713 research outputs found

    Altered function of ventral striatum during reward-based decision making in old age

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    Normal aging is associated with a decline in different cognitive domains and local structural atrophy as well as decreases in dopamine concentration and receptor density. To date, it is largely unknown how these reductions in dopaminergic neurotransmission affect human brain regions responsible for reward-based decision making in older adults. Using a learning criterion in a probabilistic object reversal task, we found a learning stage by age interaction in the dorsolateral prefrontal cortex (dlPFC) during decision making. While young adults recruited the dlPFC in an early stage of learning reward associations, older adults recruited the dlPFC when reward associations had already been learned. Furthermore, we found a reduced change in ventral striatal BOLD signal in older as compared to younger adults in response to high probability rewards. Our data are in line with behavioral evidence that older adults show altered stimulus–reward learning and support the view of an altered fronto-striatal interaction during reward-based decision making in old age, which contributes to prolonged learning of reward associations

    Correlação da pressĂŁo arterial com a circunferĂȘncia da cintura em escolares

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    Introdução: BERGMAN (2010) afirma que indivĂ­duos com valores de CC (circunferĂȘncia da cintura) elevados se comparados aqueles com valores adequados tĂȘm maior chance de apresentar fatores de rico para doenças cardiovasculares. Objetivo: Avaliar a possĂ­vel correlação da pressĂŁo arterial com a circunferĂȘncia da cintura em escolares. Materiais e MĂ©todos: Este estudo foi transversal, realizado com a força de preensĂŁo manual obtida com dinamĂŽmetro mecĂąnico manual (SAEHAN CORPORATION), em 30 alunos de ambos os sexos, de 08 a 10 anos de idade de um Centro Educacional da cidade satĂ©lite Estrutural. Foram mensurados o peso (kg), a estatura (cm), circunferĂȘncia do pescoço (cm), cintura (cm) e quadril (cm). Resultados: Apesar de serem realizados vĂĄrios testes, a força de preensĂŁo manual obteve correlação positiva e significativa apenas com a PAS e com a circunferĂȘncia da cintura (r=0,46 e p = 0,01). No entanto para a PAD a correlação foi baixa e nĂŁo significativa (r = 0,25 e p = 0,21). ConsideraçÔes finais: A circunferĂȘncia da cintura apresentou correlação positiva e significativa com a PAS, e correlação positiva baixa nĂŁo significativa com a PAD, o que parece demonstrar que ao aumentar a circunferĂȘncia da cintura, tambĂ©m aumentaria PAS e PAD

    Highly Constrained Intergenic Drosophila Ultraconserved Elements Are Candidate ncRNAs

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    Eukaryotes contain short (∌80–200 bp) regions that have few or no substitutions among species that represent hundreds of millions of years of evolutionary divergence. These ultraconserved elements (UCEs) are candidates for containing essential functions, but their biological roles remain largely unknown. Here, we report the discovery and characterization of UCEs from 12 sequenced Drosophilaspecies. We identified 98 elements ≄80 bp long with very high conservation across the Drosophila phylogeny. Population genetic analyses reveal that these UCEs are not present in mutational cold spots. Instead we infer that they experience a level of selective constraint almost 10-fold higher compared with missense mutations in protein-coding sequences, which is substantially higher than that observed previously for human UCEs. About one-half of these Drosophila UCEs overlap the transcribed portion of genes, with many of those that are within coding sequences likely to correspond to sites of ADAR-dependent RNA editing. For the remaining UCEs that are in nongenic regions, we find that many are potentially capable of forming RNA secondary structures. Among ten chosen for further analysis, we discovered that the majority are transcribed in multiple tissues of Drosophila melanogaster. We conclude that Drosophilaspecies are rich with UCEs and that many of them may correspond to novel noncoding RNAs

    Late diagnosis of abdominal aortic aneurysms substantiates underutilization of abdominal aortic aneurysm screening for Medicare beneficiaries

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    ObjectiveAbdominal aortic aneurysm (AAA) screening remains largely underutilized in the U.S., and it is likely that the proportion of patients with aneurysms requiring prompt treatment is much higher compared with well-screened populations. The goals of this study were to determine the proportion of AAAs that required prompt repair after diagnostic abdominal imaging for U.S. Medicare beneficiaries and to identify patient and hospital factors contributing to early vs late diagnosis of AAA.MethodsData were extracted from Medicare claims records for patients at least 65 years old with complete coverage for 2 years who underwent intact AAA repair from 2006 to 2009. Preoperative ultrasound and computed tomography was tabulated from 2002 to repair. We defined early diagnosis of AAA as a patient with a time interval of greater than 6 months between the first imaging examination and the index procedure, and late diagnosis as patients who underwent the index procedure within 6 months of the first imaging examination.ResultsOf 17,626 patients who underwent AAA repair, 14,948 met inclusion criteria. Mean age was 77.5 ± 6.1 years. Early diagnosis was identified for 60.6% of patients receiving AAA repair, whereas 39.4% were repaired after a late diagnosis. Early diagnosis rates increased from 2006 to 2009 (59.8% to 63.4%; P < .0001) and were more common for intact repair compared with repair after rupture (62.9% vs 35.1%; P < .0001) and for women compared with men (66.3% vs 59.0%; P < .0001). On multivariate analysis, repair of intact vs ruptured AAAs (odds ratio, 3.1; 95% confidence interval, 2.7-3.6) and female sex (odds ratio, 1.4; 95% confidence interval, 1.3-1.5) remained the strongest predictors of surveillance. Although intact repairs were more likely to be diagnosed early, over one-third of patients undergoing repair for ruptured AAAs received diagnostic abdominal imaging greater than 6 months prior to surgery.ConclusionsDespite advances in screening practices, significant missed opportunities remain in the U.S. Medicare population for improving AAA care. It remains common for AAAs to be diagnosed when they are already at risk for rupture. In addition, a significant proportion of patients with early imaging rupture prior to repair. Our findings suggest that improved mechanisms for observational management are needed to ensure optimal preoperative care for patients with AAAs

    Ciliary Polycystin-2 Is a Mechanosensitive Calcium Channel Involved in Nitric Oxide Signaling Cascades

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    Cardiovascular complications such as hypertension are a continuous concern in patients with autosomal dominant polycystic kidney disease (ADPKD). The PKD2 encoding for polycystin-2 is mutated in ≈15% of ADPKD patients. Here, we show that polycystin-2 is localized to the cilia of mouse and human vascular endothelial cells. We demonstrate that the normal expression level and localization of polycystin-2 to cilia is required for the endothelial cilia to sense fluid shear stress through a complex biochemical cascade, involving calcium, calmodulin, Akt/PKB, and protein kinase C. In response to fluid shear stress, mouse endothelial cells with knockdown or knockout of Pkd2 lose the ability to generate nitric oxide (NO). Consistent with mouse data, endothelial cells generated from ADPKD patients do not show polycystin-2 in the cilia and are unable to sense fluid flow. In the isolated artery, we further show that ciliary polycystin-2 responds specifically to shear stress and not to mechanical stretch, a pressurized biomechanical force that involves purinergic receptor activation. We propose a new role for polycystin-2 in transmitting extracellular shear stress to intracellular NO biosynthesis. Thus, aberrant expression or localization of polycystin-2 to cilia could promote high blood pressure because of inability to synthesize NO in response to an increase in shear stress (blood flow)

    Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome.

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    BackgroundThe choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available.ObjectiveTo determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS.DesignDecision-analytic model.Data sourcesPublished literature, Medicare claims, and life tables.Target populationPatients having percutaneous coronary intervention for ACS.Time horizonLifetime.PerspectiveSocietal.InterventionFive strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel.Outcome measuresDirect medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs).Results of base-case analysisThe clopidogrel strategy produced179301incostsand9.428QALYs.Genotypingwithprasugrelwassuperiortoprasugrelalone,withanICERof179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of 35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel (30200perQALYrelativetoclopidogrel).Ticagrelorwasthemosteffectivestrategy(30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy(52 600 per QALY relative to genotyping with ticagrelor).Results of sensitivity analysisStronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor.LimitationNo randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor.ConclusionGenotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings

    Categorization of compensatory motions in transradial myoelectric prosthesis users

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    Background: Prosthesis users perform various compensatory motions to accommodate for the loss of the hand and wrist as well as the reduced functionality of a prosthetic hand. Objectives: Investigate different compensation strategies that are performed by prosthesis users. Study Design: Comparative analysis Methods: 20 able-bodied subjects and 4 prosthesis users performed a set of bimanual activities. Movements of the trunk and head were recorded using a motion capture system, and a digital video recorder. Clinical motion angles were calculated to assess the compensatory motions made by the prosthesis users. The video recording also assisted in visually identifying the compensations. Results: Compensatory motions by the prosthesis users were evident in the tasks performed (slicing and stirring activities) as compared to the benchmark of able-bodied subjects. Compensations took the form of a measured increase in range of motion, an observed adoption of a new posture during task execution, and pre-positioning of items in the workspace prior to initiating a given task. Conclusion: Compensatory motions were performed by prosthesis users during the selected tasks. These can be categorized into three different types of compensations

    Strategic green infrastructure planning in Germany and the UK: a transnational evaluation of the evolution of urban greening policy and practice

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    The evolution of Green Infrastructure (GI) planning has varied dramatically between nations. Although a grounded set of principles are recognized globally, there is increasing variance in how these are implemented at a national and sub-national level. To investigate this the following paper presents an evaluation of how green infrastructure has been planned for in England and Germany illustrating how national policy structures facilitate variance in application. Adopting an evaluative framework linked to the identification of GI, its development and monitoring/ feedback the paper questions the impacts on delivery of intersecting factors including terminology, spatial distribution and functionality on effective GI investment. This process reviews how changing policy structures have influenced the framing of green infrastructure policy, and subsequent impact this has on the delivery of green infrastructure projects
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