Health Services Research Commons^™

The Small Intestinal Microbiome: Vibing With Intestinal Stem Cells, Victoria Poplaski, Faith Sawyer, Sarah E Blutt

Faculty, Staff and Students Publications

The epithelial lining of the small intestine mediates its absorptive and secretory function and thus is a critical component of human health. Regeneration and renewal of the epithelium is the result of proliferation of intestinal stem cells (ISCs). Many cell types and molecular factors are known to regulate the ability of ISCs to proliferate, including adjacent neighboring epithelial cells and the underlying, supportive stromal cells. The microbiome resides in the lumen of the small intestine and is in close contact with the epithelium. Due to its proximity to ISCs, it has been hypothesized that species within the microbiome have the …

Gene-Environment Interactions Underlying The Etiology Of Neural Tube Defects, Carlo Donato Caiaffa, Cristiane Sá Roriz Fonteles, Lei Yunping, Richard H Finnell

Faculty, Staff and Students Publications

Neural tube defects (NTDs) consist of severe structural malformations of the brain and spinal cord and are the second most common structural birth defect in humans, accounting for approximately 2700 affected pregnancies every year in the United States. These numbers are highly significant, considering that birth defects remain a leading cause of infant mortality in the United States, affecting approximately 120,000 babies born annually. Survivors of these congenital malformations face long-term disability and lifelong challenges imposed by severe physical burdens compromising the afflicted individual's overall quality of life. Clearly, birth defects, and especially NTDs remain a global public health challenge, …

Perspective: Developing Future Veterans Affairs Scientists Through A Diversity, Equity, And Inclusion Program, Darius B Dawson, Valerie Lewis, Terri L Fletcher, Robert Hal Scofield

Faculty, Staff and Students Publications

For >95 years, the Department of Veterans Affairs Office of Research and Development (ORD) has been improving the lives of Veterans and all Americans through health care discovery and innovation. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives and creativity to address complex health-related problems, which helps to foster scientific innovation, improve quality of research, and advance the likelihood that underserved populations participate in and benefit from clinical and health services research. In this study, we will discuss our experiences in developing future scientists through mentored research supplements supported by ORD.

Expanding Access To Evidence-Based Psychotherapy In Va Settings: Implementation Of The Brief Cognitive Behavioral Therapy For Depression Program, Joseph Mignogna, Derrecka Boykin, Raquel D Gonzalez, Andrew Robinson, Darrell Zeno, Shubhada Sansgiry, Jennifer Broderick-Mcdaniel, Richard B Roberson, Kristen Sorocco, Jeffrey A Cully

Faculty, Staff and Students Publications

Introduction: Evidence-based psychotherapies (EBPs) are effective for mental health conditions, but access to these services remains limited and rural Veterans are particularly underserved. Specialized implementation and dissemination programs are needed to improve access to known EBPs.

Methods: The current project sought to improve access to a known EBP-brief Cognitive Behavioral Therapy for depression (Brief CBT). Diverse Veterans and those from rural settings were a focus of this work. Aligned with the RE-AIM framework, a multifaceted implementation program was used to train and support VHA providers in their use of Brief CBT in VHA mental health settings, with specific outreach efforts …

Crossing The Decarbonization Chasm: A Call To Action For Hospital And Health System Leaders To Reduce Their Greenhouse Gas Emissions, Hardeep Singh, Walt Vernon, Terri Scannell, Kathy Gerwig

Faculty, Staff and Students Publications

No abstract provided.

A Pregnant Patient Presents With Leakage Of Vaginal Fluid In The Second Trimester, Alison N Goulding, Jennifer R Mckinney, Diana Crabtree Sokol, Anitra D Beasley

Faculty, Staff and Students Publications

Morning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient’s chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case.

This report examines the story of a 43-year-old (gravida 3, para 2) woman who sought evaluation for leakage of vaginal fluid at 15 weeks of gestation. Using questions, physical examination, and testing, an illness script for the presentation emerges. As her …

Effectiveness Of Elbasvir/Grazoprevir Plus Ribavirin For Hepatitis C Virus Genotype 1a Infection And Baseline Ns5a Resistance, Deanna D Hill, Jennifer R Kramer, Kassie R Chaffin, T Christopher Mast, Michael N Robertson, Fasiha Kanwal, Barbara A Haber

Faculty, Staff and Students Publications

Introduction and objectives: In clinical trials, patients with hepatitis C virus (HCV) genotype (GT)1a infection and baseline resistance-associated substitutions (RASs) at amino acid positions 28, 30, 31, or 93 receiving elbasvir/grazoprevir for 12 weeks achieved lower rates of sustained virologic response (SVR) than those without baseline RASs. SVR rates in patients with RASs were improved when elbasvir/grazoprevir treatment duration was extended from 12 to 16 weeks and administered concomitantly with ribavirin.

Materials and methods: This was a retrospective, observational analysis using electronic health record abstraction. Patients with HCV GT1a infection and RASs at positions 28, 30, 31, or 93 who …

The Effect Of A Plasma Next-Generation Sequencing Test On Antimicrobial Management In Immunocompetent And Immunocompromised Patients-A Single-Center Retrospective Study, Denise Marie A Francisco, Laila Woc-Colburn, Travis J Carlson, Todd Lasco, Miriam Barrett, Mayar Al Mohajer

Faculty, Staff and Students Publications

Objective: To describe the use of next-generation sequencing (NGS) and to determine whether NGS leads to changes in antimicrobial management.

Design and setting: This retrospective cohort study included patients aged ≥18 years admitted to a single tertiary-care center in Houston, Texas, with an NGS test performed between January 1, 2017, and December 31, 2018.

Patients: In total, 167 NGS tests were performed. Most patients were of non-Hispanic ethnicity (n = 129), white (n = 106), and male (n = 116), with a mean age of 52 years (SD, 16). Moreover, 61 patients were immunocompromised: solid-organ transplant (n = 30), patients …

Innate Immune Cell Dysfunction And Systemic Inflammation In Children With Chronic Liver Diseases Undergoing Transplantation, Krupa R Mysore, Sunil Kannanganat, Jeremy M Schraw, Philip J Lupo, John A Goss, Kenneth D R Setchell, Farrah Kheradmand, Xian C Li, Benjamin L Shneider

Faculty, Staff and Students Publications

Advanced liver diseases (ALD) can affect immune function and compromise host defense against infections. In this study, we examined the phenotypic and functional alterations in circulating monocyte and dendritic cells (DCs) in children with ALD undergoing liver transplantation (LT). Children were stratified into 2 clusters, C1 (mild) and C2 (severe), on the basis of laboratory parameters of ALD and compared with healthy pediatric controls. Children in C2 had a significant reduction in frequencies of nonclassical monocytes and myeloid DCs. Children in C2 displayed monocyte and DC dysfunction, characterized by lower human leucocyte antigen DR expression and reduced interleukin 12 production, …

Versican Provides The Provisional Matrix For Uterine Spiral Artery Dilation And Fetal Growth, Yusuke Sagae, Akihito Horie, Akihiro Yanai, Tsutomu Ohara, Baku Nakakita, Yoshimi Kitawaki, Asuka Okunomiya, Hirohiko Tani, Ken Yamaguchi, Junzo Hamanishi, John P Lydon, Takiko Daikoku, Hideto Watanabe, Masaki Mandai

Faculty, Staff and Students Publications

The extracellular matrix (ECM) in the endometrium plays a crucial role in mammalian pregnancy. We have shown that versican secreted from the endometrial epithelium promotes embryo implantation. Versican is a proteoglycan, a major player in the provisional matrix, and versikine, its N-terminal fragment cleaved by ADAMTS proteinases, serves as a bioactive molecule. Here, since versican expression in the placenta was dynamically altered in humans and mice, we investigated the role of versican in pregnancy using uterine-specific Vcan deletion mice (uKO mice) and ADAMTS-resistant versican expressing mice (V1R mice). uKO mice exhibited insufficient spiral artery dilation, followed by fetal growth restriction …

Toward More Rigorous And Informative Nutritional Epidemiology: The Rational Space Between Dismissal And Defense Of The Status Quo, Andrew W Brown, Stella Aslibekyan, Dennis Bier, Rafael Ferreira Da Silva, Adam Hoover, David M Klurfeld, Eric Loken, Evan Mayo-Wilson, Nir Menachemi, Greg Pavela, Patrick D Quinn, Dale Schoeller, Carmen Tekwe, Danny Valdez, Colby J Vorland, Leah D Whigham, David B Allison

Faculty, Staff and Students Publications

To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo …

Assessment Of The Cytolytic Potential Of A Multivirus-Targeted T Cell Therapy Using A Vital Dye-Based, Flow Cytometric Assay, Kiriakos Koukoulias, Penelope G Papayanni, Julia Jones, Manik Kuvalekar, Ayumi Watanabe, Yovana Velazquez, Sarah Gilmore, Anastasia Papadopoulou, Ann M Leen, Spyridoula Vasileiou

Faculty, Staff and Students Publications

Reliable and sensitive characterization assays are important determinants of the successful clinical translation of immunotherapies. For the assessment of cytolytic potential, the chromium 51 (51Cr) release assay has long been considered the gold standard for testing effector cells. However, attaining the approvals to access and use radioactive isotopes is becoming increasingly complex, while technical aspects [i.e. sensitivity, short (4-6 hours) assay duration] may lead to suboptimal performance. This has been the case with our ex vivo expanded, polyclonal (CD4+ and CD8+) multivirus-specific T cell (multiVST) lines, which recognize 5 difficult-to-treat viruses [Adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein Barr …

Editorial: Health Effects And Pathophysiological Mechanisms Of One-Carbon Metabolism Nutrients Intake Throughout The Life Cycle, Jufen Liu, Yunping Lei, Lei Wang, Chao Guo

Faculty, Staff and Students Publications

No abstract provided.

Astrocytic-Based Controller Shifts Epileptic Activity To The Chaotic State, Mojde Nahtani, Mehdi Siahi, Javad Razjouyan

Faculty, Staff and Students Publications

Introduction: Investigating an effective controller to shift hippocampal epileptic periodicity to normal chaotic behavior will be new hope for epilepsy treatment. Astrocytes nourish and protect neurons and maintain synaptic transmission and network activity. Therefore, this study explored the ameliorating effect of the astrocyte computational model on epileptic periodicity.

Methods: Modified Morris-Lecar equations were used to model the hippocampal CA3 network. Network inhibitory parameters were employed to generate oscillation-induced epileptiform periodicity. The astrocyte controller was based on a functional dynamic mathematical model of brain astrocytic cells.

Results: Results demonstrated that the synchronization of two neural networks shifted the brain's chaotic state …

Advances In Prosthetic Technology: A Perspective On Ethical Considerations For Development And Clinical Translation, Hayden Gavette, Cody L Mcdonald, Kristin Kostick-Quenet, Ashley Mullen, Bijan Najafi, M G Finco

Faculty, Staff and Students Publications

Technological advancements of prostheses in recent years, such as haptic feedback, active power, and machine learning for prosthetic control, have opened new doors for improved functioning, satisfaction, and overall quality of life. However, little attention has been paid to ethical considerations surrounding the development and translation of prosthetic technologies into clinical practice. This article, based on current literature, presents perspectives surrounding ethical considerations from the authors' multidisciplinary views as prosthetists (HG, AM, CLM, MGF), as well as combined research experience working directly with people using prostheses (AM, CLM, MGF), wearable technologies for rehabilitation (MGF, BN), machine learning and artificial intelligence …

Range And Consistency Of Cardiovascular Outcomes Reported By Clinical Trials In Kidney Transplant Recipients: A Systematic Review, Gregory J Wilson, Kim Van, Emma O'Lone, Allison Tong, Jonathan C Craig, Benedicte Sautenet, Klemens Budde, Derek Forfang, John Gill, William G Herrington, Tazeen H Jafar, David W Johnson, Vera Krane, Adeera Levin, Jolanta Malyszko, Patrick Rossignol, Deirdre Sawinski, Nicole Scholes-Robertons, Giovanni Strippoli, Angela Wang, Wolfgang C Winkelmayer, Carmel M Hawley, Andrea K Viecelli

Faculty, Staff and Students Publications

BACKGROIUND: Cardiovascular disease is a major cause of morbidity and mortality in kidney transplant recipients. Trial evidence to improve cardiovascular outcomes is limited by inconsistent reporting of outcomes, which may also lack patient-relevance. This study aimed to assess the range and consistency of cardiovascular outcomes reported by contemporary trials in kidney transplant recipients.

METHODS: A systematic review of all randomized controlled trials involving adult kidney transplant recipients that reported at least 1 cardiovascular outcome from January 2012 to December 2019 was performed, including Embase, MEDLINE, Cochrane, and ClinicalTrials.gov electronic databases. Trial characteristics were extracted and all levels of specification of …

Human Papillomavirus Dose Reminder Preferences Among Parents From A Diverse Clinical Sample: A Qualitative Study, Jacqueline M Hirth, Kayla A Eboreime, Leslie E Cofie, Richard E Rupp, Abbey B Berenson

Faculty, Staff and Students Publications

Reminders are an important method for encouraging patients to return for follow-up visits, such as for successive doses of the human papillomavirus (HPV) vaccine. However, patients may have preferences for different types of reminders. This study examined which reminder methods parents of pediatric patients found most useful and their thoughts on how the reminders helped them to complete their children's HPV vaccine series. This qualitative study was conducted on a purposively sampled group of parents who participated in a multi-level intervention intended to improve uptake and completion of the HPV vaccine series. Parents who agreed to participate were interviewed by …

The Microbial Etiology Of Community-Acquired Pneumonia In Adults: From Classical Bacteriology To Host Transcriptional Signatures, Naomi J Gadsby, Daniel M Musher

Faculty, Staff and Students Publications

All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. We now review the etiology of pneumonia (at present often called "community-acquired pneumonia") beginning with classic bacteriologic techniques, which identified Streptococcus pneumoniae as the overwhelmingly common cause, to more modern bacteriologic studies, which emphasize Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis,

Super-Enhanced Marco Variant Drives Triple-Negative Breast Cancer Progression, Weei-Chin Lin, Fang-Tsyr Lin

Faculty, Staff and Students Publications

No abstract provided.

Place Cells Dynamically Refine Grid Cell Activities To Reduce Error Accumulation During Path Integration In A Continuous Attractor Model, Jose A Fernandez-Leon, Ahmet Kerim Uysal, Daoyun Ji

Faculty, Staff and Students Publications

Navigation is one of the most fundamental skills of animals. During spatial navigation, grid cells in the medial entorhinal cortex process speed and direction of the animal to map the environment. Hippocampal place cells, in turn, encode place using sensory signals and reduce the accumulated error of grid cells for path integration. Although both cell types are part of the path integration system, the dynamic relationship between place and grid cells and the error reduction mechanism is yet to be understood. We implemented a realistic model of grid cells based on a continuous attractor model. The grid cell model was …

Trib3 Mediates Fibroblast Activation And Fibrosis Though Interaction With Atf4 In Ipf, Lan Wang, Wenyu Zhao, Cong Xia, Zhongzheng Li, Weiming Zhao, Kai Xu, Ningdan Wang, Hui Lian, Ivan O Rosas, Guoying Yu

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by fibroblast activation, excessive deposition of extracellular matrix, and progressive scarring; the pathogenesis remains elusive. The present study explored the role of Tribbles pseudokinase 3 (TRIB3), a well-known stress and metabolic sensor, in IPF. TRIB3 is down-regulated in the lungs of IPF patients in comparison to control subjects. Deficiency of TRIB3 markedly inhibited A549 epithelial cells’ proliferation and migration, significantly reducing wound healing. Conversely, overexpression of TRIB3 promoted A549 cell proliferation and transmigration while it inhibited its apoptosis. Meanwhile, overexpressed TRIB3 inhibited fibroblast activation and decreased ECM …

Activity Disruption Causes Degeneration Of Entorhinal Neurons In A Mouse Model Of Alzheimer’S Circuit Dysfunction, Rong Zhao, Stacy D Grunke, Caleb A Wood, Gabriella A Perez, Melissa Comstock, Ming-Hua Li, Anand K Singh, Kyung-Won Park, Joanna L Jankowsky

Faculty, Staff and Students Publications

Neurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Here, we show that entorhinal cortex layer 2 (EC2) neurons are unusually vulnerable to prolonged neuronal inactivity compared with neighboring regions of the temporal lobe, and that reelin + stellate cells connecting EC with the hippocampus are preferentially susceptible within the EC2 population. We demonstrate that neuronal death after silencing can be elicited through multiple independent means of activity inhibition, and that preventing synaptic release, either alone or in combination with electrical shunting, is sufficient to elicit silencing-induced degeneration. Finally, we …

A Narrative Review Of Sex And Gender Differences In Sleep Disordered Breathing: Gaps And Opportunities, Margaret Bublitz, Nour Adra, Leen Hijazi, Fidaa Shaib, Hrayr Attarian, Ghada Bourjeily

Faculty, Staff and Students Publications

Introduction: Sleep disordered breathing (SDB) is a common condition, associated with multiple comorbidities including cardiovascular and metabolic disease. It has been previously established that SDB is more prevalent in men than women, shifting the literature's focus away from the latter population. As such, underdiagnosis, and thus undertreatment, of SDB in women exists.

Methods: To establish the differences in prevalence, clinical presentation, and pathophysiology of SDB between the two sexes, a narrative review of the current literature was performed.

Results: Rates of SDB are higher among men, likely driven by differences in symptom presentation between men and women, with women presenting …

Loss Of Wnt4 In The Gubernaculum Causes Unilateral Cryptorchidism And Fertility Defects, Abhishek Seth, Juan C Bournat, Olga Medina-Martinez, Armando Rivera, Joshua Moore, Hunter Flores, Jill A Rosenfeld, Liya Hu, Carolina J Jorgez

Faculty, Staff and Students Publications

Undescended testis (UDT) affects 6% of male births. Despite surgical correction, some men with unilateral UDT may experience infertility with the contralateral descended testis (CDT) showing no A-dark spermatogonia. To improve our understanding of the etiology of infertility in UDT, we generated a novel murine model of left unilateral UDT. Gubernaculum-specific Wnt4 knockout (KO) mice (Wnt4-cKO) were generated using retinoic acid receptor β2-cre mice and were found to have a smaller left-unilateral UDT. Wnt4-cKO mice with abdominal UDT had an increase in serum follicle-stimulating hormone and luteinizing hormone and an absence of germ cells in the undescended testicle. Wnt4-cKO mice …

An Open-Access, Interactive Decision-Support Tool To Facilitate Guideline-Driven Care For Hepatocellular Carcinoma, Robert J Wong, Channa Jayasekera, Patricia Jones, Fasiha Kanwal, Amit G Singal, Aijaz Ahmed, Robert Taglienti, Zobair Younossi, Laura Kulik, Neil Mehta

Faculty, Staff and Students Publications

Hepatocellular carcinoma (HCC) is increasing in incidence and is a leading cause of cancer-related mortality worldwide. Adherence to HCC surveillance guidelines and appropriate treatment triage of liver lesions may improve receipt of curative-intent treatment and improved survival. Late-stage HCC diagnosis reflects sub-optimal implementation of effective HCC surveillance, whereas inappropriate treatment triage or linkage to care accounts for the non-receipt of curative-intent in close to half of early-stage HCC in the USA. A free, open-access decision-support tool for liver lesions that incorporates current guideline recommendations in a user-friendly interface could improve appropriate and timely triage of patients to appropriate care. This …

The Us Department Of Veterans Affairs Science And Health Initiative To Combat Infectious And Emerging Life-Threatening Diseases (Va Shield): A Biorepository Addressing National Health Threats, John B Harley, Saiju Pyarajan, Elizabeth S Partan, Lauren Epstein, Jason A Wertheim, Abhinav Diwan, Christopher W Woods, Victoria Davey, Sharlene Blair, Dennis H Clark, Kenneth M Kaufman, Shagufta Khan, Iouri Chepelev, Alexander Devine, Perry Cameron, Monica F Mccann, Mary Cloud B Ammons, Devin D Bolz, Jane K Battles, Jeffrey L Curtis, Mark Holodniy, Vincent C Marconi, Charles D Searles, David O Beenhouwer, Sheldon T Brown, Jonathan P Moorman, Zhi Q Yao, Maria C Rodriguez-Barradas, Shyam Mohapatra, Osmara Y Molina De Rodriguez, Emerson B Padiernos, Eric R Mcindoo, Emily Price, Hailey M Burgoyne, Ian Robey, Dawn C Schwenke, Carey L Shive, Ronald M Przygodzki, Rachel B Ramoni, Holly K Krull, Robert A Bonomo

Faculty, Staff and Students Publications

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has demonstrated the need to share data and biospecimens broadly to optimize clinical outcomes for US military Veterans.

Methods: In response, the Veterans Health Administration established VA SHIELD (Science and Health Initiative to Combat Infectious and Emerging Life-threatening Diseases), a comprehensive biorepository of specimens and clinical data from affected Veterans to advance research and public health surveillance and to improve diagnostic and therapeutic capabilities.

Results: VA SHIELD now comprises 12 sites collecting de-identified biospecimens from US Veterans affected by SARS-CoV-2. In addition, 2 …

Role Of Bacteriophage Therapy For Resistant Infections In Transplant Recipients, Paul Nicholls, Saima Aslam

Faculty, Staff and Students Publications

Purpose of review: Multidrug-resistant organisms (MDROs) are prevalent in transplant recipients and associated with poor outcomes. We review recent cases of phage therapy used to treat recalcitrant infections in transplant recipients and explore the future role of such therapy in this setting.

Recent findings: Individual case reports and small case series suggest possible efficacy of phage therapy for the treatment of MDRO infections in pre and posttransplant patients. Importantly, there have been no serious safety concerns in the reported cases that we reviewed. There are no applicable randomized controlled trials (RCTs) to better guide phage therapy at this time.

Summary: …

Association Between Cause Of Kidney Failure And Fracture Incidence In A National Us Dialysis Population Cohort Study, Susan Ziolkowski, Sai Liu, Maria E Montez-Rath, Michelle Denburg, Wolfgang C Winkelmayer, Glenn M Chertow, Michelle M O'Shaughnessy

Faculty, Staff and Students Publications

Background: Whether fracture rates, overall and by fracture site, vary by cause of kidney failure in patients receiving dialysis is unknown.

Methods: Using the US Renal Data System, we compared fracture rates across seven causes of kidney failure in patients who started dialysis between 1997 and 2014. We computed unadjusted and multivariable adjusted proportional sub-distribution hazard models, with fracture events (overall, and by site) as the outcome and immunoglobulin A nephropathy as the reference group. Kidney transplantation and death were competing events.

Results: Among 491 496 individuals, with a median follow-up of 2.0 (25%, 75% range 0.9-3.9) years, 62 954 …

Understanding Post-Covid-19 Interstitial Lung Disease (Ild): A New Fibroinflammatory Disease Entity, Puja Mehta, Ivan O Rosas, Mervyn Singer

Faculty, Staff and Students Publications

Immunomodulation and immunity from vaccination and natural infection have reduced mortality from coronavirus disease 2019 (COVID-19). However, there are ongoing concerns regarding emerging variants and residual pulmonary sequelae in survivors, given that the lungs are the principal site for the triumvirate of infection, inflammation and injury. The initial waves of acute, severe COVID-19 were profoundly inflammatory, usually manifest as organising pneumonia ± acute respiratory distress syndrome (ARDS). The extent of the fibrogenic potential of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the modifiability of the pathogenic processes and disease course are unclear. Interestingly patients can develop ‘post-COVID interstitial lung disease’ …

Human Islet Amyloid Polypeptide (Hiapp) Protofibril-Specific Antibodies For Detection And Treatment Of Type 2 Diabetes, Angelina S Bortoletto, W Vallen Graham, Gabriella Trout, Alessandra Bonito-Oliva, Manija A Kazmi, Jing Gong, Emily Weyburne, Brandy L Houser, Thomas P Sakmar, Ronald J Parchem

Faculty, Staff and Students Publications

Type 2 diabetes mellitus (T2D) is a major public health concern and is characterized by sustained hyperglycemia due to insulin resistance and destruction of insulin-producing β cells. One pathological hallmark of T2D is the toxic accumulation of human islet amyloid polypeptide (hIAPP) aggregates. Monomeric hIAPP is a hormone normally co-secreted with insulin. However, increased levels of hIAPP in prediabetic and diabetic patients can lead to the formation of hIAPP protofibrils, which are toxic to β cells. Current therapies fail to address hIAPP aggregation and current screening modalities do not detect it. Using a stabilizing capping protein, monoclonal antibodies (mAbs) can …