Using the Journey to Health and Immunization (JTHI) Framework to Engage Stakeholders in Identifying Behavioral and Social Drivers of Routine Immunization in Nepal.

Although the Government of Nepal has achieved high and sustained childhood vaccination coverage, reaching under-immunized and zero-dose children requires different approaches. Behavioral science offers promise in better understanding the drivers of vaccination and development of more effective programs; however, the application of behavioral science to immunization programs in Nepal is nascent. Through the Behavioral Science Immunization Network, JSI, UNICEF Nepal, and Dhulikhel Hospital-Kathmandu University School of Medical Sciences established a Behavioral Science Center to engage a diverse group of stakeholders in increasing the capacity of practitioners to use behavioral science in immunization programming. As a result of the engagement during formative research, government stakeholders requested and applied tools from behavioral science to solve different immunization challenges. Of particular value was the use of the Journey to Health and Immunization framework, which helped stakeholders identify behavioral and social drivers of zero-dose communities in Kathmandu. Our experience in Nepal demonstrates that there is strong demand for approaches and tools from behavioral science to use in relation to immunization and that this type of engagement model is effective for generating demand for and strengthening capacity to use behavioral science approaches.

Development of electrophysiological and morphological properties of human embryonic stem cell-derived GABAergic interneurons at different times after transplantation into the mouse hippocampus.

Transplantation of human embryonic stem cell (hESC)-derived neural progenitors is a potential treatment for neurological disorders, but relatively little is known about the time course for human neuron maturation after transplantation and the emergence of morphological and electrophysiological properties. To address this gap, we transplanted hESC-derived human GABAergic interneuron progenitors into the mouse hippocampus, and then characterized their electrophysiological properties and dendritic arborizations after transplantation by means of ex vivo whole-cell patch clamp recording, followed by biocytin staining, confocal imaging and neuron reconstruction software. We asked whether particular electrophysiological and morphological properties showed maturation-dependent changes after transplantation. We also investigated whether the emergence of particular electrophysiological properties were linked to increased complexity of the dendritic arbors. Human neurons were classified into five distinct neuronal types (Type I-V), ranging from immature to mature fast-spiking interneurons. Hierarchical clustering of the dendritic morphology and Sholl analyses suggested four morphologically distinct classes (Class A-D), ranging from simple/immature to highly complex. Incorporating all of our data regardless of neuronal classification, we investigated whether any electrophysiological and morphological features correlated with time post-transplantation. This analysis demonstrated that both dendritic arbors and electrophysiological properties matured after transplantation.

Pluripotent stem cell-derived interneuron progenitors mature and restore memory deficits but do not suppress seizures in the epileptic mouse brain.

GABAergic interneuron dysfunction has been implicated in temporal lobe epilepsy (TLE), autism, and schizophrenia. Inhibitory interneuron progenitors transplanted into the hippocampus of rodents with TLE provide varying degrees of seizure suppression. We investigated whether human embryonic stem cell (hESC)-derived interneuron progenitors (hESNPs) could differentiate, correct hippocampal-dependent spatial memory deficits, and suppress seizures in a pilocarpine-induced TLE mouse model. We found that transplanted ventralized hESNPs differentiated into mature GABAergic interneurons and became electrophysiologically active with mature firing patterns. Some mice developed hESNP-derived tumor-like NSC clusters. Mice with transplants showed significant improvement in the Morris water maze test, but transplants did not suppress seizures. The limited effects of the human GABAergic interneuron progenitor grafts may be due to cell type heterogeneity within the transplants.

Drosophila larvae fed palm fruit juice (PFJ) delay pupation via expression regulation of hormetic stress response genes linked to ageing and longevity.

Palm fruit juice (PFJ) containing oil palm phenolics is obtained as a by-product from oil palm (Elaeis guineensis) fruit milling. It contains shikimic acid, soluble fibre and various phenolic acids including p-hydroxybenzoic acid and three caffeoylshikimic acid isomers. PFJ has also demonstrated beneficial health properties in various biological models. Increasing concentrations of PFJ and different PFJ fractions were used to assess growth dynamics and possible anti-ageing properties in fruit flies (Drosophila melanogaster) genotype w1118. Microarray gene expression analysis was performed on whole fruit fly larvae and their fat bodies, after the larvae were fed a control Standard Brandeis Diet (SBD) with or without PFJ. Transcripts from Affymetrix GeneChips were utilised to identify the possible mechanisms involved, with genes having fold changes > |1.30| and p < 0.05 considered differentially expressed. PFJ dose-dependently delayed larval growth and pupation, but not percent eclosion from pupae. Eclosed male fruit flies fed PFJ or its fractions during the larval stage tended to have 20-40% improved survival ratings over controls when allowed to age on the control diet (SBD). Microarray analysis of whole fruit fly larvae revealed that 127 genes were up-regulated, while 67 were down-regulated by PFJ. Functional analysis revealed transport and metabolic processes were up-regulated, while development and morphogenesis processes, including the nutrient-sensing Tor gene, were down-regulated by PFJ, whereas microarray analysis of larval fat bodies found 161 genes were up-regulated, while 84 genes were down-regulated. Genes involved in defence response and determination of adult lifespan, including those encoding various heat shock proteins and the antioxidant enzyme Sod2, were up-regulated, while cell cycle and growth genes were down-regulated. Thus, PFJ supplementation lengthened the growth stages in fruit fly larvae that was reflected in extended ageing of adult flies, suggesting that larval expression of hormetic stress response genes was linked to subsequent ageing and longevity.