RESUMO
Congenital heart disease (CHD) is the most common and lethal birth defect, affecting 1.3 million individuals worldwide. During early embryogenesis, errors in Left-Right (LR) patterning called Heterotaxy (Htx) can lead to severe CHD. Many of the genetic underpinnings of Htx/CHD remain unknown. In analyzing a family with Htx/CHD using whole-exome sequencing, we identified a homozygous recessive missense mutation in CFAP45 in two affected siblings. CFAP45 belongs to the coiled-coil domain-containing protein family, and its role in development is emerging. When we depleted Cfap45 in frog embryos, we detected abnormalities in cardiac looping and global markers of LR patterning, recapitulating the patient's heterotaxy phenotype. In vertebrates, laterality is broken at the Left-Right Organizer (LRO) by motile monocilia that generate leftward fluid flow. When we analyzed the LRO in embryos depleted of Cfap45, we discovered "bulges" within the cilia of these monociliated cells. In addition, epidermal multiciliated cells lost cilia with Cfap45 depletion. Via live confocal imaging, we found that Cfap45 localizes in a punctate but static position within the ciliary axoneme, and depletion leads to loss of cilia stability and eventual detachment from the cell's apical surface. This work demonstrates that in Xenopus, Cfap45 is required to sustain cilia stability in multiciliated and monociliated cells, providing a plausible mechanism for its role in heterotaxy and congenital heart disease.
Assuntos
Cardiopatias Congênitas , Síndrome de Heterotaxia , Proteínas de Xenopus , Animais , Padronização Corporal/genética , Cílios/genética , Cílios/metabolismo , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Síndrome de Heterotaxia/genética , Mutação de Sentido Incorreto , Fenótipo , Xenopus/anormalidades , Proteínas de Xenopus/metabolismoRESUMO
PIP: A longitudinal study conducted in Nairobi focused on 70 Africans, 35 Indian vegetarians, and 20 Indian non-vegetarians revealed significant differences between these 3 groups in terms of the choice of milk, breastfeeding duration, age of introduction of other foods to the infant's diet, and the choice of weaning foods. African mothers tended to exclusively breastfeed their infants for longer durations than either of the 2 groups of Indian mothers. At 6 weeks, 42% of African mothers, 19% of Indian vegetarian mothers, and no Indian nonvegetarian mothers were exclusively breastfeeding. Bottle feeding was widespread in all 3 groups; however, African mothers showed a pattern of mixed feeding (at 12 weeks, 68% of African infants were being fed both breast and formula milk), while Indian mothers tended to replace breastfeeding with bottle feeding (at 12 weeks, 10% of the vegetarian mothers and 19% of the non-vegetarian mothers were following this regimen). Indian nonvegetarian mothers made extensive use of formula, while their vegetarian counterparts relied more on cow's milk. All 3 groups introduced foods earlier than the recommended 4-6 months. By 18 weeks, 98% of African infants, 86% of Indian vegetarian infants, and 89% of Indian nonvegetarian infants were receiving semi-solid or solid foods in addition to milk. In all 3 groups, cereals were the most commonly introduced 1st food, followed by fruits and pureed vegetables. The use of commercial cereals was extensive, with 97% of African mothers, 90% of Indian vegetarian mothers, and 82% of Indian nonvegetarian mothers feeding such preparations to their 6-week-old infants. As the children grew older, use of commercial cereals decreased. Despite the differences in feeding practices, the pattern of weight gain was parallel for infants from all 3 study groups. Moreover, the mean energy and protein intakes of all 3 groups were 80% or more of recommended allowances.^ieng
Assuntos
Aleitamento Materno , Alimentos Infantis , Fatores Etários , Dieta Vegetariana , Humanos , Índia/etnologia , Lactente , Recém-Nascido , Quênia , Estudos Longitudinais , População UrbanaAssuntos
Alimentos Infantis , Leite Humano , Leite/análise , Animais , Humanos , Lactente , Recém-Nascido , Leite Humano/análiseRESUMO
PIP: Vegetarian and nonvegetarian women of Asian Indian origin living in Nairobi, Kenya, and attending the antenatal clinic at the Aga Khan Hospital were followed up from 26 weeks of pregnancy to term. The objective was to observe these pregnant women in relation to pregnancy performance and outcome. The mean gestational age for both groups was 39.0 weeks. There is a progressive increase in weight from the 26th week of pregnancy up to the time of delivery among both groups. 65.4% of the women gained between 90 and 150% of the expected value. Women who gained less than 90% of the expected value (34.6%) did not produce smaller babies. The mean birth weight of the newborns was 2,869 gms in the vegetarian group and 3,026 gms in the nonvegetarian group. There was no significant difference in the outcome of pregnancy between the 2 groups. Mean birth weight, mean length and mean head circumference of the babies in both the groups fell within the 10th and 25th percentiles of the Harvard standards. The mean chest circumference of the babies in the vegetarian group fell within the 25th and 50th percentiles, while that of the babies in the nonvegetarian group fell between 50th and 75th percentiles. The pattern of weight gain in the study population corresponds favorably with that observed among British women . Other anthropometric parameters studied were height, mid-upper arm circumference and 4 skinfold thickness. Changes in muscle mass and fat area were also calculated. Tables show quantitative data.^ieng
Assuntos
Antropometria , Peso ao Nascer , Peso Corporal , Emigração e Imigração , Etnicidade , Crescimento , Fenômenos Fisiológicos da Nutrição , Resultado da Gravidez , Gravidez , População Urbana , África , África Subsaariana , África Oriental , Ásia , Biologia , Desenvolvimento Infantil , Cultura , Demografia , Países em Desenvolvimento , Saúde , Índia , Quênia , Fisiologia , População , Características da População , Dinâmica Populacional , Reprodução , Pesquisa , Projetos de PesquisaRESUMO
Anthropometric data of 1739 pregnant women followed in the period 1 May 1978 - 31 December 1980 are presented. Mean height was 157.1 +/- 5.5 cm. Weight gain between 3 months and term was 5.8 kg. Significant changes in the course of pregnancy were observed in upper arm circumference, triceps and subscapular skinfolds. Women started pregnancy with a higher mean weight-for-height ratio than the reference; in the course of pregnancy the ratio decreased from 107.0% to 95.7%.
PIP: The results of 1 phase of a longitudinal study of the impact of nutritional status during pregnancy on maternal boby weight, birth weight, lactation, and infant growth in a rural population in Ukambani, Kenya, are presented, i.e., information on maternal anthropometric changes, especially weight gains, during pregnancy. 1739 (61%) of 2874 pregnant women who were included in the May 1978 throught December 1980 study. All pregnant women were to be included, and each woman was to be examined during each trimester of her pregnancy; however, fieldworkers failed to identify many pregnancies at early stages and missed some pregnancies. The use of male fieldworkers, the mobility of the population, the tendecy for pregnant women to staty with distant relatives, and several other factors contributed to the failure to identify and examine all the women. Most of the women were examined only during the 3rd trimester (39.4%) or only during the 2nd and 3rd trimesters (35.9%). During the examination measurements were taken of weight, height, upper arm circumference, triceps, subscapular skinfold, and muscle and fat areas. Data on food intake during the previous 24-hour period were also collected. The meams of the measurements were calculated, compared with a reference standard, and the significance of changes during the pregnancy wes assessed. The reference standard, utilitzing data on British women, was 90% of the weight for height ratio of Caucasian nonpregnant women and a 20% weight gain at term 15.3% were primiparous, mean age, 19.6 years. The mean age of all the women was 26.3. Mean parity was 2.7 at 25 years of age and 8.7 at 40 years of age. During the early phase of pregnancy, the women had a higher weight for height ratio than the reference standard; however, during the later stages of pregnancy they had a lower ratio than the standard. Mean weight for height as a percentage of the standard was 107.0% during the 1st trimester and declined to 95.7% during the last trimester. Between the 3.1 st month and the 7.6 th month, the mean weight gain was 4.1 kg or 57.8% of the standard. The average weight gain at 8.6 months was 5.8 kg. This represents only an 11.1% increase over the mean nonpregnant weight. This small weight gain is close to borderline malnutriation and may constitute a net pregnancy weight loss if birth weight and the weight of the placenta, amniotic fluid, and the extra water needed for maternal circulation is taken into account. Despite the low weight gain and mean energy intake of 1500-1600 calories/day during pregnancy, the average birth weight was 93.5% of the standard, the low birth weight rate was only 9%, and the mean breast milk yield during the first 3 months was 700 ml. Means of the upper arm circumference, triceps, subscapular skinfolds, and fat areas declined of the anthropometric data are shown in tabular form.