MiRNA-149 as a Candidate for Facial Clefting and Neural Crest Cell Migration.

Nonsyndromic cleft lip with or without palate (nsCL/P) ranks among the most common human birth defects and has a multifactorial etiology. Human neural crest cells (hNCC) make a substantial contribution to the formation of facial bone and cartilage and are a key cell type in terms of nsCL/P etiology. Based on increasing evidence for the role of noncoding regulatory mechanisms in nsCL/P, we investigated the role of hNCC-expressed microRNAs (miRNA) in cleft development. First, we conducted a systematic analysis of miRNAs expressed in human-induced pluripotent stem cell-derived hNCC using Affymetrix microarrays on cell lines established from 4 unaffected donors. These analyses identified 152 candidate miRNAs. Based on the hypothesis that candidate miRNA loci harbor genetic variation associated with nsCL/P risk, the genomic locations of these candidates were cross-referenced with data from a previous genome-wide association study of nsCL/P. Associated variants were reanalyzed in independent nsCL/P study populations. Jointly, the results suggest that miR-149 is implicated in nsCL/P etiology. Second, functional follow-up included in vitro overexpression and inhibition of miR-149 in hNCC and subsequent analyses at the molecular and phenotypic level. Using 3'RNA-Seq, we identified 604 differentially expressed (DE) genes in hNCC overexpressing miR-149 compared with untreated cells. These included TLR4 and JUNB, which are established targets of miR-149, and NOG, BMP4, and PAX6, which are reported nsCL/P candidate genes. Pathway analyses revealed that DE genes were enriched in pathways including regulation of cartilage development and NCC differentiation. At the cellular level, distinct hNCC migration patterns were observed in response to miR-149 overexpression. Our data suggest that miR-149 is involved in the etiology of nsCL/P via its role in hNCC migration.

[Social inequalities and health. Socioeconomic level and infant mortality in Chile in 1985-1995]. / Desigualdades sociales y salud. Nivel socioeconómico y mortalidad infantil en Chile, 1985-1995.

BACKGROUND: The strong relationship between social inequalities and health have been extensively reported. AIM: To measure the effects of social inequalities, assessed through maternal educational level, on infant mortality in Chile. MATERIAL AND METHODS: Using death and birth electronic databases of the Instituto Nacional de Estadisticas, the annual rates of infant mortality per years of approved studies of both parents and per cause were calculated. RESULTS: In the 1990-1995 period, there is a clear gradient of infant mortality according to the level of education of the mother (38.2 per 1000 born alive among those without education versus 7.8 per 1000 born alive among those with university education). The same tendency is maintained for neonatal and post-neonatal mortality. All groups of causes had a similar effect, standing out diseases of the respiratory system with a relative risk (RR) of 14.3 and a population attributable risk (PAR) of 73%, trauma with a RR of 11.3 and a PAR of 69% and infectious diseases with a RR of 10.8 and a PAR of 62%. Between 1985 and 1995, absolute inequalities decreased but relative inequalities remained constant. CONCLUSIONS: The great social inequality in infant mortality has persisted in Chile during the last years. To adequately assess the national progresses in population health using infant mortality as an indicator, the gaps between social groups must be born in mind.

PIP: Birth and death statistics from Chile¿s National Institute of Statistics were used to determine the influence of socioeconomic status as measured through maternal educational level on infant mortality from 1990-95 and to assess trends since 1985. The rates of infant, neonatal, and postneonatal mortality were calculated for 6 educational groups for the mother and father: 0, 1-3, 4-6,7-9, 10-12, and 13 or more years. The deaths were classified by cause according to the International Classification of Diseases and to Taucher¿s classification into avoidable, difficult to avoid, poorly defined, and other causes. A clear association was observed in levels of infant mortality according to maternal education. Infant mortality rates ranged from 38.2/1000 live births for children of illiterate mothers to 7.8/1000 for children of mothers with higher education. A child of an illiterate mother had a risk of death in the first year 4.9 times higher than the child of a mother with higher education. The same trend was observed for neonatal mortality and for paternal education. The mortality gradient by maternal education was maintained for all causes of death and both classifications studied. Diseases of the respiratory system had a relative risk (RR) of 14.3 and a population attributable risk (PAR) of 73%, trauma had an RR of 11.3 and PAR of 69%, and infectious diseases had an RR of 10.8 and PAR of 62%. Infant mortality rates declined between 1985-95 in all maternal educational groups, but the inequalities remained.

Desigualdades sociales y salud: nivel socioeconómico y mortalidad infantil en Chile, 1985-1995 / Socioeconomic level and infant mortality in Chile in the period 1985-1995

Background: The strong relationship between, social inequalities and health have extensively reported. Aim: to measure the effects of social inequalities, assessed through maternal educational level,on infant mortality in Chile. Material and methods: Using death and birth electronic databases of the Instituto Nacional de Estadísticas, the annual rates of infant mortality per years of approved studies of both parents and per cause were calculated. Results: In the 1990-1995 period,there is a clear gradient of infant mortality according to the level of education of the mother (38.2 per 1000 born alive among those without education versus 7.8 per 1000 born alive among those with university education). The same tendency is maintained for neonatal and post-neonatal mortality . All groups of causes had a similar affect, standing out disease of the respiratory system with a relative risk (RR) of 14.3 and a population attributable risk (PAR) of 73 percent, trauma with a RR of 11.3 and a PAR of 69 percent and infectious disease with a RR of 10.8 and a PAR of 62percent. Between 1985 and 1995, absolute inequalities decreased but relative inequalities remained constant. Conclusions: The great social inequality in infant mortality has persisted in Chile during the last years. To adequately asses the national progresses in population healt using infant mortality as an indicator, the gaps between social groups must be born in mind