On the learning of addictive behavior: Sensation-seeking propensity predicts dopamine turnover in dorsal striatum

Brain Imaging and Behavior - We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the...     

曲马多治疗糖尿病性神经病疼痛的双盲随机试验

目的：本研究旨在评价曲马多治疗糖尿病性神经病的有效性和安全性。背景：糖尿病性神经病疼痛是糖尿病患者的主要症状，其治疗和其它的末梢神经病变一样，不能令人满意。曲马多是作用于中枢的镇痛剂，用于治疗中到重度疼痛。方法：多中心、门诊病例、随机、双盲、安慰剂做对照、设置平行组的研究，包括药效消退期（在此期间停用所有镇痛剂）和一个为期42天的双盲治疗期。总共有131名患糖尿病性神经病疼痛的患者接受曲马多（n=65）或安慰剂胶囊治疗（n=66），每日4次。42天的治疗结束后或治疗中断后比较曲马多组和安慰剂组平均疼痛强度评分，进行初级药效分析。次级药效分析为疼痛缓解评分和根据日常活动和睡眠状况作出生活质量评估。结果：曲马多平均剂量为210mg／天，治疗糖尿病性神经病疼痛较安慰剂有显著疗效（P〈0．001）。曲马多组患者生理（P=0．02）和社会功能（P=0．04）的评分显著优于安慰剂组。未发现对睡眠有显著改善作用。曲马多最常见的不良事件是恶心、便秘、头疼和嗜睡。结论：安慰剂做对照的实验结果表明曲马多在治疗糖尿病性神经病疼痛上是安全和有效的。     

Mechanisms Underlying the Effect of Acupuncture on Cognitive Improvement: A Systematic Review of Animal Studies

Acupuncture has been reported to be beneficial in treating cognitive impairment in various pathological conditions. This review describes the effort to understand the signaling pathways that underlie the acupunctural therapeutic effect on cognitive function. We searched the literature in 12 electronic databases from their inception to November 2013, with full text available and language limited to English. Twenty-three studies were identified under the selection criteria. All recruited animal studies demonstrate a significant positive effect of acupuncture on cognitive impairment. Findings suggest acupuncture may improve cognitive function through modulation of signaling pathways involved in neuronal survival and function, specifically, through promoting cholinergic neural transmission, facilitating dopaminergic synaptic transmission, enhancing neurotrophin signaling, suppressing oxidative stress, attenuating apoptosis, regulating glycometabolic enzymes and reducing microglial activation. However, the quality of reviewed studies has room for improvement. Further high-quality animal studies with randomization, blinding and estimation of sample size are needed to strengthen the recognition of group differences.     

A Novel Morphologic-Molecular Recurrence Predictive Model Refines Traditional Prognostic Tools for Invasive Breast Carcinoma

Background

Histologic grade, TNM stage, and Nottingham Prognostic Index are traditional prognostic tools for breast cancer. “IHC-molecular” classification of breast cancer can also identify patients at different recurrence risks and provides insight into cancer therapy. However, cancers in each group are heterogeneous. A model based on the comprehensive analysis of morphologic features and molecular subtype was constructed to predict recurrence and refine these traditional prognostic tools.

Methods

Morphologic features including histologic grade, fibrotic focus, extensive intraductal component, lymphocytic infiltrate, lymphovascular invasion, tumor necrosis, tumor margin and TNM stage, and molecular subtypes approximated by immunohistochemistry were analyzed in 633 patients with invasive breast carcinoma (excluding those with HER2 targeted therapy). Significant independent predictors for recurrence included: high histologic grade (p = 0.004), presence of lymphovascular invasion (p = 0.004), fibrotic focus (p = 0.020), mild lymphocytic infiltrate (p = 0.013), high TNM stage (p < 0.001), and HER2-overexpressing (p = 0.004) and basal-like (p < 0.001) molecular subtypes. A morphologic-molecular recurrence predictive model based on these features was useful in recurrence prediction, independent of treatment modalities, and was able to refine the traditional prognostic tools of histologic grade, TNM stage, and Nottingham prognostic index, particularly for intermediate-risk groups, and to refine the luminal group molecular subtypes. Such findings were reproducible with a validation cohort.

Conclusion

TNM stage, histologic grade, lymphovascular invasion, fibrotic focus, mild lymphocytic infiltrate, HER2-overexpressing and basal-like molecular subtypes were important independent recurrence risk factors for breast cancer. This morphologic-molecular model was robust in recurrence prediction and refined recurrence risk stratified by the traditional prognostic parameters, independent of treatment modalities.     

Role of Vascular Oxidative Stress in Obesity and Metabolic Syndrome

Obesity is associated with vascular diseases that are often attributed to vascular oxidative stress. We tested the hypothesis that vascular oxidative stress could induce obesity. We previously developed mice that overexpress p22phox in vascular smooth muscle, tg^sm/p22phox, which have increased vascular ROS production. At baseline, tg^sm/p22phox mice have a modest increase in body weight. With high-fat feeding, tg^sm/p22phox mice developed exaggerated obesity and increased fat mass. Body weight increased from 32.16 ± 2.34 g to 43.03 ± 1.44 g in tg^sm/p22phox mice (vs. 30.81 ± 0.71 g to 37.89 ± 1.16 g in the WT mice). This was associated with development of glucose intolerance, reduced HDL cholesterol, and increased levels of leptin and MCP-1. Tg^sm/p22phox mice displayed impaired spontaneous activity and increased mitochondrial ROS production and mitochondrial dysfunction in skeletal muscle. In mice with vascular smooth muscle–targeted deletion of p22phox (p22phox^loxp/loxp/tg^smmhc/cre mice), high-fat feeding did not induce weight gain or leptin resistance. These mice also had reduced T-cell infiltration of perivascular fat. In conclusion, these data indicate that vascular oxidative stress induces obesity and metabolic syndrome, accompanied by and likely due to exercise intolerance, vascular inflammation, and augmented adipogenesis. These data indicate that vascular ROS may play a causal role in the development of obesity and metabolic syndrome.     

Zotarolimus-eluting stent utilization in small-vessel coronary artery disease (ZEUS)

The role of the second-generation zotarolimus-eluting stent RESOLUTE in small-vessel coronary artery disease is unclear. The aim of this study was examine the angiographic results of RESOLUTE in de novo coronary lesions of ≥50 % diameter stenosis in target vessels ≤2.5 mm. From August 2008 to April 2010, 142 symptomatic patients with 159 lesions who fitted the inclusion criteria were treated with RESOLUTE. The mean age of patients was 66 ± 10 years, with male predominance (66 %). Diabetes mellitus was found in 62 (43.7 %) patients, whereas multivessel disease was observed in 105 (73.9 %). The mean stent size and length used were 2.33 ± 0.13 and 22 ± 8 mm, respectively. Follow-up angiography was performed on 143 (89.9 %) lesions in 127 (89.4 %) patients at a mean of 10.3 ± 3.6 months. Angiographic restenosis was found in 9 (6.3 %) lesions; the late loss was 0.26 ± 0.34 mm. At 1-year follow-up there were four cardiovascular deaths, two nonfatal myocardial infarctions, and six repeated revascularizations. The resultant major adverse cardiac event rate was 8.5 %. The use of RESOLUTE to treat small-vessel disease is associated with good clinical and angiographic outcomes at 1 year.