Miradas colectivas del departamento de Cundinamarca, ciudad de Bogotá, departamento de Santander, municipio Piedecuesta y departamento de Atlántico, ciudad Barranquilla

En el presente trabajo se aborda la familia como eje central del desarrollo humano, debido a su influencia en la construcción social, analizando las causas y efectos sobre el desarrollo individual y colectivo de los integrantes de las familias pertenecientes a diferentes comunidades en los departamentos de Cundinamarca, Santander y Atlántico. Se pretende, por medio de las propuestas de acompañamiento, establecer estrategias que promuevan y faciliten la adecuada conceptualización de la familia como sistema y su incidencia en el desarrollo humano, así como fortalecer y empoderar a las familias, resaltando su importancia en los procesos sociales, contemplando la labor de los progenitores más allá del suministro de recursos, entendiendo a la familia desde la perspectiva moderna así como los cambios sociales, políticos, económicos y tecnológicos, que han ocasionado cambios en la interacción familiar y su estructura.In the present work the family is addressed as the central axis of human development, due to its influence on social construction, analyzing the causes and effects on the individual and collective development of the members of families belonging to different communities in the departments of Cundinamarca, Santander and Atlantico. It is intended, through the accompanying proposals, to establish strategies that promote and facilitate the adequate conceptualization of the family as a system and its impact on human development, as well as strengthening and empowering families, highlighting their importance in social processes and contemplating the work of parents beyond the provision of resources. Also understanding the family from the modern perspective: social, political, economic and technological changes have also change family interactions and its structure

ICOS costimulation at the tumor site in combination with CTLA-4 blockade therapy elicits strong tumor immunity

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) blockade therapy is able to induce long-lasting antitumor responses in a fraction of cancer patients. Nonetheless, there is still room for improvement in the quest for new therapeutic combinations. ICOS costimulation has been underscored as a possible target to include with CTLA-4 blocking treatment. Herein, we describe an ICOS agonistic aptamer that potentiates T cell activation and induces stronger antitumor responses when locally injected at the tumor site in combination with anti-CTLA-4 antibody in different tumor models. Furthermore, ICOS agonistic aptamer was engineered as a bi-specific tumor-targeting aptamer to reach any disseminated tumor lesions after systemic injection. Treatment with the bi-specific aptamer in combination with CTLA-4 blockade showed strong antitumor immunity, even in a melanoma tumor model where CTLA-4 treatment alone did not display any significant therapeutic benefit. Thus, this work provides strong support for the development of combinatorial therapies involving anti-CTLA-4 blockade and ICOS agonist tumor-targeting agents

Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma

Objective: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterise the role of tumour-initiating cells (T-ICs) and signalling pathways involved in sorafenib resistance. Design: HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: (1) role of T-ICs by in vitro sphere formation and in vivo tumourigenesis assays using NOD/SCID mice, (2) activation of alternative signalling pathways and (3) efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, quantitative real-time PCR (qRT-PCR)) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in two independent cohorts. Results: Sorafenib-acquired resistant tumours showed significant enrichment of T-ICs (164 cells needed to create a tumour) versus sorafenib-sensitive tumours (13 400 cells) and non-treated tumours (1292 cells), p<0.001. Tumours with sorafenib-acquired resistance were enriched with insulin-like growth factor (IGF) and fibroblast growth factor (FGF) signalling cascades (false discovery rate (FDR)<0.05). In vitro, cells derived from sorafenib-acquired resistant tumours and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumour growth and improved survival in sorafenib-resistant tumours. A sorafenib-resistance 175 gene signature was characterised by enrichment of progenitor cell features, aggressive tumorous traits and predicted poor survival in two cohorts (n=442 patients with HCC). Conclusion: Acquired resistance to sorafenib is driven by T-ICs with enrichment of progenitor markers and activation of IGF and FGF signalling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1(3 release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1(3 release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers

Meat and bone meal as a partial replacement for fish meal in diets for gilthead seabream (Spares aurata): growth, feed efficiency angry amino acid utilization, and economic efficiency

[EN] A trial was conducted to evaluate fish meal (FM) replacement with meat and bone meal (MBM; 53% CP, 15% CL, 27% Ash) in diets for gilthead seabream (Sparus aurata) juveniles. Three extruded experimental diets were formulated (45% CP; 20% CL) to include 0, 50 and 75% of protein from MBM (diets MBM0; MBM50; MBM75). Triplicate groups of seabream (IBW = 25 g) were fed these diets to satiety for 12 weeks. Growth performance and feed efficiency were similar with the diets MBM0 and MBM50, but were lower with diet MBM75, while the opposite was true for feed intake. Whole-body composition was not affected by diets composition except for crude lipid and energy content, which were lower with the diet MBM75. Protein and essential amino acids retention were unaffected by diet composition, while energy retention was lower with the diet MBM75. In terms of economic efficiency, diets with MBM resulted in a lower production costs, with the lowest economic conversion ratio ( kg&#8722; 1 fish produced) being obtained for the MBM diets while the maximum economic profit ( kg fish&#8722; 1) was obtained for diet MBM50. Overall, up to 50% of FM protein can be replaced by MBM protein in diets for gilthead seabream juveniles, without compromising growth performance, feed utilization, and nutrient retention.Moutinho, S.; Martínez-Llorens, S.; Tomas-Vidal, A.; Jover Cerda, M.; Oliva-Teles, A.; Peres, H. (2017). Meat and bone meal as a partial replacement for fish meal in diets for gilthead seabream (Spares aurata): growth, feed efficiency angry amino acid utilization, and economic efficiency. Aquaculture. 468(1):271-277. doi:10.1016/j.aquaculture.2016.10.024S271277468

DIA-DB : a database and web server for the prediction of diabetes drugs

The DIA-DB is a web server for the prediction of diabetes drugs that uses two different and complementary approaches: (a) comparison by shape similarity against a curated database of approved antidiabetic drugs and experimental small molecules and (b) inverse virtual screening of the input molecules chosen by the users against a set of therapeutic protein targets identified as key elements in diabetes. As a proof of concept DIA-DB was successfully applied in an integral workflow for the identification of the antidiabetic chemical profile in a complex crude plant extract. To this end, we conducted the extraction and LC-MS based chemical profile analysis of Sclerocarya birrea and subsequently utilized this data as input for our server. The server is open to all users, registration is not necessary, and a detailed report with the results of the prediction is sent to the user by email once calculations are completed. This is a novel public domain database and web server specific for diabetes drugs and can be accessed online through http://bio-hpc.eu/software/dia-db/.http://pubs.acs.org/journal/jcics1/about.htmlhj2021BiochemistryGeneticsMicrobiology and Plant Patholog

Risk factors for non-diabetic renal disease in diabetic patients

Background. Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. Methods. Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. Results. In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 6 12.8 years, creatinine was 2.8 6 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2–5.4) g/24 h. About 39.5% (n ¼ 329) of patients had DN, 49.6% (n ¼ 413) NDRD and 10.8% (n ¼ 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n ¼ 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) ¼ 1.03, 95% CI: 1.02–1.05, P < 0.001], microhaematuria (OR ¼ 1.51, 95% CI: 1.03–2.21, P ¼ 0.033) and absence of diabetic retinopathy (DR) (OR ¼ 0.28, 95% CI: 0.19–0.42, P < 0.001) were independently associated with NDRD. Kaplan–Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P ¼ 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P ¼ 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P ¼ 0.002), higher creatinine (P ¼ 0.01) and DN (P ¼ 0.015) were independent risk factors for mortality. Conclusions. The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis

Proper assignation of reactivation in a COVID-19 recurrence initially interpreted as a reinfection

A 77-year-old-male (Case R) who had had a previous diagnosis of mild COVID-19 episode, was hospitalized 35 days later. On Day 23 post-admission, he developed a second COVID-19 episode, now severe, and finally died. Initially, Case R COVID-19 recurrence was interpreted as a reinfection due to the exposure to a SARS-CoV-2 RT-PCR-positive room-mate. However, whole-genome-sequencing indicated that case R recurrence corresponded to a reactivation of the strain involved in his first episode. Case R reactivation had major consequences, leading to a more severe episode, and causing a subsequent transmission to another two hospitalized patients, one of them with fatal outcome.Peer reviewe

Resignificando la educación: 12 reflexiones pedagógicas sobre la escuela

208 páginasEste libro reúne 12 artículos de maestros y maestras de la ciudad que reflexionan sobre el rol de la Escuela en la actualidad. Sin duda, la pandemia es un hecho que atraviesa varias de estas páginas, pues esta coyuntura ha hecho que estudiantes, docentes y familias resignifiquen su papel en la educación. Pero este libro no se agota allí, en tanto aparecen iniciativas como las redes de maestros y maestras en torno a la paz, la interculturalidad, así como nuevas miradas sobre la inclusión educativa y la evaluación que aportan al diálogo pedagógico. De esta manera, el Instituto para la Investigación Educativa y el Desarrollo Pedagógico (IDEP) busca que docentes y directivos de las instituciones educativas aporten a la transformación educativa desde sus saberes y experiencias.I. La Escuela en Casa. Página 17: Transitando por la Escuela: realidades y posibilidades. Página 29: Relación Familia- Escuela, Educación Asistida y Ambientes de Aprendizaje en Casa. Página 43: Percepciones de familias sobre su participación en la Escuela. Articulando voces de madres, padres y acudientes de estudiantes en Jardín y Transición. II. Nuevas miradas de la evaluación Página 71: Del pensamiento a la acción: la evaluación en el preescolar. Página 87: La evaluación durante el confinamiento educativo: evidencias investigativas de una crisis en sus prácticas y usos. III. Redes de paz, reconciliación y ciudadanía. Página 103: La Red Elegguá: Abriendo caminos para la tolerancia y la interculturalidad. Página 113: Pedagogías colectivas para la Paz- Tejido de esperanzas de maestras y maestros de la Red Chisua. IV. Inclusión educativa. Página 131: Experiencias de apropiación: Narrativas de maestras desde la inclusión. Página 149: El rol del docente de apoyo frente al reto de una educación inclusiva de calidad para la atención a la población estudiantil con discapacidad. Página 161: La oferta bilingüe-bicultural a nivel distrital, una apuesta en la educación de la persona sorda. V. Estudiantes y maestros en cambio. Página 177: El maestro investigador en el aula y su caracterización pedagógica. Página 195: Los Procesos de Lectura y Escritura Creativa en niños, niñas y adolescentes. Análisis de una experiencia

Anafilaxia en niños y adultos: prevención, diagnóstico y tratamiento

La anafilaxia es una condición que requiere asistencia inmediata para su resolución, se puede presentar en diferentes entornos: consultorio, hospital, escuela, hogar o en algún otro espacio público. La información aquí contenida forma parte de lineamientos conocidos sobre prevención, diagnóstico y tratamiento. Se abordan aspectos epidemiológicos, desencadenantes, factores de riesgo y cofactores; se explican de una manera didáctica los mecanismos fisiopatológicos que se traducen en fenotipos de presentación. Se enfatiza el diagnóstico clínico con base en criterios ya establecidos, se mencionan clasificaciones para evaluar la gravedad de la reacción, así como el rol de las pruebas clínicas o de laboratorio. Como aspectos de relevancia, se abordan el tratamiento de primera elección con adrenalina, instrucciones sobre autoinyectores y diferentes elementos para el tratamiento complementario y de segunda elección. También se refieren aspectos a considerar al dar de alta a un paciente y medidas de seguimiento, con un énfasis preventivo en la comunidad. Finalmente, se menciona el abordaje en el consultorio de alergia para decidir sobre opciones de inmunomodulación. ABSTRACT Anaphylaxis is a condition that requires immediate assistance for its resolution, it can occur in different settings: office, hospital, school, home or some other public space. The information contained herein forms part of known guidelines on prevention, diagnosis and treatment. Epidemiological aspects, triggers, risk factors and co-factors are addressed; physiopathological mechanisms that are translated into presentation phenotypes are explained in a didactic way. Clinical diagnosis is emphasized based on established criteria, classifications are mentioned to evaluate the severity of the reaction, as well as the role of clinical or laboratory tests. As relevant aspects, the first choice treatment with adrenaline, instructions on auto-injectors and different elements for the complementary and second choice treatment are dealt with. They also refer to aspects to consider when discharging a patient and followup measures, with a preventive emphasis on the community. Finally, the allergy clinic approach to deciding on immunomodulation options is mentione