Immunochemical Recognition of Bothrops rhombeatus Venom by Two Polyvalent Antivenoms.

The protein profile of Bothrops rhombeatus venom was compared to Bothrops asper and Bothrops atrox, and the effectiveness of antivenoms from the National Institute of Health of Colombia (INS) and Antivipmyn-Tri (AVP-T) of Mexico were analyzed. Protein profiles were studied with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and reverse-phase high-performance liquid chromatography (RP-HPLC). The neutralizing potency and the level of immunochemical recognition of the antivenoms to the venoms were determined using Western blot, affinity chromatography, and enzyme-linked immunosorbent assay (ELISA). Bands of phospholipase A2 (PLA2), metalloproteinases (svMPs) I, II, and III as well as serine proteinases (SPs) in the venom of B. rhombeatus were recognized by SDS-PAGE. With Western blot, both antivenoms showed immunochemical recognition towards PLA2 and svMP. INS showed 94% binding to B. rhombeatus venom and 92% to B. asper while AVP-T showed 90.4% binding to B. rhombeatus venom and 96.6% to B. asper. Both antivenoms showed binding to PLA2 and svMP, with greater specificity of AVP-T towards B. rhombeatus. Antivenom neutralizing capacity was calculated by species and mL of antivenom, finding the following for INS: B. asper 6.6 mgV/mL, B. atrox 5.5 mgV/mL, and B. rhombeatus 1.3 mgV/mL. Meanwhile, for AVP-T, the following neutralizing capacities were found: B. asper 2.7 mgV/mL, B. atrox 2.1 mgV/mL, and B. rhombeatus 1.4 mgV/mL. These results show that both antivenoms presented similarity between calculated neutralizing capacities in our trial, reported in a product summary for the public for the B. asper species; however, this does not apply to the other species tested in this trial.

Challenges in the design and synthesis of self-assembling molecules as selective contacts in perovskite solar cells.

Self-assembling molecules (SAMs), as selective contacts, play an important role in perovskite solar cells (PSCs), determining the performance and stability of these photovoltaic devices. These materials offer many advantages over other traditional materials used as hole-selective contacts, as they can be easily deposited on a large area of metal oxides, can modify the work function of these substrates, and reduce optical and electric losses with low material consumption. However, the most interesting thing about SAMs is that by modifying the chemical structure of the small molecules used, the energy levels, molecular dipoles, and surface properties of this assembled monolayer can be modulated to fine-tune the desired interactions between the substrate and the active layer. Due to the important role of organic chemistry in the field of photovoltaics, in this review, we will cover the current challenges for the design and synthesis of SAMs PSCs. Discussing, the structural features that define a SAM, (ii) disclosing how commercial molecules inspired the synthesis of new SAMs; and (iii) detailing the pros- and cons- of the reported synthetic protocols that have been employed for the synthesis of molecules for SAMs, helping synthetic chemists to develop novel structures and promoting the fast industrialization of PSCs.

Influence of the carbazole moiety in self-assembling molecules as selective contacts in perovskite solar cells: interfacial charge transfer kinetics and solar-to-energy efficiency effects.

The use of self-assembled molecules (SAMs) as hole transport materials (HTMs) in p-i-n perovskite solar cells (iPSCs) has triggered widespread research due to their relatively easy synthetic methods, suitable energy level alignment with the perovskite material and the suppression of chemical defects. Herein, three new SAMs have been designed and synthesised based on a carbazole core moiety and modified functional groups through an efficient synthetic protocol. The SAMs have been used to understand the SAM/perovskite interface interactions and establish the relationship between the SAM molecular structure and the resulting performance of the perovskite-based devices. The best devices show efficiencies ranging from 18.9% to 17.5% under standard illumination conditions, which are very close to that of our benchmark EADR03, which has been recently commercialised. Our work aims to provide knowledge on the structure of the molecules versus device function relationship.

Genetic Variations in the Purinergic P2X7 Receptor Are Associated with the Immune Response to Ocular Toxoplasmosis in Colombia.

Ocular toxoplasmosis (OT) is characterized by inflammation within the eye and is the most recognized clinical manifestation of toxoplasmosis. The objective of this study was to identify new single-nucleotide polymorphisms (SNPs) in the P2RX7 gene that may have significance in the immune response to OT in Colombian patients. A case-control study was conducted to investigate the associations between SNPs (rs1718119 and rs2230912) in the P2RX7 gene and OT in 64 Colombian patients with OT and 64 controls. Capillary electrophoresis was used to analyze the amplification products, and in silico algorithms were employed to predict deleterious SNPs. Stability analysis of amino acid changes indicated that both mutations could lead to decreased protein structure stability. A nonsynonymous SNP, Gln460Arg, located in the long cytoplasmic tail of the receptor, showed a significant association with OT (Bonferroni correction (BONF) = 0.029; odds ratio OR = 3.46; confidence interval CI: 1.05 to 11.39), while no significant association between rs1718119 and OT risk was observed. Based on the 3D structure analysis of the P2RX7 protein trimer, it is hypothesized that an increase in the flexibility of the cytoplasmic domain of this receptor could alter its function. This SNP could potentially serve as a biomarker for identifying Colombian patients at risk of OT.

Automatic detection of Cryptosporidium in optical microscopy images using YOLOv5x: a comparative study.

Here, a machine learning tool (YOLOv5) enables the detection of Cryptosporidium microorganisms using optical and phase contrast microscope images. The two databases were processed using 520 images (optical microscopy) and 1200 images (phase contrast microscopy). It used Python libraries to label, standardize the size, and crop the images to generate the input tensors to the YOLOv5 network (s, m, and l). It implemented two experiments using randomly initialized weights in optical and phase contrast microscope images. The other two experiments used the parameters for the best training time obtained before and after retraining the models. Metrics used to assess model accuracy were mean average accuracy, confusion matrix, and the F1 scores. All three metrics confirmed that the optimal model used the best epoch of optical imaging training and retraining with phase contrast imaging. Experiments with randomly initialized weights with optical imaging showed the lowest precision for Cryptosporidium detection. The most stable model was YOLOv5m, with the best results in all categories. However, the differences between all models are lower than 2%, and YOLOv5s is the best option for Cryptosporidium detection considering the differences in computational costs of the models.

Perfil cognitivo y social en niños y niñas con Trastorno del Espectro Autista / Cognitive and social profile in children with autism spectrum disorder

El Trastorno del Espectro Autista (TEA) es una condición que se caracteriza por presentar fallas en la conducta social y comportamientos repetitivos. Su perfil neuropsicológico muestra hallaz-gos heterogéneos que dependen de la severidad del trastorno. El objetivo del presente trabajo es describir el funcionamiento neuropsicológico de una muestra de niños y niñas con TEA que asisten al Instituto para el Desarrollo Integral del Niño en condición de Autismo (DINA). La muestra estuvo conformada por 78 participantes, 15.4% de género femenino y 84.6% de géne-ro masculino, con edades entre los 6 y los 16 años. Los instrumentos utilizados fueron protocolo neuropsicológico adaptado de la ENI, prorrateo de inteligencia del WISC-IV, Test de Sally y Ann, Test de Expresiones faciales adaptadopor Paul Ekman y el Test de la Mirada para niños, El Test de Metidas de Pata, e Historias Extrañas de Happé. Los resultados se discuten a la luz de la li-teratura científica sobre el tema.

Autism Spectrum Disorder (ASD) is a condition that is characterized by failures in social behav-ior and repetitive behaviors. The neuropsychological profile shows heterogeneous findings that depends on the severity of the disorder. The objective of this paper is to describe the neuropsychological functioning of a sample of children with ASD who attend the Institute for the Integral Development of Children with Autism (DINA). The sample consisted of 78 partici-pants, 15.4% female and 84.6% male, aged between6 and 16 years. The instruments used were the neuropsychological protocol adapted from the ENI, intelligence apportionment from the WISC-IV, Sally and Ann Test, Facial Expressions Test adapted by Paul Ekman and Reading the Mind in the Eye for children, Faux Pas Test, and The Happé’s Strange Stories test. The re-sults are discussed considering the scientific literature on the subject. (AU)

Microwave-assisted Synthesis of Pharmacologically Active 4-Phenoxyquinolines and their Benzazole-quinoline Hybrids Through SNAr Reaction of 4,7-dichloroquinoline and Phenols Using [bmim][PF6] as a Green Solvent.

BACKGROUND: Quinoline and its derivatives have been shown to display a wide spectrum of biological properties, especially anticancer activity. Particularly, diverse potent anticancer drugs are based on the 4-phenoxyquinoline skeleton, acting as small-molecules VEGR2 and/or c-Met kinase inhibitors. However, the design of new drugs based on these quinoline derivatives remains a challenge. Up till now, all approaches to 4-phenoxyquinoline skeleton construction do not obey any green chemistry principles. AIMS AND OBJECTIVES: Developing a new, and efficient protocol for the synthesis of potentially bioactive 4-phenoxyquinoline derivatives and benzazole-quinoline-quinoline hybrids from commercially available 4,7-dichloroquinoline and phenol derivatives using microwave energy (MW) in the presence of 1-methyl 3-butylimidazolium hexafluorophosphate. METHODS: Neweco-efficient protocol for valuable 7-chloro-4-phenoxyquinolines and their hybrids, which is based on SNAr reaction of 4,7-dichloroquinoline with respective simple phenols and hydroxyaryl- benzazoles under MWenergy in green reaction media, is studied for the first time. RESULTS: We found that among various solvents tested, the ionic liquid 1-methyl 3-butylimidazolium hexafluorophosphate ([bmim][PF6]) favored the SNAr reaction affording phenoxyquinolines in excellent yields (72-82%) in 10 min. The developed protocol allowed to obtain quickly in good yields (48-60%) new diverse benzazole-quinoline hybrids, which are expected to be pharmacologically active. According to the calculated bioactivity scores, new hybrids are potential kinase inhibitors that could be useful in anticancer drug research. CONCLUSION: We developed for the first time a new green, efficient method to prepare potentially bioactive functionalized 7-chloro-4-phenoxyquinolines and benzazole-quinoline molecules. Good to excellent yields of the quinoline products, use of MW irradiation in ([bmim] [PF6] as a green solvent, and short times of reactions are some of the main advantages of this new protocol.

Synthesis, In Silico and In Vivo Toxicity Assessment of Functionalized Pyridophenanthridinones via Sequential MW-Assisted Intramolecular Friedel-Crafts Alkylation and Direct C-H Arylation.

A rapid, efficient, and original synthesis of novel pyrido[3,2,1-de]phenanthridin-6-ones is reported. First, the key cinnamamide intermediates 8a-f were easily prepared from commercial substituted anilines, cinnamic acid, and 2-bromobenzylbromide in a tandem amidation and N-alkylation protocol. Then, these N-aryl-N-(2-bromobenzyl) cinnamamides 8a-f were subjected to a TFA-mediated intramolecular Friedel-Crafts alkylation followed by a Pd-catalyzed direct C-H arylation to obtain a series of potentially bioactive 4-phenyl-4,5-dihydro-6H,8H-pyrido[3,2,1-de]phenanthridin-6-one derivatives 4a-f in good yields. Finally, the toxicological profile of the prepared final compounds, including their corresponding intermediates, was explored through in silico computational methods, while the acute toxicity toward zebrafish embryos (96 hpf-LC50, 50% lethal concentration) was also determined in the present study.

Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets.

Infections of humans with the protozoan parasite Toxoplasma gondii (T. gondii) can lead to the disease's development, even in an asymptomatic status. However, the mechanisms that result in these clinical outcomes after infection are poorly understood. This study aimed to explore the molecular pathogenesis of toxoplasmosis-related inflammation through next-generation sequencing, to assess RNA expression profiles in peripheral blood from 5 female patients with chronic toxoplasmosis and 5 healthy female controls. All plasma samples were analyzed for anti-Toxoplasma IgG and IgM antibody titers by using electrochemiluminescence. Detection of acute and chronic toxoplasmosis was carried out using the ELISA IgG avidity. We evaluated the levels of INF-γ, IL-2, IL-12, TNF-α, IL-10, and IL-1ß in culture supernatants of Peripheral Blood Mononuclear Cells infected with Toxoplasma lysate antigen (TLA) prepared with tachyzoites of strain T. gondii RH. Differential expression analysis was performed using DESeq2, pathway and enrichment analysis of DEGs was done on WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and Protein-protein interaction was carried out using NetworkAnalyst with STRING. In older people with chronic asymptomatic infection, a significant difference in the levels of inflammatory cytokines INF-γ and IL-2 was observed compared to seronegative individuals. Our results revealed differences in the regulation of critical biological processes involved in host responses to chronic T. gondii infection. Gene ontology analysis revealed several biologically relevant inflammatory and immune-related pathways.

Disreflexia autonómica: conceptos esenciales desde la medicina física y la rehabilitación / Autonomicdys reflexia: Essential concepts from physica medicine and rehabilitation

El traumatismo de la médula espinal es una condición frecuente a nivel mundial, provoca impacto sobre la funcionalidad y genera un elevado índice de discapacidad. Presenta manifestaciones motoras, sensitivas y, adicionalmente, autonómicas, siendo estas últimas una causa importante de morbilidad y mortalidad. Las lesiones medulares en niveles superiores a T6 pueden generar disreflexia autonómica (DA), que se manifiesta principalmente con hipertensión arterial y otros síntomas autonómicos que se desencadenan por reflejos simpáticos no modulados, liberados por una gran variedad de estímulos viscerales y somáticos. Las manifestaciones clínicas de la DA generan complicaciones adicionales al cuadro clínico e incluso pueden generar la muerte del paciente. Por tanto, es de vital importancia el conocimiento de la patología, la identificación precoz y el manejo de la DA. En el presente artículo se realiza una revisión narrativa sobre la DA con el objetivo de dar a conocer la definición, la fisiopatología y el manejo actual

Spinal cord trauma is a common condition worldwide, it has an impact on functionality and generates a high rate of disability. It presents motor, sensory and, additionally, autonomic manifestations, the latter being an important cause of morbidity and mortality. Spinal cord injuries at levels above T6 can generate autonomic dysreflexia (AD), which manifests mainly with arterial hypertension and other autonomic symptoms that are triggered by unmodulated sympathetic reflexes, released by a wide variety of visceral and somatic stimuli. The clinical manifestations of AD generate additional complications to the clinical picture and may even lead to the death of the patient. Therefore, knowledge of the pathology, early identification and management of AD is of vital importance. In the present article, a narrative review of AD is carried out with the aim of providing the definition, pathophysiology and current management of AD.

Determinación de los valores de referencia de las ondas F para miembros superiores e inferiores en adultos sanos de Bogotá, Colombia / Determination of F-wave reference values for upper and lower limbs in healthy adults in Bogota, Colombia

Introducción. El estudio de las ondas F evalúa la fisiología normal y anormal del sistema nervioso central y periférico. Sus valores de referencia utilizados actualmente se obtienen según la edad y estatura de poblaciones europeas y estadounidenses y no existe ningún estudio que analice sistemáticamente los valores normales en población colombiana. Objetivo. Analizar los parámetros de ondas F en adultos sanos asistentes a la IPS Rangel de Bogotá para crear una base de datos de valores de referencia que permita determinarycrear una guía de parámetros de normalidad de ondas F en población colombiana adulta sana. Métodos. Estudio observacional desarrollado entre enero de 2019 y diciembre de 2020 y realizado en 53 hombres y mujeres de entre 18 y 60 años asistentes a la IPS Rangel. Se registraron los valores de las ondas F de los nervios mediano, cubital, peroneo y tibial, bilateralmente, según parámetros de latencia mínima, latencia máxima, cronodispersión y persistencia. Los datos recolectados se registraron en una base de datos para su análisis. Resultados. En los miembros superiores se encontraron latencias medias mínimas de 22-26ms y en los inferiores, de 36-46ms. No se encontraron diferencias significativas según la lateralidad y el grupo etario. En el análisis de resultados porsexo se hallaron diferencias significativas entre las latencias mínimas y máximas. La talla se dividió en 3 categorías, encontrándose diferencias significativas entre las latencias distales mínimasy máximas. Conclusiones. El presente estudio determinó los valores de referencia clínicamente útiles para los parámetros de las ondas F en bogotanos sanos de 18 a 60 años de edad para los principales nervios motores, lo cual permite incrementar la calidad de detección de la neuropatía periférica proximal.

Introduction. The study of F waves evaluates the normal and abnormal physiology of the central and peripheral nervous system. Its currently used reference values are obtained according to age and height in European and American populations and there is no study that systematically analyzes the normal values in the Colombian population. Objective. To analyze the F-wave parameters in healthy adults attending the IPS Rangel in Bogotá in order to create a database of reference values to determine and create a guide of F-wave normality parameters in a healthy adult Colombian population. Methods. Observational study developed between January 2019 and December 2020 and conducted in 53 men and women aged 18 to 60 years attending the IPS Rangel. The values of F waves of the median, ulnar, peroneal and tibial nerves were recorded bilaterally, according to parameters of minimum latency, maximum latency, chronodispersion and persistence. The collected data were recorded in a database for analysis. Results. Minimum mean latencies of 22-26ms were found in the upper limbs and 36-46ms in the lower limbs. No significant differences were found according to laterality and age group. In the analysis of results by sex, significant differences were found between minimum and maximum latencies. The height was divided into 3 categories, and significant differences were found between the minimum and maximum distal latencies. Conclusions. The present study determined clinically useful reference values for F-wave parameters in healthy Bogotanos aged 18 to 60 years for the main motor nerves, which allows to increase the quality of detection of proximal peripheral neuropathy.

Inflammatory gene expression profiling in peripheral blood from patients with Alzheimer's disease reveals key pathways and hub genes with potential diagnostic utility: a preliminary study.

BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disease caused by central nervous system disorders. Late-onset Alzheimer disease (LOAD) is the most common neurodegenerative disorder worldwide. Differences at the expression level of certain genes, resulting from either genetic variations or environmental interactions, might be one of the mechanisms underlying differential risks for developing AD. Peripheral blood genome transcriptional profiling may provide a powerful and minimally invasive tool for the identification of novel targets beyond Aß and tau for AD research. METHODS: This preliminary study explores molecular pathogenesis of LOAD-related inflammation through next generation sequencing, to assess RNA expression profiles in peripheral blood from five patients with LOAD and 10 healthy controls. RESULTS: The analysis of RNA expression profiles revealed 94 genes up-regulated and 147 down-regulated. Gene function analysis, including Gene Ontology (GO) and KOBAS-Kyoto Encyclopedia of DEGs and Genomes (KEGG) pathways indicated upregulation of interferon family (INF) signaling, while the down-regulated genes were mainly associated with the cell cycle process. KEGG metabolic pathways mapping showed gene expression alterations in the signaling pathways of JAK/STAT, chemokines, MAP kinases and Alzheimer disease. The results of this preliminary study provided not only a comprehensive picture of gene expression, but also the key processes associated with pathology for the regulation of neuroinflammation, to improve the current mechanisms to treat LOAD.

Analysis of the protein profile of the venoms of snakes Bothrops asper, Bothrocophias myersi and Crotalus durissus from the Colombian Andean Region obtained by RP-HPLC / Análisis del perfil proteico de los venenos de Bothrops asper, Bothrocophias myersi y Crotalus durissus serpientes de la Región Andina en Colombia obtenidos por RP-HPLC

ABSTRACT Snake venoms comprise a highly complex mixture of proteins, and there is also a high interspecific and intraspecific variability in their composition, even in the same region. Our aim was to compare the composition of the venoms of Bothrocophias myersi, Crotalus durissus, and Bothrops asper, snakes from the Colombian Andean region by Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC). The venoms were given to the research group under an agreement with Fundación Zoológica de Cali. The venoms pool was obtained by manual extraction, lyophilized and frozen. The venom protein was quantified by direct measurement with Nanodrop® 280 nm. The protein composition was established by RP-HPLC, using a Lichosper 100 RP, C18 column (250X4 mm) with a pore size of 5-m, as well as by Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). The highest quantity of protein was found in the venom of B. myersi (108.6 mg/ mL) followed by C. durissus (78.1 mg/mL) and B. asper (74.1 mg/mL). All venoms showed bands of 15 and 50 KDa by using SDS-PAGE. B. myersi venom chromatogram exhibited 16 peaks by RP-HPLC. We conclude that the composition of the three venoms is quite similar, being phospholipase A2 the common protein therein, and together with metalloproteinases they were the most abundant protein families in the venom of B. myersi. SDS-PAGE and RP-HPLC techniques allow a first approach to the profile of the venoms, which in turn could clarify the clinical syndrome produced.

RESUMEN Los venenos de las serpientes comprenden una mezcla compleja de proteínas, y existe una alta variabilidad interespecífica e intra-específica en su composición, incluso en la misma región. Nuestro objetivo fue comparar la composición de los venenos de Bothrocophias myersi, Crotalus durissus y Bothrops asper de la región andina de Colombia, mediante cromatografía líquida de alta eficiencia en fase reversa (RP-HPLC). Los venenos fueron entregados al grupo de investigación mediante un convenio con la Fundación Zoológica de Cali. El pool de venenos fue obtenido por extracción manual, liofilizado y congelado. La proteína de los venenos fue cuantificada por Absorbancia 280nm por medición directa con Nanodrop®. La composición proteica se estableció por RP-HPLC, utilizando una columna Lichosper 100 RP, C18 (250X4 mm) con un tamaño de poro de 5-jm, así como por electroforesis en gel dodecil sulfato de sodio-poliacrilamida (SDS-PAGE). La mayor cantidad de proteínas se encontró en el veneno de B. myersi (108.6 mg/mL), seguido de C. durissus (78.1 mg/mL) y B. asper (74.1 mg/mL). Todos los venenos mostraron bandas de 15 y 50 KDa por SDS-PAGE. El cromatograma de B. myersi exhibió 16 picos por RP-HPLC. Concluimos que la composición de los tres venenos es bastante similar, siendo la fosfolipasa A2 la proteína común en estos y junto con las metaloproteinasas fueron las familias de proteínas más abundantes en el veneno de B. myersi. Las técnicas de SDS-PAGE y el RP-HPLC permiten un primer acercamiento al perfil de los venenos, lo que a su vez podría contribuir a esclarecer el síndrome clínico producido.

Synthesis of endo-fused 5-unsubstituted Hexahydro-2H-pyrano[3,2-c]quinolinesvia Sequential Sc(OTf)3-catalyzed Cationic Imino-Diels-Alder Reaction/N-debenzylation using N-benzylanilines, 3,4-dihydro-2H-pyran and Paraformaldehyde under MW Irradiation.

BACKGROUND: Hexahydro-2H-pyrano[3,2-c]quinolines are known to have antibacterial, antifungal, and antitumor properties. Great efforts have been made to develop new synthetic methods that lead to the synthesis of valuable libraries. Extensive methodologies, low yields, excessive amounts of catalyst and expensive reactants are some of the limitations of current methodologies. AIMS AND OBJECTIVE: Developing a useful and efficient method to construct diversely substituted hexahydro-2Hpyrano[ 3,2-c]quinolines into good to excellent yields through a cationic imino-Diels-Alder/N-debenzylation methodology. METHOD: The cationic imino-Diels-Alder/N-debenzylation methodology was used for the preparation of substituted hexahydro-2H-pyrano[3,2-c]quinolines. It involves the use of Sc(OTf)3 for activation of cationic imino- Diels-Alder cycloaddition reaction of N-benzylanilines, 3,4-dihydro-2H-pyran and paraformaldehyde in MeCN; and microwave irradiation to shorten reaction time to afford new 6-benzyl-hexahydro-2H-pyrano[3,2- c]quinolines whose catalytic transfer debenzylation reactions with HCO2NH4 in the presence of Pd/C (10%) and methanol give the new 5-unsubstituted pyrano[3,2-c]quinolines in excellent yields. RESULTS: We found that optimal conditions for the preparation of hexahydro-2H-pyrano[3,2-c]quinolines were Sc(OTf)3 0.5 % and acetonitrile at 160°C for 15 min; and using paraformaldehyde obtained the 6-benzylhexahydro- 2H-pyrano [3,2-c]quinolines with excellent yields, while the N-debenzylation process using ammonium formate in the presence of Pd/C and methanol resulted in the synthesis of hexahydro-2H-pyrano [3,2-c] quinolines with quantitative yields (95-98%). CONCLUSION: We describe an efficient method to synthesize hexahydro-2H-pyrano[3,2-c]quinolines via the cationic imino-Diels-Alder/N-debenzylation methodology using Sc(OTf)3 0.5 % as Lewis Acid catalyst. Excellent yields of the products, use of MW irradiation, short times of reactions, and an efficient and highly diversified method are some of the main advantages of this new protocol.

Snake venomics, experimental toxic activities and clinical characteristics of human envenomation by Bothrocophias myersi (Serpentes: Viperidae) from Colombia.

Venoms of the viperid genus Bothrocophias, restricted to Colombia and Ecuador, are poorly known. Only a proteomic analysis of B. campbelli venom has been described. In this work we present a proteomic study of B. myersi venom, its biological activities, and describe the clinical characteristics of a patient bitten by this species. B. myersi venom mainly consists of phospholipases A2 (54.0%) and metalloproteinases (21.5%), among proteins of twelve different families. This venom exhibited proteolytic, phospholipase A2, myotoxic, edema-forming, and lethal activities. Enzymatic activities did not show statistically significant differences in comparison to Bothrops asper venom, but B. myersi venom displayed weaker hemorrhagic and coagulant activities. Polyvalent Viperidae antivenoms produced in Costa Rica and Colombia cross-recognized B. myersi venom by ELISA, however only the latter neutralized its lethal activity in mice when tested at a ratio of 3 mg venom/mL antivenom, suggesting it should be useful to treat envenomings inflicted by this species. A patient bitten by B. myersi developed edema and myotoxicity, evidenced by an increased creatine kinase activity in plasma. A good correlation was found between experimental biological activities of Bothrocophias myersi venom and the clinical features of an envenoming provoked by this species. SIGNIFICANCE: The proteomic characterization, toxicity, immunorecognition and neutralization of Bothrocophias myersi venom have been determined for the first time. The distribution of this pit viper is restricted to Colombia and Ecuador, and its venom contains a high proportion of phospholipases A2 and metalloproteinases. The polyvalent antivenom produced in Colombia neutralized the lethal activity of this venom in vivo, and therefore should be effective in the treatment of envenomings by this snake.

Opciones terapéuticas eficaces en rehabilitación para la marcha en el abordaje de los pacientes que han sido llevados a cirugía de reemplazo total de cadera - revisión sistemática de la literatura / Effective theapeutic options in rehabilitation for walking in the approach to patients who have been taken to total hip replacement surgery-systematic review of the literature

Introducción. El envejecimiento de la población y el aumento en la expectativa de vida imponen al médico rehabilitador un reto en el manejo de las comorbilidades que este acarrea. Así, la enfermedad osteodegenerativa de cadera se ha convertido una causa frecuente de consulta; además, la evolución progresiva de la enfermedad en algunos casos requiere manejo quirúrgico el cual puede llegar a ocasionar compromiso en la calidad de vida y funcionalidad. Es aquí donde el médico rehabilitador y un adecuado proceso terapéutico impactan en el reintegro familiar, social y laboral de los pacientes. Así mismo, es fundamental el reentrenamiento de la marcha para la adecuada realización de las actividades de la vida diaria. Objetivos. Revisar la literatura científica sobre las opciones terapéuticas en rehabilitación de la capacidad funcional para la marcha en pacientes intervenidos para reemplazo total de cadera. Método. Revisión sistemática. Se realizó búsqueda de la literatura pertinente en las bases de datos PubMed, Cochrane, ClinicalKey y ScienceDirect, de artículos publicados en revistas indexadas en los últimos 20 años con corte hasta el 1 de diciembre de 2019. Resultados. La primera búsqueda en las bases de datos electrónicas identificó 219 artículos totales distribuidos así: PubMed 105, Cochrane 8, ClinicalKey 103 y ScienceDirect 3; a partir de estos se obtuvieron 196 artículos al retirar duplicados, se excluyeron 166 artículos según su título y resumen, y fueron evaluados 53 artículos a los que se les aplicaron las guías sobre calidad metodológica STROBE y CONSORT, dependiendo del tipo de estudio. Finalmente se seleccionaron 10 artículos que cumplieron los criterios de inclusión y exclusión y lograron llegar a meta-análisis; estos evaluaban programas de fisioterapia supervisada. Es importante realizar una búsqueda de la literatura específica para otras estrategias de rehabilitación como los ejercicios con soporte de peso intensificado e hidroterapia entre otros. Conclusiones. Los estudios evaluados en el metaanálisis eran muy heterogéneos y poco consistentes, y no permiten definir una conclusión a favor o en contra de la fisioterapia supervisada. Serán necesarios más estudios primarios alrededor del tema que permitan responder fehacientemente la pregunta de investigación. Se deberá plantear estudios en el contexto local, ya que los estudios disponibles provienen de países con sistemas de salud diferentes

Introduction. The aging of the population and the increase in life expectancy impose a challenge to the rehabilitation physician in the management of comorbidities. Thus, osteodegenerative hip disease has become a frequent cause of consultation; in addition, the progressive evolution of the disease in some cases requires surgical management which can lead to compromise in the quality of life and functionality. It is here where the rehabilitation physician and an adequate therapeutic process have an impact on the family, social and labor reintegration of patients. Likewise, it is essential to retrain the gait for the proper performance of activities of daily living. Objectives. To review the scientific literature on the therapeutic options in rehabilitation of the functional capacity for walking in patients operated for total hip replacement. Method. Systematic review. The relevant literature was searched in PubMed, Cochrane, ClinicalKey and ScienceDirect databases for articles published in indexed journals in the last 20 years up to December 1, 2019. Results. The first search of the electronic databases identified 219 total articles distributed as follows: PubMed 105, Cochrane 8, ClinicalKey 103 and ScienceDirect 3; from these, 196 articles were obtained by removing duplicates, 166 articles were excluded according to their title and abstract, and 53 articles were evaluated to which the STROBE and CONSORT methodological quality guidelines were applied, depending on the type of study. Finally, 10 articles were selected that met the inclusion and exclusion criteria and were able to reach meta-analysis; these evaluated supervised physical therapy programs. It is important to perform a specific literature search for other rehabilitation strategies such as intensified weight-bearing exercises and hydrotherapy among others. Conclusions. The studies evaluated in the meta-analysis were very heterogeneous and inconsistent, and do not allow defining a conclusion in favor or against supervised physical therapy. More primary studies on the subject will be necessary to provide a reliable answer to the research question. Studies in the local context should be considered, since the available studies come from countries with different health systems.

Estrategias de rehabilitación en los pacientes pediátricos con infección por Sars-CoV-2/Covid-19 / Rehabilitation strategies in pediatric patients with Sars -Co V- 2 / Covid - 19 infection

Objetivo. Realizar una revisión de la literatura sobre rehabilitación en niños en tiempos de la pandemia por Covid-19, sintetizando las recomendaciones expuestas por los documentos de consenso internacional y la bibliografía reciente. Además, exponer la manera como estas recomendaciones se puedan aplicar bajo la forma de un protocolo multidisciplinar desde la tele-rehabilitación. Materiales y métodos. Se realizó una búsqueda bibliográfica de la literatura existente y de los consensos internacionales centrados en el diagnóstico, la presentación clínica y la rehabilitación en niños durante la pandemia por Covid-19, desde el 01 de enero de 2020 al 31 de mayo del 2020, en las bases de datos e Pubmed, Science Direct, Clinical Key, Embase y Ovid. Con base en estas recomendaciones se ofrecen pautas para ser implementadas en la modalidad de telerehabilitación en niños. Resultados. Se encontró un total de 471 artículos de los cuales 34 cumplieron con los criterios de inclusión. Conclusiones. La rehabilitación infantil plantea el objetivo de disminuir la limitación de la actividad y mejorar la participación en todos los entornos. A casusa de la pandemia actual, la necesidad de confinamiento ha llevado a que buena parte de la rehabilitación se implemente en casa, mediante ayudas tecnológicas conocidas como 'tele-rehabilitación'. No hay que olvidar que esta modalidad de tratamiento debe ser interdisciplinar y enfocada en la prevención de problemas a mediano y largo plazo. El impacto del Covid-19 aún es incierto y la rehabilitación no debe parar, pues el objetivo es brindar herramientas para conseguir la máxima funcionalidad de todos los niño

Objective. To review the literature on rehabilitation in children in times of the Covid-19 pandemic, synthesizing the recommendations set forth in international consensus documents and recent literature. In addition, to show how these recommendations can be applied in the form of a multidisciplinary protocol from tele-rehabilitation. Materials and methods. A bibliographic search of the existing literature and international consensus focused on diagnosis, clinical presentation and rehabilitation in children during the Covid-19 pandemic, from January 1, 2020 to May 31, 2020, was performed in Pubmed, Science Direct, Clinical Key, Embase and Ovid databases. Based on these recommendations, guidelines are offered to be implemented in the telerehabilitation modality in children. Results. A total of 471 articles were found, of which 34 met the inclusion criteria. Conclusions. Children's rehabilitation aims to reduce activity limitation and improve participation in all environments. Because of the current pandemic, the need for confinement has led to a large part of rehabilitation being implemented at home, by means of technological aids known as 'tele-rehabilitation'. It should not be forgotten that this treatment modality should be interdisciplinary and focused on the prevention of medium and long-term problems. The impact of Covid-19 is still uncertain and rehabilitation must not stop, since the objective is to provide tools to achieve maximum functionality for all children.

Biomimetic Total Synthesis of Dysoxylum Alkaloids.

A five-step total synthesis of Dysoxylum alkaloids has been achieved using a biomimetic approach from zanthoxylamide protoalkaloids. The synthesis featured a direct amidation and a Bischler-Napieralski reaction to form the dihydroisoquinoline ring, which was then subjected to a Noyori asymmetric transfer hydrogenation to establish the stereogenic center at C-1. Our synthetic sequence provides an important perspective on the biosynthetic origin of Dysoxylum alkaloids, since 6 natural alkaloids and 12 synthetic analogues were obtained with high enantioselectivity and in overall yields up to 68%. In addition, we describe the acute toxicity toward zebrafish embryos of Dysoxylum alkaloids, comparing their toxicity with that of their corresponding zanthoxylamide protoalkaloids and establishing an enantioselectivity-toxicity relationship.

Synthesis, Biological Evaluation and In Silico Computational Studies of 7-Chloro-4-(1H-1,2,3-triazol-1-yl)quinoline Derivatives: Search for New Controlling Agents against Spodoptera frugiperda (Lepidoptera: Noctuidae) Larvae.

The insecticidal and antifeedant activities of five 7-chloro-4-(1H-1,2,3-triazol-1-yl)quinoline derivatives were evaluated against the maize armyworm, Spodoptera frugiperda (J.E. Smith). These hybrids were prepared through a copper-catalyzed azide alkyne cycloaddition (CuAAC, known as a click reaction) and displayed larvicidal properties with LD50 values below 3 mg/g insect, and triazolyl-quinoline hybrid 6 showed an LD50 of 0.65 mg/g insect, making it 2-fold less potent than methomyl, which was used as a reference insecticide (LD50 = 0.34 mg/g insect). Compound 4 was the most active antifeedant derivative (CE50 = 162.1 µg/mL) with a good antifeedant index (56-79%) at concentrations of 250-1000 µg/mL. Additionally, triazolyl-quinoline hybrids 4-8 exhibited weak inhibitory activity against commercial acetylcholinesterase from Electrophorus electricus (electric-eel AChE) (IC50 = 27.7 µg/mL) as well as low anti-ChE activity on S. frugiperda larvae homogenate (IC50 = 68.4 µg/mL). Finally, molecular docking simulations suggested that hybrid 7 binds to the catalytic active site (CAS) of this enzyme and around the rim of the enzyme cavity, acting as a mixed (competitive and noncompetitive) inhibitor like methomyl. Triazolyl-quinolines 4-6 and 8 inhibit AChE by binding over the perimeter of the enzyme cavity, functioning as noncompetitive inhibitors. The results described in this work can help to identify lead triazole structures from click chemistry for the development of insecticide and deterrent products against S. frugiperda and related insect pests.

Publisher Correction: Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

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