Postnatal care and acceptability of emollient therapy in very low birthweight infants in Harare, Zimbabwe: a qualitative analysis.

BACKGROUND: Preterm birth (birth before 37 completed weeks of pregnancy) is the leading cause of neonatal and child under-five mortality globally, both of which are highest regionally in sub-Saharan Africa. The skin barrier plays a critical role in neonatal health and increasing evidence supports the use of topical emollient therapy to promote postnatal growth and reduce hospital-acquired infections in preterm infants. The World Health Organization (WHO) currently recommends emollient therapy in preterm or low birthweight infants globally but calls for further research on impacts of emollient use, especially in Africa. Little is known about postnatal skincare practices and the tradition of oil massage across sub-Saharan Africa. Further documentation is necessary to understand the context for future emollient intervention trials. METHODS: 61 semi-structured interviews with mothers who just delivered preterm or term infants and 4 focus group discussions (32 participants) with physician and nurse providers of newborn care were conducted at Sally Mugabe Central Hospital (SMCH), in Harare, Zimbabwe. SMCH is the principal public-sector tertiary care hospital for newborn infants in the northern part of the country. Mothers and healthcare professionals were questioned about newborn care at the hospital, current neonatal skincare and bathing practices, and the community's receptivity to a future emollient therapy clinical trial. RESULTS: Postnatal skincare is centrally important to Zimbabwean communities and petroleum jelly application is nearly universal. The use of cooking oil and other natural oils on infants is also part of traditional customs. The primary needs and desires of mothers who have just given birth to preterm infants are having greater agency in their children's care and financial support in purchasing prescribed medications while at the hospital. Community receptivity to emollient therapy as a cost-effective treatment is high, particularly if mothers are trained to assist with the intervention. CONCLUSION: Emollient therapy will likely be well-received by communities in and around Harare because of its accordance with current skincare practices and perceptions; however, cultural norms and the experiences of new mothers who have given birth at a facility highlight challenges and considerations for future clinical trial execution. TRIAL REGISTRATION: Clinicaltrials.gov NCT05461404.

Glioma synapses recruit mechanisms of adaptive plasticity.

The role of the nervous system in the regulation of cancer is increasingly appreciated. In gliomas, neuronal activity drives tumour progression through paracrine signalling factors such as neuroligin-3 and brain-derived neurotrophic factor1-3 (BDNF), and also through electrophysiologically functional neuron-to-glioma synapses mediated by AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors4,5. The consequent glioma cell membrane depolarization drives tumour proliferation4,6. In the healthy brain, activity-regulated secretion of BDNF promotes adaptive plasticity of synaptic connectivity7,8 and strength9-15. Here we show that malignant synapses exhibit similar plasticity regulated by BDNF. Signalling through the receptor tropomyosin-related kinase B16 (TrkB) to CAMKII, BDNF promotes AMPA receptor trafficking to the glioma cell membrane, resulting in increased amplitude of glutamate-evoked currents in the malignant cells. Linking plasticity of glioma synaptic strength to tumour growth, graded optogenetic control of glioma membrane potential demonstrates that greater depolarizing current amplitude promotes increased glioma proliferation. This potentiation of malignant synaptic strength shares mechanistic features with synaptic plasticity17-22 that contributes to memory and learning in the healthy brain23-26. BDNF-TrkB signalling also regulates the number of neuron-to-glioma synapses. Abrogation of activity-regulated BDNF secretion from the brain microenvironment or loss of glioma TrkB expression robustly inhibits tumour progression. Blocking TrkB genetically or pharmacologically abrogates these effects of BDNF on glioma synapses and substantially prolongs survival in xenograft models of paediatric glioblastoma and diffuse intrinsic pontine glioma. Together, these findings indicate that BDNF-TrkB signalling promotes malignant synaptic plasticity and augments tumour progression.