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Abstract The diagnostic odysseys for rare disease patients are getting shorter as next-generation sequencing becomes more widespread. However, the complex genetic diversity and factors influencing expressivity continue to challenge accurate diagnosis, leaving more than 50% of genetic variants categorized as variants of uncertain significance. Genomic expression intricately hinges on localized interactions among its products. Conventional variant prioritization, biased towards known disease genes and the structure-function paradigm, overlooks the potential impact of variants shaping the composition, location, size, and properties of biomolecular condensates, genuine membraneless organelles swiftly sensing and responding to environmental changes, and modulating expressivity. To address this complexity, we propose to focus on the nexus of genetic variants within biomolecular condensates determinants. Scrutinizing variant effects in these membraneless organelles could refine prioritization, enhance diagnostics, and unveil the molecular underpinnings of rare diseases. Integrating comprehensive genome sequencing, transcriptomics, and computational models can unravel variant pathogenicity and disease mechanisms, enabling precision medicine. This paper presents the rationale driving our proposal and describes a protocol to implement this approach. By fusing state-of-the-art knowledge and methodologies into the clinical practice, we aim to redefine rare diseases diagnosis, leveraging the power of scientific advancement for more informed medical decisions.

Currently, agroindustrial waste can be used to obtain bioactive compounds. The solid-state fermentation is an alternative for the valorization of these waste and to be able to release bioactive compounds that may be of interest to different industrial sectors. The aim of this study was to evaluate solid-state fermentation conditions using pineapple peel waste as the substrate with Aspergillus niger spp., to release bioactive compounds using a Plackett–Burman exploratory design. Temperature, humidity, inoculum, NaNO3, MgSO4, KCl, and KH2PO4 conditions in the fermentation process were evaluated. The antioxidant capacity was determined, and the main compounds of the fermentation extracts were identified. The results revealed that the Aspergillus niger HT3 strain reached a hydrolyzable tannin release of 10.00 mg/g, While Aspergillus niger Aa20 reached a condensed tannin release of 82.59 mg/g. The KH2PO4 affects the release of condensed tannins with A. niger Aa20, and MgSO4 affects the release of hydrolyzable tannins with A. niger HT3. In addition, a positive antioxidant activity was demonstrated for the DPPH, ABTS, and FRAP technique. The main compounds in the fermented pineapple peel were 3-feruloylquinic acid, caffeic acid, lariciresinol, and 3-hydroxyphloretin 2′-O-xylosyl-glucoside, among others. The solid-state fermentation process is a biotechnological alternative for the release of bioactive compounds.

Resumen: Introducción y objetivos: A medida que la supervivencia de los niños con cardiopatía congénita intervenidos de cirugía cardiaca ha aumentado significativamente, la necesidad de seguimiento en términos de calidad de vida relacionada con la salud se ha vuelto cada vez más importante. En este estudio, describimos la calidad de vida relacionada con la salud en niños con cardiopatía congénita con y sin reparación quirúrgica. Métodos: Estudio descriptivo. Aplicamos el cuestionario Pediatric Quality of Life Inventory (PedsQLTM) en 271 pacientes con edades de 2 a 17 años, de los que acudieron a consulta de cardiología tanto en protocolo prequirúrgico como posquirúrgico. La calidad de vida relacionada con la salud se expresó como puntaje total (100 más alto) y se proporcionó como medianas y porcentajes de 10 a 100. Resultados: Incluimos a 271 pacientes de 2 a 17 años, el 94,8% con un corazón biventricular. La cirugía cardiaca se realizó en el 67,8%. Los principales factores que afectaron de forma negativa en la calidad de vida fueron la fisiología univentricular, la presencia de cortocircuito residual, requerir otra cirugía, el manejo con polifármacos y el acceso quirúrgico por esternotomía media. Conclusión: Los pacientes con cardiopatías congénitas no solo presentan su enfermedad principal, sino que también experimentan una calidad de vida que puede afectarse por factores sociales, educativos y emocionales. La evaluación de la calidad de vida de la salud debe ser parte integral en la evaluación de estos pacientes. Abstract: Introduction and objectives: As the survival of children with congenital heart disease who have undergone cardiac surgery has increased significantly, the need for follow-up in terms of health related quality of life has become increasingly important. In this study, we sought to describe the health related quality of life in children with congenital heart disease with and without surgical repair. Methods: We applied the Pediatric Quality of Life Inventory (PedsQLTM) questionary in 271 patients aged 2 to 17 years, of the patients who attended the cardiology clinic both pre surgery and postsurgery. Health related quality of life was expressed as a total score (highest 100) and provided as medians and percentages from 10 to 100. Results: We included 271 patients from 2 to 17 years old, 94.8% had a biventricular heart. Cardiac surgery was performed in 67.8% The main factor that negatively affected quality of life were univentricular physiology, the presence of residual shunt, requiring another surgery, management with polidrugs, and surgical access through median sternotomy. Conclusion: Patients with congenital heart disease nor only suffer from their main disease, but also experience a quality of life that can be affected by social, educational and emotional factors. The assessment of quality of life by health professionals should be an integral part of the evaluation of these patients.

Resumen: Las variaciones de los vasos que surgen del arco aórtico son numerosas1, reportándose según la literatura consultada entre el 6 al 49% en diversos países. La mayoría de las variantes son descritas como asintomáticas. No obstante, algunas se han asociado con síntomas significativos y problemas quirúrgicos serios, causados por efectos de la compresión o presión que ejercen esas variantes sobre la tráquea o el esófago2. Presentamos el caso de una variante que no encontramos descripción previa en la literatura la cual fue un hallazgo transquirúrgico durante una corrección de un paciente neonato con diagnóstico de coartación aortica. Abstract: The variations of the vessels that arise from the aortic arch are numerous, reported according to the literature consulted between 6 to 49% in various countries. Most variants are described as asymptomatic. However, some have been associated with significant symptoms and serious surgical problems, caused by the effects of compression or pressure that these variants exert on the trachea or esophagus. We present the case of a variant that we found no previous description in the literature, which was a trans surgical finding during a correction of a neonatal patient with a diagnosis of aortic coarctation.

Resumen: Presentamos el caso de un paciente escolar, derivado por la presencia de dolor torácico recurrente, que fue valorado por nuestro servicio donde se diagnosticó cor triatriatum, siendo una enfermedad sumamente rara, con una frecuencia del 0,1 al 0,4% de todas las cardiopatías congénitas. Se caracteriza por una membrana fibromuscular que divide la cámara de la aurícula izquierda en 2: una posterior, proximal a la entrada de las venas pulmonares, y otra anterior, que contiene el apéndice auricular y la válvula mitral. Clínicamente puede presentarse como arritmias cardiacas o como una enfermedad obstructiva grave en el periodo neonatal, dependiendo del grado de integridad de la membrana. En este caso se realizó la corrección quirúrgica del defecto, siendo exitosa. Actualmente el paciente se encuentra asintomático y continúa en seguimiento. Abstract: We present the case of a school patient, referred due to the presence of recurrent chest pain, who was evaluated by our service where cor triatriatum was diagnosed, being an extremely rare pathology with a frequency of 0.1 to 0.4% of all congenital heart diseases, characterized by a fibromuscular membrane that divides the left atrium chamber into 2, one posterior, proximal to the entrance of the pulmonary veins, and the other anterior, which contains the atrial appendage and the mitral valve. Clinically it can present as cardiac arrhythmias or as a severe obstructive pathology in the neonatal period, depending on the degree of integrity of the membrane. In this case, the surgical correction of the defect was performed, being successful. The patient is currently asymptomatic and continues to be monitored.

La cirugía para la enfermedad obstructiva del tracto de salida del ventrículo izquierdo con enfermedad de la válvula aórtica e hipoplasia del anillo aórtico continúa siendo un reto. Se han descrito diversas técnicas quirúrgicas para la ampliación del anillo aórtico, de las cuales el procedimiento de Konno-Rastan es una opción atractiva; sin embargo, no es muy frecuente realizarla debido a su alto grado de dificultad. Se presenta el caso de una paciente femenina, de 15 años de edad, con diagnóstico de estenosis valvular aórtica grave e hipoplasia del anillo aórtico, a quien se le realizó ampliación del anillo aórtico con técnica de Konno-Rastan y reemplazo valvular aórtico.

Resumen: Introducción y objetivos: En los pacientes que presentan anomalías en las válvulas cardiacas la cirugía que se prefiere siempre es la plastia; sin embargo, existen casos en los cuales el reemplazo valvular es la única opción. El objetivo de este estudio es valorar los resultados a corto y largo plazo de pacientes pediátricos que requirieron reemplazo valvular.Material y métodos Previo consentimiento informado firmado por los padres o el tutor legal, se ingresaron los datos de los pacientes menores de 18 años de edad que fueron sometidos a reemplazo valvular entre 2012 y 2020,. Resultados: Se ingresaron 13 pacientes, de los cuales el 84,6% corresponden al género masculino, la media de edad fue de 9 años, el peso medio fue de 29 kg, la válvula más afectada fue la mitral, con el 61,5%, seguida de la aórtica, con el 23,1%. En el 61,5% la presentación corresponde a la doble lesión valvular. En cuanto a la etiología, la más frecuente fue la congénita, con el 84,6%; la prótesis más utilizada fue la St. Jude Medical® número 23, la media de tiempo de circulación extracorpórea fue de 115 min y el de pinzamiento aórtico fue de 75 min; el promedio de seguimiento fue 23 meses. Conclusiones: El reemplazo valvular en la etapa pediátrica siempre es un procedimiento que se intenta postergar el mayor tiempo posible; sin embargo, no es factible en muchas ocasiones y conlleva un alto riesgo tanto quirúrgico como de complicaciones. En nuestra experiencia, los resultados son satisfactorios; sin embargo, nuestra muestra son pacientes mayores de 5 años. Abstract: Introduction and objectives: In paediatric patients with heart valve abnormalities plasty is always preferred; however, there are cases in which valve replacement is the only option. The objective of this study is to assess the short- and long-term results of paediatric patients who required valve replacement. Material and methods: With prior informed consent signed by the patient's parents or legal guardian, the data of patients under 18 years of age who underwent valve replacement were entered from the period between 2012 and 2020. Results: Thirteen patients were admitted of whom 84.6% were male, the mean age was 9 years, the mean weight was 29 kg, the most affected valve was the mitral valve in 61.5%, followed by the aortic valve at 23.1%. In 61.5% presentation was a double valve lesion. In terms of the aetiology; the most frequent aetiology was congenital in 84.6%; the most widely used prosthesis was St. Jude Medical® number 23. The mean time for extracorporeal surgery was 115 min and the mean time for aortic clamping was 75 min. Follow-up was 23 months. Conclusions: valve replacement in the paediatric stage is always a procedure that we should attempt to postpone as long as possible, as it carries a high risk both in surgery and in complications, however this is often not feasible. Although our sample is not in children under 5 years of age, the results are good.

Different strategies have been assessed for the revalorization of guishe to obtain biomolecules. The juice obtained after the mechanical extraction of guishe is rich in phytochemicals and sugars which can be converted to other products. The objective of the present study was to evaluate the production of hydrogen and butanol at different guishe juice concentrations (and therefore, different sugar concentrations) via fermentation in batch mode using Clostridium acetobutylicum ATCC 824. Fermentation assays were performed in triplicate under anaerobic conditions at 35 °C for 142 h. Guishe juice was supplemented with all components of synthetic medium (salts, vitamins and reducing agents), except glucose, and diluted at different concentrations: 20%, 40%, 60%, 80% and 100%. For comparison purposes, a control was carried out in a synthetic medium using glucose as carbon source. Results showed a maximum butanol concentration of 5.39 g/L using 80% guishe juice, corresponding to a productivity and yield of 0.04 g/L h−1 and 0.24 g/g, respectively. Meanwhile, the highest productivity (1.16 L H2/L d−1; 1.99 mmol H2/L h−1) and yield (18.4 L/kg) of hydrogen were obtained with 40% guishe juice. This study demonstrates the potential of guishe juice to be used as a low-cost substrate for hydrogen and butanol production.

In agriculture, weed management is a significant concern because their uncontrolled proliferation decreases soil quality for food crops. Allelopathy is a natural phenomenon in which the activity of allelochemical compounds inhibits the germination and growth of invasive plants as a defense mechanism. Among allelochemicals are polyphenols, which may affect genetic material or crucial enzyme activities for proper physiological function. Agroindustrial residues are a vast source of polyphenolic compounds with allelochemical activity. The bagasse of Agave Lechuguilla, known as guishe, is an abundant residue in México. The guishe has been characterized before by its polyphenolic content. Based on that, a fungal bioconversion process was developed to increase the availability of the allelochemicals in the guishe juice. First, guishe juice was obtained by mechanical pressed and characterized by spectrophotometric analysis. Results showed (g/L): 5.62 flavonoids, 0.64 of hydrolyzable polyphenols, 12.67 of reducing sugars, and 23.3 total sugars. The compounds detected by HPLC-ESI-MS were pterostilbene, hydroxycaffeic, caffeoyltartaric, and 4-O-glucoside coumaric acids, considered allelopathic. After the fungal bioprocess, (+)-gallocatechin and 3,7-Dimethyl quercetin were detected as additional compounds of interest. The flavonoid and hydrolyzable polyphenol content were modified to the highest accumulation of 1.57 and 14.9 g/L at 72 h, meaning a 2.45- and 2.22-fold increase. A bioprocess guishe juice (BGJ) was obtained at the compound accumulation peak of 72 h and evaluated in an allelopathic assay on model seeds (tomato and corn). Results show that BGJ inhibits up to 96.67% of corn seeds and up to 76.6% of tomato seeds compared to positive control.

Abstract Background Hispanic/Latino (HL) populations bear a disproportionately high burden of type 2 diabetes (T2D). The ability to predict T2D genetic risk using polygenic risk scores (PRS) offers great promise for improved screening and prevention. However, there are a number of complications related to the accurate inference of genetic risk across HL populations with distinct ancestry profiles. We investigated how ancestry affects the inference of T2D genetic risk using PRS in diverse HL populations from Colombia and the United States (US). In Colombia, we compared T2D genetic risk for the Mestizo population of Antioquia to the Afro-Colombian population of Chocó, and in the US, we compared European-American versus Mexican-American populations. Methods Whole genome sequences and genotypes from the 1000 Genomes Project and the ChocoGen Research Project were used for genetic ancestry inference and for T2D polygenic risk score (PRS) calculation. Continental ancestry fractions for HL genomes were inferred via comparison with African, European, and Native American reference genomes, and PRS were calculated using T2D risk variants taken from multiple genome-wide association studies (GWAS) conducted on cohorts with diverse ancestries. A correction for ancestry bias in T2D risk inference based on the frequencies of ancestral versus derived alleles was developed and applied to PRS calculations in the HL populations studied here. Results T2D genetic risk in Colombian and US HL populations is positively correlated with African and Native American ancestry and negatively correlated with European ancestry. The Afro-Colombian population of Chocó has higher predicted T2D risk than Antioquia, and the Mexican-American population has higher predicted risk than the European-American population. The inferred relative risk of T2D is robust to differences in the ancestry of the GWAS cohorts used for variant discovery. For trans-ethnic GWAS, population-specific variants and variants with same direction effects across populations yield consistent results. Nevertheless, the control for bias in T2D risk prediction confirms that explicit consideration of genetic ancestry can yield more reliable cross-population genetic risk inferences. Conclusions T2D associations that replicate across populations provide for more reliable risk inference, and modeling population-specific frequencies of ancestral and derived risk alleles can help control for biases in PRS estimation.

Currently, the vast majority of genomic research cohorts are made up of participants with European ancestry. Genomic medicine will only reach its full potential when genomic studies become more broadly representative of global populations. We are working to support the establishment of genomic medicine in developing countries in Latin America via studies of ethnically and ancestrally diverse Colombian populations. The goal of this study was to analyze the effect of ethnicity and genetic ancestry on observed disease prevalence and predicted disease risk in Colombia. Population distributions of Colombia’s three major ethnic groups – Mestizo, Afro-Colombian, and Indigenous – were compared to disease prevalence and socioeconomic indicators. Indigenous and Mestizo ethnicity show the highest correlations with disease prevalence, whereas the effect of Afro-Colombian ethnicity is substantially lower. Mestizo ethnicity is mostly negatively correlated with six high-impact health conditions and positively correlated with seven of eight common cancers; Indigenous ethnicity shows the opposite effect. Malaria prevalence in particular is strongly correlated with ethnicity. Disease prevalence co-varies across geographic regions, consistent with the regional distribution of ethnic groups. Ethnicity is also correlated with regional variation in human development, partially explaining the observed differences in disease prevalence. Patterns of genetic ancestry and admixture for a cohort of 624 individuals from Medellín were compared to disease risk inferred via polygenic risk scores (PRS). African genetic ancestry is most strongly correlated with predicted disease risk, whereas European and Native American ancestry show weaker effects. African ancestry is mostly positively correlated with disease risk, and European ancestry is mostly negatively correlated. The relationships between ethnicity and disease prevalence do not show an overall correspondence with the relationships between ancestry and disease risk. We discuss possible reasons for the divergent health effects of ethnicity and ancestry as well as the implication of our results for the development of precision medicine in Colombia.

Las cardiopatías congénitas (CC) se definen como una anomalía estructural del corazón o de los grandes vasos intratorácicos. Constituyen la malformación congénita más frecuente al nacimiento. Al menos un tercio de los pacientes requieren algún tipo de intervención antes del año de edad. Las manifestaciones clínicas de las cardiopatías en la etapa neonatal se presentan con un amplio contexto clínico y se pueden confundir con problemas a nivel pulmonar o infeccioso, lo que dificulta su diagnóstico y con ello contribuyendo de forma importante a la mortalidad y morbilidad de estos pacientes, ya que se retrasa el diagnóstico y manejo oportuno. El monitoreo por oximetría de pulso en el periodo neonatal se utiliza actualmente como método diagnóstico para la detección de cardiopatías congénitas críticas; a pesar de que las detecta en forma temprana, en muchos países aún no se lleva a cabo. El objetivo de este artículo es ofrecer un panorama general de la presentación clínica, aspectos diagnósticos y manejo inicial de las CC en el primer año de edad que pueda ser de utilidad a los médicos de primer contacto para mejorar la atención en este grupo de pacientes.

Emerging scaffold structures made of carbon nanomaterials, such as graphene oxide (GO) have shown efficient bioconjugation with common biomolecules. Previous studies described that GO promotes the differentiation of neural stem cells and may be useful for neural regeneration. In this study, we examined the capacity of GO, full reduced (FRGO), and partially reduced (PRGO) powder and film to support survival, proliferation, differentiation, maturation, and bioenergetic function of a dopaminergic (DA) cell line derived from the mouse substantia nigra (SN4741). Our results show that the morphology of the film and the species of graphene (GO, PRGO, or FRGO) influences the behavior and function of these neurons. In general, we found better biocompatibility of the film species than that of the powder. Analysis of cell viability and cytotoxicity showed good cell survival, a lack of cell death in all GO forms and its derivatives, a decreased proliferation, and increased differentiation over time. Neuronal maturation of SN4741 in all GO forms, and its derivatives were assessed by increased protein levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), the glutamate inward rectifying potassium channel 2 (GIRK2), and of synaptic proteins, such as synaptobrevin and synaptophysin. Notably, PRGO-film increased the levels of Tuj1 and the expression of transcription factors specific for midbrain DA neurons, such as Pitx3, Lmx1a, and Lmx1b. Bioenergetics and mitochondrial dysfunction were evaluated by measuring oxygen consumption modified by distinct GO species and were different between powder and film for the same GO species. Our results indicate that PRGO-film was the best GO species at maintaining mitochondrial function compared to control. Finally, different GO forms, and particularly PRGO-film was also found to prevent the loss of DA cells and the decrease of the α-synuclein (α-syn) in a molecular environment where oxidative stress has been induced to model Parkinson's disease. In conclusion, PRGO-film is the most efficient graphene species at promoting DA differentiation and preventing DA cell loss, thus becoming a suitable scaffold to test new drugs or develop constructs for Parkinson's disease cell replacement therapy.

Production of xylanase enzyme by fungi strains has gained interest in the recent years due to its high productivity, high catalytic power, as well as its potential applications in different areas such as feed, food, textile, and biofuel industries. The conventional methodologies, to produce enzymes, involve complex apparatus and chemical solvents and are associated with high costs and low- yield recovery. To obtain the high-yield recovery of the enzymes, modern enzyme extraction methods are taken into account. Aqueous two-phase systems (ATPS) are an alternative separative methodology for the purification and recovery of the enzymes and other biomolecules. The advantages of ATPS are easy scale-up and extraction, volume reduction, and rapid separation. The objective of this study was to produce Trichoderma harzianum xylanase by solid-state fermentation (SSF) using corn cobs as a support/substrate and employing ATPS for its partial recovery. In this study, the results showed the ability of a microorganism to grow on the corn cobs and to produce the xylanase enzyme. Xylanolytic activity reached 7.85 U/g of corn cobs. The enzyme was efficiently concentrated by ATPS. In addition, a high purification factor (10-fold) and considerable enzyme recovery (%ER) (84%) percentage were obtained.

At least 20% of Colombians identify as having African ancestry, yielding the second largest population of Afro-descendants in Latin America. To date, there have been relatively few studies focused on the genetic ancestry of Afro-Latino populations. We report a comparative analysis of the genetic ancestry of Chocó, a state located on Colombia’s Pacific coast with a population that is >80% Afro-Colombian. We compared genome-wide patterns of genetic ancestry and admixture for Chocó to six other admixed American populations, with an emphasis on a Mestizo population from the nearby Colombian city of Medellín. One hundred sample donors from Chocó were genotyped across 610,545 genomic sites and compared with 94 publicly available whole genome sequences from Medellín. At the continental level, Chocó shows mostly African genetic ancestry (76%) with a nearly even split between European (13%) and Native American (11%) fractions, whereas Medellín has primarily European ancestry (75%), followed by Native American (18%) and African (7%). Sample donors from Chocó self-identify as having more African ancestry, and conversely less European and Native American ancestry, than can be genetically inferred, as opposed to what we previously found for Medellín, where individuals tend to overestimate levels of European ancestry. We developed a novel approach for subcontinental ancestry assignment, which allowed us to characterize subcontinental source populations for each of the three distinct continental ancestry fractions separately. Despite the clear differences between Chocó and Medellín at the level of continental ancestry, the two populations show overall patterns of subcontinental ancestry that are highly similar. Their African subcontinental ancestries are only slightly different, with Chocó showing more exclusive shared ancestry with the modern Yoruba (Nigerian) population, and Medellín having relatively more shared ancestry with West African populations in Sierra Leone and Gambia. Both populations show very similar Spanish ancestry within Europe and virtually identical patterns of Native American ancestry, with main contributions from the Embera and Waunana tribes. When the three subcontinental ancestry components are considered jointly, the populations of Chocó and Medellín are shown to be most closely related, to the exclusion of the other admixed American populations that we analyzed. We consider the implications of the existence of shared subcontinental ancestries for Colombian populations that appear, at first glance, to be clearly distinct with respect to competing notions of national identity that emphasize ethnic mixing (mestizaje) vs. group-specific identities (multiculturalism).

While genomic approaches to precision medicine hold great promise, they remain prohibitively expensive for developing countries. The precision public health paradigm, whereby healthcare decisions are made at the level of populations as opposed to individuals, provides one way for the genomics revolution to directly impact health outcomes in the developing world. Genomic approaches to precision public health require a deep understanding of local population genomics, which is still missing for many developing countries. We are investigating the population genomics of genetic variants that mediate drug response in an effort to inform healthcare decisions in Colombia. Our work focuses on two neighboring populations with distinct ancestry profiles: Antioquia and Chocó. Antioquia has primarily European genetic ancestry followed by Native American and African components, whereas Chocó shows mainly African ancestry with lower levels of Native American and European admixture. We performed a survey of the global distribution of pharmacogenomic variants followed by a more focused study of pharmacogenomic allele frequency differences between the two Colombian populations. Worldwide, we found pharmacogenomic variants to have both unusually high minor allele frequencies and high levels of population differentiation. A number of these pharmacogenomic variants also show anomalous effect allele frequencies within and between the two Colombian populations, and these differences were found to be associated with their distinct genetic ancestry profiles. For example, the C allele of the single nucleotide polymorphism (SNP) rs4149056 [Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1)∗5], which is associated with an increased risk of toxicity to a commonly prescribed statin, is found at relatively high frequency in Antioquia and is associated with European ancestry. In addition to pharmacogenomic alleles related to increased toxicity risk, we also have evidence that alleles related to dosage and metabolism have large frequency differences between the two populations, which are associated with their specific ancestries. Using these findings, we have developed and validated an inexpensive allele-specific PCR assay to test for the presence of such population-enriched pharmacogenomic SNPs in Colombia. These results serve as an example of how population-centered approaches to pharmacogenomics can help to realize the promise of precision medicine in resource-limited settings.

Evasion of apoptosis is a hallmark of cancer especially relevant in the development and the appearance of leukemia drug resistance mechanisms. The development of new drugs that could trigger apoptosis in aggressive hematological malignancies, such as AML and CML, may be considered a promising antileukemic strategy. AD0157, a natural marine pyrrolidinedione, has already been described as a compound that inhibits angiogenesis by induction of apoptosis in endothelial cells. The crucial role played by defects in the apoptosis pathways in the pathogenesis, progression and response to conventional therapies of several forms of leukemia, moved us to analyze the effect of this compound on the growth and death of leukemia cells. In this work, human myeloid leukemia cells (HL60, U937 and KU812F) were treated with AD0157 ranging from 1 to 10 μM and an experimental battery was applied to evaluate its apoptogenic potential. We report here that AD0157 was highly effective to inhibit cell growth by promotion of apoptosis in human myeloid leukemia cells, and provide evidence of its mechanisms of action. The apoptogenic activity of AD0157 on leukemia cells was verified by an increased chromatin condensation and DNA fragmentation, and confirmed by an augmentation in the apoptotic subG1 population, translocation of the membrane phosphatidylserine from the inner face of the plasma membrane to the cell surface and by cleavage of the apoptosis substrates PARP and lamin-A. In addition, AD0157 in the low micromolar range significantly enhanced the activities of the initiator caspases-8 and -9, and the effector caspases-3/-7 in a dose-dependent manner. Results presented here throw light on the apoptogenic mechanism of action of AD0157, mediated through caspase-dependent cascades, with an especially relevant role played by mitochondria. Altogether, these results suggest the therapeutic potential of this compound for the treatment of human myeloid leukemia.

Este artículo presenta un algoritmo de enseñanza-aprendizaje multi-objetivo basado en descomposición para resolver el problema del despacho óptimo de potencia reactiva (ORPD). La efectividad y el desempeño del algoritmo propuesto son comparados con respecto a un algoritmo evolutivo multi-objetivo basado en descomposición (MOEA/D) y con el NSGA-II. Un modelo de sistema de potencia de referencia se utiliza para probar el desempeño de los algoritmos. Los resultados de la reducción de las pérdidas de energía así como las métricas de desempeño indican que el algoritmo propuesto es una opción fiable para resolver el problema.

En este artículo se introduce un nuevo método de búsqueda rápida del Vecino Más Similar de un objeto dado, y se enuncia un criterio para la determinación a priori de la efectividad del método basado en la función de similaridad y la estructura interna de los datos. Nuestro método permite el trabajo con objetos descritos por rasgos numéricos y categóricos, y con ausencias de información. Está especialmente diseñado para el manejo de funciones de similaridad que no cumplen la desigualdad triangular, donde no es posible aplicar algoritmos tradicionales para esta tarea. El método propuesto mostró un buen desempeño en las bases de datos utilizadas, teniendo altos valores de Precision y Recall, así como una reducción elevada en el número de comparaciones.

Metabolism is a challenging subject for bioscience students due to the intrinsic complexity of the metabolic network, as well as that of the overlapping mechanisms of metabolic regulation. Collaborative learning based on a problem-based learning approach can help students to successfully learn and understand metabolism. In the present article, we propose a selection of exercises, problems, and cases aimed to focus students' attention on the scientific work made by Sir Hans Krebs and his collaborators to elucidate four main metabolic cycles, as well as on the study of these cycles, their regulation, and their metabolic integration. The objectives, the tools, and the implementation of this proposal are described, and the results obtained during its first implementation with volunteer students enrolled in two courses on metabolic regulation at our university are presented and discussed. These volunteer students signed a learning contract and were randomly distributed in small groups (3-4 students each). Application of this collaborative learning activity to our classrooms has been very satisfactory, as evidenced by an improvement in the volunteers' academic performance and a very positive perception by most of them, who declared to be "very satisfied" or "satisfied" with their experience and felt that they had learned more.