2,834 research outputs found
DB2 EVALUATION OF AGREEMENT BETWEEN INTERNET-BASED SELF- AND PROXY-REPORTED HEALTH CARE UTILIZATION AND ADMINISTRATIVE HEALTH CARE CLAIMS
Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)
The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80β85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery
Dietary elimination of children with food protein induced gastrointestinal allergy β micronutrient adequacy with and without a hypoallergenic formula?
Background:
The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake.
Method:
A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS).
Results:
One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS.
Conclusion:
This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies
Differences in the signaling pathways of Ξ±1A- and Ξ±1B-adrenoceptors are related to different endosomal targeting
Aims: To compare the constitutive and agonist-dependent endosomal trafficking of Ξ±1A- and Ξ±1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype.
Methods: Using CypHer5 technology and VSV-G epitope tagged Ξ±1A- and Ξ±1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot).
Results and Conclusions: Constitutive as well as agonist-induced trafficking of Ξ±1A and Ξ±1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: Ξ±1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to Ξ²-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. Ξ±1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-Ξ²-cyclodextrin
Holographic Vitrification
We establish the existence of stable and metastable stationary black hole
bound states at finite temperature and chemical potentials in global and planar
four-dimensional asymptotically anti-de Sitter space. We determine a number of
features of their holographic duals and argue they represent structural
glasses. We map out their thermodynamic landscape in the probe approximation,
and show their relaxation dynamics exhibits logarithmic aging, with aging rates
determined by the distribution of barriers.Comment: 100 pages, 25 figure
Effectiveness of initiating treatment with valsartan/hydrochlorothiazide in patients with stage-1 or stage-2 hypertension
This prospective, 6-week, multicenter, double-blind study examined the benefits of initiating treatment with combination valsartan/hydrochlorothiazide (HCTZ) compared with initial valsartan monotherapy for 648 patients with stage-1 or stage-2 hypertension (age=52.6Β±10 years; 54% male; baseline blood pressure (BP)=161/98βmmβHg, 32% stage 1). Patients were randomized to valsartan 80βmg (V-low), valsartan 160βmg (V-high) or valsartan/HCTZ 160/12.5βmg (V/HCTZ), and electively titrated after weeks 2 and 4 to the next dosage level (maximum dose valsartan/HCTZ 160/25βmg) if BP remained >140/90βmmβHg. At end of the study, patients initiated with V/HCTZ required less titration steps compared with the initial valsartan monotherapy groups (63 vs 86% required titration by study end, respectively) and reached the target BP goal of <140/90βmmβHg in a shorter period of time (2.8 weeks) (P<0.0001) vs V-low (4.3 weeks) and V-high (3.9 weeks). Initial combination therapy was also associated with higher BP control rates and greater reductions in both systolic and diastolic BP from baseline (63%, β27.7Β±13/β15.1Β±8βmmβHg) compared with V-low (46%, β21.2Β±13/β11.4Β±8βmmβHg, P<0.0001) or V-high (51%, β24.0Β±13/β12.0Β±10βmmβHg, P<0.01). Overall and drug-related AEs were mild to moderate and were similar between V/HCTZ (53.1 and 14.1%, respectively) and the two monotherapy groups, V-low (50.5 and 13.8%) and V-high (50.7 and 11.8%). In conclusion, initiating therapy with a combination of valsartan and low-dose HCTZ results in early, improved BP efficacy with similar tolerability as compared with starting treatment with a low or higher dose of valsartan for patients with stage-1 and stage-2 hypertension
MR imaging in sports-related glenohumeral instability
Sports-related shoulder pain and injuries represent a common problem. In this context, glenohumeral instability is currently believed to play a central role either as a recognized or as an unrecognized condition. Shoulder instabilities can roughly be divided into traumatic, atraumatic, and microtraumatic glenohumeral instabilities. In athletes, atraumatic and microtraumatic instabilities can lead to secondary impingement syndromes and chronic damage to intraarticular structures. Magnetic resonance (MR) arthrography is superior to conventional MR imaging in the diagnosis of labro-ligamentous injuries, intrinsic impingement, and SLAP (superior labral anteroposterior) lesions, and thus represents the most informative imaging modality in the overall assessment of glenohumeral instability. This article reviews the imaging criteria for the detection and classification of instability-related injuries in athletes with special emphasis on the influence of MR findings on therapeutic decisions
B-cell lymphoma in retrieved femoral heads: a long term follow up
<p>Abstract</p> <p>Background</p> <p>A relatively high incidence of pathological conditions in retrieved femoral heads, including a group of patients having low grade B-cell lymphoma, has been described before. At short term follow up none of these patients with low-grade B-cell lymphoma showed evidence of systemic disease. However, the long term follow up of these patients is not known.</p> <p>Methods</p> <p>From November 1994 up to and including December 2005 we screened all femoral heads removed at the time of primary total hip replacement histopathologically and included them in the bone banking protocol according to the guidelines of the American Associations of Tissue Banks (AATB) and the European Association of Musculo-Skeletal Transplantation (EAMST). We determined the percentage of B-cell lymphoma in all femoral heads and in the group that fulfilled all criteria of the bone banking protocol and report on the long-term follow-up.</p> <p>Results</p> <p>Of 852 femoral heads fourteen (1.6%) were highly suspicious for low-grade B-cell lymphoma. Of these 852 femoral heads, 504 were eligible for bone transplantation according to the guidelines of the AATB and the EAMST. Six femoral heads of this group of 504 were highly suspicious for low-grade B-cell lymphoma (1.2%). At long term follow up two (0.2%) of all patients developed systemic malignant disease and one of them needed medical treatment for her condition.</p> <p>Conclusion</p> <p>In routine histopathological screening we found variable numbers of low-grade B-cell lymphoma throughout the years, even in a group of femoral heads that were eligible for bone transplantation. Allogenic transmission of malignancy has not yet been reported on, but surviving viruses are proven to be transmissible. Therefore, we recommend the routine histopathological evaluation of all femoral heads removed at primary total hip arthroplasty as a tool for quality control, whether the femoral head is used for bone banking or not.</p
Maintaining quality of health services after abolition of user fees: A Uganda case study
<p>Abstract</p> <p>Background</p> <p>It has been argued that quality improvements that result from user charges reduce their negative impact on utilization especially of the poor. In Uganda, because there was no concrete evidence for improvements in quality of care following the introduction of user charges, the government abolished user fees in all public health units on 1<sup>st </sup>March 2001. This gave us the opportunity to prospectively study how different aspects of quality of care change, as a country changes its health financing options from user charges to free services, in a developing country setting. The outcome of the study may then provide insights into policy actions to maintain quality of care following removal of user fees.</p> <p>Methods</p> <p>A population cohort and representative health facilities were studied longitudinally over 3 years after the abolition of user fees. Quantitative and qualitative methods were used to obtain data. Parameters evaluated in relation to quality of care included availability of drugs and supplies and; health worker variables.</p> <p>Results</p> <p>Different quality variables assessed showed that interventions that were put in place were able to maintain, or improve the technical quality of services. There were significant increases in utilization of services, average drug quantities and stock out days improved, and communities reported health workers to be hardworking, good and dedicated to their work to mention but a few. Communities were more appreciative of the services, though expectations were lower. However, health workers felt they were not adequately motivated given the increased workload.</p> <p>Conclusion</p> <p>The levels of technical quality of care attained in a system with user fees can be maintained, or even improved without the fees through adoption of basic, sustainable system modifications that are within the reach of developing countries. However, a trade-off between residual perceptions of reduced service quality, and the welfare gains from removal of user fees should guide such a policy change.</p
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