Examining the effects of ambient temperature on pre-term birth in Central Australia

Preterm birth (born before 37 completed weeks of gestation) is one of the leading causes of death among children under 5 years of age. Several recent studies have examined the association between extreme temperature and preterm births, but there have been almost no such studies in arid Australia. In this paper, we explore the potential association between exposures to extreme temperatures during the last 3 weeks of pregnancy in a Central Australian town. An immediate effect of temperature exposure is observed with an increased relative risk of 1%–2% when the maximum temperature exceeded the 90th percentile of the summer season maximum temperature data. Delayed effects are also observed closer to 3 weeks before delivery when the relative risks tend to increase exponentially. Immediate risks to preterm birth are also observed for cold temperature exposures (0 to –6 ◦C), with an increased relative risk of up to 10%. In the future, Central Australia will face more hot days and less cold days due to climate change and hence the risks posed by extreme heat is of particular relevance to the community and health practitioners

Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome

International audienceGray platelet syndrome (GPS) is a rare recessive disorder caused by biallelic variants in NBEAL2 and characterized by bleeding symptoms, the absence of platelet alpha-granules, splenomegaly, and bone marrow (BM) fibrosis. Due to the rarity of GPS, it has been difficult to fully understand the pathogenic processes that lead to these clinical sequelae. To discern the spectrum of pathologic features, we performed a detailed clinical genotypic and phenotypic study of 47 patients with GPS and identified 32 new etiologic variants in NBEAL2. The GPS patient cohort exhibited known phenotypes, including macrothrombocytopenia, BM fibrosis, megakaryocyte emperipolesis of neutrophils, splenomegaly, and elevated serum vitamin B-12 levels. Novel clinical phenotypes were also observed, including reduced leukocyte counts and increased presence of autoimmune disease and positive autoantibodies. There were widespread differences in the transcriptome and proteome of GPS platelets, neutrophils, monocytes, and CD4 lymphocytes. Proteins less abundant in these cells were enriched for constituents of granules, supporting a role for Nbeal2 in the function of these organelles across a wide range of blood cells. Proteomic analysis of GPS plasma showed increased levels of proteins associated with inflammation and immune response. One-quarter of plasma proteins increased in GPS are known to be synthesized outside of hematopoietic cells, predominantly in the liver. In summary, our data show that, in addition to the well-described platelet defects in GPS, there are immune defects. The abnormal immune cells may be the drivers of systemic abnormalities such as autoimmune disease