569 research outputs found

    Cost-Effectiveness of Dabigatran versus Genotype-Guided Management of Warfarin Therapy for Stroke Prevention in Patients with Atrial Fibrillation

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    BACKGROUND: Dabigatran is associated with lower rate of stroke comparing to warfarin when anticoagulation control is sub-optimal. Genotype-guided warfarin dosing and management may improve patient-time in target range (TTR) and therefore affect the cost-effectiveness of dabigatran compared with warfain. We examined the cost-effectiveness of dabigatran versus warfarin therapy with genotype-guided management in patients with atrial fibrillation (AF). METHODOLOGY/PRINCIPAL FINDINGS: A Markov model was designed to compare life-long economic and treatment outcomes of dabigatran (110 mg and 150 mg twice daily), warfarin usual anticoagulation care (usual AC) with mean TTR 64%, and genotype-guided anticoagulation care (genotype-guided AC) in a hypothetical cohort of AF patients aged 65 years old with CHADS(2) score 2. Model inputs were derived from literature. The genotype-guided AC was assumed to achieve TTR = 78.9%, adopting the reported TTR achieved by warfarin service with good anticoagulation control in literature. Outcome measure was incremental cost per quality-adjusted life-year (QALY) gained (ICER) from perspective of healthcare payers. In base-case analysis, dabigatran 150 mg gained higher QALYs than genotype-guided AC (10.065QALYs versus 9.554QALYs) at higher cost (USD92,684 versus USD85,627) with ICER = USD13,810. Dabigatran 110 mg and usual AC gained less QALYs but cost more than dabigatran 150 mg and genotype-guided AC, respectively. ICER of dabigatran 150 mg versus genotype-guided AC would be >USD50,000 (and genotype-guided AC would be most cost-effective) when TTR in genotype-guided AC was >77% and utility value of warfarin was the same or higher than that of dabigatran. CONCLUSIONS/SIGNIFICANCE: The likelihood of genotype-guided anticoagulation service to be accepted as cost-effective would increase if the quality of life on warfarin and dabigatran therapy are compatible and genotype-guided service achieves high TTR (>77%)

    Identification and differentiation of Fasciola hepatica and Fasciola gigantica using a simple PCR-restriction enzyme method

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    Accurate morphological differentiation between the liver fluke species Fasciola hepatica and Fasciola gigantica is difficult. We evaluated PCR-restriction enzyme profiles of internal transcribed spacer 1 (ITS1) that could aid in their identification. Fifty F. hepatica and 30 F. gigantica specimens were collected from different hosts in three provinces of Iran. For DNA extraction, we crushed fragments of the worms between two glass slides as a new method to break down the cells. DNA from the crushed materials was then extracted with a conventional phenol-chloroform method and with the newly developed technique, commercial FTA cards. A primer pair was selected to amplify a 463-bp region of the ITS1 sequence. After sequencing 14 samples and in silico analysis, cutting sites of all known enzymes were predicted and TasI was selected as the enzyme that yielded the most informative profile. Crushing produced enough DNA for PCR amplification with both the phenol-chloroform and commercial FTA card method. The DNA extracted from all samples was successfully amplified and yielded a single sharp band of the expected size. Digestion of PCR products with TasI allowed us to distinguish the two species. In all samples, molecular identification was consistent with morphological identification. Our PCR-restriction enzyme profile is a simple, rapid and reliable method for differentiating F. hepatica and F. gigantica, and can be used for diagnostic and epidemiological purposes. © 2009 Elsevier Inc. All rights reserved

    Estimation of genetic parameters for productive and reproductive traits in Esfahan native chickens

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    Abstract The main aim of this research was to estimate the genetic and phenotypic parameters for productive and reproductive traits of Esfahan native chickens. Traits included body weights at hatch (BW1), 8 weeks of age (BW8), 12 weeks of age (BW12), and at sexual maturity (WSM)], age at sex maturity (ASM), egg number (EN), average egg weight (AEW) in the first 12 weeks of production, and egg production intensity (Eint). Data were collected over 13 generations (during 1998 to 2011) at the breeding center of Esfahan native chickens in Iran. Genetic parameters were estimated by a (bi)-univariate animal model using the restricted maximum likelihood (REML) procedure. Heritability estimates for body weight at different ages varied from 0.14±0.01 to 0.42±0.01. Estimated heritability for reproductive traits ranged from 0.12±0.01 for Eint to 0.36±0.01 for AEW. Estimates of heritability values were moderate but BW1 and AEW showed higher heritability values. Genetic correlation among body weight traits varied from 0.20±0.03 to 0.82±0.02. Fairly small negative Genetic correlation between body weight traits and egg traits (EN and Eint) was small (in the range of -0.22±0.05 to -0.03±0.03), while they showed positive and moderate genetic correlation with the average egg weight, ranging from 0.11±0.04 to 0.39±0.02. There was a low negative genetic correlation (-0.09±0.02) between egg number and egg weight. Therefore, during simultaneous selection for growth and egg production, probable reduction in egg production due to low reduction in egg number may be compared by increases in egg weight

    2,4-Bis(4-fluoro­phen­yl)-2,3-dihydro-1H-1,5-benzodiazepine

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    In the title compound, C21H16F2N2, the seven-membered 1,4-diazepine ring of the benzodiazepine ring system adopts a distorted-boat conformation. The benzene ring of this system makes dihedral angles of 18.6 (2) and 78.8 (2)° with those of two fluoro­phenyl substituents. In the crystal, inversion dimers linked by two weak C—H⋯F hydrogen bonds generate R 2 2(20) ring motifs. There are also weak N—H⋯π and C—H⋯π inter­actions

    Triple intussusception involving heterotopic pancreatic tissue: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Intussusception involving heterotopic pancreatic tissue is a rare condition where a portion of the bowel telescopes into an adjacent segment with intraluminal pancreatic tissue as the lead point. Cases of heterotopic pancreas are most often described in the upper intestinal tract, particularly the stomach.</p> <p>Case presentation</p> <p>We present the case of a five-month-old boy of Caucasian ethnicity suffering acute abdominal pain and vomiting with an abdominal mass in the upper right quadrant. Work-up including ultrasound scan confirmed the intussusception. Repeated attempts at radiological reduction and two laparoscopic procedures were performed within 24 hours, which eventually led to the diagnosis of a triple intussusception.</p> <p>Conclusion</p> <p>To our knowledge, such a case of triple intussusception involving isolated heterotopic pancreatic tissue is previously unreported.</p

    Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease

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    The hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates, called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present exclusively in neurons and thus that Lafora disease pathology derived from their accumulation in this cell population. However, recent evidence indicates that Lafora bodies are also present in astrocytes. To define the role of astrocytic Lafora bodies in Lafora disease pathology, we deleted glycogen synthase specifically from astrocytes in a mouse model of the disease (malinKO). Strikingly, blocking glycogen synthesis in astrocytes-thus impeding Lafora bodies accumulation in this cell type-prevented the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malinKO model. Conversely, mice that overaccumulate glycogen in astrocytes showed an increase in these markers. These results unveil the deleterious consequences of the deregulation of glycogen metabolism in astrocytes and change the perspective that Lafora disease is caused solely by alterations in neuron

    Extracellular Matrix Aggregates from Differentiating Embryoid Bodies as a Scaffold to Support ESC Proliferation and Differentiation

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    Embryonic stem cells (ESCs) have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM) components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB) as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively). Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared). The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications. © 2013 Goh et al
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