Quality of life in children with infrequent congenital heart defects: cohort study with one-year of follow-up.

BACKGROUND: The evidence regarding patient related outcomes in children with infrequent congenital heart defects (I-CHD) is very limited. We sought to measure quality of life (QoL) in children with I-CHD, and secondarily, to describe QoL changes after one-year of follow-up, self-reported by children and through their caregivers' perspective. METHODS: We assembled a cohort of children diagnosed with an I-CHD in a cardiovascular referral center in Colombia, between August 2016 and September 2018. At baseline and at one-year follow-up, a clinical psychology assessment was performed to establish perception of QoL. The Pediatric Quality of Life Inventory (PedsQL) 4.0 scale was used in both general and cardiac modules for patients and for their caregivers. We used a Mann-Whitney U test to compare scores for general and cardiac modules between patients and caregivers, while a Wilcoxon test was used to compared patients' and caregivers' baseline and follow-up scores. Results are presented as median and interquartile range. RESULTS: To date, QoL evaluation at one-year follow-up has been achieved in 112/157 patients (71%). Self-reported scores in general and cardiac modules were higher than the QoL perceived through their caregivers, both at baseline and after one-year of follow-up. When compared, there was no statistically significant difference in general module scores at baseline between patients (median = 74.4, IQR = 64.1-80.4) and caregivers scores (median = 68.4, IQR = 59.6-83.7), p = 0.296. On the contrary, there was a statistical difference in baseline scores in the cardiac module between patients (median = 79.6, IQR = 69.7-87.4) and caregivers (median = 73.6, IQR = 62.6-84.3), p = 0.019. At one-year of follow-up, scores for the general module between patients (median = 72.8, IQR = 59.2-85.9) and caregivers (median = 69.9, IQR = 58.1-83.7) were not statistically different (p = 0.332). Finally, a significant difference was found for cardiac module scores between patient (median = 75.0, IQR = 67.1-87.1) and caregivers (median = 73.1, IQR = 59.5-83.8), p = 0.034. CONCLUSIONS: QoL in children with I-CHD can be compromised. However, children have a better perception of their QoL when compared with their caregivers' assessments. To provide high-quality care, besides a thorough clinical evaluation, QoL directly elicited by the child should be an essential aspect in the integral management of I-CHD.

Production of distinct labdane-type diterpenoids using a novel cryptic labdane-like cluster from Streptomyces thermocarboxydus K155.

Bioinformatic mining of the Streptomyces thermocarboxydus K155 genome predicted the presence of four synthases for the production of geosmin, hopene, albaflavenone, and a type B-type A diterpenoid system like that described for labdane-related diterpenoids (LRD). The lrd cluster was comprised by an operon of four genes (lrdABDC). This cluster seemed to be silent in the wild-type strain, as neither labdane nor terpene-like compounds were detected by UPLC-TOF-MS and GC-MS analyses in both culture supernatants and mycelial extracts. Heterologous expression of the lrdABDC cluster in a defective cyslabdan producer (Streptomyces cyslabdanicus K04-0144Δcld) generated 8,17-epoxy-7-hydroxy labda-12,14-diene and cyslabdan. The same cluster expressed in the strains Streptomyces coelicolor M1152, Streptomyces peucetius var. caesius, and Streptomyces avermitilis SUKA22 produced the general intermediary labda-8(17), 12(E),14-triene [(E)-biformene]. Besides (E)-biformene, S. coelicolor M1152 and S. avermitilis SUKA22 produced two and three different labdane-type diterpenoids, underlying the relevance of the genetic background of the Streptomyces host in product formation.

The structure of (E)-biformene synthase provides insights into the biosynthesis of bacterial bicyclic labdane-related diterpenoids.

The labdane-related diterpenoids (LRDs) are a large group of natural products with a broad range of biological activities. They are synthesized through two consecutive reactions catalyzed by class II and I diterpene synthases (DTSs). The structural complexity of LRDs mainly depends on the catalytic activity of class I DTSs, which catalyze the formation of bicyclic to pentacyclic LRDs, using as a substrate the catalytic product of class II DTSs. To date, the structural and mechanistic details for the biosynthesis of bicyclic LRDs skeletons catalyzed by class I DTSs remain unclear. This work presents the first X-ray crystal structure of an (E)-biformene synthase, LrdC, from the soil bacterium Streptomyces sp. strain K155. LrdC was identified as a part of an LRD cluster of five genes and was found to be a class I DTS that catalyzes the Mg2+-dependent synthesis of bicyclic LRD (E)-biformene by the dephosphorylation and rearrangement of normal copalyl pyrophosphate (CPP). Structural analysis of LrdC coupled with docking studies suggests that Phe189 prevents cyclization beyond the bicyclic LRD product through a strong stabilization of the allylic carbocation intermediate, while Tyr317 functions as a general base catalyst to deprotonate the CPP substrate. Structural comparisons of LrdC with homology models of bacterial bicyclic LRD-forming enzymes (CldD, RmnD and SclSS), as well as with the crystallographic structure of bacterial tetracyclic LRD ent-kaurene synthase (BjKS), provide further structural insights into the biosynthesis of bacterial LRD natural products.

Funciones ejecutivas y atención en pacientes pediátricos con infecciónpor virus de inmunodeficiencia humana en Colombia / Executive functions and attention in colombian children with human immunodeficiency virus infection

las alteraciones neuropsicológicas asociadas a la infección por el virus de inmunodeficienciahumana (VIH) han sido descritas adultos. No se conoce el patrón de funciones ejecutivas y atención ni surelación con el control de la infección por VIH en pediatría.Objetivos: determinar los factores asociados y los patrones de las alteraciones en atención y funciones ejecutivasen niños con infección por el virus de inmunodeficiencia humana (VIH).Materiales y métodos: se realizó un estudio analítico de cohorte entre noviembre 2011 a diciembre del 2012.Resultados: 30 individuos cumplieron con los criterios de inclusión. 26 (86,6%) individuos tuvieron controlde infección por VIH, con edad promedio de 10,2 años (6-16 años), el 60% hombres. La mayor proporciónde alteraciones se encontró en flexibilidad cognitiva en el 33,3%, atención sostenida en un 26,7%, habilidadesconceptuales en 16,7%, y en planificación y organización en 13,3%. El 36,6% presentó alteración de la secuenciaciónvisomotora. La baja calidad de vida relacionada con la enfermedad presentó un mayor riesgo en todaslas áreas de atención y funciones ejecutivas. No se encontró una asociación estadísticamente significativa delcontrol de la infección por VIH en los últimos 2 años con la evaluación de atención y funciones.Conclusiones: la flexibilidad cognitiva presentó la mayor alteración dentro de las subpruebas neuropsicoló-gicas. Se encontraron bajos puntajes en calidad de vida y el control de infección en pacientes con dificultadesen áreas de atención y funciones ejecutivas, sin tener significancia estadística...

Neuropsychological abnormalities associated with infection by the human immunodeficiencyvirus (HIV) have been described adults. The pattern of executive functions and attention with regard to thecontrol of HIV infection has not ben studied in children.Objective: to determine the associated factors and patterns of alterations in attention and executive functionsin children infected with human immunodeficiency virus (HIV). Methods: a cohort study was made fromNovember 2011 to December 2012.Results. 30 individuals met the inclusion and exclusion criteria. 26 (86.6%) individuals had control HIV infection,with mean age 10.2 years (6-16 years), 60% were male, 76.6% with primary school education. The largestproportions of alterations were found in cognitive flexibility (33.3%), selective attention (26.7%), conceptualskills (16.7%), and planning and organization (13.3%). 36.6% had impaired psychomotor speed. The qualityof life related to the disease was associated with lower scores in all areas of attention and executive functions...