The development of an fMRI protocol to investigate vmPFC network functioning underlying the generalization of behavioral control.
- 作者列表："Cremers H","Keedy S","Coccaro E
:Experiencing behavioral control over stress can have long-lasting and generalizing effects. Animal research has shown that vmPFC-subcortical interactions are critical for behavioral control; however, research in humans is sparse. Therefore a paradigm was developed in which participants (n = 18) were first assigned to a controllable or uncontrollable version of a signal detection task associated with mild shocks. Subsequently, subjects underwent an fMRI task on the anticipation of speaking in public while measuring self-reported stress, heart rate, and vmPFC network topology. The signal detection task results revealed faster responses to potential shock trials and a trend difference between the controllable and uncontrollable group. The speech anticipation procedure did not show significant between-group differences on self-reported stress or heart rate. fMRI results indicated higher vmPFC efficiency in the controllable threat group at baseline and recovery but similar to the uncontrollable group during speech anticipation. The current report establishes the feasibility of the protocol. However, to evaluate the generalization effect of controllability on the behavioral, physiological, and neural levels further, adequately-powered follow-up research is needed.
: 经历对压力的行为控制可以产生持久和普遍的影响。动物研究表明，vmPFC-皮质下相互作用对行为控制至关重要; 然而，对人类的研究很少。因此，开发了一种范例，其中参与者 (n = 18) 首先被分配到与轻度冲击相关的信号检测任务的可控或不可控版本。随后，受试者在测量自我报告的压力、心率和vmPFC网络拓扑的同时，接受了关于在公共场合讲话的预期的fMRI任务。信号检测任务结果揭示了对潜在休克试验的更快反应以及可控组和不可控组之间的趋势差异。言语预测程序在自我报告的压力或心率上没有显示出显著的组间差异。fMRI结果表明，在基线和恢复时，可控威胁组的vmPFC效率较高，但与语音预期期间的不可控组相似。本报告确定了该方案的可行性。然而，为了进一步评估可控性对行为、生理和神经水平的泛化作用，需要足够有力的后续研究。
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.