METHODS: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries.
RESULTS: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p < 0.05), have a unit protocol for providing TH (50% v HIC 26%, p < 0.05), use adjunctive tools, e.g., aEEG (49% v HIC 32%, p < 0.001), conduct an MRI post TH (48% v HIC 40%, p < 0.05) and less likely to use neurological examinations as a HIE severity grading tool (80% v HIC 95%, p < 0.001). The majority of respondents (91%) would support a randomized controlled trial that was sufficiently large to examine neurodevelopmental outcomes in mild HIE after TH.
CONCLUSIONS: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider "cooling" an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported.
METHOD: A case series.
RESULTS: We present a case series of juvenile myasthenia gravis in a tertiary centre in Malaysia. Two of the three cases consist of a pair of twins who presented with ptosis of bilateral eyes; the first twin presented 4 months later than the second twin. These two cases were positive for anti-acetylcholine receptor antibodies and had generalized myasthenia gravis, whereas the other case was negative for receptor antibodies and was purely ocular myasthenia gravis.
CONCLUSION: Juvenile myasthenia gravis is relatively rare in toddlers. Early diagnosis and commencement of treatment is important to slow the progression of the disease and avoiding life-threatening events.
MAIN BODY: We argue that broader consideration of lactation, incorporating evolutionary, comparative and anthropological aspects, could provide new insights into breastfeeding practices and problems, enhance research and ultimately help to develop novel approaches to improve initiation and maintenance. Our current focus on breastfeeding as a strategy to improve health outcomes must engage with the evolution of lactation as a flexible trait under selective pressure to maximise reproductive fitness. Poor understanding of the dynamic nature of breastfeeding may partly explain why some women are unwilling or unable to follow recommendations.
CONCLUSIONS: We identify three key implications for health professionals, researchers and policymakers. Firstly, breastfeeding is an adaptive process during which, as in other mammals, variability allows adaptation to ecological circumstances and reflects mothers' phenotypic variability. Since these factors vary within and between humans, the likelihood that a 'one size fits all' approach will be appropriate for all mother-infant dyads is counterintuitive; flexibility is expected. From an anthropological perspective, lactation is a period of tension between mother and offspring due to genetic 'conflicts of interest'. This may underlie common breastfeeding 'problems' including perceived milk insufficiency and problematic infant crying. Understanding this - and adopting a more flexible, individualised approach - may allow a more creative approach to solving these problems. Incorporating evolutionary concepts may enhance research investigating mother-infant signalling during breastfeeding; where possible, studies should be experimental to allow identification of causal effects and mechanisms. Finally, the importance of learned behaviour, social and cultural aspects of primate (especially human) lactation may partly explain why, in cultures where breastfeeding has lost cultural primacy, promotion starting in pregnancy may be ineffective. In such settings, educating children and young adults may be important to raise awareness and provide learning opportunities that may be essential in our species, as in other primates.
METHODS: Cells were pre-incubated with 32µM of 15dPGJ2 and stimulated with 1ng/mL of IL-1β as an in vitro model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-κB and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-α was examined, and protein expression of COX-2 and PGE2 were detected by western immunoblotting and ELISA respectively. Myometrial contractility was examined ex-vivo using a myograph.
RESULTS: 15dPGJ2 inhibited IL-1β-induced activation of NF-κB and AP-1, and expression of IL-6, IL-8, TNF-α, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1β-induced activation of NF-κB, expression of IL-6, TNF-α, and COX-2, 15dPGJ2 led to activation of AP-1, increased production of PGE2 and increased cell death in VECs and AECs.
CONCLUSION: We conclude that 15dPGJ2 has differential effects on inflammatory modulation depending on cell type and is therefore unlikely to be a useful therapeutic agent for the prevention of preterm birth.