A whole-exome capture and next-generation sequencing was applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, and severe cognitive deficit, and without any identifiable Syndromic pattern, and to her parents, we disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated with Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated sequence, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURAwt and the PURA–Phe233del showed that the occurrence of the Phe233del affects between 220–320 amino acids. The distortion in the PURA structural conformation in the ~5 Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein–DNA docking corroborated these results in an in silico analysis that showed a loss of the contact of the PURA–Phe233del III repeat domain model with the DNA. Together, (i) the energetic and stereochemical, (ii) the hydropathic indexes and polarity surfaces, and (iii) the hybrid Quantum Mechanics–Molecular Mechanics (QM–MM) analyses of the PURA molecular models demarcate, at the atomic resolution, the specific surrounding region affected by these mutations and pave the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the etiopathogenic agent of COVID-19, a condition that has led to a formally recognized pandemic by March 2020 (World Health Organization –WHO). The SARS-CoV-2 genome is constituted of 29,903 base pairs, that code for four structural proteins (N, M, S, and E) and more than 20 non-structural proteins. Mutations in any of these regions, especially in those that encode for the structural proteins, have allowed the identification of diverse lineages around the world, some of them named as Variants of Concern (VOC) and Variants of Interest (VOI), according to the WHO and CDC. In this study, by using Next Generation Sequencing (NGS) technology, we sequenced the SARS-CoV-2 genome of 422 samples from Colombian residents, all of them collected between April 2020 and January 2021. We obtained genetic information from 386 samples, leading us to the identification of 14 new lineages circulating in Colombia, 13 of which were identified for the first time in South America. GH was the predominant GISAID clade in our sample. Most mutations were either missense (53.6%) or synonymous mutations (37.4%), and most genetic changes were located in the ORF1ab gene (63.9%), followed by the S gene (12.9%). In the latter, we identified mutations E484K, L18F, and D614G. Recent evidence suggests that these mutations concede important particularities to the virus, compromising host immunity, the diagnostic test performance, and the effectiveness of some vaccines. Some important lineages containing these mutations are the Alpha, Beta, and Gamma (WHO Label). Further genomic surveillance is important for the understanding of emerging genomic variants and their correlation with disease severity.

Objectives This study aims to explore the association between the molecular characterization of SARS-CoV-2 and disease severity on ambulatory and hospitalized patients in two main Colombian epicenters during the first year of the COVID-19 pandemic. Methods We included 1000 patients with SARS-CoV-2 infection, collected clinical data from 997, and obtained 678 whole genome sequences by massively parallel sequencing. Bivariate, multivariate, and classification and regression tree analyses were run between clinical and genomic variables. Results Age and infection with lineages B.1.1, B.1.1.388, B.1.523, and B.1.621 were related to lethality for patients 71-88 years old (OR: 6.048036; 95% CI 1.346567-32.92521, p-value: 0.01718674). The need for hospitalization was associated with higher age and comorbidities. For patients 38-51 years old infected with lineages A, B, B.1.1.388, B.1.1.434, B.1.153, B.1.36.10, B.1.411, B.1.471, B.1.558 or B.1.621, hospitalization rate increased significantly (OR 8.368427, 95% CI 2.573145-39.10672, p-value: 0.00012). Associations between clades and clinical outcomes diverged from previously reported data. Conclusions Lineage B.1.621 increased the need for hospitalization and lethality. Our findings, plus the rapidly increasing prevalence in Colombia and other countries, suggest broadly considering it as a Variant of Interest. If associated disease severity is confirmed, possible designation as Variant of Concern could be entertained.

Presentación de Caso Reto clínico en el diagnóstico y tratamiento de leptospirosis Challenge in Clinical diagnosis and Treatment of Leptospirosis desafio clínico no diagnóstico e tratamento de leptospirose

La educación interprofesional (EIP) hace referencia a aquellos escenarios donde dos o más profesionales o estudiantes de diferentes áreas del conocimiento aprenden con, de y acerca del otro para mejorar la colaboración y la calidad del cuidado en salud. Actualmente, a pesar de los diversos beneficios descritos como resultado de su implementación en escenarios académicos de formación de pregrado en ciencias de la salud, no hay suficiente evidencia de su aplicabilidad en sus contenidos curriculares. Por esta razón, en el presente estudio se analizan, por medio de un estudio cuantitativo descriptivo, los componentes de la EIP en 79 prácticas formativas de diez programas de pregrado desarrolladas en un hospital universitario de alta complejidad. Con dicho objetivo, se revisaron los anexos técnicos de estos programas, donde se calificó el cumplimiento de cinco componentes asociados a la EIP según la definición dada por Zwarenstein. Como resultados, solo el 13.9 % del total de las prácticas analizadas obtuvo un puntaje igual o mayor a tres y fue clasificado como práctica con componente de EIP, de modo que, como conclusión, resalta la importancia de promover todavía más la inclusión de prácticas de EIP en los contenidos curriculares de programas de pregrado, y esto con el objetivo de mejorar las habilidades para el trabajo en equipo de los estudiantes y para, asimismo, tener un impacto positivo en la atención por parte del sistema de salud.

A whole-exome capture and next-generation sequencing applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, severe cognitive deficit, without any identifiable Syndromic pattern, and to her parents, disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated to Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated one, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURA WT and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural confor-mation in the ~5Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA Docking corroborated these results in silico Analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, i) the energetic and stereochemical, ii) the hydropathic indices and polarity surfaces, and iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate at the atomic resolution the specific surrounding region affected by these mutations and paves the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.