Interactions between endothelin receptor B and transcription factors Sox10 and Pax3 in the melanocyte lineage

Genetic interactions that underlie developmental processes such as cell differentiation and pattern formation are complex and difficult to elucidate. Neural Crest (NC) cells and their derivatives offer an optimal system in which to probe for these complex interactions as they acquire different cell fates and constitute a variety of structures. The transcription factors Sox10 and Pax3 as well as the transmembrane receptor Endothelin receptor b (Ednrb) are temporally and spatially co-expressed early in NC cells and mutations in these genes lead to similar hypopigmentation phenotypes due to a reduced number of NC-derived melanocyte precursors, the melanoblasts. The goal of this study was to establish whether Sox10 and Ednrb or Pax3 and Ednrb interact to promote normal murine melanocyte development. Crosses of Sox10 or Pax3 with Ednrb heterozygous mutants showed that the double heterozygous hypopigmentation phenotype was significantly more pronounced than phenotypes of single heterozygotes, implying that a synergistic interaction exists between Sox10 and Ednrb and Pax3 and Ednrb. This interaction was further explored by the attempt to rescue the Sox10 and Pax3 hypopigmentation phenotypes by the transgenic addition of Ednrb to melanoblasts. Pigmentation was completely restored in the Sox10 and partially restored in the Pax3 mutant mice. The comparison of the number of melanoblasts in transgenic and non-transgenic Sox10 mutant embryos showed that the transgenic rescue occurred as early as E11.5, a critical time for melanoblast population expansion. Cell survival assays indicated that the rescue was not due to an effect of the transgene on melanoblast survival. A novel phenotype arose when studying the interaction between Ednrb and Pax3. Newborns appeared normal but by 3.5 weeks of age, the affected pups were smaller than normal littermates and developed a dome-shaped head; some also developed thoracic kyphosis. Affected pups were dead by 4 weeks of age: 80% were Pax3Sp/+ and 75% were female. When compared to normal littermates, affected mice had brains with enlarged 4th ventricles and more glia while skeletal staining showed kyphosis, wider rib cages and pelvic differences. An epistatic interaction resulting from the mixing of genetic backgrounds that is exacerbated in the presence of Pax3 heterozygosity is suspected.

Low-income first time mothers: Effects on advanced practice nurse (APN) follow up telephone calls on maternal and infant health and health care charges

The United States has over 4 million births annually. Currently healthy women with non-complicated deliveries receive little to no routine postpartum support when discharged from the hospital. This is especially problematic if mothers are first time mothers, poor, have language barriers and little to no social support after giving birth. The purpose of this randomized clinical trial was to compare maternal and infant health outcomes, and health care charges between 2 groups of mothers and newborns. A control ( n = 69) group received routine posthospital discharge care. An intervention group (n = 70) received routine posthospital discharge care plus follow up telephone calls by advanced practice nurses (APNs) on days 3,7,14,21,28 and week 8. Both groups were followed for the first 8 weeks posthospital discharge following delivery to examine maternal health outcomes (perceived maternal stress, social support and perceived maternal physical health), infant health outcomes (routine medical follow up visits immunizations, weight gain), morbidity (urgent care visits, emergency room visits, rehospitalizations), health care charges (urgent care visits, emergency room visits, rehospitalizations) in both groups and charges for APN follow up in the intervention group only. Data were analyzed using descriptive statistics and two-sample t-tests. Study findings indicated that intervention group had significantly lower perceived maternal stress, significantly higher rating of perceived maternal health and higher levels of social support and by the end of the 2nd month posthospital discharge compared to control group mothers. Infants in the intervention group had: increased number of immunizations; fewer emergency room visits; and 1 infant rehospitalization compared to 3 infant rehospitalizations in the control group. The intervention groups' health care charges were significantly lower compared to the control group $14,333/$497 vs. $70,834/$1,068. These study results indicate that an intervention of APN follow up telephone calls in this sample of first time low-income culturally diverse mothers was an effective, safe, low cost, easy to apply intervention which improved mothers' and infants' health outcomes and reduced healthcare charges.

Interactions between Endothelin Receptor B and Transcription Factors Sox10 and Pax3 in the Melanocyte Lineage

Genetic interactions that underlie developmental processes such as cell differentiation and pattern formation are complex and difficult to elucidate. Neural Crest (NC) cells and their derivatives offer an optimal system in which to probe for these complex interactions as they acquire different cell fates and constitute a variety of structures. The transcription factors Sox10 and Pax3 as well as the transmembrane receptor Endothelin receptor b (Ednrb) are temporally and spatially co-expressed early in NC cells and mutations in these genes lead to similar hypopigmentation phenotypes due to a reduced number of NC-derived melanocyte precursors, the melanoblasts. The goal of this study was to establish whether Sox10 and Ednrb or Pax3 and Ednrb interact to promote normal murine melanocyte development. Crosses of Sox10 or Pax3 with Ednrb heterozygous mutants showed that the double heterozygous hypopigmentation phenotype was significantly more pronounced than phenotypes of single heterozygotes, implying that a synergistic interaction exists between Sox10 and Ednrb and Pax3 and Ednrb. This interaction was further explored by the attempt to rescue the Sox10 and Pax3 hypopigmentation phenotypes by the transgenic addition of Ednrb to melanoblasts. Pigmentation was completely restored in the Sox10 and partially restored in the Pax3 mutant mice. The comparison of the number of melanoblasts in transgenic and non-transgenic Sox10 mutant embryos showed that the transgenic rescue occurred as early as E11.5, a critical time for melanoblast population expansion. Cell survival assays indicated that the rescue was not due to an effect of the transgene on melanoblast survival. A novel phenotype arose when studying the interaction between Ednrb and Pax3. Newborns appeared normal but by 3.5 weeks of age, the affected pups were smaller than normal littermates and developed a dome-shaped head; some also developed thoracic kyphosis. Affected pups were dead by 4 weeks of age: 80% were Pax3Sp/+ and 75% were female. When compared to normal littermates, affected mice had brains with enlarged 4th ventricles and more glia while skeletal staining showed kyphosis, wider rib cages and pelvic differences. An epistatic interaction resulting from the mixing of genetic backgrounds that is exacerbated in the presence of Pax3 heterozygosity is suspected.

Increasing nurse's knowledge of neonatal pain assessment through inservice education program

Recognizing neonatal pain is a challenge for nurses working with newborns due to the complexity of the pain phenomenon. Pain is subjective, and infants lack the ability to communicate, and their pain is difficult to recognize. The purpose of this study is to determine the effectiveness of education on the NICU nurses' ability to assess neonatal pain. With a better understanding of pain theory and the effects of pain on the newborn the nurse will be better able to assess newborns with pain. Designed as a quasi-experimental one-group pretest and posttest study, the data was collected on a convenience sample of 49 registered nurses employed in the neonatal and special care nursery units at a Childrens Hospital in the Miami area. The nurses were surveyed on the assessment of neonatal pain using the General Information and Pain Sensitivity Questionnaire. After the initial survey, the nurses were inserviced on neonatal pain assessment using a one hour inservice education program. One week after the intervention the nurse was asked to complete the questionnaire again. Data analysis involved comparision of pre and post intervention findings using descriptive methods, t test, correlation coefficients, and ANOVA , where applicable. Findings revealed a significant ( p=.006) increase in nurse's knowledge of neonatal pain assessment after completing the educational inservice when comparing the pre-test and post-test results.