RESUMO
Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remains obscure. Here, we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, T cell receptor (TCR)αß, and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a, and CD103, these cells share a gene-expression signature distinct from those of conventional NK cells, T cells, and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells, and IL-15 deficiency, but not Nfil3 deficiency, results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type-1-like innate lymphoid cells and type 1 innate-like T cells.
Assuntos
Linfócitos/imunologia , Neoplasias Mamárias Experimentais/imunologia , Monitorização Imunológica , Subpopulações de Linfócitos T/imunologia , Animais , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Granzimas/metabolismo , Interleucina-15/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismoRESUMO
Demethylation of the Foxp3 locus maintains gene expression and Treg cell stability. Yang et al. (2015) show that the gasotransmitter hydrogen sulfide co-operates with growth factor TGF-ß and interleukin-2 to activate Tet-mediated DNA demethylation of Foxp3 to promote immune tolerance.
Assuntos
Colite/imunologia , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Sulfeto de Hidrogênio/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Linfócitos T Reguladores/imunologia , Animais , HumanosRESUMO
Interleukin-7 receptor α chain (IL-7Rα) is induced upon T cell positive selection and controls thymic CD8-lineage specification and peripheral naive T cell homeostasis. How IL-7Rα expression is regulated in developing thymocytes is unclear. Here, we show that transforming growth factor ß (TGF-ß) signaling promoted IL-7Rα expression and CD8+ T cell differentiation. In addition, TGF-ß signaling was required for high IL-7Rα expression in CD4+ T cells bearing low-affinity T cell receptors, and the abrogation of TGF-ß receptor expression led to failed maintenance of peripheral CD4+ T cells. Compromised IL-7Rα expression in TGF-ß-receptor-deficient T cells was associated with increased expression of the Il7ra transcriptional repressor, Gfi-1. IL-7Rα transgenesis or T-cell-specific ablation of Gfi-1 restored IL-7Rα expression and largely ameliorated the development and homeostasis defects of TGF-ß-receptor-deficient T cells. These findings reveal functions for TGF-ß signaling in controlling IL-7Rα expression and in promoting T cell repertoire diversification.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Receptores de Interleucina-7/metabolismo , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular , Linhagem da Célula , Proteínas de Ligação a DNA/genética , Homeostase , Camundongos , Camundongos Knockout , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Antígenos de Linfócitos T , Receptores de Interleucina-7/imunologia , Receptores de Fatores de Crescimento Transformadores beta/deficiência , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Fatores de Transcrição/genéticaRESUMO
NYU School of Medicine recently embarked on a re-design of its anatomy curriculum that decreased the use of cadavers with plastinated specimens. Plastinated models provide an authentic learning experience of the human body, but lack necessary labels outlining important structures. Due to the fragile nature of the specimens, we endeavored to solve the challenge of labeling by developing a digitized supplement and archive of plastinated and pathology specimens. An interdisciplinary team of faculty and multimedia designers at NYU School of Medicine designed and developed electronic resources related to the artistic models and plastinated specimens. Over the course of three months, 60 artistic and plastinated models of different sizes were captured from dozens of angles using a digital camera or an Artec Leo Scanner. The numerous image captures of the plastinated specimens were processed in Agisoft Metashape, a stand-alone software product, that performs photogrammetric processing of digital images and generates 3D spatial data. After Agisoft Metashape exported a complex 3D mesh with a high-resolution texture, anatomy faculty added labels to the digitized 3D anatomy specimens using the Sketchfab web platform. The labeled 3D anatomy models were then uploaded into the Living Anatomy site on NYU School of Medicine's learning management system for students to explore before, during, and after their anatomy lab sessions. Quizzes using these models also were created to help students identify the structures and link them to physiology and clinical scenarios. The digitized 3D models allow students to zoom in, rotate and explore the specimens in a more interactive way, thereby enhancing the process of just observing fragile plastination models. When asked, 84% of students reported that the 3D models of plastinated specimens contributed "very much so" to their learning of anatomical relationships. We will continue to find opportunities for the meaningful integration of these 3D models within the anatomy curriculum as well as into other pre-clerkship and clerkship modules. We will also assess the educational outcomes of the 3D models and, by doing so, will incorporate instructional design into the process.
RESUMO
Peripheral T cell tolerance is promoted by the regulatory cytokine TGF-ß and Foxp3-expressing Treg cells. However, whether TGF-ß and Treg cells are part of the same regulatory module, or exist largely as distinct pathways to repress self-reactive T cells remains incompletely understood. Using a transgenic model of autoimmune diabetes, here we show that ablation of TGF-ß receptor II (TßRII) in T cells, but not Foxp3 deficiency, resulted in early-onset diabetes with complete penetrance. The rampant autoimmune disease was associated with enhanced T cell priming and elevated T cell expression of the inflammatory cytokine GM-CSF, concomitant with pancreatic infiltration of inflammatory monocytes that triggered immunopathology. Ablation of the GM-CSF receptor alleviated the monocyte response and inhibited disease development. These findings reveal that TGF-ß promotes T cell tolerance primarily via Foxp3-independent mechanisms and prevents autoimmunity in this model by repressing the cross talk between adaptive and innate immune systems.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Tolerância Periférica/imunologia , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Imunidade Adaptativa/imunologia , Animais , Autoimunidade/imunologia , Citocinas/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Imunidade Inata/imunologia , Inflamação/metabolismo , Camundongos , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Linfócitos T Reguladores/imunologiaRESUMO
Breast-fed infants have Bifidobacterium-rich gut microbiota compared to infants fed formula. Fucosylated oligosaccharides are the major components of human milk oligosaccharide (HMO) which confer various beneficial effects including prebiotic effect and protection from pathogenic infection on the host. A novel prebiotics was developed using bifidobacterial ß-galactosidase and fucose and lactose as substrates. Structure analysis revealed it as ß-D-galactopyranosyl-(1 â 3)-O-L-fucopyranose named as ß-galactosyl fucose (gal-fuc), which is different from common fucosylated HMOs with α1-2, α1-3, and α1-4 linkages. Among the four Lactobacillus strains examined, all but L. delbrueckii subsp. bilgaricus KCTC 3635 grew better on gal-fuc than on ß-GOS. Among the 11 bifidobacterial species examined, all except for B. bifium used gal-fuc as much as GOS. Moreover, the gal-fuc was noticeably better used by Bifidobacterium infantis, the major intestinal bacteria of breast fed infant. Among 15 non-probiotic bacteria, only 4 strains used gal-fuc better than ß-GOS. In conclusion, a novel gal-fuc is expected to contribute to beneficial changes of gut microbiota. Graphical abstract A novel form of ß-galactosyl fucose with an improved prebiotic effect.
Assuntos
Proteínas de Bactérias/metabolismo , Fucose/análogos & derivados , Galactose/análogos & derivados , Prebióticos , beta-Galactosidase/metabolismo , Proteínas de Bactérias/genética , Bifidobacterium/enzimologia , Biocatálise , Células CACO-2 , Fucose/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Lactose/química , beta-Galactosidase/genéticaRESUMO
Purpose: In response to the opioid epidemic and efforts to expand substance use education in medical school, the authors introduced opioid overdose prevention training (OOPT) with naloxone for all first-year medical students (MS1s) as an adjunct to required basic life support training (BLST). The authors previously demonstrated improved knowledge and preparedness following in-person OOPT with BLST; however, it remains unclear whether online-administered OOPT would produce comparable results. In this study, the authors perform a retrospective comparison of online-administered OOPT with in-person-administered OOPT. Objectives: To compare the educational outcomes: knowledge, preparedness, and attitudes, for online versus in-person OOPT. Methods: In-person OOPT was administered in 2014 and 2015 during BLST, whereas online OOPT was administered in 2016 during BLST pre-work. MS1s completed pre- and post-training tests covering 3 measures: knowledge (11-point scale), attitudes (66-point scale), and preparedness (60-point scale) to respond to an opioid overdose. Online scores from 2016 and in-person scores from 2015 were compared across all 3 measures using analysis of covariance (ANCOVA) methods. Results: After controlling for pre-test scores, there were statistical, but no meaningful, differences across all measures for in-person- and online-administered training. The estimated differences were knowledge: -0.05 (0.5%) points (95% confidence interval [CI]: -0.47, 0.36); attitudes: 0.65 (1.0%) points (95% CI: -0.22, 1.51); and preparedness: 2.16 (3.6%) points (95% CI: 1.04, 3.28). Conclusions: The educational outcomes of online-administered OOPT compared with in-person-administered OOPT were not meaningfully different. These results support the use of online-administered OOPT. As our study was retrospective, based on data collected over multiple years, further investigation is needed in a randomized controlled setting, to better understand the educational differences of in-person and online training. Further expanding OOPT to populations beyond medical students would further improve generalizability.
Assuntos
Analgésicos Opioides/intoxicação , Atitude do Pessoal de Saúde , Competência Clínica , Overdose de Drogas/prevenção & controle , Educação a Distância/métodos , Educação de Graduação em Medicina/métodos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Overdose de Drogas/tratamento farmacológico , Humanos , Estudos Retrospectivos , Estudantes de MedicinaRESUMO
The secondary cell wall polysaccharide (SCWP) is thought to be essential for vegetative growth and surface (S)-layer assembly in Bacillus anthracis; however, the genetic determinants for the assembly of its trisaccharide repeat structure are not known. Here, we report that WpaA (BAS0847) and WpaB (BAS5274) share features with membrane proteins involved in the assembly of O-antigen lipopolysaccharide in Gram-negative bacteria and propose that WpaA and WpaB contribute to the assembly of the SCWP in B. anthracis Vegetative forms of the B. anthracis wpaA mutant displayed increased lengths of cell chains, a cell separation defect that was attributed to mislocalization of the S-layer-associated murein hydrolases BslO, BslS, and BslT. The wpaB mutant was defective in vegetative replication during early logarithmic growth and formed smaller colonies. Deletion of both genes, wpaA and wpaB, did not yield viable bacilli, and when depleted of both wpaA and wpaB, B. anthracis could not maintain cell shape, support vegetative growth, or assemble SCWP. We propose that WpaA and WpaB fulfill overlapping glycosyltransferase functions of either polymerizing repeat units or transferring SCWP polymers to linkage units prior to LCP-mediated anchoring of the polysaccharide to peptidoglycan. IMPORTANCE: The secondary cell wall polysaccharide (SCWP) is essential for Bacillus anthracis growth, cell shape, and division. SCWP is comprised of trisaccharide repeats (â4)-ß-ManNAc-(1â4)-ß-GlcNAc-(1â6)-α-GlcNAc-(1â) with α-Gal and ß-Gal substitutions; however, the genetic determinants and enzymes for SCWP synthesis are not known. Here, we identify WpaA and WpaB and report that depletion of these factors affects vegetative growth, cell shape, and S-layer assembly. We hypothesize that WpaA and WpaB are involved in the assembly of SCWP prior to transfer of this polymer onto peptidoglycan.
Assuntos
Bacillus anthracis/metabolismo , Proteínas de Bactérias/metabolismo , Parede Celular/química , Regulação Bacteriana da Expressão Gênica/fisiologia , Polissacarídeos Bacterianos/metabolismo , Sequência de Aminoácidos , Bacillus anthracis/citologia , Bacillus anthracis/genética , Proteínas de Bactérias/genética , Deleção de Genes , Polissacarídeos Bacterianos/genéticaRESUMO
Bacterial endophthalmitis is a potentially blinding intraocular infection. The bacterium Bacillus cereus causes a devastating form of this disease which progresses rapidly, resulting in significant inflammation and loss of vision within a few days. The outer surface of B. cereus incites the intraocular inflammatory response, likely through interactions with innate immune receptors such as TLRs. This study analyzed the role of B. cereus pili, adhesion appendages located on the bacterial surface, in experimental endophthalmitis. To test the hypothesis that the presence of pili contributed to intraocular inflammation and virulence, we analyzed the progress of experimental endophthalmitis in mouse eyes infected with wild type B. cereus (ATCC 14579) or its isogenic pilus-deficient mutant (ΔbcpA-srtD-bcpB or ΔPil). One hundred CFU were injected into the mid-vitreous of one eye of each mouse. Infections were analyzed by quantifying intraocular bacilli and retinal function loss, and by histology from 0 to 12 h postinfection. In vitro growth and hemolytic phenotypes of the infecting strains were also compared. There was no difference in hemolytic activity (1:8 titer), motility, or in vitro growth (p > 0.05, every 2 h, 0-18 h) between wild type B. cereus and the ΔPil mutant. However, infected eyes contained greater numbers of wild type B. cereus than ΔPil during the infection course (p ≤ 0.05, 3-12 h). Eyes infected with wild type B. cereus experienced greater losses in retinal function than eyes infected with the ΔPil mutant, but the differences were not always significant. Eyes infected with ΔPil or wild type B. cereus achieved similar degrees of severe inflammation. The results indicated that the intraocular growth of pilus-deficient B. cereus may have been better controlled, leading to a trend of greater retinal function in eyes infected with the pilus-deficient strain. Although this difference was not enough to significantly alter the severity of the inflammatory response, these results suggest a potential role for pili in protecting B. cereus from clearance during the early stages of endophthalmitis, which is a newly described virulence mechanism for this organism and this infection.
Assuntos
Bacillus cereus/patogenicidade , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/microbiologia , Animais , Humor Aquoso/microbiologia , Modelos Animais de Doenças , Eletrorretinografia , Endoftalmite/diagnóstico , Infecções Oculares Bacterianas/diagnóstico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Retina/microbiologia , Retina/patologia , Retina/fisiopatologiaRESUMO
Red seabream iridovirus (RSIV), a member within genus Megalocytivirus (Iridoviridae), causes serious economic losses to marine fish aquaculture industry in East Asia. In this study, we established a Blue Striped Grunt Haemulon sciurus fin (grunt fin; GF) cell line persistently infected with RSIV (PI-GFRSIV) by subculturing GF cells that survived RSIV inoculation. PI-GFRSIV cells were morphologically indistinguishable from naive GF cells. They could stably produce RSIV at approximately 104.9 ± 0.5 genomes per microliter after 24 passages over 18 months. The optimum temperature to produce RSIV in PI-GFRSIV cells was 25°C. These cells also produced RSIV at 15, 20, and 30°C with multiple subcultures. The amount of RSIV yielded from PI-GFRSIV cells decreased gradually by multiple subculturing at 15°C or 30°C. Red seabream iridovirus was no longer detected from PI-GFRSIV cells after subcultures at these temperatures. These PI-GFRSIV cells freed from RSIV infection exhibited a level of RSIV productivity similar to those of naive GF cells after inoculation with RSIV. Therefore, we consider that these PI-GFRSIV cells were no longer infected with RSIV after multiple subculturing at 15°C or 30°C. Received October 15, 2015; accepted June 27, 2016.
Assuntos
Nadadeiras de Animais/virologia , Técnicas de Cultura de Células , Infecções por Vírus de DNA/veterinária , Doenças dos Peixes/virologia , Iridoviridae/isolamento & purificação , Perciformes , Animais , Linhagem Celular , Infecções por Vírus de DNA/virologia , TemperaturaRESUMO
UNLABELLED: D-Glutamate is an essential component of bacterial peptidoglycan and a building block of the poly-γ-D-glutamic acid (PDGA) capsule of Bacillus anthracis, the causative agent of anthrax. Earlier work suggested that two glutamate racemases, encoded by racE1 and racE2, are each essential for growth of B. anthracis, supplying D-glutamic acid for the synthesis of peptidoglycan and PDGA capsule. Earlier work could not explain, however, why two enzymes that catalyze the same reaction may be needed for bacterial growth. Here, we report that deletion of racE1 or racE2 did not prevent growth of B. anthracis Sterne (pXO1(+) pXO2(-)), the noncapsulating vaccine strain, or of B. anthracis Ames (pXO1(+) pXO2(+)), a fully virulent, capsulating isolate. While mutants with deletions in racE1 and racE2 were not viable, racE2 deletion delayed vegetative growth of B. anthracis following spore germination and caused aberrant cell shapes, phenotypes that were partially restored by exogenous D-glutamate. Deletion of racE1 or racE2 from B. anthracis Ames did not affect the production or stereochemical composition of the PDGA capsule. A model is presented whereby B. anthracis, similar to Bacillus subtilis, utilizes two functionally redundant racemase enzymes to synthesize D-glutamic acid for peptidoglycan synthesis. IMPORTANCE: Glutamate racemases, enzymes that convert L-glutamate to D-glutamate, are targeted for antibiotic development. Glutamate racemase inhibitors may be useful for the treatment of bacterial infections such as anthrax, where the causative agent, B. anthracis, requires d-glutamate for the synthesis of peptidoglycan and poly-γ-D-glutamic acid (PDGA) capsule. Here we show that B. anthracis possesses two glutamate racemase genes that can be deleted without abolishing either bacterial growth or PDGA synthesis. These data indicate that drug candidates must inhibit both glutamate racemases, RacE1 and RacE2, in order to block B. anthracis growth and achieve therapeutic efficacy.
Assuntos
Isomerases de Aminoácido/genética , Isomerases de Aminoácido/metabolismo , Bacillus anthracis/enzimologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Deleção de Sequência , Bacillus anthracis/genética , Bacillus anthracis/crescimento & desenvolvimento , Deleção de Genes , Ácido Glutâmico/metabolismo , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/metabolismoRESUMO
UNLABELLED: Bacillus anthracis vegetative forms assemble an S-layer comprised of two S-layer proteins, Sap and EA1. A hallmark of S-layer proteins are their C-terminal crystallization domains, which assemble into a crystalline lattice once these polypeptides are deposited on the bacterial surface via association between their N-terminal S-layer homology domains and the secondary cell wall polysaccharide. Here we show that slaQ, encoding a small cytoplasmic protein conserved among pathogenic bacilli elaborating S-layers, is required for the efficient secretion and assembly of Sap and EA1. S-layer protein precursors cosediment with SlaQ, and SlaQ appears to facilitate Sap assembly. Purified SlaQ polymerizes and when mixed with purified Sap promotes the in vitro formation of tubular S-layer structures. A model is discussed whereby SlaQ, in conjunction with S-layer secretion factors SecA2 and SlaP, promotes localized secretion and S-layer assembly in B. anthracis. IMPORTANCE: S-layer proteins are endowed with the propensity for self-assembly into crystalline arrays. Factors promoting S-layer protein assembly have heretofore not been reported. We identified Bacillus anthracis SlaQ, a small cytoplasmic protein that facilitates S-layer protein assembly in vivo and in vitro.
Assuntos
Bacillus anthracis/metabolismo , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Glicoproteínas de Membrana/metabolismo , Animais , Anticorpos Antibacterianos , Bacillus anthracis/genética , Proteínas de Bactérias/genética , Precipitação Química , Feminino , Proteínas Luminescentes , Glicoproteínas de Membrana/genética , Mutação , Coelhos , Proteína Vermelha FluorescenteRESUMO
A fundamental aspect of the adaptive immune system is the generation and maintenance of a diverse and self-tolerant T cell repertoire. Through its regulation of T cell development, homeostasis, tolerance, and differentiation, the highly evolutionarily conserved cytokine TGF-ß critically supports a functional T cell pool. The pleiotropic nature of this regulation is likely due to the elaborate control of TGF-ß production and activation in the immune system, and the intricacy of TGF-ß signaling pathways. In this review we discuss the current understanding of TGF-ß regulation of T cells.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Fator de Crescimento Transformador beta/imunologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Diferenciação Celular , Linhagem da Célula , Ativação Enzimática , Humanos , Ativação Linfocitária , Camundongos , Tolerância a Antígenos Próprios , Transdução de SinaisRESUMO
We have examined mechanisms underlying the formation of pathologic Th17 cells using a transgenic mouse model in which autoreactive CD4(+) T cells recognize influenza virus hemagglutinin (HA) as a ubiquitously expressed self-Ag and induce inflammatory arthritis. The lymph nodes of arthritic mice contain elevated numbers of inflammatory monocytes (iMO) with an enhanced capacity to promote CD4(+) Th17 cell differentiation, and a regional inflammatory response develops in the paw-draining lymph nodes by an IL-17-dependent mechanism. The activation of these Th17-trophic iMO precedes arthritis development and occurs in the context of an autoreactive CD4(+) Th1 cell response. Adoptive transfer of HA-specific CD4(+) T cells into nonarthritic mice expressing HA as a self-Ag similarly led to the formation of Th1 cells and of iMO that could support Th17 cell formation, and, notably, the accumulation of these iMO in the lymph nodes was blocked by IFN-γ neutralization. These studies show that autoreactive CD4(+) Th1 cells directed to a systemically distributed self-Ag can promote the development of a regional Th17 cell inflammatory response by driving the recruitment of Th17-trophic iMO to the lymph nodes.
Assuntos
Artrite Experimental/imunologia , Autoimunidade , Monócitos/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Linfócitos T CD4-Positivos/imunologia , Citocinas/imunologia , Inflamação/imunologia , Interferon gama/biossíntese , Ativação Linfocitária/imunologia , Camundongos , Camundongos Congênicos , Camundongos KnockoutRESUMO
BACKGROUND: Watching three-dimensional television (3D TV) may strain the eyes. However, other potential harmful effects of 3D TV watching have been rarely investigated. The current study examined the impact of 3D TV watching on neurophysiological responses and cognitive functioning as compared with two-dimensional TV (2D TV) watching. METHODS: A total of 72 individuals were randomly assigned to either a 3D TV watching group or a 2D TV watching group. Electroencephalography (EEG) was used to measure neurophysiological responses, and computerized neurocognitive tests were conducted immediately before and after TV watching. The Simulator Sickness Questionnaire (SSQ) was used to assess visual discomfort. RESULTS: There was a significant change in visual discomfort between the two groups (SSQ score at baseline: 2.28 ± 3.05 for the 3D TV group and 3.69 ± 3.49 for the 2D TV group; SSQ score after watching TV: 4.6 ± 3.35 for the 3D TV group and 4.03 ± 3.47 for the 2D TV group), and this change was greater for the 3D TV watching group (P = 0.025). However, 3D TV watching did not have a differential impact on EEG responses. Furthermore, there were no significant differences between the groups in terms of changes in cognitive performance, except for a subtle difference in backward digit span performance. CONCLUSION: Our findings suggest that 3D TV watching is as safe as 2D TV watching in terms of neurophysiological responses and cognitive functioning. Potential harmful effects of TV viewing might be similar regardless of whether 3D or 2D TV is viewed.
Assuntos
Cognição , Imageamento Tridimensional/psicologia , Televisão , Adulto , Idoso , Idoso de 80 Anos ou mais , Temperatura Corporal , Eletroencefalografia , Eletromiografia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Taxa Respiratória , Adulto JovemRESUMO
The Institute of Medicine identified interprofessional education (IPE) as a key innovation for achieving the triple aim of better care, better outcomes, and reduced healthcare costs. Yet, a shortage of qualified faculty and difficulty with aligning learners' schedules often prevent sustainable and scalable IPE. A virtual IPE intervention was developed to circumvent these barriers and compared to a blended-learning IPE intervention. We used a pre-test and post-test design with two comparison interventions to test the effects of these IPE interventions on changes in teamwork knowledge, skills, and attitudes. The interventions were delivered to pre-licensure learners at a large, metropolitan medical and a nursing school. We used one-sample and independent-sample t-tests to analyze data from 220 learners who received the blended-learning intervention in 2011 and 540 learners who received the virtual learning intervention in 2012. The students in the blended-learning intervention did not significantly (p < 0.05) outperform the students in the virtual learning intervention for any of the measured outcomes, except for medical students' attitudes around team value. Virtual IPE learning is an effective, scalable, and sustainable solution for imparting foundational teamwork knowledge in health profession students.
Assuntos
Instrução por Computador/métodos , Educação de Graduação em Medicina/métodos , Ocupações em Saúde/educação , Relações Interprofissionais , Estudantes de Ciências da Saúde , Interface Usuário-Computador , Humanos , Equipe de Assistência ao PacienteRESUMO
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are required to restrain the immune system from mounting an autoaggressive systemic inflammatory response, but why their activity can prevent (or allow) organ-specific autoimmunity remains poorly understood. We have examined how TCR specificity contributes to Treg activity using a mouse model of spontaneous autoimmune arthritis, in which CD4(+) T cells expressing a clonotypic TCR induce disease by an IL-17-dependent mechanism. Administration of polyclonal Tregs suppressed Th17 cell formation and prevented arthritis development; notably, Tregs expressing the clonotypic TCR did not. These clonotypic Tregs exerted Ag-specific suppression of effector CD4(+) T cells using the clonotypic TCR in vivo, but failed to mediate bystander suppression and did not prevent Th17 cells using nonclonotypic TCRs from accumulating in joint-draining lymph nodes of arthritic mice. These studies indicate that the availability of Tregs with diverse TCR specificities can be crucial to their activity in autoimmune arthritis.
Assuntos
Artrite Experimental/imunologia , Doenças Autoimunes/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Animais , Artrite Experimental/patologia , Doenças Autoimunes/patologia , Interleucina-17/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Especificidade de Órgãos/imunologia , Linfócitos T Reguladores/patologiaRESUMO
CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells are generated during thymocyte development and play a crucial role in preventing the immune system from attacking the body's cells and tissues. However, how the formation of these cells is directed by T-cell receptor (TCR) recognition of self-peptide:major histocompatibility complex (MHC) ligands remains poorly understood. We show that an agonist self-peptide with which a TCR is strongly reactive can induce a combination of thymocyte deletion and CD4(+)CD25(+)Foxp3(+) Treg cell formation in vivo. A weakly cross-reactive partial agonist self-peptide could similarly induce thymocyte deletion, but failed to induce Treg cell formation. These studies indicate that CD4(+)CD25(+)Foxp3(+) Treg cell formation can require highly stringent recognition of an agonist self-peptide by developing thymocytes. They also refine the "avidity" model of thymocyte selection by demonstrating that the quality of the signal mediated by agonist self-peptides, rather than the overall intensity of TCR signaling, can be a critical factor in directing autoreactive thymocytes to undergo CD4(+)CD25(+)Foxp3(+) Treg cell formation and/or deletion during their development.
Assuntos
Antígenos de Histocompatibilidade/imunologia , Modelos Imunológicos , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Timo/imunologia , Animais , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Reguladores/citologia , Timo/citologiaRESUMO
CD4(+)CD25(+) regulatory T (Treg) cells can play a critical role in the prevention of autoimmunity, as evidenced by the cataclysmic autoimmune disease that develops in mice and humans lacking the key transcription factor forkhead box protein 3 (Foxp3). At present, however, how and whether Treg cells participate in the development of rheumatoid arthritis (RA), which has both systemic manifestations and a joint-targeted pathology that characterizes the disease, remains unclear. In this review, we describe work that has been carried out aimed at determining the role of Treg cells in disease development in RA patients and in mouse models of inflammatory arthritis. We also describe studies in a new model of spontaneous autoimmune arthritis (TS1 x HACII mice), in which disease is caused by CD4(+) T cells recognizing a neo-self-antigen expressed by systemically distributed antigen-presenting cells. We show that TS1 x HACII mice develop arthritis despite the presence of CD4(+)CD25(+)Foxp3(+) Treg cells that recognize this target autoantigen, and we outline steps in the development of arthritis at which Treg cells might potentially act, or fail to act, in the development of inflammatory arthritis.
Assuntos
Artrite Reumatoide/imunologia , Doenças Autoimunes/imunologia , Autoimunidade , Subunidade alfa de Receptor de Interleucina-2/imunologia , Linfócitos T Reguladores/imunologia , Animais , Artrite Experimental/imunologia , Artrite Reumatoide/genética , Autoantígenos/imunologia , Doenças Autoimunes/genética , Autoimunidade/genética , Citocinas/imunologia , Fatores de Transcrição Forkhead/imunologia , Humanos , Mediadores da Inflamação/imunologia , Camundongos , Camundongos Transgênicos , Transdução de Sinais/imunologiaRESUMO
BACKGROUND: Teaching clinical pharmacology is often a challenge for medical schools. The benefits and popularity of active recall and spaced repetition through Anki flashcards are well-established and can offer a solution for teaching complex topics, but educators are often unfamiliar with this resource. APPROACH: We implemented 501 faculty-generated pharmacology flashcards in five modules across the medical preclinical curriculum, available to 104 first-year students. At the end of each module, students were surveyed on the usefulness of this novel resource. The data from the cohort who had access to flashcards was compared with the previous cohort, without access, to analyse whether student use of Anki flashcards changed students' perceptions of the pharmacology curriculum and whether there were changes in pharmacology exam performance. EVALUATION: Seventy-five percent of the respondents rated the Anki pharmacology flashcards as 'very useful' or 'somewhat useful'. Eight hundred and seventy-five responses were analysed with a natural language processing algorithm, showing that fewer students mentioned pharmacology as a difficult topic in the cardiovascular and renal modules, compared with the cohort who did not use Anki flashcards. There was not a statistically significant difference in test scores between the cohorts. IMPLICATIONS: Anki flashcards were well-received by medical students, which might have impacted their perception of the curriculum, as evidenced by the decrease in mentions of pharmacology being a difficult topic, maintaining consistency in academic performance. Educators should consider providing flashcards to offer spaced repetition opportunities in the curriculum; an additional benefit could be increasing information equality in medical schools.