- 作者列表："Petzold A","Chua SYL","Khawaja AP","Keane PA","Khaw PT","Reisman C","Dhillon B","Strouthidis NG","Foster PJ","Patel PJ","UK Biobank Eye and Vision Consortium.
:The diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72 120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were followed. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIPL) complex and ganglion cell complex. Area under the receiver operating characteristic curve (AUROC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and co-morbidities. Cut-off levels were optimized by ROC and the Youden index. The prevalence of multiple sclerosis was 0.0023 [95% confidence interval (CI) 0.00229-0.00231]. Overall the discriminatory power of diagnosing multiple sclerosis with the IEPD AUROC curve (0.71, 95% CI 0.67-0.76) and IEAD (0.71, 95% CI 0.67-0.75) for the macular GCIPL complex were significantly higher if compared to the macular ganglion cell complex IEPD AUROC curve (0.64, 95% CI 0.59-0.69, P = 0.0017); IEAD AUROC curve (0.63, 95% CI 0.58-0.68, P < 0.0001) and macular RNFL IEPD AUROC curve (0.59, 95% CI 0.54-0.63, P < 0.0001); IEAD AUROC curve (0.55, 95% CI 0.50-0.59, P < 0.0001). Screening sensitivity levels for the macular GCIPL complex IEPD (4% cut-off) were 51.7% and for the IEAD (4 μm cut-off) 43.5%. Specificity levels were 82.8% and 86.8%, respectively. The number of co-morbidities was important. There was a stepwise decrease of the AUROC curve from 0.72 in control subjects to 0.66 in more than nine co-morbidities or presence of neuromyelitis optica spectrum disease. In the multivariable analyses greater age, diabetes mellitus, other eye disease and a non-white ethnic background were relevant confounders. For most interactions, the effect sizes were large (partial ω2 > 0.14) with narrow confidence intervals. In conclusion, the OCT macular GCIPL complex IEPD and IEAD may be considered as supportive measurements for multiple sclerosis diagnostic criteria in a young patient without relevant co-morbidity. The metric does not allow separation of multiple sclerosis from neuromyelitis optica. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed.
: 多发性硬化症的诊断是基于结合临床和旁.视网膜光学相干断层扫描 (OCT) 的潜在贡献已经被认识。我们测试的可行性OCT测量视网膜不对称诊断试验多发性硬化社区一级.在这项以社区为基础的研究中，共有72-120名受试者，我们使用2007年至2010年间在22个地点收集的英国生物样本库数据，研究了视网膜内OCT数据的眼间差异对多发性硬化症的诊断潜力。OCT报告和质量控制准则被跟踪了.间眼睛百分比差异 (IEPD) 间眼睛绝对差 (IEAD) 计算黄斑区视网膜神经纤维层 (RNFL) 厚度，神经节细胞内丛状层 (GCIPL) 配合物与神经节细胞复合体.受试者工作特征曲线下面积 (AUROC) 比较后进行单变量和多变量比较，以解释大范围的疾病和共病。通过ROC和Youden指数优化截止水平。多发性硬化的患病率为0.0023 [95% 可信区间 (CI) 0.00229-0.00231]。总的来说，区分能力诊断多发性硬化IEPD AUROC曲线 (0.71，95% CI 0.67-0.76) 和IEAD (0.71，95% CI 0.67-0.75) 的黄斑GCIPL复杂均明显高于对照组相比的黄斑区视网膜神经节细胞复合体IEPD AUROC曲线 (0.64，95% CI 0.59-0.69，P = 0.0017);IEAD AUROC曲线 (0.63，95% CI 0.58-0.68，P < 0.0001) 和黄斑区视网膜神经纤维层IEPD AUROC曲线 (0.59，95% CI 0.54-0.63，P < 0.0001); IEAD AUROC曲线 (0.55，95% CI 0.50-0.59，P < 0.0001).黄斑GCIPL复合体IEPD (4% 截止值) 的筛选灵敏度水平为51.7%，IEAD (4μm m截止值) 为43.5%。特异性水平分别为82.8% 和86.8%。合并疾病的数量很重要。AUROC曲线从对照受试者的0.72逐步降低至9种以上共病或存在视神经脊髓炎谱系疾病的0.66。在多变量分析中，较大年龄、糖尿病、其他眼病和非白人种族背景是相关的混杂因素。对于大多数相互作用，效应大小较大 (部分 ω2> 0.14)，置信区间较窄。总之，OCT黄斑GCIPL复合体IEPD和IEAD可以被认为是在没有相关合并症的年轻患者中多发性硬化诊断标准的支持性测量。该指标不允许将多发性硬化与视神经脊髓炎分开。视网膜OCT成像是准确的、快速的、非侵入性的、广泛可用的，并且因此可以帮助减少对侵入性和更昂贵的手术的需要。为了可行，需要更高的灵敏度和特异性水平。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.