Association of ambient extreme heat with pediatric morbidity: a scoping review.

Global climate change is leading to higher ambient temperatures and more frequent heatwaves. To date, impacts of ambient extreme heat on childhood morbidity have been understudied, although-given children's physiologic susceptibility, with smaller body surface-to-mass ratios, and many years of increasing temperatures ahead-there is an urgent need for better information to inform public health policies and clinical approaches. In this review, we aim to (1) identify pediatric morbidity outcomes previously associated with extreme heat, (2) to identify predisposing co-morbidities which may make children more susceptible to heat-related outcomes, and (3) to map the current body of available literature. A scoping review of the current full-text literature was conducted using the Arksey and O'Malley framework Int J Soc Res Methodol 8:19-32, (2015). Search terms for (1) pediatric population, (2) heat exposures, (3) ambient conditions, and (4) adverse outcomes were combined into a comprehensive PubMed and Medline literature search. Of the 1753 publications identified, a total of 20 relevant studies were ultimately selected based on selection criteria of relevance to US urban populations. Most identified studies supported positive associations between high extreme temperature exposures and heat-related illness, dehydration/electrolyte imbalance, general symptoms, diarrhea and digestion disorders, infectious diseases/infections, asthma/wheeze, and injury. Most studies found no association with renal disease, cardiovascular diseases, or diabetes mellitus. Results were mixed for other respiratory diseases and mental health/psychological disorders. Very few of the identified studies examined susceptibility to pre-existing conditions; Cystic Fibrosis was the only co-morbidity for which we found significant evidence. Further research is needed to understand the nuances of associations between extreme heat and specific outcomes-particularly how associations may vary by child age, sex, race/ ethnicity, community characteristics, and other pre-existing conditions.

Interactions between the WEE-1.3 kinase and the PAM-1 aminopeptidase in oocyte maturation and the early C. elegans embryo.

Puromycin-sensitive aminopeptidases are found across phyla and are known to regulate the cell-cycle and play a protective role in neurodegenerative disease. PAM-1 is a puromycin-sensitive aminopeptidase important for meiotic exit and polarity establishment in the one-cell Caenorhabditis elegans embryo. Despite conservation of this aminopeptidase, little is known about its targets during development. In order to identify novel interactors, we conducted a suppressor screen and isolated four suppressing mutations in three genes that partially rescued the maternal-effect lethality of pam-1 mutants. Suppressed strains show improved embryonic viability and polarization of the anterior-posterior axis. We identified a missense mutation in wee-1.3 in one of these suppressed strains. WEE-1.3 is an inhibitory kinase that regulates maturation promoting factor. Although the missense mutation suppressed polarity phenotypes in pam-1, it does so without restoring centrosome-cortical contact or altering the cortical actomyosin cytoskeleton. To see if PAM-1 and WEE-1.3 interact in other processes, we examined oocyte maturation. Although depletion of wee-1.3 causes sterility due to precocious oocyte maturation, this effect was lessened in pam-1 worms, suggesting that PAM-1 and WEE-1.3 interact in this process. Levels of WEE-1.3 were comparable between wild-type and pam-1 strains, suggesting that WEE-1.3 is not a direct target of the aminopeptidase. Thus, we have established an interaction between PAM-1 and WEE-1.3 in multiple developmental processes and have identified suppressors that are likely to further our understanding of the role of puromycin-sensitive aminopeptidases during development.