- 作者列表："Aschwanden D","Strickhouser JE","Luchetti M","Stephan Y","Sutin AR","Terracciano A
:This study provides a quantitative synthesis of the prospective associations between personality traits (neuroticism, extraversion, openness, agreeableness, conscientiousness) and the risk of incident Alzheimer's disease and related dementias. We conducted five separate meta-analyses with 8-12 samples (N = 30,036 to 33,054) that were identified through a systematic literature search following the MOOSE guidelines. Higher neuroticism (HR = 1.24, 95% CI [1.17, 1.31]) and lower conscientiousness (HR = 0.77, 95% CI [0.73, 0.81]) were associated with increased dementia risk, even after accounting for covariates such as depressive symptoms. Lower extraversion (HR = 0.92, 95% CI [0.86, 0.97]), openness (HR = 0.91, 95% CI [0.86, 0.96]), and agreeableness (HR = 0.90, 95% CI [0.83, 0.98]) were also associated with increased risk, but these associations were less robust and not significant in fully adjusted models. No evidence of publication bias was found. The strength of associations was unrelated to publication year (i.e., no evidence of winner's curse). Meta-regressions indicated consistent effects for neuroticism, openness, and conscientiousness across methods to assess dementia, dementia type, follow-up length, sample age, minority, country, and personality measures. The association of extraversion and agreeableness varied by country. Our findings indicate robust associations of neuroticism and conscientiousness with dementia risk.
: 本研究定量综合了人格特征 (神经质、外向性、开放性、宜人性、责任心) 与阿尔茨海默病和相关痴呆风险之间的前瞻性关联。我们对8-12个样本 (N = 30,036 ~ 33,054) 进行了5项独立的荟萃分析，这些样本是按照MOOSE指南通过系统文献检索确定的。较高的神经质 (HR = 1.24，95% CI [1.17，1.31]) 和较低的责任心 (HR = 0.77，95% CI [0.73，0.81]) 与痴呆风险增加相关，即使在考虑抑郁症状等协变量之后。较低的外向性 (HR = 0.92，95% CI [0.86，0.97])，开放性 (HR = 0.91，95% CI [0.86，0.96]) 和宜人性 (HR = 0.90，95% CI [0.83，0.98]) 也与风险增加相关，但是这些关联在完全调整的模型中不太稳健并且不显著。未发现发表偏倚的证据。协会的强度与出版年份无关 (即没有证据表明赢家的诅咒)。元回归表明，在评估痴呆、痴呆类型、随访时间长度、样本年龄、少数民族、国家和人格测量的方法中，神经质、开放性和责任心的影响一致。外向性和宜人性的关联因国家而异。我们的研究结果表明神经质和责任心与痴呆风险密切相关。
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.