Effect of Social Service Prenatal Care Utilization on Perinatal Outcomes among Women with Socioeconomic Problems in the Tokyo Metropolitan Area

Background. To investigate the effect of social service prenatal care (PNC) utilization on perinatal outcomes among women with socioeconomic problems in the Tokyo metropolitan area. Methods. Retrospective study. The study enrolled all women at our hospital who either attended PNC utilizing social services (attenders) or who did not attend PNC (nonattenders) between January 1, 2007, and December 31, 2010. We compared the maternal characteristics and perinatal outcome of attenders with those of nonattenders. Results. A total of 83 attenders and 45 nonattenders were enrolled. The mean gestational age at the first PNC visit was 31.1 weeks in the attenders. Attenders were found to have a lower incidence of preterm delivery, pregnancy-induced hypertension, emergency cesarean section, low birth weight, and the NICU admission than nonattenders (P < 0.05). Conclusions. The utilization of social service PNC greatly improved perinatal outcomes among women with socioeconomic problems problems in the Tokyo metropolitan area

ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3-5 years from onset. Familial ALS (FALS) comprises 5%-10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis.We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions.6 page(s