Predictors of volitional motor recovery with epidural stimulation in individuals with chronic spinal cord injury.
- 作者列表："Mesbah S","Ball T","Angeli C","Rejc E","Dietz N","Ugiliweneza B","Harkema S","Boakye M
:Spinal cord epidural stimulation (scES) has enabled volitional lower extremity movements in individuals with chronic and clinically motor complete spinal cord injury and no clinically detectable brain influence. The aim of this study was to understand whether the individuals' neuroanatomical characteristics or positioning of the scES electrode were important factors influencing the extent of initial recovery of lower limb voluntary movements in those with clinically motor complete paralysis. We hypothesized that there would be significant correlations between the number of joints moved during attempts with scES prior to any training interventions and the amount of cervical cord atrophy above the injury, length of post-traumatic myelomalacia and the amount of volume coverage of lumbosacral enlargement by the stimulation electrode array. The clinical and imaging records of 20 individuals with chronic and clinically motor complete spinal cord injury who underwent scES implantation were reviewed and analysed using MRI and X-ray integration, image segmentation and spinal cord volumetric reconstruction techniques. All individuals that participated in the scES study (n = 20) achieved, to some extent, lower extremity voluntary movements post scES implant and prior to any locomotor, voluntary movement or cardiovascular training. The correlation results showed that neither the cross-section area of spinal cord at C3 (n = 19, r = 0.33, P = 0.16) nor the length of severe myelomalacia (n = 18, r = -0.02, P = 0.93) correlated significantly with volitional lower limb movement ability. However, there was a significant, moderate correlation (n = 20, r = 0.59, P = 0.006) between the estimated percentage of the lumbosacral enlargement coverage by the paddle electrode as well as the position of the paddle relative to the maximal lumbosacral enlargement and the conus tip (n = 20, r = 0.50, P = 0.026) with the number of joints moved volitionally. These results suggest that greater coverage of the lumbosacral enlargement by scES may improve motor recovery prior to any training, possibly because of direct modulatory effects on the spinal networks that control lower extremity movements indicating the significant role of motor control at the level of the spinal cord.
: 脊髓硬膜外刺激 (scES) 已经在患有慢性和临床运动性完全性脊髓损伤并且没有临床上可检测到的脑影响的个体中实现了意志性下肢运动。这项研究的目的是了解个人的神经解剖学特征或定位scES电极是重要因素影响程度初期恢复下肢自愿者临床电机完全瘫痪.我们假设，在任何训练干预之前，在尝试scES时移动的关节数量与损伤上方的颈髓萎缩量、创伤后骨髓软化的长度以及刺激电极阵列对腰骶部增大的体积覆盖量之间存在显著相关性.临床及影像资料，记录20慢性临床电机完全性脊髓损伤行scES植入进行回顾和分析使用磁共振成像 (MRI) 和X-ray集成、图像分割和脊髓容积重建技术.参与scES研究的所有个体 (n = 20) 在一定程度上实现了scES植入后和任何运动、自主运动或心血管训练之前的下肢自主运动。相关结果显示，C3处脊髓横截面积 (n = 19，r = 0.33，p = 0.16 0.02) 和严重骨髓软化的长度 (n = 18，r =-0.93，p = ) 均不与意志性下肢运动能力显著相关。然而，存在显著的中度相关 (n = 20，r = 0.59，p = 0.006) 在桨状电极对腰骶部扩大覆盖的估计百分比以及桨状部相对于最大腰骶部扩大和圆锥尖端的位置之间 (n = 20，r = 0.50，p = 0.026)随着关节数量的移动。这些结果表明，scES对腰骶部扩大的更大覆盖可能改善任何训练前的运动恢复，可能是因为对控制下肢运动的脊柱网络的直接调节作用，表明运动控制在脊髓水平上的重要作用。
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.