839 research outputs found

    Postpartum Group A Streptococcus Sepsis and Maternal Immunology

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90336/1/j.1600-0897.2011.01083.x.pd

    The characterization and manipulation of the bacterial microbiome of the Rocky Mountain wood tick, Dermacentor andersoni

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    BACKGROUND: In North America, ticks are the most economically impactful vectors of human and animal pathogens. The Rocky Mountain wood tick, Dermacentor andersoni (Acari: Ixodidae), transmits Rickettsia rickettsii and Anaplasma marginale to humans and cattle, respectively. In recent years, studies have shown that symbiotic organisms are involved in a number of biochemical and physiological functions. Characterizing the bacterial microbiome of D. andersoni is a pivotal step towards understanding symbiont-host interactions. FINDINGS: In this study, we have shown by high-throughput sequence analysis that the composition of endosymbionts in the midgut and salivary glands in adult ticks is dynamic over three generations. Four Proteobacteria genera, Rickettsia, Francisella, Arsenophonus, and Acinetobacter, were identified as predominant symbionts in these two tissues. Exposure to therapeutic doses of the broad-spectrum antibiotic, oxytetracycline, affected both proportions of predominant genera and significantly reduced reproductive fitness. Additionally, Acinetobacter, a free-living ubiquitous microbe, invaded the bacterial microbiome at different proportions based on antibiotic treatment status suggesting that microbiome composition may have a role in susceptibility to environmental contaminants. CONCLUSIONS: This study characterized the bacterial microbiome in D. andersoni and determined the generational variability within this tick. Furthermore, this study confirmed that microbiome manipulation is associated with tick fitness and may be a potential method for biocontrol

    Determination of vancomycin and gentamicin clearance in an in vitro, closed loop dialysis system

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    Background\ud The purpose of this study was to evaluate the feasibility of utilizing an in-vitro, closed loop hemodialysis system as a method to assess drug clearance. Secondarily, this study tested the influence of variables (blood flow rate, dialysate flow rate, and type of filter) in the hemodialysis procedure on the clearance of vancomycin and gentamicin.\ud \ud Methods\ud An in-vitro, closed loop hemodialysis system was constructed. The vancomycin (30 mg/L) and gentamicin (25 mg/L) were added to a simulated blood system (SBS). Four conditions (C1-C4) were tested by defining the filter (Polyflux 170H or F180) and the blood and dialysate flow rates (BFR and DFR). All hemodialysis sessions were 3 hours in length and each condition was completed in duplicate. Dialysate effluent was collected in a 50 gallon polyethylene drum. Samples were collected (in duplicate) from the SBS and the dialysate effluent at baseline and at the end of the hemodialysis session. Samples were analyzed for vancomycin and gentamicin with an ultrahigh performance liquid chromatography/tandem mass spectrometry method.\ud \ud Results\ud A total of eight 3-hour hemodialysis sessions were conducted. For all tested conditions (C1-C4), vancomycin was undetectable in the SBS at the end of dialysis. However, total vancomycin recovery in the dialysis effluent was 85±18%, suggesting that up to 15% may have adsorbed to the dialysis filter or tubing. Gentamicin clearance from SBS was >98% in all tested conditions. Average gentamicin recovery in the dialysate effluent was 99±15%.\ud \ud Conclusion\ud Both vancomycin and gentamicin were readily removed by high-flux hemodialysis under all conditions studied. No significant differences in drug clearance were observed between conditions used in this in vitro study. The clinical implications of changing these hemodialysis parameters are unknown

    Outcomes of adjunctive radiation therapy for the treatment of mast cell tumors in dogs and assessment of toxicity: A multicenter observational study of 300 dogs.

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    BACKGROUND: Radiation therapy is commonly used as an adjunct to incomplete surgical excision in dogs with mast cell tumors (MCT), but the optimal dose and fractionation regimen have yet to be determined. HYPOTHESIS: We assessed outcomes (time to local recurrence, patient survival and toxicity) of a large population of dogs with MCT that received adjunctive radiation therapy. ANIMALS: Three hundred dogs with 302 MCT treated using adjunctive radiation therapy. METHODS: Retrospective observational study. Clinical records of 4 veterinary radiation centers were reviewed. RESULTS: Local recurrence rates were similar regardless of radiation protocol with 6.6% of patients developing recurrent cutaneous MCT at a median of 526 days. Local recurrence rate was similar between high and low-risk MCT. Mast cell tumor related death was reported in 19% of all dogs, with 13% of dogs with low-risk MCT dying of their disease compared to 29% of dogs with high-risk MCT. No SC MCT (SCMCT) recurred after radiation therapy and only 7% of dogs with SCMCT were reported to have died of their disease. Mild late toxicity was common in both protocols and severe late toxicity occurred in 1.9% of dogs many years after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study supports the use of adjunctive radiation for the long-term control of incompletely or narrowly excised cutaneous and SCMCT in dogs. More moderate dose and fractionation protocols may be appropriate in the adjunctive treatment of low-risk MCT in dogs. Large multicenter prospective studies are required to establish the optimal dose and fractionation for MCT of different risk categories

    Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

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    Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

    Articulating the effect of food systems innovation on the Sustainable Development Goals

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    Acknowledgments MH, DM-D, JP, JRB, AH, GDB, CMG, CLM, and KR acknowledge funding from the Commonwealth Scientific and Industrial Research Organisation. PKT, BMC, AJ, and AML acknowledge funding from the CGIAR Research Program on Climate Change, Agriculture and Food Security, which is supported by the CGIAR Trust Fund and through bilateral funding agreements. PP acknowledges funding from the German Federal Ministry of Education and Research for the BIOCLIMAPATHS project.Peer reviewedPublisher PD

    The Genetic Links to anxiety and depression (GLAD) study: Online recruitment into the largest recontactable study of depression and anxiety

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    Background: Anxiety and depression are common, debilitating and costly. These disorders are influenced by multiple risk factors, from genes to psychological vulnerabilities and environmental stressors, but research is hampered by a lack of sufficiently large comprehensive studies. We are recruiting 40,000 individuals with lifetime depression or anxiety and broad assessment of risks to facilitate future research. Methods: The Genetic Links to Anxiety and Depression (GLAD) Study (www.gladstudy.org.uk) recruits individuals with depression or anxiety into the NIHR Mental Health BioResource. Participants invited to join the study (via media campaigns) provide demographic, environmental and genetic data, and consent for medical record linkage and recontact. Results: Online recruitment was effective; 42,531 participants consented and 27,776 completed the questionnaire by end of July 2019. Participants’ questionnaire data identified very high rates of recurrent depression, severe anxiety, and comorbidity. Participants reported high rates of treatment receipt. The age profile of the sample is biased toward young adults, with higher recruitment of females and the more educated, especially at younger ages. Discussion: This paper describes the study methodology and descriptive data for GLAD, which represents a large, recontactable resource that will enable future research into risks, outcomes, and treatment for anxiety and depression

    Geospatial Resolution of Human and Bacterial Diversity with City-Scale Metagenomics

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    The panoply of microorganisms and other species present in our environment influence human health and disease, especially in cities, but have not been profiled with metagenomics at a city-wide scale. We sequenced DNA from surfaces across the entire New York City (NYC) subway system, the Gowanus Canal, and public parks. Nearly half of the DNA (48%) does not match any known organism; identified organisms spanned 1,688 bacterial, viral, archaeal, and eukaryotic taxa, which were enriched for harmless genera associated with skin (e.g., Acinetobacter). Predicted ancestry of human DNA left on subway surfaces can recapitulate U.S. Census demographic data, and bacterial signatures can reveal a station’s history, such as marine-associated bacteria in a hurricane-flooded station. Some evidence of pathogens was found (Bacillus anthracis), but a lack of reported cases in NYC suggests that the pathogens represent a normal, urban microbiome. This baseline metagenomic map of NYC could help long-term disease surveillance, bioterrorism threat mitigation, and health management in the built environment of citie

    The enhanced future Flows and Groundwater dataset: development and evaluation of nationally consistent hydrological projections based on UKCP18

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    This paper details the development and evaluation of the enhanced future FLows and Groundwater (eFLaG) dataset of nationally consistent hydrological projections for the UK, based on the latest UK Climate Projections (UKCP18). The projections are derived from a range of hydrological models. For river flows, multiple models (Grid-to-Grid, PDM (Probability Distributed Model) and GR (Génie Rural; both four- and six-parameter versions, GR4J and GR6J)) are used to provide an indication of hydrological model uncertainty. For groundwater, two models are used, a groundwater level model (AquiMod) and a groundwater recharge model (ZOODRM: zooming object-oriented distributed-recharge model). A 12-member ensemble of transient projections of present and future (up to 2080) daily river flows, groundwater levels and groundwater recharge was produced using bias-corrected data from the UKCP18 regional (12 km) climate ensemble. Projections are provided for 200 river catchments, 54 groundwater level boreholes and 558 groundwater bodies, all sampling across the diverse hydrological and geological conditions of the UK. An evaluation was carried out to appraise the quality of hydrological model simulations against observations and also to appraise the reliability of hydrological models driven by the regional climate model (RCM) ensemble in terms of their capacity to reproduce hydrological regimes in the current period. The dataset was originally conceived as a prototype climate service for drought planning for the UK water sector and so has been developed with drought, low river flow and low groundwater level applications as the primary objectives. The evaluation metrics show that river flows and groundwater levels are, for the majority of catchments and boreholes, well simulated across the flow and level regime, meaning that the eFLaG dataset could be applied to a wider range of water resources research and management contexts, pending a full evaluation for the designated purpose. Only a single climate model and one emissions scenario are used, so any applications should ideally contextualise the outcomes with other climate model–scenario combinations. The dataset can be accessed in Hannaford et al. (2022): https://doi.org/10.5285/1bb90673-ad37-4679-90b9-0126109639a9
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