- 作者列表："Arnaldi D","Chincarini A","Hu MT","Sonka K","Boeve B","Miyamoto T","Puligheddu M","De Cock VC","Terzaghi M","Plazzi G","Tachibana N","Morbelli S","Rolinski M","Dusek P","Lowe V","Miyamoto M","Figorilli M","Verbizier D","Bossert I","Antelmi E","Meli R","Barber TR","Trnka J","Miyagawa T","Serra A","Pizza F","Bauckneht M","Bradley KM","Zogala D","McGowan DR","Jordan L","Manni R","Nobili F
:This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used to identify the baseline features predicting phenoconversion to parkinsonism or dementia. After quality check of the data, 263 iRBD patients (67.6 ± 7.3 years, 229 males) and 243 control subjects (67.2 ± 10.1 years, 110 males) were analysed. Fifty-two (20%) patients developed a synucleinopathy after average follow-up of 2 years. The best combination of risk factors was putamen dopaminergic dysfunction of the most affected hemisphere on imaging, defined as the lower value between either putamina (P < 0.000001), constipation, (P < 0.000001) and age over 70 years (P = 0.0002). Combined features obtained from the generalized logistic regression achieved a hazard ratio of 5.71 (95% confidence interval 2.85-11.43). Bayesian classifier suggested that patients with higher Mini-Mental State Examination score and lower caudate SBR asymmetry were more likely to develop parkinsonism, while patients with the opposite pattern were more likely to develop dementia. This study shows that iRBD patients older than 70 with constipation and reduced nigro-putaminal dopaminergic function are at high risk of short-term phenoconversion to an overt synucleinopathy, providing an effective stratification approach for future neuroprotective trials. Moreover, we provide cut-off values for the significant predictors of phenoconversion to be used in single subjects.
: 这是一项国际多中心研究，旨在评估多巴胺能神经影像学和临床特征在预测特发性REM睡眠行为 (iRBD) 受试者未来表型向显性突触核蛋白病的综合价值。9个中心发送了344例iRBD患者和256例对照的123I-FP-CIT-SPECT数据进行集中分析。使用DaTQUANTTM对123I-FP-CIT-SPECT图像进行半定量，获得对不可置换结合率 (sbr) 具有特异性的壳核和尾状核。还分析了以下临床变量 :( i) 运动障碍协会赞助的统一帕金森病评定量表修订版，运动部分评分; (ii) 迷你精神状态检查评分; (iii) 便秘; 和 (iv) 嗅觉减退。进行Kaplan-Meier生存分析以估计转化风险。用Cox回归计算每个变量的风险比。应用广义逻辑回归模型确定危险因素的最佳组合。贝叶斯分类器用于鉴定预测表型转化为帕金森病或痴呆的基线特征。经过数据质量检查，分析了263例iRBD患者 (67.6 ± 7.3岁，229名男性) 和243例对照 (67.2 ± 10.1岁，110名男性)。平均随访2年，52例 (20%) 患者出现突触核蛋白病。风险因素的最佳组合是影像学上最受影响半球的壳核多巴胺能功能障碍，定义为在壳核 (p <0.000001) 、便秘 (p <0.000001) 和年龄超过70岁 (p = 0.0002) 之间的较低值。从广义逻辑回归获得的组合特征实现了5.71的风险比 (95% 置信区间2.85-11.43)。贝叶斯分类器提示，微型精神状态检查评分较高、尾状核SBR不对称程度较低的患者更容易发生帕金森综合征，而模式相反的患者更容易发生痴呆。这项研究表明，70岁以上便秘和黑质-嘌呤多巴胺能功能降低的iRBD患者短期表型转化为显性突触核蛋白病的风险很高，为未来的神经保护试验提供了有效的分层方法。此外，我们提供了在单个受试者中使用的表型转换的显著预测因子的截止值。
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.