CÁNCER DE COLON Y EMBARAZO: REPORTE DE CASO Y REVISIÓN DE LA LITERATURA

El cáncer colorrectal asociado al embarazo es una patología extremadamente infrecuente. Se presenta el caso de una paciente de 38 años con antecedentes familiares de cáncer de colon, cursando un embarazo de 35 semanas en la que se diagnosticó un cáncer de colon derecho. Se efectúa una revisión de la literatura en relación al diagnóstico y manejo de esta rara entida

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

Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association

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 CD21(low) 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-beta 1, 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-beta 1 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.Transplantation and immunomodulatio

Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association

Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study

Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age ≥0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0·7% (95% UI 0·7–0·9), corresponding to 56·8 million (95% UI 55·2–67·8) infections, on Jan 1, 2020. This number represents a decrease of 6·8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63·6 million (61·8–75·8) infections (0·9% [0·8–1·0] prevalence). By the end of 2020, an estimated 12·9 million (12·5–15·4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641000 (623000–765000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56·8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination

A global metagenomic map of urban microbiomes and antimicrobial resistance

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.Funding: the Tri-I Program in Computational Biology and Medicine (CBM) funded by NIH grant 1T32GM083937; GitHub; Philip Blood and the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant number ACI-1548562 and NSF award number ACI-1445606; NASA (NNX14AH50G, NNX17AB26G), the NIH (R01AI151059, R25EB020393, R21AI129851, R35GM138152, U01DA053941); STARR Foundation (I13- 0052); LLS (MCL7001-18, LLS 9238-16, LLS-MCL7001-18); the NSF (1840275); the Bill and Melinda Gates Foundation (OPP1151054); the Alfred P. Sloan Foundation (G-2015-13964); Swiss National Science Foundation grant number 407540_167331; NIH award number UL1TR000457; the US Department of Energy Joint Genome Institute under contract number DE-AC02-05CH11231; the National Energy Research Scientific Computing Center, supported by the Office of Science of the US Department of Energy; Stockholm Health Authority grant SLL 20160933; the Institut Pasteur Korea; an NRF Korea grant (NRF-2014K1A4A7A01074645, 2017M3A9G6068246); the CONICYT Fondecyt Iniciación grants 11140666 and 11160905; Keio University Funds for Individual Research; funds from the Yamagata prefectural government and the city of Tsuruoka; JSPS KAKENHI grant number 20K10436; the bilateral AT-UA collaboration fund (WTZ:UA 02/2019; Ministry of Education and Science of Ukraine, UA:M/84-2019, M/126-2020); Kyiv Academic Univeristy; Ministry of Education and Science of Ukraine project numbers 0118U100290 and 0120U101734; Centro de Excelencia Severo Ochoa 2013–2017; the CERCA Programme / Generalitat de Catalunya; the CRG-Novartis-Africa mobility program 2016; research funds from National Cheng Kung University and the Ministry of Science and Technology; Taiwan (MOST grant number 106-2321-B-006-016); we thank all the volunteers who made sampling NYC possible, Minciencias (project no. 639677758300), CNPq (EDN - 309973/2015-5), the Open Research Fund of Key Laboratory of Advanced Theory and Application in Statistics and Data Science – MOE, ECNU, the Research Grants Council of Hong Kong through project 11215017, National Key RD Project of China (2018YFE0201603), and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01) (L.S.