Abnormal dorsal attention network activation in memory impairment after traumatic brain injury.
- 作者列表："Mallas EJ","De Simoni S","Scott G","Jolly AE","Hampshire A","Li LM","Bourke NJ","Roberts SAG","Gorgoraptis N","Sharp DJ
:Memory impairment is a common, disabling effect of traumatic brain injury. In healthy individuals, successful memory encoding is associated with activation of the dorsal attention network as well as suppression of the default mode network. Here, in traumatic brain injury patients we examined whether: (i) impairments in memory encoding are associated with abnormal brain activation in these networks; (ii) whether changes in this brain activity predict subsequent memory retrieval; and (iii) whether abnormal white matter integrity underpinning functional networks is associated with impaired subsequent memory. Thirty-five patients with moderate-severe traumatic brain injury aged 23-65 years (74% males) in the post-acute/chronic phase after injury and 16 healthy control subjects underwent functional MRI during performance of an abstract image memory encoding task. Diffusion tensor imaging was used to assess structural abnormalities across patient groups compared to 28 age-matched healthy controls. Successful memory encoding across all participants was associated with activation of the dorsal attention network, the ventral visual stream and medial temporal lobes. Decreased activation was seen in the default mode network. Patients with preserved episodic memory demonstrated increased activation in areas of the dorsal attention network. Patients with impaired memory showed increased left anterior prefrontal activity. White matter microstructure underpinning connectivity between core nodes of the encoding networks was significantly reduced in patients with memory impairment. Our results show for the first time that patients with impaired episodic memory show abnormal activation of key nodes within the dorsal attention network and regions regulating default mode network activity during encoding. Successful encoding was associated with an opposite direction of signal change between patients with and without memory impairment, suggesting that memory encoding mechanisms could be fundamentally altered in this population. We demonstrate a clear relationship between functional networks activated during encoding and underlying abnormalities within the structural connectome in patients with memory impairment. We suggest that encoding failures in this group are likely due to failed control of goal-directed attentional resources.
: 记忆障碍是创伤性脑损伤常见的致残作用。在健康个体中，成功的记忆编码与背侧注意网络的激活以及默认模式网络的抑制相关联。在这里，在创伤性脑损伤患者中，我们检查了是否 :( i) 记忆编码的损伤与这些网络中的异常脑激活相关; (ii) 这种脑活动的变化是否预测随后的记忆检索; 和 (iii) 支持功能网络的白质完整性异常是否与后续记忆受损有关。35名年龄在23-65岁的中重度创伤性脑损伤患者 (74% 名男性) 在损伤后急性/慢性期和16名健康对照受试者在执行抽象图像记忆编码任务期间接受了功能性MRI。与28个年龄匹配的健康对照相比，扩散张量成像用于评估患者组的结构异常。所有参与者的成功记忆编码与背侧注意网络、腹侧视觉流和内侧颞叶的激活相关。在默认模式网络中看到激活减少。保留情景记忆的患者表现出背侧注意网络区域的激活增加。患者的记忆障碍增高左前额活动.脑白质微结构支撑之间的连接的核心节点的编码网络明显降低患者的记忆障碍.我们的结果首次显示，情景记忆受损的患者在编码过程中表现出背侧注意网络和调节默认模式网络活动的区域内关键节点的异常激活。成功的编码与有记忆障碍和无记忆障碍的患者之间的相反方向的信号变化相关，这表明在该人群中记忆编码机制可以从根本上改变。我们证明了记忆障碍患者在编码过程中激活的功能网络与结构连接体内潜在异常之间的明确关系。我们认为，这组编码失败可能是由于目标导向注意力资源控制失败。
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.