Variantes genómicas asociadas a errores congénitos en el metabolismo de los carbohidratos en el suroccidente colombiano

Introducción: Los Errores Innatos del Metabolismo (EIM) de carbohidratos son el resultado de la interrupción de las vías catabólicas o anabólicas de diferentes carbohidratos, siendo la fructosa, la galactosa y el glucógeno los más comunes y pertenecen a un grupo heterogéneo de trastornos que pueden ser hereditarios o pueden ocurrir como resultado de variantes genéticas espontáneas. En los EIM, están las vías de los carbohidratos alteradas, tanto las vías catabólicas como las anabólicas, incluyendo el metabolismo de la fructosa, galactosa y glucógeno, dando lugar a un grupo heterogéneo de trastornos. Sin embargo, los datos sobre estas patologías en Colombia son escasos. Nuestro estudio tuvo como objetivo identificar variantes genómicas asociadas a EIM por carbohidratos en población del suroccidente colombiano carente de diagnóstico clínico. Resultados: Realizamos un estudio transversal, secuenciando 320 exomas y clasificando las variantes de acuerdo a guías estándar. Identificamos 286 variantes, incluyendo 206 nuevas y 73 variantes benignas o probablemente benignas. En particular, seis variantes en genes como GALT, GAK1, ALDOB, GAA y SLC2A1 tenían un significado incierto, y una variante patogénica en el gen GALT se asoció con la galactosemia clásica. Curiosamente, el 18% eran intrónicas, el 5% con sentido erroneo, el 10% sinónimas y el 67% variantes no notificadas. Conclusiones: Estos hallazgos ponen de relieve la necesidad de programas de diagnóstico precoz para aplicar tratamientos específicos, incluido el manejo transdisciplinar para minimizar la morbilidad y la mortalidad. El consejo genético y la educación sobre el riesgo son cruciales, facilitando enfoques de medicina anticipatoria y preventiva, avanzando así en la medicina de precisión.   (provisto por Infomedic International)

Introduction: Carbohydrate Inborn Errors of Metabolism (IEMs) result from disruption of the catabolic or anabolic pathways of different carbohydrates, fructose, galactose and glycogen being the most common and belong to a heterogeneous group of disorders that may be inherited or may occur as a result of spontaneous genetic variants. In IEM, there are altered carbohydrate pathways, both catabolic and anabolic pathways, including fructose, galactose and glycogen metabolism, resulting in a heterogeneous group of disorders. However, data on these pathologies in Colombia are scarce. The aim of our study was to identify genomic variants associated with carbohydrate IEM in the southwestern Colombian population lacking clinical diagnosis. Results: We performed a cross-sectional study, sequencing 320 exomes and classifying variants according to standard guidelines. We identified 286 variants, including 206 new variants and 73 benign or probably benign variants. Notably, six variants in genes such as GALT, GAK1, ALDOB, GAA and SLC2A1 were of uncertain significance, and one pathogenic variant in the GALT gene was associated with classic galactosemia. Interestingly, 18% were intronic, 5% missense, 10% synonymous, and 67% unreported variants. Conclusions: These findings highlight the need for early diagnostic programs to implement targeted treatments, including transdisciplinary management to minimize morbidity and mortality. Genetic counseling and risk education are crucial, facilitating anticipatory and preventive medicine approaches, thus advancing precision medicine. (provided by Infomedic International)

Assessing the conservation value of cemeteries to urban biota worldwide.

Cemeteries are key urban green spaces with multifaceted societal and ecological importance. Their biodiversity is shaped by unique environmental and cultural factors. They can potentially protect rare and endangered species, yet their conservation value compared with other urban green spaces remains largely unexplored. We sought to fill this gap by systematically reviewing literature to investigate the conservation value of cemeteries relative to other urban green spaces (botanical gardens, institutional premises, natural remnants, and parks) by comparing species richness and proportions of native and unique species. We analyzed data from 70 papers covering 50 cities in 27 countries with linear and binomial mixed-effects models at both site and city level. Cemetery conservation value was similar to urban parks, except for the proportion of unique species, for which parks had significantly higher proportions (21.9% vs. 14.2%, p < 0.001). Cemeteries hosted slightly higher proportions of native species at the city level than botanical gardens (99.7% vs. 99.6%, p < 0.001) and institutional green spaces (96.3% vs. 94.1%, p = 0.034) and proportions comparable to parks and natural remnants (p > 0.05). They also had similar or higher values than institutional premises in species richness and unique species proportions (p > 0.05) and a higher site-level proportion of native species (p < 0.001). In contrast, species richness (slopes = -0.11 and -0.25, respectively) and unique species proportions (4.4% and 6.9%, respectively, p < 0.001 for both) were lower in cemeteries than in remnants of natural areas and in botanical gardens. The conservation value of cemeteries and parks was similar for animals, but parks had a higher value for plants. Overall, cemeteries were generally at least as valuable as some other green spaces for urban biodiversity and mostly native biota. Their religious and cultural significance suggests they will remain intact in the long term; thus, it is essential to prioritize and further promote their biodiversity in conservation and sustainable urban design plans.

Análisis del valor de conservación que tienen los cementerios para la biota urbana a nivel mundial Resumen Los cementerios son espacios urbanos verdes con una importancia social y ecológica multifacética. Su biodiversidad está moldeada por factores ambientales y culturales únicos. Los cementerios tienen el potencial para proteger especies raras y en peligro, pero su valor de conservación sigue sin ser explorado cuando se compara con otros espacios urbanos verdes. Buscamos llenar este vacío con una revisión sistemática de la bibliografía para investigar el valor de conservación de los cementerios en relación a otros espacios urbanos verdes (jardines botánicos, sedes institucionales, remanentes naturales y parques) al comparar la riqueza de especies y la proporción de especies nativas y únicas. Analizamos con modelos lineales y binomiales de efectos mixtos a nivel de sitio y de ciudad los datos de 70 artículos enfocados en 50 ciudades de 27 países. El valor de conservación de los cementerios fue similar al de los parques urbanos, excepto para la proporción de especies únicas, para la cual los parques tuvieron una proporción significativamente más alta (21.9% vs. 14.2%, p<0.001). A nivel de ciudad, los cementerios albergaron una proporción ligeramente mayor de especies nativas en comparación con los jardines botánicos (99.7% vs. 99.6%, p<0.001) y las sedes institucionales (96.3% vs. 94.1%, p = 0.034) y tuvieron una proporción comparable a los parques y los remanentes naturales (p>0.05). Los cementerios también tuvieron un valor similar o mayor a los espacios verdes institucionales en cuanto a riqueza de especies y proporción de especies únicas (p>0.05) y una proporción mayor a nivel de sitio de especies nativas (p<0.001). Al contrario, la riqueza de especies (pendientes = ­0.11 y ­0.25, respectivamente) y la proporción de especies únicas (4.4% y 6.9%, respectivamente, p<0.001 para ambas) fueron menores en los cementerios que en los remanentes de las áreas naturales y en los jardines botánicos. El valor de conservación de los cementerios y los parques fue similar para los animales, pero los parques tuvieron un valor mayor para las plantas. En general, los cementerios fueron al menos tan valiosos como otros espacios verdes para la biodiversidad urbana y casi toda la biota nativa. El significado religioso y cultural que tienen los cementerios sugiere que seguirán intactos a largo plazo; por ello, es esencial priorizar y promover aún más su biodiversidad en la conservación y en los planes de diseño urbano sustentable.

Cribado prenatal de aneuploidías mediante análisis de ácido desoxirribonucleíco libre total circulante en plasma materno. Revisión narrativa / Prenatal screening for aneuploidies by analysis of circulating total free deoxyribonucleic acid in maternal plasma. Narrative review

La prueba prenatal no invasiva es un método de cribado de aneuploidías fetales y de resultar con riesgo alto debe ser confirmado a través de prueba genética diagnóstica. Es la prueba de detección más sensible y específica para las aneuploidías fetales comunes y minimiza la realización de técnicas invasivas, solo para las gestantes con riesgo elevado. Se debe realizar asesoramiento genético pre- y poscribado. Este estudio tiene como objetivo describir los fundamentos básicos de la prueba prenatal no invasiva mediante el análisis del ácido desoxirribonucleíco libre circulante en plasma materno para cribado de aneuploidías, y de los métodos primordiales y avances en biología molecular incluyendo las tecnologías de secuenciación de nueva generación, que lo han facilitado, considerando sus beneficios y limitaciones al aplicarla en la práctica clínica, en este campo que cambia con tanta rapidez(AU)

The non-invasive prenatal test is a screening method for fetal aneuploidies and if the result is at high risk, it must be confirmed through diagnostic genetic test. It is the most sensitive and specific detection test for common fetal aneuploidies and minimizes the use of invasive techniques, only for pregnant women at high risk. Genetic counseling should be performed before and after screening. This study aims to describe the basic fundamentals of non-invasive prenatal testing by analyzing free circulating deoxyribonucleic acid in maternal plasma for aneuploidy screening, and the primary methods and advances in molecular biology, including next-generation sequencing technologies, which have facilitated it, considering its benefits and limitations when applying it in clinical practice, in this rapidly changing field(AU)

In silico evaluation of the gene expression profile of syndecan-4 in different breast tumor subtypes / Avaliação in silico do perfil de expressão gênica do sindecam-4 nos diferentes subtipos de tumores de mama

INTRODUCTION: Breast cancer is one of the main causes of death in women. Luminal tumors A and B show good response with hormonal treatments, tumors that overexpress HER-2 can be treated with monoclonal antibodies, whereas triple negative tumors have few treatments available because they present low or absent expression of hormone receptors and HER-2, in addition, they present worse tumor progression. Syndecans are heparan sulfate proteoglycans that have the function of interacting with growth factors, cytokines, and extracellular matrix, thus modulating important processes in tumor progression. OBJECTIVE: Analyze the expression of syndecan-4 in different subtypes of breast tumors. METHODS: Bioinformatics is a useful tool for the study of new biomarkers. In the present study, the TCGA database (514 patients) and Metabric (1,898 patients) were analyzed using the cBioportal software. Gene expression data were analyzed by RNA-Seq and Microarray from biopsies of breast tumors. RESULTS: An alteration in syndecan-4 gene expression was observed among the different subtypes of breast tumors. Patients with a triple-negative tumor had decreased expression for syndecan-4 in both databases. CONCLUSION: Syndecan-4 is a potential biomarker for breast tumor prognosis since decreased expression of syndecan-4 is related to triple-negative breast cancer.

INTRODUÇÃO: O câncer de mama corresponde a uma das principais causas de morte em mulheres. Os tumores luminais A e B apresentam boa resposta com tratamentos hormonais, os tumores que superexpressam HER-2 podem ser tratados com anticorpos monoclonais, já os tumores triplo-negativos apresentam poucos tratamentos disponíveis por apresentarem expressão baixa ou ausente dos receptores hormonais e HER-2, além de pior progressão tumoral. Os sindecans são proteoglicanos de heparam sulfato que tem função de interagir com fatores de crescimento, citocinas e matriz extracelular, modulando assim processos importantes na progressão tumoral. OBJETIVO: Analisar a expressão o sindecam-4 nos diferentes subtipos de tumores de mama. MÉTODOS: A bioinformática vem se mostrando útil para estudo de novos biomarcadores. No presente estudo, foi analisado o banco de dados TCGA (514 pacientes) e Metabric (1898 pacientes) utilizando o software cBioportal. Foram analisados os dados de expressão gênica por RNA-Seq e Microarray. RESULTADOS: Foi verificada alteração de expressão gênica do sindecam-4 entre os diferentes subtipos de tumores de mama. Pacientes com tumor triplo-negativo tiveram a expressão diminuída para sindecam-4 em ambos os bancos de dados. CONCLUSÃO: Foi verificado que sindecam-4 parece ser um potencial biomarcador em tumores de mama, a expressão diminuída de sindecam-4 parece estar relacionada a um pior prognóstico.

[Clinico-pathological evaluation of tumor budding in the oncological progression of colorectal cancer]. / Evaluación clínico-patológica del tumorbudding en la progresión oncológica del cáncer colorrectal.

INTRODUCTION: Tumor budding (TB), defined as the presence of individual neoplastic cells or isolated groups of up to 4 cells at the front of tumor invasion, has become an adverse prognostic marker in colorectal cancer (CRC) in recent decades. The prognostic impact of TB in CRC remains not clearly defined and histological methods for its evaluation vary depending on the center. The objective of this study is to investigate the association between TB and CRC, in terms of oncological evolution and pathological stage. METHODS: A retrospective observational study was conducted, including patients undergoing curative oncological surgery for CRC between January 2017 and December 2022. The effects of TB on disease-free survival (DFS) and overall survival (OS) were evaluated according to the Kaplan-Meier curves. RESULTS: In 78 cases TB was described in the pathology report. TB was present in 56 patients (71.8%), divided into the following categories: low grade in 22 (39.3%), intermediate grade in 17 (30.4%) and high grade in 17 (30.4%). The proportion of patients who presented lymph node metastases, lympho-vascular and perineural invasion was significantly higher in patients with TB (26.8% vs 0%, P=.008; 41.1% vs 4.5%, P=.002; 16.1% vs 0% P=.054; respectively). DFS was 86.3% in low-grade TB, 75.3% in intermediate-grade TB, and 70.3% in high-grade TB. Cases with intermediate and high grade were associated with a shorter OS compared to the low grade group (93.7% and 75.4% vs 100% P=.012, respectively). CONCLUSION: These results suggest that TB expression may be a useful risk factor as a prognostic factor for the detection of lymph node metastasis, local recurrence, and distant metastasis in CRC.

Utilidad de GeneXpert MTB/RIF en el diagnóstico de tuberculosis frente a la baciloscopia / Utility of GeneXpert MTB/RIF in the Diagnosis of Tuberculosis Compared to Sputum Smear Microscopy

Introducción: La implementación de un método diagnóstico adecuado y eficiente es crucial para la detección temprana de la tuberculosis. Esto no solo permite un control efectivo de la enfermedad para evitar su transmisión y progresión hacia estadios más graves, además previene el desarrollo de resistencia a los fármacos en los pacientes.Objetivo: Evaluar la utilidad de la prueba molecular GeneXpert MTB/RIF en el diag-nóstico de Mycobacterium tuberculosis complex, en comparación con la bacilos-copia, utilizando el cultivo como referencia.Material y Métodos: Se realizó un estudio descriptivo, observacional y no expe-rimental de corte transversal, se incluyeron 253 muestras de pacientes de ambos sexos y de variados rangos de edad, que fueron evaluadas mediante baciloscopia, GeneXpert MTB/RIF y cultivo. El estudio se centró en muestras procesadas en un Hospital público de la ciudad de Quito durante el período de enero de 2021 a mayo de 2022Resultados: La prueba molecular GeneXpert MTB/RIF mostró una sensibilidad del 94,7% y una especificidad del 93,9% para el diagnóstico de Mycobacterium tu-berculosis complex. Además, se identificó un caso de resistencia a la rifampicina.Conclusión: Este estudio confirma la eficacia de la prueba molecular GeneXpert MTB/RIF sobre la baciloscopia para el diagnóstico oportuno de Mycobacterium tu-berculosis complex. Sin embargo, es esencial considerar las diversas condiciones de las muestras y pacientes para optimizar la precisión diagnóstica

Introduction: Implementing an appropriate and efficient diagnostic method is cru-cial for the early detection of tuberculosis. This not only allows for effective control of the disease to prevent its transmission and progression to more severe stages but also prevents the development of drug resistance in patients.Objective: To evaluate the utility of the GeneXpert MTB/RIF molecular test in diag-nosing Mycobacterium tuberculosis complex, compared to sputum smear micros-copy, using culture as the reference. Material and Methods: A descriptive, observational, and non-experimental cross-sectional study was conducted, including 253 samples from patients of both sexes and various age ranges, which were assessed using sputum smear micros-copy, GeneXpert MTB/RIF, and culture. The study focused on samples processed at a Quito ́s Public Hospital during the period from January 2021 to May 2022.Results: The GeneXpert MTB/RIF molecular test showed a sensitivity of 94.7% and a specificity of 93.9% for the diagnosis of Mycobacterium tuberculosis com-plex. Additionally, a case of resistance to rifampicin was identified.Conclusion: This study confirms the effectiveness of the GeneXpert MTB/RIF mo-lecular test over sputum smear microscopy for the timely diagnosis of tuberculosis. However, it is essential to consider the diverse conditions of the samples and pa-tients to optimize diagnostic accuracy

Hipertensión pulmonar y leiomiomas uterinos, ¿existe relación causal? Serie de casos y revisión fisiopatológica / Pulmonary Hypertension and Uterine Leiomyomas, Is there a Causal Relationship? Case Series and Pathophysiological Review

Introducción: Los leiomiomas uterinos son un tipo de neoplasia benigna de frecuente aparición en mujeres de edad reproductiva, relacionados con enfermedad tromboem- bólica venosa. Este vínculo surge del efecto producido por la compresión de fibromas que genera estasis venosa en la región pelviana. Sin embargo, este pareciera no ser el único factor que lo relaciona con el desarrollo posterior de hipertensión pulmonar, sino que su presencia es gatillo de una serie de fenómenos que influyen sobre la vasculatu - ra pulmonar y también a nivel sistémico. Método: Revisión de una serie de casos (seis) atendidos en nuestra unidad, seguido de una revisión sobre la relación entre leiomio- mas y distintas formas de hipertensión pulmonar con una revisión desde la fisiopatología. Resultado y conclusiones: Encontramos sustento bibliográfico en los múltiples caminos fisiopatológicos que relacionan los mediadores vasculares comunes, que parecieran ser el punto clave en la relación entre estas dos patologías.

Introduction: Uterine leiomyomas are a type of benign neoplasm that frequently appears in women of reproductive age, related to venous thromboembolic disease. This link arises from the effect produced by the compression of fibroids, which generates venous stasis in the pelvic region. However, this seems not to be the only factor that re- lates it to the subsequent development of pulmonary hypertension, but rather its presence is a trigger for a series of phenomena that influence the pulmonary vasculature and also at a systemic level. Method: Review of a series of cases (six) cared for in our unit, followed by a review on the relationship between leiomyomas and different forms of pulmonary hypertension with a review from the pathophysiology. Result and conclusions: We found bibliographic support in the multiple pathophysiological paths that relate the common vascular mediators, which appear to be the key point in the relationship between these two pathologies.

La matriz extracelular en la curación de las heridas cutáneas. Aspectos físicos, químicos y biológicos / Extracellular matrix in healing of cutaneous wounds. Physical, chemical and biological aspects

Se revisan los nuevos conocimientos sobre la matriz extracelular (MEC), que han permitido descubrir su importante rol en la cicatrización de las heridas cutáneas. Se describen sus características morfofisiológicas y cómo interviene en la curación de las heridas cutáneas. Se presentan cuatro casos clínicos en los que se aplicó este enfoque terapéutico: los sustitutos de piel y la "cura húmeda"

We review the new knowledge about the extracellular ma-trix (ECM) that has allowed us to discover its important role in the healing of cutaneous wounds. The morpho-physiological characteristics of ECM and its role in the healing of cutaneous wounds are described. Four clinical cases are presented where this therapeutic approach was applied: the skin substitutes and the "moist wound healing".

In Memory of Anthony Stevens: A Career Retrospective with Emphasis on His Formative Role in the Archetype Debate.

This paper celebrates the life and legacy of psychiatrist and Jungian author Anthony Stevens, who passed away at age 90 on July 13, 2023. It outlines Stevens's origins as a research fellow in Greece, where his work on infant attachment led to a lifelong dedication to establishing the biological and evolutionary foundation of psychiatry. It details his instrumental role in the debate about the theory of archetypes and describes the current state of the literature including the responses and reactions to Stevens's biological innatist position. The paper concludes with a career retrospective in which Stevens's major works are introduced and briefly described.

Cet article célèbre la vie et l'héritage du psychiatre et auteur jungien Anthony Stevens, décédé à l'âge de 90 ans le 13 juillet 2023. L'article décrit les origines de Stevens en tant que chercheur en Grèce, où ses travaux sur l'attachement du nourrisson l'ont conduit à se consacrer toute sa vie à établir le fondement biologique de la psychiatrie, dans une perspective évolutionniste. L'article détaille son rôle important dans le débat sur la théorie des archétypes et décrit l'état actuel de la littérature, y compris les réponses et réactions à la position biologique innéiste de Stevens. L'article se termine par une rétrospective de sa carrière, dans laquelle les œuvres majeures de Stevens sont présentées et brièvement décrites.

Este artículo celebra la vida y el legado del psiquiatra y autor Junguiano Anthony Stevens, quien falleció a los 90 años el 13 de julio de 2023. Describe los orígenes de Stevens como investigador en Grecia, donde su trabajo sobre el apego infantil lo llevó a una dedicación de por vida para establecer los fundamentos biológicos y evolutivos de la psiquiatría. Detalla su papel instrumental en el debate sobre la teoría de los arquetipos y describe el estado actual del arte, incluyendo las respuestas y reacciones a la posición biológica innatista de Stevens. El artículo concluye con una retrospectiva de su carrera en la que se presentan y describen brevemente las principales obras de Stevens.

Borderline ovarian tumors: a review of its biology, molecular profile, and management / Tumores borderline de ovário: uma revisão de sua biologia, perfil molecular e manejo

Borderline ovarian tumors typically exhibit indolent behavior and boast a favorable prognosis; however, a subset of patients experiences disease recurrence and progression to low-grade ovarian carcinoma. The complex biology underlying these phenomena has been illuminated through molecular analyses. KRAS and BRAF mutations have emerged as recurrent ?ndings in borderline ovarian tumors. Speci?cally, KRAS mutations have been linked to a higher risk of recurrence and progression to low-grade ovarian carcinoma, while BRAF mutations seem to confer a protective e?ect, inducing a senescent state that mitigates the likelihood of progression. In this comprehensive review, we explore the biology and the molecular pro?le of borderline ovarian tumors, shedding light on recent discoveries that have enriched our comprehension. Additionally, we discuss the current state of borderline ovarian tumors management. Surgery remains the cornerstone of treatment. While cytotoxic therapies role is limited so far, molecular characterization emphasizes the imminent potential for personalized therapeutic approaches.

Os tumores borderline de ovário geralmente exibem comportamento indolente e apresentam prognóstico favorável; no entanto, um subconjunto de pacientes apresenta recorrência da doença e progressão para carcinoma de ovário de baixo grau. A biologia complexa subjacente a estes fenômenos foi iluminada através de análises moleculares. Mutações KRAS e BRAF surgiram como achados recorrentes em tumores borderline de ovário. Especificamente, as mutações KRAS têm sido associadas a um maior risco de recorrência e progressão para carcinoma de ovário de baixo grau, enquanto as mutações BRAF parecem conferir um efeito protetor, induzindo um estado senescente que mitiga a probabilidade de progressão. Nesta revisão abrangente, exploramos a biologia e o perfil molecular dos tumores borderline de ovário, lançando luz sobre descobertas recentes que enriqueceram nossa compreensão. Além disso, discutimos o estado atual do manejo de tumores borderline de ovário. A cirurgia continua sendo o pilar de tratamento. Embora o papel das terapias citotóxicas seja limitado até o momento, a caracterização molecular enfatiza o potencial iminente para abordagens terapêuticas personalizadas.

Beak deformity in three bird species from the southwest of the Brazilian Amazon / Deformidad del pico en tres especies de aves del sudoeste de la Amazonia brasileña

Abstract Beak deformity have a frequency of 0.5% in wild bird populations. In addition to being rare, beak deformities are also poorly reported in the Brazilian scientific literature. Here we report beak deformities in the species: Dendrocincla merula, Amazona ochrocephala and Pheugopedius genibarbis, all of which occurred in southwestern Brazilian Amazon. Dendrocolaptids make intensive use of their beaks in the search for insects and small vertebrates, where they explore in cracks in wood with lateral blows. In the case presented here, this behaviour may have been the cause of the breakage of the tip of this individual's maxilla. In Brazilian territory, few species of parrots were recorded with deformity in the beak and in the individual in this work, everything indicates that Amazona ochrocephala was a captive animal, as it was excessively thin and its diet probably had a low content of vitamins and calcium, where their deficiency even when the animal was a puppy may have contributed to the deformity of the maxilla. Cases of beak deformities in species of the Troglodytidae family are rare, but the individual in this work presented an unusual curvature in the maxilla not observed in other individuals in museum collections. Only with more reports will we be able to better understand the occurrence and causes of these beak deformities in wild birds.

Resumen La deformidad del pico es una característica rara y tiene una frecuencia baja, con 0.5% de casos en poblaciones de aves silvestres. Además de ser raras, las deformidades del pico también son escasamente reportadas en la literatura científica brasileña. Reportamos aquí deformidades en los picos de aves de las especies: Dendrocincla merula, Amazona ochrocephala y Pheugopedius genibarbis, en los cuales todos los registros ocurrieron en el sudoeste de la Amazonia brasileña. Los dendrocoláptidos hacen uso intensivo del pico en la búsqueda de insectos y pequeños vertebrados, explorando en grietas de la madera con golpes laterales. En el caso aquí presentado, este comportamiento de exploración pudo haber sido la causa de la rotura de la punta del maxilar de este individuo. En el territorio brasileño, pocas especies de loros fueron registradas con deformidad en el pico y en el individuo de este trabajo, todo indica que Amazona ochrocephala era un animal de cautiverio, ya que estaba excesivamente delgado y su dieta probablemente tenía un bajo contenido de vitaminas y calcio, donde su deficiencia incluso cuando el animal era un joven puede haber contribuido a la deformidad del maxilar. Los casos de deformidades del pico en especies de la familia Troglodytidae son raros, pero el individuo de este trabajo presentaba una curvatura inusual en el maxilar no observada en otros individuos de esta especie depositados en la colección científica. Sólo con más informes podremos entender mejor la ocurrencia y las causas de estas deformidades del pico en aves silvestres.

Effective conservation of subterranean-roosting bats.

Bats frequently inhabit caves and other subterranean habitats and play a critical role in subterranean food webs. With escalating threats to subterranean ecosystems, identifying the most effective measures to protect subterranean-roosting bats is critical. We conducted a meta-analysis to evaluate the effectiveness of conservation and management interventions for subterranean-roosting bats. We used network analyses to determine to what extent interventions for bats overlap those used for other subterranean taxa. We conducted our analyses with data extracted from 345 papers recommending a total of 910 conservation interventions. Gating of roost entrances was applied to preserve bat populations in 21 studies, but its effectiveness was unclear. Habitat restoration and disturbance reduction positively affected bat populations and bat behavior, respectively, in ≤4 studies. Decontamination was assessed in 2 studies and positively affected bat populations, particularly in studies focused on reducing fungal spores associated with white-nose syndrome in North America. Monitoring of bat populations as an effective conservation strategy was unclear and infrequently tested. Only 4% of bat studies simultaneously considered other subterranean organisms. However, effective interventions for bat conservation had similarities with all other organisms. If other subterranean organisms are considered when applying interventions to conserve bats, they might also benefit.

Conservación eficiente de murciélagos subterráneos Resumen Es común que los murciélagos habiten en cuevas y otros hábitats subterráneos y contribuyan a las redes alimenticias bajo tierra. Ya que estos ecosistemas cada vez se enfrentan a más amenazas, es importante identificar las medidas más efectivas para proteger a los murciélagos subterráneos. Realizamos un metaanálisis para evaluar la eficiencia de la conservación y las intervenciones de manejo para estos mamíferos. Usamos un análisis de redes para determinar el grado al que las intervenciones en pro de los murciélagos se traslapan con aquellas usadas para otros taxones subterráneos. Realizamos nuestros análisis con datos extraídos de 345 artículos que recomendaban 910 intervenciones de conservación. Se aplicó la colocación de compuertas en la entrada de los dormideros para conservar la población de murciélagos en 21 estudios, pero no quedó clara su efectividad. La restauración del hábitat y la reducción de las perturbaciones afectaron, respectivamente, a las poblaciones y al comportamiento de los murciélagos en ≤ 4 cuatro estudios. Se evaluó a la desinfección en dos estudios y ésta tuvo un efecto positivo sobre las poblaciones, particularmente en los estudios enfocados en la reducción de esporas micóticas asociadas con el síndrome de nariz blanca en América del Norte. La eficiencia del monitoreo de las poblaciones de murciélagos como una estrategia de conservación no fue clara y casi nunca se evaluó. Sólo el 4% de los estudios sobre murciélagos consideró simultáneamente a otros organismos subterráneos. Sin embargo, las intervenciones eficientes para la conservación de murciélagos tuvieron similitudes con las de todos los demás organismos. Otros organismos pueden beneficiarse si se les considera cuando se aplican las intervenciones para conservar a los murciélagos.

Gut microbiome as a key monitoring indicator for reintroductions of captive animals.

Reintroduction programs seek to restore degraded populations and reverse biodiversity loss. To examine the hypothesis that gut symbionts could be used as an indicator of reintroduction success, we performed intensive metagenomic monitoring over 10 years to characterize the ecological succession and adaptive evolution of the gut symbionts of captive giant pandas reintroduced to the wild. We collected 63 fecal samples from 3 reintroduced individuals and 22 from 9 wild individuals and used 96 publicly available samples from another 3 captive individuals. By microbial composition analysis, we identified 3 community clusters of the gut microbiome (here termed enterotypes) with interenterotype succession that was closely related to the reintroduction process. Each of the 3 enterotypes was identified based on significant variation in the levels of 1 of 3 genera: Clostridium, Pseudomonas, and Escherichia. The enterotype of captive pandas was Escherichia. This enterotype was gradually replaced by the Clostridium enterotype during the wild-training process, which in turn was replaced by the Pseudomonas enterotype that resembled the enterotype of wild pandas, an indicator of conversion to wildness and a successful reintroduction. We also isolated 1 strain of Pseudomonas protegens from the wild enterotype, a previously reported free-living microbe, and found that its within-host evolution contributed to host dietary adaptation in the wild. Monitoring gut microbial structure provides a novel, noninvasive tool that can be used as an indicator of successful reintroduction of a captive individual to the wild.

Microbiomas intestinales como indicadores clave de monitoreo para la reintroducción de animales cautivos Resumen Los programas de reintroducción buscan restaurar las poblaciones degradadas y revertir la pérdida de la biodiversidad. Realizamos un monitoreo metagenómico intensivo durante más de diez años para caracterizar la sucesión ecológica y la evolución adaptativa de los simbiontes intestinales de pandas reintroducidos en la naturaleza y así comprobar la hipótesis de que estos simbiontes pueden usarse como indicadores de una reintroducción exitosa. Recolectamos 63 muestras fecales de tres individuos reintroducidos y 22 de nueve individuos silvestres y usamos 96 muestras disponibles al público de otros tres individuos cautivos. Mediante el análisis de la composición microbiana identificamos tres grupos comunitarios del microbioma intestinal (denominados como enterotipos) con una sucesión entre enterotipos relacionada cercanamente al proceso de reintroducción. Identificamos cada uno de los tres enterotipos con base en la variación significativa en los niveles de uno de los tres géneros: Clostridium, Pseudomonas, y Escherichia. El enterotipo de los pandas cautivos fue Escherichia. A este enterotipo lo reemplazó gradualmente el enterotipo de Clostridium durante el proceso de adaptación a la naturaleza, y a su vez fue reemplazado por el enterotipo de Pseudomonas similar al de los pandas silvestres, un indicador de la conversión a la vida silvestre y de una reintroducción exitosa. También aislamos una cepa de Pseudomonas protegens del enterotipo silvestre, un microbio reportado previamente como de vida libre, y descubrimos que su evolución dentro del hospedero contribuyó a que este se adaptara a la naturaleza de la dieta. El monitoreo de la estructura microbiana intestinal proporciona una herramienta novedosa y no invasiva que puede usarse como indicador del éxito de la reintroducción de un individuo cautivo a la naturaleza.

Survey of Portulacaceae family flora in Taif, Saudi Arabia

Abstract The presence of weeds in areas of agricultural activities is a hinderance to the development of these activities. It is important to take advantage of the vast open spaces suitable for agriculture and provide food security for humans, and also it is an important indicator for determining the feasibility of growing crops, benefiting from yield and determining the percentage of loss, clearing fields through agricultural practices, that protect crops from weed attack and agricultural practice method must be followed that will reduce weed presence. This study was conducted during the years 2018 to 2020 to evaluate Portulacaceae of Flora in the Taif area in the Kingdom of Saudi Arabia at different altitudes (Area 1 =1700 m, Area 2 =1500 m, Area 3 =1500 m, Area 4 =500 m Area 5 = 2200 m, and Area 6 = 2200 m). The results show that there were 2,816 individuals of Portulaca oleracea weed, with the highest density found in A 1, followed by A 2, while in A 5 and A 6, no weeds were recorded. The highest density of weeds were in the Pomegranate fields, followed by Grape fields. The lowest density was found in A man field. The results of this study will help to take the necessary measures to combat weeds and its management in areas of agricultural activity, while more studies are needed to survey the ecology of weeds of Taif in The Kingdom of Saudi Arabia.

Resumo A presença de plantas daninhas em áreas de atividades agrícolas é um entrave ao desenvolvimento dessas atividades. É importante aproveitar os vastos espaços abertos adequados para a agricultura e dar segurança alimentar para o homem. Também é um indicador importante para determinar a viabilidade de cultivo de lavouras, beneficiando-se da produtividade e determinando o percentual de perda, desmatando campos agrícolas, práticas que protegem as lavouras do ataque de ervas daninhas, e métodos de práticas agrícolas devem ser seguidos para reduzir a presença de ervas daninhas. Este estudo foi realizado durante os anos de 2018 a 2020 para avaliar Portulacaceae de flora na área de Taif, no Reino da Arábia Saudita, em diferentes altitudes (Área 1 = 1.700 m, Área 2 = 1.500 m, Área 3 = 1.500 m, Área 4 = 500 m, Área 5 = 2.200 m, e Área 6 = 2.200 m). Os resultados mostram que houve 2.816 indivíduos de planta daninha Portulaca oleracea, com a maior densidade encontrada em A 1, seguida de A 2, enquanto em A 5 e A 6, nas plantas daninhas foram registrados. A maior densidade de ervas daninhas estava nos campos de romã, seguido pelos campos de uva. A densidade mais baixa foi encontrada no campo A man. Os resultados deste estudo ajudarão a tomar as medidas necessárias para combater as ervas daninhas e seu manejo em áreas de atividade agrícola, enquanto mais estudos são necessários para levantar a ecologia das ervas daninhas de Taif na Arábia Saudita.

Survey of Portulacaceae family flora in Taif, Saudi Arabia / Levantamento da flora da família Portulacaceae em Taif, Arábia Saudita

Abstract The presence of weeds in areas of agricultural activities is a hinderance to the development of these activities. It is important to take advantage of the vast open spaces suitable for agriculture and provide food security for humans, and also it is an important indicator for determining the feasibility of growing crops, benefiting from yield and determining the percentage of loss, clearing fields through agricultural practices, that protect crops from weed attack and agricultural practice method must be followed that will reduce weed presence. This study was conducted during the years 2018 to 2020 to evaluate Portulacaceae of Flora in the Taif area in the Kingdom of Saudi Arabia at different altitudes (Area 1 =1700 m, Area 2 =1500 m, Area 3 =1500 m, Area 4 =500 m ِ Area 5 = 2200 m, and Area 6 = 2200 m). The results show that there were 2,816 individuals of Portulaca oleracea weed, with the highest density found in A 1, followed by A 2, while in A 5 and A 6, no weeds were recorded. The highest density of weeds were in the Pomegranate fields, followed by Grape fields. The lowest density was found in A man field. The results of this study will help to take the necessary measures to combat weeds and its management in areas of agricultural activity, while more studies are needed to survey the ecology of weeds of Taif in The Kingdom of Saudi Arabia.

Resumo A presença de plantas daninhas em áreas de atividades agrícolas é um entrave ao desenvolvimento dessas atividades. É importante aproveitar os vastos espaços abertos adequados para a agricultura e dar segurança alimentar para o homem. Também é um indicador importante para determinar a viabilidade de cultivo de lavouras, beneficiando-se da produtividade e determinando o percentual de perda, desmatando campos agrícolas, práticas que protegem as lavouras do ataque de ervas daninhas, e métodos de práticas agrícolas devem ser seguidos para reduzir a presença de ervas daninhas. Este estudo foi realizado durante os anos de 2018 a 2020 para avaliar Portulacaceae de flora na área de Taif, no Reino da Arábia Saudita, em diferentes altitudes (Área 1 = 1.700 m, Área 2 = 1.500 m, Área 3 = 1.500 m, Área 4 = 500 m, Área 5 = 2.200 m, e Área 6 = 2.200 m). Os resultados mostram que houve 2.816 indivíduos de planta daninha Portulaca oleracea, com a maior densidade encontrada em A 1, seguida de A 2, enquanto em A 5 e A 6, nas plantas daninhas foram registrados. A maior densidade de ervas daninhas estava nos campos de romã, seguido pelos campos de uva. A densidade mais baixa foi encontrada no campo A man. Os resultados deste estudo ajudarão a tomar as medidas necessárias para combater as ervas daninhas e seu manejo em áreas de atividade agrícola, enquanto mais estudos são necessários para levantar a ecologia das ervas daninhas de Taif na Arábia Saudita.

Identificação de Potenciais Biomarcadores Cruciais em IAMCSST por Meio de Análise Bioinformática Integrada / Identification of Potential Crucial Biomarkers in STEMI Through Integrated Bioinformatic Analysis

Resumo Fundamento O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. Objetivos Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. Métodos Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de -log2fold change- > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Resultados 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. Conclusões Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST.

Abstract Background ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking. Objectives In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI. Methods We obtained GSE59867 for STEMI and stable coronary artery disease (SCAD) patients. Differentially expressed genes (DEGs) were screened with the threshold of -log2fold change- > 0.5 and p <0.05. Based on these genes, we conducted enrichment analysis to explore the potential relevance between genes and to screen hub genes. Subsequently, hub genes were analyzed to detect related miRNAs and DAVID to detect transcription factors for further analysis. Finally, GSE62646 was utilized to assess DEGs specificity, with genes demonstrating AUC results exceeding 75%, indicating their potential as candidate biomarkers. Results 133 DEGs between SCAD and STEMI were obtained. Then, the PPI network of DEGs was constructed using String and Cytoscape, and further analysis determined hub genes and 6 molecular complexes. Functional enrichment analysis of the DEGs suggests that pathways related to inflammation, metabolism, and immunity play a pivotal role in the progression from SCAD to STEMI. Besides, related-miRNAs were predicted, has-miR-124, has-miR-130a/b, and has-miR-301a/b regulated the expression of the largest number of genes. Meanwhile, Transcription factors analysis indicate that EVI1, AML1, GATA1, and PPARG are the most enriched gene. Finally, ROC curves demonstrate that MS4A3, KLRC4, KLRD1, AQP9, and CD14 exhibit both high sensitivity and specificity in predicting STEMI. Conclusions This study revealed that immunity, metabolism, and inflammation are involved in the development of STEMI derived from SCAD, and 6 genes, including MS4A3, KLRC4, KLRD1, AQP9, CD14, and CCR1, could be employed as candidate biomarkers to STEMI.

La Food and Agricultural Organization y la institucionalización de la biología pesquera en Brasil, 1955-1978: complejidades de la circulación del conocimiento científico / The Food and Agricultural Organization and the institutionalization of fishery biology in Brazil, 1955-1978: complexities of the circulation of scientific knowledge

Resumen Este trabajo analiza el programa de asistencia técnica a la investigación y el desarrollo pesquero, implementado por la Food and Agriculture Organization (FAO) en Brasil, entre 1955 y 1978. Nos interrogamos cuáles son las motivaciones de los países desarrollados, de la FAO y de Brasil para movilizar ese conocimiento y cómo se construyó el soporte socio-institucional para su afincamiento. Siguiendo el itinerario de los expertos y atendiendo a las características del campo de la biología pesquera, mostramos cómo se construyeron, de manera simultánea, el campo de investigación, la política y la actividad pesquera brasileñas. Para eso, recurrimos a los informes de varios expertos de la FAO y de organismos públicos brasileños.

Abstract This paper analyzes the technical assistance program for research and fishery development, implemented by the Food and Agriculture Organization (FAO) in Brazil, between 1955 and 1978. We argue what were the motivations of the developed countries, the FAO and Brazil to mobilize this knowledge and how the socio-institutional support for its achievement was built. Following the itinerary of experts and attending to the characteristics of the field of fishing biology, we show how the Brazilian field of research, policies and fishing activity were built simultaneously. For this purpose, we used reports from several experts from the FAO and Brazilian public bodies.

Pathophysiology of posttraumatic ankle osteoarthritis: a multicenter perspective / Fisiopatologia da osteoartrite pós-traumática do tornozelo: perspectiva multicêntrica

ABSTRACT Besides the acute injury and trauma-induced macroscopic alterations, the evolution to posttraumatic ankle osteoarthritis (PTOA) is a complex process progressing at the tissue and molecular level. Furthermore, changes in the molecular pathways affect chondrocyte viability. Treatment modalities for PTOA focal or confined disease include innovative techniques. Objective: Our purpose is to increase medical awareness based on scientific evidence of pathophysiology, molecular biology, and treatment of post-traumatic ankle osteoarthritis. Methods: To support the perspectives of the experts, evidence from the scientific literature respected the PRISMA guidelines and the PICOS search strategy was used. We included case-control, cohort, experimental studies and case reports, written in English. Results: The authors were homogeneously exposed to 282 selected abstracts and 114 full articles directly related to post-traumatic osteoarthritis after malleolar fractures. Conclusion: The pathophysiological factors involved in posttraumatic ankle osteoarthritis, such as biological, structural, mechanical, and molecular changes must be studied together, as the interaction between these factors determines the risk of progression of PTOA. Inhibition of a single catabolic molecule or cascade probably is not sufficient to alter the natural progression of the pathological process. Evidence level V, expert opinion.

RESUMO A evolução para a osteoartrite pós-traumática do tornozelo (PTOA) a partir da lesão aguda e das alterações macroscópicas induzidas pelo trauma é um processo complexo, que progride em nível tecidual e molecular. Além disso, as alterações nas vias moleculares afetam a viabilidade dos condrócitos. As modalidades focais ou confinadas de tratamento para PTOA incluem técnicas inovadoras. Objetivo: Nosso objetivo é aumentar a conscientização médica, com base em evidências científicas de fisiopatologia, biologia molecular e tratamento da osteoartrite pós-traumática do tornozelo. Métodos: Para o embasamento das perspectivas dos autores experts, as evidências da literatura científica respeitaram as diretrizes Prisma e a estratégia de busca Picos foi empregada. Incluímos estudos de caso-controle, de coorte, experimentais e relatos de caso, escritos em inglês. Resultados: Os autores foram expostos de forma homogênea a 282 resumos e 114 artigos completos, diretamente relacionados à osteoartrite pós-traumática após fraturas maleolares. Conclusão: Os fatores fisiopatológicos envolvidos na osteoartrite pós-traumática do tornozelo, como alterações biológicas, estruturais, mecânicas e moleculares, devem ser estudados em conjunto, pois a interação entre esses fatores determina o risco de progressão da PTOA. A inibição de uma única molécula catabólica ou cascata provavelmente não é suficiente para alterar a progressão natural do processo patológico. Nível de evidência V, opinião do especialista.

Understanding distribution and survey gaps of Mammals from the Atlantic Forest and Cerrado Biomes / Compreendendo Lacunas na Distribuição e Amostragem de Mamíferos dos Biomas da Mata Atlântica e Cerrado

Abstract The Atlantic Forest and Cerrado (Brazilian Savannah) contain a large number of endemic species and high species diversity, particularly for medium and large-bodied mammals. However, there is no large-scale assessment of these animals and their spatial distribution. Our study synthesises the literature on medium and large-bodied mammal surveys in the Cerrado and Atlantic Forest to provide insights into their distributions across large spatial scales and identify knowledge gaps to guide future research. We synthesised papers published in three databases, focusing on mammals weighing more than 1kg. Of the 84 papers we found, the majority (57.14%) were on mammals in the Atlantic Forest, while 42.85% were on mammals found in the Cerrado. We gathered records for 116 species, the most common of which were Cerdocyon thous (Linnaeus, 1766), Procyon cancrivorus (Cuvier, 1798) and Chrysocyon brachyurus (Illiger, 1815) (Cerrado); Dasypus novemcinctus (Linnaeus, 1758), Cerdocyon thous (Linnaeus, 1766) and Nasua nasua (Linnaeus, 1766; Atlantic Forest). Our study allowed us to access, for the first time in the Atlantic Forest and Cerrado, the information available about medium and large-bodied mammals. We also highlight important sampling gaps, especially concerning the northern parts of both biomes that we need to address, as well as the differences in density of sampling points that are caused by a smaller concentration of sampling efforts in the Atlantic Forest than what we found in Cerrado. As a consequence, larger extensions of Cerrado present knowledge gaps concerning mammal surveys that need to be investigated in future research.

Resumo A Mata Atlântica e o Cerrado brasileiro abrigam uma enorme quantidade de espécies endêmicas e alta diversidade de espécies, especialmente de mamíferos de médio e grande porte. No entanto, não há uma avaliação em larga escala desses animais e de sua distribuição espacial. Nosso estudo sintetiza a literatura sobre levantamentos de mamíferos de médio e grande porte no Cerrado e na Mata Atlântica, com o objetivo de fornecer informações sobre suas distribuições em larga escala e identificar lacunas no conhecimento para guiar futuras pesquisas. Sintetizamos artigos publicados em três bases de dados, com foco em mamíferos com peso superior a 1 kg. Dos 84 artigos encontrados, a maioria (57,14%) tratava de mamíferos na Mata Atlântica, enquanto 42,85% abordavam mamíferos encontrados no Cerrado. Coletamos registros para 116 espécies, sendo as mais comuns Cerdocyon thous (Linnaeus, 1766), Procyon cancrivorus (Cuvier, 1798) e Chrysocyon brachyurus (Illiger, 1815) (Cerrado); Dasypus novemcinctus (Linnaeus, 1758), Cerdocyon thous (Linnaeus, 1766) e Nasua nasua (Linnaeus, 1766; Mata Atlântica). Nosso estudo também mostra as lacunas no levantamento especialmente em relação às distribuições ao norte dos biomas, que precisam ser resolvidas, assim como a diferença na densidade de pontos que é causada pela menor concentração de amostragens na Mata Atlântica do que o que encontramos no Cerrado. Como consequência, existem largas extensões do Cerrado que apresentam lacunas no levantamento de mamíferos que precisam ser investigados em pesquisas futuras.

Análisis de los sitios de unión de la ivermectina en la estructura de importinas α humanas

La ivermectina demostró importantes acciones antivirales ante varios virus con genoma de ARN, inclusive contra el SARS-CoV-2. Este fármaco inhibe la actividad del heterodímero importina α/ß1, sin embargo, se desconoce los blancos específicos de interacción de la molécula. Objetivos: analizar in silico los blancos de interacción de la ivermectina en interacción con la estructura de la importina α humana, utilizando la estrategia del acoplamiento molecular. Métodos: se realizaron simulaciones del acoplamiento utilizando un modelo semiflexible y el algoritmo Broyden-Fletcher-Goldfarb-Shanno entre las estructuras de ivermectina y la importina α. Resultados: los datos obtenidos revelan una mayor afinidad de interacción de la ivermectina a la región mayor de unión (armadillo ARM2-ARM4) de las importinas α humanas, con energías de unión favorables de -9,5 a -8,0 kcal.mol-1. Los aminoácidos activos de importancia en las uniones fueron el Triptófano, Asparagina y Arginina, los cuales también son fundamentales para el reconocimiento de secuencias NLS (secuencias de localización nuclear) de las proteínas virales. También se registró afinidades por los dominios H1-ARM5, H2-ARM6 y H2-ARM7, con energía de unión de -7,5 kcal.mol-1. Conclusiones: los hallazgos demuestran que la ivermectina presenta afinidades de unión favorables a la región mayor de unión (ARM2-ARM4) de las importinas a el cual es un sitio importante de unión a proteínas virales.

Ivermectin has demonstrated significant antiviral actions against several RNA-genome viruses, including SARS-CoV-2. This drug inhibits the activity of the α/ß1 importin heterodimer; however, the specific interaction targets of the molecule are unknown yet. Objectives: to analyze in silico the interaction targets of ivermectin interacting with the human α-importin structure using the molecular docking strategy. Methods: simulations of the molecular docking were carried out using a semi-flexible model and the Broyden-Fletcher-Goldfarb- Shanno algorithm between the structures of ivermectin and importin α. Results: data obtained reveal a higher interaction affinity of ivermectin to the major binding region (armadillo ARM2-ARM4) of human importins α, with favorable binding energies of -9,5 to -8,0 kcal.mol-1. The active amino acids of importance in the bindings were Tryptophan, Asparagine and Arginine, which are also critical for the recognition of NLS sequences (nuclear location sequences) of viral proteins. Affinities for H1-ARM5, H2-ARM6 and H2-ARM7 domains were also recorded, with binding energy of -7,5 kcal.mol-1. Conclusions: the findings demonstrate that ivermectin exhibits favorable binding affinities to the major binding region (ARM2-ARM4) of importins a which is an important viral protein binding site.