Medical Specialties Commons^™

Expert Clinical Management Of Inflammatory Immune-Related Arthritis In Patients With Cancer Receiving Immune Checkpoint Inhibitors, Sebastian Bruera, Mar Riveiro-Barciela, Alexa Meara, Maria E Suarez-Almazor

Faculty, Staff and Students Publications

Introduction: Treatment guidelines for immune-related inflammatory arthritis (irAE-IA) in patients with cancer receiving immune checkpoint inhibitors (ICIs) are vague with respect to the use of specific agents. Patients are usually referred to rheumatologists for treatment. We conducted a survey of expert rheumatologists to determine current practices. We also assessed experts' views on the potential deleterious effects of various agents on tumor progression.

Methods: We conducted a survey of international experts in the treatment of irAE-IA, identified as members of collaborative scientific workgroups in this area. Experts were presented with a case of a patient with moderate irAE-IA and were asked …

Home Dialysis For Undocumented Individuals: A Five-Year Single Center Experience, Laurene M Asare, Dia R Waguespack, Jose J Perez, Jade M Teakell

Faculty, Staff and Students Publications

No abstract provided.

Cardiac Surgical Bleeding, Transfusion, And Quality Metrics: Joint Consensus Statement By The Enhanced Recovery After Surgery Cardiac Society And Society For The Advancement Of Patient Blood Management, Rawn Salenger, Rakesh C Arora, Arthur Bracey, Mario D'Oria, Daniel T Engelman, Caroline Evans, Michael C Grant, Serdar Gunaydin, Vicki Morton, Sherri Ozawa, Prakash A Patel, Jacob Raphael, Todd K Rosengart, Linda Shore-Lesserson, Pierre Tibi, Aryeh Shander

Faculty, Staff and Students Publications

Background: Excessive perioperative bleeding is associated with major complications in cardiac surgery, resulting in increased morbidity, mortality, and cost.

Methods: An international expert panel was convened to develop consensus statements on the control of bleeding and management of transfusion and to suggest key quality metrics for cardiac surgical bleeding. The panel reviewed relevant literature from the previous 10 years and used a modified RAND Delphi methodology to achieve consensus.

Results: The panel developed 30 consensus statements in 8 categories, including prioritizing control of bleeding, prechest closure checklists, and the need for additional quality indicators beyond reexploration rate, such as time …

Virus-Specific T-Cell Therapy For The Management Of Viral Infections In The Immunocompromised, Kiriakos Koukoulias, Penelope Georgia Papayanni, Ann Marie Leen, Spyridoula Vasileiou

Faculty, Staff and Students Publications

Background: Immunocompromised individuals are at major risk for severe infectious complications. This is particularly relevant in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT) - a treatment modality that has proven curative for a range of malignant and nonmalignant hematological diseases. However, transplant-associated immune suppression leaves patients susceptible to infectious complications from viruses such as cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and BK virus (BKV). While pharmacological agents are available to prevent and/or treat some of these viruses, they can be associated with significant toxicities and are often ineffective. To circumvent these issues, several groups have explored the …

Oxidative Stress Promotes Lipid-Laden Macrophage Formation Via Cyp1b1, Yin Zhu, Saugata Dutta, Yohan Han, Dooyoung Choi, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Emerging evidence suggests that lipid-laden macrophages (LLM) participate in lung damage in various clinical conditions. However, the mechanisms involved in LLM formation are not fully understood. In this study, we aimed to investigate the link between reactive oxygen species (ROS) and LLM formation. We found that ROS triggered by cigarette smoke extract (CSE) or H2O2 significantly promoted LLM formation. Given the key role of ROS in LLM formation, we further demonstrated that LLM formation is induced by various ROS-producing stimuli, including bacteria, oxidized low-density lipoprotein (OxLDL), hyperoxia, and E-cigarette vapor extract (EVE). Meanwhile, cytochrome P450 family-1 subfamily B member 1 …

Atypical Presentation Of Non-Small Cell Lung Carcinoma With Metastasis To Breast Tissue, Tylar P. Seckman, Diane Krutzler-Berry, Mohamed Ashal, Waqas Mahmud, Krista L. Denning, Logan M. Lawrence

Marshall Journal of Medicine

Malignant neoplasms of the lung commonly metastasize to lymph nodes, bone, brain, and liver via hematogenous and lymphatic routes. Much less commonly, metastasis occurs in the breast. Secondary metastatic disease of the breast is very rare, with a reported incidence ranging from 0.4-1.3%­­—with primary lung cancer being one of the most anomalous sources. This case details non-small cell lung cancer metastasis to the breast with proven primary contralateral lung origination. This atypical finding prompts medical professionals to consider these malignant cells' immunologic, histologic, and pathologic makeup to understand further and treat the neoplasm.

Molecular Modification Of Queen Bee Acid And 10-Hydroxydecanoic Acid With Specific Tripeptides: Rational Design, Organic Synthesis, And Assessment For Prohealing And Antimicrobial Hydrogel Properties, Song Hong, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Weilie Zhou

School of Medicine Faculty Publications

Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. …

Establishing A Student-Run Mobile Clinic In Appalachian Kentucky: A Community-Based Pilot Program To Address Health Inequities, Bradley A. Firchow, John C. Cornelius

Journal of Appalachian Health

The establishment of a student-run mobile clinic in Morehead, Kentucky, led by students from the University of Kentucky College of Medicine’s (UKCOM) Rural Physician Leadership Program (RPLP), aims to address health inequities in rural Appalachian communities. This pilot program is designed to serve vulnerable populations, including the unhoused, by delivering free, accessible healthcare services directly to underserved populations. This program serves as a model for expanding access to healthcare in rural regions while promoting a collaborative, community-based approach to addressing social determinants of health.

Current Attitudes And Barriers Among Appalachian Patients Towards Orthopaedic Surgery, Dylan Smith Md, Justin B. West Ms, Wade Smith Md, Micah Macaskill Md, Jonathan Lash, Matthew W. Bullock Do, Mpt

Journal of Appalachian Health

Introduction: This study explores the challenges faced by residents of rural West Virginia in accessing orthopaedic care due to geographic and socioeconomic barriers.

Purpose: This study seeks to survey rural West Virginia residents about their attitudes and experiences regarding access to orthopaedic care in southern West Virginia.

Methods: A total of 132 electronic surveys were collected from rural West Virginia residents during an appointment with their primary care provider located at an affiliated outreach clinic. The survey was designed to investigate various factors influencing their access to orthopaedic care.

Results: Delays in seeking orthpaedic care are common in rural West …

Implementation Of Endometriosis Toolkit: A Quality Improvement Project To Enhance Nurse Practitioners’ Knowledge And Management, Hasbun Rachel

DNP Qualifying Manuscripts

Abstract

Background: Endometriosis, characterized by the ectopic growth of endometrial-like tissue, affects approximately 11% of reproductive-aged women in the United States. Diagnosing endometriosis is challenging due to its diverse clinical presentations, reliance on laparoscopic procedures, absence of biomarkers, and limited awareness among healthcare providers and patients.

Local Problem: The diagnostic complexity of endometriosis, compounded by reduced provider awareness and a lack of comprehensive resources, leads to delayed and suboptimal care for affected women.

Methods: This Doctor of Nursing Practice quality improvement project aimed to enhance nurse practitioners’ (NPs) knowledge and management of endometriosis through a 1-hour educational session at the …

Interventions To Prevent And Manage Infections In Pregnancy, Rahima Yasin, Li Jiang, Jai K. Das, Zulfiqar Ahmed Bhutta

Institute for Global Health and Development

Background: Care interventions aimed at preventing and treating maternal infections during the gestational period are of paramount importance. Timely immunizations, screening strategies, and management of maternal infections reduce the risk of complications for the developing fetus and play a pivotal role in improving neonatal outcomes.
Summary: We aim to summarize evidence for a total of thirteen interventions, pertaining to the prevention and treatment of maternal infections during the antenatal period, from Every Newborn Series published in The Lancet 2014. We identified the most recent systematic reviews, extracted data from each review, and conducted a sub-group meta-analysis for low-income countries and …

Sex-Specific Astrocyte Regulation Of Spinal Motor Circuits By Nkx61, Navish A Bosquez Huerta, Zhung-Fu Lee, Eun-Ah Christine Song, Junsung Woo, Yi-Ting Cheng, Debosmita Sardar, Ozlem Sert, Ehson Maleki, Kwanha Yu, Ekin Su Akdemir, Kaitlyn Sanchez, Juyeon Jo, Matthew N Rasband, Hyun Kyoung Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.1 is specifically expressed in ventral astrocytes of the spinal cord and that its deletion results in sex-specific effects on astrocyte morphology. Astrocytes from males exhibit enhanced morphological complexity, accompanied by increased motor function and cholinergic synapses. In contrast, female astrocytes exhibit reduced complexity and no changes in motor function. Mechanistically, we found that Nkx6.1 …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M Kusminski, Terry D Hinds, Philipp E Scherer

Faculty, Staff and Students Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Understanding The Impacts Of Surgical Drains On Postoperative Pain And Quality Of Life, Goutam K. Gadiraju, Matthew R. Prospero, Finn Tobias, Andrew J. Malek, Erik Reiche, Justin M. Broyles

School of Medicine Faculty Publications

Background: Surgical drains are commonly used in breast surgery and breast reconstruction for seroma prevention. Although many surgeons are aware that surgical drains can cause considerable discomfort to patients, less is understood about the specific impacts of drains on postoperative pain and quality of life (QOL). Methods: A cross-sectional survey was conducted among patients at our institution who had previously undergone mastectomy or breast reconstruction procedures to better understand patients' experiences with surgical drains. Patients were asked to report their attitudes toward a series of QOL statements and rate postoperative pain using numeric pain scales. Pair-wise analysis was used to …

Correlates Of Inaccuracy In Reporting Of Energy Intake Among Persons With Multiple Sclerosis, Stephanie L Silveira, Brenda Jeng, Barbara A Gower, Gary R Cutter, Robert W Motl

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Persons with multiple sclerosis (MS) are interested in diet as a second-line approach for disease management. This study examined potential variables that correlate with inaccuracy of self-reported energy intake (EI) in adults with MS.

METHODS: Twenty-eight participants completed two assessment appointments within a 14-day period that included a standard doubly labeled water (DLW) protocol for estimating total energy expenditure (TEE). The participants reported their EI using the Automated Self-Administered 24 h (ASA24) Dietary Assessment Tool. The primary variables of interest for explaining the discrepancy between TEE and ASA24 EI (i.e., inaccuracy) included cognition (processing speed, visuospatial memory, and verbal …

Virginia Academy Of Sleep Medicine Position Statement On School Start Times In Virginia, Sean Hesselbacher, Mariana Szklo-Coxe, Sachin Relia, Jonathan Gellman, Nicole Mcintyre

Eastern Virginia Medical Journal

The VASM endorses the 2017 AASM position statement that middle and high schools should begin no earlier than 8:30 a.m. The existing and updated scientific literature repeatedly identifies the detrimental impact of early high school start times, and the benefits of delaying start times, on the safety and well-being of students in Virginia. The adverse effects of early school start times on Virginia’s students have been demonstrated, with regards to academic performance, mental health, and driving risks. Data published since the AASM position paper highlight these dangers further. Importantly, recent studies also demonstrate some of the benefits that can come …

Social, Racial, And Economic Disparities Affecting Outcomes Of Hypertensive Adolescents, Kanya Singhapakdi, Amelia Haydel, Marla Johnston, Shengping Yang, Tamara Bradford, Dedrick Moulton, Thomas R. Kimball

School of Medicine Faculty Publications

Essential hypertension is one of the most common conditions managed in pediatric cardiology and can result in lasting deleterious effects on the cardiovascular system. Pediatric hypertension is so prevalent in the United States that it is often referred to as a public health challenge. Social determinants of health (SDH) are the cultural, economic, educational, healthcare accessibility, and political influences in the environment in which an individual is born or lives, all of which can affect that individual's overall health. This study investigated the impact of social determinants such as rurality, food insecurity, transportation challenges, minority status, income, and race on …

Coronavirus Disease 2019 (Covid-19) Real World Data Infrastructure: A Big-Data Resource For Study Of The Impact Of Covid-19 In Patient Populations With Immunocompromising Conditions, James M. Crawford, Lynne Penberthy, Ligia A. Pinto, Keri N. Althoff, Magdalene M. Assimon, Oren Cohen, Laura Gillim, Tracy L. Hammonds, Shilpa Kapur, Harvey W. Kaufman, David Kwasny, Jean W. Liew, William A. Meyer 3rd, Shannon L. Reynolds, Cheryl B. Schleicher, Suki Subbiah, Catherine Theruviparampil, Zachary S. Wallace, Jeremy L. Warner, Suhyeon Yoon, Yonah C. Ziemba

School of Medicine Faculty Publications

Background. We developed a United States–based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials. Methods. The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and …

Multicenter Prospective Pilot Study Identifying Thrombomodulin As A Potential Biomarker For Neurocognitive Outcomes In Immune Thrombotic Thrombocytopenic Purpura, Aaron B Boothby, Michael D Evans, Shangbin Yang, Senthil Sukumar, James G Scott, Deirdra R Terrell, Spero Cataland, Marshall Mazepa

Faculty, Staff and Students Publications

Background/Objectives: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, chronically relapsing disorder that causes life-threatening thrombotic microangiopathy. Many survivors in clinical remission show evidence of ongoing silent cerebral infarction and neurocognitive deficits. Prospective longitudinal studies of this population are needed to acquire a complete understanding of the mechanism behind this ongoing neurologic injury. We aimed to assess the feasibility of a multicenter prospective study of neuropsychological and cognitive function in iTTP survivors in remission and examine novel biomarkers.

Methods: We aimed to enroll 50 iTTP patients across three USTMA consortium sites between 2019 and 2022 in a 24-month …

Case Report On Endocrine Induced Paralysis - " Unraveling The Impact Of Thyrotoxicosis On Potassium Homeostasis.", Srujith Pullipudi, Basava Chethan, Srinath K. M, Savitha Vijayakumar, Meghna B.S.

Digital Journal of Clinical Medicine

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism, marked by episodes of muscle weakness and hypokalaemia. Although it predominantly affects young Asian men, it can also occur in females and individuals from non-Asian ethnic groups. TPP is a treatable form of hypokalaemic periodic paralysis and can often be the first indication of thyrotoxicosis. Triggers such as a high-carbohydrate diet, strenuous exercise, emotional stress, and steroid use can provoke TPP attacks. During an acute episode, the key diagnostic indicators are hypokalaemia along with elevated levels of thyroxine (T4) and triiodothyronine (T3). Treatment consists of two phases: promptly correcting hypokalaemia …

Abortion Training In Family Medicine: A Post-Dobbs Examination, Innes Tounkel, Lauren Kasoff, Brittany Macdonald, Krys Foster, Allison Casola, Glen Atlas

Cooper Rowan Medical Journal

No abstract for this article type.

Geographic Disparities Impacting Oral Vaccine Performance: Observations And Future Directions, Rachel M Burke, Sasirekha Ramani, Julia Lynch, Laura V Cooper, Haeun Cho, Ananda S Bandyopadhyay, Carl D Kirkwood, A Duncan Steele, Gagandeep Kang

Faculty, Staff and Students Publications

Oral vaccines have several advantages compared with parenteral administration: they can be relatively cheap to produce in high quantities, easier to administer, and induce intestinal mucosal immunity that can protect against infection. These characteristics have led to successful use of oral vaccines against rotavirus, polio, and cholera. Unfortunately, oral vaccines for all three diseases have demonstrated lower performance in the highest-burden settings where they are most needed. Rotavirus vaccines are estimated to have >85% effectiveness against hospitalization in children < 12 months in countries with low child mortality, but only ~65% effectiveness in countries with high child mortality. Similarly, oral polio vaccines have lower immunogenicity in developing country settings compared with high-resource settings. Data are more limited for oral cholera vaccines, but suggest lower titers among children compared with adults, and, for some vaccines, lower efficacy in endemic settings compared with non-endemic settings. These disparities are likely multifactorial, and available evidence suggests a role for maternal factors (e.g. transplacental antibodies, breastmilk), host factors (e.g. genetic polymorphisms-with the best evidence for rotavirus-or previous infection), and environmental factors (e.g. gut microbiome, co-infections). Overall, these data highlight the rather ambiguous and often contradictory nature of evidence on factors affecting oral vaccine response, cautioning against broad extrapolation of outcomes based on one population or one vaccine type. Meaningful impact on performance of oral vaccines will likely only be possible with a suite of interventions, given the complex and multifactorial nature of the problem, and the degree to which contributing factors are intertwined.

Comparative Outcomes Of Endovascular Vs. Surgical Treatment In Craniocervical Junction Dural Arteriovenous Fistulas: A Systematic Review And Meta-Analysis, Basel Musmar, Joanna Roy, Atakan Orscelik, Sravanthi Koduri, Spyridon Karadimas, Saman Sizdahkhani, Elias Atallah, Stavropoula Tjoumakaris, Michael Gooch, Hekmat Zarzour, Ritam Ghosh, Richard Schmidt, Robert Rosenwasser, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND: Craniocervical junction dural arteriovenous fistulas (CCJ-DAVFs) are rare and complex vascular malformations that are challenging to diagnose and treat. This study aims to compare surgical and endovascular treatments for CCJ-DAVFs through a systematic review and meta-analysis.

METHODS: A systematic review and meta-analysis was conducted according to the PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched from inception to July 2024.

RESULTS: Fifteen studies involving 266 patients were included. Of these, 143 (53.8 %) patients underwent surgical treatment alone and 123 (46.2 %) underwent endovascular treatment alone. In the surgical group, the complete obliteration rate at last …

Racial And Ethnic Disparities In Human Papillomavirus Vaccination Among Us-Born And Foreign-Born Adults Aged 18 To 26 Years In The United States, Itunu Sokale, Jane Montealegre, Ann O Amuta, Abiodun Oluyomi, Aaron P Thrift

Faculty, Staff and Students Publications

Background/objectives: Human papillomavirus (HPV) is linked to multiple cancers that can be prevented through vaccination. While the optimal age for vaccination is in childhood and adolescence, vaccination recommendations include adults through age 26 who missed childhood/adolescent vaccination. There are limited data about disparities among adults eligible for catch-up HPV vaccination. We conducted a comprehensive examination of HPV vaccination among US young adults, disaggregating the group by race/ethnicity and nativity status to identify subgroups that may require additional interventions.

Methods: We analyzed 2019 and 2022 data of individuals aged 18-26 years from the National Health Interview Survey. Generalized linear models using …

Decriminalizing Disease: A Health Justice Approach To Infectious Diseases And Criminal Law, Sean E. Bland

Arkansas Law Review

Infectious diseases, also called communicable diseases, are largely a public health issue and should not be criminalized. This Article seeks to re-frame the discussion around the legal framework for infectious diseases in a way that moves beyond a punishment mindset and toward a health justice mindset. The focus in this Article is on health justice rather than traditional understandings of public health, defined as the science and practice of improving the health of people and their communities. The Article makes three novel contributions. First, it applies a health justice framework to the critique of infectious disease criminalization. Second, the Article …

Prevalence Of Flat Foot Among School-Age Girls And Its Relationship With Body Mass Index And Activity Level, Hisham Mohamed Hussein, Ehab Kamel, Walid Mohamed Kamel, Ibrahim Metwally Dewir, Ahmed Abdelmoniem Ibrahim

Internet Journal of Allied Health Sciences and Practice

Background: The foot and ankle are important structures in the skeletal system of the human body. Deviation in normal structure of the foot,such as in flat foot deformity, can lead to many health problems. Our study aimed to explore the prevalence of flexible flat foot (FFF) among school-age female students in the Ha’il region, Saudi Arabia, and to assess the association between the body mass index (BMI), activity level, and FFF in the selected samples. Materials and Methods: This cross-sectional study included 543 female students between 7 and 12 years of age. Data regarding age, height, weight, level …

Congenital Rickets, Melissa Intriago

Mako: NSU Undergraduate Student Journal

No abstract provided.

How Did Covid-19 Impact Physiology Research Globally? – Lessons Learned And Future Recommendations, Jeet Patel, Santanu De

Mako: NSU Undergraduate Student Journal

The Coronavirus Infectious Disease 2019 (COVID-19) pandemic caused massive changes in the medical field across the globe. As the whole world moved from in-person to remote activities, students found themselves in a predicament where they were compelled towards schooling and work online from home. This would mean that all projects, research, tests, and meetings were conducted over Zoom or other online meeting platforms. Laboratories were shut down or only a limited number of people were allowed to enter to conduct the necessary research. This paper discusses how the COVID-19 pandemic affected research process and experiments within various aspects of the …

Neutralizing Antibody Immune Correlates In Covail Trial Recipients Of An Mrna Second Covid-19 Vaccine Boost, Bo Zhang, Youyi Fong, Lauren Dang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Daniel S Graciaa, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Sydney Busch, David Benkeser, Antonia Netzl, Derek J Smith, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Peter B Gilbert, Dean Follmann

Faculty, Staff and Students Publications

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. …

Viroporin Activity Is Necessary For Intercellular Calcium Signals That Contribute To Viral Pathogenesis, J Thomas Gebert, Francesca J Scribano, Kristen A Engevik, Ethan M Huleatt, Michael R Eledge, Lauren E Dorn, Asha A Philip, Takahiro Kawagishi, Harry B Greenberg, John T Patton, Joseph M Hyser

Faculty, Staff and Students Publications

Viruses engage in a variety of processes to subvert host defenses and create an environment amenable to replication. Here, using rotavirus as a prototype, we show that calcium conductance out of the endoplasmic reticulum by the virus encoded ion channel, NSP4, induces intercellular calcium waves that extend beyond the infected cell and contribute to pathogenesis. Viruses that lack the ability to induce this signaling show diminished viral shedding and attenuated disease in a mouse model of rotavirus diarrhea. This implicates nonstructural protein 4 (NSP4) as a virulence factor and provides mechanistic insight into its mode of action. Critically, this …