Background: Preterm birth and low birth weight (LBW) affect one in ten and one in seven livebirths, respectively, primarily in low-income and middle-income countries (LMIC) and are major predictors of poor child health outcomes. However, both have been recalcitrant to public health intervention. The maternal intestinal microbiome may undergo substantial changes during pregnancy and may influence fetal and neonatal health in LMIC populations. Methods: Within a subgroup of 207 mothers and infants enrolled in the SHINE trial in rural Zimbabwe, we performed shotgun metagenomics on 351 fecal specimens provided during pregnancy and at 1-month postpartum to investigate the relationship between the pregnancy gut microbiome and infant gestational age, birth weight, 1-month length-, and weight-for-age z-scores using extreme gradient boosting machines. Findings: Pregnancy gut microbiome taxa and metabolic functions predicted birth weight and WAZ at 1 month more accurately than gestational age and LAZ. Blastoscystis sp, Brachyspira sp and Treponeme carriage were high compared to Western populations. Resistant starch-degraders were important predictors of birth outcomes. Microbiome capacity for environmental sensing, vitamin B metabolism, and signalling predicted increased infant birth weight and neonatal growth; while functions involved in biofilm formation in response to nutrient starvation predicted reduced birth weight and growth. Interpretation: The pregnancy gut microbiome in rural Zimbabwe is characterized by resistant starchdegraders and may be an important metabolic target to improve birth weight. Funding: Bill and Melinda Gates Foundation,
Stunting affects one-in-five children globally and is associated with greater infectious morbidity, mortality and neurodevelopmental deficits. Recent evidence suggests that the early-life gut microbiome affects child growth through immune, metabolic and endocrine pathways. Using whole metagenomic sequencing, we map the assembly of the gut microbiome in 335 children from rural Zimbabwe from 1–18 months of age who were enrolled in the Sanitation, Hygiene, Infant Nutrition Efficacy Trial (SHINE; NCT01824940), a randomized trial of improved water, sanitation and hygiene (WASH) and infant and young child feeding (IYCF). Here, we show that the early-life gut microbiome undergoes programmed assembly that is unresponsive to the randomized interventions intended to improve linear growth. However, maternal HIV infection is associated with over-diversification and over-maturity of the early-life gut microbiome in their uninfected children, in addition to reduced abundance of Bifidobacterium species. Using machine learning models (XGBoost), we show that taxonomic microbiome features are poorly predictive of child growth, however functional metagenomic features, particularly B-vitamin and nucleotide biosynthesis pathways, moderately predict both attained linear and ponderal growth and growth velocity. New approaches targeting the gut microbiome in early childhood may complement efforts to combat child undernutrition.
Background Oral rotavirus vaccine (RVV) immunogenicity is considerably lower in low- versus high-income populations; however, the mechanisms underlying this remain unclear. Previous evidence suggests that the gut microbiota may contribute to differences in oral vaccine efficacy. Methods We performed whole metagenome shotgun sequencing on stool samples and measured anti-rotavirus immunoglobulin A in plasma samples from a subset of infants enrolled in a cluster randomized 2 × 2 factorial trial of improved water, sanitation and hygiene and infant feeding in rural Zimbabwe (SHINE trial: NCT01824940). We examined taxonomic microbiome composition and functional metagenome features using random forest models, differential abundance testing and regression analyses to explored associations with RVV immunogenicity. Results Among 158 infants with stool samples and anti-rotavirus IgA titres, 34 were RVV seroconverters. The median age at stool collection was 43 days (IQR: 35–68), corresponding to a median of 4 days before the first RVV dose. The infant microbiome was dominated by Bifidobacterium longum . The gut microbiome differed significantly between early (≤42 days) and later samples (>42 days) however, we observed no meaningful differences in alpha diversity, beta diversity, species composition or functional metagenomic features by RVV seroconversion status. Bacteroides thetaiotaomicron was the only species associated with anti-rotavirus IgA titre. Random forest models poorly classified seroconversion status by both composition and functional microbiome variables. Conclusions RVV immunogenicity is low in this rural Zimbabwean setting, however it was not associated with the composition or function of the early-life gut microbiome in this study. Further research is warranted to examine the mechanisms of poor oral RVV efficacy in low-income countries.
BACKGROUND Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non‐Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. STUDY DESIGN AND METHODS The Stem Cell Club is a non‐profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (http://www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. RESULTS To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor‐database. Of the recruited registrants, 58.3% were male; 60.3% of males self‐reported as non‐Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. CONCLUSION The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor‐database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.
Background and Objectives: Communities of practice (CoPs) represent effective models to achieve quality outcomes in health care. We report the development and evaluation of a CoP to improve stem cell donor recruitment in Canada. Materials and Methods:In September 2017, we invited national stakeholders in stem cell donor recruitment to participate in a Facebook group and regular e-meetings. E-meetings involved speakers and roundtable discussion on topics related to donor recruitment. The Facebook group facilitated sharing of resources. We evaluated stakeholder perspective of the CoP and the impact on recruitment outcomes.Results: As of December 2020, the CoP included 382 members who published 243 posts to the Facebook group about patient/donor stories (40%), resources (27%), updates/questions (21%) and recruitment outcomes (12%). In January 2020, we surveyed 44 CoP participants; the majority felt that the Facebook group (86%) and e-meetings (59%) supported the community, and that the CoP fostered collaboration (82%), improved their donor recruitment knowledge (75%) and practice (77%) and improved their ability to recruit needed donors (64%). The launch of the CoP
Aedes japonicus japonicus (Theobald) is a relatively recent immigrant to the Pacific Northwest, having been collected in Washington State in 2001 and in British Columbia (BC) since 2014. We applied a molecular barcoding approach to determine the phylogenetic relationship of Ae. j. japonicus populations in BC with those from around the world. We sequenced a 617 base‐pair segment of the cytochrome c oxidase 1 gene and a 330 base‐pair region of the NADH dehydrogenase 4 gene to find genetic variation and characterize phylogenetic and haplotypic relationships based on nucleotide divergences. Our results revealed low genetic diversity in the BC samples, suggesting that these populations arose from the same introduction event. However, our approach lacked the granularity to identify the exact country of origin of the Ae. j. japonicus collected in BC. Future efforts should focus on detecting and preventing new Ae. j. japonicus introductions, recognizing that current molecular techniques are unable to pin‐point the precise source of an introduction.
Background: A community of practice (COP) is a group of people who share a passion for something, and learn how to perform better as they interact regularly. COPs have been shown to be effective models for achieving quality outcomes in healthcare. We report the development and evaluation of a COP in stem cell donor recruitment in Canada. Methodology: In 09/2017, we launched a COP in stem cell donor recruitment in Canada. Stakeholders in donor recruitment were invited via email and Facebook posts to participate in regular e-meetings and a Facebook group. E-meeting topics included running larger stem cell drives, recruiting the most needed donors, redirecting non-optimal donors, reviews of drive outcomes and strategies to improve, using patient stories to support donor recruitment, and reducing donor attrition. Each e-meeting included speakers and roundtable discussion relevant to the theme. The Facebook group facilitated discussion and sharing of resources between e-meetings (see Fig. A for examples of posts). COP participants were also invited to join subcommittees which focused on developing needed resources or achieving specific objectives identified by the COP. A survey was sent to COP participants in 01/2020 to evaluate the perceived impact of the COP to donor recruitment practice. Recruitment outcomes by COP participants of the Canadian donor recruitment organization Stem Cell Club were compared before and after the launch of the COP. Results: As of 07/2020, the COP Facebook group included 333 stakeholders in donor recruitment (312 donor recruiters from Stem Cell Club; 15 patients/donors; 6 donor registry staff). 51 unique attendees participated in 7 e-meetings, 21 of whom attended 2 or more meetings. COP participants collaboratively set the following goals for the COP: 1) to foster teamwork and collaboration in donor recruitment efforts; 2) to improve knowledge and practice related to donor recruitment; 3) to improve recruitment of the most-needed donors; and 4) to improve donor recruiters' ability to run high quality stem cell drives. 141 posts were published to the Facebook group about patient/donor stories (41%), resources in stem cell donation (23%), stem cell drive outcomes and campaigns (15%), updates related to donor recruitment (14%), and questions posed to the community by COP participants (5%). 44 COP participants completed the COP evaluation survey. The majority agreed/strongly agreed that the Facebook group (86%) and e-meetings (59%) supported the development of a community. 64-84% agreed/strongly agreed that participating in the COP fostered collaboration; improved their knowledge and practice in donor recruitment; and improved their ability to run higher quality drives and recruit most-needed donors (Fig. B). Stem Cell Club's donor recruitment outcomes improved following the launch of the COP: in 2016-2017, Stem Cell Club recruited 2918 donors (46% male; 55.9% of males non-Caucasian) compared to 3418 donors in 2017-2018 (52.7% male; 57.8% of males non-Caucasian), and 4531 donors in 2018-2019 (52.9% male; 62.7% of males non-Caucasian) (Fig C). Finally, a number of outputs were generated as a result of collaboration through the COP, including development of resources such as an infographic (stemcellclub.ca/promo.html), a whiteboard video series (youtu.be/V4fVBtxnWfM), and a stem cell donation story library (#WhyWeSwab; facebook.com/WhyWeSwab). COP participants collaborated on national donor recruitment campaigns, securing coverage in major media outlets across Canada (including Toronto Star: thestar.com/life/2019/11/15/stem-cell-donors-wanted-get-swabbed-campaign-coming-to-university-campuses.html; Toronto Sun: torontosun.com/news/local-news/working-to-build-canadas-network-of-stem-cell-donors; London Free Press: lfpress.com/news/local-news/toddlers-case-proves-patients-must-harness-social-media-in-quest-for-stem-cell-donors-advocates; and Victoria News: vicnews.com/news/stem-cell-drive-at-uvic-aims-to-find-lifesaving-donors-for-patients-in-need) and recruiting thousands of needed donors (Fig. D). Conclusion: We describe the first COP in stem cell donor recruitment to our knowledge. The COP was valued by participants and supported efforts to improve donor recruitment. The COP model can be adapted by donor recruitment organizations around the world to improve recruitment outcomes. Figure Disclosures No relevant conflicts of interest to declare.
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