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La Serpiente y el Arco Iris (1988) de Wes Craven supone un modelo docente atractivo que combina la farmacología y las alteraciones fisiológicas en muchos sistemas funcionales. Basada en un hecho real, este clásico del terror convertido en una película de culto analiza como el método científico es capaz de dar respuestas al mito del muerto viviente, a través del vudú en la población de Haití, por la inhalación de una potente droga en polvo que contiene altas dosis de tetrodotoxina. Este filme simula el estado agudo de catalepsia de los pacientes y las pruebas sometidas para certificar la aparente defunción tras la confirmación del cese irreversible de las funciones cardiorrespiratorias o encefálica, debido a la ausencia de reflejos troncoencefálicos a causa de los efectos a largo plazo que presenta la droga. Además, a pesar de que el paciente no fallece y es enterrado siendo consciente de todo el proceso, el filme permite reflexionar en los estudiantes la alta carga psicológica, tanto del propio paciente como de la población, que profundiza en los estados de terror al suponer que es un esclavo retornado de la muerte sin alma y sin voluntad.

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown remarkable results in melanoma, but only modest clinical benefits in other cancers, even after TIL have been genetically modified to improve their tumor homing, cytotoxic potential or overcome cell exhaustion. The required ex vivo TIL expansion process may induce changes in the T cell clonal composition, which could likely compromise the tumor reactivity of TIL preparations and ultimately the success of TIL therapy. A promising approach based on the production of bispecific T cell-engagers (TCE) by engineered T cells (STAb-T therapy) improves the efficacy of current T cell redirection strategies against tumor-associated antigens in hematological tumors. We studied the TCRβ repertoire in non-small cell lung cancer (NSCLC) tumors and in ex vivo expanded TIL from two unrelated patients. We generated TIL secreting anti-epidermal growth factor receptor (EGFR) × anti-CD3 TCE (TILSTAb) and tested their antitumor efficacy in vitro and in vivo using a NSCLC patient-derived xenograft (PDX) model in which tumor fragments and TIL from the same patient were transplanted into hIL-2 NOG mice. We confirmed that the standard TIL expansion protocol promotes the loss of tumor-dominant T cell clones and the overgrowth of virus-reactive TCR clonotypes that were marginally detectable in primary tumors. We demonstrated the antitumor activity of TILSTAb both in vitro and in vivo when administered intratumorally and systemically in an autologous immune-humanized PDX EGFR+ NSCLC mouse model, where tumor regression was mediated by TCE-redirected CD4+ TIL bearing non-tumor dominant clonotypes.

Editorial.

Abstract Background Using harmonized aggregated data on health and socioeconomic environments in Latin American cities (from the Salud Urbana en América Latina (SALURBAL) study), we assessed the association of city‐level contextual factors with the prevalence of the double burden of malnutrition (DBM) in urban settings. Methods This ecological study used aggregated survey data from 115 Latin American cities within five countries (Colombia, El Salvador, Guatemala, Mexico and Peru) collected between 2008 and 2016. DBM was defined as the coexistence of stunting in children under 5 years and overweight/obesity among adult women at the city‐level. We ran ordinal logistic regression models to examine macrolevel contextual factors that might explain the city‐level DBM. Independent variables were city‐level socioeconomic development index, women educational attainment and women labor force. Results Out of 115 Latin American cities, 19 cities from five countries were experiencing a moderate to high burden of stunting and simultaneously a very high burden of overweight/obesity in adult women. All cities had overweight/obesity prevalence above 40%. A poor social environment, higher levels of women education and greater women labor force at the city level were associated with greater levels of DBM. Conclusion Some Latin American cities are still facing moderate and high DBM, while all cities are experiencing an alarming high burden of overweight/obesity. Social macro‐level factors such as poor social environment, high women education and high women labor force were associated with the coexistence of stunting in children and overweight/obesity in adult women.

IntroductionFanconi anemia (FA) is an inherited disorder characterized by bone marrow failure, congenital malformations, and predisposition to malignancies. Alterations in hematopoietic stem cells (HSC) have been reported, but little is known regarding the bone marrow (BM) stroma. Thus, the characterization of Mesenchymal Stromal Cells (MSC) would help to elucidate their involvement in the BM failure.MethodsWe characterized MSCs of 28 FA patients (FA-MSC) before and after treatment (hematopoietic stem cell transplantation, HSCT; or gene therapy, GT). Phenotypic and functional properties were analyzed and compared with MSCs expanded from 26 healthy donors (HD-MSCs). FA-MSCs were genetically characterized through, mitomycin C-test and chimerism analysis. Furthermore, RNA-seq profiling was used to identify dysregulated metabolic pathways.ResultsOverall, FA-MSC had the same phenotypic and functional characteristics as HD-MSC. Of note, MSC-GT had a lower clonogenic efficiency. These findings were not confirmed in the whole FA patients’ cohort. Transcriptomic profiling identified dysregulation in HSC self-maintenance pathways in FA-MSC (HOX), and was confirmed by real-time quantitative polymerase chain reaction (RT-qPCR).DiscussionOur study provides a comprehensive characterization of FA-MSCs, including for the first time MSC-GT and constitutes the largest series published to date. Interestingly, transcript profiling revealed dysregulation of metabolic pathways related to HSC self-maintenance. Taken together, our results or findings provide new insights into the pathophysiology of the disease, although whether these niche defects are involved in the hematopoietic defects seen of FA deserves further investigation.

Abstract Background The HEARTS technical package was developed by the World Health Organization to address the implementation gap in cardiovascular disease prevention in low- and middle-income countries. Guatemala is a middle-income country that is currently implementing HEARTS. National authorities in Guatemala are interested in exploring how hypertension and diabetes management can be integrated in HEARTS implementation. The objective of this study is to conduct a feasibility and acceptability pilot trial of integrated hypertension and diabetes management based on HEARTS in the publicly funded primary care system in Guatemala. Methods A single-arm pilot trial for 6 months will be carried out in 11 Ministry of Health primary care facilities starting in September 2023. A planned sample of 100 adult patients diagnosed with diabetes (n = 45), hypertension (n = 45), or both (n = 10) will be enrolled. The intervention will consist of HEARTS-aligned components: Training health workers on healthy-lifestyle counseling and evidence-based treatment protocols, strengthening access to medications and diagnostics, training on risk-based cardiovascular disease management, team-based care and task sharing, and systems monitoring and feedback, including implementation of a facility-based electronic monitoring tool at the individual level. Co-primary outcomes of feasibility and acceptability will be assessed using an explanatory sequential mixed-methods design. Secondary outcomes include clinical effectiveness (treatment with medication, glycemic control, and blood pressure control), key implementation outcomes (adoption, fidelity, usability, and sustainability), and patient-reported outcome measures (diabetes distress, disability, and treatment burden). Using an implementation mapping approach, a Technical Advisory Committee will develop implementation strategies for subsequent scale-up planning. Discussion This trial will produce evidence on implementing HEARTS-aligned hypertension and diabetes care in the MOH primary care system in Guatemala. Results also will inform future HEARTS projects in Guatemala and other low- and middle-income countries. Trial registration ClinicalTrials.gov ID NCT06080451. The trial was prospectively registered on October 12, 2023.

The ability of flow cytometry to identify and quantify the presence of cell populations defined by their expression profile of specific markers has made this technique a powerful and routinary tool in clinical diagnostic practice. Specifically in the field of hematological malignancies, flow cytometry allows the identification of the correct type and lineage of each patient’s disease and also sensitively quantifies the presence of the disease at precise moments during treatment, that is, levels of measurable residual disease (MRD). The quantification of MRD by flow cytometry has allowed the adaptation of tailored therapies to patients, contributing to the improvement of the results of the different protocols in recent decades. In this context, our objective in the present work was to evaluate the potential impact that spectral flow cytometry can provide compared to conventional cytometry, which is the one usually used in clinics. We present here a comparative study of both technologies, spectral versus conventional flow cytometry, in primary samples corresponding to the diagnosis and follow-up of children and adolescents with acute lymphoblastic leukemia. Our initial experience demonstrates the feasibility of incorporating spectral flow cytometry into the routine workflow of a reference laboratory.

We previously described the circadian variation and bilateral distribution of pyroglutamate aminopeptidase I (pGluPI) activity levels in photoneuroendocrine locations of adult male rats during a standard 12:12 h light–dark cycle. However, the correlational analysis between such locations has not yet been studied. This may provide new data about the unilateral and bilateral functional interaction between photoneuroendocrine locations under light and dark conditions. We analyzed the correlations between locations of a photoneuroendocrine circuit consisting of retina, anterior hypothalamus, superior cervical ganglion, and pineal gland, as well as other related photoneuroendocrine locations: posterior hypothalamus, anterior pituitary, posterior pituitary, occipital cortex, and serum. In particular, we analyzed the correlations between the left retina or the right retina versus the rest of the locations, as well as the correlations between the left and right sides of paired structures at the different time points selected from 12 h light and 12 h dark periods. Also, the profiles of correlational results were compared with the corresponding mean levels. The results demonstrate the complexity of asymmetrical brain behavior. The correlation profile did not always parallel the profile observed with the mean activity values. The diurnal behavior of correlations with the left or right retina differed from one location to another. Likewise, the diurnal variation of correlations between the left and right sides of the paired structures differed between them. Particularly, while most correlations between the left versus right sides of paired structures showed positive values, that of the posterior hypothalamus showed a negative value at 13 h of light period. In addition, except the posterior hypothalamus, most paired locations only correlated significantly with right retina at 07 h of the light period. The results demonstrate the dynamic complexity of brain asymmetry, which represents a challenge for understanding its functional meaning.

Background: Antimicrobial consumption (AMC) data in Latin America are scarce and usually spread out across different sources used to make AMC calculations, making it difficult to both standardize and compare regions through similar time frames. The main objective was to analyze AMC trends in Social Security tertiary care hospitals in Costa Rica in the period spanning January 2017 to December 2021, using both the defined daily dose (DDD)/100 bed days and DDD/100 discharges. Methods: This is a retrospective observational study of antimicrobial consumption. Global consumption trends were calculated and expressed as DDD/100 bed days and DDD/100 discharges. Trends in antimicrobial consumption were analyzed using a simple linear regression model to determine potential differences in antimicrobial usage throughout the study’s duration. Results: A statistically significant increase in the consumption expressed in DDD/100 discharges was observed in the following groups: carbapenems, 7.6% (trend: 64.68, p < 0.0001), trimethoprim-sulfamethoxazole: 12.6% (trend: 16.45, p < 0.0001), quinolones 9.4% (trend: 36.80, p = 0.02), vancomycin 2.0% (trend: 16.30, p = 0.03), echinocandins: 6.0% (trend: 15.17, p = 0.01) and azole antifungals: 12.10% (trend: 102.05, p < 0.0001). Additionally, a statistically significant increase of 10.30% in the consumption of azole antifungals expressed in DDD/100 bed days was observed (p = 0.0008). In contrast, a statistically significant decrease in consumption, expressed in DDD/100 discharges, was identified for cephalosporins −6.0% (p < 0.0001) and macrolides −16.5% (p < 0.0001). Macrolides also showed a downward trend in consumption, as expressed in DDD/100 bed days (−14.3%, p < 0.0001). According to World Health Organization (WHO) access, watch and reserve (AWaRe) classification trend analysis, only the reserve group showed a statistically significant upward change of 9.2% (p = 0.016). Conclusions: This five-year analysis demonstrated trends over time in overall antimicrobial consumption measured in DDD/100 bed days and DDD/100 discharge rates that correlate. In general, for all antimicrobials, after the implementation of antimicrobial stewardship programs (ASP), a downward trend is reported; in contrast, during the COVID-19 pandemic the AMC shows a general upward trend. The comparison between DDD/100 bed days and DDD/100 discharges allows for complementary comparisons to be made regarding antimicrobial exposure in a clinical setting.

Adoptive T cellular immunotherapies have emerged as relevant approaches for treating cancer patients who have relapsed or become refractory (R/R) to traditional cancer treatments. Chimeric antigen receptor (CAR) T-cell therapy has improved survival in various hematological malignancies. However, significant limitations still impede the widespread adoption of these therapies in most cancers. To advance in this field, six research groups have created the “NEXT Generation CART MAD Consortium” (NEXT CART) in Madrid’s Community, which aims to develop novel cell-based immunotherapies for R/R and poor prognosis cancers. At NEXT CART, various basic and translational research groups and hospitals in Madrid concur to share and synergize their basic expertise in immunotherapy, gene therapy, and immunological synapse, and clinical expertise in pediatric and adult oncology. NEXT CART goal is to develop new cell engineering approaches and treatments for R/R adult and pediatric neoplasms to evaluate in multicenter clinical trials. Here, we discuss the current limitations of T cell-based therapies and introduce our perspective on future developments. Advancement opportunities include developing allogeneic products, optimizing CAR signaling domains, combining cellular immunotherapies, multi-targeting strategies, and improving tumor-infiltrating lymphocytes (TILs)/T cell receptor (TCR) therapy. Furthermore, basic studies aim to identify novel tumor targets, tumor molecules in the tumor microenvironment that impact CAR efficacy, and strategies to enhance the efficiency of the immunological synapse between immune and tumor cells. Our perspective of current cellular immunotherapy underscores the potential of these treatments while acknowledging the existing hurdles that demand innovative solutions to develop their potential for cancer treatment fully.

La región latinoamericana ha sido pionera en la implementación del etiquetado frontal de advertencia nutricional (EFAN), mismo que ha demostrado su eficacia y efectividad para identificar correctamente cuando un producto contiene cantidades excesivas de nutrientes asociados a Enfermedades no transmisibles (ENT). Sin embargo, ningún país del Sistema de la Integración Centroamericana (SICA); que incluye a Belice, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, Panamá y República Dominicana, lo ha adoptado. Por esta razón, el Instituto de Nutrición de Centro América y Panamá, convocó a un grupo de expertos de la academia y la sociedad civil con el objetivo de establecer una postura técnica, basada en la mejor evidencia científica, en relación al etiquetado frontal para los nutrientes críticos de alimentos y bebidas pre- envasados en la región centroamericana. Se presenta evidencia específica de la región del SICA que demuestran la superioridad del EFAN frente a otros etiquetados como las Guías Diarias de Alimentación (GDA), el semáforo y el Nutriscore para seleccionar opciones más saludables. Dentro del marco de los derechos de la niñez y de los consumidores, se brindan argumentos y se hace un llamado a los gobiernos para la pronta adopción del EFAN como una política costo-efectiva para la prevención de ENT. Además, se proveen recomendaciones para su monitoreo y evaluación, así como recomendaciones de otras políticas costo-efectivas como la regulación de la publicidad de alimentos no saludables dirigido a la niñez y adolescencia, entre otros, para la prevención de las ENT y la creación de ambientes y sistemas alimentarios más saludables y sostenibles.

Abstract The initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children. Several preclinical studies have shown that exposure to immune stressors triggers the transformation of preleukemic B cells to full-blown B-ALL, but how this takes place is still a longstanding and unsolved challenge. Here we show that dysregulation of innate immunity plays a driving role in the clonal evolution of pre-malignant Pax5 +/− B-cell precursors toward leukemia. Transcriptional profiling reveals that Myd88 is downregulated in immune-stressed pre-malignant B-cell precursors and in leukemic cells. Genetic reduction of Myd88 expression leads to a significant increase in leukemia incidence in Pax5 +/−Myd88+/− mice through an inflammation-dependent mechanism. Early induction of Myd88-independent Toll-like receptor 3 signaling results in a significant delay of leukemia development in Pax5 +/− mice. Altogether, these findings identify a role for innate immunity dysregulation in leukemia, with important implications for understanding and therapeutic targeting of the preleukemic state in children.

IntroductionThe clinical success of chimeric antigen receptor-modified T cells (CAR-T cells) for hematological malignancies has not been reproduced for solid tumors, partly due to the lack of cancer-type specific antigens. In this work, we used a novel combinatorial approach consisting of a versatile anti-FITC CAR-T effector cells plus an FITC-conjugated neuroblastoma (NB)-targeting linker, an FITC-conjugated monoclonal antibody (Dinutuximab) that recognizes GD2.MethodsWe compared cord blood (CB), and CD45RA-enriched peripheral blood leukapheresis product (45RA) as allogeneic sources of T cells, using peripheral blood (PB) as a control to choose the best condition for anti-FITC CAR-T production. Cells were manufactured under two cytokine conditions (IL-2 versus IL-7+IL-15+IL-21) with or without CD3/CD28 stimulation. Immune phenotype, vector copy number, and genomic integrity of the final products were determined for cell characterization and quality control assessment. Functionality and antitumor capacity of CB/45RA-derived anti-FITC CAR-T cells were analyzed in co-culture with different anti-GD2-FITC labeled NB cell lines.ResultsThe IL-7+IL-15+IL-21 cocktail, in addition to co-stimulation signals, resulted in a favorable cell proliferation rate and maintained less differentiated immune phenotypes in both CB and 45RA T cells. Therefore, it was used for CAR-T cell manufacturing and further characterization. CB and CD45RA-derived anti-FITC CAR-T cells cultured with IL-7+IL-15+IL-21 retained a predominantly naïve phenotype compared with controls. In the presence of the NB-FITC targeting, CD4+ CB-derived anti-FITC CAR-T cells showed the highest values of co-stimulatory receptors OX40 and 4-1BB, and CD8+ CAR-T cells exhibited high levels of PD-1 and 4-1BB and low levels of TIM3 and OX40, compared with CAR-T cells form the other sources studied. CB-derived anti-FITC CAR-T cells released the highest amounts of cytokines (IFN-γ and TNF-α) into co-culture supernatants. The viability of NB target cells decreased to 30% when co-cultured with CB-derived CAR-T cells during 48h.ConclusionCB and 45RA-derived T cells may be used as allogeneic sources of T cells to produce CAR-T cells. Moreover, ex vivo culture with IL-7+IL-15+IL-21 could favor CAR-T products with a longer persistence in the host. Our strategy may complement the current use of Dinutuximab in treating NB through its combination with a targeted CAR-T cell approach.

Abstract Background Front-of-package warning labels (FOPWL) have been adopted in many countries aiming at reducing the consumption of unhealthy food and drink products and have also been considered in Guatemala. The aim of the study is to evaluate the efficacy of FOPWL versus Guidelines for Daily Amount (GDA) on products’ healthfulness perception (HP), purchase intention (PI) and the objective understanding of the nutrient content (UNC) in Guatemala. Methods Participants (children and adults) (n = 356) were randomly assigned to evaluate either FOPWL or GDA during a crossover cluster randomized experiment in rural and urban areas across 3 phases of exposure. During phase 1, participants evaluated mock-up images of single products (single task) and compared pairs of products within the same food category (comparison task) without any label. In phase 2, participants evaluated labels only (without any product), and during phase 3, they evaluated the same products and questions from phase 1, now depicting the assigned front-of-package label. We generated indicators for single-task questions and scores for comparison tasks, one for each HP, PI and UNC questions. We used intention-to-treat, difference-in-difference regression analysis to test whether exposure to FOPWL was associated with HP, PI and UNC, compared to GDA. We also tested models for children and adults and by area (rural/urban) separately adjusting for sociodemographic variables. Results In single tasks, FOPWL significantly decreased the PI (β -18.1, 95%CI -23.3, -12.8; p

Este artículo aborda el tema de la participación ciudadana en estudiantes de la licenciatura en Sociología de la Facultad de Estudios Superiores Aragón, perteneciente a la Universidad Nacional Autónoma de México. El objetivo de este artículo es identificar las nociones de la participación ciudadana entre los estudiantes de sociología. El método de investigación es cualitativo, mediante un cuestionario abierto. Los resultados enmarcan a jóvenes universitarios propensos a participar en actividades sociales, con una centralidad de la motivación individual para alcanzar fines comunes en lo comunitario, lo social y lo político. Como conclusión, los jóvenes universitarios observan la imagen de la participación ciudadana en formas convencionales y no convencionales.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, and the infiltration of leukemic cells is critical for disease progression and relapse. Nuclear deformability plays a critical role in cancer cell invasion through confined spaces; however, the direct impact of epigenetic changes on the nuclear deformability of leukemic cells remains unclear. Here, we characterized how 3D collagen matrix conditions induced H3K4 methylation in ALL cell lines and clinical samples. We used specific shRNA and chemical inhibitors to target WDR5 (a core subunit involved in H3K4 methylation) and determined that targeting WDR5 reduced the H3K4 methylation induced by the 3D environment and the invasiveness of ALL cells in vitro and in vivo. Intriguingly, targeting WDR5 did not reduce the adhesion or the chemotactic response of leukemia cells, suggesting a different mechanism by which H3K4 methylation might govern ALL cell invasiveness. Finally, we conducted biochemical, and biophysical experiments to determine that 3D environments promoted the alteration of the chromatin, the morphology, and the mechanical behavior of the nucleus in ALL cells. Collectively, our data suggest that 3D environments control an upregulation of H3K4 methylation in ALL cells, and targeting WDR5 might serve as a promising therapeutic target against ALL invasiveness in vivo.

Although children and adolescents with acute lymphoblastic leukaemia (ALL) have high survival rates, approximately 15-20% of patients relapse. Risk of relapse is routinely estimated at diagnosis by biological factors, including flow cytometry data. This high-dimensional data is typically manually assessed by projecting it onto a subset of biomarkers. Cell density and "empty spaces" in 2D projections of the data, i.e. regions devoid of cells, are then used for qualitative assessment. Here, we use topological data analysis (TDA), which quantifies shapes, including empty spaces, in data, to analyse pre-treatment ALL datasets with known patient outcomes. We combine these fully unsupervised analyses with Machine Learning (ML) to identify significant shape characteristics and demonstrate that they accurately predict risk of relapse, particularly for patients previously classified as 'low risk'. We independently confirm the predictive power of CD10, CD20, CD38, and CD45 as biomarkers for ALL diagnosis. Based on our analyses, we propose three increasingly detailed prognostic pipelines for analysing flow cytometry data from ALL patients depending on technical and technological availability: 1. Visual inspection of specific biological features in biparametric projections of the data; 2. Computation of quantitative topological descriptors of such projections; 3. A combined analysis, using TDA and ML, in the four-parameter space defined by CD10, CD20, CD38 and CD45. Our analyses readily extend to other haematological malignancies.

B‐cell acute lymphoblastic leukemia (B‐ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B‐ALL. Although hyperdiploidy represents an important prognostic factor in childhood B‐ALL, the specific chromosome gains with prognostic value in HHD‐B‐ALL remain controversial, and the current knowledge about the hierarchy of chromosome gains, clonal heterogeneity and chromosomal instability in HHD‐B‐ALL remains very limited. We applied automated sequential‐iFISH coupled with single‐cell computational modeling to identify the specific chromosomal gains of the eight typically gained chromosomes in a large cohort of 72 primary diagnostic (DX, n = 62) and matched relapse (REL, n = 10) samples from HHD‐B‐ALL patients with either favorable or unfavorable clinical outcome in order to characterize the clonal heterogeneity, specific chromosome gains and clonal evolution. Our data show a high degree of clonal heterogeneity and a hierarchical order of chromosome gains in DX samples of HHD‐B‐ALL. The rates of specific chromosome gains and clonal heterogeneity found in DX samples differ between HHD‐B‐ALL patients with favorable or unfavorable clinical outcome. In fact, our comprehensive analyses at DX using a computationally defined risk predictor revealed low levels of trisomies +18+10 and low levels of clonal heterogeneity as robust relapse risk factors in minimal residual disease (MRD)‐negative childhood HHD‐B‐ALL patients: relapse‐free survival beyond 5 years: 22.1% versus 87.9%, P

IntroductionThe use of peripheral blood progenitor cells (PBPCs) as a source for hematopoietic stem cell transplantation (HSCT) in pediatric healthy donors is still under debate. The risk of a central venous catheter (CVC) placement and catheter-related complications continue to be the main arguments to discourage its use.Methodswe present a retrospective analysis of 140 PBPC collections in pediatric patients and donors, describing adverse events (AE) related to CVCs as well as the influence of catheterrelated variables on the efficiency of the leukapheresis.Results14 CVC-related AEs were recorded (10%). The most common was fever in 5 patients, 4 of which had a catheter-related bacteriemia. Thrombotic events were only observed in 3 patients with active malignancy. A healthy donor presented a moderate bleeding after catheter withdrawal that resolved with local measures, and none of the rest presented any AE. Regarding variables related to the development of AEs, the subject group (patient or donor) was the only one significantly associated (p

Salmonella Gallinarum (SG) is a host-restricted enterobacteria and the causative agent of fowl typhoid in poultry. Here, we report the complete genomes of two strains belonging to this serotype. SA68 is a field strain isolated from the livers of dead hen carcasses of a commercial layer farm presenting high mortality located in São Paulo city, Brazil, in 1990. Strain 9R corresponds to a live attenuated SG commercial vaccine. DNA was extracted from pure cultures and subjected to whole genome sequencing (WGS) using the Ion Torrent PGM System. The assemblies reached lengths of 4,657,435 (SA68) and 4,657,471 (9R) base pairs. Complete genomes were deposited in GenBank under the accession numbers CP110192 (SA68) and CP110508 (9R). Both genomes were analyzed and compared in terms of molecular typing, antibiotic resistance genes, virulence genes, Salmonella pathogenic islands (SPIs), insertion sequences and prophages. The data obtained show many similarities in the genetic content, with the exception of the SPI-12 and CS54 pathogenic islands, which are exclusive to the field strain. The information generated will help to understand the virulence differences of field and vaccinal SG strains and can be used to perform evolutionary and epidemiologic studies.

El artículo analiza la articulación de los poderes locales en una sociedad de frontera, como el caso de Concepción, en el antiguo reino de Chile, centrándonos en la reconstrucción de su institucionalidad municipal y su relación con los órganos del poder monárquico durante los años más álgidos del reformismo borbón. Para ello comenzamos analizando las características de la corporación edilicia durante el último cuarto del siglo XVIII, para posteriormente adentrarnos en su composición, así como en las distintas prácticas que caracterizaban el accionar de estos individuos a finales del antiguo régimen. Paralelamente, analizamos la aparición de los intendentes y sus efectos en el seno del municipio, poniendo especial énfasis en los conflictos de poder que envolvieron a ambas instituciones. Por último, en las conclusiones, destacamos la evolución y el peso que tuvieron estas disputas durante los años que siguieron a la crisis imperial, de cara a los procesos de independencia.

Objective We examined associations among serial measures of linear growth and relative weight with adult body composition.Design Secondary data analysis of prospective birth cohort studies.Settings Six birth cohorts from Brazil, Guatemala, India, the Philippines and South Africa.Participants 4173 individuals followed from birth to ages 22–46 years with complete and valid weight and height at birth, infancy, childhood and adolescence, and body composition in adult life.Exposures Birth weight and conditional size (standardised residuals of height representing linear growth and of relative weight representing weight increments independent of linear size) in infancy, childhood and adolescence.Primary outcome measures Body mass index, fat mass index (FMI), fat-free mass index (FFMI), fat mass/fat-free mass ratio (FM/FFM), and waist circumference in young and mid-adulthood.Results In pooled analyses, a higher birth weight and relative weight gains in infancy, childhood and adolescence were positively associated with all adult outcomes. Relative weight gains in childhood and adolescence were the strongest predictors of adult body composition (β (95% CI) among men: FMI (childhood: 0.41 (0.26 to 0.55); adolescence: 0.39 (0.27 to 0.50)), FFMI (childhood: 0.50 (0.34 to 0.66); adolescence: 0.43 (0.32 to 0.55)), FM/FFM (childhood: 0.31 (0.16 to 0.47); adolescence: 0.31 (0.19 to 0.43))). Among women, similar patterns were observed, but, effect sizes in adolescence were slightly stronger than in childhood. Conditional height in infancy was positively associated with FMI (men: 0.08 (0.03 to 0.14); women: 0.11 (0.07 to 0.16)). Conditional height in childhood was positively but weakly associated with women’s adiposity. Site-specific and sex-stratified analyses showed consistency in the direction of estimates, although there were differences in their magnitude.Conclusions Prenatal and postnatal relative weight gains were positive predictors of larger body size and increased adiposity in adulthood. A faster linear growth in infancy was a significant but weak predictor of higher adult adiposity.

This paper proposes a Python tool for the analysis of balanced, unbalanced, sinusoidal and nonsinusoidal three-phase systems based on the IEEE Std. 1459. The proposed tool was developed to be used by electrical engineers and professionals of related careers providing a free access for electrical power calculations that allows validation and power analysis in power systems. The proposed tool is available for use on a GitHub link and only requires voltage and current signals as inputs, making it possible to dispense expensive commercial network analyzers. The tool is made of two interfaces, one for making power calculations of sinusoidal three-phase systems and the other one for making calculations of nonsinusoidal three-phase systems; both interfaces can be accessed through a main menu. The proposed tool facilitates decision-making in electrical system issues, which helps improving the efficiency and power quality of electrical systems.

Non-conventional yeasts such as Torulaspora delbrueckii (Td) have been proposed for sparkling winemaking. Unfortunately, this yeast has poor efficiency in completing wine fermentation as compared to Saccharomyces cerevisiae (Sc). New mutants with increased resistance to SO2, ethanol, and high CO2 pressure were previously isolated from spore clones of Td. Although these mutants showed improved capability for base wine fermentation, there is still room for genetic improvement of Td yeasts until the fermentative capacity of Sc is achieved. As an alternative approach, yeast mixture for eventual hybridization of Td with Sc was assayed in this study. The new yeast mixture clones (Sc-mixed Td) showed an intermediate phenotype between both parent yeasts for some relevant biotechnological properties, such as resistance to SO2, ethanol, copper, high CO2 pressure, and high temperature, as well as flocculation potential. These properties varied depending on the specific Sc-mixed Td clone. Several mixture clones showed improved capability for base wine fermentation as compared to the Td parent strain, approaching the fermentation capability of the Sc parent strain. The organoleptic quality of sparkling wine was also improved by using some mixture clones and this improved quality coincided with an increased amount of acetate and ethyl esters. The genetic stability of some Sc-mixed Td clones was good enough for commercial yeast production and winery applications.

Abstract Background Little is known about associations of psychological and mental well-being with cognitive and socioemotional factors in low and middle-income countries, particularly among vulnerable populations born in adverse environments that may restrict developmental potential. This study aimed to examine the cognitive and socioemotional correlates of psychological well-being and mental health in a cohort of Guatemalan adults born in contexts of poverty and malnutrition. Methods From Dec 2017 to Apr 2019, data were collected from 704 women and 564 men ages 40–57 years living in four rural villages in eastern Guatemala and Guatemala City. We measured latent domains of psychological well-being, spirituality and religion, emotional support, and executive function using Confirmatory Factor Analysis (CFA). Under a Structural Equation Modeling framework, we examined intercorrelations among latent domains and observed measures of intelligence and mental health. Results CFA supported the construct validity of factor structures in this population. Correlations of psychological well-being with spirituality and religion were moderate in women (r = 0.68, p

Previous studies demonstrated an asymmetry of left predominance for mean values of soluble leucine aminopeptidase (LeuAP) activity in the frontal cortex (FC) and hypothalamus of adult male rats, fluorimetrically analyzed by the hydrolysis of Leu-β-naphthylamide as a substrate. No asymmetries were observed in nine other left (L) and right (R) regions obtained from rostro-caudally sectioned coronal slices. Neither had inter-hemispheric differences observed for lactate dehydrogenase (LDH), analyzed simultaneously in the same brain regions (L and R) of the same animals. However, the level of intra-hemispheric or inter-hemispheric correlation of LeuAP or LDH between such brain regions has not been analyzed. In order to obtain additional suggestions on the functional heterogeneity between regions of LeuAP and LDH, in the present investigation, the level of intra-hemispheric and inter-hemispheric correlations of the frontal cortex with the rest of the regions studied is described: (A) between the left frontal cortex (LFC) and the rest of the left regions; (B) between the right frontal cortex (RFC) and the rest of the right regions; (C) between the left frontal cortex and all of the right regions; and (D) between the right frontal cortex and all of the left regions. All of the correlations obtained were positive. The intra-hemispheric analysis showed a greater heterogeneity of values in the correlations observed between RFC and the rest of the right regions than between LFC and the rest of the left regions. Greater heterogeneity is observed when comparing RFC correlations with left regions than when comparing LFC correlations with right regions. In conclusion, the greatest heterogeneity (suggesting a greater functional variability) was observed in the right intra-hemispheric analysis and in the inter-hemispheric analysis between the RFC and the left hemisphere. The results for LDH showed a great homogeneity between regions both in the intra- and inter-hemispheric studies.

Neuroblastoma is a highly metastatic tumor that emerges from neural crest cell progenitors. Focal Adhesion Kinase (FAK) is a regulator of cell migration that binds to the receptor Neogenin-1 and is upregulated in neuroblastoma. Here, we show that Netrin-1 ligand binding to Neogenin-1 leads to FAK autophosphorylation and integrin β1 activation in a FAK dependent manner, thus promoting neuroblastoma cell migration. Moreover, Neogenin-1, which was detected in all tumor stages and was required for neuroblastoma cell migration, was found in a complex with integrin β1, FAK, and Netrin-1. Importantly, Neogenin-1 promoted neuroblastoma metastases in an immunodeficient mouse model. Taken together, these data show that Neogenin-1 is a metastasis-promoting protein that associates with FAK, activates integrin β1 and promotes neuroblastoma cell migration.

Although at present depression is one of the most disabling disorders in our social environment, the understanding of its pathogenesis and the resources for its treatment are still unsatisfactory. The importance of brain asymmetry in the pathogenesis of disorders in brain function, including mood disorders such as depression, is a highly unexplored, sometimes underrated, and even ignored topic. It is important to note that the basal and pathological functional lateralization must have an underlying neurochemical substrate. It is also necessary to indicate that the brain asymmetry extends to a neurovisceral integration whose behavior may also be lateralized. One of the most studied axis from the functional point of view is the brain-heart connection, in whose operation there are observations that suggest an asymmetric behavior in basal conditions that is modified by central and peripheral changes, as well as by pharmacological treatments. There are evidences that connect cardiovascular function, neurochemical asymmetries, and depression. A deep understanding of the bilateral behavior of the brain following pathophysiological changes in blood pressure as well as pharmacologically induced, can provide us with therapeutic suggestions for the treatment of depression. In this article, we analyze remarkable results of some representative selected contributions, with which we discuss our proposal on the relationship between hypertension, depression and neurochemical asymmetry.

Reseña de: Andreu, Javier, Ozcáriz, Pablo, Mateo, Txaro: Epigrafía romana de Santa Criz de Eslava (Eslava, Navarra), Faenza, Fratelli Lega Editori, 2019, 187 pp., ISBN: 978-88-7594-140-6.

Milk is a food that has a great importance in society because, for its commercialization, payment for quality is used, where the physical-chemical and microbiological parameters determine the price of milk. Therefore, the objective of this research was to determine the influence of environmental factors (temperature, rain precipitation, humidity, solar radiation) on the physicochemical and microbiological quality of bovine milk in the zones of the San Martín Region - Peru. For it samples of milk were gathered in every zone of study and were analyzed to obtain his characteristics of density, acidity, fat, protein, solid total, aerobic mesophiles and numbering of coliforms. Duncan test at 5% was used to compare means, in addition Spearman correlation was performed in order to determine the degree of association between the variables of physicochemical and microbiological quality of milk with environmental factors. Concluded that environmental factors affect the density, fat and thus in the number of total solids in milk. Besides environmental factors directly affecting the numbering of aerobic mesophilic, especially solar radiation and temperature.

Abstract The nucleus is fundamentally composed by lamina and nuclear membranes that enclose the chromatin, nucleoskeletal components and suspending nucleoplasm. The functional connections of this network integrate external stimuli into cell signals, including physical forces to mechanical responses of the nucleus. Canonically, the morphological characteristics of the nucleus, as shape and size, have served for pathologists to stratify and diagnose cancer patients; however, novel biophysical techniques must exploit physical parameters to improve cancer diagnosis. By using multiple particle tracking (MPT) technique on chromatin granules, we designed a SURF (Speeded Up Robust Features)-based algorithm to study the mechanical properties of isolated nuclei and in living cells. We have determined the apparent shear stiffness, viscosity and optical density of the nucleus, and how the chromatin structure influences on these biophysical values. Moreover, we used our MPT-SURF analysis to study the apparent mechanical properties of isolated nuclei from patients of acute lymphoblastic leukemia. We found that leukemia cells exhibited mechanical differences compared to normal lymphocytes. Interestingly, isolated nuclei from high-risk leukemia cells showed increased viscosity than their counterparts from normal lymphocytes, whilst nuclei from relapsed-patient's cells presented higher density than those from normal lymphocytes or standard- and high-risk leukemia cells. Taken together, here we presented how MPT-SURF analysis of nuclear chromatin granules defines nuclear mechanical phenotypic features, which might be clinically relevant.

Ofrecemos el repertorio depurado de las referencias epigráficas del teónimo Coso y sus variantes documentadas en las inscripciones religiosas de época altoimperial halladas en el conventus Lucensis y en el territorio español de los conventus Asturum y Bracaraugustanus. A partir del examen directo de los epígrafes llevamos a cabo un análisis epigráfico de cada inscripción y proponemos excluir cinco supuestas menciones de este teónimo hasta la fecha consideradas como seguras.

Butter and virgin olive oil (EVOO) are two fats differing in their degree of saturation and insaponifiable fraction. EVOO, enriched in polyphenols and other minority components, exerts a distinct effect on health. Using next generation sequencing, we have studied early and long-term effects of both types of fats on the intestinal microbiota of mice, finding significant differences between the two diets in the percentage of certain bacterial taxa, correlating with hormonal, physiological and metabolic parameters in the host. These correlations are not only concomitant, but most noticeably some of the changes detected in the microbial percentages at six weeks are correlating with changes in physiological values detected later, at twelve weeks. Desulfovibrionaceae/Desulfovibrio/D. sulfuricans stand out by presenting at six weeks a statistically significant higher percentage in the butter-fed mice with respect to the EVOO group, correlating with systolic blood pressure, food intake, water intake and insulin at twelve weeks. This not only suggests an early implication in the probability of developing altered physiological and biochemical responses later on in the host lifespan, but also opens the possibility of using this genus as a marker in the risk of suffering different pathologies in the future.

Objetivo: Evaluar los resultados queratométricos y refractivos tempranos de pacientes con queratocono operados con anillos intracorneales. Método: Se evaluaron 50 ojos de 25 pacientes con queratocono de grado 2 o 3, posoperados con colocación de anillos intracorneales mediante el uso de láser de femtosegundos, al mes del posoperatorio, comparando las queratometrías y las refracciones antes y después de la operación. Resultados: El promedio preoperatorio de las queratometrías planas fue de 48.8 ± 3.65 D y en el posoperatorio fue de 46.44 ± 3.65 D (p < 0.005). El promedio preoperatorio de las queratometrías curvas fue de 53.92 ± 4.50 y en el posoperatorio fue de 49.65 ± 4.15 (p < 0.005). El equivalente esférico preoperatorio fue de −7.39 ± 2.42 D y en el posoperatorio fue de −3.48 ± 2.47 D (p < 0.005). El promedio del cilindro preoperatorio fue de −5.65 ± 2.02 D y en el posoperatorio fue de −3.48 ± 2.47 D (p < 0.005). Conclusiones: La colocación de anillos intracorneales reduce de forma significativa tanto las queratometrías como los equivalentes esféricos y el astigmatismo en pacientes con queratocono en forma temprana.

Abstract Background and Aims Metabolic conditions such as obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in Guatemala and increase the risk for a number of disorders, including hepatocellular carcinoma (HCC). Aflatoxin B1 (AFB1) levels are also notably elevated in the population and are known to be associated with HCC risk. Whether AFB1 also contributes to the high prevalence of the metabolic disorders has not been previously examined. Therefore, the purpose of this study was to assess the association between AFB1 and the metabolic conditions. Methods Four‐hundred twenty‐three individuals were included in the study, in which AFB1‐albumin adduct levels were measured in sera. Metabolic conditions included diabetes, obesity, central obesity, metabolic syndrome, and NAFLD. Crude and adjusted prevalence odds ratios (PORs) and 95% confidence intervals (95% CI) were estimated for the associations between the metabolic conditions and AFB1‐albumin adduct levels categorized into quartiles. Results The study found a significant association between AFB1‐albumin adduct levels and diabetes (Q4 vs Q1 POR = 3.74, 95%CI: 1.71‐8.19; P‐trend .003). No associations were observed between AFB1‐albumin adduct levels and the other conditions. Conclusions As diabetes is the metabolic condition most consistently linked to HCC, the possible association between AFB1 exposure and diabetes may be of public health importance. Further studies are warranted to replicate the findings and examine potential mechanisms.

Extra virgin olive oil (EVOO) has proven to yield a better health outcome than other saturated fats widely used in the Western diet, including a distinct dysbiosis-preventive modulation of gut microbiota. Besides its high content in unsaturated fatty acids, EVOO also has an unsaponifiable polyphenol-enriched fraction that is lost when undergoing a depurative process that gives place to refined olive oil (ROO). Comparing the effects of both oils on the intestinal microbiota of mice can help us determine which benefits of EVOO are due to the unsaturated fatty acids, which remain the same in both, and which benefits are a consequence of its minority compounds, mainly polyphenols. In this work, we study these variations after only six weeks of diet, when physiological changes are not appreciated yet but intestinal microbial alterations can already be detected. Some of these bacterial deviations correlate in multiple regression models with ulterior physiological values, at twelve weeks of diet, including systolic blood pressure. Comparison between the EVOO and ROO diets reveals that some of these correlations can be explained by the type of fat that is present in the diet, while in other cases, such as the genus Desulfovibrio, can be better understood if the antimicrobial role of the virgin olive oil polyphenols is considered.

Background: The COVID-19 pandemic presents a challenge to health care for patients with chronic diseases, especially hypertension, because of the important association and increased risk of these patients with a severe presentation of COVID-19 disease. The Guatemalan Ministry of Health has been implementing a multi-component program aimed at improving hypertension control in rural communities since 2019 as a part of an intervention research cluster randomized trial. When the first cases of COVID-19 were reported (March 13, 2020) in Guatemala, our study paused all study field activities, and began monitoring participants through phone calls. The objective of this paper is to describe the approach used to monitor study participants during the COVID-19 pandemic and compare data obtained during phone calls for intervention and control group participants. Methods: We developed a cross-sectional study within the HyTREC (Hypertension Outcomes for T4 Research within Lower Middle-Income Countries) project ‘Multicomponent Intervention to Improve Hypertension Control in Central America: Guatemala’ in which phone calls were made to participants from both intervention and control groups to monitor measures important to the study: delivery of antihypertensive medications in both groups, receipt of coaching sessions and use of a home blood pressure monitor by intervention group participants, as well as reasons that they were not implemented. Results: Regarding the delivery of antihypertensive drugs by the MoH to participants, those in the intervention group had a higher level of medication delivery (73%) than the control group (51%), p

Using the concept of a fractional derivative, in Caputo’s sense, we derive and solve a fractional differential equation that models the deflection of beams. The scheme to introduce the fractional concept can be used for different situations; in the article, we only consider four cases as an example of its usefulness. In addition, we establish a relationship between the fractional index and the level of stiffness (or flexibility) of the material with which the beam is made.

Brain dopamine, in relation to the limbic system, is involved in cognition and emotion. These functions are asymmetrically processed. Hypertension not only alters such functions but also their asymmetric brain pattern as well as their bilateral pattern of neurovisceral integration. The central and peripheral renin-angiotensin systems, particularly the aminopeptidases involved in its enzymatic cascade, play an important role in blood pressure control. In the present study, we report how these aminopeptidases from left and right cortico-limbic locations, plasma and systolic blood pressure interact among them in spontaneously hypertensive rats (SHR) unilaterally depleted of dopamine. The study comprises left and right sham and left and right lesioned (dopamine-depleted) rats as research groups. Results revealed important differences in the bilateral behavior comparing sham left versus sham right, lesioned left versus lesioned right, and sham versus lesioned animals. Results also suggest an important role for the asymmetrical functioning of the amygdala in cardiovascular control and an asymmetrical behavior in the interaction between the medial prefrontal cortex, hippocampus and amygdala with plasma, depending on the left or right depletion of dopamine. Compared with previous results of a similar study in Wistar-Kyoto (WKY) normotensive rats, the asymmetrical behaviors differ significantly between both WKY and SHR strains.

Multiple targeted therapies are currently explored for pediatric and young adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. However, this new armamentarium of therapies faces an old problem: choosing the right treatment for each patient. The lack of predictive biomarkers is particularly worrying for pediatric patients since it impairs the implementation of new treatments in the clinic. In this study, we used the functional assay dynamic BH3 profiling (DBP) to evaluate two new treatments for BCP-ALL that could improve clinical outcome, especially for relapsed patients. We found that the MEK inhibitor trametinib and the multi-target tyrosine kinase inhibitor sunitinib exquisitely increased apoptotic priming in an NRAS-mutant and in a KMT2A-rearranged cell line presenting a high expression of FLT3, respectively. Following these observations, we sought to study potential adaptations to these treatments. Indeed, we identified with DBP anti-apoptotic changes in the BCL-2 family after treatment, particularly involving MCL-1 – a pro-survival strategy previously observed in adult cancers. To overcome this adaptation, we employed the BH3 mimetic S63845, a specific MCL-1 inhibitor, and evaluated its sequential addition to both kinase inhibitors to overcome resistance. We observed that the metronomic combination of both drugs with S63845 was synergistic and showed an increased efficacy compared to single agents. Similar observations were made in BCP-ALL KMT2A-rearranged PDX cells in response to sunitinib, showing an analogous DBP profile to the SEM cell line. These findings demonstrate that rational sequences of targeted agents with BH3 mimetics, now extensively explored in clinical trials, may improve treatment effectiveness by overcoming anti-apoptotic adaptations in BCP-ALL.

Aflatoxin B1 (AFB1) is a known human hepatocarcinogen and a recent study reported elevated AFB1 levels, measured by serum albumin biomarkers, among Guatemalan adults. While AFB1 can contaminate a variety of foodstuffs, including maize, Guatemala’s main dietary staple, the relationship of maize intake to serum AFB1-albumin adducts levels in Guatemala has not been previously examined. As a result, a cross-sectional study was conducted among 461 Guatemalan adults living in five geographically distinct departments of the country. Participants provided a serum sample and completed a semi-quantitative food frequency questionnaire and a sociodemographic questionnaire. Multiple linear regression analysis was used to estimate the least square means (LSQ) and 95% confidence intervals (95% CI) of log-transformed AFB1-albumin adducts by quintiles of maize consumption in crude and adjusted models. Additionally, analyses of tortilla consumption and levels of maize processing were conducted. The median maize intake was 344.3 g per day [Interquartile Range (IQR): 252.2, 500.8], and the median serum AFB1-albumin adduct level was 8.4 pg/mg albumin (IQR: 3.8, 22.3). In adjusted analyses, there was no association between overall maize consumption and serum AFB1-albumin levels. However, there was a statistically significant association between tortilla consumption and AFB1-albumin levels (ptrend = 0.01). The LSM of AFB1-albumin was higher in the highest quintile of tortilla consumption compared to the lowest quintile [LSM:9.03 95%CI: 7.03,11.70 vs 6.23, 95%CI: 4.95,8.17, respectively]. These findings indicate that tortilla may be an important source of AFB1 exposure in the Guatemalan population. Therefore, efforts to control or mitigate AFB1 levels in contaminated maize used for tortillas may reduce overall exposure in this population. Keywords: Aflatoxins, Maize, Tortilla, Consumption, Guatemala

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. It arises during development of the sympathetic nervous system. Netrin-4 (NTN4), a laminin-related protein, has been proposed as a key factor to target NB metastasis, although there is controversy about its function. Here, we show that NTN4 is broadly expressed in tumor, stroma and blood vessels of NB patient samples. Furthermore, NTN4 was shown to act as a cell adhesion molecule required for the migration induced by Neogenin-1 (NEO1) in SK-N-SH neuroblastoma cells. Therefore, we propose that NTN4, by forming a ternary complex with Laminin γ1 (LMγ1) and NEO1, acts as an essential extracellular matrix component, which induces the migration of SK-N-SH cells.

En este artículo se analiza el efecto de las advertencias sanitarias con pictogramas en la demanda de tabaco de México. Se estiman los modelos de demanda convencional, miope y racional con una serie de tiempo trimestral de 1994 a 2013, usando mínimos cuadrados ordinarios y mínimos cuadrados en dos etapas con variables instrumentales. Se aplica el método de Prais-Winsten para corregir autocorrelación y se estiman errores robustos para corregir heteroscedasticidad. Se encontró evidencia de que la segunda y tercera rondas de pictogramas causaron una reducción significativa en el consumo de aproximadamente una cajetilla de cigarros per cápita. La política regulatoria de empaquetado y etiquetado de cajetillas de cigarro ha sido efectiva para reducir la demanda de tabaco en México.

El objetivo de este artículo es analizar cómo las ligas femeninas de distintos Estados de la República de México se dotaron de entidad jurídica y se constituyeron en sujeto político reivindicativo que, junto a la lucha por los derechos de las mujeres, reivindicó otro tipo de mejoras materiales como reducir las altas tasas de alcoholismo y mejorar las condiciones de salubridad en sus localidades. Concretamente se estudiarán aquellos grupos y asambleas impulsados por o vinculados al Frente Único Pro Derechos de la Mujer (1935-1940) y al Bloque Nacional de Mujeres Revolucionarias (1940-1946) durante los gobiernos de Lázaro Cárdenas y Manuel Ávila Camacho.

Summary: Background: Approximately 80% of the 463 million adults worldwide with diabetes live in low-income and middle-income countries (LMICs). A major obstacle to designing evidence-based policies to improve diabetes outcomes in LMICs is the scarce availability of nationally representative data on the current patterns of treatment coverage. The objectives of this study were to estimate the proportion of adults with diabetes in LMICs who receive coverage of recommended pharmacological and non-pharmacological diabetes treatment; and to describe country-level and individual-level characteristics that are associated with treatment. Methods: We did a cross-sectional analysis of pooled, individual data from 55 nationally representative surveys in LMICs. Our primary outcome of self-reported diabetes treatment coverage was based on population-level monitoring indicators recommended in the 2020 WHO Package of Essential Noncommunicable Disease Interventions. Surveys were included if they were done in 2008 or after in an LMIC, as classified by the World Bank in the year the survey was done; were nationally representative; had individual-level data; contained a diabetes biomarker (fasting glucose, random glucose, or glycated haemoglobin); and had data on one or more diabetes treatments. Our sample included non-pregnant individuals with an available diabetes biomarker who were at least 25 years of age. We assessed coverage of three pharmacological and three non-pharmacological treatments among people with diabetes. At the country level, we estimated the proportion of individuals reporting coverage by per-capita gross national income and geographical region. At the individual level, we used logistic regression models to assess coverage along several key individual characteristics including sex, age, body-mass index, wealth quintile, and educational attainment. In the primary analysis, we scaled sample weights such that countries were weighted equally. Findings: The final pooled sample from the 55 LMICs included 680 102 total individuals and 37 094 individuals with diabetes. Using equal weights for each country, diabetes prevalence was 9·0% (95% CI 8·7–9·4), with 43·9% (41·9–45·9) reporting a previous diabetes diagnosis. Overall, 4·6% (3·9–5·4) of individuals with diabetes self-reported meeting need for all treatments recommended for them. Coverage of glucose-lowering medication was 50·5% (48·6–52·5); antihypertensive medication was 41·3% (39·3–43·3); cholesterol-lowering medication was 6·3% (5·5–7·2); diet counselling was 32·2% (30·7–33·7); exercise counselling was 28·2% (26·6–29·8); and weight-loss counselling was 31·5% (29·3–33·7). Countries at higher-income levels tended to have greater coverage. Female sex and higher age, body-mass index, educational attainment, and household wealth were also associated with greater coverage. Interpretation: Fewer than one in ten people with diabetes in LMICs receive coverage of guideline-based comprehensive diabetes treatment. Scaling up the capacity of health systems to deliver treatment not only to lower glucose but also to address cardiovascular disease risk factors, such as hypertension and high cholesterol, are urgent global diabetes priorities. Funding: National Clinician Scholars Program at the University of Michigan Institute for Healthcare Policy & Innovation, National Institute of Diabetes and Digestive and Kidney Diseases, Harvard Catalyst, and National Center for Advancing Translational Sciences of the National Institutes of Health.

Objectives Few studies have used longitudinal data to study the development of cognition over the life course in low-income and middle-income countries. The objectives of this study were to assess predictors of cognitive development trajectories from 6 months through 7 years, and if these trajectories predicted adult cognitive function in a birth cohort from Guatemala.Design We analysed data from the INCAP Nutrition Supplementation Trial Longitudinal Study in Guatemala. Cognition was assessed at eight different time points between 6 months and 7 years. We derived childhood development trajectories using latent class growth analysis. We assessed predictors of the trajectories using ordinal logistic regression, and associations between childhood trajectories and adult non-verbal intelligence and literacy at age 18–52 years (mean±SD =42.7±6.4 years) using mixed models.Setting The study was conducted in four Guatemalan villages.Participants The study included 927 participants from Guatemala with repeated measurements of cognitive function during the first 7 years of life.Results We identified three trajectories of cognitive development (high: n=214, average: n=583, low: n=130). Participants whose mothers were taller (proportional log odds (PO)=0.03, 95% CI=0.01 to 0.06), had more years of schooling (PO=0.15, 95% CI=0.06 to 0.25), or lived in households with higher socioeconomic scores (PO=0.19, 95% CI=0.09 to 0.29) were more likely to follow higher trajectories. Childhood trajectories predicted adult non-verbal intelligence (high=18.4±0.3, average=14.6±0.53, low=11.4±0.9) and literacy (high=63.8±2.0, average=48.6±1.2, low=33.9± 2.6) scores.Conclusions In this sample from Guatemala, cognitive development trajectories from 6 months through 7 years were associated with adult non-verbal intelligence and literacy. These findings provide evidence of tracking of cognition over time in a transitioning low-income setting.

Las estrategias educativas y pedagógicas del Centro Internacional de Investigación de Economía Social y Solidaria (CIIESS) están orientadas a impulsar las actividades socioeconómicas a partir del fortalecimiento de la interculturalidad y las capacidades de los movimientos sociales de base como actores protagonistas de una economía alternativa distinta al modelo económico neoliberal capitalista.