ErbB4 is unusual among receptor tyrosine kinases because some isoforms can be efficiently cleaved at the plasma membrane to release a soluble intracellular domain. The cleavage product has high ...kinase activity and homes to the nucleus. A screen for proteins that associate with the ErbB4 intracellular domain identified candidate interactors including ITCH, WWP2, Nucleolin, and Krab-associated protein 1 (Kap1). Kap1 binds to multiple isoforms of ErbB4 but does not require ErbB4 kinase activity for binding, nor is it an ErbB4 substrate. Kap1 reduces ERBB4 transcription and either directly or indirectly modulates the expression of genes that are themselves regulated by ErbB4. Upregulation of ErbB4 and suppression of MDM2 jointly enhance and accelerate the accumulation of p21(CIP1) in response to DNA damage. Overall, these findings further substantiate the role of ErbB4 in conjoint regulation of growth factor signaling and DNA damage responses.
IntroductionMore than 33 000 healthcare-associated infections occur in neonatal intensive care units (NICUs) each year in the USA. Parents, rather than healthcare workers, may be a reservoir from ...which neonates acquire Staphylococcus aureus (S. aureus) colonisation in the NICU. This study looks to measure the effect of treating parents with short course intranasal mupirocin and topical chlorhexidine antisepsis on acquisition of S. aureus colonisation and infection in neonates.Methods and analysisThe TREAT PARENTS trial (Treating Parents to Reduce Neonatal Transmission of S. aureus) is a multicentre randomised, masked, placebo-controlled trial. Shortly after a neonate is admitted to the NICU, parents will be tested for S. aureus colonisation. If either parent screens positive for S. aureus, then both parents as a pair will be enrolled and randomised to one of the two possible masked treatment arms. Arm 1 will include assignment to intranasal 2% mupirocin plus topical antisepsis with chlorhexidine gluconate impregnated cloths for 5 days. Arm 2 will include assignment to placebo ointment and placebo cloths for skin antisepsis for 5 days. The primary outcome will be neonatal acquisition of an S. aureus strain that is concordant to the parental baseline S. aureus strain as determined by periodic surveillance cultures or a culture collected during routine clinical care that grows S. aureus. Secondary outcomes will include neonatal acquisition of S. aureus, neonatal S. aureus infection, eradication of S. aureus colonisation in parents, natural history of S. aureus colonisation in parents receiving placebo, adverse reactions to treatment, feasibility of intervention, and attitudes and behaviour in consented parents. Four hundred neonate-parent pairs will be enrolled.Ethics and disseminationThe study was approved by Johns Hopkins University IRB in June 2014 (IRB number 00092982). Protocol V.7 was approved in November 2014. Findings will be published in peer-reviewed journals.Trial registration numberNCT02223520.
The overexpression of the colony-stimulating factor-1(CSF-1) by epithelial ovarian cancer cells enhances invasiveness and metastatic properties, contributing to the poor prognosis of the patients. It ...has been suggested that CSF-1 3' untranslated region containing AU-rich elements (ARE) could regulate CSF-1 posttranscriptional expression and be responsible for its aberrant abundance in such cancer cells. In this study, normal (NOSE.1) and malignant (Hey) ovarian epithelial cells were used to examine CSF-1 expression and regulation. CSF-1 overexpression in Hey cells was found to associate with increased invasiveness, motility, urokinase activity, and virulence of tumorigenicity, compared with NOSE.1 cells, which expressed little CSF-1. CSF-1 ARE was further found to serve as an mRNA decay element that correlates with down-regulation of protein translation. Moreover, such down-regulation was found more prominent in NOSE.1 than in Hey cells, suggesting differences in posttranscriptional regulation. As a variety of trans-acting factors AU-binding protein (AUBP) are known to modulate messenger stability through binding to such elements, we examined the protein content of both cell lines for their ability to bind the CSF-1 ARE. Our results strongly suggested the abundance of such AUBP activity in Hey cells. We isolated a 37-kDa AUBP, which was identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). To summarize, our study identified GAPDH as an AUBP abundant in Hey cells, where it binds to CSF-1 ARE that imparts mRNA decay. These data suggest that GAPDH binding to CSF-1 ARE sequence prevents CSF-1 mRNA decay and subsequent down-regulation of CSF-1 protein translation, leading to CSF-1 overexpression and increased metastatic properties seen in ovarian cancer.
The research sought to evaluate whether providing personalized information services by libraries can improve satisfaction with information services for specific types of patients.
Adult breast cancer ...(BrCa) clinic patients and mothers of inpatient neonatal intensive care unit (NICU) patients were randomized to receive routine information services (control) or an IRx intervention.
The BrCa trial randomized 211 patients and the NICU trial, 88 mothers. The BrCa trial showed no statistically significant differences in satisfaction ratings between the treatment and control groups. The IRx group in the NICU trial reported higher satisfaction than the control group regarding information received about diagnosis, treatments, respiratory tradeoffs, and medication tradeoffs. BrCa patients posed questions to librarians more frequently than did NICU mothers, and a higher percentage reported using the website. Questions asked of the librarians by BrCa patients were predominantly clinical and focused on the areas of treatment and side effects.
Study results provide some evidence to support further efforts to both implement information prescription projects in selected settings and to conduct additional research on the costs and benefits of services.
Limited data are available about the outcomes of COVID-19 during pregnancy and risk of vertical transmission in exposed neonates. We reviewed studies published February 1, 2020, through August 15, ...2020, on outcomes in pregnant women with COVID-19 and neonates with perinatal exposure. Among pregnant women with COVID-19, 181 (11%) required ICU admission and 123 (8%) required mechanical ventilation. There were 22 maternal deaths. Most infections occurred in the third trimester. Among women who delivered, 28% had a preterm birth and 57% had a Caesarean section. Sixty-one (4%) of 1222 neonates with reported testing had at least one positive SARS-CoV-2 polymerase chain reaction (PCR) test. The most common symptom among neonates was respiratory distress (n=126, 21%). There were 14 neonatal deaths, one of which occurred in a neonate with positive testing. Further study of COVID-19 in pregnant women and neonates, including standardized reporting of outcomes, testing, and treatment protocols, are essential to optimize maternal and neonatal care.
In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required <10 days of ...intubation. However, in infants requiring intubation for ≥10 days, prolonged PDA exposure (≥11 days) was associated with an increased risk of moderate/severe BPD.
To assess chlorhexidine absorption and skin tolerability in premature infants, following skin antisepsis with 2% aqueous chlorhexidine gluconate (CHG) prior to peripherally inserted central catheter ...(PICC) placement.
Neonates less than 32 weeks gestation had skin cleansed with CHG prior to PICC placement. CHG concentrations were measured on serial blood samples. Skin integrity was evaluated for 2 weeks after CHG exposure.
Twenty infants were enrolled; median gestational age was 28 2/7 weeks (range 24 3/7 to 31 4/7). Ten infants had detectable serum chlorhexidine concentrations (range 1.6 to 206 ng ml(-1)). Seven of these infants had their highest serum concentration 2 to 3 days following exposure. No CHG-related skin irritation occurred in any infant.
CHG was detected in the blood of preterm infants receiving CHG skin antisepsis for PICC insertion. Highest serum concentrations occurred 2 to 3 days after exposure. Further investigation is needed to determine the clinical relevance of CHG absorption in preterm infants.
Cardiopulmonary injury is common in neonatal encephalopathy, but the link with cerebrovascular dysfunction is unknown. We hypothesized that alterations of cerebral autoregulation are associated with ...cardiopulmonary injury in neonates treated with therapeutic hypothermia (TH) for neonatal encephalopathy.
The cerebral hemoglobin volume index (HVx) from near-infrared spectroscopy was used to identify the mean arterial blood pressure (MAP) with optimal autoregulatory vasoreactivity (MAP
). We measured associations between MAP relative to MAP
and indicators of cardiopulmonary injury (duration of mechanical respiratory support and administration of inhaled nitric oxide (iNO), milrinone, or steroids).
We identified associations between cerebrovascular autoregulation and cardiopulmonary injury that were often sex-specific. Greater MAP deviation above MAP
was associated with shorter duration of intubation in boys but longer ventilatory support in girls. Greater MAP deviation below MAP
related to longer intensive care stay in boys. Milrinone was associated with greater MAP deviation below MAP
in girls.
MAP deviation from MAP
may relate to cardiopulmonary injury after neonatal encephalopathy, and sex may modulate this relationship. Whereas MAP above MAP
may protect the brain and lungs in boys, it may be related to cardiopulmonary injury in girls. Future studies are needed to characterize the role of sex in these associations.
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