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This article reviews key recent findings in the field of human cortical development. This development is divided into three major time-dependent phases: neural proliferation of inhibitory and excitatory neurons in spatially distinct regions, migration through multiple cellular boundaries, and maturation through morphologic changes that result in the elaboration of dendrites and axons and that establish the multitude of cellular contacts that underlie neuronal processing. Many of the neurocognitive disorders treated in the clinic can trace their origin to a disorder in one or more of these key steps. Along with this update, work is highlighted that offers a glimpse at the future of therapy for developmental brain disorders that can result from disorders of these cellular events.

Accurate spatial and temporal expression of gonadotrope-specific genes, such as the gonadotropin-releasing hormone receptor (GnRHR) gene, is critical for gonadotrope maturation. Herein, we show that a specific E-box in the mouse GnRHR promoter binds two group A basic-helix-loop-helix (bHLH) transcription factors. Mutation of this E-box decreases expression in mouse gonadotrope-derived alphaT3-1 and LbetaT2 cell lines. Microarray and western blots show that the bHLH transcription factor NeuroD1 is strongly expressed in the gonadotrope progenitor, alphaT3-1, whereas Mash1 is strongly expressed in the more mature gonadotrope, LbetaT2. Over-expression of NeuroD1 or Mash1 increases expression of the GnRHR gene or a multimer of the E-box and this increase is lost upon mutation of the E-box. Electrophoretic mobility shift assays reveal that the GnRHR E-box binds NeuroD1 from alphaT3-1 cells, but binds Mash1 from LbetaT2 cells. The sequential binding of different members of the group A bHLH transcription factor family to mouse GnRHR E-box 3 as the gonadotrope differentiates may represent a mechanism necessary for proper spatial and temporal expression of the GnRHR during gonadotrope development.

Danazol (17alpha-pregna-2,4-dien-20-yno [2,3-d]-isoxazol-17beta-ol), is a synthetic derivative of ethisterone, structurally related to stanozolol. For this reason its use as doping agent has been investigated. Danazol (Runch) (200 mg) were orally administered to two healthy male volunteers. Urine samples were collected up to 1-week post-dose. Four new metabolites have been identified in addition to the five previously reported. We propose the monitorization of 6beta-hydroxy-2-hydroxymethyl-1,2-dehydroethisterone and 6beta,16epsilon-dihydroxy-2epsilon-hydroxymethyl-ethisterone by free fraction analysis. In a same way, we proposed to detect the principal isomer of a mono-hydroxylated metabolite of 6beta-hydroxy-2epsilon-hydroxymethylethisterone in the conjugated fraction. We conclude that new metabolites can be included for the detection of danazol abuse since the main metabolite ethisterone is excreted relatively fast in urine.

Objective: To evaluate the impact of individualized, developmentally supportive family-centered care on infant physiological variables, growth, behavioral stress cues, return to sleep state, medical and developmental progress, complications, resource utilization, parental perception of the neonatal intensive-care unit experience, and overall parental satisfaction., Design: Quasi-experimental, repeated measures design., Setting: Developmental and a control nursery in a 78-bed, level II/III neonatal intensive-care unit., Participants: A convenience sample of 114 premature infants and their parents., Interventions: Control group infants received the routine neonatal intensive-care unit standard of care. Experimental infants received routine care plus the addition of individualized, developmentally supportive family-centered interventions., Main Outcome Measures: Between groups, there were no statistically significant differences in demographic factors, days to medical or developmental milestones, length of stay, or direct cost/case. Repeated measures analysis of variance determined that at every point of data collection, the average number of baseline, activity, and postactivity stress cues were lower in the developmentally supportive group. Infants in the developmental group had 8% less sedatives/narcotics and 15% less vasopressors costs than the control group. There were no differences in complication rates, parental perceptions of the neonatal intensive-care unit experience, or parental satisfaction between groups., Conclusions: Preterm infants who received developmentally supportive family-centered care demonstrated fewer behavioral stress cues and comparable short-term outcomes and resource utilization than infants who received routine care.

The hypothalamic neuropeptide hormone GnRH is the central regulator of reproductive function. GnRH stimulates the synthesis and release of the gonadotropins LH and FSH by the gonadotropes of the anterior pituitary through activation of the G-protein-coupled GnRH receptor. In this study, we investigated the role of translational control of hormone synthesis by the GnRH receptor in the novel gonadotrope cell line LbetaT2. Using immunohistochemical and RIA studies with this model, we show that acute GnRH-induced synthesis and secretion of LH are dependent upon new protein synthesis but not new mRNA synthesis. We examined the response to GnRH and found that activation of cap-dependent translation occurs within 4 h. LHbeta promoter activity was also examined, and we found no increases in LHbeta promoter activity after 6 h of GnRH stimulation. Additionally, we show that increased phosphorylation of translation initiation proteins, 4E-binding protein 1, eukaryotic initiation factor 4E, and eukaryotic initiation factor 4G, occur in a dose- and time-dependent manner in response to GnRH stimulation. Quantitative luminescent image analysis of Western blots shows that 10 nm GnRH is sufficient to cause a maximal increase in factor phosphorylation, and maximal responses occur within 30 min of stimulation. Further, we demonstrate that the MAPK kinase inhibitor, PD 98059, abolishes the GnRH-mediated stimulation of a cap-dependent translation reporter. More specifically, we demonstrate that PD 98059 abolishes the GnRH-mediated stimulation of a downstream target of the ERK pathway, MAPK-interacting kinase. Based on these findings, we conclude that acute GnRH stimulation of LbetaT2 cells increases translation initiation through ERK signaling. This may contribute to the acute increases in LHbeta subunit production.

Women Connected and the Maternal Child Clinic are two unique dyad-centered programs for providing quality care to HIV-infected women and their children. Each is a collaborative effort to maintain standard of care for these patients within a large county facility. Women Connected facilitates their inpatient treatment and care, while the Maternal Child HIV Clinic provides follow-up outpatient health and social services.