RESUMEN

MOTIVATION: After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here, we address the performance of AlphaFold2 predictions obtained through ColabFold under this ensemble paradigm. RESULTS: Using a curated collection of apo-holo pairs of conformers, we found that AlphaFold2 predicts the holo form of a protein in ∼70% of the cases, being unable to reproduce the observed conformational diversity with the same error for both conformers. More importantly, we found that AlphaFold2's performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo-holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions. AVAILABILITY AND IMPLEMENTATION: Data and code used in this manuscript are publicly available at https://gitlab.com/sbgunq/publications/af2confdiv-oct2021. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Asunto(s)

RESUMEN

INTRODUCTION: Single nucleotide polymorphisms (SNP) in the fat mass and obesity-associated (FTO) gene have been associated with type 2 diabetes (T2D) and its complications. The aim of the present research was to investigate which and how (directly or indirectly) clinical and metabolic variables mediate the association between fat mass and the FTO gene and early chronic kidney disease (CKD) in individuals with T2D. METHODS: This cross-sectional study was conducted in a sample of 236 participants with T2D (53.4% women, mean age 60 ± 10 years). DNA samples were genotyped for the rs7204609 polymorphism (C/T) in the FTO gene. Clinical, anthropometric, and metabolic data were collected. Path analysis was used to evaluate the associations. RESULTS: Of the sample, 78 individuals with T2D had CKD (33%). Presence of the risk allele (C) was higher among participants with CKD (21.8 vs. 10.8%; p = 0.023). This polymorphism was positively associated with higher waist circumference, which in turn was associated with higher glycated hemoglobin and higher blood pressure. A higher blood-pressure level was associated with higher urinary albumin excretion (UAE) and as expected, higher UAE was associated with CKD. Path analysis showed an indirect relationship between the FTO gene and early CKD, mediated by waist circumference, blood-pressure levels, and UAE. CONCLUSIONS: These findings suggest that the C allele may contribute to genetic susceptibility to CKD in individuals with T2D through the presence of central obesity, hypertension, and high albuminuria.

Asunto(s)

RESUMEN

Intrinsically disordered proteins (IDPs) lack stable tertiary structure under physiological conditions. The unique composition and complex dynamical behaviour of IDPs make them a challenge for structural biology and molecular evolution studies. Using NMR ensembles, we found that IDPs evolve under a strong site-specific evolutionary rate heterogeneity, mainly originated by different constraints derived from their inter-residue contacts. Evolutionary rate profiles correlate with the experimentally observed conformational diversity of the protein, allowing the description of different conformational patterns possibly related to their structure-function relationships. The correlation between evolutionary rates and contact information improves when structural information is taken not from any individual conformer or the whole ensemble, but from combining a limited number of conformers. Our results suggest that residue contacts in disordered regions constrain evolutionary rates to conserve the dynamic behaviour of the ensemble and that evolutionary rates can be used as a proxy for the conformational diversity of IDPs.

Asunto(s)

RESUMEN

BACKGROUND: Identification of nutritional risk in critically ill patients is a challenge because each nutritional screening tool has its specific characteristics. The objective was to evaluate the performance of the modified Nutrition Risk in Critically ill (mNUTRIC) score, used alone or in combination with the Nutritional Risk Screening 2002 (NRS-2002) score, to predict hospital mortality in critically ill patients. METHODS: A prospective study was performed with patients admitted to the intensive care unit (ICU) from October 2017 to April 2018. Multiple logistic regression analysis was used to test for complementarity between the mNUTRIC and NRS-2002. A receiver operating characteristic (ROC) curve was used to identify the performance of the instruments to predict mortality. This study was conducted in accordance with the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement. RESULTS: 384 patients were evaluated (51.8% female mean age 59.6 ± 16.7 years). High nutritional risk was detected in 54.4% by the NRS-2002 and 48.4% by mNUTRIC. The overall mortality rate was 36.5% (n = 140). Patients in whom nutritional risk was identified both by mNUTRIC and by NRS-2002 (score ≥5) had a twofold greater risk of in-hospital mortality (RR = 2.29; 95%CI: 1.42-3.68; p = 0.001). The area under the ROC curve to predict mortality was 0.693 for mNUTRIC; 0.645 for NRS-2002; and 0.666 for mNUTRIC and NRS-2002 combined. CONCLUSIONS: The mNUTRIC and NRS-2002 scores had similar performance in predicting hospital mortality. The mNUTRIC has better discriminant ability to quantify the risk of mortality in critically ill patients.

Asunto(s)

RESUMEN

ABSTRACT Objective To evaluate the agreement between the modified version of the Nutritional Risk in the Critically Ill Score (without Interleukin-6) and a variant composed of C-Reactive Protein as well as its capacity to predict mortality. Methods A prospective cohort study was carried out with 315 patients in an Intensive Care Unit of a university hospital from October 2017 to April 2018. The agreement between the instruments was evaluated using the Kappa test. The predictive capacity for estimating mortality was assessed with the Receiver Operating Characteristic curve. Results The critical patients involved in the study had a mean age of 60.8±16.3 years and 53.5% were female. Most patients had C-Reactive Protein levels ?10mg/dL (n=263, 83.5%) and their admission in the Intensive Care Unit was medical (n=219, 69.5%). The prevalence of mortality was observed in 41.0% of the evaluated patients. The proportions at high nutritional risk according to Nutritional Risk in the Critically Ill without Interleukin-6 and with C-Reactive Protein were 57.5% and 55.6%, respectively. The tools showed strong and significant agreement(Kappa=0.935; p=0.020) and satisfactory performances in predicting mortality (area under the curve 0.695 [0.636-0.754] and 0.699 [0.640-0.758]). Conclusion Both versions of the Nutritional Risk in the Critically Ill tool show a satisfactory agreement and performance as predictors of mortality in critically ill patients. Further analysis of this variant and the association between nutrition adequacy and mortality is needed.

RESUMO Objetivo Avaliar a concordância entre a versão modificada do Escore de Risco Nutricional em Pacientes Críticos (sem Interleucina-6) e uma variante composta de Proteína C-Reativa, bem como a capacidade de ambas as versões para predizer mortalidade em pacientes críticos. Métodos Trata-se de um estudo de coorte prospectivo em 315 pacientes admitidos em uma Unidade de Tratamento Intensivo de um hospital universitário brasileiro no período de outubro de 2017 a abril de 2018. A concordância entre os instrumentos foi avaliada pelo teste Kappa. A capacidade preditiva de mortalidade foi avaliada pela curva Receiver Operating Characteristic. Resultados Os pacientes apresentaram idade média de 60,8±16,3 anos, dos quais 53,5% eram mulheres. A maioria dos pacientes apresentou níveis de Proteína C-Reativa ?10mg/dL (n=263; 83,5%). O tipo de admissão na Unidade de Terepia Intensiva foi clínica (n=219; 69,5%), sendo que a prevalência da mortalidade foi observada em41,0% dos pacientes avaliados. O alto risco nutricional, avaliado pelo Nutritional Risk in the Critically Ill sem Interleucina-6 e pela variante com Proteína C-Reativa, foi demonstrado em 57,5% e 55,6% dos pacientes críticos, respectivamente. Os instrumentos demostraram concordância forte e significativa (Kappa=0,935; p=0,020) e desempenho satisfatório para predizer mortalidade (área sob a curva 0,695 [0,636-0,774] e 0,699 [0,640-0,758]). Conclusão Ambas as versões do Escore de Risco Nutricional em Pacientes Críticos apresentam boa concordância e desempenho satisfatório como preditores de mortalidade em pacientes críticos. É ainda necessária uma análise mais aprofundada desta variante, bem como da associação entre adequação nutricional e mortalidade.

Asunto(s)

RESUMEN

OBJECTIVE: To evaluate possible associations between nutritional risk and the clinical outcomes of critical patients admitted to an intensive care unit. METHODS: A prospective study was carried out with a cohort comprising 200 patients admitted to a university hospital intensive care unit. Nutritional risk was assessed with the NRS-2002 and NUTRIC scores. Patients with scores ≥ 5 were considered at high nutritional risk. Clinical data and outcome measures were obtained from patients' medical records. Multiple logistic regression analysis was used to calculate odds ratios and their respective 95% confidence intervals (for clinical outcomes). RESULTS: This sample of critical patients had a mean age of 59.4 ± 16.5 years and 53.5% were female. The proportions at high nutritional risk according to NRS-2002 and NUTRIC were 55% and 36.5%, respectively. Multiple logistic regression models adjusted for gender and type of admission indicated that high nutritional risk assessed by the NRS-2002 was positively associated with use of mechanical ventilation (OR = 2.34; 95%CI 1.31 - 4.19; p = 0.004); presence of infection (OR = 2.21; 95%CI 1.24 - 3.94; p = 0.007), and death (OR = 1.86; 95%CI 1.01 - 3.41; p = 0.045). When evaluated by NUTRIC, nutritional risk was associated with renal replacement therapy (OR = 2.10; 95%CI 1.02 - 4.15; p = 0.040) and death (OR = 3.48; 95%CI 1.88 - 6.44; p < 0.001). CONCLUSION: In critically ill patients, high nutritional risk was positively associated with an increased risk of clinical outcomes including hospital death.

OBJETIVO: Avaliar possíveis associações do risco nutricional com os desfechos clínicos desfavoráveis em pacientes críticos internados na unidade de terapia intensiva. MÉTODOS: Estudo de coorte, prospectivo, realizado em 200 pacientes em unidade de terapia intensiva de hospital universitário. O risco nutricional foi avaliado pelos escores NRS-2002 e NUTRIC. Pacientes com escore ≥ 5 foram considerados de alto risco nutricional. Os dados e desfechos clínicos foram obtidos de registros clínicos dos pacientes. Utilizou-se análise de regressão logística múltipla para calcular os riscos relativos e seus respectivos intervalos de confiança de 95% para os desfechos clínicos. RESULTADOS: Os pacientes críticos apresentaram idade de 59,4 ± 16,5 anos, e 53,5% eram do sexo feminino. O alto risco nutricional, segundo NRS-2002 e NUTRIC, foi de 55% e 36,5%, respectivamente. Em modelos de regressão logística múltipla, ajustados por sexo e motivo de internação, o alto risco nutricional avaliado pelo NRS-2002 associou-se positivamente ao uso de ventilação mecânica (RR = 2,34; IC95% 1,31 - 4,19; p = 0,004); presença de infecção (RR = 2,21; IC95% 1,24 - 3,94; p = 0,007) e óbito (RR = 1,86; IC95% 1,01 - 3,41; p = 0,045). Quando avaliado pelo NUTRIC, o risco nutricional foi associado à terapia de substituição renal (RR = 2,10; IC95% 1,02 - 4,15; p = 0,040) e óbito (RR = 3,48; IC95% 1,88 - 6,44; p < 0,001). CONCLUSÃO: Em pacientes gravemente doentes, o alto risco nutricional foi positivamente associado a um maior risco de desfechos clínicos desfavoráveis, incluindo óbito hospitalar.

Asunto(s)

RESUMEN

RESUMO Objetivo: Avaliar possíveis associações do risco nutricional com os desfechos clínicos desfavoráveis em pacientes críticos internados na unidade de terapia intensiva. Métodos: Estudo de coorte, prospectivo, realizado em 200 pacientes em unidade de terapia intensiva de hospital universitário. O risco nutricional foi avaliado pelos escores NRS-2002 e NUTRIC. Pacientes com escore ≥ 5 foram considerados de alto risco nutricional. Os dados e desfechos clínicos foram obtidos de registros clínicos dos pacientes. Utilizou-se análise de regressão logística múltipla para calcular os riscos relativos e seus respectivos intervalos de confiança de 95% para os desfechos clínicos. Resultados: Os pacientes críticos apresentaram idade de 59,4 ± 16,5 anos, e 53,5% eram do sexo feminino. O alto risco nutricional, segundo NRS-2002 e NUTRIC, foi de 55% e 36,5%, respectivamente. Em modelos de regressão logística múltipla, ajustados por sexo e motivo de internação, o alto risco nutricional avaliado pelo NRS-2002 associou-se positivamente ao uso de ventilação mecânica (RR = 2,34; IC95% 1,31 - 4,19; p = 0,004); presença de infecção (RR = 2,21; IC95% 1,24 - 3,94; p = 0,007) e óbito (RR = 1,86; IC95% 1,01 - 3,41; p = 0,045). Quando avaliado pelo NUTRIC, o risco nutricional foi associado à terapia de substituição renal (RR = 2,10; IC95% 1,02 - 4,15; p = 0,040) e óbito (RR = 3,48; IC95% 1,88 - 6,44; p < 0,001). Conclusão: Em pacientes gravemente doentes, o alto risco nutricional foi positivamente associado a um maior risco de desfechos clínicos desfavoráveis, incluindo óbito hospitalar.

ABSTRACT Objective: To evaluate possible associations between nutritional risk and the clinical outcomes of critical patients admitted to an intensive care unit. Methods: A prospective study was carried out with a cohort comprising 200 patients admitted to a university hospital intensive care unit. Nutritional risk was assessed with the NRS-2002 and NUTRIC scores. Patients with scores ≥ 5 were considered at high nutritional risk. Clinical data and outcome measures were obtained from patients' medical records. Multiple logistic regression analysis was used to calculate odds ratios and their respective 95% confidence intervals (for clinical outcomes). Results: This sample of critical patients had a mean age of 59.4 ± 16.5 years and 53.5% were female. The proportions at high nutritional risk according to NRS-2002 and NUTRIC were 55% and 36.5%, respectively. Multiple logistic regression models adjusted for gender and type of admission indicated that high nutritional risk assessed by the NRS-2002 was positively associated with use of mechanical ventilation (OR = 2.34; 95%CI 1.31 - 4.19; p = 0.004); presence of infection (OR = 2.21; 95%CI 1.24 - 3.94; p = 0.007), and death (OR = 1.86; 95%CI 1.01 - 3.41; p = 0.045). When evaluated by NUTRIC, nutritional risk was associated with renal replacement therapy (OR = 2.10; 95%CI 1.02 - 4.15; p = 0.040) and death (OR = 3.48; 95%CI 1.88 - 6.44; p < 0.001). Conclusion: In critically ill patients, high nutritional risk was positively associated with an increased risk of clinical outcomes including hospital death.

Asunto(s)

RESUMEN

The conformations accessible to proteins are determined by the inter-residue interactions between amino acid residues. During evolution, structural constraints that are required for protein function providing biologically relevant information can exist. Here, we studied the proportion of sites evolving under structural constraints in two very different types of ensembles, those coming from ordered and disordered proteins. Using a structurally constrained model of protein evolution, we found that both types of ensembles show comparable, near 40%, number of positions evolving under structural constraints. Among these sites, ~68% are in disordered regions and ~57% of them show long-range inter-residue contacts. Also, we found that disordered ensembles are redundant in reference to their structurally constrained evolutionary information and could be described on average with ~11 conformers. Despite the different complexity of the studied ensembles and proteins, the similar constraints reveal a comparable level of selective pressure to maintain their biological functions. These results highlight the importance of the evolutionary information to recover meaningful biological information to further characterize conformational ensembles.

Asunto(s)

RESUMEN

The dynamic nature of technological developments invites us to rethink the learning spaces. In this context, science education can be enriched by the contribution of new computational resources, making the educational process more up-to-date, challenging, and attractive. Bioinformatics is a key interdisciplinary field, contributing to the understanding of biological processes that is often underrated in secondary schools. As a useful resource in learning activities, bioinformatics could help in engaging students to integrate multiple fields of knowledge (logical-mathematical, biological, computational, etc.) and generate an enriched and long-lasting learning environment. Here, we report our recent project in which high school students learned basic concepts of programming applied to solving biological problems. The students were taught the Python syntax, and they coded simple tools to answer biological questions using resources at hand. Notably, these were built mostly on the students' own smartphones, which proved to be capable, readily available, and relevant complementary tools for teaching. This project resulted in an empowering and inclusive experience that challenged differences in social background and technological accessibility.

Asunto(s)

RESUMEN

O objetivo do estudo foi conhecer as percepções de famílias em fase de aquisição, quanto à sua inclusão social na comunidade em que vivem. Inquérito de base populacional com 101 famílias, por meio de visitas domiciliares e aplicação de um instrumento que contemplou variáveis de diversas naturezas quanto à inclusão social. As entrevistas foram realizadas no período de julho a setembro de 2012 no município de Palmitos, Santa Catarina. A análise foi de cluster (agrupamento). Os respondentes avaliaram como "boa" e "regular" as questões que mediam a percepção familiar sobre o exercício da cidadania. "Muito boa" foi a percepção sobre o apoio que recebem de algumas redes sociais. A renda familiar foi o maior motivo de descontentamento. Quanto aos serviços de saúde, a avaliação das Unidades Básicas de Saúde foi predominantemente positiva, ao contrário da Estratégia de Saúde da Família, avaliada com baixo desempenho. As questões de saneamento básico também receberam avaliação negativa. Diante dos resultados, deve-se considerar a importância do trabalho interdisciplinar, do esforço coletivo dos profissionais de saúde, da intersetorialidade, com ação imediata, fundamentais para promover a saúde e melhorar a qualidade de vida da população assistida.

This study evaluated the perceptions of families in the acquisition phase about their social inclusion in the community where they live. A population-based survey was conducted with 101 families through home visits and the application of an instrument that included different variables referring to social inclusion. The interviews were conducted from July to September of 2012 in the city of Palmitos in Santa Catarina State. The cluster analysis was performed(grouping). The respondents rated as "good" and "regular" the issues that mediate the family perception of the exercise of citizenship. The perception of the support received from some social networks was"very good". The family income was the greatest reason of discontentment. As for health care, the ratingsof the Basic Health Units was predominantly positive, unlike that about the Family Health Strategy, which was ratedas underperforming. Basic sanitation issues also received a negative rating. Therefore, the importance of interdisciplinary work, joint effort of health professionals, and intersectionality with immediate action are fundamental to promote health and improve the quality of life of the population assisted.

El objetivo del estudio fue el de conocer las percepciones de familias en fase de adquisición, en cuanto a su inclusión social en la comunidad donde viven. Se realizó una encuesta de base poblacional con 101 familias a través de visitas domiciliarias y la aplicación de un instrumento que incluyó variables de distintas naturalezas en cuanto a la inclusión social. Las entrevistas fueron realizadas en el período de julio a septiembre de 2012 en la ciudad de Palmitos, Santa Catarina, Brasil. El análisis fue de Cluster (conglomerados). Los encuestados calificaron como "buena" y "regular" cuestiones que median la percepción familiar sobre el ejercicio de la ciudadanía. "Muy buena" fue la percepción sobre el apoyo que reciben de algunas redes sociales. El ingreso familiar fue el mayor motivo de descontento. En cuanto a los servicios de salud, la evaluación de las Unidades Básicas de Salud fue predominantemente positiva, adiferencia de la Estrategia de Salud de la Familia, evaluada con bajo rendimiento. Problemas de saneamiento básicos también recibieron una evaluación negativa. Con base en los resultados, hay que considerar la importancia del trabajo interdisciplinario, el esfuerzo conjunto de los profesionales de la salud, la intersectorialidad, con una acción inmediata, fundamentales para promover la salud y mejorar la calidad de vida de la población asistida.

Asunto(s)