629 research outputs found

    Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model

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    peer-reviewedThe aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~109microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~109 L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.The authors and their work were supported by the APC Microbiome Institute. The APC Microbiome Institute is funded by Science Foundation Ireland (SFI). This publication has emanated from research supported by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2273

    Gut reactions: breaking down xenobiotic–microbiome interactions

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    The microbiome plays a key role in health and disease, and there has been considerable interest in therapeutic targeting of the microbiome as well as mining this rich resource in drug discovery efforts. However, a growing body of evidence suggests that the gut microbiota can itself influence the actions of a range of xenobiotics, in both beneficial and potentially harmful ways. Traditionally, clinical studies evaluating the pharmacokinetics of new drugs have mostly ignored the important direct and indirect effects of the gut microbiome on drug metabolism and efficacy. Despite some important observations from xenobiotic metabolism in general, there is only an incomplete understanding of the scope of influence of the microbiome specifically on drug metabolism and absorption, and how this might influence systemic concentrations of parent compounds and toxic metabolites. The significance of both microbial metabolism of xenobiotics and the impact of the gut microbiome on host hepatic enzyme systems is nonetheless gaining traction and presents a further challenge in drug discovery efforts, with implications for improving treatment outcomes or counteracting adverse drug reactions. Microbial factors must now be considered when determining drug pharmacokinetics and the impact that an evolving and dynamic microbiome could have in this regard. In this review, we aim to integrate the contribution of the gut microbiome in health and disease to xenobiotic metabolism focusing on therapeutic interventions, pharmacological drug action, and chemical biotransformations that collectively will have implications for the future practice of precision medicine

    Banking union in historical perspective: the initiative of the European Commission in the 1960s-1970s

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    This article shows that planning for the organization of EU banking regulation and supervision did not just appear on the agenda in recent years with discussions over the creation of the eurozone banking union. It unveils a hitherto neglected initiative of the European Commission in the 1960s and early 1970s. Drawing on extensive archival work, this article explains that this initiative, however, rested on a number of different assumptions, and emerged in a much different context. It first explains that the Commission's initial project was not crisis-driven; that it articulated the link between monetary integration and banking regulation; and finally that it did not set out to move the supervisory framework to the supranational level, unlike present-day developments

    Analysis of the UK Government's 2011 tourism policy

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    This review considers the UK Government's 2011 tourism policy document. The policy was produced during a period of public sector restructuring in the UK and also during the global economic crisis, which began in 2008. The policy sets out a number of reforms to the governance of tourism at the national and local levels, which aim to increase the level of private sector involvement in leading and developing the tourism sector and to reduce the sector's dependence on public funding. During a period of economic slowdown in the UK, the tourism industry can make a significant contribution to growth, but it is not yet clear whether these proposed reforms will support or impede the future development of the tourism industry in the UK

    Predictors of Chronic Opioid Use: A Population-Level Analysis of North Carolina Cancer Survivors Using Multi-Payer Claims

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    Background: No population-based studies have examined chronic opioid use among cancer survivors who are diverse with respect to diagnosis, age group, and insurance status. Methods: We conducted a retrospective cohort study using North Carolina cancer registry data linked with claims from public and private insurance (2006-2016). We included adults with nonmetastatic cancer who had no prior chronic opioid use (n = 38 366). We used modified Poisson regression to assess the adjusted relative risk of chronic opioid use in survivorship (>90-day continuous supply of opioids in the 13-24 months following diagnosis) associated with patient characteristics. Results: Only 3.0% of cancer survivors in our cohort used opioids chronically in survivorship. Predictors included younger age (adjusted risk ratio [aRR] 50-59 vs 60-69 = 1.23, 95% confidence interval [CI] = 1.05 to 1.43), baseline depression (aRR = 1.22, 95% CI = 1.06 to 1.41) or substance use (aRR = 1.43, 95% CI = 1.15 to 1.78) and Medicaid (aRR vs private = 1.93, 95% CI = 1.56 to 2.40). Survivors who used opioids intermittently (vs not at all) before diagnosis were twice as likely to use opioids chronically in survivorship (aRR = 2.62, 95% CI = 2.28 to 3.02). Those who used opioids chronically (vs intermittently or not at all) during active treatment had a nearly 17-fold increased likelihood of chronic use in survivorship (aRR = 16.65, 95% CI = 14.30 to 19.40). Conclusions: Younger and low-income survivors, those with baseline depression or substance use, and those who require chronic opioid therapy during treatment are at increased risk for chronic opioid use in survivorship. Our findings point to opportunities to improve assessment of psychosocial histories and to engage patients in shared decision-making around long-term pain management, when chronic opioid therapy is required during treatment

    Temporospatial shifts in Sandhill Crane staging in the Central Platte River Valley in response to climatic variation and habitat change

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    Over 80% of the Mid-Continent Sandhill Crane (Antigone canadensis) Population (MCP), estimated at over 660,000 individuals, stops in the Central Platte River Valley (CPRV) during spring migration from mid-February through mid-April. Research suggests that the MCP may be shifting its distribution spatially and temporally within the CPRV. From 2002 to 2017, we conducted weekly aerial surveys of Sandhill Cranes staging in the CPRV to examine temporal and spatial trends in their abundance and distribution. Then, we used winter temperature and drought severity measures from key wintering and early migratory stopover locations to assess the impacts of weather patterns on annual migration chronology in the CPRV. We also evaluated channel width and land cover characteristics using aerial imagery from 1938, 1998, and 2016 to assess the relationship between habitat change and the spatial distribution of the MCP in the CPRV. We used generalized linear models, cumulative link models, and Akaike’s information criterion corrected for small sample sizes (AICc) to compare temporal and spatial models. Temperatures and drought conditions at wintering and migration locations that are heavily used by Greater Sandhill Cranes (A. c. tabida) best predicted migration chronology of the MCP to the CPRV. The spatial distribution of roosting Sandhill Cranes from 2015 to 2017 was best predicted by the proportion of width reduction in the main channel since 1938 (rather than its width in 2016) and the proportion of land cover as prairie-meadow habitat within 800 m of the Platte River. Our data suggest that Sandhill Cranes advanced their migration by an average of just over 1 day per year from 2002 to 2017, and that they continued to shift eastward, concentrating at eastern reaches of the CPRV. Climate change, land use change, and habitat loss have all likely contributed to Sandhill Cranes coming earlier and staying longer in fewer reaches of the CPRV, increasing their site use intensity. These historically unprecedented densities may present a disease risk to Sandhill Cranes and other waterbirds, including Whooping Cranes (Grus americana). Our models suggest that conservation actions may be maintaining Sandhill Crane densities in areas that would otherwise be declining in use. We suggest that management actions intended to mitigate trends in the distribution of Sandhill Cranes, including wet meadow restoration, may similarly benefit prairie- and braided river–endemic species of concern. Más del 80% de la población de grullas canadienses (Antigone canadensis), de la zona central del continente (MCP por sus siglas en inglés), estimada en más de 660,000, descansa en el valle central del Río Platte (CPRV por sus siglas en inglés) durante su migración de primavera, desde mediados de febrero hasta mediados de abril. Diversos estudios indican que su distribución espacial y temporal podría estar cambiando dentro del CPRV. Desde el año 2002 hasta el 2017 realizamos sondeos aéreos semanales de grullas canadienses en el CPRV para estudiar las tendencias temporales y espaciales relacionadas a su abundancia y distribución. Usamos mediciones de temperatura durante el invierno y de la severidad de la sequía de lugares claves de invernada y de sitios de descanso durante su migración temprana para evaluar el impacto de los patrones climáticos en la cronología migratoria anual del CPRV. También analizamos la amplitud del canal y las características de la cubierta terrestre usando imágenes aéreas de 1938, 1998 y 2016 con el fin de evaluar la relación entre el cambio de hábitat y la distribución espacial de la MCP en el CPRV. Utilizamos modelos lineales generalizados, modelos de enlace acumulativo y el criterio de información de Akaike adecuados a muestras pequeñas (AICc), para comparar modelos temporales y espaciales. Las condiciones climáticas y de sequía en los sitios de invernada y migración más usados por la grulla canadiense mayor (A. c. tabida) predijeron mejor la cronología migratoria de la MCP en el CPRV. La reducción de la amplitud del canal principal desde 1938, junto con el porcentaje de cubierta terrestre como hábitat de pradera dentro de los 800 m del río Platte, fue el mejor predictor de la distribución espacial de la grulla canadiense desde el año 2015 hasta el 2017. Nuestros estudios indican que las grullas canadienses adelantaron su migración en un promedio poco más de un día por año entre el 2002 y el 2017 y que continuaron desplazándose hacia el este, concentrándose en los extremos orientales del CPRV. El cambio climático, el cambio de uso del suelo y la pérdida del hábitat probablemente contribuyeron a la migración temprana de esta especie y a su permanencia más prolongada en algunos sectores del CPRV, aumentando la intensidad del uso del sitio. Estas densidades sin precedentes podrían presentar un riesgo de enfermedad para la grulla canadiense y otras aves acuáticas, incluidas las grullas trompeteras (Grus americana). Nuestros modelos indican que las medidas actuales de conservación podrían ser la causa de preservación de la densidad poblacional de la grulla canadiense en áreas en las que, de otra forma, su presencia estaría disminuyendo. Sugerimos que las medidas de control destinadas a mitigar la tendencia de distribución de la grulla canadiense, incluyendo la restauración de los prados húmedos, pueden beneficiar de igual manera a las especies endémicas, praderas y ríos trenzados de nuestro interés
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