Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10−62, SLC24A5 P = 9.6×10−9) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10−27, TYR P = 1.1×10−9, APBA2[OCA2] P = 1.5×10−8, SLC45A2 P = 6×10−9) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (∼44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ∼70% of the estimated heritability.

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We studied the effect of caffeine on voluntary and electrically stimulated contractions of the adductor pollicis muscle in five adult volunteers. Caffeine (500 mg) was administered orally in a double-blind fashion. Electrical stimulation of the ulnar nerve was performed at 10, 20, 30, 50, and 100 Hz before and after a sustained voluntary contraction held at 50% of the maximal voluntary contraction (MVC). A brief tetanus at 30 Hz was also performed to calculate relaxation rate in the fresh muscle. Contractile properties, relaxation rate, and endurance were then assessed after caffeine and placebo, as well as the response of the fatigued muscle to different frequencies of stimulation. There was no difference in the maximal tension obtained with electrical stimulation (T100) or in the MVC between placebo and caffeine. The tensions developed with electrical stimulation at lower frequencies increased significantly with caffeine ingestion, shifting the frequency-force curve to the left, both before and after fatigue. Mean plasma caffeine concentration associated with these responses was 12.2 +/- 4.9 mg/l. We conclude that caffeine has a direct effect on skeletal muscle contractile properties both before and after fatigue as demonstrated by electrical stimulation.

Important perinatal factors that are associated with early neonatal deaths in very low birth weight preterm infants can be modified by interventions such as improving fetal vitality at birth and reducing the incidence and severity of respiratory distress syndrome. The heterogeneity of early neonatal rates across the different centers studied indicates that best clinical practices should be identified and disseminated throughout the country.

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Objetivo: Avaliar os fatores perinatais associados ao óbito neonatal precoce em prematuros com peso ao nascer entre 400 e 1.500 g. Métodos:Coorte prospectiva e multicêntrica dos nascidos vivos com idade gestacional de 23 a 33 semanas e peso de 400-1.500 g, sem malformações em oito maternidades públicas terciárias universitárias entre junho de 2004 e maio de 2005. As características maternas e neonatais e a morbidade nas primeiras 72 horas de vida foram comparadas entre os prematuros que morreram ou sobreviveram até o sexto dia de vida. As variáveis perinatais associadas ao óbito neonatal precoce foram determinadas por regressão logística.Resultados: No período, 579 recém-nascidos preencheram os critérios de inclusão. O óbito precoce ocorreu em 92 (16%) neonatos, variando entre as unidades de 5 a 31%, e tal diferença persistiu controlando-se por um escore de gravidade clínica (SNAPPE-II). A análise multivariada para o desfecho óbito neonatal intra-hospitalar precoce mostrou associação com: idade gestacional de 23-27 semanas (odds ratio -OR = 5,0; IC95% 2,7-9,4), ausência de hipertensão materna (OR = 1,9; IC95% 1,0-3,7), Apgar 0-6 no 5º minuto (OR = 2,8; IC95% 1,4-5,4), presença de síndrome do desconforto respiratório (OR = 3,1; IC95% 1,4-6,6) e centro em que o paciente nasceu.Conclusão: Importantes fatores associados ao óbito neonatal precoce em prematuros de muito baixo peso são passíveis de intervenção, como a melhora da vitalidade fetal ao nascer e a diminuição da incidência e gravidade da síndrome do desconforto respiratório. As diferenças de mortalidade encontradas entre os centros apontam para a necessidade de identificar as melhores práticas e adotá-las de maneira uniforme em nosso meio.

The importance of inspiratory muscle tone in the maintenance of functional residual capacity (FRC) in newborns was studied in eight premature infants with birth weights of 1,166 +/- 217 g and gestational age 29 +/- 1.9 wk (mean +/- SD). Rib cage and abdominal anteroposterior diameters were monitored with magnetometers, and electromyograms of the diaphragm and intercostal muscles were recorded with surface electrodes. Sleep state was monitored using electrooculogram and behavioral criteria. We assessed the decrease in tonic activity of the inspiratory muscles and the fall in end-expiratory lung volume during apnea compared with the period just preceding apnea. A total of 98 apneas were analyzed. In all instances a decrease in diaphragmatic and intercostal tone was associated with a decrease in the anteroposterior diameter of both rib cage and abdomen, indicating a fall in FRC. These changes were more marked during quiet sleep than during rapid-eye-movement sleep (P less than 0.01). Our results suggest that inspiratory muscle tone is a major determinant of FRC in the newborn.

The caudocephalad profile of esophageal pressure swings was studied in 10 preterm and 5 full-term infants, and the effect of chest wall distortion on esophageal pressure swings was analyzed in 12 preterm infants. Esophageal pressure was measured with a fluid-filled catheter, tidal volume with a pneumotachograph, mouth pressure with a face mask and pressure transducer, and rib cage and abdominal motion with magnetometers. In preterm infants the profile of esophageal pressure swings fell very steeply in the caudocephalad direction. In full-term infants it was flat during quiet sleep and steep during rapid-eye-movement sleep. When breaths, standardized for pleural pressure, were compared between a period with maximal and a period with minimal chest wall distortion, esophageal pressure swings for both spontaneous and occluded breaths were higher in the former period. We conclude that the complaint preterm rib cage results in an uneven distribution of pleural pressure and that this distribution varies with changes in chest wall distortion. Esophageal pressure measurements are therefore an unreliable estimate of mean pleural pressure in the preterm infant and can be unreliable in the term infant.