Medicine and Health Sciences Commons^™

Granulocytic Myeloid-Derived Suppressor Cell Activity During Biofilm Infection Is Regulated By A Glycolysis/Hif1a Axis, Christopher M. Horn, Prabhakar Arumugam, Zachary Van Roy, Cortney E. Heim, Rachel W. Fallet, Blake P. Bertrand, Dhananjay Shinde, Vinai Chittezham Thomas, Svetlana Romanova, Tatiana K. Bronich, Curtis Hartman, Kevin Garvin, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI). A primary contributor to infection chronicity is an expansion of granulocytic myeloid-derived suppressor cells (G-MDSCs), which are critical for orchestrating the antiinflammatory biofilm milieu. Single-cell sequencing and bioinformatic metabolic algorithms were used to explore the link between G-MDSC metabolism and S. aureus PJI outcome. Glycolysis and the hypoxia response through HIF1a were significantly enriched in G-MDSCs. Interfering with both pathways in vivo, using a 2-deoxyglucose nanopreparation and granulocyte-targeted Hif1a conditional KO mice, respectively, attenuated G-MDSC-mediated immunosuppression and reduced bacterial burden in a mouse model of S. aureus PJI. …

Metabolism Shapes Immune Responses To Staphylococcus Aureus., Prabhakar Arumugam, Tammy Kielian

Journal Articles: Pathology and Microbiology

BACKGROUND: Staphylococcus aureus (S. aureus) is a common cause of hospital- and community-acquired infections that can result in various clinical manifestations ranging from mild to severe disease. The bacterium utilizes different combinations of virulence factors and biofilm formation to establish a successful infection, and the emergence of methicillin- and vancomycin-resistant strains introduces additional challenges for infection management and treatment.

SUMMARY: Metabolic programming of immune cells regulates the balance of energy requirements for activation and dictates pro- versus anti-inflammatory function. Recent investigations into metabolic adaptations of leukocytes and S. aureus during infection indicate that metabolic crosstalk plays a crucial role in …

Bioactive Metabolites Of Omega-6 And Omega-3 Fatty Acids Are Associated With Inflammatory Cytokine Concentrations In Maternal And Infant Plasma At The Time Of Delivery, Rebecca Slotkowski, Matthew Van Ormer, Anum Akbar, Taija Hahka, Maranda Thompson, Rebekah Rapoza, Arzu Ulu, Melissa Thoene, Elizabeth Lyden, Maheswari Mukherjee, Ana G. Yuil-Valdes, Sathish Kumar Natarajan, Tara Nordgren, Corrine K. Hanson, Ann Anderson-Berry

Journal Articles: Pediatrics

Background & aims

Inflammation is necessary for a healthy pregnancy. However, unregulated or excessive inflammation during pregnancy is associated with severe maternal and infant morbidities, such as pre-eclampsia, abnormal infant neurodevelopment, or preterm birth. Inflammation is regulated in part by the bioactive metabolites of omega-6 (n-6) and omega-3 (n-3) fatty acids (FAs). N-6 FAs have been shown to promote pro-inflammatory cytokine environments in adults, while n-3 FAs have been shown to contribute to the resolution of inflammation; however, how these metabolites affect maternal and infant inflammation is still uncertain. The objective of this study was to predict the influence of …

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. …

Quality Of Life Among Cancer Survivors: Comparison Of Multiple Cancers Using Icare2, Shinobu Watanabe-Galloway, Rachael L. Schmidt, Kendra Ratnapradipa, Kristin Dickinson, Abbey Fingeret, Whitney Goldner

Manuscripts: Epidemiology

Background: The number of cancer survivors continues to increase due to dramatic improvements in cancer treatment, accounting for approximately 5% of the entire population. As cancer survivors continue to live longer, it is important to understand their quality of life (QoL) in order to maximize supportive care efforts.

Objectives: In this study, the quality of life (QoL) among patients with different types of cancer was examined. The objectives were to: 1) compare patient-reported outcome measures of QoL using the Short-Form (SF-36) Health Survey scores among patients of different cancer types and 2) identify demographic, oncologic, and clinical factors that are …

Search Strategies For "Community Engagement Definition And Evaluation For Cancer Center: Scoping Review", Heidi Keeler, Brooke Fitzpatrick, Nicole Carritt, Emma Hymel, Josiane Kabayundo, Jordan Mccullough, Krishtee Napit, Regina Idoate, Shinobu Watanabe-Galloway

Search Strategies

No abstract provided.

Search Strategies For "Characterizing Metastatic Anogenital Squamous Cell Carcinoma In Immunosuppressed Patients: A Systematic Review", Sierra Thomas, Molly Antonson, Megan Wackel, Cynthia M. Schmidt, Ashley Wysong

Search Strategies

No abstract provided.

The Impact Of Iron Supplementation On The Preterm Neonatal Gut Microbiome: A Pilot Study, Matthew Van Ormer, Maranda Thompson, Melissa Thoene, Jean-Jack Riethoven, Sathish Kumar Natarajan, Corrine K. Hanson, Ann Anderson-Berry

Journal Articles: Pediatrics

OBJECTIVE: The gastrointestinal microbiome in preterm infants exhibits significant influence on optimal outcomes-with dysbiosis shown to substantially increase the risk of the life-threatening necrotizing enterocolitis. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurodevelopment. However, excess colonic iron exhibits potent oxidation capacity and alters the gut microbiome-potentially facilitating the proliferation of pathological bacterial strains. Breastfed preterm infants routinely receive iron supplementation starting 14 days after delivery and are highly vulnerable to morbidities associated with gastrointestinal dysbiosis. Therefore, we set out to determine if routine iron supplementation alters the preterm gut …

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 …

Elucidating Granulocytic Myeloid-Derived Suppressor Cell Heterogeneity During Staphylococcus Aureus Biofilm Infection, Blake P. Bertrand, Cortney E. Heim, Scott A. Koepsell, Tammy Kielian

Journal Articles: Pathology and Microbiology

Myeloid-derived suppressor cells (MDSCs) are pathologically activated immature myeloid cells with immunosuppressive activity that expand during chronic inflammation, such as cancer and prosthetic joint infection (PJI). Myeloid-derived suppressor cells can be broadly separated into 2 populations based on surface marker expression and function: monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic myeloid-derived suppressor cells (G-MDSCs). Granulocytic myeloid-derived suppressor cells are the most abundant leukocyte infiltrate during PJI; however, how this population is maintained in vivo and cellular heterogeneity is currently unknown. In this study, we identified a previously unknown population of Ly6G+Ly6C+F4/80+MHCII+ MDSCs during PJI that displayed immunosuppressive properties ex vivo. …

Dual Gallium Drug Treatment Against Carbapenem-Resistant Klebsiella Pneumoniae: Efficacy And Potential Mechanism(S) Of Action And Resistance, Zachary Scott, Seoung-Ryoung Choi, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Klebsiella pneumoniae (KLP) is a Gram-negative pathogen that can be highly antibiotic-resistant. Our group has worked with gallium-based compounds as a means of treating bacterial infections. Here the possible mechanism is investigated for dual therapy comprised of gallium nitrate (Ga(NO₃)₃) and gallium protoporphyrin (GaPP) on KLP. It is found that in vitro the combination of Ga(NO₃)₃ and GaPP is synergistic against KLP. The in vivo efficacy is of the dual therapy is additionally tested by treating pulmonary KLP infections in mice. Much greater effectiveness are observed in bacterial clearance and survival of mice …

Metabolic Diversity Of Human Macrophages: Potential Influence On Staphylococcus Aureus Intracellular Survival, Blake P. Bertrand, Dhananjay Shinde, Vinai C. Thomas, Marvin Whiteley, Carolyn B. Ibberson, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of medical device-associated biofilm infections. This is influenced by the ability of S. aureus biofilm to evade the host immune response, which is partially driven by the anti-inflammatory cytokine interleukin-10 (IL-10). Here, we show that treatment of human monocyte-derived macrophages (HMDMs) with IL-10 enhanced biofilm formation, suggesting that macrophage anti-inflammatory programming likely plays an important role during the transition from planktonic to biofilm growth. To identify S. aureus genes that were important for intracellular survival in HMDMs and how this was affected by IL-10, transposon sequencing was performed. The size of the S. aureus …

C1q Is Elevated During Chronic Staphylococcus Epidermidis Central Nervous System Catheter Infection, Matthew K. Beaver, Lara Bergdolt, Anna Dunaevsky, Tammy Kielian, Gwenn Skar

Journal Articles: Pathology and Microbiology

INTRODUCTION: Significant neurologic morbidity is caused by pediatric cerebrospinal fluid (CSF) shunt infections. The underlying mechanisms leading to impaired school performance and increased risk of seizures are unknown, however, a better understanding of these mechanisms may allow us to temper their consequences. Recent evidence has demonstrated important roles for complement proteins in neurodevelopment and neuroinflammation.

METHODS: We examined complement activation throughout

RESULTS: We found that MASP2 predominated early in catheter infection, but that Factor B was elevated at intermediate time points. Unexpectedly C1q was elevated at late timepoints when bacterial burdens were low or undetectable. Based on these findings and …

Novel Spirocyclic Dimer, Spid3, Targets Chronic Lymphocytic Leukemia Survival Pathways With Potent Preclinical Effects, Alexandria Eiken, Audrey L. Smith, Sydney A. Skupa, Elizabeth Schmitz, Sandeep Rana, Sarbjit Singh, Siddhartha Kumar, Jayapal Reddy Mallareddy, Aguirre A. De Cubas, Akshay Krishna, Achyuth Kalluchi, M. Jordan Rowley, Christopher R. D'Angelo, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Amarnath Natarajan, Dalia El-Gamal

Journal Articles: Oncology and Hematology

Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by the induction of B-cell receptor (BCR) signaling within the tumor microenvironment (TME) driving activation of NFκB signaling and the unfolded protein response (UPR). Malignant cells have higher basal levels of UPR posing a unique therapeutic window to combat CLL cell growth using pharmacologic agents that induce accumulation of misfolded proteins. Frontline CLL therapeutics that directly target BCR signaling such as Bruton tyrosine kinase (BTK) inhibitors (e.g., ibrutinib) have enhanced patient survival. However, resistance mechanisms wherein tumor cells bypass BTK inhibition through acquired BTK mutations, and/or activation of alternative survival …

Bet Inhibition Reforms The Immune Microenvironment And Alleviates T Cell Dysfunction In Chronic Lymphocytic Leukemia, Audrey L. Smith, Sydney A. Skupa, Alexandria P. Eiken, Timothy E. Reznicek, Elizabeth Schmitz, Nolan Williams, Dalia Y. Moore, Christopher R. D'Angelo, Avyakta Kallam, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Eslam Mohamed, Anna R. Mahr, Paul W. Denton, Ben Powell, Gideon Bollag, M. Jordan Rowley, Dalia El-Gamal

Journal Articles: Oncology and Hematology

Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T cell exhaustion greatly hinder functional antitumor immune responses in chronic lymphocytic leukemia (CLL). Bromodomain and extraterminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent CLL T cell defects. The pan-BET inhibitor OPN-51107 reduced exhaustion-associated cell signatures resulting in improved T cell proliferation and effector function in the Eμ-TCL1 splenic TME. Following BET inhibition (BET-i), TME T cells coexpressed significantly fewer …

Evaluation Of Vitamin E Isoforms In Placental Tissue And Their Relationship With Maternal Dietary Intake And Plasma Concentrations In Mother-Infant Dyads, Ishani Jhamb, Alyssa Freeman, Michelle R. Lotfi, Matthew Van Ormer, Corrine K. Hanson, Ann Anderson-Berry, Melissa K. Thoene

Journal Articles: Pediatrics

α-tocopherol is a vitamin E isoform with potent antioxidant activity, while the γ-tocopherol isoform of vitamin E exerts more pro-inflammatory effects. In maternal-fetal environments, increased plasma α-tocopherol concentrations are associated with positive birth outcomes, while higher γ-tocopherol concentrations are linked with negative pregnancy outcomes. However, little is known about tocopherol concentrations in placental tissue and their role in modulating placental oxidative stress, a process that is implicated in many complications of pregnancy. The objectives of this research are to evaluate the concentrations of α- and γ-tocopherol in placental tissue and assess relationships with maternal and umbilical cord plasma concentrations. A …

Something Smells Fishy: How Lipid Mediators Impact The Maternal-Fetal Interface And Neonatal Development, Maranda Thompson, Arzu Ulu, Maheswari Mukherjee, Ana G. Yuil-Valdes, Melissa K. Thoene, Matthew Van Ormer, Rebecca Slotkowski, Teri Mauch, Ann Anderson-Berry, Corrine K. Hanson, Tara M. Nordgren, Sathish Kumar Natarajan

Journal Articles: Pediatrics

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled inflammation can lead to poor maternal and infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and -6 fatty acids obtained through the diet are metabolized into bioactive compounds that effect inflammation. Recent evidence has shown that the downstream products of omega-3 and -6 fatty acids may influence physiology during pregnancy. In this review, the current knowledge relating to omega-3 and omega-6 metabolites during pregnancy will be summarized.

Ventricular Tachycardia In A Pediatric Patient With High-Risk Thrombotic Thrombocytopenia Purpura, Taylor J. Kratochvil, Jeffrey A. Robinson

Journal Articles: Pediatrics

An 8-year-old previously healthy male was diagnosed with thrombotic thrombocytopenic purpura (TTP) and increased serum cardiac troponin I. Telemetry recorded non-sustained ventricular tachycardia, without ST-segment changes or other abnormalities on serial electrocardiogram. This case illustrates that cardiac monitoring by telemetry should be considered in high-risk TTP with elevated cardiac troponin.

Retinol And Pro-Vitamin A Carotenoid Nutritional Status During Pregnancy Is Associated With Newborn Hearing Screen Results, Rebecca Slotkowski, Matthew Van Ormer, Anum Akbar, Olivia Paetz, Taija Hahka, Maranda Thompson, Alyssa Freeman, Alexandra Hergenrader, Sarah Sweeney, Zeljka Korade, Thiago Genaro-Mattos, Corrine K. Hanson, Ann Anderson-Berry, Melissa K. Thoene

Journal Articles: Pediatrics

The prenatal period is critical for auditory development; thus, prenatal influences on auditory development may significantly impact long-term hearing ability. While previous studies identified a protective effect of carotenoids on adult hearing, the impact of these nutrients on hearing outcomes in neonates is not well understood. The purpose of this study is to investigate the relationship between maternal and umbilical cord plasma retinol and carotenoid concentrations and abnormal newborn hearing screen (NHS) results. Mother-infant dyads (n = 546) were enrolled at delivery. Plasma samples were analyzed using HPLC and LC-MS/MS. NHS results were obtained from medical records. Statistical analysis …

Plasma Retinol Concentrations And Dietary Intakes Of Mother-Infant Sets In Singleton Versus Twin Pregnancy, Anum Akbar, Sarah Duvall, Matthew Van Ormer, Rebecca Slotkowski, Taija Hahka, Thiago Genaro-Mattos, Zeljka Korade, Corrine K. Hanson, Ann Anderson-Berry, Melissa K. Thoene

Journal Articles: Pediatrics

Vitamin A (retinol) is essential for normal fetal development, but the recommendation for maternal dietary intake (Retinol Activity Equivalent, RAE) does not differ for singleton vs. twin pregnancy, despite the limited evaluation of retinol status. Therefore, this study aimed to evaluate plasma retinol concentrations and deficiency status in mother-infant sets from singleton vs. twin pregnancies as well as maternal RAE intake. A total of 21 mother-infant sets were included (14 singleton, 7 twin). The HPLC and LC-MS/HS evaluated the plasma retinol concentration, and data were analyzed using the Mann-Whitney U test. Plasma retinol was significantly lower in twin vs. singleton …

An International Real-World Analysis Of Relapsed/Refractory Lymphoma Occurring During Pregnancy, Faheem Farooq, Justin S. Brandt, Elyce Cardonick, Evgeniya Polushkina, Julie M. Vose, Sairah Ahmed, Praveen Ramakrishnan Geethakumari, Adam J. Olszewski, Hesham Yasin, Umar Farooq, Nada Hamad, Yong Lin, Charlotte Maggen, Robert Fruscio, Mina Mhallem Gziri, Karina Dahl Steffensen, Frédéric Amant, Andrew M. Evens

Journal Articles: Oncology and Hematology

No abstract provided.

The Salento Prognostic Model For Limited-Stage Peripheral T-Cell Lymphoma From The International T-Cell Project Network, Greg Hapgood, Monica Civallero, Yana Stepanishyna, Julie M. Vose, Monica Elena Cabrera, Ranjana H Advani, Stefano A. Pileri, Martina Manni, Steven M. Horwitz, Francine M. Foss, Felicitas Hitz, John Radford, Ivan Dlouhy, Carlos Chiattone, Won Seog Kim, Tetiana Skrypets, Arnon Nagler, Judith Trotman, Stefano Luminari, Massimo Federico

Journal Articles: Oncology and Hematology

The natural history of limited-stage peripheral T-cell lymphomas (PTCLs) remains poorly defined. We investigated outcomes and prognostic variables in patients registered in the T-Cell Project (TCP) (#NCT01142674) to develop a model to predict overall survival (OS) for the common nodal PTCL subtypes (PTCL-NOS, AITL, ALCL). The model was validated in an independent data set from Australian and Brazilian registries. 211 patients registered in the TCP between 2006-2018 were studied. The median age was 59 years (range 18-88) and median follow-up was 49 months. One hundred twenty-seven patients (78%) received anthracycline-based regimens, 5 patients (3%) radiotherapy alone (RT), 24 patients (15%) …

Integrative Analysis Of Clinicopathological Features Defines Novel Prognostic Models For Mantle Cell Lymphoma In The Immunochemotherapy Era: A Report From The North American Mantle Cell Lymphoma Consortium, Julie M. Vose, Kai Fu, Lu Wang, Adnan Mansoor, Douglas Stewart, Hongxia Cheng, Lynette M. Smith, Ji Yuan, Hina Naushad Qureishi, Brian K. Link, Melissa H. Cessna, Paul M. Barr, Brad S. Kahl, Matthew S. Mckinney, Nadia Khan, Ranjana H. Advani, Peter Martin, Andre H. Goy, Tycel J. Phillips, Amitkumar Mehta, Manali Kamdar, Michael Crump, Barbara Pro, Christopher R. Flowers, Caron A. Jacobson, Sonali M. Smith, Deborah M. Stephens, Veronika Bachanova, Zhaohui Jin, Shishou Wu, Francisco Hernandez-Ilizaliturri, Pallawi Torka, Andrea Anampa-Guzmán, Farshid Kashef, Xing Li, Sunandini Sharma, Timothy Greiner, James O. Armitage, Matthew A. Lunning, Dennis D. Weisenburger, Gregory Bociek, Javeed Iqbal, Guohua Yu, Chengfeng Bi, North American Mantle Cell Lymphoma Consortium

Journal Articles: Oncology and Hematology

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.

METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed …

Molecular Characterization Of Streptococcus Pneumoniae Causing Disease Among Children In Nigeria During The Introduction Of Pcv10 (Gsk), Stephanie W. Lo, Paulina A. Hawkins, Binta Jibir, Fatimah Hassan-Hanga, Mahmoud Gambo, Rasaq Olaosebikan, Grace Olanipekun, Huda Munir, Nicholas Kocmich, Amy J. Rezac-Elgohary, Safiya Gambo, Danstan Bagenda, Paul D. Fey, Robert F. Breiman, Lesley Mcgee, Stephen D. Bentley, Stephen K. Obaro, Community Acquired Pneumonia And Invasive Bacterial Disease Capibd Consortium

Journal Articles: Anesthesiology

Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and …

Novel Rna-Seq Signatures Post-Methamphetamine And Oxycodone Use In A Model Of Hiv-Associated Neurocognitive Disorders, Pranavi Athota, Nghi M. Nguyen, Victoria L. Schaal, Sankarasubramanian Jagadesan, Chittibabu Guda, Sowmya V. Yelamanchili, Gurudutt Pendyala

Journal Articles: Anesthesiology

In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of antiretroviral therapies (ARTs). However, the growing epidemic of polysubstance use (PSU) has led to concern for the effects of PSU on HIV-seropositive individuals. To effectively treat individuals affected by HAND, it is critical to understand the biological mechanisms affected by PSU, including the identification of novel markers. To fill this important knowledge gap, we used an in vivo HIV-1 Transgenic (HIV-1 Tg) animal model to investigate the effects of the combined use of chronic methamphetamine (METH) and oxycodone …

Identification Of Ywhah As A Novel Brain-Derived Extracellular Vesicle Marker Post Long-Term Midazolam Exposure During Early Development, Nghi M. Nguyen, Daniel Meyer, Luke Meyer, Subhash Chand, Jagadesan Sankarasubramanian, Maireen Miravite, Chittibabu Guda, Sowmya V. Yelamanchili, Gurudutt Pendyala

Journal Articles: Anesthesiology

Recently, the long-term use of sedative agents in the neonatal intensive care unit (NICU) has raised concerns about neurodevelopmental outcomes in exposed neonates. Midazolam (MDZ), a common neonatal sedative in the NICU, has been suggested to increase learning disturbances and cognitive impairment in children. However, molecular mechanisms contributing to such outcomes with long-term MDZ use during the early stages of life remain unclear. In this study, we for the first time elucidate the role of brain-derived extracellular vesicles (BDEVs), including mining the BDEV proteome post long-term MDZ exposure during early development. Employing our previously established rodent model system that mimics …

In Utero And Post-Natal Opioid Exposure Followed By Mild Traumatic Brain Injury Contributes To Cortical Neuroinflammation, Mitochondrial Dysfunction, And Behavioral Deficits In Juvenile Rats, Austin M. Gowen, Jina Yi, Kelly L. Stauch, Luke Miles, Sanjay Srinivasan, Katherine Odegaard, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Maternal opioid use poses a significant health concern not just to the expectant mother but also to the fetus. Notably, increasing numbers of children born suffering from neonatal opioid withdrawal syndrome (NOWS) further compounds the crisis. While epidemiological research has shown the heightened risk factors associated with NOWS, little research has investigated what molecular mechanisms underly the vulnerabilities these children carry throughout development and into later life. To understand the implications of in utero and post-natal opioid exposure on the developing brain, we sought to assess the response to one of the most common pediatric injuries: minor traumatic brain injury …

Effectiveness And Safety Of Bictegravir/Emtricitabine/Tenofovir Alafenamide In Patients With Hiv-1 Infection And Ongoing Substance Use Disorder: The Base Study, Joshua P. Havens, Sara Bares, Elizabeth Lyden, Anthony T. Podany, Kimberly Scarsi, Nada A. Fadul, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: People with human immunodeficiency virus (HIV) and substance use disorder (PWH/SUD) are at higher risk of nonadherence to antiretroviral therapy. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) exhibits high rates of efficacy with a favorable adverse event profile. The BASE study (NCT03998176) is a phase 4, single-arm study evaluating the effectiveness and safety of B/F/TAF among PWH/SUD.

METHODS: Viremic (HIV RNA >1000 copies/mL) PWH/SUD initiated B/F/TAF once daily for 48 weeks (W). The primary endpoint was proportion of participants with HIV RNA/mL at W24. Secondary endpoints were proportion of participants with HIV-1 RNA/mL at W48, safety, B/F/TAF adherence (dried blood spot [DBS] concentrations …

Factors Associated With Prevalent Mycobacterium Tuberculosis Infection And Disease Among Adolescents And Adults Exposed To Rifampin-Resistant Tuberculosis In The Household, Soyeon Kim, Anneke C. Hesseling, Xingye Wu, Michael D. Hughes, N. Sarita Shah, Sanjay Gaikwad, Nishi Kumarasamy, Erika Mitchell, Mey Leon, Pedro Gonzales, Sharlaa Badal-Faesen, Madeleine Lourens, Sandy Nerette, Justin Shenje, Petra De Koker, Supalert Nedsuwan, Lerato Mohapi, Unoda A. Chakalisa, Rosie Mngqbisa, Rodrigo Otávio Da Silva Escada, Samuel Ouma, Barbara Heckman, Linda Naini, Amita Gupta, Susan Swindells, Gavin Churchyard, Actg A5300/Impaact 2003 Phoenix Feasibility Study Team

Journal Articles: Infectious Diseases

BACKGROUND: Understanding factors associated with prevalent Mycobacterium tuberculosis infection and prevalent TB disease in household contacts of patients with drug-resistant tuberculosis (TB) may be useful for TB program staff conducting contact investigations.

METHODS: Using data from a cross-sectional study that enrolled index participants with rifampin-resistant pulmonary TB and their household contacts (HHCs), we evaluated HHCs age ≥15 years for factors associated with two outcomes: Mycobacterium tuberculosis infection and TB disease. Among HHCs who were not already diagnosed with current active TB disease by the TB program, Mycobacterium tuberculosis infection was determined by interferon-gamma release assay (IGRA). TB disease was adjudicated …

Citrullinated And Malondialdehyde-Acetaldehyde Modified Fibrinogen Activates Macrophages And Promotes An Aggressive Synovial Fibroblast Phenotype In Patients With Rheumatoid Arthritis, Nozima Aripova, Michael J. Duryee, Bryant England, Carlos D. Hunter, Jack E. Mordeson, Evan Ryan, Eric C. Daubach, Debra J. Romberger, Geoffrey M. Thiele, Ted R. Mikuls

Journal Articles: Internal Medicine

Objective: Post-translational protein modifications with malondialdehyde-acetaldehyde (MAA) and citrulline (CIT) are implicated in the pathogenesis of rheumatoidarthritis (RA). Although precise mechanisms have not been elucidated, macrophage-fibroblast interactions have been proposed to play a central role in the development and progression of RA. The purpose of our study was to evaluate the downstream effects of macrophage released soluble mediators, following stimulation with fibrinogen (FIB) modified antigens, on human fibroblast-like synoviocytes (HFLS).

Methods: PMA-treated U-937 monocytes (Mϕ) and macrophage-differentiated peripheral blood mononuclear cells (MP) were stimulated with FIB, FIB-MAA, FIB-CIT, or FIB-MAA-CIT. HFLS-RA cells were stimulated directly with FIB antigens or with …