Antisaccade, a predictive marker for freezing of gait in Parkinson's disease and gait/gaze network connectivity.
- 作者列表："Gallea C","Wicki B","Ewenczyk C","Rivaud-Péchoux S","Yahia-Cherif L","Pouget P","Vidailhet M","Hainque E
:Freezing of gait is a challenging sign of Parkinson's disease associated with disease severity and progression and involving the mesencephalic locomotor region. No predictive factor of freezing has been reported so far. The primary objective of this study was to identify predictors of freezing occurrence at 5 years. In addition, we tested whether functional connectivity of the mesencephalic locomotor region could explain the oculomotor factors at baseline that were predictive of freezing onset. We performed a prospective study investigating markers (parkinsonian signs, cognitive status and oculomotor recordings, with a particular focus on the antisaccade latencies) of disease progression at baseline and at 5 years. We identified two groups of patients defined by the onset of freezing at 5 years of follow-up; the 'Freezer' group was defined by the onset of freezing in the ON medication condition during follow-up (n = 17), while the 'non-Freezer' group did not (n = 8). Whole brain resting-state functional MRI was recorded at baseline to determine how antisaccade latencies were associated with connectivity of the mesencephalic locomotor region networks in patients compared to 25 age-matched healthy volunteers. Results showed that, at baseline and compared to the non-Freezer group, the Freezer group had equivalent motor or cognitive signs, but increased antisaccade latencies (P = 0.008). The 5-year course of freezing of gait was correlated with worsening antisaccade latencies (P = 0.0007). Baseline antisaccade latencies was also predictive of the freezing onset (χ2 = 0.008). Resting state connectivity of mesencephalic locomotor region networks correlated with (i) antisaccade latency differently in patients and healthy volunteers at baseline; and (ii) the further increase of antisaccade latency at 5 years. We concluded that antisaccade latency is a predictive marker of the 5-year onset of freezing of gait. Our study suggests that functional networks associated with gait and gaze control are concurrently altered during the course of the disease.
: 步态冻结是与疾病严重程度和进展相关并涉及中脑运动区域的帕金森病的挑战性体征。到目前为止，还没有关于冻结的预测因子的报道。本研究的主要目的是确定5年冷冻发生的预测因子。此外，我们测试了中脑运动区域的功能连接是否可以解释基线时预测冷冻发作的动眼因素。我们进行了一项前瞻性研究，调查基线和5年时疾病进展的标志物 (帕金森病体征、认知状态和眼球运动记录，特别关注抗扫视潜伏期)。我们确定了两组患者，定义为在5年随访时开始冷冻; “冻结” 组定义为在随访期间药物治疗条件下开始冷冻 (n = 17)，而 “非freezer” 组没有 (n = 8)。在基线时记录全脑静息态功能MRI，以确定与25名年龄匹配的健康志愿者相比，患者的反扫视潜伏期与中脑运动区域网络的连通性之间的关联。结果显示，在基线时，与非冷冻组相比，冷冻组具有等同的运动或认知体征，但增加了抗扫视潜伏期 (p = 0.008)。步态冻结的5年病程与抗扫视潜伏期恶化相关 (p = 0.0007)。基线抗扫视潜伏期也可预测冻结开始 (χ2 2 = 0.008)。中脑运动区域网络的静息状态连通性与 (i) 基线时患者和健康志愿者的抗扫视潜伏期不同; (ii) 抗扫视潜伏期在5年时进一步增加。我们得出结论，反扫视潜伏期是步态冻结5年发作的预测指标。我们的研究表明，与步态和注视控制相关的功能网络在疾病过程中同时改变。
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.