RESUMEN
A double-blind, randomized, controlled, parallel-group prospective trial was conducted to determine whether a dose-response existed for four different levels of docosahexaenoic acid (DHA) supplementation on the cognitive performance of infants. A total of 122 term infants were fed one of four different formulas varying in their DHA composition (0.00, 0.32, 0.64, and 0.96% of total fatty acids as DHA) from birth to 12 mo. The three DHA-supplemented formulas also contained 0.64% of total fatty acids as arachidonic acid (ARA, 20:4n-6). Infants were tested at 4, 6, and 9 mo of age on a visual habituation protocol that yielded both behavioral and psychophysiological indices of attention. Infants in all DHA+ARA-supplemented conditions had lower heart rates than those in the unsupplemented condition; there was no dose-response for this effect. The distribution of time that infants spent in different phases of attention (a cognitive index derived from the convergence of behavioral and cardiac responses) varied as a function of dosage. Infants supplemented at the two lower DHA doses spent proportionately more time engaged in active stimulus processing than infants fed the unsupplemented formula, whereas infants fed the highest dose were intermediate and did not differ from any other group.
Asunto(s)
Atención/efectos de los fármacos , Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Grasos Insaturados/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Animales , Método Doble Ciego , Humanos , Lactante , Fórmulas Infantiles/química , Pruebas Neuropsicológicas , Estudios ProspectivosRESUMEN
Duchenne muscular dystrophy is a progressive muscle disease characterized by increasing muscle weakness and death by the third decade. mdx mice exhibit the underlying muscle disease but appear physically normal with ordinary lifespans, possibly due to compensatory expression of utrophin. In contrast, double mutant mice (mdx/utrn(-/-)), deficient for both dystrophin and utrophin die by approximately 3 months and suffer from severe muscle weakness, growth retardation, and severe spinal curvature. The capacity of human retinal dystrophin (Dp260) to compensate for the missing 427 kDa muscle dystrophin was tested in mdx/utrn(-/-) mice. Functional outcomes were assessed by histology, EMG, MRI, mobility, weight and longevity. MCK-driven transgenic expression of Dp260 in mdx/utrn(-/-) mice converts their disease course from a severe, lethal muscular dystrophy to a viable, mild myopathic phenotype. This finding is relevant to the design of exon-skipping therapeutic strategies since Dp260 lacks dystrophin exons 1-29.
Asunto(s)
Distrofina/genética , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Distrofia Muscular Animal/terapia , Transgenes , Factores de Edad , Animales , Western Blotting/métodos , Distrofina/deficiencia , Electromiografía/métodos , Expresión Génica/fisiología , Terapia Genética , Humanos , Inmunohistoquímica/métodos , Imagen por Resonancia Magnética/métodos , Ratones , Ratones Endogámicos mdx , Ratones Transgénicos , Necrosis , Tomografía Computarizada por Rayos X/métodos , Utrofina/genéticaRESUMEN
Previous attempts at unequivocal specification of signal strength in fetal magnetocardiographic (fMCG) recordings have used an equivalent current dipole (ECD) to estimate the cardiac vector at the peak of the averaged QRS complex. However, even though the magnitude of fetal cardiac currents are anticipated to be relatively stable, ECD-based estimates of signal strength show substantial and unrealistic variation when comparing results from different time windows of the same recording session. The present study highlights the limitations of the ECD model, and proposes a new methodology for fetal cardiac source reconstruction. The proposed strategy relies on recursive subspace projections to estimate multiple dipoles that account for the distributed myocardial currents. The dipoles are reconstructed from spatio-temporal fMCG data, and are subsequently used to derive estimators of the cardiac vector over the entire QRS. The new method is evaluated with respect to simulated data derived from a model of ventricular depolarization, which was designed to account for the complexity of the fetal cardiac source configuration on the QRS interval. The results show that the present methodology overcomes the drawbacks of conventional ECD fitting, by providing robust estimators of the cardiac vector. Additional evaluation with real fMCG data show fetal cardiac vectors whose morphology closely resembles that obtained in adult MCG.
Asunto(s)
Algoritmos , Cardiotocografía/métodos , Diagnóstico por Computador/métodos , Magnetocardiografía/métodos , Modelos Cardiovasculares , Vectorcardiografía/métodos , Simulación por Computador , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The range of human milk docosahexaenoic acid (DHA) concentrations worldwide is much broader than the range explored in randomized clinical trials to date. OBJECTIVE: The primary objective was to determine the effect of 4 amounts of DHA supplementation on the visual acuity of formula-fed infants at 12 mo of age. Secondary objectives were to evaluate visual acuity maturation, red blood cell fatty acids, tolerance, anthropometric measures, and adverse events. DESIGN: This double-masked, randomized trial was conducted at 2 sites (Dallas and Kansas City). Three hundred forty-three healthy, term, formula-fed infants were enrolled at 1-9 d of age and were randomly assigned to be fed 1 of the following 4 infant formulas containing equivalent nutrient amounts, except for long-chain polyunsaturated fatty acids: control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96% DHA; DHA-supplemented formulas also provided 0.64% arachidonic acid. Visual acuity was measured by visual evoked potentials in 244 infants who completed the 12-mo primary outcome examination. RESULTS: Infants fed control formula had significantly poorer visual evoked potential visual acuity at 12 mo of age than did infants who received any of the DHA-supplemented formulas (P < 0.001). There were no significant differences in visual evoked potential visual acuity between the 3 amounts of DHA supplementation for either site at any age tested. CONCLUSIONS: DHA supplementation of infant formula at 0.32% of total fatty acids improves visual acuity. Higher amounts of DHA supplementation were not associated with additional improvement of visual acuity. This trial was registered at clinicaltrials.gov as NCT00753818.