1,606 research outputs found

    Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells - Activation of protein kinase B by wortmannin-sensitive and -insensittve mechanisms

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    Previous studies using L6 myotubes have suggested that glycogen synthase kinase-3 (GSK-3) is phosphoryl ated and inactivated in response to insulin by protein kinase B (PKB, also known as Akt or RAG) (Cross, D, A, E., Alessi, D, R., Cohen, P., Andjelkovic, M., and Hemmings, B, A. (1995) Nature 378, 785-789), In the present study, marked increases in the activity of PKB have been shown to occur in insulin-treated rat epididymal fat cells with a time course compatible with the observed decrease in GSK-3 activity, Isoproterenol, acting primarily through beta(3)-adrenoreceptors, was found to decrease GSK-3 activity to a similar extent (approximately 50%) to insulin, However, unlike the effect of insulin, the inhibition of GSK by isoproterenol was not found to be sensitive to inhibition by the phosphatidylinositol 3'-kinase inhibitors, wortmannin or LY 294002, The change in GSK-3 activity brought about by isoproterenol could not be mimicked by the addition of permeant cyclic AMP analogues or forskolin to the cells, although at the concentrations used, these agents were able to stimulate lipolysis. Isoproterenol, but again not the cyclic AMP analogues, was found to increase the activity of PKB, although to a lesser extent than insulin. While wortmannin abolished the stimulation of PKB activity by insulin, it was without effect on the activation seen in response to isoproterenol, The activation of PKB by isoproterenol was not accompanied by any detectable change in the electrophoretic mobility of the protein on SDS-polyacrylamide gel electrophoresis. It would therefore appear that distinct mechanisms exist for the stimulation of PKB by insulin and isoproterenol in rat fat cells

    Ecophysiology of coral reef primary producers across an upwelling gradient in the tropical central Pacific

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    © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Johnson, M. D., Fox, M. D., Kelly, E. L. A., Zgliczynski, B. J., Sandin, S. A., & Smith, J. E. Ecophysiology of coral reef primary producers across an upwelling gradient in the tropical central Pacific. Plos One, 15(2), (2020): e0228448, doi:10.1371/journal.pone.0228448.Upwelling is an important source of inorganic nutrients in marine systems, yet little is known about how gradients in upwelling affect primary producers on coral reefs. The Southern Line Islands span a natural gradient of inorganic nutrient concentrations across the equatorial upwelling region in the central Pacific. We used this gradient to test the hypothesis that benthic autotroph ecophysiology is enhanced on nutrient-enriched reefs. We measured metabolism and photophysiology of common benthic taxa, including the algae Porolithon, Avrainvillea, and Halimeda, and the corals Pocillopora and Montipora. We found that temperature (27.2–28.7°C) was inversely related to dissolved inorganic nitrogen (0.46–4.63 μM) and surface chlorophyll a concentrations (0.108–0.147 mg m-3), which increased near the equator. Contrary to our prediction, ecophysiology did not consistently track these patterns in all taxa. Though metabolic rates were generally variable, Porolithon and Avrainvillea photosynthesis was highest at the most productive and equatorial island (northernmost). Porolithon photosynthetic rates also generally increased with proximity to the equator. Photophysiology (maximum quantum yield) increased near the equator and was highest at northern islands in all taxa. Photosynthetic pigments also were variable, but chlorophyll a and carotenoids in Avrainvillea and Montipora were highest at the northern islands. Phycobilin pigments of Porolithon responded most consistently across the upwelling gradient, with higher phycoerythrin concentrations closer to the equator. Our findings demonstrate that the effects of in situ nutrient enrichment on benthic autotrophs may be more complex than laboratory experiments indicate. While upwelling is an important feature in some reef ecosystems, ancillary factors may regulate the associated consequences of nutrient enrichment on benthic reef organisms.This work was supported by funding from the Moore Family Foundation, the Gordon and Betty Moore Foundation, the Scripps family, and anonymous donors. The funders had no role in study design, data collection and analysis, or preparation of the manuscript

    Who trusts Twitter? Openness to ideas as a predictor of trust and interest in news of an international disaster presented in Twitter and traditional on-line journalism formats

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    Twitter is an increasingly utilized tool for communication during major events including natural disasters; however, there is little research investigating this topic and how individual differences might predict reactions to information in this medium. The current study seeks to understand how the personality trait of openness to ideas predicts perceptions of a Twitter source\u27s trustworthiness and interest relative to a journalistic source. Participants were randomly assigned to read a simulated account of a flood presented either as a Twitter account or a journalistic account and then rated perceptions of the sources. Results indicate that Twitter is trusted less than a journalistic account; however, moderator effects revealed that openness to ideas was positively correlated with trust in the Twitter condition but negatively correlated with trust in the journalistic format. The present study helps to clarify the role of personality in the process of consuming information on-line

    Hospital discharges for fever and neutropenia in pediatric cancer patients: United States, 2009

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    Background Fever and neutropenia (FN) is a common complication of pediatric cancer treatment, but hospital utilization patterns for this condition are not well described. Methods Data were analyzed from the Kids’ Inpatient Database (KID), an all-payer US hospital database, for 2009. Pediatric FN patients were identified using: age ≤19 years, urgent or emergent admit type, non-transferred, and a combination of ICD-9-CM codes for fever and neutropenia. Sampling weights were used to permit national inferences. Results Pediatric cancer patients accounted for 1.5 % of pediatric hospital discharges in 2009 (n = 110,967), with 10.1 % of cancer-related discharges meeting FN criteria (n = 11,261). Two-fifths of FN discharges had a “short length of stay” (SLOS) of ≤3 days, which accounted for approximately $65.5 million in hospital charges. Upper respiratory infection (6.0 %) and acute otitis media (AOM) (3.7 %) were the most common infections associated with SLOS. Factors significantly associated with SLOS included living in the Midwest region (OR = 1.65, 1.22–2.24) or West region (OR 1.54, 1.11–2.14) versus Northeast, having a diagnosis of AOM (OR = 1.39, 1.03–1.87) or viral infection (OR = 1.63, 1.18–2.25) versus those without those comorbidities, and having a soft tissue sarcoma (OR = 1.47, 1.05–2.04), Hodgkin lymphoma (OR = 2.33, 1.62–3.35), or an ovarian/testicular tumor (OR = 1.76, 1.05–2.95) compared with patients without these diagnoses. Conclusion FN represents a common precipitant for hospitalizations among pediatric cancer patients. SLOS admissions are rarely associated with serious infections, but contribute substantially to the burden of hospitalization for pediatric FN

    A modified Delphi study to gain consensus for a taxonomy to report and classify physical activity referral schemes (PARS)

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    Background: Physical Activity Referral Schemes (PARS), including exercise referral schemes, are a popular approach to health improvement, but understanding of effectiveness is limited by considerable heterogeneity in reporting and evaluation. We aimed to gain consensus for a PARS taxonomy as a comprehensive method for reporting and recording of such schemes. Methods: We invited 62 experts from PARS policy, research and practice to complete a modified Delphi study. In round one, participants rated the need for a PARS taxonomy, the suitability of three proposed classification levels and commented on proposed elements. In round two, participants rated proposed taxonomy elements on an 11-point Likert scale. Elements scoring a median of ≥7, indicating high agreement, were included in the final taxonomy. Results: Of those invited, 47 (75.8%) participated in round one, with high retention in round two (n = 43; 91.5%). 42 were UK-based, meaning the resultant taxonomy has been scrutinised for fit to the UK context only. The study gained consensus for a three-level taxonomy: Level 1: PARS classification (primary classification, provider, setting, conditions accepted [have or at risk of], activity type and funding). Level 2: scheme characteristics (staff structure, staff qualifications, behaviour change theories, behaviour change techniques, referral source, referrers, referral process, scheme duration, session frequency, session length, session times, session type, exit routes, action in case of non-attendance, baseline assessment, exit assessment, feedback to referrer and exclusion criteria) and Level 3: participant measures (demographics, monitoring and evaluation, and measures of change). Conclusion: Using a modified Delphi method, this study developed UK-based consensus on a PARS classification taxonomy. We encourage PARS practitioners and public health colleagues, especially those working with similar service models internationally, to test, refine and use this taxonomy to inform policy and practice

    Predicting and Manipulating Cardiac Drug Inactivation by the Human Gut Bacterium Eggerthella lenta

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    Despite numerous examples of the effects of the human gastrointestinal microbiome on drug efficacy and toxicity, there is often an incomplete understanding of the underlying mechanisms. Here, we dissect the inactivation of the cardiac drug digoxin by the gut Actinobacterium Eggerthella lenta. Transcriptional profiling, comparative genomics, and culture-based assays revealed a cytochrome-encoding operon up-regulated by digoxin, inhibited by arginine, absent in nonmetabolizing E. lenta strains, and predictive of digoxin inactivation by the human gut microbiome. Pharmacokinetic studies using gnotobiotic mice revealed that dietary protein reduces the in vivo microbial metabolism of digoxin, with significant changes to drug concentration in the serum and urine. These results emphasize the importance of viewing pharmacology from the perspective of both our human and microbial genomes.Chemistry and Chemical Biolog

    Knowledge Gaps in the Fetal to Neonatal Transition of Infants With a Congenital Diaphragmatic Hernia

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    Clinical research for infants born with a congenital diaphragmatic hernia (CDH) has until recently mainly focused on advances in prenatal and postnatal treatment. However, during the early perinatal transition period there are major physiological adaptations. For most infants these changes will happen uneventfully, but for CDH infants this marks the beginning of serious respiratory complications. In recent years, there is emerging evidence that the clinical management during the perinatal stabilization period in the delivery room may influence postnatal outcomes. Herein, we discuss major knowledge gaps and novel concepts that aim to optimize fetal to neonatal transition for infants with CDH. One such novel and interesting approach is performing resuscitation with an intact umbilical cord, the efficacy of this procedure is currently being investigated in several clinical trials. Furthermore, close evaluation of neonatal physiological parameters in the first 24 h of life might provide early clues concerning the severity of lung hypoplasia and the risk of adverse outcomes. We will provide an overview of trending concepts and discuss potential areas for future research

    The economic impact of diabetes through lost labour force participation on individuals and government: evidence from a microsimulation model

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    Background\ud \ud Diabetes is a costly and debilitating disease. The aim of the study is to quantify the individual and national costs of diabetes resulting from people retiring early because of this disease, including lost income; lost income taxation, increased government welfare payments; and reductions in GDP.\ud \ud Methods\ud \ud A purpose-built microsimulation model, Health&WealthMOD2030, was used to estimate the economic costs of early retirement due to diabetes. The study included all Australians aged 45–64 years in 2010 based on Australian Bureau of Statistics' Surveys of Disability, Ageing and Carers. A multiple regression model was used to identify significant differences in income, government welfare payments and taxation liabilities between people out of the labour force because of their diabetes and those employed full time with no chronic health condition.\ud \ud Results\ud \ud The median annual income of people who retired early because of their diabetes was significantly lower (AU11784)comparedtothoseemployedfulltimewithoutachronichealthconditionwhoreceivedalmostfivetimesmoreincome.Atthenationallevel,therewasalossofAU11 784) compared to those employed full time without a chronic health condition who received almost five times more income. At the national level, there was a loss of AU384 million in individual earnings by those with diabetes, an extra AU4millionspentingovernmentwelfarepayments,alossofAU4 million spent in government welfare payments, a loss of AU56 million in taxation revenue, and a loss of AU$1 324 million in GDP in 2010: all attributable to diabetes through its impact on labour force participation. Sensitivity analysis was used to assess the impact of different diabetes prevalence rates on estimates of lost income, lost income taxation, increased government welfare payments, and reduced GDP.\ud \ud Conclusions\ud \ud Individuals bear the cost of lost income in addition to the burden of the disease. The Government endures the impacts of lost productivity and income taxation revenue, as well as spending more in welfare payments. These national costs are in addition to the Government's direct healthcare costs

    Addressing Childhood Obesity in Georgia: Past, Present, and Future

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    Background: The Trust for America\u27s Health ranks Georgia 17th (16.5%) in the nation for childhood obesity prevalence among youth aged 10-17 years. Georgia has a long history of addressing childhood obesity at the state, regional, and local levels. This report outlines the historical efforts in childhood obesity in Georgia from the mid-1990’s to the present, summarizes current childhood obesity prevention and management strategies, and provides childhood obesity-related data relevant to the current strategies. Methods: Childhood obesity-related efforts in Georgia from 1996 to the present are documented, along with how these efforts led to the creation of Georgia Shape. The Georgia Shape Childhood Obesity Prevention Initiative, created by Governor Nathan Deal in 2012, established a statewide, 10-year plan of action to address childhood obesity. It convenes more than 125 governmental, philanthropic, academic and business community partners quarterly to work towards reducing the incidence of childhood obesity and overweight in Georgia. Evidence supporting the Georgia Shape objectives is described, along with current program and policy efforts that may allow achievement of its goal of having 69% of Georgia’s children in a healthy weight range by the year 2023. Results: Georgia\u27s obesity rate for low-income, 2- to 4-year old children has decreased. Over the 2013-2015 school years, there has been no increase in BMI at the population level among school age children and youth, and the percentage of boys and girls with increased aerobic capacity has improved. Future efforts should focus on middle and high school students; engaging and educating parents of young children; and state policies that support safe, daily physical activity and access to healthy, local food. Conclusions: A long history of childhood obesity activities in Georgia has led to a strategic plan of action, with contributions from many stakeholders. These efforts aim to reduce the prevalence of childhood overweight and obesity in Georgia over 10 years
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