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Articles 31 - 60 of 223

Full-Text Articles in Allergy and Immunology

Downregulation Of Mirlet7 Mirna Family Promotes Tc17 Differentiation And Emphysema Via De-Repression Of Rorγt, Phillip A Erice, Xinyan Huang, Matthew J Seasock, Matthew J Robertson, Hui-Ying Tung, Melissa A Perez-Negron, Shivani L Lotlikar, David B Corry, Farrah Kheradmand, Antony Rodriguez May 2024

Downregulation Of Mirlet7 Mirna Family Promotes Tc17 Differentiation And Emphysema Via De-Repression Of Rorγt, Phillip A Erice, Xinyan Huang, Matthew J Seasock, Matthew J Robertson, Hui-Ying Tung, Melissa A Perez-Negron, Shivani L Lotlikar, David B Corry, Farrah Kheradmand, Antony Rodriguez

Faculty, Staff and Students Publications

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with …


Clinical Outcomes After Acute Coronary Syndromes Or Revascularization Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mohammed Haji, Michael Capilupi, Michael Kwok, Nouran Ibrahim, Gerald S Bloomfield, Christopher T Longenecker, Maria C Rodriguez-Barradas, Chester N Ashong, Eric Jutkowitz, Tracey H Taveira, Michelle Richard, Jennifer L Sullivan, James L Rudolph, Wen-Chih Wu, Sebhat Erqou May 2024

Clinical Outcomes After Acute Coronary Syndromes Or Revascularization Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mohammed Haji, Michael Capilupi, Michael Kwok, Nouran Ibrahim, Gerald S Bloomfield, Christopher T Longenecker, Maria C Rodriguez-Barradas, Chester N Ashong, Eric Jutkowitz, Tracey H Taveira, Michelle Richard, Jennifer L Sullivan, James L Rudolph, Wen-Chih Wu, Sebhat Erqou

Faculty, Staff and Students Publications

IMPORTANCE: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately.

OBJECTIVE: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group.

DATA SOURCES: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023.

STUDY SELECTION: Included studies met the following criteria: patients living with …


Primary Hypertrophic Osteoarthropathy: A Case Series, Varuni Pragya, Mahabaleshwar Mamadapur Dr, Rahul Bisaralli Dr, Deepak Benny Dr, Purna Bansal Apr 2024

Primary Hypertrophic Osteoarthropathy: A Case Series, Varuni Pragya, Mahabaleshwar Mamadapur Dr, Rahul Bisaralli Dr, Deepak Benny Dr, Purna Bansal

Digital Journal of Clinical Medicine

Skeletal dysplasia encompasses a spectrum of over 400 rare inheritable skeletal abnormalities typically manifested early in childhood. Hypertrophic Osteoarthropathy is a clinical syndrome marked by abnormal skin and osseous tissue proliferation at the distal extremities. It is characterized by unique clinical features such as digital clubbing, periostosis of tubular bones, and synovial effusions.

We report three cases of HPOA for further understanding and insight into this infrequent cause of clubbing. Case 1 involved a 25-year-old male presenting with joint pain, primarily in wrists and knees, accompanied by progressive swelling in both lower limbs for the past 3 years. Case 2 …


The Utility Of Interventional Anesthesia, Kylie Daguio, Kiley Jackson, Samantha Boever, Andrew Chang, James Keane, Leonard B. Goldstein Mar 2024

The Utility Of Interventional Anesthesia, Kylie Daguio, Kiley Jackson, Samantha Boever, Andrew Chang, James Keane, Leonard B. Goldstein

SOMA Faculty Publications

no abstract


Advancing Virtual At-Home Care For Community Health Center Patients Using Patient Self-Care Tools, Technology, And Education [Letter], Cheryl Modica, Joy H. Lewis, Curtis Bay Feb 2024

Advancing Virtual At-Home Care For Community Health Center Patients Using Patient Self-Care Tools, Technology, And Education [Letter], Cheryl Modica, Joy H. Lewis, Curtis Bay

SOMA Faculty Publications

Abstract

Introduction

Health centers are community-based, patient directed primary care providers that offer accessible, high-quality primary care within medically underserved communities. Screening for cancer and managing complex chronic conditions such as diabetes, hypertension, obesity, and depression are vital services for the vulnerable populations seen by community health centers. Delivering care for complex chronic conditions and preventive services using virtual models that integrate self-care tools and technology is an important approach to increasing access for hard-to-reach patients served by health centers.

Objective

This study aimed to explore the use of a virtual care model, applied using a systems approach and patient-driven …


Ubr5 Promotes Antiviral Immunity By Disengaging The Transcriptional Brake On Rig-I Like Receptors, Duomeng Yang, Tingting Geng, Andrew G Harrison, Jason G Cahoon, Jian Xing, Baihai Jiao, Mark Wang, Chao Cheng, Robert E Hill, Huadong Wang, Anthony T Vella, Gong Cheng, Yanlin Wang, Penghua Wang Jan 2024

Ubr5 Promotes Antiviral Immunity By Disengaging The Transcriptional Brake On Rig-I Like Receptors, Duomeng Yang, Tingting Geng, Andrew G Harrison, Jason G Cahoon, Jian Xing, Baihai Jiao, Mark Wang, Chao Cheng, Robert E Hill, Huadong Wang, Anthony T Vella, Gong Cheng, Yanlin Wang, Penghua Wang

Faculty, Staff and Students Publications

The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines and identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator of RLR transcription. UBR5 deficiency reduces antiviral immune responses to RNA viruses, while increases viral replication in primary cells and mice. Ubr5 knockout mice are …


D-Mannose Reduces Cellular Senescence And Nlrp3/Gasdermind/Il-1Β-Driven Pyroptotic Uroepithelial Cell Shedding In The Murine Bladder, Chetanchandra S Joshi, Arnold M Salazar, Caihong Wang, Marianne M Ligon, Rayvanth R Chappidi, Bisiayo E Fashemi, Paul A Felder, Amy Mora, Sandra L Grimm, Cristian Coarfa, Indira U Mysorekar Jan 2024

D-Mannose Reduces Cellular Senescence And Nlrp3/Gasdermind/Il-1Β-Driven Pyroptotic Uroepithelial Cell Shedding In The Murine Bladder, Chetanchandra S Joshi, Arnold M Salazar, Caihong Wang, Marianne M Ligon, Rayvanth R Chappidi, Bisiayo E Fashemi, Paul A Felder, Amy Mora, Sandra L Grimm, Cristian Coarfa, Indira U Mysorekar

Faculty, Staff and Students Publications

Aging is a risk factor for disease via increased susceptibility to infection, decreased ability to maintain homeostasis, inefficiency in combating stress, and decreased regenerative capacity. Multiple diseases, including urinary tract infection (UTI), are more prevalent with age; however, the mechanisms underlying the impact of aging on the urinary tract mucosa and the correlation between aging and disease remain poorly understood. Here, we show that, relative to young (8-12 weeks) mice, the urothelium of aged (18-24 months) female mice accumulates large lysosomes with reduced acid phosphatase activity and decreased overall autophagic flux in the aged urothelium, indicative of compromised cellular homeostasis. …


Features Of Acute Covid-19 Associated With Post-Acute Sequelae Of Sars-Cov-2 Phenotypes: Results From The Impacc Study, Al Ozonoff, Naresh Doni Jayavelu, Shanshan Liu, Esther Melamed, Carly E Milliren, Jingjing Qi, Linda N Geng, Grace A Mccomsey, Charles B Cairns, Lindsey R Baden, Joanna Schaenman, Albert C Shaw, Hady Samaha, Vicki Seyfert-Margolis, Florian Krammer, Lindsey B Rosen, Hanno Steen, Caitlin Syphurs, Ravi Dandekar, Casey P Shannon, Rafick P Sekaly, Lauren I R Ehrlich, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Harm Van Bakel, Seunghee Kim-Schulze, David A Hafler, Ofer Levy, Monica Kraft, Chris Bime, Elias K Haddad, Carolyn S Calfee, David J Erle, Charles R Langelier, Walter Eckalbar, Steven E Bosinger, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Holden T Maecker, Matthew C Altman, Ruth R Montgomery, Patrice M Becker, Nadine Rouphael Jan 2024

Features Of Acute Covid-19 Associated With Post-Acute Sequelae Of Sars-Cov-2 Phenotypes: Results From The Impacc Study, Al Ozonoff, Naresh Doni Jayavelu, Shanshan Liu, Esther Melamed, Carly E Milliren, Jingjing Qi, Linda N Geng, Grace A Mccomsey, Charles B Cairns, Lindsey R Baden, Joanna Schaenman, Albert C Shaw, Hady Samaha, Vicki Seyfert-Margolis, Florian Krammer, Lindsey B Rosen, Hanno Steen, Caitlin Syphurs, Ravi Dandekar, Casey P Shannon, Rafick P Sekaly, Lauren I R Ehrlich, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Harm Van Bakel, Seunghee Kim-Schulze, David A Hafler, Ofer Levy, Monica Kraft, Chris Bime, Elias K Haddad, Carolyn S Calfee, David J Erle, Charles R Langelier, Walter Eckalbar, Steven E Bosinger, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Holden T Maecker, Matthew C Altman, Ruth R Montgomery, Patrice M Becker, Nadine Rouphael

Faculty, Staff and Students Publications

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B …


Targeting Transitioning Lung Monocytes/Macrophages As Treatment Strategies In Lung Disease Related To Environmental Exposures, Aaron Schwab, Todd A. Wyatt, Grace Moravec, Geoffrey M. Thiele, Amy J. Nelson, Angela Gleason, Oliver Schanze, Michael J. Duryee, Debra J. Romberger, Ted R. Mikuls, Jill A. Poole Jan 2024

Targeting Transitioning Lung Monocytes/Macrophages As Treatment Strategies In Lung Disease Related To Environmental Exposures, Aaron Schwab, Todd A. Wyatt, Grace Moravec, Geoffrey M. Thiele, Amy J. Nelson, Angela Gleason, Oliver Schanze, Michael J. Duryee, Debra J. Romberger, Ted R. Mikuls, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Background: Environmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce recruited,transitioning murine lung monocytes/macrophages, yet their cellular role remains unclear.

Methods: CCR2 RFP+ mice were intratracheally instilled with high concentration ODE (25%), LPS (10 μg), or gram-positive peptidoglycan (PGN, 100 μg) for monocyte/macrophage cell-trafficking studies. CCR2 knockout (KO) mice and administration of intravenous clodronate liposomes strategies were employed to reduce circulating monocytes available for lung recruitment following LPS exposure.Lung tissues and bronchoalveolar lavage fluid (BALF) were collected. Pro-inflammatory and/or pro-fibrotic cytokines, chemokines, and lung extracellular matrix mediators were quantitated by ELISA. …


Lung-Delivered Il-10 Therapy Elicits Beneficial Effects Via Immune Modulation In Organic Dust Exposure-Induced Lung Inflammation, Aaron D. Schwab, Todd A. Wyatt, Amy J. Nelson, Angela Gleason, Rohit Gaurav, Debra J. Romberger, Jill A. Poole Jan 2024

Lung-Delivered Il-10 Therapy Elicits Beneficial Effects Via Immune Modulation In Organic Dust Exposure-Induced Lung Inflammation, Aaron D. Schwab, Todd A. Wyatt, Amy J. Nelson, Angela Gleason, Rohit Gaurav, Debra J. Romberger, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Efficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute organic dust exposure in mice. Here, C57BL/6J mice were intratracheally instilled with swine confinement organic dust extract (ODE) (12.5%, 25%, 50% concentrations) with IL-10 (1 μg) treatment or vehicle control intratracheally-administered three times: 5 hr post-exposure and then daily for 2 days. The results showed that IL-10 treatment reduced ODE (25%)-induced weight loss by 66% and 46% at Day 1 and Day 2 post-exposure, respectively. IL-10 …


Polygenic And Transcriptional Risk Scores Identify Chronic Obstructive Pulmonary Disease Subtypes In The Copdgene And Eclipse Cohort Studies, Matthew Moll, Julian Hecker, John Platig, Jingzhou Zhang, Auyon J. Ghosh, Katherine A. Pratte, Rui-Sheng Wang, Davin Hill, Iain R. Konigsberg, Joe W. Chiles, Craig P. Hersh, Peter J. Castaldi, Kimberly Glass, Jennifer G. Dy, Don D. Sin, Ruth Tal-Singer, Majd Mouded, Stephen I. Rennard, Gary P. Anderson, Gregory L. Kinney, Russell P. Bowler, Jeffrey L. Curtis, Merry-Lynn Mcdonald, Edwin K. Silverman, Brian D. Hobbs, Michael H. Cho Jan 2024

Polygenic And Transcriptional Risk Scores Identify Chronic Obstructive Pulmonary Disease Subtypes In The Copdgene And Eclipse Cohort Studies, Matthew Moll, Julian Hecker, John Platig, Jingzhou Zhang, Auyon J. Ghosh, Katherine A. Pratte, Rui-Sheng Wang, Davin Hill, Iain R. Konigsberg, Joe W. Chiles, Craig P. Hersh, Peter J. Castaldi, Kimberly Glass, Jennifer G. Dy, Don D. Sin, Ruth Tal-Singer, Majd Mouded, Stephen I. Rennard, Gary P. Anderson, Gregory L. Kinney, Russell P. Bowler, Jeffrey L. Curtis, Merry-Lynn Mcdonald, Edwin K. Silverman, Brian D. Hobbs, Michael H. Cho

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

METHODS: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing …


To Compare The Efficacy Of Oral Deflazacort, Oral Prednisolone And Inhaled Budesonide In The Treatment Of Salbutamol Refractory Acute Asthma In Children, Santosh Kondekar, Unmesh Dev M, Surbhi Rathi, Gulrej N. Shaikh Jan 2024

To Compare The Efficacy Of Oral Deflazacort, Oral Prednisolone And Inhaled Budesonide In The Treatment Of Salbutamol Refractory Acute Asthma In Children, Santosh Kondekar, Unmesh Dev M, Surbhi Rathi, Gulrej N. Shaikh

Digital Journal of Clinical Medicine

Abstract

Background: A 22-month open-label randomized comparative study was conducted at tertiary care centre attached to medical college in metropolitan city in Maharashtra from Dec 2011 to Oct 2013, aiming to compare the effectiveness of three corticosteroid treatments - oral deflazacort, oral prednisolone, and inhaled budesonide in managing salbutamol-refractory asthma in children aged 1-14 years.

Methods: 90 afebrile children were equally allocated to the different treatment arms. Treatment arm A received oral Deflazacort (1mg/kg/day alternate day), treatment arm B received oral prednisolone (1mg/kg/day), and treatment arm C received budesonide inhaler (100 mcg/puff twice a day) for seven days, along with …


Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Katherine Figarella, Jieun Kim, Wei Ruan, Tingting Mills, Holger Klaus Eltzschig, Xiaoyi Yuan Jan 2024

Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Katherine Figarella, Jieun Kim, Wei Ruan, Tingting Mills, Holger Klaus Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially …


Early Administration Of Steroids In The Ambulance Setting: An Observational Design Trial (Easi-As-Odt), Jennifer N Fishe, Gerard Garvan, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David W Ashby, Daniel Ostermeyer, Lauren Riney, Olga Semenova, Benjamin Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Kathryn V Blake Jan 2024

Early Administration Of Steroids In The Ambulance Setting: An Observational Design Trial (Easi-As-Odt), Jennifer N Fishe, Gerard Garvan, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David W Ashby, Daniel Ostermeyer, Lauren Riney, Olga Semenova, Benjamin Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Kathryn V Blake

Faculty, Staff and Students Publications

BACKGROUND: In the emergency department (ED), prompt administration of systemic corticosteroids for pediatric asthma exacerbations decreases hospital admission rates. However, there is sparse evidence for whether earlier administration of systemic corticosteroids by emergency medical services (EMS) clinicians, prior to ED arrival, further improves pediatric asthma outcomes.

METHODS: Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial is a multicenter, observational, nonrandomized stepped-wedge design study with seven participating EMS agencies who adopted an oral systemic corticosteroid (OCS) into their protocols for pediatric asthma treatment. Using univariate analyses and multivariable mixed-effects models, we compared hospital admission rates for pediatric …


A Case Report Navigating Cvid And Sarcoidosis Overlaps In Pediatric Nephritis, Amanda Salih, Amanda Brown, Amanda Grimes, Sana Hasan, Manuel Silva-Carmona, Leyat Tal, Joud Hajjar Jan 2024

A Case Report Navigating Cvid And Sarcoidosis Overlaps In Pediatric Nephritis, Amanda Salih, Amanda Brown, Amanda Grimes, Sana Hasan, Manuel Silva-Carmona, Leyat Tal, Joud Hajjar

Faculty, Staff and Students Publications

Common variable immunodeficiency (CVID) can be complicated by granulomatous disease, often granulomatous lymphocytic interstitial lung disease (GLILD). Granulomatous interstitial nephritis represents an atypical presentation in pediatrics. Our patient is a previously healthy 13-year-old white male with a recent diagnosis of CVID. He presented with a rash and laboratory findings included pancytopenia (white blood cells 2.6 cells × 103/μl, hemoglobin 11.8 g/dl, platelets 60 × 103/μl), hypercalcemia (14.9 mg/dl), elevated Vit D 1,25 OH level (>200 pg/ml), hyperuricemia (8.8 mg/dl), and acute kidney injury (AKI) (serum creatinine 1.1 mg/dl; baseline 0.64 mg/dl). A broad infectious workup was unremarkable. The rash …


Genetic Variation Between Small Bowel And Colon-Predominant Crohn's Disease, Halee Patel, R Alan Harris, Justin H Qian, Numan Oezguen, Ashleigh Watson, Reka G Szigeti, Stanley Cho, Wenly Ruan, Savini Britto, Antone Opekun, Geoffrey Preidis, Richard Kellermayer Jan 2024

Genetic Variation Between Small Bowel And Colon-Predominant Crohn's Disease, Halee Patel, R Alan Harris, Justin H Qian, Numan Oezguen, Ashleigh Watson, Reka G Szigeti, Stanley Cho, Wenly Ruan, Savini Britto, Antone Opekun, Geoffrey Preidis, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.


Clinical Utility Of Plasma Microbial Cell-Free Dna Sequencing In Determining Microbiologic Etiology Of Infectious Syndromes In Solid Organ Transplant Recipients, Jesal R Shah, Muhammad Rizwan Sohail, Todd Lasco, John A Goss, Mayar Al Mohajer, Sarwat Khalil Jan 2024

Clinical Utility Of Plasma Microbial Cell-Free Dna Sequencing In Determining Microbiologic Etiology Of Infectious Syndromes In Solid Organ Transplant Recipients, Jesal R Shah, Muhammad Rizwan Sohail, Todd Lasco, John A Goss, Mayar Al Mohajer, Sarwat Khalil

Faculty, Staff and Students Publications

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is increasingly being used for microbial detection in various infectious syndromes. However, data regarding the use of mNGS in solid organ transplant recipients (SOTR) are lacking.

OBJECTIVES: To describe and analyze real-world clinical impact of mNGS using plasma microbial cell-free DNA (mcfDNA) in SOTR.Design: Retrospectively reviewed all adult SOTR who underwent mNGS testing using plasma mcfDNA at Baylor St Luke's Medical Center from March 2017 to February 2023.

METHODS: Clinical impact (positive, neutral, and negative) was assessed using standardized objective criteria. Three Infectious Diseases physicians independently performed clinical adjudication to determine the correlation of mcfDNA …


The Dna Glycosylase Neil2 Is Protective During Sars-Cov-2 Infection, Nisha Tapryal, Anirban Chakraborty, Kaushik Saha, Azharul Islam, Lang Pan, Koa Hosoki, Ibrahim M Sayed, Jason M Duran, Joshua Alcantara, Vanessa Castillo, Courtney Tindle, Altaf H Sarker, Maki Wakamiya, Victor J Cardenas, Gulshan Sharma, Laura E Crotty Alexander, Sanjiv Sur, Debashis Sahoo, Gourisankar Ghosh, Soumita Das, Pradipta Ghosh, Istvan Boldogh, Tapas K Hazra Dec 2023

The Dna Glycosylase Neil2 Is Protective During Sars-Cov-2 Infection, Nisha Tapryal, Anirban Chakraborty, Kaushik Saha, Azharul Islam, Lang Pan, Koa Hosoki, Ibrahim M Sayed, Jason M Duran, Joshua Alcantara, Vanessa Castillo, Courtney Tindle, Altaf H Sarker, Maki Wakamiya, Victor J Cardenas, Gulshan Sharma, Laura E Crotty Alexander, Sanjiv Sur, Debashis Sahoo, Gourisankar Ghosh, Soumita Das, Pradipta Ghosh, Istvan Boldogh, Tapas K Hazra

Faculty, Staff and Students Publications

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant …


Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer’S Disease: Research Outline And Call For Collaboration, Richard Lathe, Nikki M Schultek, Brian J Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi, Intracell Research Group Consortium Collaborators Nov 2023

Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer’S Disease: Research Outline And Call For Collaboration, Richard Lathe, Nikki M Schultek, Brian J Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi, Intracell Research Group Consortium Collaborators

Faculty, Staff and Students Publications

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will …


Toll-Like Receptor 4 And Cd11b Expressed On Microglia Coordinate Eradication Of Candida Albicans Cerebral Mycosis, Yifan Wu, Shuqi Du, Lynn H Bimler, Kelsey E Mauk, Léa Lortal, Nessim Kichik, James S Griffiths, Radim Osicka, Lizhen Song, Katherine Polsky, Lydia Kasper, Peter Sebo, Jill Weatherhead, J Morgan Knight, Farrah Kheradmand, Hui Zheng, Jonathan P Richardson, Bernhard Hube, Julian R Naglik, David B Corry Oct 2023

Toll-Like Receptor 4 And Cd11b Expressed On Microglia Coordinate Eradication Of Candida Albicans Cerebral Mycosis, Yifan Wu, Shuqi Du, Lynn H Bimler, Kelsey E Mauk, Léa Lortal, Nessim Kichik, James S Griffiths, Radim Osicka, Lizhen Song, Katherine Polsky, Lydia Kasper, Peter Sebo, Jill Weatherhead, J Morgan Knight, Farrah Kheradmand, Hui Zheng, Jonathan P Richardson, Bernhard Hube, Julian R Naglik, David B Corry

Faculty, Staff and Students Publications

The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of brain anti-Candida immunity remains unknown. We show that C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) and candidalysin. Saps disrupt tight junction proteins of the blood-brain barrier (BBB) to permit fungal brain invasion. Saps also hydrolyze amyloid precursor protein (APP) into amyloid β (Aβ)-like peptides that bind to Toll-like receptor 4 (TLR4) and promote fungal killing in vitro while candidalysin engages the integrin CD11b (Mac-1) on microglia. …


Multisystem Inflammatory Syndrome In Children (Mis-C): Is There A Relationship To Typhus?, Sravani Mannuru, Juliana Hager, Jacob Smith Oct 2023

Multisystem Inflammatory Syndrome In Children (Mis-C): Is There A Relationship To Typhus?, Sravani Mannuru, Juliana Hager, Jacob Smith

Research Colloquium

The United Kingdom first reported in April 2020 a group of eight previously healthy children with a link to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that presented with systemic inflammation and multi-organ involvement, now named multisystem inflammatory syndrome in children (MIS-C). The Centers of Disease Control and Prevention (CDC) have reported over 1000 cases since the primary discovery as of October 2020 with 20 total deaths. [1] The clinical features of MIS-C have been previously compared to inflammatory syndromes including Kawasaki disease (KD) and toxic shock syndrome (TSS). We describe the clinical presentation and management for 3 pediatric cases with …


Heterogenous Lung Inflammation Ct Patterns Distinguish Pneumonia And Immune Checkpoint Inhibitor Pneumonitis And Complement Blood Biomarkers In Acute Myeloid Leukemia: Proof Of Concept, Muhammad Aminu, Naval Daver, Myrna C B Godoy, Girish Shroff, Carol Wu, Luis F Torre-Sada, Alberto Goizueta, Vickie R Shannon, Saadia A Faiz, Mehmet Altan, Guillermo Garcia-Manero, Hagop Kantarjian, Farhad Ravandi-Kashani, Tapan Kadia, Marina Konopleva, Courtney Dinardo, Sherry Pierce, Aung Naing, Sang T Kim, Dimitrios P Kontoyiannis, Fareed Khawaja, Caroline Chung, Jia Wu, Ajay Sheshadri Sep 2023

Heterogenous Lung Inflammation Ct Patterns Distinguish Pneumonia And Immune Checkpoint Inhibitor Pneumonitis And Complement Blood Biomarkers In Acute Myeloid Leukemia: Proof Of Concept, Muhammad Aminu, Naval Daver, Myrna C B Godoy, Girish Shroff, Carol Wu, Luis F Torre-Sada, Alberto Goizueta, Vickie R Shannon, Saadia A Faiz, Mehmet Altan, Guillermo Garcia-Manero, Hagop Kantarjian, Farhad Ravandi-Kashani, Tapan Kadia, Marina Konopleva, Courtney Dinardo, Sherry Pierce, Aung Naing, Sang T Kim, Dimitrios P Kontoyiannis, Fareed Khawaja, Caroline Chung, Jia Wu, Ajay Sheshadri

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers.

MATERIALS AND METHODS: We studied CT images from 97 patients with pneumonia and 29 patients with pneumonitis from acute myeloid leukemia treated with ICIs. We developed a CT-derived signature using a habitat imaging algorithm, whereby infected lungs are segregated into clusters ("habitats"). We validated the model and compared it with a clinical-blood model to determine whether imaging can add …


Loss Of Stearoyl-Coa Desaturase 2 Disrupts Inflammatory Response In Macrophages, Joseph B Lin, Amy Mora, Tzu Jui Wang, Andrea Santeford, Darksha Usmani, Marianne M Ligon, Indira U Mysorekar, Rajendra S Apte Aug 2023

Loss Of Stearoyl-Coa Desaturase 2 Disrupts Inflammatory Response In Macrophages, Joseph B Lin, Amy Mora, Tzu Jui Wang, Andrea Santeford, Darksha Usmani, Marianne M Ligon, Indira U Mysorekar, Rajendra S Apte

Faculty, Staff and Students Publications

Macrophages are innate immune cells that patrol tissues and are the first responders to detect infection. They orchestrate the host immune response in eliminating invading pathogens and the subsequent transition from inflammation to tissue repair. Macrophage dysfunction contributes to age-related pathologies, including low-grade inflammation in advanced age that is termed "inflammaging." Our laboratory has previously identified that macrophage expression of a fatty acid desaturase, stearoyl-CoA desaturase 2 (SCD2), declines with age. Herein, we delineate the precise cellular effects of SCD2 deficiency in murine macrophages. We found that deletion of


Pediatric Acute Liver Failure Secondary To Autoimmune Hepatitis In An Infant With Thrombocytopenia-Absent Radius (Tar) Syndrome: A Case Report, Rebecca Mercedes, Kalyani Patel, Henry Shiau, Krupa R Mysore, Wenly Ruan, Daniel H Leung, Mary Elizabeth M Tessier, Dana Cerminara, Sarah Nicholas, Kelby Fuller, Marielle Faraone, N Thao N Galvan, John Goss, Anna M Banc-Husu Aug 2023

Pediatric Acute Liver Failure Secondary To Autoimmune Hepatitis In An Infant With Thrombocytopenia-Absent Radius (Tar) Syndrome: A Case Report, Rebecca Mercedes, Kalyani Patel, Henry Shiau, Krupa R Mysore, Wenly Ruan, Daniel H Leung, Mary Elizabeth M Tessier, Dana Cerminara, Sarah Nicholas, Kelby Fuller, Marielle Faraone, N Thao N Galvan, John Goss, Anna M Banc-Husu

Faculty, Staff and Students Publications

Thrombocytopenia absent radius (TAR) syndrome is a rare genetic disorder that has been associated with food protein-induced allergic proctocolitis and transient leukemoid reactions, among other manifestations. There has been no prior reports of its association with autoimmune disease, more specifically, autoimmune hepatitis (AIH) or the development of pediatric acute liver failure (PALF). We present a case of an 8-month-old infant with TAR syndrome who presented with PALF, secondary to AIH with elevated liver-kidney microsomal antibody (>1:2560). She received a liver transplant and had a very complicated postoperative course including severe T-cell-mediated rejection, infection, biliary stricture, persistently elevated liver-kidney microsomal …


Performance Of A Modified Fracture Risk Assessment Tool For Fragility Fracture Prediction Among Older Veterans Living With Hiv, Julie A Womack, Terrence E Murphy, Linda Leo-Summers, Farah Kidwai-Khan, Melissa Skanderson, Thomas M Gill, Barbara Gulanski, Maria C Rodriguez-Barradas, Phyllis C Tien, Michael T Yin, Evelyn Hsieh Jul 2023

Performance Of A Modified Fracture Risk Assessment Tool For Fragility Fracture Prediction Among Older Veterans Living With Hiv, Julie A Womack, Terrence E Murphy, Linda Leo-Summers, Farah Kidwai-Khan, Melissa Skanderson, Thomas M Gill, Barbara Gulanski, Maria C Rodriguez-Barradas, Phyllis C Tien, Michael T Yin, Evelyn Hsieh

Faculty, Staff and Students Publications

OBJECTIVE: Fragility fractures (fractures) are a critical outcome for persons aging with HIV (PAH). Research suggests that the fracture risk assessment tool (FRAX) only modestly estimates fracture risk among PAH. We provide an updated evaluation of how well a 'modified FRAX' identifies PAH at risk for fractures in a contemporary HIV cohort.

DESIGN: Cohort study.

METHODS: We used data from the Veterans Aging Cohort Study to evaluate veterans living with HIV, aged 50+ years, for the occurrence of fractures from 1 January 2010 through 31 December 2019. Data from 2009 were used to evaluate the eight FRAX predictors available to …


Realizing The Promise Of Dolutegravir In Effectively Treating Children And Adolescents Living With Hiv In Real-World Settings In 6 Countries In Eastern And Southern Africa, Jason Michael Bacha, Sandile Dlamini, Florence Anabwani, Judith Gwimile, Jacqueline Balungi Kanywa, John Farirai, Menard Bvumbwe, Mabene Tsotako, Teresa Steffy, Diane Nguyen, Jose Euberto Mendez-Reyes, Peter Elyanu, Heather Haq Jul 2023

Realizing The Promise Of Dolutegravir In Effectively Treating Children And Adolescents Living With Hiv In Real-World Settings In 6 Countries In Eastern And Southern Africa, Jason Michael Bacha, Sandile Dlamini, Florence Anabwani, Judith Gwimile, Jacqueline Balungi Kanywa, John Farirai, Menard Bvumbwe, Mabene Tsotako, Teresa Steffy, Diane Nguyen, Jose Euberto Mendez-Reyes, Peter Elyanu, Heather Haq

Faculty, Staff and Students Publications

BACKGROUND: Despite encouraging results from clinical trials and in high-income countries, large-scale data on the effectiveness and safety of dolutegravir (DTG) in children and adolescents living with HIV (CALHIV) are lacking in low- and middle-income countries (LMICs).

METHODS: Retrospective analysis was performed among CALHIV 0-19 years old and weighing greater than or equal to 20 kg who received DTG from 2017 to 2020 at sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania and Uganda to determine effectiveness, safety and predictors of viral load suppression (VLS) among CALHIV using DTG, including through single drug substitutions (SDS).

RESULTS: Among 9419 CALHIV using DTG, …


Designing A Local Policy To Reduce Hiv In Mexico City, Mayar Al Mohajer Jul 2023

Designing A Local Policy To Reduce Hiv In Mexico City, Mayar Al Mohajer

Faculty, Staff and Students Publications

The Joint United Nations Program on human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (Joint United Nations Program on HIV/AIDS, UNAIDS) has recommended 90-90-90 goals to increase the number of patients who are aware of their status, on antiretroviral therapy, and have undetectable viral loads. Mexico City has made several achievements to aid in prevention, early diagnosis, and treatment; however, the incidence of HIV has not decreased over the past decade. This article reviews global initiatives that were successful in achieving some or all these metrics and provide a road map for Mexico to reach the desired goals.


Extrinsic Allergic Alveolitis: A Systematic Review Of Hla-Dr In Pigeon Breeder’S Disease, Dylan Thibaut, Ryan A. Witcher, Anitha Kunnath, James Toldi Jun 2023

Extrinsic Allergic Alveolitis: A Systematic Review Of Hla-Dr In Pigeon Breeder’S Disease, Dylan Thibaut, Ryan A. Witcher, Anitha Kunnath, James Toldi

Advances in Clinical Medical Research and Healthcare Delivery

Abstract

Introduction: Pigeon Breeder’s Pneumonitis (PBP) results due to a complex pathophysiology that includes exposure to avian antigens. Susceptibility has been linked to human leukocyte antigen (HLA) class II, though consensus has not been reached. The goal of this systematic review is to further elucidate the association between PBP and HLA-DR subtypes.

Methods: Databases utilized included PubMed, Google Scholar, ScienceDirect, and Cochrane Library. Inclusion required a minimum of three studies in English presenting HLA-DR alleles of PBP and control subgroups. Exclusion was due to insufficient data or non-feasible control groups. Forest plots were created for HLA-DR subtypes’ association …


Review Of Natural Compounds For Potential Psoriasis Treatment, Omali Y Elkhawaga, Mohamed M Ellety, Sheref O Mofty, Mohamed S Ghanem, Abdallah O Mohamed Jun 2023

Review Of Natural Compounds For Potential Psoriasis Treatment, Omali Y Elkhawaga, Mohamed M Ellety, Sheref O Mofty, Mohamed S Ghanem, Abdallah O Mohamed

Faculty, Staff and Student Publications

Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in inflammation in various parts of the skin. There could be obvious symptoms, such as elevated plaques; these plaques may appear differently depending on the type of skin. This disease can cause inflammation in the elbows, lower back, scalp, knees, or other regions of the body. It can begin at any age, although it most commonly affects individuals between the ages of 50 and 60. Specific cells (such as T cells) have been observed to play an obvious …


A Case Of Dock8 Deficiency Treated With Dupilumab, Melissa Anderson, Brandon D. Newell, Hugo Escobar, Erin Stahl, Nikita Raje May 2023

A Case Of Dock8 Deficiency Treated With Dupilumab, Melissa Anderson, Brandon D. Newell, Hugo Escobar, Erin Stahl, Nikita Raje

Research Days

Background: Dedicator of cytokinesis 8 gene (DOCK8) deficiency is an immune disorder associated with autosomal recessive hyper-IgE syndrome, characterized by elevated IgE levels, atopic dermatitis, and predisposition to recurrent skin and lung infections.

Objectives/Goal: A 12-year-old male presented to Immunology clinic for DOCK8 deficiency. He was diagnosed in infancy due to diffuse papulopustular eruption positive for candidiasis and known family history. Past medical history included severe eczematous dermatitis, asthma, interstitial lung disease, food allergies, and poor growth, with cutaneous HSV and fungal infections, HSV keratitis, and MRSA bacteremia. Family history was notable for two siblings with DOCK8 deficiency, both deceased. …