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result(s) for
"Andra A. Hutton"
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Comparative fitness of West Nile virus isolated during California epidemics
by
Hutton, Andra A.
,
Brault, Aaron C.
,
Reisen, William K.
in
Adulticides
,
Amplification
,
Animals
2019
West Nile virus (WNV) has been circulating in California since its first detection in 2003, causing repeated outbreaks affecting public, wildlife and veterinary health. Epidemics of WNV are difficult to predict due to the multitude of factors influencing transmission dynamics among avian and mosquito hosts. Typically, high levels of WNV amplification are required for outbreaks to occur, and therefore associated viral strains may exhibit enhanced virulence and mortality in competent bird species resulting in increased mosquito infection prevalence. In our previous study, most WNV isolates made from California during 2007-08 showed increased fitness when competed in House Finches (HOFI, Haemorhous mexicanus) and Culex tarsalis Coquillett mosquitoes against COAV997-5nt, a genetically marked recombinant virus derived from a 2003 California strain. Herein, we evaluated the competitive fitness of WNV strains isolated during California epidemics in 2004, 2005, 2007, 2011 and 2012 against COAV997-5nt. These outbreak isolates did not produce elevated mortality in HOFIs, but replicated more efficiently than did COAV997-5nt based on quantification of WNV RNA copies in sera, thereby demonstrating increased competitive fitness. Oral co-infections in Cx. tarsalis resulted in similar virus-specific infection and transmission rates, indicating that outbreak isolates did not have a fitness advantage over COAV997-5nt. Collectively, WNV isolates from outbreaks demonstrated relatively greater avian, but not vector, replicative fitness compared to COAV997-5nt, similar to previously characterized non-outbreak isolates of WNV. Our results indicated that ecological rather than viral factors may facilitate WNV amplification to outbreak levels, but monitoring viral phenotypes through competitive fitness studies may provide insight into altered replication and transmission potential among emerging WNV strains.
Journal Article
Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of Bifidobacterium over the Past Century
2018
Historically,
Bifidobacterium
species were reported as abundant in the breastfed infant gut. However, recent studies in resource-rich countries show an increased abundance of taxa regarded as signatures of dysbiosis.
Historically,
Bifidobacterium
species were reported as abundant in the breastfed infant gut. However, recent studies in resource-rich countries show an increased abundance of taxa regarded as signatures of dysbiosis. It is unclear whether these differences are the product of genetics, geographic factors, or interventions such as formula feeding, antibiotics, and caesarean section. Fecal pH is strongly associated with
Bifidobacterium
abundance; thus, pH could be an indicator of its historical abundance. A review of 14 clinical studies published between 1926 and 2017, representing more than 312 healthy breastfed infants, demonstrated a change in fecal pH from 5.0 to 6.5 (adjusted
r
2
= 0.61). This trend of increasing infant fecal pH over the past century is consistent with current reported discrepancies in
Bifidobacterium
species abundance in the gut microbiome in resource-rich countries compared to that in historical reports. Our analysis showed that increased fecal pH and abundance of members of the families
Enterobacteriaceae
,
Clostridiaceae
,
Peptostreptococcaceae
, and
Veillonellaceae
are associated, indicating that loss of highly specialized
Bifidobacterium
species may result in dysbiosis, the implications of which are not yet fully elucidated. Critical assessment of interventions that restore this ecosystem, measured by key parameters such as ecosystem productivity, gut function, and long-term health, are necessary to understand the magnitude of this change in human biology over the past century.
Journal Article
Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants
2017
The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of
B. infantis
EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by
B. infantis
EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated
Bifidobacterium
sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.
Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of
Bifidobacterium longum
subsp.
infantis
(
B. infantis
) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed
B. infantis
EVC001 to their infants from day 7 to day 28 of life (
n
= 34), and the second group did not administer any probiotic (
n
= 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement.
B. infantis
-fed infants had significantly higher populations of fecal
Bifidobacteriaceae
, in particular
B. infantis
, while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in
B. infantis
EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by
B. infantis
EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by
Bifidobacteriaceae
at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative
Proteobacteria
and
Bacteroidetes
.
IMPORTANCE
The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of
B. infantis
EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by
B. infantis
EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated
Bifidobacterium
sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.
Journal Article
Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of italic toggle=\yes\>Bifidobacterium /italic> over the Past Century
by
Andra A. Hutton
,
Michelle C. Palumbo
,
Ryan D. Mitchell
in
Bifidobacterium
,
biochemistry
,
infant microbiome
2018
ABSTRACT Historically, Bifidobacterium species were reported as abundant in the breastfed infant gut. However, recent studies in resource-rich countries show an increased abundance of taxa regarded as signatures of dysbiosis. It is unclear whether these differences are the product of genetics, geographic factors, or interventions such as formula feeding, antibiotics, and caesarean section. Fecal pH is strongly associated with Bifidobacterium abundance; thus, pH could be an indicator of its historical abundance. A review of 14 clinical studies published between 1926 and 2017, representing more than 312 healthy breastfed infants, demonstrated a change in fecal pH from 5.0 to 6.5 (adjusted r2 = 0.61). This trend of increasing infant fecal pH over the past century is consistent with current reported discrepancies in Bifidobacterium species abundance in the gut microbiome in resource-rich countries compared to that in historical reports. Our analysis showed that increased fecal pH and abundance of members of the families Enterobacteriaceae, Clostridiaceae, Peptostreptococcaceae, and Veillonellaceae are associated, indicating that loss of highly specialized Bifidobacterium species may result in dysbiosis, the implications of which are not yet fully elucidated. Critical assessment of interventions that restore this ecosystem, measured by key parameters such as ecosystem productivity, gut function, and long-term health, are necessary to understand the magnitude of this change in human biology over the past century.
Journal Article
Persistence of Supplemented Bifidobacterium longum subsp. italic toggle=\yes\>infantis /italic> EVC001 in Breastfed Infants
by
Jasmine C. C. Davis
,
Andra A. Hutton
,
David A. Mills
in
bifidobacteria
,
breast milk
,
human milk oligosaccharides
2017
ABSTRACT Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of Bifidobacterium longum subsp. infantis (B. infantis) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed B. infantis EVC001 to their infants from day 7 to day 28 of life (n = 34), and the second group did not administer any probiotic (n = 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement. B. infantis-fed infants had significantly higher populations of fecal Bifidobacteriaceae, in particular B. infantis, while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in B. infantis EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by B. infantis EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by Bifidobacteriaceae at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative Proteobacteria and Bacteroidetes. IMPORTANCE The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.
Journal Article
Impacts of medical and non-medical cannabis on the health of older adults: Findings from a scoping review of the literature
2023
Cannabis legalization has enabled increased consumption in older adults. Age-related mental, physical, and physiological changes may lead to differences in effects of cannabis in older adults compared to younger individuals.
To perform a scoping review to map the evidence regarding the health effects of cannabis use for medical and non-medical purposes in older adults.
Electronic databases (MEDLINE, Embase, PsycINFO, Cochrane Library) were searched for systematic reviews (SRs), randomized controlled trials (RCTs) and non-randomized/observational studies (NRSs) assessing the health effects and associations of cannabis use (medical or non-medical) in adults ≥ 50 years of age. Included studies met age-related inclusion criteria or involved a priori identified health conditions common among older adults. Records were screened using a liberal accelerated approach and data charting was performed independently by two reviewers. Descriptive summaries, structured tables, effect direction plots and bubble plots were used to synthesize study findings.
From 31,393 citations, 133 publications describing 134 unique studies (26 SRs, 36 RCTs, 72 NRSs) were included. Medical cannabis had inconsistent therapeutic effects in specific patient conditions (e.g., end-stage cancer, dementia), with a number of studies suggesting possible benefits while others found no benefit. For medical cannabis, harmful associations outnumbered beneficial, and RCTs reported more negative effects than NRSs. Cannabis use was associated with greater frequencies of depression, anxiety, cognitive impairment, substance use and problematic substance use, accidents/injuries, and acute healthcare use. Studies often were small, did not consistently assess harms, and did not adjust for confounding.
The effects of medical cannabis are inconsistent within specific patient conditions. For older adults, generally, the available evidence suggests cannabis use may be associated with greater frequencies of mental health issues, substance use, and acute healthcare use, and the benefit-to-risk ratio is unclear. Studies with a balanced assessment of benefits and harms may guide appropriate public health messaging to balance the marketing pressures of cannabis to older adults.
Journal Article
THE EFFECT OF ENGLISH-LANGUAGE RESTRICTION ON SYSTEMATIC REVIEW-BASED META-ANALYSES: A SYSTEMATIC REVIEW OF EMPIRICAL STUDIES
by
Moulton, Kristen
,
Clark, Michelle
,
Mierzwinski-Urban, Monika
in
Alternative medicine
,
Bias
,
Bibliographic data bases
2012
Objectives: The English language is generally perceived to be the universal language of science. However, the exclusive reliance on English-language studies may not represent all of the evidence. Excluding languages other than English (LOE) may introduce a language bias and lead to erroneous conclusions. Study Design and Setting: We conducted a comprehensive literature search using bibliographic databases and grey literature sources. Studies were eligible for inclusion if they measured the effect of excluding randomized controlled trials (RCTs) reported in LOE from systematic review-based meta-analyses (SR/MA) for one or more outcomes. Results: None of the included studies found major differences between summary treatment effects in English-language restricted meta-analyses and LOE-inclusive meta-analyses. Findings differed about the methodological and reporting quality of trials reported in LOE. The precision of pooled estimates improved with the inclusion of LOE trials. Conclusions: Overall, we found no evidence of a systematic bias from the use of language restrictions in systematic review-based meta-analyses in conventional medicine. Further research is needed to determine the impact of language restriction on systematic reviews in particular fields of medicine.
Journal Article
Effects of medical and non-medical cannabis use in older adults: protocol for a scoping review
2020
IntroductionWith its legalisation and regulation in Canada in 2018, the proportion of Canadians reporting cannabis use in 2019 increased substantially over the previous year, with half of new users being aged 45+ years. While use in older adults has been low historically, as those born in the 1950s and 1960s continue to age, this demographic will progressively have more liberal attitudes, prior cannabis exposure and higher use rates. However, older adults experience slower metabolism, increased likelihood of polypharmacy, cognitive decline and chronic physical/mental health problems. There is a need to enhance knowledge of the effects of cannabis use in older adults. The following question will be addressed using a scoping review approach: what evidence exists regarding beneficial and harmful effects of medical and non-medical cannabis use in adults >50 years of age? Given that beneficial and harmful effects of cannabis may be mediated by patient-level (eg, age, sex and race) and cannabis-related factors (eg, natural vs synthetic, consumption method), subgroup effects related to these and additional factors will be explored.Methods and analysisMethods for scoping reviews outlined by Arksey & O’Malley and the Joanna Briggs Institute will be used. A librarian designed a systematic search of the literature from database inception to June 2019. Using the OVID platform, Ovid MEDLINE will be searched, including Epub Ahead of Print and In-Process and Other Non-Indexed Citations, Embase Classic+Embase, and PsycINFO for reviews, randomised trials, non-randomised trials and observational studies of cannabis use. The Cochrane Library on Wiley will also be searched. Eligibility criteria will be older adult participants, currently using cannabis (medical or non-medical), with studies required to report a cannabis-related health outcome to be eligible. Two reviewers will screen citations and full texts, with support from artificial intelligence. Two reviewers will chart data. Tables/graphics will be used to map evidence and identify evidence gaps.Ethics and disseminationThis research will enhance awareness of existing evidence addressing the health effects of medical and non-medical cannabis use in older adults. Findings will be disseminated through a peer-reviewed publication, conference presentations and a stakeholder meeting.Trial registration numberDOI 10.17605/OSF.IO/5JTAQ.
Journal Article
West Nile Evolution: Using Cell Culture Competition Assays to Assess Replicative Fitness
2015
West Nile virus (WNV) was first detected in California near El Centro, Imperial County on July 16, 2003. WNV outbreaks in Los Angeles (2004, 2008 and 20012), Sacramento (2005) and Bakersfield (2007) highlighted the need to track the spatio-temporal evolution of WNV, predict WNV movement, and gain a better understanding of the factors that facilitate WNV epidemics. An in vivo fitness competition model was previously developed to study the phenotypic changes in WNV as it adapted to different mosquito vector and avian host systems throughout California. This fitness competition assay allowed us to evaluate the replicative fitness of an unknown strain to a labelled reference strain (a clone derived California founding COAV997-2003 WNV strain) within the same system (host, cell etc.) instead of by concurrent single infections. In this study, we evaluated the replicative fitness of four Coachella Valley isolates, COAV1573_07, COAV1091_08, COAV1333_08 and COAV1722_08 in an avian cell line [duck embryonic fibroblasts (DEF)] and Aedes albopictus-derived C6/36 cell cultures using the same competition fitness model. An in vitro competition fitness model allowed for the rapid screening for relative fitness differences among field strains of WNV against the labelled reference strain. We found that in vitro COAV997-5nt representing the 2003 founding isolate generally outcompeted these more recent isolates of WNV from Coachella Valley. This rapid screening could be useful for research or diagnostic purposes not only for WNV, but other viruses that affect public health, to assess how viruses change to become more or less pathogenic over time.
Dissertation