Medicine and Health Sciences Commons^™

Protective Effects Of Epigallocatechin-3-Gallate Counteracting The Chronic Hypobaric Hypoxia-Induced Myocardial Injury In Plain-Grown Rats At High Altitude, Haotian Chen, Chen Chen, Yuhui Qin, Lei Wang, Jie Zheng, Fabao Gao

2020-Current year OA Pubs

Exposure to hypobaric hypoxia (HH) environment causes stress to the body, especially the oxygen-consuming organs. Chronic HH conditions have adverse effects on the myocardium. Thus, we conducted this experiment and aim to evaluate such adverse effects and explore the therapeutic role of epigallocatechin-3-gallate (EGCG) in rats' heart under chronic HH conditions. For that purpose, we transported rats from plain to a real HH environment at high altitude for establishing the HH model. At high altitude, animals were treated with EGCG while the salidroside was used as the positive control. General physiological data were collected, and routine blood test results were …

Modeling The Normal:Abnormal Spectrum Of Early Childhood Internalizing Behaviors: A Clinical-Developmental Approach For The Multidimensional Assessment Profiles Internalizing Dimensions, Lauren S Wakschlag, Phillip Sherlock, Courtney K Blackwell, James L Burns, Sheila Krogh-Jespersen, Richard C Gershon, David Cella, Kristin A Buss, Joan L Luby

2020-Current year OA Pubs

BACKGROUND: We expanded the Multidimensional Assessment Profiles (MAPS) Scales developmental specification model to characterize the normal:abnormal spectrum of internalizing (anxious and depressive) behaviors in early childhood via the MAPS-Internalizing (MAPS-INT) scale.

METHODS: The MAPS-INT item pool was generated based on clinical expertise and prior research. Analyses were conducted on a sub-sample of families (n = 183) from the diverse When to Worry early childhood sample.

RESULTS: Normal:abnormal descriptive patterns for both anxious and depressive behaviors were consistent with prior work: (1) extremes of normative variation are abnormal when very frequent; and (2) pathognomonic indicators that most children do not engage …

Operational Ontology For Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical And Research Use Of Real-World Data From Patients Treated For Cancer, Charles S Mayo, Walter Bosch, Et Al.

2020-Current year OA Pubs

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships.

METHODS AND MATERIALS: The American Association of Physicists in Medicine's Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders' collective experience of issues that typically compromise the formation of large inter- …

Steatosis Drives Monocyte-Derived Macrophage Accumulation In Human Metabolic Dysfunction-Associated Fatty Liver Disease, Mandy M Chan, Joseph W Beals, Marina Terekhova, Christina F Fu, Li He, Arick C Park, Gordon I Smith, Kathleen Byrnes, Wandy L Beatty, Shaina R Eckhouse, J Christopher Eagon, Daniel Ferguson, Brian N Finck, Samuel Klein, Maxim N Artyomov, Joel D Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MAFLD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear.

METHODS: Liver tissue from 21 participants was collected at time of bariatric surgery and analysed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n = 3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. …

Foreign Body Granulomas To Polymethylmethacrylate Soft Tissue Filler Following Covid-19 Infection, Nathan Vengalil, Laurin M Council, Basia M Michalski

2020-Current year OA Pubs

No abstract provided.

Pemphigoid Gestationis Treated With Dupilumab, Rita E Chen, Christine C Yokoyama, Milan J Anadkat

2020-Current year OA Pubs

No abstract provided.

Plain Language Summary Of The Topaz-1 Study: Durvalumab And Chemotherapy For Advanced Biliary Tract Cancer, Do-Youn Oh, Benjamin Tan, Et Al.

2020-Current year OA Pubs

WHAT IS THIS SUMMARY ABOUT?: This is a summary describing the results of a Phase III study called TOPAZ-1. The study looked at treatment with durvalumab (a type of immunotherapy) and chemotherapy to treat participants with advanced biliary tract cancer (BTC). Advanced BTC is usually diagnosed at late stages of disease, when it cannot be cured by surgery. This study included participants with advanced BTC who had not received previous treatment, or had their cancer come back at least 6 months after receiving treatment or surgery that aimed to cure their disease. Participants received treatment with durvalumab and chemotherapy or …

Disrupting Actin Filaments Enhances Glucose-Stimulated Insulin Secretion Independent Of The Cortical Actin Cytoskeleton, Alexander J Polino, Xue Wen Ng, Rebecca Rooks, David W Piston

2020-Current year OA Pubs

Just under the plasma membrane of most animal cells lies a dense meshwork of actin filaments called the cortical cytoskeleton. In insulin-secreting pancreatic β cells, a long-standing model posits that the cortical actin layer primarily acts to restrict access of insulin granules to the plasma membrane. Here we test this model and find that stimulating β cells with pro-secretory stimuli (glucose and/or KCl) has little impact on the cortical actin layer. Chemical perturbations of actin polymerization, by either disrupting or enhancing filamentation, dramatically enhance glucose-stimulated insulin secretion. Using scanning electron microscopy, we directly visualize the cortical cytoskeleton, allowing us to …

The Structure Of Nad+ Consuming Protein Acinetobacter Baumannii Tir Domain Shows Unique Kinetics And Conformations, Erik Klontz, Kow Essuman, Jeffrey Milbrandt, Aaron Diantonio, Et Al.

2020-Current year OA Pubs

Toll-like and interleukin-1/18 receptor/resistance (TIR) domain-containing proteins function as important signaling and immune regulatory molecules. TIR domain-containing proteins identified in eukaryotic and prokaryotic species also exhibit NAD+ hydrolase activity in select bacteria, plants, and mammalian cells. We report the crystal structure of the Acinetobacter baumannii TIR domain protein (AbTir-TIR) with confirmed NAD

Copy-Back Viral Genomes Induce A Cellular Stress Response That Interferes With Viral Protein Expression Without Affecting Antiviral Immunity, Lavinia J González Aparicio, Yanling Yang, Matthew Hackbart, Carolina B. López

2020-Current year OA Pubs

Antiviral responses are often accompanied by translation inhibition and formation of stress granules (SGs) in infected cells. However, the triggers for these processes and their role during infection remain subjects of active investigation. Copy-back viral genomes (cbVGs) are the primary inducers of the mitochondrial antiviral signaling (MAVS) pathway and antiviral immunity during Sendai virus (SeV) and respiratory syncytial virus (RSV) infections. The relationship between cbVGs and cellular stress during viral infections is unknown. Here, we show that SGs form during infections containing high levels of cbVGs, and not during infections with low levels of cbVGs. Moreover, using RNA fluorescent in …

Dominant Negative Variants In Kif5b Cause Osteogenesis Imperfecta Via Down Regulation Of Mtor Signaling, Ronit Marom, Anika Lindsey, Jacob Lesinski, Michael L. Nonet, Jian Chen, Dustin Baldridge, Gary A. Silverman, Stephen C. Pak, Et Al.

2020-Current year OA Pubs

BACKGROUND: Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown.

METHODS: To understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, …

Hepatic Pyruvate And Alanine Metabolism Are Critical And Complementary For Maintenance Of Antioxidant Capacity And Resistance To Oxidative Insult, Nicole K H Yiew, Joel H Vazquez, Michael R Martino, Stefanie Kennon-Mcgill, Jake R Price, Felicia D Allard, Eric U Yee, Alexander J Layman, Laura P James, Kyle S Mccommis, Brian N Finck, Mitchell R Mcgill

2020-Current year OA Pubs

OBJECTIVE: Mitochondrial pyruvate is a critical intermediary metabolite in gluconeogenesis, lipogenesis, and NADH production. As a result, the mitochondrial pyruvate carrier (MPC) complex has emerged as a promising therapeutic target in metabolic diseases. Clinical trials are currently underway. However, recent in vitro data indicate that MPC inhibition diverts glutamine/glutamate away from glutathione synthesis and toward glutaminolysis to compensate for loss of pyruvate oxidation, possibly sensitizing cells to oxidative insult. Here, we explored this in vivo using the clinically relevant acetaminophen (APAP) overdose model of acute liver injury, which is driven by oxidative stress.

METHODS: We used pharmacological and genetic approaches …

Regional Vulnerability Indices In Youth With Persistent And Distressing Psychoticlike Experiences, Nicole R Karcher, Hailey Modi, Peter Kochunov, Si Gao, Deanna M Barch

2020-Current year OA Pubs

IMPORTANCE: Distressing and persistent psychoticlike experiences (PLEs) in youth are associated with greater odds of developing psychiatric conditions in adulthood. Despite this risk, it is unclear whether early PLEs show similar brain patterns compared with adults with psychiatric and neurologic conditions.

OBJECTIVE: To examine the degree to which persistent and distressing PLEs exhibit neural metrics that show similarity to adults with chronic psychiatric and neurologic conditions.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Adolescent Brain Cognitive Development (ABCD) Study examining the persistence and distress associated with PLEs across the first 3 waves of data with baseline structural magnetic resonance …

Reducing Length Of Antibiotics For Children With Ear Infections: Protocol For A Cluster-Randomized Trial In The Usa, Amy Keith, Timothy C Jenkins, Sonja O'Leary, Amy B Stein, Sophie E Katz, Jason Newland, Deborah J Rinehart, Aiden Gilbert, Sherry Dodd, Cindy M Terrill, Holly M Frost

2020-Current year OA Pubs

No abstract provided.

Small Molecule Screen Identifies Pyrimethamine As An Inhibitor Of Nrf2-Driven Esophageal Hyperplasia, Chorlada Paiboonrungruang, Brittany Bowman, Julius Chembo, M Ben Major, Et Al.

2020-Current year OA Pubs

OBJECTIVE: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2

DESIGN: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays.

RESULTS: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as …

Effect Of Amoxicillin On The Gut Microbiome Of Children With Severe Acute Malnutrition In Madarounfa, Niger: A Retrospective Metagenomic Analysis Of A Placebo-Controlled Trial, Drew J Schwartz, Amy Langdon, Xiaoqing Sun, Céline Langendorf, Fatou Berthé, Rebecca F Grais, Indi Trehan, Sheila Isanaka, Gautam Dantas

2020-Current year OA Pubs

BACKGROUND: Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition.

METHODS: We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of …

Outcomes Of Therapy And Ulnar Nerve Transposition For Elbow Stiffness After Pediatric Medial Epicondyle Fractures, Emma R Payne, Lindley B Wall, Stacy Baker, Valeri Calhoun, Summer Roberts, Charles A Goldfarb

2020-Current year OA Pubs

PURPOSE: Following medial epicondyle fractures, a subset of pediatric patients has persistent limitations in elbow motion. This study soughted to understand the patient characteristics of this group and to assess the effectiveness of intensive therapy and ulnar nerve transposition in improving elbow range of motion and patient-reported outcomes.

METHODS: A cohort of 31 pediatric patients with stiffness after elbow trauma was narrowed to 8 pediatric patients (7 female) ranging in age from 9 to 14 years, who were diagnosed with medial epicondyle fractures and underwent intensive therapy and ulnar nerve transposition with or without elbow joint release. We collected demographic …

A Not-So-Sweet Syndrome: A Case Report Of A Male Presenting With Acute Febrile Neutrophilic Dermatosis, Kim-Long R. Nguyen, Aaron J. Lacy, Suelin Hilbert, Rosanne S. Naunheim

2020-Current year OA Pubs

Physicians often encounter patients who present with a chief complaint of skin changes or lesions in both acute and primary care settings. Early initiation of appropriate treatment and pharmacotherapy in patients who present with rash is crucial to prevent decompensation, morbidity, and further downstream utilization of hospital resources. Acute febrile neutrophilic dermatosis, more commonly known as Sweet syndrome, is a rare and highly symptomatic inflammatory skin condition. Early recognition of Sweet syndrome is important as it requires specific treatment considerations and often can be a sign of an underlying pro-inflammatory condition, malignancy, or reaction to new medication that must be …

Experimentally Induced Active And Quiet Sleep Engage Non-Overlapping Transcriptional Programs In Drosophila, Niki Anthoney, Lucy Tainton-Heap, Hang Luong, Eleni Notaras, Amber B Kewin, Qiongyi Zhao, Trent Perry, Philip Batterham, Paul J Shaw, Bruno Van Swinderen

2020-Current year OA Pubs

Sleep in mammals can be broadly classified into two different physiological categories: rapid eye movement (REM) sleep and slow-wave sleep (SWS), and accordingly REM and SWS are thought to achieve a different set of functions. The fruit fly

Identifying And Reverting The Adverse Effects Of White Matter Hyperintensities On Cortical Surface Analyses, Yuki Oi, Masakazu Hirose, Hiroki Togo, Kenji Yoshinaga, Thai Akasaka, Tomohisa Okada, Toshihiko Aso, Ryosuke Takahashi, Matthew F Glasser, Takuya Hayashi, Takashi Hanakawa

2020-Current year OA Pubs

The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert …

Advances In Screening For Radiation-Associated Cardiotoxicity In Cancer Patients, Walter Schiffer, Lauren N Pedersen, Matthew Lui, Carmen Bergom, Joshua D Mitchell

2020-Current year OA Pubs

PURPOSE OF REVIEW: Radiation is foundational to the treatment of cancer and improves overall survival. Yet, it is important to recognize the potential cardiovascular effects of radiation therapy and how to best minimize or manage them. Screening-both through imaging and with biomarkers-can potentially identify cardiovascular effects early, allowing for prompt initiation of treatment to mitigate late effects.

RECENT FINDINGS: Cardiac echocardiography, magnetic resonance imaging (MRI), computed tomography, and measurements of troponin and natriuretic peptides serve as the initial screening tests of choice for RICD. Novel imaging applications, including positron emission tomography and specific MRI parameters, and biomarker testing, including myeloperoxidase, …

Novel Academic Tabletop 2022 (Nat22): A Dynamic Dice-Based Emergency Medicine Education Tool, Adam Heilmann, Jessica Pelletier, Collyn Murray, Alexander Croft

2020-Current year OA Pubs

Gamification is an effective teaching tool that improves engagement and knowledge retention. Tabletop role-playing games are dynamic games that use random chance and foster player/leader partnership. To date, there are no teaching tools that mimic dynamic or unpredictable patient presentations. This style of game may work well as a tool for medical education in a simulation-based modality. In this report, we document the rules, materials, and training required to reproduce a hybrid game created to combine facets of simulation and tabletop role-playing games (TRPGs) to create a dynamic medical education tool. After testing the game for flaws and fluidity of …

Cytokine Release Syndrome In Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: A Retrospective Study Analyzing Risks, Outcomes, And Healthcare Burden, Rushin Patel, Mrunal Patel, Fehmida Laxmidhar, Khushboo Lakhatariya, Darshil Patel, Zalak Patel, Safia Shaikh

2020-Current year OA Pubs

Background Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising immunotherapy for various malignancies. However, its use is associated with challenges, including cytokine release syndrome (CRS), a potentially severe complication. This retrospective study aims to analyze the risks, outcomes, and healthcare burden of CRS in patients undergoing CAR-T therapy. Method Data from the 2020 National Inpatient Sample (NIS) were utilized, comprising 415 CAR-T-related hospitalizations. They were categorized into those with CRS (n = 68) and those without CRS (n = 347). Baseline characteristics, including age, gender, race, income, insurance status, and comorbidities, were compared. Outcomes of interest included …

Repeated Measures Of Mammographic Density And Texture To Evaluate Prediction And Risk Of Breast Cancer: A Systematic Review Of The Methods Used In The Literature, Akila Anandarajah, Yongzhen Chen, Carolyn Stoll, Angela Hardi, Shu Jiang, Graham A Colditz

2020-Current year OA Pubs

PURPOSE: It may be important for women to have mammograms at different points in time to track changes in breast density, as fluctuations in breast density can affect breast cancer risk. This systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk.

METHODS: The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021. Eligibility criteria included published articles in English describing the relationship of change in mammographic features with risk of breast cancer. Risk of bias was assessed using the …

Scientific Document Development Standards For The Society Of Cardiovascular Computed Tomography (Scct): A Statement From The Scct Guidelines Committee, Lauren A Baldassarre, Lynne Koweek, Daniele Andreini, Kelley Branch, Dawn Brennaman, Ricardo P J Budde, Stacy De La O, Timothy Fairbairn, Sandeep S Hedgire, Jonathan R Weir-Mccall, Pam K Woodard, Dennis Wong, Marcus Y Chen, Scct Guidelines Committee

2020-Current year OA Pubs

The Society of Cardiovascular Computed Tomography (SCCT) is an international community of physicians, scientists and technologists advocating for research, education, and clinical excellence in the use of cardiovascular computed tomography (CCT). SCCT members are committed to improving health outcomes through effective use of CCT. The SCCT routinely authors, endorses, and jointly collaborates on scientific documents that reflect the best available evidence and expert consensus supported in practice of CCT. This paper outlines SCCT's methodology for developing scientific documents. It was formulated by members of the SCCT Guidelines Committee and approved by the SCCT Board of Directors.

Six-Month Outcomes Of Mechanical Thrombectomy For Treating Deep Vein Thrombosis: Analysis From The 500-Patient Clout Registry, Abdullah Shaikh, Vipul Khetarpaul, Et Al.

2020-Current year OA Pubs

PURPOSE: Mechanical thrombectomy for the treatment of deep vein thrombosis (DVT) is being increasingly utilized to reduce symptoms and prevent postthrombotic syndrome (PTS), but more data on clinical outcomes are needed. Mechanical thrombectomy was studied in the ClotTriever Outcomes (CLOUT) registry with 6-month full analysis outcomes reported herein.

MATERIALS AND METHODS: The CLOUT registry is a prospective, all-comer study that enrolled 500 lower extremity DVT patients across 43 US sites treated with mechanical thrombectomy using the ClotTriever System. Core-lab assessed Marder scores and physician-assessed venous patency by duplex ultrasound, PTS assessment using Villalta score, venous symptom severity, pain, and quality …

Iuphar Themed Review: Opioid Efficacy, Bias, And Selectivity, Nokomis Ramos-Gonzalez, Barnali Paul, Susruta Majumdar

2020-Current year OA Pubs

Drugs acting at the opioid receptor family are clinically used to treat chronic and acute pain, though they represent the second line of treatment behind GABA analogs, antidepressants and SSRI's. Within the opioid family mu and kappa opioid receptor are commonly targeted. However, activation of the mu opioid receptor has side effects of constipation, tolerance, dependence, euphoria, and respiratory depression; activation of the kappa opioid receptor leads to dysphoria and sedation. The side effects of mu opioid receptor activation have led to mu receptor drugs being widely abused with great overdose risk. For these reasons, newer safer opioid analgesics are …

A Human Mitofusin 2 Mutation Can Cause Mitophagic Cardiomyopathy, Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina De Guzman Strong, Gerald W Dorn

2020-Current year OA Pubs

Cardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is 15-20× over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical, and functional characteristics of MFN2 Q400 versus wild-type and CMT2A-causing MFN2 mutants. All MFN2 mutants had impaired mitochondrial fusion, the canonical MFN2 function. Compared to MFN2 T105M that lacked catalytic GTPase activity and exhibited normal …

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 At 2 Children's Hospitals, Eric E Engstrom, Alexander S Plattner, J Chase Mcneil, Kristina G Hulten, Patrick J Reich, Mary G Boyle, James J Dunn, Stephanie A Fritz, Sheldon L Kaplan

2020-Current year OA Pubs

BACKGROUND: Invasive infections caused by

METHODS: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution.

RESULTS: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In …

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 …