Exogenous Short Chain Fatty Acid Effects in APP/PS1 Mice

Elucidating the impact of the gut microbiome on Alzheimer’s Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and amyloid burden as assessed by histochemistry and MSD ELISA. We report that SCFA treatment increased alpha-diversity and impacted the gut microbiome profile by increasing, in part, the relative abundance of several bacteria that typically produce SCFAs. However, SCFA treatment did not significantly affect behavior. Similarly, SCFAs did not affect cortical or hippocampal astrocyte activation observed in the APP/PS1 mice. Lastly, although robust levels of soluble and insoluble amyloid were present in the APP/PS1 mice, SCFA treatment had no effect on these indices. Overall, our findings are that SCFA treatment modifies the microbiome in a fashion that may increase further SCFA production. However, SCFA treatment did not alter behavior, astrocyte activation, nor amyloid neuropathology in APP/PS1 mice maintained with a conventional microbiome

The Nucleotide Excision Repair Pathway Protects Borrelia burgdorferi from Nitrosative Stress in Ixodes scapularis Ticks

The Lyme disease spirochete Borrelia burgdorferi encounters a wide range of environmental conditions as it cycles between ticks of the genus Ixodes and its various mammalian hosts. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are potent antimicrobial molecules generated during the innate immune response to infection, however, it is unclear whether ROS and RNS pose a significant challenge to B. burgdorferi in vivo. In this study, we screened a library of B. burgdorferi strains with mutations in DNA repair genes for increased susceptibility to ROS or RNS in vitro. Strains with mutations in the methyl-directed mismatch repair (MMR) gene mutS1 are hypersensitive to killing by ROS, while strains lacking the nucleotide excision repair (NER) gene uvrB show increased susceptibility to both ROS and RNS. Therefore, mutS1-deficient and uvrB-deficient strains were compared for their ability to complete their infectious cycle in Swiss Webster mice and I. scapularis ticks to help identify sites of oxidative and nitrosative stresses encountered by B. burgdorferi in vivo. Both mutS1¬ and uvrB were dispensable for infection of mice, while uvrB promoted the survival of spirochetes in I. scapularis ticks. The decreased survival of uvrB-deficient B. burgdorferi was associated with the generation of RNS in I. scapularis midguts and salivary glands during feeding. Collectively, these data suggest that B. burgdorferi must withstand cytotoxic levels of RNS produced during infection of I. scapularis ticks

Environmental risk factors for canine atopic dermatitis: a retrospective large‐scale study in Labrador and golden retrievers

Background - canine atopic dermatitis (cAD) is one the most common and distressing skin disorders seen in dogs. It is characterised by dysfunction in the skin barrier, with a complex pathogenesis combining both genetic and environmental factors.Objectives - to evaluate associations between environmental factors and case-control status in two closely related, at-risk breeds, the Labrador and Golden retriever.Animals - 2,445 pet dogs, of which 793 were classed as cases (575 Labradors and218 Golden retrievers) and 1,652 as controls (1,120 Labradors and 532 Golden retrievers). Methods – case-control status was assigned based upon owner response to a standardised validated questionnaire. Retrospective data on rearing environment was collected via additional questions. Univariate and multivariate logistic regressions were utilised to evaluate associations between environmental factors and case-control status.Results - risk factors included being reared in an urban environment (not living currently in an urban environment), being male, being neutered, receiving flea control, and being allowed on upholstered furniture. Protective factors included living with other dogs (not cats) and walking in woodlands, fields or beaches. Additionally, amongst Labradors, chocolate coated dogs were at greater risk of having cAD than black or yellow coated dogs.Conclusions and clinical importance - This study is the largest of its kind to date to investigate the role of the environment in canine atopic dermatitis. Although precise triggers are unclear, this study contributes to those of earlier studies to highlight the protective role of a rural environment and highlights some novel associations with disease development

Employer Policies and Practices to Manage and Prevent Disability: Foreword to the Special Issue

Purpose Employer policies and practices have been shown to impact workplace disability, but research in this area has waned in recent years despite an aging workforce, a growing prevalence of chronic health conditions, and a larger proportion of working-age adults on permanent work disability in many jurisdictions. The purpose of this article is to describe the background rationale and methodology for an invited conference designed to improve research of employer strategies to curtail work disability. Methods A multidisciplinary team of 26 international researchers with published research in employer-based disability management or related fields were invited to attend a 3-day conference in Hopkinton, Massachusetts, USA. The overall goal was to review the status of current research of workplace disability management and prevention, examine its relevance for employer decision-making, compare conceptual frameworks or theoretical perspectives, and recommend future research directions. Working groups were organized and draft manuscripts were prepared in advance. Conference activities included working group presentations and critiques, discussions with a panel of industry consultants and advisors, group interaction and debate, generation of final recommendations, and manuscript revision. Results/Conclusion Six principal domains were established with respect to future research: (a) further elucidation of the key workplace factors that buffer the disabling effects of injury and illness; (b) more innovative and feasible options for workplace intervention; (c) measurement of workplace-relevant disability outcomes; (d) a stronger theoretical framework for understanding the factors behind employer uptake and implementation; (e) a focus on special clinical populations and occupations where disability risk is most troubling; and (f) better representation of workers and employers that reflect the diverse and changing nature of work. Final comments and recommendations of the working groups are presented in the following six articles in this special issue of the Journal of Occupational Rehabilitation. Conference attendees recommended changes in methodology, collaboration strategies, and theoretical perspectives to improve the practical and scientific impact of future research of employer practices

International Space Station Common Cabin Air Assembly Condensing Heat Exchanger Hydrophilic Coating Operation, Recovery, and Lessons Learned

The ability to control the temperature and humidity of an environment or habitat is critical for human survival. These factors are important to maintaining human health and comfort, as well as maintaining mechanical and electrical equipment in good working order to support the human and to accomplish mission objectives. The temperature and humidity of the International Space Station (ISS) United States On-orbit Segment (USOS) cabin air is controlled by the Common Cabin Air Assembly (CCAA). The CCAA consists of a fan, a condensing heat exchanger (CHX), an air/water separator, temperature and liquid sensors, and electrical controlling hardware and software. The CHX is the primary component responsible for control of temperature and humidity. The CCAA CHX contains a chemical coating that was developed to be hydrophilic and thus attract water from the humid influent air. This attraction forms the basis for water removal and therefore cabin humidity control. However, there have been several instances of CHX coatings becoming hydrophobic and repelling water. When this behavior is observed in an operational CHX in the ISS segments, the unit s ability to remove moisture from the air is compromised and the result is liquid water carryover into downstream ducting and systems. This water carryover can have detrimental effects on the ISS cabin atmosphere quality and on the health of downstream hardware. If the water carryover is severe and widespread, this behavior can result in an inability to maintain humidity levels in the USOS. This paper will describe the operation of the five CCAAs within the USOS, the potential causes of the hydrophobic condition, and the impacts of the resulting water carryover to downstream systems. It will describe the history of this behavior and the actual observed impacts to the ISS USOS. Information on mitigation steps to protect the health of future CHX hydrophilic coatings as well as remediation and recovery of the full heat exchanger will be discussed

Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments

Neurofilaments possess side arms that comprise the carboxy-terminal domains of neurofilament middle and heavy chains (NFM and NFH); that of NFH is heavily phosphorylated in axons. Here, we demonstrate that phosphorylation of NFH side arms is a mechanism for regulating transport of neurofilaments through axons. Mutants in which known NFH phosphorylation sites were mutated to preclude phosphorylation or mimic permanent phosphorylation display altered rates of transport in a bulk transport assay. Similarly, application of roscovitine, an inhibitor of the NFH side arm kinase Cdk5/p35, accelerates neurofilament transport. Analyses of neurofilament movement in transfected living neurons demonstrated that a mutant mimicking permanent phosphorylation spent a higher proportion of time pausing than one that could not be phosphorylated. Thus, phosphorylation of NFH slows neurofilament transport, and this is due to increased pausing in neurofilament movement

Should We Consider Patients with Coexistent Hepatitis B or C Infection for Orthotopic Heart Transplantation?

Heart transplantation (HTX) is the gold standard surgical treatment for patients with advanced heart failure. The prevalence of hepatitis B and hepatitis C infection in HTX recipients is over 10%. Despite its increased prevalence, the long-term outcome in this cohort is still not clear. There is a reluctance to place these patients on transplant waiting list given the increased incidence of viral reactivation and chronic liver disease after transplant. The emergence of new antiviral therapies to treat this cohort seems promising but their long-term outcome is yet to be established. The aim of this paper is to review the literature and explore whether it is justifiable to list advanced heart failure patients with coexistent hepatitis B/C infection for HTX

Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants.

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