Digital Commons Network^™

Recognizing Strokes In The Pacu In Adult Versus Pediatric Patients, Juliet Velhagen, Thomas Ferrer, Ricardo Falcon, Tim Petersen, Codruta Soneru

Brain & Behavioral Health Research Day

This poster discusses strokes in the post-anesthesia care unit in both adult and pediatric patients. We discuss stroke incidence, post-anesthesia stroke symptoms to be aware of, what symptoms overlap between adult and pediatric patients, and the importance of early stroke recognition.

Digital Twins For Health: A Scoping Review, Evangelia Katsoulakis, Qi Wang, Huanmei Wu, Leili Shahriyari, Richard Fletcher, Jinwei Liu, Luke Achenie, Hongfang Liu, Pamela Jackson, Ying Xiao, Tanveer Syeda-Mahmood, Richard Tuli, Jun Deng

Faculty, Staff and Student Publications

The use of digital twins (DTs) has proliferated across various fields and industries, with a recent surge in the healthcare sector. The concept of digital twin for health (DT4H) holds great promise to revolutionize the entire healthcare system, including management and delivery, disease treatment and prevention, and health well-being maintenance, ultimately improving human life. The rapid growth of big data and continuous advancement in data science (DS) and artificial intelligence (AI) have the potential to significantly expedite DT research and development by providing scientific expertise, essential data, and robust cybertechnology infrastructure. Although various DT initiatives have been underway in the …

Emulating Paul’S Ministry Leadership In A Diverse And Changing Cultural Landscape, Mark J. Lee

Doctoral Dissertations and Projects

The purpose of this Doctor of Ministry project is to train ministry leaders by studying the cross-cultural leadership characteristics of Apostle Paul. Central Steele Creek Presbyterian Church is part of the sad statistic of traditional churches that have been declining for the past thirty years. This will continue unless leaders of the church embrace the diverse culture and nature of the surrounding community. Cross-cultural leadership is needed in this time of multi-cultural communities and there is no one better than Paul to demonstrate this indispensable cross-cultural ministry paradigm. If leaders at Central are trained and motivated to embrace Paul’s cross-cultural …

Physician Assistant Students' Attitudes Toward Satisfaction And Self-Confidence In Learning Of Summative Standardized Patient Simulations In Relationship To Their Prior Healthcare Experience Hours And The Number Of Formative Assessments: A Quantitative Predictive Correlational Study, Juanita W. Skillman

Doctoral Dissertations and Projects

This quantitative, non-experimental, predictive correlational study aimed to determine if there is a relationship between the criterion variable of physician assistant students' attitudes of satisfaction and self-confidence in learning among the linear combination of the predictor variables of prior healthcare experience hours and the number of formative assessments before the summative assessment. The experiential learning theory guided this study and is valuable to physician assistant programs because the data obtained on students' perceived attitudes is crucial to improving future student simulation experiences in which competencies are measured and compared against outcomes standards set by accreditation bodies. The study included 136 …

The Inequitable Burden Of Infectious Diseases Among Remote-Living Aboriginal And Torres Strait Islander Australians: A Product Of History, Stephanie L. Enkel, Rebecca Famlonga, Hannah M. M. Thomas, Nina Lansbury, Jonathan R. Carapetis, Glenn Pearson, Asha C. Bowen

Journal of the Australian Indigenous HealthInfoNet

Insufficient and poorly maintained housing and plumbing in many remote Australian Indigenous communities in Australia results in reduced capacity to maintain personal hygiene, contributing to infectious disease inequalities. Infections from Streptococcus pyogenes (Strep A) and sequalae are often noted to be the result of contextual poverty; a product of over 230 years of discriminatory practice that has excluded Indigenous people from the basic human rights of healthy, maintained housing afforded to most in the nation. The solutions for eliminating diseases of inequity among Australian Indigenous population are known, their success is historically documented, and yet they are to be comprehensively …

The Koolungar Moorditj Healthy Skin Project: Elder And Community Led Resources Strengthen Aboriginal Voice For Skin Health, Bernadette M. Ricciardo, Jacinta Walton, Noel Nannup, Dale Tilbrook, Heather-Lynn Kessaris, Carol Michie, Brad Farrant, Roni Forrest, Annette Garlett, Joanne Hill, Larissa Jones, Natasha Kickett, Sally Smith, Delys Walton, Taleah Ugle, Nadia Rind, Richelle Douglas, Jodie Ingrey, Brenda Carter, Ainslie Poore, Ingrid Amgarth-Duff, Hannah Thomas, Prasad S. Kumarasinghe, Jonathan R. Carapetis, Asha C. Bowen

Journal of the Australian Indigenous HealthInfoNet

In partnership with local Aboriginal Community Controlled Health Organisations, the Elder-led co-designed Koolungar Moorditj Healthy Skin project is guided by principles of reciprocity, capacity building, respect, and community involvement. Through this work, the team of Elders, community members, clinicians and research staff have gained insight into the skin health needs of urban-living Aboriginal koolungar (children); and having identified a lack of targeted and culturally appropriate health literacy and health promotion resources on moorditj (strong) skin, prioritised development of community-created healthy skin resources. Community members self-appointed to Aboriginal Community Advisory Groups (CAG) on Whadjuk (Perth) …

Lepocreadiidae (Trematoda) Associated With Gelatinous Zooplankton (Cnidaria And Ctenophora) And Fishes In Australian And Japanese Waters, Thomas H. Cribb, Scott C. Cutmore, Nicholas Q.-X. Wee, Joanna G. Browne, Pablo Diaz Morales, Kylie A. Pitt

Harold W. Manter Laboratory of Parasitology: Library Materials

We examined gelatinous zooplankton from off eastern Australia for lepocreadiid trematode metacercariae. From 221 specimens of 17 species of cnidarian medusae and 218 specimens of four species of ctenophores, infections were found in seven cnidarian and two ctenophore species. Metacercariae were distinguished using cox1 mtDNA, ITS2 rDNA and morphology. We identified three species of Prodistomum Linton, 1910 [P. keyam Bray & Cribb, 1996, P. orientale (Layman, 1930), and Prodistomum Type 3], two species of Opechona Looss, 1907 [O. kahawai Bray & Cribb, 2003 and O. cf. olssoni], and Cephalolepidapedon saba Yamaguti, 1970. Two species were found in cnidarians …

Intrathecal Gene Therapy For Giant Axonal Neuropathy, Diana X Bharucha-Goebel, Joshua J Todd, Dimah Saade, Gina Norato, Minal Jain, Tanya Lehky, Rachel M Bailey, Jessica A Chichester, Roberto Calcedo, Diane Armao, A Reghan Foley, Payam Mohassel, Eshetu Tesfaye, Bradley P Carlin, Beth Seremula, Melissa Waite, Wadih M Zein, Laryssa A Huryn, Thomas O Crawford, Charlotte J Sumner, Ahmet Hoke, John D Heiss, Lawrence Charnas, Jody E Hooper, Thomas W Bouldin, Elizabeth M Kang, Denis Rybin, Steven J Gray, Carsten G Bönnemann

Faculty, Staff and Student Publications

Background: Giant axonal neuropathy is a rare, autosomal recessive, pediatric, polysymptomatic, neurodegenerative disorder caused by biallelic loss-of-function variants in GAN, the gene encoding gigaxonin.

Methods: We conducted an intrathecal dose-escalation study of scAAV9/JeT-GAN (a self-complementary adeno-associated virus-based gene therapy containing the GAN transgene) in children with giant axonal neuropathy. Safety was the primary end point. The key secondary clinical end point was at least a 95% posterior probability of slowing the rate of change (i.e., slope) in the 32-item Motor Function Measure total percent score at 1 year after treatment, as compared with the pretreatment slope.

Results: One of …

Case 9-2024: An 84-Year-Old Man With A Fall, Zaven Sargsyan, Sunita D Srivastava, Virginia A Triant, Brian B Ghoshhajra

Faculty, Staff and Students Publications

No abstract provided.

How Individuals’ Opinions Influence Society’S Resistance To Epidemics: An Agent-Based Model Approach, Geonsik Yu, Michael Garee, Mario Ventresca, Yuehwern Yih

Purdue University Libraries Open Access Publishing Fund

Background

Protecting public health from infectious diseases often relies on the cooperation of citizens, especially when self-care interventions are the only viable tools for disease mitigation. Accordingly, social aspects related to public opinion have been studied in the context of the recent COVID-19 pandemic. However, a comprehensive understanding of the effects of opinion-related factors on disease spread still requires further exploration.

Methods

We propose an agent-based simulation framework incorporating opinion dynamics within an epidemic model based on the assumption that mass media channels play a leading role in opinion dynamics. The model simulates how opinions about preventive interventions change over …

Design Of The Strive-Ipf Trial-Study Of Therapeutic Plasma Exchange, Rituximab, And Intravenous Immunoglobulin For Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, Tejaswini Kulkarni, Gerard Criner, Daniel Kass, Ivan Rosas, Mary Beth Scholand, Daniel Dilling, Ross Summer, Steven Duncan

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.

METHODS: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population …

Sanitation In Urban Areas May Limit The Spread Of Antimicrobial Resistance Via Flies, Drew Capone, Oliver Cumming, Abeoseh Flemister, Victor Ilevbare, Seth R. Irish, Ishi Keenum, Jackie Knee, Rassul Nala, Joe Brown

Michigan Tech Publications

Synanthropic filth flies are common where sanitation is poor and fecal wastes are accessible to them. These flies have been proposed as mechanical vectors for the localized transport of fecal microbes including antimicrobial resistant (AMR) organisms and associated antimicrobial resistance genes (ARGs), increasing exposure risks. We evaluated whether an onsite sanitation intervention in Maputo, Mozambique reduced the concentration of enteric bacteria and the frequency of detection of ARGs carried by flies collected in household compounds of low-income neighborhoods. Additionally, we assessed the phenotypic resistance profile of Enterobacteriaceae isolates recovered from flies during the pre-intervention phase. After fly enumeration at study …

Epitope Mapping Of Japanese Encephalitis Virus Neutralizing Antibodies By Native Mass Spectrometry And Hydrogen/Deuterium Exchange, Jagat Adhikari, James Heffernan, Melissa Edeling, Estefania Fernandez, Prashant N Jethva, Michael S Diamond, Daved H Fremont, Michael L Gross

2020-Current year OA Pubs

Japanese encephalitis virus (JEV) remains a global public health concern due to its epidemiological distribution and the existence of multiple strains. Neutralizing antibodies against this infection have shown efficacy in in vivo studies. Thus, elucidation of the epitopes of neutralizing antibodies can aid in the design and development of effective vaccines against different strains of JEV. Here, we describe a combination of native mass spectrometry (native-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) to complete screening of eight mouse monoclonal antibodies (MAbs) against JEV E-DIII to identify epitope regions. Native-MS was used as a first pass to identify the antibodies that …

Development Of Solitary Keratoacanthoma From A Cutaneous Wart, Joshua M. Ninan, Veronica Salazar

Research Symposium

Background: Common cutaneous warts, referred to in medicine as verrucae vulgaris, are proliferative lesions caused by human papillomavirus. These lesions are mostly benign and usually resolve without incident, except in the case of the patient mentioned in this report. Our patient developed a solitary keratoacanthoma, currently accepted as a clinical variant of squamous cell carcinoma, as a result of several risk factors and traumatic exposure. The current literature does not have an established association of HPV with solitary keratoacanthomas. This case report explores the presentation and pathogenesis of solitary keratoacanthomas within the setting of HPV.

Case Presentation: 48-year-old Caucasian female …

Organizing Knowledge Through Revealing Data In Knowledgebases., Jian Qin, Qiaoyi Liu

School of Information Studies - Faculty Scholarship

This paper uses the knowledgebases in the biomedical field as a case study to discuss the characteristics and requirements of knowledge organization (KO) practices and products by looking at the constructs, cross-linking, and curation methods. Modern knowledgebases such as Gene Ontology and Disease Ontology reflect the major expansions in KO to be more computational, portable (entification allows individual nodes to be extracted and used in combination with multiscale resources) and connected. Many techniques and methods used are not covered in KO textbooks. The interdisciplinary nature of KB development will be a worthwhile research area for the field of knowledge organization.

March 19, 2024 Ereporter, University Of Alabama At Birmingham

eReporter (campus newsletter)

No abstract provided.

Momkk1 And Moatg1 Dichotomously Regulating Autophagy And Pathogenicity Through Moatg9 Phosphorylation In Magnaporthe Oryzae, Yun Kong, Pusheng Guo, Jiayun Xu, Jiaxu Li, Miao Wu, Ziqi Zhang, Yifan Wang, Xinyu Liu, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

Autophagy is a central biodegradation pathway critical in eliminating intracellular cargo to maintain cellular homeostasis and improve stress resistance. At the same time, the key component of the mitogen-activated protein kinase cascade regulating cell wall integrity signaling MoMkk1 has an essential role in the autophagy of the rice blast fungus Magnaporthe oryzae. Still, the mechanism of how MoMkk1 regulates autophagy is unclear. Interestingly, we found that MoMkk1 regulates the autophagy protein MoAtg9 through phosphorylation. MoAtg9 is a transmembrane protein subjected to phosphorylation by autophagy-related protein kinase MoAtg1. Here, we provide evidence demonstrating that MoMkk1-dependent MoAtg9 phosphorylation is required for phospholipid …

Examining Health-Seeking Behavior Among Diverse Ethnic Subgroups Within Black Populations In The United States And Canada: A Cross-Sectional Study, Yordanos M. Tiruneh, Oluwatunmininu Anwoju, Ariel C. Harrison, Martha T. Garcia, Shauna K. Elbers

School of Medicine Faculty Publications and Presentations

The Black populations, often treated as ethnically homogenous, face a constant challenge in accessing and utilizing healthcare services. This study examines the intra-group differences in health-seeking behavior among diverse ethnic subgroups within Black communities. A cross-sectional analysis included 239 adults ≥18 years of age who self-identified as Black in the United States and Canada. Multiple logistic regression assessed the relationship between health-seeking behaviors and ethnic origin, controlling for selected social and health-related factors. The mean age of the participants was 38.6 years, 31% were male, and 20% were unemployed. Sixty-one percent reported a very good or excellent health status, and …

Efficacy Of Photodynamic Therapy As An Adjunct To Scaling And Root Planing On Clinical Parameters And Microbial Composition In Subgingival Plaque Of Periodontitis Patients: A Split-Mouth Randomized Clinical Trial, Paul W. Bible, Min Nie, Peien Huang, Peiyao Peng, Daonan Shen, Lei Zhao, Duan Jiang, Yuqin Shen, Lai Wei, Jingmei Yang, Jun Wang, Yafei Wu

Computer Science Faculty publications

Background

The aim of this study was to assess the efficacy of photodynamic therapy (PDT) as an adjunct to scaling and root planing (SRP) on clinical parameters and microbial composition in subgingival plaque of periodontitis patients.

Methods

Seventeen patients were included in this split-mouth randomized clinical trial. Sites with probing pocket depth (PPD) ≥5 mm in combination with bleeding on probing in different quadrants were randomized into the control group, the group with a single PDT application right after SRP, and the group with three repeated PDT applications 1 week after SRP. The subgingival plaque was collected for 16S rRNA …

Individual Risk Factors Associated With Cesarean Section Surgical Site Infections Among African American Women In California, Paula St Hill

Frank Dilley Award for Outstanding Doctoral Study

Healthcare-associated infections (HAIs) are a significant public health issue. More than 600,000 patients in the United States develop HAIs every year. Surgical site infections (SSIs) are a very common HAI and can develop when a woman has a Cesarean section (C-section). The complications from the development of an SSI can be severe. SSIs and C-section rates are high among African American women. The purpose of this quantitative study, utilizing secondary data provided by the California Health and Human Services Open Data Portal, was to determine if age at the time of delivery, smoking status of tobacco and non-tobacco products during …

Clinical Characteristics Of Idiopathic Granulomatous Mastitis In A Hispanic Border Population: A Case Series And Literature Review, Percy M. Thomas, Laura R. Uribe, Aminadab G. Flores, Emilia C. Dulgheru

School of Medicine Publications

Idiopathic granulomatous mastitis (IGM) is an autoimmune condition of the breast that is commonly encountered in women of non-white ethnicity such as Southeast Asians, Middle Easterners, and Hispanics. This condition often presents as a painful breast mass, and many patients undergo invasive diagnostic procedures or surgical excision, which can lead to disfiguring scars. Early recognition and prompt treatment with immunosuppressive medications can prevent invasive workups and management. Although previously thought to require an exclusively surgical approach, it now prompts interdisciplinary management. In this context, we present a case series of patients with IGM in a Hispanic population of South Texas.

Individual Risk Factors Associated With Cesarean Section Surgical Site Infections Among African American Women In California, Paula St Hill

Walden Dissertations and Doctoral Studies

No abstract provided.

Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …

Delayed Diagnosis Of Mycobacterium Bovis Bacillus Calmette-Guérin Periprosthetic Joint Infection Following Total Knee Arthroplasty, Christopher E. Pelt, Salika Shakir, Michael J. Cahill, Jakrapun Pupaibool, Barbara C. Cahill

SKMC Student Presentations and Publications

Periprosthetic joint infection (PJI) can present challenges in diagnosis and treatment, particularly in the setting of atypical causative organisms such as fungi and mycobacteria. Herein, we present a case and provide a review of the diagnosis and treatment of an unusual PJI caused by bacillus Calmette-Guérin, administered during the treatment of bladder cancer 3 years prior to total knee arthroplasty and subsequent PJI. Although the patient's history of bladder cancer was known, neither his Bacillus Calmette-Guérin treatment nor its potential for distant site spread that could lead to PJI were appreciated, leading to a prolonged diagnostic evaluation and treatment course.

The Prevalence Of Gram-Negative Bacteria With Difficult-To-Treat Resistance And Utilization Of Novel Β-Lactam Antibiotics In The Southeastern United States, Y. Vivian Tsai, P. Brandon Bookstaver Pharm.D., Joseph Kohn, Julie Ann Justo, Darrell Childress, Stefanie Stramel, Douglas Slain, Patrick Tu, Mary Joyce B. Wingler, Bruce M. Jones, Daniel T. Anderson, Megan M. Seddon, David A. Cretella, Joshua Eudy, Hana Winders, Kayla Antosz Pharm.D., Pamela Bailey, Majdi N. Al-Hasan

Faculty Publications

Objective:

To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel β-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design:

Retrospective, multicenter, cohort. Setting:

Ten hospitals in the southeastern United States. Methods:

GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel β-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) …

Reaching The Unheard: Overcoming Challenges In Health Research With Hard-To-Reach Populations, Venera Bekteshi, Munjireen Sifat, Darla Kendzor

Kimmel Cancer Center Faculty Papers

PURPOSE: Addressing obstacles such as logistical complexities, social stigma, and the impact of historical traumas is essential for the successful inclusion of underrepresented groups in health research.

METHODS: This article reviews engagement and interview techniques used to ethically engage recently settled Afghan refugees in Oklahoma and rural Mexican-born women in Illinois in research. The paper concludes with a reflective discussion on the challenges and lessons learned.

RESULTS: Creative strategies to engage hard-to-reach populations in research included considering the participants' socioeconomic and cultural contexts in their interactions and developing community partnerships to establish trust and obtain reliable data. Other engagement strategies …

What Do Cervical Cancer Patients Know, How Do They Learn, And Who Do They Tell? A Pilot Study, Sharon Larson, Brian Mcanany, Ilene Ladd, Radhika Gogoi

College of Population Health Faculty Papers

BACKGROUND: This study explored what patients identified with cervical cancer know about the link between human papillomavirus (HPV) and cervical cancer and where they learned this information. Patients share a great deal of information with family, friends and colleagues and we were interested in the accuracy and sources of information they are sharing.

METHODS: Patients identified through the EHR of a health system who had a history of cervical cancer were invited to participate in a brief survey of their experience. The sample represents an opportunity sample of patients who responded.

RESULTS: Generally, these patients, drawn from the Geisinger Health …

Sequence-Structure-Function Characterization Of The Emerging Tetracycline Destructase Family Of Antibiotic Resistance Enzymes, Kevin S Blake, Hirdesh Kumar, Anisha Loganathan, Emily E Williford, Luke Diorio-Toth, Yao-Peng Xue, Wai Kwan Tang, Tayte P Campbell, David D Chong, Steven Angtuaco, Timothy A Wencewicz, Niraj H Tolia, Gautam Dantas

2020-Current year OA Pubs

Tetracycline destructases (TDases) are flavin monooxygenases which can confer resistance to all generations of tetracycline antibiotics. The recent increase in the number and diversity of reported TDase sequences enables a deep investigation of the TDase sequence-structure-function landscape. Here, we evaluate the sequence determinants of TDase function through two complementary approaches: (1) constructing profile hidden Markov models to predict new TDases, and (2) using multiple sequence alignments to identify conserved positions important to protein function. Using the HMM-based approach we screened 50 high-scoring candidate sequences in Escherichia coli, leading to the discovery of 13 new TDases. The X-ray crystal structures of …

Lifestyle And Demographic Associations With 47 Inflammatory And Vascular Stress Biomarkers In 9876 Blood Donors, Bertram Kjerulff, Joseph Dowsett, Rikke Louise Jacobsen, Josephine Gladov, Margit Hørup Larsen, Agnete Troen Lundgaard, Karina Banasik, David Westergaard, Susan Mikkelsen, Khoa Manh Dinh, Lotte Hindhede, Kathrine Agergård Kaspersen, Michael Schwinn, Anders Juul, Betina Poulsen, Birgitte Lindegaard, Carsten Bøcker Pedersen, Clive Eric Sabel, Henning Bundgaard, Henriette Svarre Nielsen, Janne Amstrup Møller, Jens Kjærgaard Boldsen, Kristoffer Sølvsten Burgdorf, Lars Vedel Kessing, Linda Jenny Handgaard, Lise Wegner Thørner, Maria Didriksen, Mette Nyegaard, Niels Grarup, Niels Ødum

School of Geography, Earth and Environmental Sciences

Background The emerging use of biomarkers in research and tailored care introduces a need for information about the association between biomarkers and basic demographics and lifestyle factors revealing expectable concentrations in healthy individuals while considering general demographic differences. Methods A selection of 47 biomarkers, including markers of inflammation and vascular stress, were measured in plasma samples from 9876 Danish Blood Donor Study participants. Using regression models, we examined the association between biomarkers and sex, age, Body Mass Index (BMI), and smoking. Results Here we show that concentrations of inflammation and vascular stress biomarkers generally increase with higher age, BMI, and …

Homodimeric Granzyme A Opsonizes Mycobacterium Tuberculosis And Inhibits Its Intracellular Growth In Human Monocytes Via Toll-Like Receptor 4 And Cd14, Valerio Rasi, Kathleen R. Phelps, Keegan R. Paulson, Christopher S. Eickhoff, Mathivanan Chinnaraj, Nicola Pozzi, Marco Di Gioia, Ivan Zanoni, Shubha Shakya, Haley L. Carlson, David A. Ford, Grant R. Kolar, Daniel F. Hoft

Biological Sciences Faculty Research & Creative Works

Mycobacterium tuberculosis (Mtb)-specific γ9δ2 T cells secrete granzyme A (GzmA) protective against intracellular Mtb growth. However, GzmA-enzymatic activity is unnecessary for pathogen inhibition, and the mechanisms of GzmA-mediated protection remain unknown. We show that GzmA homodimerization is essential for opsonization of mycobacteria, altered uptake into human monocytes, and subsequent pathogen clearance within the phagolysosome. Although monomeric and homodimeric GzmA bind mycobacteria, only homodimers also bind cluster of differentiation 14 (CD14) and Toll-like receptor 4 (TLR4). Without access to surface-expressed CD14 and TLR4, GzmA fails to inhibit intracellular Mtb. Upregulation of Rab11FIP1 was associated with inhibitory activity. Furthermore, GzmA colocalized with …