Publications by authors named "J Ryan Butcher"

504 Publications

Examining the Effects of an Anti-Salmonella Bacteriophage Preparation, BAFASAL, on Ex-Vivo Human Gut Microbiome Composition and Function Using a Multi-Omics Approach.

Viruses 2021 Aug 31;13(9). Epub 2021 Aug 31.

Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H-8M5, Canada.

infections (salmonellosis) pose serious health risks to humans, usually via food-chain contamination. This foodborne pathogen causes major food losses and human illnesses, with significant economic impacts. Overuse of antibiotics in the food industry has led to multidrug-resistant strains of bacteria, and governments are now restricting their use, leading the food industry to search for alternatives to secure food chains. Bacteriophages, viruses that infect and kill bacteria, are currently being investigated and used as replacement treatments and prophylactics due to their specificity and efficacy. They are generally regarded as safe alternatives to antibiotics, as they are natural components of the ecosystem. However, when specifically used in the industry, they can also make their way into humans through our food chain or exposure, as is the case for antibiotics. In particular, agricultural workers could be repeatedly exposed to bacteriophages supplemented to animal feeds. To our knowledge, no studies have investigated the effects of such exposure to bacteriophages on the human gut microbiome. In this study, we used a novel in-vitro assay called RapidAIM to investigate the effect of a bacteriophage mixture, BAFASAL, used in poultry farming on five individual human gut microbiomes. Multi-omics analyses, including 16S rRNA gene sequencing and metaproteomic, revealed that ex-vivo human gut microbiota composition and function were unaffected by BAFASAL treatment, providing an additional measure for its safety. Due to the critical role of the gut microbiome in human health and the known role of bacteriophages in regulation of microbiome composition and function, we suggest assaying the impact of bacteriophage-cocktails on the human gut microbiome as a part of their safety assessment.
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http://dx.doi.org/10.3390/v13091734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473076PMC
August 2021

Evaluation of a "tummy time" intervention to improve motor skills in infants after cardiac surgery.

Cardiol Young 2021 Sep 27:1-6. Epub 2021 Sep 27.

Department of Pediatrics, University of Michigan Mott Children's Hospital, Ann Arbor, MI, USA.

Background: Infants who require open heart surgery are at increased risk for developmental delays including gross motor impairments which may have implications for later adaptive skills and cognitive performance. We sought to evaluate the feasibility and efficacy of a tummy time intervention to improve motor skill development in infants after cardiac surgery.

Methods: Infants <4 months of age who underwent cardiac surgery were randomly assigned to tummy time with or without outpatient reinforcement or standard of care prior to hospital discharge. The Alberta Infant Motor Scale (AIMS) was administered to each infant prior to and 3 months after discharge. Groups were compared, and the association between parent-reported tummy time at home and change in motor scores at follow-up was examined.

Results: Parents of infants (n = 64) who had cardiac surgery at a median age of 5 days were randomly assigned to tummy time instruction (n = 20), tummy time + outpatient reinforcement (n = 21) or standard of care (n = 23). Forty-nine (77%) returned for follow-up. At follow-up, reported daily tummy time was not significantly different between groups (p = 0.17). Fifteen infants had <15 minutes of tummy time daily. Infants who received >15 minutes of tummy time daily had a significantly greater improvement in motor scores than infants with <15 minutes of tummy time daily (p = 0.01).

Conclusion: In infants following cardiac surgery, <15 minutes of tummy time daily is associated with increased motor skill impairment. Further research is needed to elucidate the best strategies to optimise parental compliance with tummy time recommendations.
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http://dx.doi.org/10.1017/S1047951121003930DOI Listing
September 2021

Local fluid shear stress operates a molecular switch to drive fetal semilunar valve extension.

Dev Dyn 2021 Sep 18. Epub 2021 Sep 18.

The Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA.

Background: While much is known about the genetic regulation of early valvular morphogenesis, mechanisms governing fetal valvular growth and remodeling remain unclear. Hemodynamic forces strongly influence morphogenesis, but it is unknown whether or how they interact with valvulogenic signaling programs. Side-specific activity of valvulogenic programs motivates the hypothesis that shear stress pattern-specific endocardial signaling controls the elongation of leaflets.

Results: We determined that extension of the semilunar valve occurs via fibrosa sided endocardial proliferation. Low OSS was necessary and sufficient to induce canonical Wnt/β-catenin activation in fetal valve endothelium, which in turn drives BMP receptor/ligand expression, and pSmad1/5 activity essential for endocardial proliferation. In contrast, ventricularis endocardial cells expressed active Notch1 but minimal pSmad1/5. Endocardial monolayers exposed to LSS attenuate Wnt signaling in a Notch1 dependent manner.

Conclusions: Low OSS is transduced by endocardial cells into canonical Wnt signaling programs that regulate BMP signaling and endocardial proliferation. In contrast, high LSS induces Notch signaling in endocardial cells, inhibiting Wnt signaling and thereby restricting growth on the ventricular surface. Our results identify a novel mechanically regulated molecular switch, whereby fluid shear stress drives the growth of valve endothelium, orchestrating the extension of the valve in the direction of blood flow.
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http://dx.doi.org/10.1002/dvdy.419DOI Listing
September 2021

Oligosaccharides and Microbiota in Human Milk Are Interrelated at 3 Months Postpartum in a Cohort of Women with a High Prevalence of Gestational Impaired Glucose Tolerance.

J Nutr 2021 Sep 11. Epub 2021 Sep 11.

Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.

Background: Human milk is a rich source of human milk oligosaccharides (HMOs) and bacteria. It is unclear how these components interact within the breast microenvironment.

Objectives: The objectives were first, to investigate the association between maternal characteristics and HMOs, and second, to assess the association between HMOs and microbial community composition and predicted function in milk from women with high rates of gestational glucose intolerance.

Methods: This was an exploratory analysis of a previously completed prospective cohort study (NCT01405547) where milk samples (n = 107) were collected at 3 mo postpartum. Milk microbiota composition was analyzed by V4-16S ribosomal RNA gene sequencing and HMOs by rapid high-throughput HPLC. Data were stratified and analyzed by maternal secretor status phenotype and associations between HMOs and microbiota were determined using linear regression models (ɑ-diversity), Adonis (B-diversity), Poisson regression models (differential abundance), and general linear models (predicted microbial function).

Results: Prepregnancy BMI, race, and frequency of direct breastfeeding, but not gestational glucose intolerance, were found to be significantly associated with a number of HMOs among secretors and non-secretors. Fucosyllacto-N-hexaose was negatively associated with microbial richness (Chao1) among secretors [B-estimate (SE): -9.3 × 102 (3.4 × 102); P = 0.0082] and difucosyllacto-N-hexaose was negatively associated with microbiota diversity (Shannon index) [-1.7 (0.78); P = 0.029] among secretors. Lacto-N-neotetraose (LNnT) was associated with both microbial B-diversity (weighted UniFrac R2 = 0.040, P = 0.036) and KEGG ortholog B-diversity (Bray-Curtis R2 = 0.039, P = 0.043) in secretors. Additionally, difucosyllactose in secretors and disialyllacto-N-hexaose and LNnT in non-secretors were associated with enrichment of predicted microbial genes encoding for metabolism- and infection-related pathways (P-false discovery rate < 0.1).

Conclusions: HMOs are associated with the microbial composition and predicted microbial functions in human milk at 3 mo postpartum. Further research is needed to investigate the role these relations play in maternal and infant health.
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http://dx.doi.org/10.1093/jn/nxab270DOI Listing
September 2021

An Efficient Statistical Approach to Develop Intensity-Duration-Frequency Curves for Precipitation and Runoff under Future Climate.

Clim Change 2021 Jan;164(1-2):1-3

Tetra Tech, Inc., Fairfax, VA.

Ongoing and potential future changes in precipitation will affect water management infrastructure. Urban drainage systems are particularly vulnerable. Design standards for many stormwater practices rely on precipitation intensity-duration-frequency (IDF) curves based on extreme value analysis. General Circulation Models (GCMs) project increases in future average temperature but are less clear on changes in precipitation. In many areas, climate projections suggest relatively small changes in total precipitation volume, but also suggest increased magnitude of extreme events. Model skill in predicting extreme precipitation events, however, is limited. We develop an approach for estimating future IDF curves that is efficient, uses widely available statistically downscaled GCM output, and is consistent with published IDF curves for the United States that are often incorporated into local stormwater regulations and design guides (and are GCM model agnostic). The method provides a relatively simple way to develop scenarios in a format directly useful to assessing risk to stormwater management infrastructure. Model biases are addressed through equidistant quantile mapping, in which the modeled change in the cumulative distribution of storm events from historical to future conditions is used to adjust the extreme value fit used for IDF curve development. The approach is efficient because it requires only annual maxima and is readily automated, allowing rapid examination of results across projections. We estimate future IDF curves at locations throughout the United States and link IDF-derived design storms to a rainfall-runoff model to evaluate the potential change in storage volume requirements for capture-based stormwater management practices by 2065.
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http://dx.doi.org/10.1007/s10584-021-02963-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320669PMC
January 2021
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