[Molecular characterization of Listeria monocytogenes isolates from human and food sources in Argentina, 2018-2023]. / Caracterización molecular de aislamientos de Listeria monocytogenes de origen humano y alimentario en Argentina, 2018-2023.

Human listeriosis is an infectious disease caused by Listeria monocytogenes. The invasive form of this disease leads to a high rate of hospitalizations and fatality. The main mode of transmission is through contaminated ready-to-eat foods such as dairy, vegetables and meat products. The knowledge of the diversity and population dynamics of isolates collected from human and food sources is essential for the detection of clusters and the identification of common sites of infection. The aim of this study was the molecular characterization of L. monocytogenes isolates in Argentina. We sequenced a total of 63 isolates, 35 from human and 28 from food sources, collected between 2018 and 2023. Our genomic study divided the isolates into two lineages, four serogroups, 17 sequence types and 15 clonal complexes (CCs). The hypervirulent clone CC1 (lineage I; serogroup IVb) predominated in human and food samples. The phylogenomic analysis showed a high and possible epidemiological relationship between isolates from human and/or food sources, suggesting the presence of transmission chains in our country. These findings highlight the need to strengthen genomic surveillance of L. monocytogenes in Argentina. The identification of geographic distribution and characteristics of predominant and emerging clones from human and food sources might help to focus action plans and public health policies better directed at the control and prevention of listeriosis.

First molecular characterization of Escherichia coli O157:H7 isolates from clinical samples in Paraguay using whole-genome sequencing.

Escherichia coli O157:H7 is a foodborne pathogen implicated in numerous outbreaks worldwide that has the ability to cause extra-intestinal complications in humans. The Enteropathogens Division of the Central Public Health Laboratory (CPHL) in Paraguay is working to improve the genomic characterization of Shiga toxin-producing E. coli (STEC) to enhance laboratory-based surveillance and investigation of foodborne disease outbreaks. Whole genome sequencing (WGS) is proposed worldwide to be used in the routine laboratory as a high-resolution tool that allows to have all the results in a single workflow. This study aimed to carry out for the first time, the genomic characterization by WGS of nine STEC O157:H7 strains isolated from human samples in Paraguay. We were able to identify virulence and resistance mechanisms, MLST subtype, and even establish the phylogenetic relationships between isolates. Furthermore, we detected the presence of strains belonging to hypervirulent clade 8 in most of the isolates studied.

Bayesian network analysis of plasma microRNA sequencing data in patients with venous thrombosis.

MicroRNAs (miRNAs) are small regulatory RNAs participating to several biological processes and known to be involved in various pathologies. Measurable in body fluids, miRNAs have been proposed to serve as efficient biomarkers for diseases and/or associated traits. Here, we performed a next-generation-sequencing based profiling of plasma miRNAs in 344 patients with venous thrombosis (VT) and assessed the association of plasma miRNA levels with several haemostatic traits and the risk of VT recurrence. Among the most significant findings, we detected an association between hsa-miR-199b-3p and haematocrit levels (P = 0.0016), these two markers having both been independently reported to associate with VT risk. We also observed suggestive evidence for association of hsa-miR-370-3p (P = 0.019), hsa-miR-27b-3p (P = 0.016) and hsa-miR-222-3p (P = 0.049) with VT recurrence, the observations at the latter two miRNAs confirming the recent findings of Wang et al. Besides, by conducting Genome-Wide Association Studies on miRNA levels and meta-analyzing our results with some publicly available, we identified 21 new associations of single nucleotide polymorphisms with plasma miRNA levels at the statistical significance threshold of P < 5 × 10-8, some of these associations pertaining to thrombosis associated mechanisms. In conclusion, this study provides novel data about the impact of miRNAs' variability in haemostasis and new arguments supporting the association of few miRNAs with the risk of recurrence in patients with venous thrombosis.

Los micro-ARN (miARN) son pequeñas moléculas de ARN reguladoras que participan en varios procesos biológicos y están implicados en diversas patologías. Mensurables en los líquidos corporales, se ha planteado que los miARN pueden ser biomarcadores eficaces para el diagnóstico de enfermedades y/o características asociadas. Aquí hemos llevado a cabo un análisis de miARN plasmático con tecnología de secuenciación de última generación en 344 pacientes con trombosis venosa (TV) y hemos evaluado la asociación de los niveles de miARN con distintas características hemostáticas y el riesgo de recidiva de TV. Entre los hallazgos más significativos, hemos detectado una asociación entre hsa-miR-199b-3p y los niveles de hematocritos (p = 0,0016); dos marcadores que se habían asociado de forma independiente con el riesgo de sufrir TV. Asimismo, hemos observado una evidencia indicativa de asociación entre hsa-miR-370-3p (p = 0,019), hsa-miR-27b-3p (p = 0,016) y hsa-miR-222-3p (p = 0,049) y la recidiva de TV; los resultados los dos últimos miARN confirman los hallazgos recientes de Wang et al. (Clin Epigenetics, 2019). Además, al efectuar estudios de asociación del genoma completo sobre los niveles de miARN y al metaanalizar nuestros resultados con otros disponibles públicamente, hemos identificado 21 asociaciones nuevas de polimorfismos de un solo nucleótido (PSN) con niveles de miARN plasmático con un umbral de significación estadística de p < 5 × 10−8; algunas de estas asociaciones pertenecen a los mecanismos patogénicos de la trombosis.Como conclusión, en este estudio se proporcionan nuevos datos sobre el impacto de la variabilidad de miARN en la hemostasia y nuevos argumentos que apoyan la asociación de algunas secuencias de miARN con el riesgo de recidiva en pacientes con trombosis venosa.

Salmonella Typhi genomics: envisaging the future of typhoid eradication.

Next-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding have transformed the field of molecular microbiology, epidemiology, infection treatments and vaccine developments. We review the key findings of the publicly accessible genomes of Salmonella enterica serovar Typhi since the first complete genome to the most recent release of thousands of Salmonella Typhi genomes, which remarkably shape the genomic research of S. Typhi and other pathogens. Important new insights acquired from the genome sequencing of S. Typhi, pertaining to genomic variations, evolution, population structure, antibiotic resistance, virulence, pathogenesis, disease surveillance/investigation and disease control are discussed. As the numbers of sequenced genomes are increasing at an unprecedented rate, fine variations in the gene pool of S. Typhi are captured in high resolution, allowing deeper understanding of the pathogen's evolutionary trends and its pathogenesis, paving the way to bringing us closer to eradication of typhoid through effective vaccine/treatment development.

[Current perspectives on genome-based diagnostic tests in Pediatrics]. / Perspectivas actuales sobre el diagnóstico genómico en pediatría.

Etiological diagnosis is essential in the clinical management of individual patients. Some children with complex medical conditions are subjected to numerous testing, known as "diagnostic odyssey", which often gives no conclusive results. In recent years, a revolution in genomic medicine is underway with the use of technologies that promise to increase the ability to make a diagnosis and reduce the time involved. The main advantages and limitations of genomic diagnosis, as opposed to usual methodologies are reviewed with an emphasis on Pediatrics.

[Genetic predisposition and Pediatric Acute Respiratory Distress Syndrome: New tools for genetic study]. / Predisposición genética y síndrome de distrés respiratorio agudo pediátrico: nuevas herramientas de estudio genético.

Acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure. Theoretically, any acute lung condition can lead to ARDS, but only a small percentage of individuals actually develop the disease. On this basis, genetic factors have been implicated in the risk of developing ARDS. Based on the pathophysiology of this disease, many candidate genes have been evaluated as potential modifiers in patient, as well as in animal models, of ARDS. Recent experimental data and clinical studies suggest that variations of genes involved in key processes of tissue, cellular and molecular lung damage may influence susceptibility and prognosis of ARDS. However, the pathogenesis of pediatric ARDS is complex, and therefore, it can be expected that many genes might contribute. Genetic variations such as single nucleotide polymorphisms and copy-number variations are likely associated with susceptibility to ARDS in children with primary lung injury. Genome-wide association (GWA) studies can objectively examine these variations, and help identify important new genes and pathogenetic pathways for future analysis. This approach might also have diagnostic and therapeutic implications, such as predicting patient risk or developing a personalized therapeutic approach to this serious syndrome.

Epidemiological changes in invasive Streptococcus pyogenes infection during the UK alert period: A molecular comparative analysis from a tertiary Spanish hospital in 2023.

OBJECTIVES: To study the genomic epidemiology of Streptococcus pyogenes causing bloodstream infections (GAS-BSI) in a Spanish tertiary hospital during the United Kingdom invasive S. pyogenes outbreak alert. METHODS: Retrospective epidemiological analysis of GAS-BSI during the January-May 2017-2023 period. WGS was performed using Ion torrent GeneStudio™ S5 system for emm typing and identification of superantigen genes in S. pyogenes isolated during the 2022-2023 UK outbreak alert. RESULTS: During 2023, there were more cases of GAS-BSI compared to the same period of previous year with a non-significant increase in children. Fourteen isolates were sequenced. The emm1 (6/14, 42.9%) and emm12 (2/14, 14.3%) types predominated; 5 of 6 (75%) emm1 isolates were from the M1UK clone. The most detected superantigen genes were speG (12/14, 85.7%), speC (10/14, 71.4%), speJ (7/14, 50%), and speA (5/15, 33.3%). speA and speJ were predominant in M1UK clone. CONCLUSIONS: Our genomic epidemiology in 2023 is similar to the reported data from the UK outbreak alert in the same period and different from previous national S. pyogenes surveillance reports.

Population structure of Neisseria meningitidis ST-9493 identified in Colombian isolates.

INTRODUCTION: Neisseria meningitidis is associated with invasive infections causing high mortality rates. The objective of this study was to describe the population structure of Colombian invasive isolates with ST-9493, a potentially emerging clonal group in the country. METHODS: The complete genomes of 34 invasive isolates of serogroup B with ST-9493 and its variants at one or two loci were sequenced by Illumina to describe the phenotypic and genotypic characteristics of these isolates. RESULTS: The relationship of a clonal group associated with ST-136 CC41/44 was phylogenetically established, identifying two main clades composed of isolates from an outbreak or endemic. The most frequent alleles and peptides included porA 17, porB 44, fHbp 2.24, NHBA 10, and the FetA F5-17 variant. Most of the isolates were susceptible to the antibiotics evaluated. CONCLUSION: This study shows that meningococcal isolates with ST-9493 are an autochthonous clonal group with population dynamics and the capacity to cause endemic and epidemic meningococcal disease in Colombia.

Phenotypic plasticity and archetype: a response to common objections to the biological theory of archetype and instinct.

Since Jung's death in 1961, scholars have attempted to integrate growing biological science data into Jungian concepts such as the collective unconscious, instincts and the archetypes. This enterprise has been challenging due to persistent false dichotomies of gene and environment occasionally arising. Recent works by Roesler (2022a, 2022b) for example, have raised objections to the biological theory of archetypes, but the objections are plagued by such dichotomies. The concept of phenotypic plasticity, however, helps to both avoid this problem as well as bridge the gap between competing theories into a more integrated model with solid biological foundations.

Depuis la mort de Jung en 1961, les chercheurs ont tenté d'intégrer les données nouvelles de la biologie avec les concepts Jungiens tels que l'inconscient collectif, les instincts et les archétypes. Cette initiative a rencontré des difficultés car des dichotomies fausses mais tenaces sur le sujet des gènes et de l'environnement se manifestaient. Les travaux récents de Roesler (2022a, 2022b) par exemple ont exprimé des objections à la théorie biologique des archétypes. Cependant ces objections sont biaisées par les dichotomies mentionnées. Le concept de plasticité phénotypique, cependant, aide à la fois à éviter ce problème et à former une passerelle entre des théories rivales et un modèle mieux intégré et doté de solides fondements biologiques.

Desde la muerte de Jung en 1961, académicos han intentado integrar data creciente de las ciencias biológicas a conceptos Junguianos como inconsciente colectivo, instintos y arquetipos. Esta empresa ha sido desafiada debido al surgimiento ocasional de persistentes falsas dicotomías entre genes y medio ambiente. Trabajos recientes de Roesler (2022a, 2022b), por ejemplo, han planteado objeciones a la teoría biológica del arquetipo, pero las objeciones se encuentran afectadas por semejantes dicotomías. El concepto de plasticidad fenotípica, sin embargo, ayuda a evitar este problema, así como a subsanar la brecha entre teorías contrapuestas, hacia un modelo más integrado con fundamentos biógicos sólidos.

Archetypes and clinical application: how the genome responds to experience.

The continuing dialogue within analytical psychology regarding the relationship to Jung's "collective unconscious" and biological research calls for a more sophisticated treatment of terminology that is consilient with modern neurogenetics. This essay explores how fully understanding the way genome and environment interact can help us parse out clinical material, enabling us to judge what expressions are repeats of early experiences vs. what are innately driven re-organizations of experience.

Le dialogue qui se poursuit dans la psychologie analytique au sujet de la relation entre 'l'inconscient collectif' de Jung et la recherche en biologie appelle à un traitement plus sophistiqué de la terminologie qui soit consilient avec la neurogénétique moderne. Cet article explore comment une pleine compréhension de la manière dont le génome et l'environnement interagissent peut nous aider à analyser le matériel clinique, nous rendant capables de juger quelles expressions sont des répétitions d'expériences précoces et lesquelles sont par contre des réorganisations de l'expérience résultant de l'inné.

El diálogo continuo, al interior de la psicología analítica, acerca de la relación del inconsciente colectivo de Jung y la investigación biológica demanda un tratamiento más sofisticado de la terminología, concordante con la neurogenética moderna. El presente ensayo explora como la plena comprensión del modo en que el genoma y el entorno interactúan puede ayudarnos a analizar el material clínico, permitiéndonos juzgar que expresiones son repeticiones de experiencias tempranas y cuales son reorganizaciones de la experiencia motivadas de manera innata.

Archetypes and the 'impoverished environment' argument: a response to Goodwyn (2020).

Goodwyn's (2020) paper 'Archetypes and the "Impoverished Genome" argument: updates from evolutionary genetics' continues the ongoing discussion forged in this Journal to do with the bio-genetic, socio-cultural and environmental underpinnings to archetypal experience. Goodwyn's central focus considers the way in which the genome and environment both contribute causally to the development of the collective unconscious across the lifespan, arguing that others in the debate have minimized the genome's contribution. This paper contrasts the research evidence Goodwyn outlines with contemporary gene-environment coaction research within the psychological domain, concluding that the issue may be more one of emphasis by showing that both genome and environment are important in the activation of archetypal imagery. This highlights that 'pre-formationism' (as some kind of automatic archetypal read-out mechanism) and the idea of 'autochthonous revival' of archetypes are suspect concepts, and this needs to be taken into account in clinical work. Furthermore, the central issue as to which is causally more significant in generating archetypal imagery, the genome or the environment, will be examined. Illustrative examples of the importance of environmental input in activating archetypal imagery are presented from Jung's own life experience, alongside a contemporary case, as well as with an historical case of Jung's.

L'article de Goodwyn (2020) « Les Archétypes et le débat sur le 'Génome Appauvri': les avancées récentes de la génétique évolutive ¼ poursuit la discussion ouverte lancée dans ce journal et qui concerne les fondements biogénétiques, socioculturels et environnementaux de l'expérience archétypale. L'axe principal de Goodwyn examine la manière dont le génome et l'environnement contribuent tous deux causalement au développement de l'inconscient collectif tout au long de la vie, argumentant que d'autres interlocuteurs dans ce débat avaient minimisé la contribution du génome. Cet article-ci met en contraste les éléments de la recherche soulignés par Goodwyn avec la recherche actuelle sur la coaction gène-environnement dans le domaine psychologique. La conclusion est qu'il s'agirait plutôt de là où l'on met l'accent, montrant que le génome et l'environnement sont tous deux importants dans l'activation de l'imagerie archétypale. Ceci souligne que le « préformationnisme ¼ (en tant qu'une sorte de mécanisme de lecture archétypale automatique) et l'idée de « renouveau autochtone ¼ des archétypes sont des concepts douteux, et ceci doit être pris en compte dans le travail clinique. De plus, nous examinerons la question centrale duquel est le plus significatif causalement pour générer l'imagerie archétypale, entre le génome et l'environnement. Des exemples venant de l'expérience de vie de Jung sont présentés, qui illustrent l'importance de l'apport de l'environnement pour activer l'imagerie archétypale, ainsi qu'un cas contemporain et un cas historique de Jung.

El argumento del artículo de Goodwyn (2020) 'Arquetipos y el "Genoma Empobrecido": actualizaciones desde la genética evolutiva' continúa el debate en curso forjado en esta revista respecto a los fundamentos bio-genéticos, socio-culturales y ambientales, y la experiencia arquetípica. El foco central de Goodwyn considera el modo en el cual el genoma y el ambiente, ambos contribuyen causalmente al desarrollo del inconsciente colectivo a través de la vida, argumentando que en este debate, otros han minimizado la contribución del genoma. El presente artículo contrasta la evidencia de la investigación descripta por Goodwyn con la investigación contemporánea sobre la coacción gen-ambiente en el ámbito psicológico, concluyendo que el tema puede ser una cuestión de énfasis, al mostrar que ambos genoma y ambiente son importantes en la activación de la imaginería arquetípica. Esto subraya que el 'pre-formacionismo' (como un tipo de mecanismo arquetípico automático) y la idea de 'resurgimiento autóctono' del arquetipo son conceptos sospechosos, y esto necesita ser tenido en cuenta en el trabajo clínico. Además, se examinará el tema central respecto a aquello que es causalmente más significativo en generar imaginería arquetípica, el genoma o el ambiente. Se presentan ejemplos ilustrativos sobre la importancia de estímulos del medio en activar imaginaría arquetípica a partir de la experiencia de vida de Jung, junto a un caso contemporáneo, así como también a partir de un caso histórico de Jung.

Use of next generation sequencing technologies for the diagnosis and epidemiology of infectious diseases. / Uso de las tecnologías de secuenciación masiva para el diagnóstico y epidemiología de enfermedades infecciosas.

For the first time, next generation sequencing technologies provide access to genomic information at a price and scale that allow their implementation in routine clinical practice and epidemiology. While there are still many obstacles to their implementation, there are also multiple examples of their major advantages compared with previous methods. Their main advantage is that a single determination allows epidemiological information on the causative microorganism to be obtained simultaneously, as well as its resistance profile, although these advantages vary according to the pathogen under study. This review discusses several examples of the clinical and epidemiological use of next generation sequencing applied to complete genomes and microbiomes and reflects on its future in clinical practice.

Escores de Risco Poligênico: O Próximo Passo para Melhorar a Estratificação de Risco na Doença Arterial Coronariana? / Polygenic Risk Scores: The Next Step for Improved Risk Stratification in Coronary Artery Disease?

Resumo Apesar dos avanços significativos no tratamento da doença arterial coronariana (DAC) e das reduções nas taxas de mortalidade anuais nas últimas décadas, a DAC continua sendo a principal causa de morte no mundo. Consequentemente, há uma necessidade contínua de esforços para abordar essa situação. Os algoritmos clínicos atuais para identificar pacientes em risco são particularmente imprecisos para indivíduos de risco moderado. Por esse motivo, foi sugerido que são necessários testes auxiliares, incluindo triagem genética preditiva. À medida que os estudos genéticos se expandem rapidamente e os dados genômicos se tornam mais acessíveis, diversos escores de risco genético têm sido propostos para identificar e avaliar a suscetibilidade de um indivíduo ao desenvolvimento de doenças, incluindo a DAC. De fato, o campo da genética tem contribuído substancialmente para a previsão de risco, particularmente nos casos em que as crianças têm genitores com DAC prematura, resultando em um risco aumentado de até 75%. Os escores de risco poligênico (PRSs, do inglês polygenic risk scores) surgiram como uma ferramenta potencialmente valiosa para compreender e estratificar o risco genético de um indivíduo. O PRS é calculado como uma soma ponderada de variantes de nucleotídeo único presentes em todo o genoma humano, identificáveis por meio de estudos de associação genômica ampla, e associadas a várias doenças cardiometabólicas. O uso dos PRSs é promissor, pois permite o desenvolvimento de estratégias personalizadas para prevenir ou diagnosticar patologias específicas de forma precoce. Ademais, seu uso é capaz de complementar os escores clínicos existentes, aumentando a precisão da previsão de risco individual. Consequentemente, a aplicação dos PRSs tem o potencial de impactar positivamente os custos e os desfechos adversos associados à DAC. A presente revisão narrativa oferece uma visão ampla do papel dos PRSs no contexto da DAC.

Abstract Despite significant advances in the management of coronary artery disease (CAD) and reductions in annual mortality rates in recent decades, this disease remains the leading cause of death worldwide. Consequently, there is an ongoing need for efforts to address this situation. Current clinical algorithms to identify at-risk patients are particularly inaccurate in moderate-risk individuals. For this reason, the need for ancillary tests has been suggested, including predictive genetic screening. As genetic studies rapidly expand and genomic data becomes more accessible, numerous genetic risk scores have been proposed to identify and evaluate an individual's susceptibility to developing diseases, including CAD. The field of genetics has indeed made substantial contributions to risk prediction, particularly in cases where children have parents with premature CAD, resulting in an increased risk of up to 75%. The polygenic risk scores (PRSs) have emerged as a potentially valuable tool for understanding and stratifying an individual's genetic risk. The PRS is calculated as a weighted sum of single-nucleotide variants present throughout the human genome, identifiable through genome-wide association studies, and associated with various cardiometabolic diseases. The use of PRSs holds promise, as it enables the development of personalized strategies for preventing or diagnosing specific pathologies early. Furthermore, it can complement existing clinical scores, increasing the accuracy of individual risk prediction. Consequently, the application of PRSs has the potential to impact the costs and adverse outcomes associated with CAD positively. This narrative review provides an overview of the role of PRSs in the context of CAD.

The Future of TB Resistance Diagnosis: The Essentials on Whole Genome Sequencing and Rapid Testing Methods.

Tuberculosis resistance diagnostics have vastly improved in recent years thanks to the development of standardised phenotypic and molecular testing methods. However, these methods are either slow or limited in the number of resistant genotypes they can detect. With the advent of next-generation sequencing (NGS) we can sidestep all those problems, as we can sequence whole tuberculosis genomes at increasingly smaller costs and requiring less and less DNA. In this review, we explain how accumulated knowledge in the field has allowed us to go from phenotypic testing to molecular methods to Whole Genome Sequencing (WGS) for resistance diagnostics. We compare current diagnostic methods with WGS as to their efficacy in detecting resistant cases, and show how forthcoming advances in NGS technologies will be crucial in widespread implementation of WGS as a diagnostic tool.

Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization / Variantes genéticas asociadas con la vitamina D en la población brasileña: investigación de potenciales instrumentos para aleatorización mendeliana

Abstract Introduction. Vitamin D is required for bone and mineral metabolism and participates in the regulation of the immune response. It is also linked to several chronic diseases and conditions, usually in populations of European descent. Brazil presents a high prevalence of vitamin D deficiency and insufficiency despite the widespread availability of sunlight in the country. Thus, it is important to investigate the role of vitamin D as a risk factor for disease and to establish causal relationships between vitamin D levels and health-related outcomes in the Brazilian population. Objective. To examine genetic variants identified as determinants of serum vitamin D in genome-wide association studies of European populations and check whether the same associations are present in Brazil. If so, these single nucleotide polymorphisms (SNPs) could be developed locally as proxies to use in genetically informed causal inference methods, such as Mendelian randomization. Materials and methods. We extracted SNPs associated with vitamin D from the genome-wide association studies catalog. We did a literature search to select papers ascertaining these variants and vitamin D concentrations in Brazil. Results. GC was the gene with the strongest association with vitamin D levels, in agreement with existing findings in European populations. However, VDR was the most investigated gene, regardless of its non-existing association with vitamin D in the genomewide association studies. Conclusions. More research is needed to validate sound proxies for vitamin D levels in Brazil, for example, prioritizing GC rather than VDR.

Resemen Introducción. La vitamina D es necesaria para el metabolismo óseo y mineral, y participa en la regulación de la respuesta inmunitaria. También está relacionada con enfermedades crónicas en poblaciones europeas. En Brasil, existe una prevalencia elevada de deficiencia e insuficiencia de vitamina D, a pesar de la amplia disponibilidad de luz solar. Por lo tanto, es importante investigar el papel de la vitamina D como factor de riesgo de diversas enfermedades y establecer relaciones causales entre los niveles de vitamina D y los problemas de salud en la población brasileña. Objetivo. Examinar variantes genéticas relacionadas con la vitamina D sérica en estudios de asociación genómica de poblaciones europeas y comprobar si estas mismas están presentes en Brasil. De ser así, estos SNPs podrían utilizarse como proxies en métodos de inferencia causal, tales como la aleatorización mendeliana. Materiales y métodos. A partir del catálogo de estudios de asociación de genoma completo se extrajeron SNPs relacionados con los niveles de vitamina D. Luego se hizo una búsqueda bibliográfica para identificar los artículos que evaluaran estos SNPs y la concentración de vitamina D en Brasil. Resultados. GC fue el gen más fuertemente asociado con los niveles de vitamina D, en concordancia con los resultados existentes en poblaciones europeas. Sin embargo, el gen VDR fue el más investigado, aunque no esté vinculado con la vitamina D en los estudios de asociación de genoma completo. Conclusiones. Se necesita más investigación para validar proxies genéticos de los niveles de vitamina D en Brasil y se recomienda priorizar el gen GC en lugar de VDR.

Estudios de asociación de genoma completo (GWAS) versus validación funcional: reto de la era post-GWAS / Genome-wide association studies (GWAS) versus functional validation: challenge of the post-GWAS era

En los últimos años se han dedicado muchos esfuerzos a la determinación de variantes y genes que pueden ser impor-tantes en la determinación de la densidad mineral ósea (DMO) y, a su vez, en diversas patologías óseas. Para conseguiresto, la aproximación que ha presentado mayores éxitos ha sido la de los estudios de asociación de genoma completo(GWAS). En particular, en la investigación sobre la biología ósea, se han publicado más de 50 grandes GWAS o metaa-nálisis de GWAS identificando más de 500 loci genéticos asociados con diferentes parámetros óseos como son la DMO,la resistencia ósea y el riesgo de fractura. Si bien el descubrimiento de las variantes asociadas es un aspecto esencial,es igualmente importante la validación funcional de dichas variantes para dilucidar su efecto y la relación causal quetienen con la enfermedad genética. Al tratarse de un aspecto mucho más lento y tedioso, se ha convertido en el nuevoreto de esta era post-GWAS. Entre los genes que ya se han abordado se incluyen varios de la vía de WNT y en especialel gen SOST, que juega un papel muy importante tanto en la determinación de la DMO poblacional como en enferme-dades monogénicas con elevada masa ósea y que ha dado lugar a un nuevo tratamiento contra la osteoporosis. En estarevisión recogemos los principales estudios GWAS con relación a fenotipos del hueso, así como algunos ejemplos devalidaciones funcionales para analizar las asociaciones encontradas en los mismos.(AU)

La viruela sísmica aspectos relacionados a la fisiopatología, genoma, patogénesis, transmisión, replicación e inmunología / Aspects Related to pathophysiology, Genome, Pathogenesis, Transmission, Replication and Immunology of Monkeypox

Introducción: La viruela símica es una enfermedad zoonótica identificada por primera vez en 1958. El virus es un miembro del género Orthopoxvirus, de la familia Poxviridae. Infecta a una amplia variedad de mamíferos y se desconoce su reservorio natural. Objetivos: Describir los aspectos importantes relacionados a la fisiopatología, genoma, patogénesis, transmisión, replicación e inmunología de la viruela símica. Métodos: Se realizó una búsqueda de artículos originales, reportes de casos, revisiones bibliográficas y sistemáticas en el Portal Regional de la BVS, PubMed, Science, Nature y Lancet. Se consultaron los informes de la Organización Mundial de la Salud y la Organización Panamericana de la Salud sobre la viruela símica. Resultados: La propagación del virus de la viruela símica puede ocurrir a través del contacto cercano con lesiones, fluidos corporales, gotitas respiratorias y objetos contaminados. Una vez dentro del organismo, el virus infecta mucosas, células epiteliales y células inmunitarias de los tejidos adyacentes. El virus se replica y disemina rápidamente a través del sistema hemático y linfático. Las células T desempeñan un papel importante en la regulación de la respuesta inmunitaria contra el virus. Sin embargo, los Orthopoxvirus han desarrollado varios mecanismos para la evasión de la respuesta inmunitaria. Conclusiones: Los aspectos importantes descritos que se tuvieron en cuenta acerca de la transmisión de la viruela símica han tenido cambio significativo con el tiempo. El brote mundial de viruela símica de 2022 presentó una cadena de transmisión principalmente entre humanos asociada al contacto sexual(AU).

Introduction: Monkeypox is a zoonotic disease that was first identified in 1958. The virus is a member of Orthopoxvirus genus, of Poxviridae family. It infects wide variety of mammals and its natural reservoir is unknown. Objectives: To describe the important aspects related to pathophysiology, genome, pathogenesis, transmission, replication and immunology of monkeypox. Methods: A search of original articles, case reports, bibliographic and systematic reviews was carried out in VHL Regional Portal, PubMed, Science, Nature and Lancet. Reports from the World Health Organization and the Pan American Health Organization on monkeypox were consulted. Results: Spread of monkeypox virus can occur through close contact with lesions, body fluids, respiratory droplets, and contaminated objects. Once inside the body, the virus infects mucous membranes, epithelial cells and immune cells of adjacent tissues. The virus replicates and spreads rapidly through the blood and lymphatic system. T cells play an important role in regulating the immune response against the virus. However, Orthopoxviruses have developed several mechanisms to evade the immune response. Conclusions: The important aspects described, taken into account about monkeypox transmission, have significantly changed over time. 2022 global monkeypox outbreak presented a chain of transmission primarily among humans associated with sexual contact(AU)

Viruela símica: una revisión narrativa de la fisiopatología / Monkeypox: a narrative review of pathophysiology

La viruela símica es una enfermedad zoonótica identificada por primera vez en 1958. El virus es un miembro del género Orthopoxvirus, de la familia Poxviridae. Infecta a una amplia variedad de mamíferos, pero se desconoce su reservorio natural. El virus del brote de 2022 pertenece a los clados IIa y IIb. Es probable que la aparición del brote actual se deba a las importaciones del brote de Nigeria de 2017-2018. La propagación de persona a persona puede ocurrir a través del contacto cercano con lesiones, fluidos corporales, gotitas respiratorias y objetos contaminados. Una vez dentro del organismo, el virus infecta las mucosas, células epiteliales y células inmunitarias de los tejidos adyacentes. Luego, el virus se replica y disemina rápidamente a través del sistema hemático y linfático. Las células T desempeñan un papel importante en la regulación de la respuesta inmunitaria contra el virus. Sin embargo, los Orthopoxvirus han desarrollado varios mecanismos para la evasión de la respuesta inmunitaria. La vigilancia de la enfermedad es un factor crucial en la evaluación de riesgo del virus y del control del brote. Para esta revisión se realizó la búsqueda de los principales artículos relacionados a la patogenia del virus, publicados hasta la fecha. El artículo destaca la necesidad de nuevos estudios sobre transmisibilidad y patogenicidad de las cepas asociadas al brote de 2022.

Monkeypox is a zoonotic disease first identified in 1958. The virus is a member of the genus Orthopoxvirus, family Poxviridae. It infects a wide variety of mammals, but its natural reservoir is unknown. The virus in the 2022 outbreak belongs to clades IIa and IIb. The emergence of the current outbreak is likely to be due to importations from the 2017-2018 Nigerian outbreak. Person to person spread can occur through close contact with lesions, body fluids, respiratory droplets and contaminated objects. Once inside the body, the virus infects mucous membranes, epithelial cells and immune cells in adjacent tissues. The virus then replicates and spreads rapidly through the blood and lymphatic system. Tcells play an important role in regulating the immune response against the virus. However, Orthopoxvirus have evolved several mechanisms for evasion of the immune response. Disease surveillance is a crucial factor in virus risk assessment and outbreak control. For this review we searched for the main articles related to the pathogenesis of the virus published to date. The article highlights the need for further studies on transmissibility and pathogenicity of the strains associated with the 2022 outbreak.

Whole-genome sequencing for surveillance of antimicrobial resistance in Ecuador: present and future implications / Secuenciación del genoma completo para la vigilancia de la resistencia a los antimicrobianos en Ecuador: implicaciones actuales y futuras / Sequenciamento do genoma completo para vigilância da resistência aos antimicrobianos no Equador: implicações presentes e futuras

ABSTRACT Whole-genome sequencing is becoming the gold standard for pathogen characterization and offers considerable advantages for understanding the evolution and dissemination of new determinants of antimicrobial resistance. Despite the benefits of whole-genome sequencing for pathogen characterization, implementation costs and lack of expertise may limit its use by public health laboratories. This article reviews the advantages of whole-genome sequencing for pathogen characterization and the current status of the use of whole-genome sequencing for antimicrobial resistance surveillance in Ecuador. A roadmap is suggested for including whole-genome sequencing for pathogen characterization based on the needs of the health reference institutions through alliances with Ecuadorian universities. Establishing a partnership between public health institutions and academia would be valuable for clinicians, policy-makers, and epidemiologists who could then take reasonable measures in those areas and establish a basis for adapting One Health strategies to tackle antimicrobial resistance in Ecuador.

RESUMEN La secuenciación del genoma completo, que está pasando a ser el estándar de referencia para la caracterización de agentes patógenos, ofrece ventajas considerables para comprender la evolución y la diseminación de los nuevos determinantes de la resistencia a los antimicrobianos. Sin embargo, a pesar de los beneficios que genera, los costos de ejecución y la falta de experiencia pueden limitar su uso por parte de los laboratorios de salud pública. En este artículo se evalúan las ventajas de la secuenciación del genoma completo para la caracterización de agentes patógenos y el estado actual del uso de la secuenciación del genoma completo en la vigilancia de la resistencia a los antimicrobianos en Ecuador. Se propone una hoja de ruta para incluir la secuenciación del genoma completo para la caracterización de agentes patógenos según las necesidades de las instituciones de salud de referencia, lo que se haría por medio de alianzas con universidades ecuatorianas. Establecer una asociación entre las instituciones de salud pública y los círculos académicos sería sumamente valioso para los médicos, los responsables de las políticas y los epidemiólogos, que podrían adoptar medidas razonables en sus ámbitos y sentar una base para adaptar las estrategias de "Una salud" a fin de abordar la resistencia a los antimicrobianos en Ecuador.

RESUMO O sequenciamento do genoma completo está se tornando o padrão ouro para a caracterização de patógenos e oferece vantagens consideráveis para a compreensão da evolução e disseminação de novos determinantes de resistência aos antimicrobianos. Apesar dos benefícios do sequenciamento do genoma completo para a caracterização de patógenos, os custos de implementação e a falta de especialização podem limitar seu uso pelos laboratórios de saúde pública. Este artigo analisa as vantagens do sequenciamento do genoma completo para a caracterização de patógenos e a situação atual do uso desta técnica para a vigilância da resistência aos antimicrobianos no Equador. Sugere-se um roteiro para incluir o sequenciamento de genomas completos para caracterização de patógenos com base nas necessidades das instituições de saúde de referência, por meio de alianças com universidades equatorianas. A criação de uma parceria entre instituições de saúde pública e entidades acadêmicas seria valiosa para clínicos, formuladores de políticas e epidemiologistas, que poderiam, assim, tomar medidas razoáveis nessas áreas e estabelecer uma base para adaptar estratégias de Saúde Única para combater a resistência aos antimicrobianos no Equador.

Genomic surveillance and sequencing of SARS-CoV-2 across South America / Vigilancia genómica y secuenciación del SARS-CoV-2 en América del Sur / Vigilância genômica e sequenciamento do SARS-CoV-2 na América do Sul

ABSTRACT After 2 years of the COVID-19 pandemic, the protocols used to control infection lack attention and analysis. We present data about deposits of complete genomic sequences of SARS-CoV-2 in the Global Initiative on Sharing All Influenza Data (GISAID) database made between January 2021 and May 31, 2022. We build the distribution profile of SARS-CoV-2 variants across South America, highlighting the contribution and influence of each variant over time. Monitoring the genomic sequences in GISAID illustrates negligence in the follow up of infected patients in South America and also the discrepancies between the number of complete genomes deposited throughout the pandemic by developed and developing countries. While Europe and North America account for more than 9 million of the genomes deposited in GISAID, Africa and South America deposited less than 400 000 genome sequences. Genomic surveillance is important for detecting early warning signs of new circulating viruses, assisting in the discovery of new variants and controlling pandemics.

RESUMEN Tras dos años de pandemia del COVID-19, los protocolos empleados para controlar la infección carecen de atención y análisis. En este artículo se presentan datos sobre depósitos de secuencias genómicas completas del SARS-CoV-2 en la base de datos de secuenciación GISAID, la Iniciativa mundial para intercambiar todos los datos sobre la gripe aviar, realizadas entre enero del 2021 y el 31 de mayo del 2022. Se creó el perfil de distribución de las variantes del SARS-CoV-2 en América del Sur, en el que se destacaron la contribución y la influencia de cada variante a lo largo del tiempo. El monitoreo de las secuencias genómicas en GISAID ilustra la negligencia en el seguimiento de los pacientes infectados en América del Sur, así como las discrepancias entre el número de genomas completos depositados a lo largo de la pandemia por parte de los países desarrollados y los países en desarrollo. Mientras que Europa y América del Norte han depositado más de 9 millones de genomas en GISAID, África y América del Sur han aportado menos de 400 000 secuencias genómicas. La vigilancia genómica es importante para detectar los primeros signos de alerta de virus nuevos en circulación, ayudar en el descubrimiento de nuevas variantes y controlar las pandemias.

RESUMO Após 2 anos da pandemia de covid-19, os protocolos usados para controlar a infecção necessitam maior atenção e análise. Apresentamos dados sobre as sequências genômicas completas do SARS-CoV-2 depositadas no banco de dados do a iniciativa internacional para o intercâmbio de dados sobre os vírus da influenza (GISAID) entre janeiro de 2021 e 31 de maio de 2022. Construímos o perfil de distribuição das variantes do SARS-CoV-2 na América do Sul, destacando a contribuição e a influência de cada variante ao longo do tempo. O monitoramento das sequências genômicas do GISAID ilustra a negligência no acompanhamento de pacientes infectados na América do Sul e as discrepâncias entre os países desenvolvidos e em desenvolvimento com relação ao número de genomas completos depositados ao longo da pandemia. Enquanto a Europa e a América do Norte respondem por mais de 9 milhões dos genomas depositados no GISAID, a África e a América do Sul depositaram menos de 400 000 sequências genômicas. A vigilância genômica é importante para detectar sinais de alerta precoces de novos vírus circulantes, auxiliar na descoberta de novas variantes e controlar pandemias.