MEJORANDO LA SALUD HUMANA: ENFOQUE DE PROMOCIÓN DE LA SALUD, PREVENCIÓN DE LA ENFERMEDAD Y EDUCACIÓN EN SALUD

Objetivos: Refexionar sobre los avances de la promoción de la salud y prevención de la enfermedad, la educación en salud y los retos en la formación de los estudiantes en medicina y salud publica en América Latina. Métodos: Se realizó revisión de bases de datos sobre promoción de la salud, prevención de la enfermedad, educación en salud, educación y formación en medicina, atención primaria en salud, se tomó las últimas dos décadas para llegar a conclusiones diseñadas a fortalecer la formación educativa de médicos y especialistas en promoción de la salud. Resultados: La promoción de la salud y prevención de enfermedad y el componente educación han tenido legado de distintas declaraciones y conferencias internacionales y han defnido estrategias y acciones claras que van desde acciones intersectoriales y un compromiso en las instituciones formadoras de recursos en salud. La educación en salud ha fortalecido los programas de promoción y prevención de ahí que el reto de instituciones directivas de la salud y formadoras de recursos humanos en salud han trabajado guías y materiales educativos que han sido considerados fundamentales para el trabajo con los determinantes sociales de la salud. Conclusiones: En esta revisión se destaca el aporte de los países para el trabajo en promoción de la salud y prevención de la enfermedad, dejando claro el esfuerzo que realizan instituciones rectoras de salud y formadoras de recursos para fortalecer los currículos educativos, sin embargo se requiere continuar con este tipo de iniciativas para fortalecer los currículos de salud.   DOI:https://doi.org/10.25176/RFMH.v16.n3.65

The role of the interactome in the maintenance of deleterious variability in human populations

Recent genomic projects have revealed the existence of an unexpectedly large amount of deleterious variability in the human genome. Several hypotheses have been proposed to explain such an apparently high mutational load. However, the mechanisms by which deleterious mutations in some genes cause a pathological effect but are apparently innocuous in other genes remain largely unknown. This study searched for deleterious variants in the 1,000 genomes populations, as well as in a newly sequenced population of 252 healthy Spanish indi-viduals. In addition, variants causative of monogenic diseases and somatic variants from 41 chronic lymphocytic leukaemia patients were analysed. The deleterious variants found were analysed in the context of the interactome to understand the role of network topology in the maintenance of the observe

How Prosecutors and Defense Attorneys Differ in Their Use of Neuroscience Evidence

Much of the public debate surrounding the intersection of neuroscience and criminal law is based on assumptions about how prosecutors and defense attorneys differ in their use of neuroscience evidence. For example, according to some commentators, the defense’s use of neuroscience evidence will abdicate criminals of all responsibility for their offenses. In contrast, the prosecution’s use of that same evidence will unfairly punish the most vulnerable defendants as unfixable future dangers to society. This “double- edged sword” view of neuroscience evidence is important for flagging concerns about the law’s construction of criminal responsibility and punishment: it demonstrates that the same information about the defendant can either be mitigating or aggravating depending on who is raising it. Yet empirical assessments of legal decisions reveal a far more nuanced reality, showing that public beliefs about the impact of neuroscience on the criminal law can often be wrong. This Article takes an evidence-based and multidisciplinary approach to examining how courts respond to neuroscience evidence in capital cases when the defense presents it to argue that the defendant’s mental state at the time of the crime was below the given legal requisite due to some neurologic or cognitive deficiency

CellPhoneDB v5: inferring cell-cell communication from single-cell multiomics data

Cell-cell communication is essential for tissue development, regeneration and function, and its disruption can lead to diseases and developmental abnormalities. The revolution of single-cell genomics technologies offers unprecedented insights into cellular identities, opening new avenues to resolve the intricate cellular interactions present in tissue niches. CellPhoneDB is a bioinformatics toolkit designed to infer cell-cell communication by combining a curated repository of bona fide ligand-receptor interactions with a set of computational and statistical methods to integrate them with single-cell genomics data. Importantly, CellPhoneDB captures the multimeric nature of molecular complexes, thus representing cell-cell communication biology faithfully. Here we present CellPhoneDB v5, an updated version of the tool, which offers several new features. Firstly, the repository has been expanded by one-third with the addition of new interactions. These encompass interactions mediated by non-protein ligands such as endocrine hormones and GPCR ligands. Secondly, it includes a differentially expression-based methodology for more tailored interaction queries. Thirdly, it incorporates novel computational methods to prioritise specific cell-cell interactions, leveraging other single-cell modalities, such as spatial information or TF activities (i.e. CellSign module). Finally, we provide CellPhoneDBViz, a module to interactively visualise and share results amongst users. Altogether, CellPhoneDB v5 elevates the precision of cell-cell communication inference, ushering in new perspectives to comprehend tissue biology in both healthy and pathological states.Comment: 30 pages, 3 figures and 2 tables. Added previously missing figures and tables; Updated the reference for 'An integrated single-cell reference atlas of the human endometrium' pape

CMV hyperimmune globulin as salvage therapy for recurrent or refractory CMV infection in children undergoing hematopoietic stem cell transplantation

Children; Cytomegalovirus; Hematopoietic stem cell transplantationNens; Citomegalovirus; Trasplantament de cèl·lules mare hematopoètiquesNiños; Citomegalovirus; Trasplante de células madre hematopoyéticasCytomegalovirus (CMV) is a major cause of allogeneic hematopoietic stem cell transplant (HSCT)-related morbidity and mortality. Treatment failure continues to be a major issue in patients with CMV infection due to both drug resistance and intolerance. This single-center brief retrospective analysis of a case series aims to investigate the safety and efficacy of CMV-hyperimmune globulin as salvage therapy for CMV infection in children undergoing HSCT. Fifteen pediatric patients received human CMV-specific immunoglobulin (CMVIG) between July 2018 and December 2021 as a salvage therapy for refractory or recurrent CMV infection. At the time of CMVIG prescription, eight children presented with recurrent CMV infection and seven with refractory CMV infection. The overall response rate was 67% at 50 days from the CMVIG administration [95% confidence interval (CI): 44–88]. Overall survival (OS) from CMVIG administration at 100 days was 87% (95% CI: 56–96), and OS from HSCT at 1 year was 80% (95% CI: 50–93). Four patients died, three unrelated to CMV infection and one due to CMV pneumonia. CMVIG as salvage therapy was well tolerated, and no infusion-related adverse events were observed.Biotest supported the English revision of the manuscript

Babelomics 5.0: functional interpretation for new generations of genomic data

This article has been accepted for publication in Nucleic Acids Research Published by Oxford University Press.Babelomics has been running for more than one decade offering a user-friendly interface for the functional analysis of gene expression and genomic data. Here we present its fifth release, which includes support for Next Generation Sequencing data including gene expression (RNA-seq), exome or genome resequencing. Babelomics has simplified its interface, being now more intuitive. Improved visualization options, such as a genome viewer as well as an interactive network viewer, have been implemented. New technical enhancements at both, client and server sides, makes the user experience faster and more dynamic. Babelomics offers user-friendly access to a full range of methods that cover: (i) primary data analysis, (ii) a variety of tests for different experimental designs and (iii) different enrichment and network analysis algorithms for the interpretation of the results of such tests in the proper functional context. In addition to the public server, local copies of Babelomics can be downloaded and installed. Babelomics is freely available at: http://www.babelomics.org.Spanish Ministry of Economy and Competitiveness [BIO2011-27069], Conselleria d'Educacio of the Valencian Community [PROMETEOII/2014/025]; EU FP7-PEOPLE Project MLPM [316861]; Fundació la Marató TV3 [151/C/2013]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [BIO2011-27069]

Pathogenic variants in the human m(6)A reader YTHDC2 are associated with primary ovarian insufficiency

Primary ovarian insufficiency (POI) affects 1% of women and carries significant medical and psychosocial sequelae. Approximately 10% of POI has a defined genetic cause, with most implicated genes relating to biological processes involved in early fetal ovary development and function. Recently, Ythdc2, an RNA helicase and N6-methyladenosine reader, has emerged as a regulator of meiosis in mice. Here, we describe homozygous pathogenic variants in YTHDC2 in 3 women with early-onset POI from 2 families: C. 2567C>G, p.P856R in the helicase-associated (HA2) domain and c.1129G>T, p.E377*. We demonstrated that YTHDC2 is expressed in the developing human fetal ovary and is upregulated in meiotic germ cells, together with related meiosisassociated factors. The p.P856R variant resulted in a less flexible protein that likely disrupted downstream conformational kinetics of the HA2 domain, whereas the p.E377*variant truncated the helicase core. Taken together, our results reveal that YTHDC2 is a key regulator of meiosis in humans and pathogenic variants within this gene are associated with POI

A novel thymidylate synthase from the Vibrionales, Alteromonadales, Aeromonadales, and Pasteurellales (VAAP) clade with altered nucleotide and folate binding sites

Thymidylate synthase (TS, E.C. 2.1.1.45) is a crucial enzyme for de novo deoxythymidine monophosphate (dTMP) biosynthesis. The gene for this enzyme is thyA, which encodes the folate-dependent TS that converts deoxyuridine monophosphate group (dUMP) into (dTMP) using the cofactor 5,10-methylenetetrahydrofolate (mTHF) as a carbon donor. We identified the thyA gene in the genome of the Vibrio parahaemolyticus strain FIM-S1708+ that is innocuous to humans but pathogenic to crustaceans. Surprisingly, we found changes in the residues that bind the substrate dUMP and mTHF, previously postulated as invariant among all TSs known (Finer-Moore, Santi & Stroud, 2003). Interestingly, those amino acid changes were also found in a clade of microorganisms that contains Vibrionales, Alteromonadales, Aeromonadales, and Pasteurellales (VAAP) from the Gammaproteobacteria class. In this work, we studied the biochemical properties of recombinant TS from V. parahemolyticus FIM-S1708+ (VpTS) to address the natural changes in the TS amino acid sequence of the VAAP clade. Interestingly, the Km for dUMP was 27.3 ± 4.3 µM, about one-fold larger compared to other TSs. The Km for mTHF was 96.3 ± 18 µM, about three- to five-fold larger compared to other species, suggesting also loss of affinity. Thus, the catalytic efficiency was between one or two orders of magnitude smaller for both substrates. We used trimethoprim, a common antibiotic that targets both TS and DHFR for inhibition studies. The IC50 values obtained were high compared to other results in the literature. Nonetheless, this molecule could be a lead for the design antibiotics towards pathogens from the VAAP clade. Overall, the experimental results also suggest that in the VAAP clade the nucleotide salvage pathway is important and should be investigated, since the de novo dTMP synthesis appears to be compromised by a less efficient thymidylate synthase