Considerations for Familial Chylomicronemia Diagnosis in the Era of Next-Generation Sequencing: A Latin American Perspective

Abstract Familial chylomicronemia syndrome (FCS) is an autosomal recessive disorder, characterized by alterations in the catabolism of chylomicrons and by increased levels of plasma triglycerides. It has been shown that about 60-90% of FCS patients have biallelic mutations in the LPL gene and the remaining patients have mutations in genes encoding proteins closely related to LPL function. The objective of this manuscript is to illustrate the different clinical scenarios of FCS presentation, and to guide practitioners on the usefulness of genetic tests in each of them. To this end, several published papers about recommendations for the diagnosis of FCS are discussed briefly, in addition to the presentation of several hypothetical cases, highlighting different clinical presentations and possible associated genetic findings. These cases illustrate the multiplicity of potential aspects of family history, clinical manifestations, biochemical parameters, and patterns of genetic variants found in genomic analyses of FCS.

Enzootic calcinosis in sheep in Uruguay: a brief review and report of two outbreaks / Calcinose enzoótica em ovinos no Uruguai: revisão de literatura e descrição de dois surtos

This study aimed to do a brief review of enzootic calcinosis in sheep and to report two outbreaks of Nierembergia rivularis poisoning in sheep in Uruguay. The outbreaks occurred in farms located on an island (Outbreak A) and on the border (Outbreak B) of the Rincón del Bonete lake. Sheep of all ages were affected, with the exception of suckling lambs. The first clinical signs occurred in early October, and deaths occurred from December to February. Outbreaks A and B had morbidity of 10%, and the mortality was 7.2% and 2.8% in Outbreaks A and B, respectively. The clinical signs included weight loss, retracted abdomen, stiff gait, and kyphosis. An autopsy was performed on one sheep from each outbreak. Pulmonary and arterial calcification, nephrocalcinosis, and osteopetrosis were observed in gross and microscopic examination in both sheep. Thyroid C-cell hyperplasia and carcinoma was observed in sheep A. Sheep B showed thyroid C-cell hyperplasia and parathyroid chief cell atrophy. The parathyroid was not examined in the sheep from Outbreak A. The differential diagnosis of enzootic calcinosis in southern South America should consider four toxic plants in the Solanaceae family: Solanum glaucophyllum, Solanum stuckertii, Nierembergia veitchii, and Nierembergia rivularis.(AU)

Este trabalho faz uma breve revisão da calcinose enzoótica em ovinos e descreve dois surtos de intoxicação por Nierembergia rivularis em ovinos no Uruguai. Os surtos ocorreram em propriedades localizadas em uma ilha (Surto A), e nas margens (Surto B) do lago do Rincón del Bonete. Foram afetados ovinos de todas as idades, exceto cordeiros lactentes. Os primeiros sinais clínicos ocorreram no início de outubro e as mortes de dezembro a fevereiro. Morbidade de 10% foi observada nos Surtos A e B. A mortalidade foi de 7,2% e 2,8% nos Surtos A e B, respectivamente. Os sinais clínicos incluíram perda de peso, abdômen retraído, marcha rígida e cifose. Foram necropsiados um animal de cada rebanho. Observou-se mineralização arterial e pulmonar, nefrocalcinose e osteopetrose no exame macroscópico e histológico dos dois ovinos. Hiperplasia e carcinoma de células C da tireoide foram observados no ovino A. O ovino B apresentou hiperplasia de células C da tireoide e atrofia das células principais da paratireoide. As paratireoides do ovino A não foram examinadas. O diagnóstico diferencial da calcinose enzoótica no Sul da América do Sul deve considerar quatro plantas calcinogênicas da família Solanaceae: Solanum glaucophyllum, Solanum stuckertii, Nierembergia veitchii e Nierembergia rivularis.(AU)

Quilomicronemia familiar / Familial chylomicronemia

Resumen La quilomicronemia familiar es una condición en que una mutación genética altera la capacidad de metabolizar los triglicéridos que viajan en las lipoproteínas, causando elevación extrema de triglicéridos plasmáticos y complicaciones asociadas. La complicación más frecuente es la pancreatitis, que puede llevar a falla multiorgánica o insuficiencia pancreática. La quilomicronemia familiar también afecta la calidad de vida, las relaciones sociales y el desarrollo profesional. El gen más frecuentemente afectado en la quilomicronemia familiar es el de lipoproteína lipasa-1 (LPL), enzima que hidroliza triglicéridos circulantes para su captación tisular. Mutaciones en genes (como APOC2, APOAV, LMF-1, GPIHBP-1) que codifican para proteínas que regulan la maduración, transporte o polimerización de lipoproteína lipasa-1, también pueden estar involucradas. Sin embargo, en cerca del 30% de los pacientes no se encuentra la variante causal. La quilomicronemia familiar debe sospecharse en casos de hipertrigliceridemia extrema, resistente al tratamiento convencional, o que se acompaña de xantomas eruptivos, lipemia retinalis o dolor abdominal. La disponibilidad de escalas de riesgo y pruebas genéticas deben promover la detección oportuna. La nutrición se basa en una dieta muy baja en grasa con adecuada suplencia de vitaminas liposolubles y ácidos grasos esenciales, además de evitar el consumo de alcohol. Si bien el tratamiento farmacológico incluye fibratos y ácidos grasos omega 3, el enfoque actual privilegia agentes biotecnológicos dirigidos a los defectos moleculares propios de la enfermedad. Ello incluye un oligonucleótido antisentido dirigido contra apoC-III (volanesorsen), un anticuerpo monoclonal contra la proteína similar a angiopoietina tipo 3 (evinacumab), y otros compuestos en desarrollo.

Abstract Familial chylomicronemia is a disease in which a genetic mutation affects the ability of the organism to metabolize triglycerides bound to lipoproteins, causing extremely high plasma triglycerides and associated consequences. The most frequent complication is acute pancreatitis, which may lead to multiorganic failure or pancreatic insufficiency. Familial chylomicronemia also exerts a profound negative impact on quality of life, social relationships and professional development. The gene most frequently affected is lipoprotein lipase-1 gene (LPL), the enzyme in charge of hydrolyzing circulating triglycerides for tissue uptake. Mutations in other genes regulating maturation, transport or polymerization (eg. APOC2, APOAV, LMF-1, GPIHBP-1) of lipoprotein lipase-1, may also be involved. However, in about 30% of patients the causal variant is not identified. Familial chylomicronemia should be suspected in patients with severe hypertriglyceridemia with poor response to conventional treatment, or accompanied by eruptive xanthomas, lipemia retinalis or abdominal pain. The availability of risk scores and genetic tests should facilitate its opportune detection and management. Nutritional therapy is based on a very-low-fat diet with adequate supply of lipid-soluble vitamins and essential fatty acids, plus avoidance of alcohol consumption. Current pharmacological treatment may include fibrates and omega-3 fatty acids but prioritizes biotechnological agents targeting the molecular disturbances of the disease. These include an antisense oligonucleotide against apoC-III (volanesorsen), a monoclonal antibody against angiopoietin-like protein-3 (evinacumab), and other agents currently in development.

Impact of hHLA-DPB1 matching on clinical outcomes after haploidentical-related hematopoietic stem cell transplantation

ABSTRACT Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis / Das descrições de Charcot à compreensão atual dos sintomas neuropsiquiátricos na esclerose múltipla

ABSTRACT Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

RESUMO Os distúrbios neuropsiquiátricos na esclerose múltipla são conhecidos desde a descrição clínico-patológica original de Charcot no final do século XIX. Charcot nas últimas décadas de sua vida se envolveu no campo da neuropsiquiatria. Isso produziu uma batalha de escolas rivais na época que ainda ecoa até hoje. A intuição de Charcot, incluindo a linha de pensamento de Babinski, um de seus discípulos mais famosos, foi a teoria correta da conexão entre os transtornos do humor e muitas das doenças do sistema nervoso. A preocupação da Medicina em estabelecer uma relação entre transtornos do humor e doenças vem das idades antiga e média, com referências encontradas na doutrina hipocrática. No entanto, foi apenas na segunda metade do século XIX e início do século XX que, com as descobertas de Charcot essa discussão foi realizada de maneira estruturada, estabelecendo os fundamentos da neuropsiquiatria.

Fenología de Crescentia alata (Bignoniaceae) en Guanacaste, Costa Rica

Los estudios fenológicos generan información que contribuye con el conocimiento de las relaciones entre especies y componentes abióticos de los ecosistemas, disponibilidad de alimento para animales y regeneración de cobertura boscosa. Crescentia alata es una especie arbórea abundante en el bosque tropical seco (BTs); su importancia ecológica, cultural y económica ha sido ampliamente reconocida y por eso existe interés en reproducir esta especie, pero antes es necesario conocer detalladamente su desarrollo fenológico. El objetivo de este estudio fue describir la fenología de C. alata en el BTs de Costa Rica. Se seleccionaron 20 árboles reproductivos en el Parque Nacional Santa Rosa para observar las siguientes fenofases: follaje, floración y fructificación por 14 meses entre 2015 y 2016. Esta especie produjo más follaje en junio, máxima floración en junio y octubre y mayor número de frutos maduros en enero. Los patrones fenológicos en C. alata se relacionaron con factores climáticos comunes, sobre todo precipitación, temperatura y humedad relativa. Los resultados más relevantes de este estudio podrían contribuir a la propagación, el manejo adecuado y la conservación de esta especie.

Phenological studies generate information that contributes knowledge on relationships of species and abiotic components of ecosystems, availability of food for animals and regeneration of forest cover. Crescentia alata is an abundant tree species in tropical dry forests; its ecological, cultural and economic importance has been widely recognized and for this reason there is an interest in reproducing this species, but previously it is necessary to understand its detailed phenological development. The aim of this work was to describe C. alata phenology in dry Costa Rican forests. Twenty reproductive trees were selected at the Santa Rosa National Park to observe phenophases (leaf flushing, flower production, and fructification) during 14 months from 2015 to 2016. Most foliage was observed in June, maximal floration in June and October, and the highest ripe-fruit number in January. Phenological patterns in C. alata were related to common climatic factors as rainfall, temperature, and relative humidity; other factors considered were wind speed, and sun radiation. The most significant phenological data registered for C. alata in this work may contribute to a better management and conservation of this species.

Germinación de semillas de Crescentia alata (Bignoniaceae) en distintas condiciones de temperatura, luminosidad y almacenamiento

Crescentia alata (Bignoniaceae) es una especie arborescente de gran interés cultural y económico desde México hasta Costa Rica. Sin embargo, la protección de las poblaciones naturales y el establecimiento de plantaciones son limitados por la carencia de información sobre germinación de semillas y crecimiento de plántulas. Este estudio pretende caracterizar los frutos y las semillas, evaluar el proceso de germinación a diferentes temperaturas y niveles de luminosidad, y determinar las condiciones óptimas de temperatura, humedad y almacenamiento para mantener viables las semillas. Se midieron altura, diámetro y masa de frutos, así como largo, ancho y masa de semillas; además, se contó el número de semillas por fruto. Asimismo, se evaluó el porcentaje de germinación a cinco temperaturas (15, 20, 30, 20-30 y 25-30 °C), en condiciones de luz-oscuridad, con almacenamiento a tres temperaturas (5° C, 15 °C y ambiente: 22-24 °C) durante 36 meses. También se observó la viabilidad de las semillas conservadas dentro del fruto. El valor promedio del índice de redondez (IR) fue -1.86; esto indica que los frutos son redondeado-achatados. En promedio el fruto midió 7.90 ± 2.58 cm de altura y 9.62 ± 1.21 cm de diámetro; las semillas midieron 0.75 ± 0.07 cm de largo y 0.67 ± 0.05 cm de ancho. La masa promedio del fruto fue 414.57 g y cada fruto tuvo en promedio ca. 691 semillas, que no germinaron a 15 °C ni a 20 °C; en la oscuridad disminuyó la germinación y la viabilidad de las semillas se redujo cuando se almacenaron a temperatura ambiente (22-24 °C) y cuando permanecieron dentro del fruto. Los resultados indican que las semillas de C. alata germinan mejor a 30 °C, en condiciones de luz y separadas de la pulpa del fruto antes de almacenarse; además, almacenadas a temperaturas bajas (5 °C y 15 °C) los porcentajes de germinación y la viabilidad se mantienen altos (ca. 90 %) hasta por tres años. Estos datos pueden contribuir a mejorar el almacenamiento de semillas y la obtención de plántulas para propagación; así podría aumentar el tamaño de las poblaciones con fines económicos o de conservación, lo que favorecería tanto a la especie estudiada como al bosque tropical seco en que habita.

Crescentia alata is a natural resource with cultural and economic value from Mexico to Costa Rica. Nevertheless, protection of natural populations and establishment of plantations are limited by lack of information on seed germination and plant growth. This study aims to characterize size, weight and number of fruits and seeds, to evaluate the seed germination process at different temperatures and light conditions, and to determine the optimal conditions of temperature, humidity, and storage periods for viable seeds. We measured germination at five different temperatures (15, 20, 30, 20-30, and 25-30 °C), in light-dark conditions, with seed storage at three temperatures (5 °C, 15 °C, and ambient temperature: 22-24 °C) during 36 months. Mean values: fruit roundness index -1.86 (i.e. they are flattened-rounded). Fruit height 7.90 ± 2.58 cm, diameter 9.62 ± 1.21 cm; seeds were 0.75 ± 0.07 cm long and 0.67 ± 0.05 cm wide. Fruit mass 414.57 g; each fruit contained on average ca. 691 seeds. Seeds did not germinate at 15 °C or 20 °C; germination decreased in darkness; germination and viability decreased when seeds were stored at ambient temperature (22-24 °C), and when they were preserved inside fruits. The seeds of C. alata germinate better at 30 °C, exposed to light, and separated from the pulp before storage. When seeds are stored at low temperatures (5 °C and 15 °C), high germination and viability percentages (ca. 90 %) can be maintained for three years, allowing conservation programs for the species.

Efecto del almacenamiento ex situ de semillas y de condiciones lumínicas sobre la tasa de crecimiento de plántulas de Crescentia alata (Bignoniaceae)

En el bosque tropical seco, el árbol Crescentia alata (Bignoniaceae) es un recurso cultural y económico, pero han fracasado algunos intentos para establecer plantaciones, que podrían satisfacer la producción comercial y, así, evitar el impacto en las poblaciones naturales. Por tanto, existe la necesidad de generar información biológica sobre esta especie para obtener plantas en condiciones de invernaderos. El objetivo de este trabajo fue evaluar la tasa de crecimiento de plantas de C. alata obtenidas de semillas que se almacenaron en diferentes períodos y a varias temperaturas, y determinar el efecto de la intensidad de la luz sobre el crecimiento de las plántulas. Se recolectaron frutos en Liberia (Guanacaste, Costa Rica) y se almacenaron semillas por 0, 4, 8 y 14 meses a 5 °C, 15 °C y a temperatura ambiente (22-24 °C). Las plántulas de las semillas almacenadas por 0, 4, 8 y 14 meses se trasplantaron para evaluar el crecimiento después de 8 días, 2 y 16 meses, y en dos condiciones de luminosidad. La morfología de las plántulas de 8 días cambió según el tiempo de almacenamiento. El análisis de componentes principales de la evaluación de 2 meses indica que las variables más significativas fueron biomasa total seca, biomasa seca de hojas, de raíz-vástago, de tallo y de raíz, mientras que en el análisis de la evaluación de 16 meses tales variables fueron biomasa seca de raíz, de raíz-vástago y de hojas, también número de hojas y longitud del vástago. El área foliar específica de plantas con 16 meses de edad obtenidas de semillas almacenadas 14 meses no cambió con la temperatura de almacenamiento. Además, dos condiciones de luminosidad influyeron en la altura, el diámetro del tallo o el número de hojas. El almacenamiento de semillas a 5 °C y 15 °C favoreció el desarrollo de los cotiledones, así como la longitud de la raíz y del hipocótilo. Plantas de 2 meses obtenidas de 0 y 8 meses asignaron mayor biomasa a raíces que a tallos, mejorando así la absorción de agua. Plantas de 16 meses provenientes de semillas no almacenadas desarrollaron el mayor número de hojas, y aquellas de semillas de 8 meses a 5 °C y 15 °C mostraron tallos más cortos. Las semillas almacenadas hasta 14 meses se convirtieron en plantas bien desarrolladas. Se recomienda a futuros investigadores evaluar la viabilidad a diferentes temperaturas de secado de las semillas y en niveles de intensidad lumínica más contrastantes durante el crecimiento.

The dry tropical forest tree Crescentia alata is a cultural and economical resource, but efforts to establish plantations, which could satisfy commercial production and avoid impact on natural populations, have been unsuccessful. So there is a need to generate biological information on this species for obtaining plants in greenhouses. The aim of this work was to evaluate the vigor and growth rate of C. alata seedlings born from seeds that were stored at different periods and temperatures, and to determine the effect of light intensity on the seedlings. Fruits were collected in Liberia (Guanacaste, Costa Rica) and seeds stored for 0, 4, 8, and 14 months at 5 °C, 15 °C, and ambient temperature (22-24 °C). Seedlings from seeds stored for 0, 4, 8 and 14 months were grown to evaluate growth after 8 days, 2 months, and 16 months, and in two different light conditions. Morphology of 8-day-seedlings changed according to storage time. Principal component analysis of 2-month evaluation indicates that the most significant variables were total dry biomass, dry biomass of leaves, root-shoot, stem, and root, while for the analysis of 16-month evaluation these variables were dry biomass of root, root-shoot, and leaves, also leaf number, and shoot length. Specific leaf area of 16-month plants from seeds stored for 14 months did not change with storage temperature. In addition, two different light conditions influence seedling height, stem diameter or leaf number. Seed storage at 5 °C and 15 °C favored development of seedling cotyledons, and length of both root and hypocotyl. Two month-seedlings from 0M and 8M allocated most biomass to roots and less to stems, enhancing this way water absorption. Sixteen-month-plants from non-stored seeds developed the highest leaf numbers, and those plants from 8M seeds at 5 °C and 15 °C showed shorter stems. Seeds stored up to 14 months kept viable, becoming healthy seedlings. We recommend that future researchers evaluate seed viability at different drying temperatures and more contrasting light levels.

The forgotten habitats in conservation: early successional vegetation

Conservation efforts in terrestrial environments have focused on preserving patches of natural habitats and restoring disturbed habitats, with the main goal of transforming them into forests or habitats that resemble the original conditions. This approach tends to overlook the importance of conserving early successional vegetation (e.g., riverside vegetation, natural regeneration, young secondary forests), which often includes a large number of species (e.g., plants and animals) associated with or restricted to these habitats. In this paper we want to bring to attention the importance of preserving early successional vegetation, and to encourage scientists to investigate, e.g., the diversity, distribution, and species interactions occurring in these habitats. To address these goals, we focus on two main objectives: (1) to identify the common types of early successional vegetation in the Costa Rican Central Valley; and (2) to use some case studies to draw attention to the importance that such areas have as reservoirs of a large portion of the diversity unique to early successional stages. We first include an example to show the diversity of plants in small forest patches immersed in a large urbanized area. We provide general information on the insects that occur in early successional vegetation in urban areas, and in further detail examples of butterflies. Additionally, we provide examples of birds and mammals that are restricted to early successional vegetation, and how the reduction of this vegetation type affects species conservation. Finally, we encourage scientists to investigate these early successional habitats, particularly those species exclusive to early successional stages. Special attention should be paid to endemic species and those with a restricted distribution. Information of this type will make conservation of the diversity contained in these habitats possible.

Los esfuerzos de conservación en ambientes terrestres se han centrado principalmente en la preservación de ambientes naturales y la restauración de diferentes hábitats, con la meta principal de transformar estos ambientes en bosques maduros o hábitats que asemejen las condiciones originales. Este enfoque tiende a pasar por alto la importancia de conservar la vegetación de estados de regeneración temprana (e.g., vegetación riparia, regeneración natural, bosque secundario joven), la cual incluye un gran número de especies (e.g., plantas y animales) asociadas o restringidas a estos hábitats. Con este artículo queremos llamar la atención sobre la importancia de preservar áreas cubiertas con vegetación de sucesión temprana, e instar a científicos y naturalistas a investigar, e.g., la diversidad, distribución, e interacciones entre las especies presentes en estos ambientes. Para apoyar esta meta, nos enfocamos en dos objetivos principales: (1) identificar los tipos más comunes de vegetación pionera en el Valle Central de Costa Rica; y (2) utilizar algunos casos de estudio para llamar la atención sobre la importancia que tales áreas tienen como reservorio de gran parte de la diversidad, mucha de la cual es única de los estados de sucesión temprana. Primero se incluye un ejemplo particular en el cual se muestra la diversidad de plantas en pequeños fragmentos de bosque y matorral inmersos en una gran área urbanizada. Después se presenta una revisión general de los insectos que habitan en la vegetación de sucesión temprana en áreas urbanas, para luego discutir en mayor detalle ejemplos de mariposas. Además, proporcionamos ejemplos de especies de aves y mamíferos que están restringidos a vegetación de sucesión temprana, y cómo la reducción de este ambiente afecta su conservación. Finalmente, instamos a los científicos de diferentes áreas a investigar los diversos procesos ecológicos e interacciones biológicas inherentes a los estados de regeneración temprana. Especial atención requieren aquellas especies exclusivas o endémicas de estos ambientes. Sin esta información es imposible conservar la diversidad de estos hábitats.

Resultados de la cirugia minimamente invasiva y la cirugia abierta tipo scarf para la correccion del hallux valgus moderado y severo: Estudio observacional retrospectivo / Results of minimally invasive surgery versus scarf osteotomy for correcting moderate and severe hallux valgus. Retrospective observational study

Introducción: Cuando el dolor asociado a deformidad en hallux valgus es el principal sintoma y el tratamiento conservador no es eficaz, esta indicada la cirugia. El objetivo de este articulo fue evaluar nuestra experiencia con la tecnica minimamente invasiva y la osteotomia tipo scarf, mediante la escala AOFAS, radiografias con la correccion del angulo intermetatarsiano, el angulo metatarsofalangico, la escala Regnauld y los criterios de Reynolds. Materiales y Métodos: Estudio observacional descriptivo de tipo cohorte retrospectiva. Se incluyeron los pies operados mediante las tecnicas minimamente invasiva y tipo scarf. Se revisaron los datos clinicos preoperatorios, y a los 3 y 6 meses de la cirugia, sobre funcionalidad, hallazgos imagenologicos de tres angulos, y las clasificaciones de Reynolds y Regnauld. Resultados: Se incluyeron 123 pacientes en quienes se realizaron 150 procedimientos: cirugia minimamente invasiva (44,7%) y tipo scarf (55,3%). La mediana de edad era de 56 anos (RIC 42-61), el 88,6% eran mujeres. No hubo diferencias entre el preoperatorio inmediato, y a los 3 y 6 meses para el angulo intermetatarsiano entre las dos tecnicas; sin embargo, el angulo metatarsofalangico se corrigio (p <0,001) y el puntaje AOFAS fue mejor a los 3 meses con la cirugia minimamente invasiva (p <0,001). Conclusiones: Ambas tecnicas corrigen la deformidad a valores normales. Con la tecnica minimamente invasiva, la correccion fue mayor y el puntaje AOFAS resulto mejor. La incidencia de complicaciones agudas fue similar. Se necesitan ensayos clinicos sobre este tema para confirmar los hallazgos de este estudio. Nivel de Evidencia: III

Introduction: When pain associated with hallux valgus deformity is the main symptom and traditional treatment is not effective, then surgery is indicated. The aim of the study was to evaluate our experience with minimally invasive technique and scarf osteotomy using AOFAS scale and radiologically intermetatarsal angle correction, metatarsophalangeal angle, Regnauld scale and Reynolds criteria. Methods: Retrospective cohort observational study. Feet treated with minimally invasive technique and scarf osteotomy were included. Preoperative clinical data and those obtained at 3 and 6 months after surgery were reviewed to evaluate functionality, image findings on three angles, and Reynolds and Regnauld classifications. Results: A total of 123 patients were included, and 150 procedures were performed: minimally invasive surgery (44.7%) and scarf osteotomy (55.3%). Average age was 56 years (IQR 42-61), and 88.6% were women. No differences were observed at the immediate preoperative period, 3 months and 6 months for intermetatarsal angle between both techniques; however metatarsophalangeal angle was corrected (p<0.001) and AOFAS score (p<0.001) was better 3 months after the minimally invasive surgery. Conclusions: Both techniques provide correction to normal values. Minimally invasive technique achieved higher correction levels and a better AOFAS score. Incidence of acute complications was similar. Clinical studies on this issue are necessary to confirm these findings. Level of Evidence: III

Zornioside, a dihydrochalcone C-glycoside, and other compounds from Zornia brasiliensis

ABSTRACT The secondary metabolites of the aerial parts of Zornia brasiliensis Vogel, Fabaceae, and the biological activity of one of these secondary metabolites were characterized in this study. A phytochemical investigation was performed using chromatographic techniques including analytical and preparative reverse-phase HPLC column sequences, which resulted in the isolation of fourteen compounds: one previously undescribed C-glycosylated dihydrochalcone (zornioside), one cyclitol (D-pinitol), one glycosylated megastigmane (roseoside) and eleven phenolic compounds: 7-methoxyflavanone, 7,4'-dimethoxyisoflavone, medicarpin, 2'-4'-dihydroxychalcone, onionin, isoorientin-3'-O-methyl ether, isovitexin, glycosylated (Z)-O-coumaric acid, glycosylated (E)-O-coumaric acid, dihydromelilotoside, and isoorientin. The structures of the isolated compounds were determined based on 1D and 2D-NMR, HRESIMS, IR and CD spectroscopic analyses. The cytotoxic activity of zornoside was assessed against tumor cell lines (MCF-7, HCC1954, T-47D, 4T1, HL60), and a non-tumor cell line (RAW264.7) using MTT assay. The compound zornioside was selectively cytotoxic for HL60 leukemia cells (IC50: 37.26 µM).

Perinatal impact of cesarean delivery on maternal request compared with vaginal delivery among low-risk pregnancies in a university hospital: a prospective observational study in Bogotá, Colombia / Impacto perinatal de la cesárea por solicitud materna comparada con el parto vaginal en embarazos de bajo riesgo en un Hospital Universitario: estudio observacional prospectivo en Bogotá, Colombia

ABSTRACT Objective: There is insufficient evidence about the impact of cesarean delivery on maternal request (CDMR). This study was designed to evaluate different maternal and neonatal outcomes comparing CDMR with vaginal deliveries in low-risk pregnancies. Materials and methods: Prospective observational study including women aged 18 to 45 with a low-risk, term pregnancy, who delivered between June 2008 and April 2012 at a University Hospital in Bogota Colombia. The occurrence of any of 5 pre-specified adverse maternal events (maternal outcome) and of any of 17 pre-specified adverse neonatal events (neonatal outcome) was compared between CDMR and vaginal deliveries. Induced vaginal deliveries were analyzed separately. All women received the same standard of care. The effect of confounders was adjusted using multivariate logistic regression. Results: The study included 214 women with CDMR, 341 with spontaneous vaginal delivery (SVD) and 376 with induced vaginal delivery (IVD). Relative to the SVD group, the multivariate-adjusted odds ratios for adverse maternal outcomes were 0.21 (95% CI: 0.05-0.97) in the CDMR group and 0.93 (95% CI: 0.42-2.06) in the IVD group. The multivariate ORs for adverse neonatal outcomes were 0.59 (95% CI: 0.36-0.93) for CDMR and 0.84 (95% CI: 0.59-1.21) for IVD. The frequency of hospitalization of the newborn was lowest in the cesarean delivery group (10.3% versus 15.8% for spontaneous deliveries, 16.2% for induced vaginal deliveries). Conclusions: Among low-risk pregnancy women who entered a standardized obstetric care protocol, CDMR was associated with a lower rate of adverse perinatal outcomes when compared to spontaneous vaginal delivery. Further studies are needed to assess long-term the safety of CDMR.

RESUMEN Objetivo: Existe evidencia insuficiente sobre el impacto de la cesárea por solicitud materna (CSM); este estudio evalúa el efecto de la CSM en los múltiples desenlaces maternos y neonatales comparando CSM con parto vaginal entre embarazos de bajo riesgo. Materiales y métodos: Estudio observacional prospectivo que incluyó mujeres entre 18 y 45 años de edad, con un embarazo a término y de bajo riesgo, que tuvieron parto entre junio de 2008 y abril de 2012 en un hospital universitario en Bogotá, Colombia. Se comparó la ocurrencia de cualquiera de 5 eventos adversos maternos preespecificados, y de cualquiera de 17 eventos neonatales preespecificados, entre CSM y partos vaginales. Los partos vaginales inducidos fueron analizados separadamente. Todas las mujeres recibieron el mismo cuidado estandarizado. El efecto de variables confusoras se ajustó mediante regresión logística múltiple. Resultados: Se incluyeron 214 mujeres con CSM, 341 con parto vaginal espontáneo (PVE) y 376 con parto vaginal inducido (PVI). Respecto al grupo PVE, el OR ajustado del desenlace materno fue 0,21 (IC 95 %: 0,05-0,97) en el grupo CSM y 0,93 (IC 95%: 0,42-2,06) en el grupo PVI. El OR de presentar un mal desenlace neonatal fue: 0,59 (95% CI: 0,36-0,93) para CSM y 0,84 (95% CI: 0,59-1,21) para PVI. La frecuencia de hospitalización del neonato más baja fue en el grupo de CSM (10,3 % frente a 15,8 % para PVE, 16,2 % para PVI). Conclusiones: En pacientes con embarazo de bajo riesgo que ingresaron a un protocolo estándar de cuidado obstétrico, CSM se acompañó de una menor tasa de eventos adversos perinatales respecto al parto vaginal espontáneo. Sin embargo, se requieren estudios que evalúen la seguridad de CSM en el largo plazo.

Identification and management of prediabetes: results of the Latin America Strategic Prediabetes Meeting / Identificación y manejo de la prediabetes: resultados del Encuentro Estratégico de Prediabetes de América Latina / Identificação e gerenciamento de prediabetes: resultados da Reunião Estratégica de Prediabetes da América Latina

ABSTRACT To understand the status of prediabetes diagnosis and treatment in Latin America and to evaluate the use of metformin for diabetes prevention in this context. A panel of 15 diabetes experts from seven countries in Latin America met on 14 - 15 August 2014 in Lima, Peru, to review the available literature, discuss the role of prediabetes in type 2 diabetes mellitus and cardiovascular disease, analyze collected information, and make conclusions for prediabetes diagnosis and treatment in Latin America. Prediabetes diagnosis, screening, and treatment, including lifestyle changes, pharmacological treatment, and cost-effectiveness were discussed. Five resulting statements were issued for Latin America: prediabetes is a clinical and public health problem; health care systems do not currently diagnose/treat prediabetes; use of prediabetes risk detection tools are needed region-wide; treatment includes lifestyle changes, multidisciplinary education, and metformin; and registries of patient records and further studies should be supported. The expert panel concluded that in Latin America, preventive treatment through lifestyle changes and metformin are cost-effective interventions. It is important to improve prediabetes identification and management at the primary care level.(AU)

RESUMEN Comprender el estado del diagnóstico y el tratamiento de la prediabetes en América Latina y evaluar el uso de la metformina para la prevención de la diabetes en este contexto. Un panel de 15 expertos en diabetes de siete países de América Latina se reunió del 14 al 15 de agosto de 2014 en Lima, Perú, para revisar la literatura disponible, discutir el papel de la prediabetes en la diabetes mellitus tipo 2 y la enfermedad cardiovascular, analizar la información recolectada y formular conclusiones para el diagnóstico y el tratamiento de la prediabetes en América Latina. Se analizaron el diagnóstico, el tamizaje y el tratamiento de la prediabetes, inclusive los cambios en el estilo de vida, el tratamiento farmacológico y la relación costo-eficacia. Se emitieron cinco conclusiones para América Latina: la prediabetes es un problema clínico y de salud pública; los sistemas de atención de la salud actualmente no diagnostican o no tratan la prediabetes; el uso de herramientas de detección del riesgo de prediabetes es necesario en toda la región; el tratamiento incluye cambios en el estilo de vida, educación multidisciplinaria y metformina; y se debe brindar apoyo para llevar registros de historias clínicas y realizar estudios adicionales. El panel de expertos concluyó que en América Latina el tratamiento preventivo basado en cambios en el estilo de vida y administración de metformina son intervenciones eficaces en relación al costo. Es importante mejorar la identificación y el manejo de la prediabetes en el nivel de atención primaria.(AU)

RESUMO Entender o estado do diagnóstico e tratamento do prediabetes na América Latina e avaliar o uso de metformina para prevenção de diabetes neste contexto. Um painel de 15 especialistas em diabetes de sete países da América Latina reuniu-se de 14 a 15 de agosto de 2014 em Lima, Peru, para analisar a literatura disponível, discutir o papel do prediabetes em diabetes mellitus tipo 2 e doenças cardiovasculares, analisar informações coletadas e fazer conclusões para o diagnóstico e tratamento do prediabetes na América Latina. O diagnóstico, rastreio e tratamento pré-diabetes, incluindo mudanças de estilo de vida, tratamento farmacológico e custo-efetividade foram discutidos. Foram emitidas cinco conclusões resultantes para a América Latina: o prediabetes é um problema clínico e de saúde pública; os sistemas de saúde atualmente não diagnosticam/tratam prediabetes; o uso de ferramentas de detecção de risco de prediabetes é necessário em toda a região; o tratamento inclui mudanças de estilo de vida, educação multidisciplinar e metformina; e devem ser suportados registros de pacientes e outros estudos. O painel de especialistas concluiu que na América Latina, o tratamento preventivo através de mudanças de estilo de vida e metformina são intervenções efetivas em relação ao custo. É importante melhorar a identificação e gestão do prediabetes no nível de atenção primária.(AU)

The Phospholipid Linoleoylglycerophosphocholine as a Biomarker of Directly Measured Insulin Resistance

BACKGROUND: Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their potential as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles. METHODS: We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secretion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glucose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices. RESULTS: Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in-dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=−0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC). CONCLUSION: In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.

Curso básico em cirurgia plástica para acadêmicos: enxertos e retalhos / Basic course in plastic surgery for medical students: grafts and flaps

O processo de ensino na Medicina, principalmente nas áreas cirúrgicas, ocorre pela observação do ato cirúrgico e pela participação direta do estudante. A prática em cadáveres de seres humanos e em animais vivos está associada a custos elevados, risco de infecções, necessidade de instalações especializadas, bem como com aspectos legais e éticos a serem observados. A educação médica é baseada em modelos de simulação para o treinamento de habilidades, sendo de grande ajuda na aquisição e manutenção de habilidades cirúrgicas. O objetivo deste artigo é descrever uma metodologia para o ensino e a aprendizagem dos princípios básicos de retalhos cutâneos em um programa de graduação em Medicina, utilizando um modelo em pele suína (pele de porco). O curso baseia-se na formação em técnica cirúrgica básica de retalhos cutâneos entre acadêmicos de Medicina e residentes de áreas cirúrgicas, através do treinamento prático após uma aula teórica presencial. Os autores concluem que o ensino de uma metodologia para os princípios de cirurgia de retalhos cutâneos, utilizando um modelo de pele de porco, é versátil, fácil de montar e de baixo custo. Mostrou-se uma opção complementar ao arsenal de métodos baseados em outros modelos descritos (AU)

The teaching process in medicine, especially in the surgical areas, occurs through observation of the surgical act and direct student participation. The practice in human cadavers and live animals is associated with high costs, risk of infection, need for specialized facilities, as well as legal and ethical aspects to be observed. Medical education is based on simulation models for skills training, which are very helpful in acquiring and maintaining surgical skills. The aim of this article is to describe a methodology for teaching and learning the basic principles of cutaneous flaps in a medical degree program using a porcine skin model. The course is based on training in basic surgical technique of cutaneous flaps for medical students and residents of surgical areas through practical training after a theoretical lecture in person. The authors conclude that teaching a methodology for the principles of skin flap surgery using a pig skin model is versatile, easy to implement and inexpensive. It turned out to be a complementary option to the arsenal of methods based on other described models (AU)

Microcirurgia: modelo de treinamento básico para estudantes de Medicina / Microsurgery: basic training model for medical students

Introdução: Atualmente, existe uma carência de exposição à cirurgia plástica durante a graduação. A maioria dos currículos universitários não possui uma forma específica de ensino em cirurgia plástica. Para reverter essa situação, algumas universidades fomentam o contato precoce com a cirurgia plástica através de cursos extracurriculares. Método: Foi desenvolvido um Curso Básico de Microcirurgia para acadêmicos de Medicina com uma aula teórica e uma prática, anualmente e ao longo de 3 anos; na última edição, foi aplicado um questionário sobre o interesse na área e a importância no ensino durante a graduação. Resultados: Dentre os alunos, 65% apresentaram grande interesse pela microcirurgia, 95% relataram um aumento de interesse. Todos os alunos concordaram que os acadêmicos de Medicina devem ser mais envolvidos e treinados na área microcirúrgica durante a graduação. Conclusões: O desenvolvimento de um curso de treinamento básico de microcirurgia para acadêmicos de Medicina é benéfico para o aprendizado dos alunos, para obtenção de informações acerca da disciplina e para o aprimoramento de habilidades(AU)

Introduction: Currently there is a lack of exposure to plastic surgery during medical graduation. Most college curricula do not have a specific form of education in plastic surgery. To reverse this situation, some universities encourage early contact with plastic surgery through extracurricular courses. Methods: We developed a basic course of microsurgery for medical students with a lecture and a practical class, annually and over 3 years; in the last edition, a questionnaire on the interest in the area and the importance in education during graduation was applied. Results: Among the students, 65% showed great interest in microsurgery, and 95% reported an increase of interest. All students agreed that medical students should be more involved and trained in the microsurgical area during graduation. Conclusions: The development of a basic training course of microsurgery for medical students is beneficial for student learning, obtaining information about the discipline, and improving skills(AU)

Mapping malaria in municipalities of the Coffee Triangle region of Colombia using Geographic Information Systems [GIS]

Geographical Information Systems [GIS] have been used extensively for the development of epidemiological maps of malaria but not in the Coffee Triangle region of Colombia, endemic for P. vivax, P. falciparum and P. malariae. Surveillance case data [2007-2011] were used to estimate annual incidence rates per Plasmodium spp. [cases/100,000 pop] to develop the first malaria maps in the 53 municipalities of this region [departments Caldas, Quindio, Risaralda]. The GIS software used was Kosmo Desktop 3.0RC1[R]. Thirty thematic maps were developed according to the municipalities, years, parasite etiology, and uncomplicated and complicated cases. A total of 6582 cases were reported [6478 uncomplicated and 104 complicated, 77.8% Risaralda], for a cumulated rate of 269.46 cases/100,000 pop. Among uncomplicated cases, 5722 corresponded to P. vivax [234.25 cases/100,000 pop], 475 to P. falciparum [19.45 cases/100,000 pop], 8 to P. malariae [0.33 cases/100,000 pop] and 273 mixed [P. falciparum/P. vivax] [11.18 cases/100,000 pop]. The highest rate reported was in the more undeveloped and rural municipality of Risaralda [Pueblo Rico, 57.7 cases/1000 pop, 2009]. The burden of disease was concentrated in one department [>75% of the region]. The use of GIS-based epidemiological maps helps to guide decision-making for the prevention and control of this public health problem that still represents a significant issue in the region and the country, particularly in children

Estudio del proceso de clarificación de hidrolizados de almidón de yuca utilizando membranas cerámicas / Study of clarification process of cassava starch hydrolysates using ceramic membranes

Antecedentes: La etapa de clarificación de hidrolizados de almidón para la producción de jarabes de glucosa es la principal causa de su producción por lotes, además de acarrear altos costos al utilizar filtros rotatorios al vacío, carbón activado y tierras diatomeas que aseguren la calidad del producto. Objetivos: Evaluar la etapa de clarificación de hidrolizados de almidón de yuca obtenidos por vía enzimática utilizando tecnología con membranas, a diferentes temperaturas, diámetros de poro de membrana y presiones transmembrana. Métodos: La clarificación se realizó utilizando un piloto compuesto por un tanque enchaquetado, donde se llevó a cabo la reacción de hidrólisis. La filtración se realizaba conectando el tanque a una bomba que permitía enviar el fluido al módulo membranario; la presión transmembrana fue fijada con una válvula a la salida del módulo. Los experimentos se llevaron a cabo usando membranas con diferentes tamaños de poro en un diseño factorial 22, evaluando dos niveles de temperatura (50 y 70ºC) y dos niveles de presión transmembrana (0,15 y 0,30 MPa). Se midieron los caudales obtenidos para el retenido y el permeado. Las muestras obtenidas fueron analizadas para evaluar la calidad del permeado (turbidez, cantidad de proteína retenida, contenido de materia seca y ºBrix). El análisis estadístico se llevó a cabo con el software Statgraphic Centurion XVI.I®. Resultados: Los resultados obtenidos mostraron que las presiones transmembrana (0,15 y 0,30 MPa) y temperaturas (50 y 70ºC) evaluadas no influyen significativamente sobre la permeabilidad ni calidad del permeado (p-valores > 0,05) permitiendo trabajar con la menor presión tranmembrana (menor desgaste de equipos y menor gasto energético), y a la temperatura de hidrólisis, lo cual permitiría trabajar bajo condiciones de producción en continuo. Además, se observó que es posible utilizar membranas con diámetro de poro de hasta 0,8 µm; aumentado hasta en 5 veces la productividad y disminuyendo la turbidez en un 99%. Conclusiones: Es posible utilizar membranas cerámicas de microfiltración de hasta 0,8 µm, en condiciones moderadas de presión transmembrana y a la temperatura de hidrólisis para la clarificación de hidrolizados de almidón de yuca sin disminuir la calidad del permeado.

Background: Clarification step of starch hydrolysates for the production of glucose syrups is the main responsible for batch production; in addition, it causes high costs when using rotary vacuum filters, activated carbon and diatomaceous earth to ensure product quality. Objective: To evaluate the clarification step of hydrolyzed cassava starch obtained enzymatically, using membrane technology at different temperatures, membrane cut-off and transmembrane pressures. Methods: Clarification was conducted using a pilot composed by a jacketed tank, where the hydrolysis reaction was carried out. The filtration was performed by connecting the tank to a pump to send the fluid to the membrane carter; transmembrane pressure was fixed with a valve placed at the end of the module. The experiments were carried out using membranes with different cut-off sizes in a factorial design 22, two temperatures (50 and 70°C) and two transmembrane pressure levels (0.15 and 0.30 MPa) were evaluated. The flows obtained for the retentate and permeate were measured. The obtained samples were analyzed to assess the permeate quality (turbidity, amount of retained protein, dry matter content and °Brix). Statistical analysis was performed with software Statgraphic Centurion XVI.I®. Results: The results showed that the pressures (0.15 to 0.30 MPa) and temperatures (50 and 70°C) evaluated did not influence significantly the permeability, or the quality of the permeate (p-values > 0.05), it can allow to work with lower pressure (less wear on equipment and less energy), at hydrolysis temperature, it would allow to work under conditions of continuous production. Moreover, the possibility to use membranes with pore diameters up to 0.8 µm was observed; it allow to increase up to 5 times the productivity and decrease the turbidity by 99%. Conclusions: It is possible to use ceramic microfiltration membranes up to 0.8 µm in moderate transmembrane pressure, at hydrolysis temperature for clarification of cassava starch hydrolysates without decreasing the quality of the permeate flow.

Legado imperecedero de un botánico costarricense singular: -Jorge Gómez Laurito (1947-2014)-

The life and professional work of the Costa Rican botanist Jorge Gómez Laurito (1947-2014) are here depicted. His 91 scientific publications and 50 new plant taxa (including a family, a genus, and 48 species) represent a long-lasting legacy. The description and publication of Ticodendraceae was his most notable professional achievement. Rev. Biol. Trop. 62 (4): 1261-1272. Epub 2014 December 01.

Aquí se relata la vida y se analiza la obra profesional del botánico costarricense Jorge Gómez Laurito (1947-2014). Su legado más perdurable son 91 publicaciones científicas y 50 taxa nuevos de plantas (una familia, un género y 48 especies). La descripción y publicación de Ticodendraceae fue su mayor logro profesional.