Lectura de contexto y abordaje psicosocial desde los enfoques narrativos. Dosquebradas, Florencia, Ibagué, Valledupar, Bogotá José Acevedo y Gómez

De la siguiente tesis podemos analizar que todo hecho de violencia trae consigo más violencia como lo vemos plasmado en nuestro territorio nacional donde lo hechos de violencia están presentes constantemente, llevando a una falta constante de los derechos humanos. Dejando atrás personas desplazadas, mutiladas o incluso creando traumas en la psiquis de las personas víctimas de este flagelo. Es aquí donde el estado juega un papel importante en el sentido patriarcal, con decir patriarcal debemos tomarlos en el sentido de protección, por lo que vemos el estado a través de los entes gubernamentales las diferentes medidas que toman por lo que vemos programas de beneficio o ayuda orientado ayudar a estas personas todo esto en el nombre de la reparación económica, pero no de la reparación subjetiva. Entonces es aquí donde el papel del profesional en el alma humana, toma gran relevancia en su noble labor, donde la única herramienta que tiene para su trabajo será la palabra del sujeto.From the following thesis we can analyze that every act of violence brings with it more violence as we see it reflected in our national territory where acts of violence are constantly present, leading to a constant lack of human rights. Leaving behind people displaced, mutilated or even creating traumas in the psyche of the victims of this scourge. It is here where the state plays an important role in the patriarchal sense, with patriarchal say we must take them in the sense of protection, so we see the state through the government agencies the different measures taken by what we see benefit programs or Help oriented help these people all this in the name of economic reparation, but not of subjective reparation. Then it is here where the role of the professional in the human soul, takes great relevance in his noble work, where the only tool he has for his work will be the word of the subject

Inmunodeficiencia común variable: caracterización clínica e inmunológica de pacientes e identificación de subgrupos homogéneos con base en la tipificación de subpoblaciones de linfocitos B

Introduction: Common variable immunodeficiency is a heterogeneous syndrome characterized by recurrent infections, hypogammaglobulinemia and defective production of specific antibodies. Abnormalities in peripheral blood lymphocyte subpopulations, in particular of B lymphocytes, allow the classification of patients into homogeneous groups.Objective: To perform a clinical and immunological characterization and to evaluate lymphocyte subpopulations of twelve Colombian patients with common variable immunodeficiency in order to define homogeneous groups.Materials and methods: We reviewed medical records and evaluated serum immunoglobulins (Ig), lymphoproliferation, delayed hypersensitivity and used flow cytometry to quantify peripheral blood total lymphocyte and B cell populations.Results: All patients had recurrent respiratory and/or gastrointestinal infections, while some also had infections affecting other systems. All patients had abnormally low serum IgG levels, while IgA and IgM levels were reduced in nine and ten patients, respectively. Lymphoproliferation to mitogen was lower in patients than in healthy controls but lymphoproliferation to specific antigen was normal in all. Flow cytometry revealed high numbers of T cells in three patients, while seven had a low CD4+/CD8+ ratio and four had reduced NK cells. Eleven patients had normal B cell counts, and eight of them also showed decreased memory B lymphocytes, and four had increased transitional or CD21low B lymphocytes.Conclusion: Lymphocyte typing allowed assigning all but one patient to homogeneous groups according to international classification schemes, indicating the necessity of including more criteria until an ideal classification is achieved. This study will lead to a better medical monitoring of common variable immunodeficiency patients in groups at high risk of developing clinical complications.Introducción. La inmunodeficiencia común variable es un síndrome heterogéneo caracterizado por infecciones recurrentes, hipogammaglobulinemia y producción deficiente de anticuerpos específicos. Las anormalidades en subpoblaciones de linfocitos en sangre periférica, particularmente de linfocitos B, permiten la clasificación de los pacientes en grupos homogéneos.Objetivo. Caracterizar clínica e inmunológicamente los linfocitos B y tipificar sus subpoblaciones en doce pacientes colombianos con inmunodeficiencia común variable, para clasificarlos en grupos homogéneos.Materiales y métodos. Se revisaron las historias clínicas de los pacientes y se evaluaron las inmunoglobulinas séricas, la proliferación de linfocitos y la hipersensibilidad retardada, así como las subpoblaciones de linfocitos y de linfocitos B mediante citometría de flujo.Resultados. Todos los pacientes presentaron infecciones respiratorias o gastrointestinales recurrentes y, algunos, infecciones en otros sistemas. Además, todos presentaban disminución de la IgG, en tanto que la IgA y la IgM fueron bajas en nueve y diez pacientes, respectivamente. En todos hubo disminución de la proliferación de linfocitos inducida por mitógenos, pero fue normal frente a antígenos específicos. La tipificación de subpoblaciones reveló valores elevados de linfocitos T en tres pacientes; siete presentaron disminución en la relación CD4+/CD8+ y, cuatro, linfocitos NK bajos. El conteo de linfocitos B fue normal en once pacientes, ocho de los cuales presentaron linfocitos B de memoria bajos, en tanto que cuatro presentaron aumento de linfocitos B de transición o de linfocitos B CD21low.Conclusión. La tipificación de subpoblaciones de linfocitos solo permitió asignar a 11 de los pacientes a grupos homogéneos según los esquemas de clasificación internacionales, lo que indica la necesidad de agregar más criterios hasta lograr una clasificación ideal. Este estudio permitirá establecer mejores seguimientos médicos para pacientes con inmunodeficiencia común variable en grupos con alto riesgo de desarrollar complicaciones clínicas

Defective formation of IgA memory B cells, Th1 and Th17 cells in symptomatic patients with selective IgA deficiency

Objective: Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency in Western countries. Patients can suffer from recurrent infections and autoimmune diseases because of a largely unknown aetiology. To increase insights into the pathophysiology of the disease, we studied memory B and T cells and cytokine concentrations in peripheral blood. Methods: We analysed 30 sIgAD patients (12 children, 18 adults) through detailed phenotyping of peripheral B-cell, CD8+ T-cell and CD4+ T-cell subsets, sequence analysis of IGA and IGG transcripts, in vitro B-cell activation and blood cytokine measurements. Results: All patients had significantly decreased numbers of T-cell-dependent (TD; CD27+) and T-cell-independent (TI; CD27−) IgA memory B cells and increased CD21low B-cell numbers. IgM+IgD− memory B cells were decreased in children and normal in adult patients. IGA and IGG transcripts contained normal SHM levels. In sIgAD children, IGA transcripts more frequently used IGA2 than controls (58.5% vs. 25.1%), but not in adult patients. B-cell activation after in vitro stimulation was normal. However, adult sIgAD patients exhibited increased blood levels of TGF-β1, BAFF and APRIL, whereas they had decreased Th1 and Th17 cell numbers. Conclusion: Impaired IgA memory formation in sIgAD patients is not due to a B-cell activation defect. Instead, decreased Th1 and Th17 cell numbers and high blood levels of BAFF, APRIL and TGF-β1 might reflect disturbed regulation of IgA responses in vivo. These insights into B-cell extrinsic immune defects suggest the need for a broader immunological focus on genomics and functional analyses to unravel the pathogenesis of sIgAD

Genome-wide detection of human intronic AG-gain variants located between splicing branchpoints and canonical splice acceptor sites

Human genetic variants that introduce an AG into the intronic region between the branchpoint (BP) and the canonical splice acceptor site (ACC) of protein-coding genes can disrupt pre-mRNA splicing. Using our genome-wide BP database, we delineated the BP-ACC segments of all human introns and found extreme depletion of AG/YAG in the [BP+8, ACC-4] high-risk region. We developed AGAIN as a genome-wide computational approach to systematically and precisely pinpoint intronic AG-gain variants within the BP-ACC regions. AGAIN identified 350 AG-gain variants from the Human Gene Mutation Database, all of which alter splicing and cause disease. Among them, 74% created new acceptor sites, whereas 31% resulted in complete exon skipping. AGAIN also predicts the protein-level products resulting from these two consequences. We performed AGAIN on our exome/genomes database of patients with severe infectious diseases but without known genetic etiology and identified a private homozygous intronic AG-gain variant in the antimycobacterial gene SPPL2A in a patient with mycobacterial disease. AGAIN also predicts a retention of six intronic nucleotides that encode an in-frame stop codon, turning AG-gain into stop-gain. This allele was then confirmed experimentally to lead to loss of function by disrupting splicing. We further showed that AG-gain variants inside the high-risk region led to misspliced products, while those outside the region did not, by two case studies in genes STAT1 and IRF7. We finally evaluated AGAIN on our 14 paired exome-RNAseq samples and found that 82% of AG-gain variants in high-risk regions showed evidence of missplicing

Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria.

Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with mycobacterial disease from kindreds of different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete deficiency of this translation re-initiation factor impairs the translation of a subset of proteins, including the kinase JAK2 in all cell types tested, including T lymphocytes and phagocytes. JAK2 expression is sufficiently low to impair cellular responses to interleukin-23 (IL-23) and partially IL-12, but not other JAK2-dependent cytokines. Defective responses to IL-23 preferentially impair the production of IFN-γ by innate-like adaptive mucosal-associated invariant T cells (MAIT) and γδ T lymphocytes upon mycobacterial challenge. Surprisingly, the lack of MCTS1-dependent translation re-initiation and ribosome recycling seems to be otherwise physiologically redundant in these patients. These findings suggest that X-linked recessive human MCTS1 deficiency underlies isolated mycobacterial disease by impairing JAK2 translation in innate-like adaptive T lymphocytes, thereby impairing the IL-23-dependent induction of IFN-γ

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population