RECENT FINDINGS: p53 plays a major physiological role in embryonic development, by controlling cell proliferation, differentiation and responses to cellular stress. Tumor suppressor function of p53 is commonly lost in adult cancers through genetic alterations. However, both somatic and germline p53 mutations are rare in childhood blastomas, suggesting that in these cancers, p53 may be inactivated through other mechanisms than mutation. In this review, we summarize current knowledge about p53 pathway inactivation in childhood blastomas (specifically neuroblastoma, retinoblastoma and Wilms' tumor) through various upstream mechanisms. Laboratory evidence and clinical trials of targeted therapies specific to exploiting p53 upstream regulators are discussed.
SUMMARY: Despite the low rate of inherent TP53 mutations, p53 pathway inactivation is a common denominator in childhood blastomas. Exploiting p53 and its regulators is likely to translate into more effective targeted therapies with minimal late effects for children. (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/COON/A23).
METHODS: Currently available indicators from both household and facility surveys were collated through publicly available global databases and respective survey instruments. We then developed a suite of potential indicators and associated data points for the 45 WHO Essential Interventions spanning preconception to newborn care. Four types of performance indicators were identified (where applicable): process (i.e. coverage) and outcome (i.e. impact) indicators for both screening and treatment/prevention. Indicators were evaluated by an international expert panel against the eRegistries indicator evaluation criteria and further refined based on feedback by the eRegistries technical team.
RESULTS: Of the 45 WHO Essential Interventions, only 16 were addressed in any of the household survey data available. A set of 216 potential indicators was developed. These indicators were generally evaluated favourably by the panel, but difficulties in data ascertainment, including for outcome measures of cause-specific morbidity and mortality, were frequently reported as barriers to the feasibility of indicators. Indicators were refined based on feedback, culminating in the final list of 193 total unique indicators: 93 for preconception and antenatal care; 53 for childbirth and postpartum care; and 47 for newborn and small and ill baby care.
CONCLUSIONS: Large gaps exist in the availability of information currently collected to support the implementation of the WHO Essential Interventions. The development of this suite of indicators can be used to support the implementation of eRegistries and other data platforms, to ensure that data are utilised to support evidence-based practice, facilitate measurement and accountability, and improve maternal and child health outcomes.
METHODS: A group of 33 healthy children, aged from 5 years 9 months-12 years 4 months (mean ± SD = 8.83 ± 1.92 years), was recruited. Their otolith saccular function was assessed using 750 Hz tone burst for cVEMPs (with ER3A insert phone), while their utricular function was assessed using Brüel & Kjaer Mini-shaker Type 4810 (Naerum, Denmark) for oVEMPs.
RESULTS: For cVEMPs, the mean value of P13 latency, N23 latency, P13-N23 interamplitude and asymmetry ratio were 12.62 ± 1.38 ms, 19.85 ± 1.95 ms, 92.47 ± 50.35 μV and 14.03 ± 9.75%, respectively. For oVEMPs, the mean value of N10 latency, P15 latency, N10-P15 interamplitude and asymmetry ratio were 9.23 ± 1.07 ms, 14.41 ± 1.04 ms, 10.32 ± 5.65 μV and 15.84 ± 11.49%, respectively. Two-way ANOVA analysis found that ear laterality and gender had no significant effect on all cVEMPs and oVEMPs parameters. No significant correlation was found between age and all VEMPs parameters.
CONCLUSIONS: The normative data for cVEMPs and oVEMPs obtained in this study can be used as a guide by health professionals to assess saccular and utricular functions among children age from 5 to 12 years of age.