Fine-scale predictions of distributions of Chagas disease vectors in the state of Guanajuato, Mexico

One of the most daunting challenges for Chagas disease surveillance and control in Mexico is the lack of community level data on vector distributions. Although many states now have assembled representative domestic triatomine collections, only two triatomine specimens had been collected and reported previously from the state of Guanajuato. Field personnel from the stateÕs Secretarõ´a de Salud conducted health promotion activities in 43 of the 46 counties in the state and received donations of a total of 2,522 triatomine specimens between 1998 and 2002. All specimens were identiÞed, and live insects examined for Trypanosoma cruzi. In an effort to develop Þne-scale distributional data for Guanajuato, collection localities were georeferenced and ecological niches were modeled for each species by using evolutionary-computing approaches. Five species were collected: Triatoma mexicana (Herrich-Schaeffer), Triatoma longipennis (Usinger), Triatoma pallidipennis (Stål), Triatoma barberi (Usinger), and Triatoma dimidiata (Latreille) from 201 communities located at elevations of 870Ð2,200 m. Based on collection success, T. mexicana had the broadest dispersion, although niche mapping indicates that T. barberi represents the greatest risk for transmission of Chagas disease in the state. T. dimidiata was represented in collections by a single adult collected from one village outside the predicted area for all species. For humans, an estimated 3,755,380 individuals are at risk for vector transmission in the state, with an incidence of 3,500 new cases per year; overall seroprevalences of 2.6% indicate that 97,640 individuals are infected with T. cruzi at present, including 29,300 chronic cases

Clinical, biological, and prognostic implications of SF3B1 co-occurrence mutations in very low/low- and intermediate-risk MDS patients

SF3B1 is a highly mutated gene in myelodysplastic syndrome (MDS) patients, related to a specific subtype and parameters of good prognosis in MDS without excess blasts. More than 40% of MDS patients carry at least two myeloid-related gene mutations but little is known about the impact of concurrent mutations on the outcome of MDS patients. In applying next-generation sequencing (NGS) with a 117 myeloid gene custom panel, we analyzed the co-occurrence of SF3B1 with other mutations to reveal their clinical, biological, and prognostic implications in very low/low- and intermediate-risk MDS patients. Mutations in addition to those of SF3B1 were present in 80.4% of patients (median of 2 additional mutations/patient, range 0–5). The most frequently mutated genes were as follows: TET2 (39.2%), DNMT3A (25.5%), SRSF2 (10.8%), CDH23 (5.9%), and ASXL1, CUX1, and KMT2D (4.9% each). The presence of at least two mutations concomitant with that of SF3B1 had an adverse impact on survival compared with those with the SF3B1 mutation and fewer than two additional mutations (median of 54 vs. 87 months, respectively: p = 0.007). The co-occurrence of SF3B1 mutations with specific genes is also linked to a dismal prognosis: SRSF2 mutations were associated with shorter overall survival (OS) than SRSF2wt (median, 27 vs. 75 months, respectively; p = 0.001), concomitant IDH2 mutations (median OS, 11 [mut] vs. 75 [wt] months; p = 0.001), BCOR mutations (median OS, 11 [mut] vs. 71 [wt] months; p = 0.036), and NUP98 and STAG2 mutations (median OS, 27 and 11 vs. 71 months, respectively; p = 0.008 and p = 0.002). Mutations in CHIP genes (TET2, DNMT3A) did not significantly affect the clinical features or outcome. Our results suggest that a more comprehensive NGS study in low-risk MDS SF3B1mut patients is essential for a better prognostic evaluation.This work was supported by grants from the following: Contrato Rio Hortega, CM17/00171; Gerencia Regional de Salud (Castilla y León) para proyectos de investigación año 2018, 1850/A/18; Spanish Fondo de Investigaciones Sanitarias, PI15/01471, PI18/01500; Instituto de Salud Carlos III (ISCIII); European Regional Development Fund (ERDF) “Una manera de hacer Europa”; Consejería de Educación, Junta de Castilla y León (SA271P18); Proyectos de Investigación del SACYL, Spain, GRS1847/A/18, GRS1653/A17; SYNtherapy, Synthetic Lethality for Personalized Therapy-based Stratification In Acute Leukemia (ERAPERMED2018–275); ISCIII (AC18/00093), co-funded by ERDF/ESF, “Investing in your future”, by grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC) (RD12/0036/0069) and Centro de Investigación Biomédica en Red de Cáncer (CIBERONC CB16/12/00233). JMHS is supported by a research grant from Fundación Española de Hematología y Hemoterapia. MM is currently supported by an Ayuda predoctoral de la Junta de Castilla y León from the Fondo Social Europeo (JCYL- EDU/556/2019 PhD scholarship)

Apolipoprotein L genes are novel mediators of inflammation in beta cells

Aims/hypothesisInflammation induces beta cell dysfunction and demise but underlying molecular mechanisms remain unclear. The apolipoprotein L (APOL) family of genes has been associated with innate immunity and apoptosis in non-pancreatic cell types, but also with metabolic syndrome and type 2 diabetes mellitus. Here, we hypothesised that APOL genes play a role in inflammation-induced beta cell damage.MethodsWe used single-cell transcriptomics datasets of primary human pancreatic islet cells to study the expression of APOL genes upon specific stress conditions. Validation of the findings was carried out in EndoC-βH1 cells and primary human islets. Finally, we performed loss- and gain-of-function experiments to investigate the role of APOL genes in beta cells.ResultsAPOL genes are expressed in primary human beta cells and APOL1, 2 and 6 are strongly upregulated upon inflammation via the Janus kinase (JAK)−signal transducer and activator of transcription (STAT) pathway. APOL1 overexpression increases endoplasmic reticulum stress while APOL1 knockdown prevents cytokine-induced beta cell death and interferon-associated response. Furthermore, we found that APOL genes are upregulated in beta cells from donors with type 2 diabetes compared with donors without diabetes mellitus.Conclusions/interpretationAPOLs are novel regulators of islet inflammation and may contribute to beta cell damage during the development of diabetes.Therapeutic cell differentiatio

In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19

Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively.Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19.Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs, obtaining several approved drugs, compounds under investigation, and experimental compounds with the highest area under the receiver operating characteristics.Conclusion: After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Retos para la integración social de los pobres en América Latina

En América Latina continúan en marcha procesos económicos, políticos y culturales que reproducen o incrementan la pobreza, la desigualdad y la exclusión social. Sin embargo, en el ámbito de las políticas sociales, la mayoría de los gobiernos de la región mantienen un enfoque minimalista. Cada vez es más evidente que la ecuación liberalización de la economía + crecimiento económico promovido exclusivamente por actores privados + políticas sociales fundamentalmente residuales no sólo no han disminuido significativamente los rezagos sociales heredados del pasado, sino que ha generado nuevas formas de pobreza, desigualdad, descalificación y exclusión. A pesar de ello, la intención de este libro no es documentar la crisis del paradigma de bienestar residual que ahora es hegemónico, ni realizar un recuento de daños. Intentamos contribuir a trascender la fragmentación de la discusión académica reinante, dedicada frecuentemente a impugnar índices de pobreza, a mostrar dinámicas sectoriales o a levantar la bandera por nuevos programas sociales diseñados para paliar situaciones de emergencia. El Grupo Pobreza y Políticas Sociales de CLACSO propone en esta obra algunos enfoques conceptuales más integrales, interdisciplinarios y comparativos, que ponen en el centro de la agenda académica la superación de la pobreza y la integración socioeconómica. Los temas centrales abordados aquí son: la dinámica del cambio de paradigmas, regímenes de bienestar y políticas sociales en la región; la interacción entre procesos de estabilización, ajuste, integración regional y pobreza; y algunos aspectos puntuales de la política social urbana, la vivienda y la pobreza en tres países de la región.Reconocimientos | 13 Introducción Carlos Barba Solano | 15 Parte I Paradigmas, regímenes de bienestar y políticas sociales en transición Anete Brito Leal Ivo La agudización del conflicto distributivo en la base: el nuevo tratamiento de la política social focalizada | 27 Carlos Barba Solano Reforma social y ciudadanía social en América Latina durante los años noventa: una perspectiva comparada | 51 Carmen Midaglia Entre la tradición, la modernización ingenua y los intentos de refundar la casa: la reforma social en el Uruguay de las últimas tres décadas | 85 Enrique Valencia Crecimiento, política social y pobreza en Corea del Sur y México | 109 Laura Golbert Los olvidados de la política social | 155 Parte II Procesos de ajuste e integración y pobreza Alicia Puyana y José Romero El sector agropecuario mexicano bajo el Tratado de Libre Comercio de América del Norte. La pobreza y la desigualdad se intensifican, crece la migración | 187 Carlos Larrea Crisis, dolarización y pobreza en el Ecuador | 215 Parte III Política social urbana, vivienda y pobreza Alicia Ziccardi Políticas de inclusión social de la Ciudad de México | 237 Carlos Fidel, Cristina Farías y Raúl Di Tomaso Rasgos de las insuficiencias urbanas y habitacionales en el partido de Quilmes, Argentina | 259 María Elena Ducci La política habitacional como instrumento de desintegración social. Efectos de una política de vivienda exitosa | 293 Vania Salles y María de la Paz López Viviendas pobres en México: un estudio desde la óptica de género | 311 Parte IV Enfoques sobre pobreza rural Salomón Nahmad, Tania Carrasco y Elena Nava Elementos para la construcción de una tipología de la pobreza rural en México | 351 Gustavo Verduzco Igartúa Trayectorias laborales del proletariado rural: estudio de caso en una zona del centro de México | 37