High schizotypy traits are associated with reduced hippocampal resting state functional connectivity.
- 作者列表："P K","F S","A D","P A
:Altered hippocampal functioning is proposed to play a critical role in the development of schizophrenia-spectrum disorders. Previous resting state functional Magnetic Resonance Imaging (rs-fMRI) studies report disrupted hippocampal connectivity in patients with psychosis and in individuals with clinical high risk, yet hippocampal connectivity has not been investigated in people with high schizotypy traits. Here we used rs-fMRI to examine hippocampal connectivity in healthy people with low (LS, n = 23) and high levels (HS, n = 22) of schizotypal traits assessed using the Schizotypy Personality Questionnaire. Using a bilateral hippocampal seed region, we examined resting state functional connectivity (RSFC) between hippocampus and striatal, thalamic and prefrontal cortex regions of interest. Compared to LS, HS participants showed lower RSFC between hippocampus and striatum and between hippocampus and thalamus. Whilst the group effect of reduced hippocampal RSFC in striatal and thalamic regions was driven by total schizotypy scores, positive schizotypy subfactor scores were significantly positively correlated with hippocampus-caudate/thalamus RSFC. Group differences in RSFC were not observed between hippocampus and prefrontal cortex. These results demonstrate that subclinical schizotypal traits are associated with altered hippocampal connectivity in striatal and thalamic regions and provide further support that hippocampal dysconnectivity confers risk for schizophrenia spectrum disorders.
: 海马功能改变被认为在精神分裂症谱系障碍的发展中发挥关键作用。先前的静息态功能磁共振成像 (rs-fMRI) 研究报告精神病患者和临床高风险个体的海马连接被破坏，然而海马连接尚未在具有高分裂型特征的人群中进行研究。在这里，我们使用rs-fMRI检查健康人的海马连接性，使用分裂型人格问卷评估低 (LS，n = 23) 和高 (HS，n = 22) 的分裂型特征。使用双侧海马种子区，我们检查了海马与纹状体、丘脑和前额叶皮层感兴趣区域之间的静息状态功能连接 (RSFC)。与LS相比，HS参与者在海马和纹状体之间以及海马和丘脑之间显示出较低的RSFC。虽然纹状体和丘脑区域减少的海马RSFC的组效应是由总分裂型评分驱动的，阳性分裂型亚因子评分与海马-尾状核/丘脑RSFC显著正相关。在海马和前额叶皮层之间未观察到RSFC的组差异。这些结果表明，亚临床分裂型性状与纹状体和丘脑区海马连接改变相关，并进一步支持海马连接障碍赋予精神分裂症谱系障碍的风险。
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.