1,040 research outputs found

    Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

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    <p>Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.</p> <p>Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).</p> <p>Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.</p> <p>Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.</p&gt

    In vitro and in vivo evaluation of human adenovirus type 49 as a vector for therapeutic applications

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    The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-exist-ing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile— remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a rela-tively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications

    Autoantibodies against a 43 KDa Muscle Protein in Inclusion Body Myositis

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    BACKGROUND: Inclusion body myositis (IBM) is a poorly understood and refractory autoimmune muscle disease. Though widely believed to have no significant humoral autoimmunity, we sought to identify novel autoantibodies with high specificity for this disease. METHODOLOGY/PRINCIPAL FINDINGS: Plasma autoantibodies from 65 people, including 25 with IBM, were analyzed by immunoblots against normal human muscle. Thirteen of 25 (52%) IBM patient samples recognized an approximately 43 kDa muscle protein. No other disease (N = 25) or healthy volunteer (N = 15) samples recognized this protein. CONCLUSIONS: Circulating antibodies against a 43-kDa muscle autoantigen may lead to the discovery of a novel biomarker for IBM. Its high specificity for IBM among patients with autoimmune myopathies furthermore suggests a relationship to disease pathogenesis

    Quantitative trait loci for bone traits segregating independently of those for growth in an F-2 broiler X layer cross

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    An F broiler-layer cross was phenotyped for 18 skeletal traits at 6, 7 and 9 weeks of age and genotyped with 120 microsatellite markers. Interval mapping identified 61 suggestive and significant QTL on 16 of the 25 linkage groups for 16 traits. Thirty-six additional QTL were identified when the assumption that QTL were fixed in the grandparent lines was relaxed. QTL with large effects on the lengths of the tarsometatarsus, tibia and femur, and the weights of the tibia and femur were identified on GGA4 between 217 and 249 cM. Six QTL for skeletal traits were identified that did not co-locate with genome wide significant QTL for body weight and two body weight QTL did not coincide with skeletal trait QTL. Significant evidence of imprinting was found in ten of the QTL and QTL x sex interactions were identified for 22 traits. Six alleles from the broiler line for weight- and size-related skeletal QTL were positive. Negative alleles for bone quality traits such as tibial dyschondroplasia, leg bowing and tibia twisting generally originated from the layer line suggesting that the allele inherited from the broiler is more protective than the allele originating from the layer

    Reliability of Community Health Worker Collected Data for Planning and Policy in a Peri-Urban Area of Kisumu, Kenya

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    A general introduction of this article is as follows: Reliable and timely health information is an essential foundation of public health action and health systems strengthening, both nationally and internationally (Aqil et al. in Health Policy Plan 24(3): 217–228, 2009; Bradshaw et al. in initial burden of disease estimates for South Africa, 2000. South African Medical Research Council, Cape Town, 2003). The need for sound information is especially urgent in the case of emergent diseases and other acute health threats, where rapid awareness, investigation and response can save lives and prevent broader national outbreaks and even global pandemics (Aqil et al. in Health Policy Plan 24(3): 217–228, 2009). The government of Kenya, through the ministry of public health and sanitation has rolled out the community health strategy as a way of improving health care at the household level. This involves community health workers collecting health status data at the household level, which is then used for dialogue at all the levels to inform decisions and actions towards improvement in health status. A lot of health interventions have involved the community health workers in reaching out to the community, hence successfully implementing these health interventions. Large scale involvement of community health workers in government initiatives and most especially to collect health data for use in the health systems has been minimal due to the assumption that the data may not be useful to the government, because its quality is uncertain. It was therefore necessary that the validity and reliability of the data collected by community health workers be determined, and whether this kind of data can be used for planning and policy formulation for the communities from which it is collected. This would go a long way to settle speculation on whether the data collected by these workers is valid and reliable for use in determining the health status, its causes and distribution, of a community. Our general objective of this article is to investigate the validity and reliability of Community Based Information, and we deal with research question “What is the reliability of data collected at the Community level by Community health workers?”. The methods which we use to find an reliable answer to this question is “Ten percent of all households visited by CHWs for data collection were recollected by a technically trained team. Test/retest method was applied to the data to establish reliability. The Kappa score, sensitivity, specificity and positive predictive values were also used to measure reliability”. Finally our findings are as follows: Latrine availability and Antenatal care presented good correspondence between the two sets of data. This was also true for exclusive breast feeding indicator. Measles immunization coverage showed less consistency than the rest of the child health indicators. At last we conclude and recommend that CHWs can accurately and reliably collect household data which can be used for health decisions and actions especially in resource poor settings where other approaches to population based data are too expensive

    Size and shape constancy in consumer virtual reality

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    With the increase in popularity of consumer virtual reality headsets, for research and other applications, it is important to understand the accuracy of 3D perception in VR. We investigated the perceptual accuracy of near-field virtual distances using a size and shape constancy task, in two commercially available devices. Participants wore either the HTC Vive or the Oculus Rift and adjusted the size of a virtual stimulus to match the geometric qualities (size and depth) of a physical stimulus they were able to refer to haptically. The judgments participants made allowed for an indirect measure of their perception of the egocentric, virtual distance to the stimuli. The data show under-constancy and are consistent with research from carefully calibrated psychophysical techniques. There was no difference in the degree of constancy found in the two headsets. We conclude that consumer virtual reality headsets provide a sufficiently high degree of accuracy in distance perception, to allow them to be used confidently in future experimental vision science, and other research applications in psychology
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