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Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisticated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance. 相似文献
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Emily E. Brown Yi Zhen Joan Lee Marc K. Halushka Charles Steenbergen Nicole M. Johnson Johana Almansa 《Amyloid》2017,24(2):92-95
Amyloidosis is a group of conditions characterized by the accumulation of amyloid deposits in various tissues. Among these disorders, ATTR amyloidosis occurs either with or without a TTR pathogenic variant. Treatment for amyloidosis depends on the subtype, which is often identified through a tissue biopsy followed by liquid chromatography tandem mass spectrometry (LC–MS/MS). Genetic testing may be done to confirm these results for patients with ATTR amyloidosis; however, the necessity of genetic testing after LC–MS/MS has not been evaluated. A retrospective review identified 153 patients diagnosed with biopsy-proven ATTR amyloidosis, and 56 of these patients underwent both genetic testing and LC–MS/MS. LC–MS/MS and proteomics correctly reported the mutant peptide and heterozygosity in 47/56 (84%) cases. It failed to identify two individuals who were homozygous for the ATTRV122I mutation and failed to detect the following mutations in six other individuals: ATTRA19D, ATTRF44L, ATTRT60A, ATTRI68L and ATTRV122I. Therefore, LC–MS/MS is not sufficient to rule out a pathogenic mutation in cases of ATTR amyloid, and genetic testing should be performed in most cases of ATTR amyloidosis. Correct recognition of hereditary ATTR amyloidosis is important for estimating prognosis, proper familial counselling and guiding use of therapies, such as liver transplantation. 相似文献
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Ischaemia of the extremity from the use of a tourniquet and the subsequent reperfusion contribute to the release of reactive oxygen species. This release may result in injury to remote organs. We performed a qualitative systematic review exploring the interventions used to prevent tourniquet‐related oxidative damage in adults undergoing orthopaedic surgery, and the possible relationship between biochemical oxidative stress markers and postoperative clinical outcomes. Seventeen randomised controlled studies were included in the qualitative synthesis. Most trials were of low methodological quality and only two studies reported postoperative clinical outcomes. Nine studies tested anaesthetics (propofol, dexmedetomidine, ketamine, and spinal anaesthesia); four studies tested antioxidants (N‐acetyl‐cysteine, vitamin C, and mannitol); and four studies tested ischaemic pre‐conditioning. Fifteen studies showed a significant reduction in biochemical oxidative stress markers. We conclude that propofol and ischaemic pre‐conditioning, in particular, appear to show some benefit at reducing oxidative stress following operations under tourniquet; the correlation between a reduction in oxidative stress and postoperative clinical outcomes should be further investigated in the future. 相似文献
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Steven Stanos Charles Argoff Daniel J. Clauw Yvonne D’Arcy Sean Donevan 《Postgraduate medicine》2016,128(5):502-515
Chronic pain substantially impacts patient function and quality of life and is a burden to society at large in terms of increased health care utilization and loss of productivity. As a result, there is an increasing recognition of chronic pain as a public health crisis. However, there remains wide variability in clinical practices related to the prevention, assessment, and treatment of chronic pain. Certain fundamental aspects of chronic pain are often neglected including the contribution of the psychological, social, and contextual factors associated with chronic pain. Also commonly overlooked is the importance of understanding the likely neurobiological mechanism(s) of the presenting pain and how they can guide treatment selection. Finally, physicians may not recognize the value of using electronic medical records to systematically capture data on pain and its impact on mood, function, and sleep. Such data can be used to monitor onset and maintenance of treatments effects at the patient level and evaluate costs at the systems level. In this review we explain how these factors play a critical role in the development of a coordinated, evidence-based treatment approach tailored to meet specific needs of the patient. We also discuss some practical approaches and techniques that can be implemented by clinicians in order to enhance the assessment and management of individuals with chronic pain in primary care settings. 相似文献
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