Building a Global Evidence Base to Guide Policy and Implementation for Group Antenatal Care in Low‐ and Middle‐Income Countries: Key Principles and Research Framework Recommendations from the Global Group Antenatal Care Collaborative

Evidence from high‐income countries suggests that group antenatal care, an alternative service delivery model, may be an effective strategy for improving both the provision and experience of care. Until recently, published research about group antenatal care did not represent findings from low‐ and middle‐income countries, which have health priorities, system challenges, and opportunities that are different than those in high‐income countries. Because high‐quality evidence is limited, the World Health Organization recommends group antenatal care be implemented only in the context of rigorous research. In 2016 the Global Group Antenatal Care Collaborative was formed as a platform for group antenatal care researchers working in low‐ and middle‐income countries to share experiences and shape future research to accelerate development of a robust global evidence base reflecting implementation and outcomes specific to low‐ and middle‐income countries. This article presents a brief history of the Collaborative’s work to date, proposes a common definition and key principles for group antenatal care, and recommends an evaluation and reporting framework for group antenatal care research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163383/2/jmwh13143.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163383/1/jmwh13143_am.pd

A multi-site, non-randomized study of the feasibility and acceptability of a family-led postnatal care model in the Ada District, Ethiopia

Postnatal care is a critical intervention to reduce newborn and maternal mortality in high-mortality settings. However, it is underutilized in many countries. Family-led postnatal care (FPNC) is an innovative postnatal care service delivery model that leverages self-care principles to address key barriers identified in the Ethiopian context, including women’s preference to stay home in the first week after delivery and receive support from trusted family members. Utilizing an improved discharge process, coupled with user-friendly monitoring devices made available as a home care kit kept with preferred community custodians, this self-care model for postnatal care will be evaluated as a potential solution to very low coverage of postnatal care in the first week of life. METHODS: The study will use mixed sequential methods: quantitative pre-intervention and post-intervention survey and phenomenological qualitative study. Four health centers in Ada Districtof Oromia, Ethiopia will be purposively selected. A pre-intervention survey will measure coverage and content of postnatal checks and care-seeking behavior. Health centers will then implement family led postnatal care. Once FPNC is initiated, post-intervention quantitative data will be collected. Approximately 218 postnatal women are to be included in the quantitative survey.  Qualitative interviews with approximately 20 mothers, 20 partners, 20 families, eight health managers, 12 postnatal discharge counselors, 20 health extension workers, and eight home care kit custodians will be conducted. A quantitative measurement of sustainability six months after the endline will also be assessed. CONCLUSIONS: Optimally, the study will contribute evidence to inform decision makers locally and globally on whether FPNC is a feasible and acceptable service delivery model for postnatal care, and whether it improves women’s empowerment and/or increases men’s support and connection to women and newborns in the early postnatal period

Checkpoint-Dependent and -Independent Roles of Swi3 in Replication Fork Recovery and Sister Chromatid Cohesion in Fission Yeast

Multiple genome maintenance processes are coordinated at the replication fork to preserve genomic integrity. How eukaryotic cells accomplish such a coordination is unknown. Swi1 and Swi3 form the replication fork protection complex and are involved in various processes including stabilization of replication forks, activation of the Cds1 checkpoint kinase and establishment of sister chromatid cohesion in fission yeast. However, the mechanisms by which the Swi1–Swi3 complex achieves and coordinates these tasks are not well understood. Here, we describe the identification of separation-of-function mutants of Swi3, aimed at dissecting the molecular pathways that require Swi1–Swi3. Unlike swi3 deletion mutants, the separation-of-function mutants were not sensitive to agents that stall replication forks. However, they were highly sensitive to camptothecin that induces replication fork breakage. In addition, these mutants were defective in replication fork regeneration and sister chromatid cohesion. Interestingly, unlike swi3-deleted cell, the separation-of-functions mutants were proficient in the activation of the replication checkpoint, but their fork regeneration defects were more severe than those of checkpoint mutants including cds1Δ, chk1Δ and rad3Δ. These results suggest that, while Swi3 mediates full activation of the replication checkpoint in response to stalled replication forks, Swi3 activates a checkpoint-independent pathway to facilitate recovery of collapsed replication forks and the establishment of sister chromatid cohesion. Thus, our separation-of-function alleles provide new insight into understanding the multiple roles of Swi1-Swi3 in fork protection during DNA replication, and into understanding how replication forks are maintained in response to different genotoxic agents

Maternal and neonatal data collection systems in low- and middle-income countries: Scoping review protocol

Background: Pregnant women and neonates represent one of the most vulnerable groups, especially in low- and middle-income countries (LMICs). A recent analysis reported that most vaccine pharmacovigilance systems in LMICs consist of spontaneous (passive) adverse event reporting. Thus, LMICs need effective active surveillance approaches, such as pregnancy registries. We intend to identify currently active maternal and neonatal data collection systems in LMICs, with the potential to inform active safety electronic surveillance for novel vaccines using standardized definitions. Methods: A scoping review will be conducted based on established methodology. Multiple databases of indexed and grey literature will be searched with a specific focus on existing electronic and paper-electronic systems in LMICs that collect continuous, prospective, and individual-level data from antenatal care, delivery, neonatal care (up to 28 days), and postpartum (up to 42 days) at the facility and community level, at the national and district level, and at large hospitals. Also, experts will be contacted to identify unpublished information on relevant data collection systems. General and specific descriptions of Health Information Systems (HIS) extracted from the different sources will be combined and duplicated HIS will be removed, producing a list of unique statements. We will present a final list of Maternal, Newborn, and Child Health systems considered flexible enough to be updated with necessary improvements to detect, assess and respond to safety concerns during the introduction of vaccines and other maternal health interventions. Selected experts will participate in an in-person consultation meeting to select up to three systems to be further explored in situ. Results and knowledge gaps will be synthesized after expert consultation.Fil: Berrueta, Mabel. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Bardach, Ariel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Xiong, Xu. University of Tulane; Estados UnidosFil: Stergachis, Andy. University of Washington; Estados UnidosFil: Zaraa, Sabra. University of Washington; Estados UnidosFil: Buekens, Pierre. University of Tulane; Estados UnidosFil: Absalon, Judith. No especifíca;Fil: Anderson, Steve. No especifíca;Fil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Madhi, Shabir A.. No especifíca;Fil: McClure, Elizabeth. No especifíca;Fil: Munoz, Flor M.. No especifíca;Fil: Mwamwitwa, Kissa W.. No especifíca;Fil: Nakimuli, Annettee. No especifíca;Fil: Clark Nelson, Jennifer. No especifíca;Fil: Noguchi, Lisa. No especifíca;Fil: Panagiotakopoulos, Lakshmi. No especifíca;Fil: Sevene, Esperanca. No especifíca;Fil: Zuber, Patrick. No especifíca;Fil: Belizan, Maria. No especifíca;Fil: Bergel, Eduardo. No especifíca;Fil: Rodriguez Cairoli, Federico. No especifíca;Fil: Castellanos, Fabricio. No especifíca;Fil: Ciganda, Alvaro. No especifíca;Fil: Comande, Daniel. No especifíca;Fil: Pingray, Veronica. No especifíca

Host Galaxy Properties of the Swift BAT Ultra Hard X-ray Selected AGN

We have assembled the largest sample of ultra hard X-ray selected (14-195 keV) AGN with host galaxy optical data to date, with 185 nearby (z<0.05), moderate luminosity AGN from the Swift BAT sample. The BAT AGN host galaxies have intermediate optical colors (u-r and g-r) that are bluer than a comparison sample of inactive galaxies and optically selected AGN from the Sloan Digital Sky Survey (SDSS) which are chosen to have the same stellar mass. Based on morphological classifications from the RC3 and the Galaxy Zoo, the bluer colors of BAT AGN are mainly due to a higher fraction of mergers and massive spirals than in the comparison samples. BAT AGN in massive galaxies (log M_*>10.5) have a 5 to 10 times higher rate of spiral morphologies than in SDSS AGN or inactive galaxies. We also see enhanced far-IR emission in BAT AGN suggestive of higher levels of star formation compared to the comparison samples. BAT AGN are preferentially found in the most massive host galaxies with high concentration indexes indicative of large bulge-to-disk ratios and large supermassive black holes. The narrow-line BAT AGN have similar intrinsic luminosities as the SDSS NL Seyferts based on measurements of [O III]. There is also a correlation between the stellar mass and X-ray emission. The BAT AGN in mergers have bluer colors and greater ultra hard X-ray emission compared to the BAT sample as whole. In agreement with the Unified Model of AGN, and the relatively unbiased nature of the BAT sources, the host galaxy colors and morphologies are independent of measures of obscuration such as X-ray column density or Seyfert type. The high fraction of massive spiral galaxies and galaxy mergers in BAT AGN suggest that host galaxy morphology is related to the activation and fueling of local AGN.Comment: 30 pages, 30 figures, accepted for publication in Ap

Where are the pregnant and breastfeeding women in new pre-exposure prophylaxis trials? The imperative to overcome the evidence gap

Pregnant and breastfeeding populations are at substantial risk of acquiring HIV in some settings, yet are underrepresented in clinical trials of new pre-exposure prophylaxis (PrEP) agents. Several PrEP formulations are in development (eg, vaginal rings, long-acting injectables, and other modalities). Pregnant and breastfeeding populations are typically excluded from initial clinical trials. We identified 14 PrEP trials of novel agents in non-pregnant or non-breastfeeding populations, and six phase 1–3 trials and open label extensions among pregnant and breastfeeding populations, that are currently ongoing or complete. A framework shift is needed to consider the ethical costs of excluding pregnant and breastfeeding populations at risk for HIV in PrEP clinical trials and promote inclusion to maximise the benefits from PrEP tools in the pipeline. Research on new PrEP agents should include pregnant and breastfeeding populations to avoid delays in reaching those who could benefit from PrEP after efficacy is established.https://www.thelancet.com/journals/lanhiv/homehj2023Paediatrics and Child Healt

Interplay between HIV-1 infection and host microRNAs

Using microRNA array analyses of in vitro HIV-1-infected CD4+ cells, we find that several host microRNAs are significantly up- or downregulated around the time HIV-1 infection peaks in vitro. While microRNA-223 levels were significantly enriched in HIV-1-infected CD4+CD8− PBMCs, microRNA-29a/b, microRNA-155 and microRNA-21 levels were significantly reduced. Based on the potential for microRNA binding sites in a conserved sequence of the Nef-3′-LTR, several host microRNAs potentially could affect HIV-1 gene expression. Among those microRNAs, the microRNA-29 family has seed complementarity in the HIV-1 3′-UTR, but the potential suppressive effect of microRNA-29 on HIV-1 is severely blocked by the secondary structure of the target region. Our data support a possible regulatory circuit at the peak of HIV-1 replication which involves downregulation of microRNA-29, expression of Nef, the apoptosis of host CD4 cells and upregulation of microRNA-223

Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children

Candidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between children of European and African ancestry.Using a custom-designed Illumina SNP array, we genotyped 1,485 children within the Greater Cincinnati Pediatric Clinic Repository and Cincinnati Genomic Control Cohort for 259 SNPs in 28 genes and evaluated their associations with asthma. We identified 14 SNPs located in 6 genes that were significantly associated (p-values <0.05) with childhood asthma in African Americans. Among Caucasians, 13 SNPs in 5 genes were associated with childhood asthma. Two SNPs in IL4 were associated with asthma in both races (p-values <0.05). Gene-gene interaction studies identified race specific sets of genes that best discriminate between asthmatic children and non-allergic controls.We identified IL4 as having a role in asthma susceptibility in both African American and Caucasian children. However, while IL4 SNPs were associated with asthma in asthmatic children with European and African ancestry, the relative contributions of the most replicated asthma-associated SNPs varied by ancestry. These data provides valuable insights into the pathways that may predispose to asthma in individuals with European vs. African ancestry

Galvanizing collective action to accelerate reductions in maternal and newborn mortality and prevention of stillbirths

Every day, there are an estimated 810 maternal and 7,000 newborn deaths, and more than 5,000 stillbirths, most of which are preventable.1-3 While progress has been made in reducing maternal and neonatal morbidity and mortality and preventing stillbirths worldwide, inequities and gaps in quality of care persist4 and are disproportionately most dire in countries affected by conflict.5 In 2020, the coronavirus disease (COVID19) pandemic and response exposed multiple system vulnerabilities, exacerbated inequities to accessing care, and caused widespread disruption in reproductive, maternal, newborn, and child health services.6,7 Emerging evidence and modeling estimates of the indirect effects of the COVID-19 pandemic on maternal and newborn mortality in low- and middle-income countries (LMICs) reflect a sobering picture of what could lay ahead, with additional deaths estimated to be in the tens of thousands for mothers and hundreds of thousands for stillbirths and children aged under 5 years.3, 8-10 A dedicated, focused effort must be made to ensure maternal and newborn health (MNH) and prevention of stillbirths remain a priority

Altered Responses to Homeostatic Cytokines in Patients with Idiopathic CD4 Lymphocytopenia

Idiopathic CD4 lymphocytopenia (ICL) is a rare immune deficiency characterized by a protracted CD4+ T cell loss of unknown etiology and by the occurrence of opportunistic infections similar to those seen in AIDS. We investigated whether a defect in responses to cytokines that control CD4+ T cell homeostasis could play a role in ICL. Immunophenotype and signaling responses to interleukin-7 (IL-7), IL-2, and thymic stromal lymphopoietin (TSLP) were analyzed by flow cytometry in CD4+ T cells from 15 ICL patients and 15 healthy blood donors. The induction of phospho-STAT5 after IL-7 stimulation was decreased in memory CD4+ T cells of some ICL patients, which correlated with a decreased expression of the IL-7R\uce\ub1 receptor chain (R = 0.74, p<0.005) and with lower CD4+ T cell counts (R = 0.69, p<0.005). IL-2 responses were also impaired, both in the Treg and conventional memory subsets. Decreased IL-2 responses correlated with decreased IL-7 responses (R = 0.75, p<0.005), pointing to combined defects that may significantly perturb CD4+ T cell homeostasis in a subset of ICL patients. Unexpectedly, responses to the IL-7-related cytokine TSLP were increased in ICL patients, while they remained barely detectable in healthy controls. TSLP responses correlated inversely with IL-7 responses (R = -0.41; p<0.05), suggesting a cross-regulation between the two cytokine systems. In conclusion, IL-7 and IL-2 signaling are impaired in ICL, which may account for the loss of CD4+ T cell homeostasis. Increased TSLP responses point to a compensatory homeostatic mechanism that may mitigate defects in \uce\ub3c cytokine responses. \uc2\ua9 2013 Bugault et al