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951.
952.
Joanna L. Elson Helen Swalwell Emma L. Blakely Robert McFarland Robert W. Taylor Doug M. Turnbull 《Human mutation》2009,30(11):E984-E992
Mitochondrial transfer RNA (mt-tRNA) mutations are the commonest mitochondrial (mtDNA) mutations to cause human disease. The majority of mt-tRNA mutations are heteroplasmic and while some exhibit maternal transmission within families, many others are only seen as sporadic mutations. Using the available clinical, biochemical and genetic data from published pathogenic mt-tRNA mutations, we have explored several different factors thought to influence the transmission of mt-tRNA mutations. Our data show that the most important factor in predicting whether a mutation is transmitted to offspring is whether the mt-tRNA mutation is selected against in a rapidly replicating tissue such as blood. This suggests that those mt-tRNA mutations which exert a major phenotype in dividing cells are unlikely to be inherited. This is entirely compatible with recent observations on the mitochondrial genetic bottleneck in early development and has important implications for families with mt-tRNA disease. © 2009 Wiley-Liss, Inc. 相似文献
953.
Reddy MC Paul SA Abraham J McNeese M DeFlitch C Yen J 《International journal of medical informatics》2009,78(4):259-269
OBJECTIVE: The purpose of this study is to identify the major challenges to coordination between emergency department (ED) teams and emergency medical services (EMS) teams. DESIGN: We conducted a series of focus groups involving both ED and EMS team members using a crisis scenario as the basis of the focus group discussion. We also collected organizational workflow data. RESULTS: We identified three major challenges to coordination between ED and EMS teams including ineffectiveness of current information and communication technologies, lack of common ground, and breakdowns in information flow. DISCUSSION: The three challenges highlight the importance of designing systems from socio-technical perspective. In particular, these inter-team coordination systems must support socio-technical issues such as awareness, context, and workflow between the two teams. 相似文献
954.
955.
Andrew M McMillan Karl B Landorf Joanna T Barrett Hylton B Menz Adam R Bird 《Journal of foot and ankle research》2009,2(1):1-11
Approximately one-quarter of the population are affected by foot pain at any given time. It is often disabling and can impair mood, behaviour, self-care ability and overall quality of life. Currently, the nature and mechanism underlying many types of foot pain is not clearly understood. Here we comprehensively review the literature on foot pain, with specific reference to its definition, prevalence, aetiology and predictors, classification, measurement and impact. We also discuss the complexities of foot pain as a sensory, emotional and psychosocial experience in the context of clinical practice, therapeutic trials and the placebo effect. A deeper understanding of foot pain is needed to identify causal pathways, classify diagnoses, quantify severity, evaluate long term implications and better target clinical intervention. 相似文献
956.
We present an interesting and unusual case of an acutely calcified pin-site infection hematoma mimicking a displaced cartilaginous medial epicondyle, in a child with a Gartland type III fracture. The treatment of such pathology could be confusing and may interfere with the correct clinical decision-making process. To our knowledge, this is the first presentation of such a case. 相似文献
957.
958.
Beta-thalassaemia is an inherited disease caused by defective synthesis of the beta-globin chain of haemoglobin, leading to an imbalance in globin chains. Excess alpha-globin chains precipitate in erythroid progenitor cells resulting in cell death, ineffective erythropoiesis and severe anaemia. Decreased alpha-globin synthesis leads to milder symptoms, exemplified by individuals who co-inherit alpha-thalassaemia and beta-thalassaemia. In this study, we set out to investigate whether co-inheritance of alpha- and beta-thalassaemia in mice leads to reduced anaemia. Heterozygous murine beta-globin knockout (KO) mice (beta+/-) which display severe anaemia were mated with heterozygous alpha-globin KO mice (alpha++/--). The resulting progeny were genotyped and classed as wild-type WT (alpha++/++;beta+/+), heterozygous alpha-KO (alpha++/--;beta+/+), heterozygous beta-KO (alpha++/++;beta+/-) or double heterozygous (DH) alpha-KO/beta-KO (alpha++/--;beta+/-). Mice were bled and full blood examinations (FBE) performed. FBE results for heterozygous beta-KO mice (beta+/-) showed marked reductions in haemoglobin and haematocrit levels and significant increases in red cell distribution widths and reticulocyte counts compared to WT mice. In contrast, FBE results for DH alpha-KO/beta-KO mice showed near normal red blood cell indices. These results indicate that reduction of alpha-globin expression leads to correction of the globin chain imbalance in beta-thalassaemic mice and therefore an improved phenotype. The analysis of DH alpha-KO/beta-KO mice leads to the following conclusions: (1) co-inheritance of alpha- and beta-thalassaemia in mice improves the thalassaemic phenotype, identical to the situation in humans; (2) the heterozygous murine beta-globin KO mouse model is a suitable in vivo model to test for therapeutic knockdown of alpha-globin. 相似文献
959.
Half-truths and selective memory: Interferon gamma, CD4(+) T cells and protective memory against tuberculosis 总被引:1,自引:0,他引:1
Efforts to develop a new, more effective vaccine for tuberculosis have been hampered by a lack of understanding of what constitutes a protective memory immune response. While interferon gamma production by CD4(+) T cells after vaccination is commonly used as a surrogate of protective memory immunity, its use in this regard appears to have little predictive value. We argue that this is due to the different requirements for interferon gamma-mediated protection in the primary response versus the memory recall response. In this review, we present evidence that suggests memory CD4(+) T cells can protect against tuberculosis in the absence of interferon gamma, and discuss potential mechanisms that may be involved such as IL-17 and regulatory T cells. A comprehensive understanding of the requirements for protective memory immunity to tuberculosis is essential for the development of an effective vaccine. 相似文献
960.
Lynch J Mead G Greig C Young A Lewis S Sharpe M 《Journal of psychosomatic research》2007,63(5):539-544
OBJECTIVE: While fatigue after stroke is a common problem, it has no generally accepted definition. Our aim was to develop a case definition for post-stroke fatigue and to test its psychometric properties. METHODS: A case definition with face validity and an associated structured interview was constructed. After initial piloting, the feasibility, reliability (test-retest and inter-rater) and concurrent validity (in relation to four fatigue severity scales) were determined in 55 patients with stroke. RESULTS: All participating patients provided satisfactory answers to all the case definition probe questions demonstrating its feasibility For test-retest reliability, kappa was 0.78 (95% CI, 0.57-0.94, P<.01) and for inter-rater reliability kappa was 0.80 (95% CI, 0.62-0.99, P<.01). Patients fulfilling the case definition also had substantially higher fatigue scores on four fatigue severity scales (P<.001) indicating concurrent validity. CONCLUSION: The proposed case definition is feasible to administer and reliable in practice, and there is evidence of concurrent validity. It requires further evaluation in different settings. 相似文献