Studies on Germinal Center Biology

The germinal center reaction is at the heart of the humoral immune response; it comprises one major arm of the immune system, with the other arm being the cellular response. It is the site where B cells undergo somatic hyper-mutation, class switching, affinity maturation, and selection. The precise molecular regulation of germinal center development remains largely unknown. We isolated B cells from the mesenteric lymph node germinal center of a C57BL/6 mice and assessed their gene regulation programs by using ATAC-seq, a method for mapping open chromatin region, and RNA-seq, to determine global gene expression profiles with the aim of revealing new insights into the formation and maturation of germinal centers. We are also interested in the role of the germinal center in autoimmunity; using MRL/MpJ mice as a model, we found that there is an increase in 9-O-acetylation of sialic acid in MRL/MpJ germinal center B cells compared to C57BL/6 and BALB/c mice. MRL/MpJ mouse B-cells also show defect in BCR induced apoptosis. Ganglioside GD3 is a membranebound glycosphingolipid containing sialic acid, known to have a role in apoptosis induction by targeting the mitochondria. Interestingly, the pro-apoptotic effects of GD3 can be counteracted by 9-O-acetylation of the terminal sialic acid residue, giving 9-O-acetyl-GD3. We hypothesize that 9-O-acetylation of GD3 disrupts the apoptotic process of auto-reactive B cells in the germinal center, which ultimately results in autoimmunity

The Mst1 Kinase Is Required for Follicular B Cell Homing and B-1 B Cell Development

The Mst1 and 2 cytosolic serine/threonine protein kinases are the mammalian orthologs of the Drosophila Hippo protein. Mst1 has been shown previously to participate in T-cell and B-cell trafficking and the migration of lymphocytes into secondary lymphoid organs in a cell intrinsic manner. We show here that the absence of Mst1 alone only modestly impacts B cell homing to lymph nodes. The absence of both Mst1 and 2 in hematopoietic cells results in relatively normal B cell development in the bone marrow and does not impact migration of immature B cells to the spleen. However, follicular B cells lacking both Mst1 and Mst2 mature in the splenic white pulp but are unable to recirculate to lymph nodes or to the bone marrow. These cells also cannot traffic efficiently to the splenic red pulp. The inability of late transitional and follicular B cells lacking Mst 1 and 2 to migrate to the red pulp explains their failure to differentiate into marginal zone B cell precursors and marginal zone B cells. Mst1 and Mst2 are therefore required for follicular B cells to acquire the ability to recirculate and also to migrate to the splenic red pulp in order to generate marginal zone B cells. In addition B-1 a B cell development is defective in the absence of Mst1

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Aprendizagem assistida por pares: percepção e satisfação dos estudantes de licenciatura em medicina

Introduction: Peer-assisted learning (PAL) is a teaching method that develops new knowledge and skills through active learning support from peers. Objectives: To assess the impact of PAL in medical education, by collecting quantitative data that explore its effectiveness. To evaluate students’ perception of and satisfaction with PAL. Methods: A 5-point Likert scale survey was developed for students participating in the PAL program either as tutors or learners. Data were compared and statistically analyzed according to gender, GPA, and year of study. Moreover, follow up of peer tutors and peer learner’s achievement was done through comparing their grades with those that not shared in PAL and with their GPA of previous year. Results: Statistical analysis of questionnaire data revealed that medical students regarded voluntary peer-teaching similarly to faculty teaching and have a generally positive perception of PAL. Most of the respondents reported that they benefited both professionally and personally from PAL activities. They recommended expanding the role of PAL and officially incorporating PAL sessions into the curriculum. Students’ achievement was significantly increased for those who acted as peer learners and peer tutors. Conclusions: Using PAL in conjunction with other teaching and learning methods provides additional value by fostering cooperation and social interaction among medical students and further prepares them for their future role as medical science educators. Additional research into the impact of PAL on academic achievement, both short- and long-term learning outcomes, in medical programs is warranted.Introdução: A Aprendizagem Assistida por Pares (AAP) é um método de ensino que desenvolve novos conhecimentos e competências através do apoio ativo à aprendizagem por pares. Objetivos: Avaliar o impacto do AAP na educação médica, recolhendo dados quantitativos que exploram a sua eficácia. Avaliar a perceção e a satisfação dos estudantes com AAP. Métodos: Foi desenvolvido um inquérito à escala Likert de 5 pontos para estudantes participantes no programa AAP, quer como tutores, quer como alunos. Os dados foram comparados e analisados estatisticamente de acordo com o género, GPA, e ano de estudo. Além disso, o acompanhamento dos tutores e dos alunos foi feito através da comparação das suas notas com as que não foram partilhadas no AAP e com o seu GPA do ano anterior. Resultados: A análise estatística dos dados do questionário revelou que os estudantes de medicina consideraram o ensino voluntário por pares semelhante ao ensino docente e têm uma perceção geralmente positiva do AAP. A maioria dos inquiridos relatou ter beneficiado tanto profissionalmente como pessoalmente das atividades de AAP. Recomendaram a expansão do papel do AAP e a incorporação oficial das sessões AAP no currículo. A realização dos estudantes foi significativamente aumentada para aqueles que atuaram como alunos e tutores de pares. Conclusões: A utilização do AAP em conjunto com outros métodos de ensino e aprendizagem proporciona um valor adicional ao promover a cooperação e interação social entre estudantes de medicina e prepara-os ainda mais para o seu futuro papel como educadores de ciências médicas. É necessária investigação adicional sobre o impacto do AAP nos resultados académicos, tanto a curto como a longo prazo, em programas médicos.Introducción: El aprendizaje asistido por pares (AAP) es un método de enseñanza que desarrolla nuevos conocimientos y habilidades a través del apoyo activo del aprendizaje por parte de los compañeros. Objetivos: Evaluar el impacto del AAP en la educación médica, mediante la recopilación de datos cuantitativos que exploran su eficacia. Evaluar la percepción y la satisfacción de los estudiantes con el AAP. Métodos: Se elaboró una encuesta con una escala de Likert de 5 puntos para los estudiantes que participaban en el programa AAP como tutores o como alumnos. Los datos se compararon y analizaron estadísticamente en función del género, el promedio académico y el año de estudio. Además, se realizó un seguimiento del rendimiento de los compañeros tutores y de los compañeros alumnos mediante la comparación de sus notas con las de los que no compartían el AAP y con su GPA del año anterior. Resultados: El análisis estadístico de los datos del cuestionario reveló que los estudiantes de medicina consideraban la enseñanza voluntaria entre pares de forma similar a la enseñanza en la facultad y tienen una percepción generalmente positiva de la AAP. La mayoría de los encuestados afirmaron haberse beneficiado tanto profesional como personalmente de las actividades de AAP. Recomendaron ampliar el papel de la AAP e incorporar oficialmente las sesiones de AAP en el plan de estudios. El rendimiento de los estudiantes aumentó significativamente en el caso de los que actuaron como alumnos y tutores de sus compañeros. Conclusiones: El uso de AAP junto con otros métodos de enseñanza y aprendizaje proporciona un valor adicional al fomentar la cooperación y la interacción social entre los estudiantes de medicina y los prepara aún más para su futuro papel como educadores de ciencias médicas. Se justifica la realización de más investigaciones sobre el impacto de la AAP en el rendimiento académico, tanto a corto como a largo plazo, en los programas de medicina

DOCK2 Sets the Threshold for Entry into the Virtual Memory CD8 + T Cell Compartment by Negatively Regulating Tonic TCR Triggering

Copyright © 2019 by The American Association of Immunologists, Inc. The control of cytoskeletal dynamics by dedicator of cytokinesis 2 (DOCK2), a hematopoietic cell-specific actin effector protein, has been implicated in TCR signaling and T cell migration. Biallelic mutations in Dock2 have been identified in patients with a recessive form of combined immunodeficiency with defects in T, B, and NK cell activation. Surprisingly, we show in this study that certain immune functions of CD8+ T cells are enhanced in the absence of DOCK2. Dock2-deficient mice have a pronounced expansion of their memory T cell compartment. Bone marrow chimera and adoptive transfer studies indicate that these memory T cells develop in a cell-intrinsic manner following thymic egress. Transcriptional profiling, TCR repertoire analyses, and cell surface marker expression indicate that Dock2-deficient naive CD8+ T cells directly convert into virtual memory cells without clonal effector T cell expansion. This direct conversion to memory is associated with a selective increase in TCR sensitivity to self-peptide MHC in vivo and an enhanced response to weak agonist peptides ex vivo. In contrast, the response to strong agonist peptides remains unaltered in Dock2-deficient T cells. Collectively, these findings suggest that the regulation of the actin dynamics by DOCK2 enhances the threshold for entry into the virtual memory compartment by negatively regulating tonic TCR triggering in response to weak agonists

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study (vol 46, pg 2021, 2022)

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Correction: Evolving Trends in the Management of Acute Appendicitis During COVID-19 Waves: The ACIE Appy II Study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Evolving Trends in the Management of Acute Appendicitis During COVID-19 Waves: The ACIE Appy II Study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide