RESUMEN
Studying the human placenta through in vitro cell culture methods is necessary due to limited access and amenability of human placental tissue to certain experimental methods as well as distinct anatomical and physiological differences between animal and human placentas. Selecting an in vitro culture model of the human placenta is challenging due to representation of different trophoblast cell types with distinct biological roles and limited comparative studies that define key characteristics of these models. Therefore, the aim of this research was to create a comprehensive transcriptomic comparison of common in vitro models of the human placenta compared to bulk placental tissue from the CANDLE and GAPPS cohorts (N=1083). We performed differential gene expression analysis on publicly available RNA sequencing data from 6 common in vitro models of the human placenta (HTR-8/SVneo, BeWo, JEG-3, JAR, Primary Trophoblasts, and Villous Explants) and compared to CANDLE and GAPPS bulk placental tissue or cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast cell types derived from bulk placental tissue. All in vitro placental models had a substantial number of differentially expressed genes (DEGs, FDR<0.01) compared to the CANDLE and GAPPS placentas (Average DEGs=10,873), and the individual trophoblast cell types (Average DEGs=5,346), indicating that there are vast differences in gene expression compared to bulk and cell-type specific human placental tissue. Hierarchical clustering identified 53 gene clusters with distinct expression profiles across placental models, with 22 clusters enriched for specific KEGG pathways, 7 clusters enriched for high-expression placental genes, and 7 clusters enriched for absorption, distribution, metabolism, and excretion genes. In vitro placental models were classified by fetal sex based on expression of Y-chromosome genes that identified HTR-8/SVneo cells as being of female origin, while JEG-3, JAR, and BeWo cells are of male origin. Overall, none of the models were a close approximation of the transcriptome of bulk human placental tissue, highlighting the challenges with model selection. To enable researchers to select appropriate models, we have compiled data on differential gene expression, clustering, and fetal sex into an accessible web application: "Comparative Transcriptomic Placental Model Atlas (CTPMA)" which can be utilized by researchers to make informed decisions about their selection of in vitro placental models.
RESUMEN
Background: Every PreemieSCALE developed and piloted the Family-Led Care model, an innovative, locally developed model of care for preterm and low birth weight babies receiving kangaroo mother care. Aim: The aim of this study was to describe healthcare workers' experience using Family-Led Care. Setting: This study was conducted in five health facilities and their catchment areas in Balaka district, Malawi. Methods: The mixed-methods design, with two data collection periods, included record reviews, observations and questionnaires for facility staff and qualitative interviews with health workers of these facilities and their catchment areas. The total convenience sample comprised 123 health professionals, support staff and non-professional community health workers. Results: Facility-based staff generally had positive perceptions of Family-Led Care (83%). Knowledge and application-of-knowledge scores were 69% and 52%, respectively. A major change between the first and the second data periods was improvement in client record-keeping. Documentation of newborn vital signs increased from 62% to 92%. Themes emerging from the qualitative interview analysis were the following: benefits of Family-Led Care; activities supporting the implementation of Family-Led Care; own care practices; and families' reaction to and experience of Family-Led Care. Conclusion: This article reports improved quality of care through better documentation and better follow-up of preterm and low birth weight babies receiving kangaroo mother care according to the Family-Led Care model. Overall, health workers were positive about their involvement, and they reported positive reactions from families. Lessons learned have been incorporated into a universal Family-Led Care package that is available for adaptation by other countries