completed a 72-hour time diary. Focus group results indicated that …

Peroxide Antimalarial Drugs Target Redox Homeostasis In Plasmodium Falciparum Infected Red Blood Cells, Ghizal Siddiqui, Carlo Giannangelo, Amanda De Paoli, Anna Katharina Schuh, Kim C. Heimsch, Dovile Anderson, Timothy G. Brown, Christopher A. Macraild, Jianbo Wu, Xiaofang Wang, Yuxiang Dong, Jonathan L. Vennerstrom, Katja Becker, Darren J. Creek

Journal Articles: Pharmaceutical Sciences

Plasmodium falciparum causes the most lethal form of malaria. Peroxide antimalarials based on artemisinin underpin the frontline treatments for malaria, but artemisinin resistance is rapidly spreading. Synthetic peroxide antimalarials, known as ozonides, are in clinical development and offer a potential alternative. Here, we used chemoproteomics to investigate the protein alkylation targets of artemisinin and ozonide probes, including an analogue of the ozonide clinical candidate, artefenomel. We greatly expanded the list of proteins alkylated by peroxide antimalarials and identified significant enrichment of redox-related proteins for both artemisinins and ozonides. Disrupted redox homeostasis was confirmed by dynamic live imaging of the glutathione …

Extracellular Mechanotransduction, Stephen J. Haller, Andrew T. Dudley

Journal Articles: Genetics, Cell Biology & Anatomy

We highlight the force-sensing function of extracellular matrix and present a complementary mechanotransduction paradigm.

Mintruls: Prediction Of Mirna-Mrna Target Site Interactions Using Regularized Least Square Method, Sushil Kumar Shakyawar, Siddesh Southekal, Chittibabu Guda

Journal Articles: Genetics, Cell Biology & Anatomy

Identification of miRNA-mRNA interactions is critical to understand the new paradigms in gene regulation. Existing methods show suboptimal performance owing to inappropriate feature selection and limited integration of intuitive biological features of both miRNAs and mRNAs. The present regularized least square-based method, mintRULS, employs features of miRNAs and their target sites using pairwise similarity metrics based on free energy, sequence and repeat identities, and target site accessibility to predict miRNA-target site interactions. We hypothesized that miRNAs sharing similar structural and functional features are more likely to target the same mRNA, and conversely, mRNAs with similar features can be targeted by …

Ifn-Γ Attenuates Eosinophilic Inflammation But Is Not Essential For Protection Against Rsv-Enhanced Asthmatic Comorbidity In Adult Mice, Abenaya Muralidharan, Md Bashir Uddin, Christopher Bauer, Wenzhe Wu, Xiaoyong Bao, Keer Sun

Journal Articles: Pathology and Microbiology

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage …

The Staphylococcus Aureus Cida And Lrga Proteins Are Functional Holins Involved In The Transport Of By-Products Of Carbohydrate Metabolism, Jennifer L. Endres, Sujata S. Chaudhari, Xinyan Zhang, Janani Prahlad, Shu-Qi Wang, Lily A. Foley, Sorin Luca, Jeffrey L. Bose, Vinai C. Thomas, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

The Staphylococcus aureus cidABC and lrgAB operons encode members of a well-conserved family of proteins thought to be involved in programmed cell death (PCD). Based on the structural similarities that CidA and LrgA share with bacteriophage holins, we have hypothesized that these proteins function by forming pores within the cytoplasmic membrane. To test this, we utilized a "lysis cassette" system that demonstrated the abilities of the cidA and lrgA genes to support bacteriophage endolysin-induced cell lysis. Typical of holins, CidA- and LrgA-induced lysis was dependent on the coexpression of endolysin, consistent with the proposed holin-like functions of these proteins. In …

Improved Database Filtering Technology Enables More Efficient Ab Initio Design Of Potent Peptides Against Ebola Viruses, Thomas Ripperda, Yangsheng Yu, Atul Verma, Elizabeth Klug, Michellie Thurman, St. Patrick Reid, Guangshun Wang

Journal Articles: Pathology and Microbiology

The rapid mutations of viruses such as SARS-CoV-2 require vaccine updates and the development of novel antiviral drugs. This article presents an improved database filtering technology for a more effective design of novel antiviral agents. Different from the previous approach, where the most probable parameters were obtained stepwise from the antimicrobial peptide database, we found it possible to accelerate the design process by deriving multiple parameters in a single step during the peptide amino acid analysis. The resulting peptide DFTavP1 displays the ability to inhibit Ebola virus. A deviation from the most probable peptide parameters reduces antiviral activity. The designed …

Biofilms: Formation, Research Models, Potential Targets, And Methods For Prevention And Treatment, Yajuan Su, Jaime T. Yrastorza, Mitchell Matis, Jenna Cusick, Siwei Zhao, Guangshun Wang, Jingwei Xie

Journal Articles: Pathology and Microbiology

Due to the continuous rise in biofilm-related infections, biofilms seriously threaten human health. The formation of biofilms makes conventional antibiotics ineffective and dampens immune clearance. Therefore, it is important to understand the mechanisms of biofilm formation and develop novel strategies to treat biofilms more effectively. This review article begins with an introduction to biofilm formation in various clinical scenarios and their corresponding therapy. Established biofilm models used in research are then summarized. The potential targets which may assist in the development of new strategies for combating biofilms are further discussed. The novel technologies developed recently for the prevention and treatment …

Expanding The Landscape Of Amino Acid-Rich Antimicrobial Peptides: Definition, Deployment In Nature, Implications For Peptide Design And Therapeutic Potential, Aaron P. Decker, Abraham F. Mechesso, Guangshun Wang

Journal Articles: Pathology and Microbiology

Unlike the α-helical and β-sheet antimicrobial peptides (AMPs), our knowledge on amino acid-rich AMPs is limited. This article conducts a systematic study of rich AMPs (>25%) from different life kingdoms based on the Antimicrobial Peptide Database (APD) using the program R. Of 3425 peptides, 724 rich AMPs were identified. Rich AMPs are more common in animals and bacteria than in plants. In different animal classes, a unique set of rich AMPs is deployed. While histidine, proline, and arginine-rich AMPs are abundant in mammals, alanine, glycine, and leucine-rich AMPs are common in amphibians. Ten amino acids (Ala, Cys, Gly, His, …

Type I Ifn Signaling Protects Mice From Lethal Sars-Cov-2 Neuroinvasion., Md Bashir Uddin, Yuejin Liang, Shengjun Shao, Sunil Palani, Michael Mckelvey, Scott C. Weaver, Keer Sun

Journal Articles: Pathology and Microbiology

Multiple organ damage is common in patients with severe COVID-19, even though the underlying pathogenic mechanisms remain unclear. Acute viral infection typically activates type I IFN (IFN-I) signaling. The antiviral role of IFN-I is well characterized in vitro. However, our understanding of how IFN-I regulates host immune response to SARS-CoV-2 infection in vivo is incomplete. Using a human ACE2-transgenic mouse model, we show in the present study that IFN-I receptor signaling is essential for protection against the acute lethality of SARS-CoV-2 in mice. Interestingly, although IFN-I signaling limits viral replication in the lung, the primary infection site, it is dispensable …

Catabolic Ornithine Carbamoyltransferase Activity Facilitates Growth Of Staphylococcus Aureus In Defined Medium Lacking Glucose And Arginine, Itidal Reslane, Cortney R. Halsey, Amanda Stastny, Barbara J. Cabrera, Jong-Sam Ahn, Dhananjay Shinde, Madeline R. Galac, Margaret F. Sladek, Fareha Razvi, Mckenzie K. Lehman, Kenneth W. Bayles, Vinai Chittezham Thomas, Luke D. Handke, Paul D. Fey

Journal Articles: Pathology and Microbiology

Previous studies have found that arginine biosynthesis in Staphylococcus aureus is repressed via carbon catabolite repression (CcpA), and proline is used as a precursor. Unexpectedly, however, robust growth of S. aureus is not observed in complete defined medium lacking both glucose and arginine (CDM-R). Mutants able to grow on agar-containing defined medium lacking arginine (CDM-R) were selected and found to contain mutations within ahrC, encoding the canonical arginine biosynthesis pathway repressor (AhrC), or single nucleotide polymorphisms (SNPs) upstream of the native arginine deiminase (ADI) operon arcA1B1D1C1. Reverse transcription-PCR (RT-PCR) studies found that mutations within ccpA or ahrC or …

Clinical Laboratory Testing Practices In Diffuse Gliomas Prior To Publication Of 2021 World Health Organization Classification Of Central Nervous System Tumors, Shakti H. Ramkissoon, Helen Fernandes, Dolores H. Lopez-Terrada, Meera R. Hameed, Dimitri G. Trembath, Julia A. Bridge, Neal I. Lindeman, Rhona J. Souers, Patricia Vasalos, Daniel J Brat, Joel T. Moncur

Journal Articles: Pathology and Microbiology

CONTEXT.—: Integration of molecular data into glioma classification supports diagnostic, prognostic, and therapeutic decision-making; however, testing practices for these informative biomarkers in clinical laboratories remain unclear.

OBJECTIVE.—: To examine the prevalence of molecular testing for clinically relevant biomarkers in adult and pediatric gliomas through review of a College of American Pathologists proficiency testing survey prior to the release of the 2021 World Health Organization Classification of Central Nervous System Tumors.

DESIGN.—: College of American Pathologists proficiency testing 2020 survey results from 96 laboratories performing molecular testing for diffuse gliomas were used to determine the use of testing for molecular biomarkers …