Trabajadores portuarios en Dakar:Organización, legislación laboral e Instituciones (1914-1939)

Este artículo pretende analizar la evolución y actuaciones de los miembros de la comunidad portuaria en Dakar entre 1914 y 1939. En este caso, el objeto de análisis serán los miembros de la clase obrera (estibadores, obreros, amarradores, conductores) y sus relaciones con los demás miembros de la comunidad portuaria del puerto de Dakar. Además, estableceremos las condiciones de trabajo así como el tipo de oferta de trabajo y el impacto que ello tuvo sobre la actividad sindical. El marco temporal viene definido por la elección de Blaise Diagne como primer diputado senegalés en la Asamblea Nacional, los comienzos de un sindicalismo visible en la ciudad senegalesa y el final del análisis motivado por la interrupción de la acción modernizadora tras la derrota del Frente Popular en Francia

Precision medicine in pediatric inflammatory bowel disease: an omics and non-omics data-driven patient-centered translational research approach

Background: Inflammatory bowel disease (IBD) is a spectrum of multifactorial disorders characterized by dysregulated gut immune response to environmental factors in genetically predisposed individuals, leading to chronic relapsing intestinal inflammation. The contribution of genetic factors is inversely related to the age of onset, being greater in pediatric-onset IBD (PIBD), which represents 20-25% of cases. Conventional IBDs exhibit a polygenic inheritance, while monogenic IBDs are caused by rare variants. Although great progress has been made in our understanding of PIBD, translating this knowledge into personalized clinical decisions remains an unmet goal. Aim: To develop tools to stratify patients and individualize pediatric IBD care. Methods: Collection of phenotypic and genotypic data from PIBD patients, using bioinformatics tools, to 1) identify, validate, and characterize new variants of genes implicated in PIBD pathogenesis 2) establish diagnostic-therapeutic clinical pathways and biomarkers that could help to manage PIBD. Results: 1.1) 1 missense and 2 nonsense biallelic variants of CARMIL2 were identified in 3 patients presenting with PIBD who underwent whole exome sequencing and in one with autoimmune polyendocrine syndrome (APS). None manifested signs of immunodeficiency before. Immunostaining of bowel biopsies showed reduced CARMIL2 expression in the IBD patients. Western blot and immunofluorescence of transfected cells revealed an altered expression pattern of the missense variant, which was also associated with reduced NF-κB promoter activation. 2.1) 84 children with PIBD underwent sugar intestinal permeability test (SIPT) with lactulose and mannitol at diagnosis. The lactulose/mannitol ratio (LMR) was significantly higher in CD compared to UC patients. 136 SIPT were performed in 71 CD patients either at diagnosis or during follow-up. LMR positively correlated with PCDAI, CRP, ESR, calprotectin, and SES-CD and was significantly higher in patients with histologic CD activity. An increased urinary excretion of lactulose at CD diagnosis predicted the development of a stricturing phenotype. 2.2) 73 fecal FilmArray® tests from 40 PIBD patients with active disease were included. 27% were positive for enteric pathogens, the most frequent being Pathogenic E. coli, toxigenic C. difficile, and norovirus. 17 patients with bacterial pathogens or Cryptosporidium received antimicrobials. Among the symptomatic patients, 80% improved, while the others required surgery (n=2) or escalation of immunosuppressive therapy (n=1). 2.3) 12 children with IBD contracted COVID-19 during the study period (02/2020-02/2021). 11/12 were under immunomodulatory treatment. SARS-CoV-2 infection remained asymptomatic in 4/12 children and caused mild COVID-19 in the others. Mean anti-SARS-CoV-2 IgG S-RBD titer was similar between IBD patients and controls. No children experienced IBD flares. Conclusions: 1.1) Our work expands spectrum of CARMIL2 deficiency, which can present with either IBD or APS, aside from classic immunodeficiency. 2.1) Alterations of IP are highly prevalent in PIBD. SIPT is a useful tool to discriminate CD from other IBD subtypes at diagnosis, to detect luminal inflammation during follow-up, and to predict the development of a stricturing phenotype over time. 2.2) Gastrointestinal infections are common in PIBD patients with active disease. FilmArray® increases the detection of enteric pathogens, providing timely and sensitive results that might guide clinical management. 2.3) PIBD patients can mount a protective humoral response against SARS-CoV-2, comparable to that of their healthy peers regardless of immunomodulatory treatment. The course of PIBD during COVID-19 is favourable, and vice-versa. A systems biology approach aiming to integrate biological omics and non-omics datasets through bioinformatic tools could resolve IBD etiopathology and define its endotypes, establish new biomarkers, and personalize treatment.Background: Inflammatory bowel disease (IBD) is a spectrum of multifactorial disorders characterized by dysregulated gut immune response to environmental factors in genetically predisposed individuals, leading to chronic relapsing intestinal inflammation. The contribution of genetic factors is inversely related to the age of onset, being greater in pediatric-onset IBD (PIBD), which represents 20-25% of cases. Conventional IBDs exhibit a polygenic inheritance, while monogenic IBDs are caused by rare variants. Although great progress has been made in our understanding of PIBD, translating this knowledge into personalized clinical decisions remains an unmet goal. Aim: To develop tools to stratify patients and individualize pediatric IBD care. Methods: Collection of phenotypic and genotypic data from PIBD patients, using bioinformatics tools, to 1) identify, validate, and characterize new variants of genes implicated in PIBD pathogenesis 2) establish diagnostic-therapeutic clinical pathways and biomarkers that could help to manage PIBD. Results: 1.1) 1 missense and 2 nonsense biallelic variants of CARMIL2 were identified in 3 patients presenting with PIBD who underwent whole exome sequencing and in one with autoimmune polyendocrine syndrome (APS). None manifested signs of immunodeficiency before. Immunostaining of bowel biopsies showed reduced CARMIL2 expression in the IBD patients. Western blot and immunofluorescence of transfected cells revealed an altered expression pattern of the missense variant, which was also associated with reduced NF-κB promoter activation. 2.1) 84 children with PIBD underwent sugar intestinal permeability test (SIPT) with lactulose and mannitol at diagnosis. The lactulose/mannitol ratio (LMR) was significantly higher in CD compared to UC patients. 136 SIPT were performed in 71 CD patients either at diagnosis or during follow-up. LMR positively correlated with PCDAI, CRP, ESR, calprotectin, and SES-CD and was significantly higher in patients with histologic CD activity. An increased urinary excretion of lactulose at CD diagnosis predicted the development of a stricturing phenotype. 2.2) 73 fecal FilmArray® tests from 40 PIBD patients with active disease were included. 27% were positive for enteric pathogens, the most frequent being Pathogenic E. coli, toxigenic C. difficile, and norovirus. 17 patients with bacterial pathogens or Cryptosporidium received antimicrobials. Among the symptomatic patients, 80% improved, while the others required surgery (n=2) or escalation of immunosuppressive therapy (n=1). 2.3) 12 children with IBD contracted COVID-19 during the study period (02/2020-02/2021). 11/12 were under immunomodulatory treatment. SARS-CoV-2 infection remained asymptomatic in 4/12 children and caused mild COVID-19 in the others. Mean anti-SARS-CoV-2 IgG S-RBD titer was similar between IBD patients and controls. No children experienced IBD flares. Conclusions: 1.1) Our work expands spectrum of CARMIL2 deficiency, which can present with either IBD or APS, aside from classic immunodeficiency. 2.1) Alterations of IP are highly prevalent in PIBD. SIPT is a useful tool to discriminate CD from other IBD subtypes at diagnosis, to detect luminal inflammation during follow-up, and to predict the development of a stricturing phenotype over time. 2.2) Gastrointestinal infections are common in PIBD patients with active disease. FilmArray® increases the detection of enteric pathogens, providing timely and sensitive results that might guide clinical management. 2.3) PIBD patients can mount a protective humoral response against SARS-CoV-2, comparable to that of their healthy peers regardless of immunomodulatory treatment. The course of PIBD during COVID-19 is favourable, and vice-versa. A systems biology approach aiming to integrate biological omics and non-omics datasets through bioinformatic tools could resolve IBD etiopathology and define its endotypes, establish new biomarkers, and personalize treatment