Medicine and Health Sciences Commons^™

Chronic Stress-Induced Neuroinflammation: Relevance Of Rodent Models To Human Disease., Abigail G White, Elias Elias, Andrea Orozco, Shivon A Robinson, Melissa T Manners

Faculty Scholarship for the College of Science & Mathematics

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress-a …

The Neuroprotective Role Of Lipoxin A4 In Reinstating Blood Brain Barrier Integrity In Neuroinflammatory Disease Processes, Minjal Patel, Nimish Acharya

Rowan-Virtua Research Day

Background: The blood-brain barrier (BBB), formed by the vascular endothelium, astrocytic foot processes, pericytes, is a highly selective barrier that is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI).¹ Loss of BBB integrity leads to the proliferation of pro-inflammatory cytokines, including TNFɑ, IL-1β, and IL-6.² Moderate inflammation has a beneficial response in the system following an acute injury. However, prolonged inflammation has been known to perturb homeostasis and have …

The Role Of Inflammation In Diabetic Retinopathy In Patients With Type Ii Diabetes; Potential Therapeutic Perspectives, Adriana Georgescu, Ana Dascalu, Daniela Stana, Cristina Alexandrescu, Anca Bobirca, Bogdan Mihai Cristea, Geta Vancea, Crenguta Sorina Serboiu, Dragos Serban, Corneliu Tudor, Andreea Letitia Arsene, Laura Carina Tribus

Journal of Mind and Medical Sciences

Diabetic retinopathy is one of the major causes of visual impairment and blindness in adult population. The pathology is complex, the metabolic changes induced by the hyperglycemic environment leading to neurodegeneration, microvascular damage, with secondary ischemic and inflammatory changes in the retina. This review aims to update the literature data related to the role of inflammation in the onset and progression of diabetic retinopathy. Thus, the molecular and biochemical mechanisms triggered by excess glucose increase the expression of genes involved in inflammatory processes, which leads to the synthesis of inflammatory cytokines such as Il1, Il6, TNF alpha as well as …

Role Of Mechanoregulation In Mast Cell-Mediated Immune Inflammation Of The Smooth Muscle In The Pathophysiology Of Esophageal Motility Disorders, Raj Goyal, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Major esophageal disorders involve obstructive transport of bolus to the stomach, causing symptoms of dysphagia and impaired clearing of the refluxed gastric contents. These may occur due to mechanical constriction of the esophageal lumen or loss of relaxation associated with deglutitive inhibition, as in achalasia-like disorders. Recently, immune inflammation has been identified as an important cause of esophageal strictures and the loss of inhibitory neurotransmission. These disorders are also associated with smooth muscle hypertrophy and hypercontractility, whose cause is unknown. This review investigated immune inflammation in the causation of smooth muscle changes in obstructive esophageal bolus transport. Findings suggest that …

Effects Of Endurance Training On Skeletal Muscle Mass And Inflammation In A Rat Model Of Heart Failure, Aaron Garcia, Dillon Harris, Quinten Pigg, Daniela Sayuri Inoue, Mariana Janini Gomes

International Journal of Exercise Science: Conference Proceedings

Chronic disease states including heart failure (HF) often lead to reduced physical activity, resulting in disuse and low-level systemic inflammation, which contribute to the decline in muscle mass and function. An important goal of therapy in HF patients is to counteract or prevent the development of skeletal muscle alterations in order to restore a normal functional capacity. Exercise is an established means of improving exercise capacity and quality of life in patients with HF. Therefore, we aimed to evaluate the impact of an endurance program on skeletal muscle mass and inflammation in a rat model of pulmonary arterial hypertension (PAH)-induced …

Systemic Inflammation Persists In Rats With Heart Failure After A Short-Term Endurance Training Protocol, Quinten Pigg, Dillon Harris, Aaron Garcia, Daniela Sayuri Inoue, Mariana Janini Gomes

International Journal of Exercise Science: Conference Proceedings

Exercise has been shown to produce an anti-inflammatory response and an increased exercise tolerance in heart failure (HF) patients. In rats, monocrotaline (MCT) leads to pulmonary arterial hypertension-induced HF (PAH-HF), resulting in exercise intolerance and chronic inflammation. However, little is known about the effects of endurance training in rats with PAH-HF induced by monocrotaline. PURPOSE: To investigate the effects of an endurance training protocol on systemic inflammatory markers and exercise tolerance in rats with HF. METHODS: 30 male Wistar rats (~250g) were randomly divided into 4 groups: control untrained (CU); control trained (CT), PAH-HF untrained (HFU), and PAH-HF trained (HFT). …

Chimeric Antigen Receptor Macrophages Target And Resorb Amyloid Plaques, Alexander B. Kim, Qingli Xiao, Ping Yan, Qiuyun Pan, Gaurav Pandey, Susie Grathwohl, Ernesto Gonzales, Isabella Xu, Yoonho Cho, Hans Haecker, Slava Epelman, Abhinav Diwan, Jin-Moo Lee, Carl J Deselm

2020-Current year OA Pubs

Substantial evidence suggests a role for immunotherapy in treating Alzheimer's disease (AD). While the precise pathophysiology of AD is incompletely understood, clinical trials of antibodies targeting aggregated forms of β amyloid (Aβ) have shown that reducing amyloid plaques can mitigate cognitive decline in patients with early-stage AD. Here, we describe what we believe to be a novel approach to target and degrade amyloid plaques by genetically engineering macrophages to express an Aβ-targeting chimeric antigen receptor (CAR-Ms). When injected intrahippocampally, first-generation CAR-Ms have limited persistence and fail to significantly reduce plaque load, which led us to engineer next-generation CAR-Ms that secrete …

Prenatal Exposure To Maternal Disadvantage-Related Inflammatory Biomarkers: Associations With Neonatal White Matter Microstructure, Ashley F P Sanders, Brian Tirado, Nicole A Seider, Regina L Triplett, Rachel E Lean, Jeffrey J Neil, J Philip Miller, Rebecca Tillman, Tara A Smyser, Deanna M Barch, Joan L Luby, Cynthia E Rogers, Christopher D Smyser, Barbara B Warner, Et Al.

2020-Current year OA Pubs

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal …

Mucosal Boosting Enhances Vaccine Protection Against Sars-Cov-2 In Macaques, Katherine Mcmahan, Adrianus C M Boon, Et Al.

2020-Current year OA Pubs

A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants

Covid-19 Convalescent Plasma Therapy Decreases Inflammatory Cytokines: A Randomized Controlled Trial, Feben Habtehyimer, Xianming Zhu, Andrew D Redd, Kelly A Gebo, Alison G Abraham, Eshan U Patel, Oliver Laeyendecker, Thomas J Gniadek, Reinaldo E Fernandez, Owen R Baker, Malathi Ram, Edward R Cachay, Judith S Currier, Yuriko Fukuta, Jonathan M Gerber, Sonya L Heath, Barry Meisenberg, Moises A Huaman, Adam C Levine, Aarthi Shenoy, Shweta Anjan, Janis E Blair, Daniel Cruser, Donald N Forthal, Laura L Hammitt, Seble Kassaye, Giselle S Mosnaim, Bela Patel, James H Paxton, Jay S Raval, Catherine G Sutcliffe, Matthew Abinante, Kevin S Oei, Valerie Cluzet, Marie Elena Cordisco, Benjamin Greenblatt, William Rausch, David Shade, Amy L Gawad, Sabra L Klein, Andrew Pekosz, Shmuel Shoham, Arturo Casadevall, Evan M Bloch, Daniel Hanley, Aaron A R Tobian, David J Sullivan

Journal Articles

This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Sensory Neurons Promote Immune Homeostasis In The Lung, Masato Tamari, Aaron M Ver Heul, Masato Hoshi, Anna M Trier, Ting-Lin Yang, Sanjay Jain, Steven Van Dyken, Et Al.

2020-Current year OA Pubs

Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant (JAK1

A Population-Based Study Of Children Suggests Blunted Morning Cortisol Rhythms Are Associated With Alterations Of The Systemic Inflammatory State, Runia Roy, Utkarsh J. Dang, Kim M. Huffman, Tchilabalo Alayi, Yetrib Hathout, Kanneboyina Nagaraju, Paul S. Visich, Eric P. Hoffman

Pharmacy Faculty Scholarship

Background: In children, digital media, lifestyle, and the COVID pandemic have impacted sunlight exposure, exercise, and diet patterns - cues that entrain the circadian clock. We hypothesized that low morning cortisol reflects a weak circadian clock, impacting the pro-inflammatory state. The primary objective was to test relationships between diurnal cortisol fluctuations and the inflammatory state in children as a means of providing indirect support for this hypothesis. Methods: The Cardiovascular Health Intervention Program (CHIP) was a population-based cross-sectional and longitudinal study of circadian health in public elementary school children in Southern Maine, USA (recruitment period 2012–2017). Participants were 689 students …

Orthodontically Induced Changes To The Genetic Profile In Periodontal Ligament Tissue And Cytokine Release In Gingival Crevicular Fluid - A Pilot Investigation, Nutthakarn Ratanasereeprasert, Li-Fang Hsu, Shih-Kai Wang, Chung-Chen Jane Yao

Journal Articles

BACKGROUND/PURPOSE: It has been known that genetic factors influence orthodontic tooth movement, however, scientific research on humans is lacking. Therefore, this study aimed to investigate dynamic changes to the genetic profile in human periodontal ligament (PDL) tissue and cytokine release in gingival crevicular fluid (GCF) during the first 28 days of orthodontic treatment.

MATERIALS AND METHODS: Fifteen teeth from three patients were recruited. Full-mouth fixed appliances with extraction of four premolars and one maxillary third molar was planned for orthodontic treatment. GCF collection and tooth extraction were performed following force application for 0, 1, 3, 7, and 28 days. GCF …

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 …

Para-Infectious Brain Injury In Covid-19 Persists At Follow-Up Despite Attenuated Cytokine And Autoantibody Responses, Benedict D Michael, Cordelia Dunai, Edward J Needham, Kukatharmini Tharmaratnam, Robyn Williams, Yun Huang, Sarah A Boardman, Jordan J Clark, Parul Sharma, Krishanthi Subramaniam, Greta K Wood, Ceryce Collie, Richard Digby, Alexander Ren, Emma Norton, Maya Leibowitz, Soraya Ebrahimi, Andrew Fower, Hannah Fox, Esteban Tato, Mark A Ellul, Geraint Sunderland, Marie Held, Claire Hetherington, Franklyn N Egbe, Alish Palmos, Kathy Stirrups, Alexander Grundmann, Anne-Cecile Chiollaz, Jean-Charles Sanchez, James P Stewart, Michael Griffiths, Tom Solomon, Gerome Breen, Alasdair J Coles, Nathalie Kingston, John R Bradley, Patrick F Chinnery, Jonathan Cavanagh, Sarosh R Irani, Angela Vincent, J Kenneth Baillie, Peter J Openshaw, Malcolm G Semple, Covid-Cns Consortium, Isaric4c Investigators, Leonie S Taams, David K Menon

Journal Articles

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common …

Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala

Center for Translational Medicine Faculty Papers

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …

The Inflammatory Response To Different Hiit Modalities, John G. Wallace Iii, Jared Moore, E. Todd Schroeder

International Journal of Exercise Science: Conference Proceedings

Pro-inflammatory and anti-inflammatory cytokines have been documented to change in response to long-duration, aerobic exercise. Little work has been performed in high-intensity interval training (HIIT). Furthermore, it has yet to be elucidated whether the modality of HIIT affects this inflammatory response. PURPOSE: The purpose of this study was to investigate the changes in IL-8 and IL-10 cytokine concentrations pre-post and post-1hr following HIIT protocols using two different exercise modalities, treadmill running (TM) and stationary cycling (CE). METHODS: Eight young, healthy, recreationally active volunteers (1 female, 7 males; 25.50 ± 3.25 years) completed a 4x4 HIIT protocol (4-minute 85-95% …

Infection And Inflammation Stimulate Expansion Of A Cd74+ Paneth Cell Subset To Regulate Disease Progression, Iyshwarya Balasubramanian, Shengxiang Sun, Ta-Chiang Liu, Et Al.

2020-Current year OA Pubs

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74

Type 2 Immunity In The Brain And Brain Borders, Tornike Mamuladze, Jonathan Kipnis

2020-Current year OA Pubs

Recent research in neuroimmunology has revolutionized our understanding of the intricate interactions between the immune system and the central nervous system (CNS). The CNS, an "immune-privileged organ", is now known to be intimately connected to the immune system through different cell types and cytokines. While type 2 immune responses have traditionally been associated with allergy and parasitic infections, emerging evidence suggests that these responses also play a crucial role in CNS homeostasis and disease pathogenesis. Type 2 immunity encompasses a delicate interplay among stroma, Th2 cells, innate lymphoid type 2 cells (ILC2s), mast cells, basophils, and the cytokines interleukin (IL)-4, …

T Cell Control Of Inflammaging, Irina Shchukina, Pavla Bohacova, Maxim N Artyomov

2020-Current year OA Pubs

T cells are a critical component of the immune system, found in abundance in blood, secondary lymphoid organs, and peripheral tissues. As individuals age, T cells are particularly susceptible to changes, making them one of the most affected immune subsets. These changes can have significant implications for age-related dysregulations, including the development of low-grade inflammation - a hallmark of aging known as inflammaging. In this review, we first present age-related changes in the functionality of the T cell compartment, including dysregulation of cytokine and chemokine production and cytotoxicity. Next, we discuss how these changes can contribute to the development and …

Il-6 Selectively Suppresses Cdc1 Specification Via C/Ebpβ, Sunkyung Kim, Jing Chen, Suin Jo, Feiya Ou, Stephen T Ferris, Tian-Tian Liu, Ray A Ohara, David A Anderson, Renee Wu, Michael Y Chen, William E Gillanders, William E Gillanders, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPβ in the common dendritic cell progenitor (CDP). C/EBPβ and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively. At homeostasis, pre-cDC1 specification occurs upon Nfil3 induction and consequent Zeb2 suppression. However, IL-6 strongly induces C/EBPβ expression in …

Social And Psychological Adversity Are Associated With Distinct Mother And Infant Gut Microbiome Variations, Barbara B Warner, Bruce A Rosa, I Malick Ndao, Phillip I Tarr, J Philip Miller, Sarah K England, Joan L Luby, Cynthia E Rogers, Carla Hall-Moore, Renay E Bryant, Jacqueline D Wang, Laura A Linneman, Tara A Smyser, Christopher D Smyser, Deanna M Barch, John Martin, Makedonka Mitreva, Et Al.

2020-Current year OA Pubs

Health disparities are driven by underlying social disadvantage and psychosocial stressors. However, how social disadvantage and psychosocial stressors lead to adverse health outcomes is unclear, particularly when exposure begins prenatally. Variations in the gut microbiome and circulating proinflammatory cytokines offer potential mechanistic pathways. Here, we interrogate the gut microbiome of mother-child dyads to compare high-versus-low prenatal social disadvantage, psychosocial stressors and maternal circulating cytokine cohorts (prospective case-control study design using gut microbiomes from 121 dyads profiled with 16 S rRNA sequencing and 89 dyads with shotgun metagenomic sequencing). Gut microbiome characteristics significantly predictive of social disadvantage and psychosocial stressors in …

Hyperferritinemic Sepsis, Macrophage Activation Syndrome, And Mortality In A Pediatric Research Network: A Causal Inference Analysis, Zhenziang Fan, John C Lin, Allan Doctor, Et Al.

2020-Current year OA Pubs

BACKGROUND: One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network's objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis.

METHODS: We assessed differences in 32 cytokines, immune depression (low whole blood ex vivo TNF response to endotoxin) and thrombotic microangiopathy (low ADAMTS13 activity) biomarkers, seven viral DNAemias, and macrophage activation syndrome (MAS) defined by combined hepatobiliary dysfunction and disseminated intravascular coagulation, and mortality in 117 children with hyperferritinemic sepsis (ferritin level > 500 ng/mL) compared to 280 children with sepsis …

Sex-Dependent Effects Of Intestinal Microbiome Manipulation In A Mouse Model Of Alzheimer’S Disease, Harpreet Kaur, Suba Nookala, Surjeet Singh, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin K. Combs

Biomedical Sciences Faculty Publications

Mechanisms linking intestinal bacteria and neurodegenerative diseases such as Alzheimer’s disease (AD) are still unclear. We hypothesized that intestinal dysbiosis might potentiate AD, and manipulating the microbiome to promote intestinal eubiosis and immune homeostasis may improve AD-related brain changes. This study assessed sex differences in the effects of oral probiotic, antibiotics, and synbiotic treatments in the AppNL-G-F mouse model of AD. The fecal microbiome demonstrated significant correlations between bacterial genera in AppNL-G-F mice and Aβ plaque load, gliosis, and memory performance. Female and not male AppNL-G-F mice fed probiotic but not synbiotic exhibited a decrease in Aβ plaques, microgliosis, brain …

Hla-Ii Alleles Influence Physical And Behavioral Responses To A Whey Allergen In A Transgenic Mouse Model Of Cow's Milk Allergy, Danielle L. Germundson, Suba Nookala, Nicholas A. Smith, Yassmine Warda, Kumi Nagamoto-Combs

Biomedical Sciences Faculty Publications

The symptoms of food allergies vary significantly between individuals, likely due to genetic determinants. In humans, allergy development is initiated by antigen-presenting cells via class II human leukocyte antigen (HLA-II). The HLA-II gene is highly polymorphic, and its allelic variance is thought to influence the susceptibility of individuals to a particular allergen. However, whether antigen presentation by different HLA-II variants contributes to symptom variation is not clear. We hypothesized that HLA-II allelic variance affects symptom phenotypes, including immediate physical reactions and delayed behavioral changes, in individuals with food hypersensitivity. To test our hypothesis, male and female mice of three transgenic …

Lower Levels Of Th1 And Th2 Cytokines In Cerebrospinal Fluid (Csf) At The Time Of Initial Csf Shunt Placement In Children Are Associated With Subsequent Shunt Revision Surgeries, Tamara D Simon, Sabrina Sedano, Yael Rosenberg-Hasson, Ramon Durazo-Arvizu, Kathryn B Whitlock, Paul Hodor, Jason S Hauptman, David D Limbrick, Patrick Mcdonald, Jeffrey G Ojemann, Holden T Maecker, Cerebrospinal Fluid Microbiota In Shunts Climb Study Group

2020-Current year OA Pubs

OBJECTIVE: We compare cytokine profiles at the time of initial CSF shunt placement between children who required no subsequent shunt revision surgeries and children requiring repeated CSF shunt revision surgeries for CSF shunt failure. We also describe the cytokine profiles across surgical episodes for children who undergo multiple subsequent revision surgeries.

METHODS: This pilot study was nested within an ongoing prospective multicenter study collecting CSF samples and clinical data at the time of CSF shunt surgeries since August 2014. We selected cases where CSF was available for children who underwent an initial CSF shunt placement and had no subsequent shunt …

Dynamics Of Inflammatory Responses After Sars-Cov-2 Infection By Vaccination Status In The Usa: A Prospective Cohort Study, Xianming Zhu, Kelly A Gebo, Alison G Abraham, Feben Habtehyimer, Eshan U Patel, Oliver Laeyendecker, Thomas J Gniadek, Reinaldo E Fernandez, Owen R Baker, Malathi Ram, Edward R Cachay, Judith S Currier, Yuriko Fukuta, Jonathan M Gerber, Sonya L Heath, Barry Meisenberg, Moises A Huaman, Adam C Levine, Aarthi Shenoy, Shweta Anjan, Janis E Blair, Daniel Cruser, Donald N Forthal, Laura L Hammitt, Seble Kassaye, Giselle S Mosnaim, Bela Patel, James H Paxton, Jay S Raval, Catherine G Sutcliffe, Matthew Abinante, Patrick Broderick, Valerie Cluzet, Marie Elena Cordisco, Benjamin Greenblatt, Joann Petrini, William Rausch, David Shade, Karen Lane, Amy L Gawad, Sabra L Klein, Andrew Pekosz, Shmuel Shoham, Arturo Casadevall, Evan M Bloch, Daniel Hanley, David J Sullivan, Aaron A R Tobian

Journal Articles

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection.

METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples …

Association Of Inflammatory Markers And Growth Factors With Radiographically Assessed Wound Healing Of Extraction Sockets, Sasha Mohammadi

Theses & Dissertations

The purpose of this prospective cohort pilot study was to investigate the association of the periodontal status and inflammatory markers from the gingival crevicular and wound fluid with the healing outcomes following tooth extraction. The central research hypothesis is that extraction sites and the adjacent teeth that exhibit increased markers of inflammation, or decreased growth factors, at baseline or 2 weeks will be associated with reduced healing outcomes observed radiographically 3 months following surgery. Nine patients at the UNMC College of Dentistry who were seeking care to extract a posterior tooth due to advanced periodontal bone loss, non-restorable caries or …

Cell Surface B2m-Free Human Leukocyte Antigen (Hla) Monomers And Dimers: Are They Neo-Hla Class And Proto-Hla?, Mepur H. Ravindranath, Narendranath M. Ravindranath, Senthamil R. Selvan, Fatiha El Hilali, Carly J. Amato-Menker, Edward J. Filippone

Division of Nephrology Faculty Papers

Cell surface HLA-I molecules (Face-1) consist of a polypeptide heavy chain (HC) with two groove domains (G domain) and one constant domain (C-domain) as well as a light chain, B2-microglobulin (B2m). However, HCs can also independently emerge unfolded on the cell surface without peptides as B2m-free HC monomers (Face-2), B2m-free HC homodimers (Face 3), and B2m-free HC heterodimers (Face-4). The transport of these HLA variants from ER to the cell surface was confirmed by antiviral antibiotics that arrest the release of newly synthesized proteins from the ER. Face-2 occurs at low levels on the normal cell surface of the lung, …

T-Bet And Eomes Sustain Mature Human Nk Cell Identity And Antitumor Function, Pamela Wong, Jennifer A. Foltz, Lily Chang, Carly C. Neal, Tony Yao, Celia C. Cubitt, Jennifer Tran, Samantha Kersting-Schadek, Sathvik Palakurty, Natalia Jaeger, David A. Russler-Germain, Nancy D. Marin, Margery Gang, Julia A. Wagner, Alice Y. Zhou, Miriam T. Jacobs, Mark Foster, Timothy Schappe, Lynne Marsala, Ethan Mcclain, Patrick Pence, Michelle Becker-Hapak, Bryan Fisk, Allegra A. Petti, Obi L. Griffith, Malachi Griffith, Melissa M. Berrien-Elliott, Todd A. Fehniger

2020-Current year OA Pubs

Since the T-box transcription factors (TFs) T-BET and EOMES are necessary for initiation of NK cell development, their ongoing requirement for mature NK cell homeostasis, function, and molecular programming remains unclear. To address this, T-BET and EOMES were deleted in unexpanded primary human NK cells using CRISPR/Cas9. Deleting these TFs compromised in vivo antitumor response of human NK cells. Mechanistically, T-BET and EOMES were required for normal NK cell proliferation and persistence in vivo. NK cells lacking T-BET and EOMES also exhibited defective responses to cytokine stimulation. Single-cell RNA-Seq revealed a specific T-box transcriptional program in human NK cells, which …