Streaking artifact reduction for quantitative susceptibility mapping of sources with large dynamic range

Quantitative susceptibility mapping (QSM) is a novel MRI technique for the measurement of tissue magnetic susceptibility in three dimensions. Although numerous algorithms have been developed to solve this ill‐posed inverse problem, the estimation of susceptibility maps with a wide range of values is still problematic. In cases such as large veins, contrast agent uptake and intracranial hemorrhages, extreme susceptibility values in focal areas cause severe streaking artifacts. To enable the reduction of these artifacts, whilst preserving subtle susceptibility contrast, a two‐level QSM reconstruction algorithm (streaking artifact reduction for QSM, STAR‐QSM) was developed in this study by tuning a regularization parameter to automatically reconstruct both large and small susceptibility values. Compared with current state‐of‐the‐art QSM methods, such as the improved sparse linear equation and least‐squares (iLSQR) algorithm, STAR‐QSM significantly reduced the streaking artifacts, whilst preserving the sharp boundaries for blood vessels of mouse brains in vivo and fine anatomical details of high‐resolution mouse brains ex vivo. Brain image data from patients with cerebral hematoma and multiple sclerosis further illustrated the superiority of this method in reducing streaking artifacts caused by large susceptibility sources, whilst maintaining sharp anatomical details. STAR‐QSM is implemented in STI Suite, a comprehensive shareware for susceptibility imaging and quantification. Copyright © 2015 John Wiley & Sons, Ltd.     

耐碳青霉烯肠杆菌科细菌的流行病学特点以及抗生素应用策略

耐碳青霉烯肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae, CRE)在全球范围内的快速增长和流行，直接影响临床治疗与患者预后，并给社会经济带来了严重负担。目前CRE临床治疗可供选择的药物有黏菌素、氨基糖苷类、替加环素和磷霉素等；美国食品药品监督局(FDA)批准的新药即头孢他啶/阿维巴坦(ceftazidime/avibactam, CAZ-AVI)、美罗培南/瓦博巴坦(meropenem/vaborbactam, MER-VAB)、亚胺培南/雷巴坦(imipenan/ribatan, AMI-LEI)和plazomicin也为CRE感染治疗提供了新的选择，但各类药物的治疗效果、新的耐药产生及不良反应各有不同，为优化临床治疗方案，提高治疗效果，本文对CRE的治疗药物的现状做一分析。     

常见非发酵菌的临床分布及耐药性分析

目的了解医院常见非发酵菌的临床分布及耐药特征,为临床合理使用抗菌药物提供依据。方法对2012-2014年医院临床送检各类标本检出的病原菌构成比、标本来源、科室分布、MDR、XDR、PDR菌株分离率及药敏结果进行统计分析。结果 2012-2014年共分离出非发酵菌5 270株,占全部分离菌株的27.48%。分布构成比:主要为鲍曼不动杆菌(占50.70%),铜绿假单胞菌占38.35%,嗜麦芽寡养单胞菌占4.95%。5 270株非发酵菌主要分离自痰液,占66.26%,其他标本类型均在7%以下。科室分布主要以第一重症监护病房(占21.14%)和第一呼吸内科病房(含内科重症监护病房,占12.33%)为主;其余科室分离率均在10%以下。MDR、XDR、PDR鲍曼不动杆菌和铜绿假单胞菌除痰标本外的标本类型分离率远低于总分离率。3年医院鲍曼不动杆菌对常用抗菌药物均产生了较严重的耐药性,大多数耐药率>80%。铜绿假单胞菌对多种抗菌药物的耐药率均>90%,对亚胺培南、美罗培南耐药率呈逐年上升趋势,已超过40%。嗜麦芽寡养单胞菌的耐药率总体上升比较缓慢。除痰标本外,其他标本的鲍曼不动杆菌和铜绿假单胞菌对绝大部分抗菌药物的耐药率低于总耐药率(P<0.05),而嗜麦芽寡养单胞菌对抗菌药物的耐药率与总耐药率比较差异无统计学意义(P>0.05)。结论非发酵菌对常用抗菌药物的耐药率较高,耐药机制多样复杂,临床在治疗非发酵菌感染时,应结合实验室药敏结果,合理使用抗菌药物,有效地控制医院感染。     

Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) rs10845498 Polymorphism Is Associated with a Decreased Risk of Non-Small Cell Lung Cancer

Objectives: Low-density lipoprotein receptor-related protein 6 (LRP6) modulates Wnt signaling transduction. Altered LRP6 expression leads to abnormal Wnt protein activation, cell proliferation and tumorigenesis. This study investigated the association between LRP6 single-nucleotide polymorphisms (SNPs) and non-small-cell lung cancer (NSCLC) in a Chinese population. Methods: A total of 500 NSCLC patients and 500 healthy controls were recruited for assessment of four LRP6 SNPs using the SEQUENOM MassARRAY matrix-assisted laser desorption ionization-time of flight mass spectrometry. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses. Results: The frequency of the LRP6 rs10845498 genotype was 60.9% (A/A), 35.5% (AG) and 3.6% (GG) in patients with lung squamous cell carcinoma (SCC) and 69.2% (A/A), 27.2% (A/G) and 3.6% (GG) in controls. Logistic regression analysis revealed that the LRP6 rs10845498 A/A major allele was associated with a reduced risk in developing lung SCC (OR = 0.69; 95% CI, 0.48-1.00; P=0.04), and tobacco smokers had a 2.21 fold greater risk in developing SCC than nonsmokers (p<0.01, 95% CI, 1.72-2.85), and tobacco smokers who carried an “A” allele (AA+AG) in rs6488507 had a 2.34-fold greater risk in developing NSCLC than other patients (p< 0.01, 95%CI, 1.74-3.13). Conclusions: The LRP6 rs10845498 SNP is associated with a reduced risk of lung SCC, while tobacco smoke increases the risk. LRP6 rs6488507 polymorphism synergistically increased the risk of NSCLC in tobacco smokers. Further studies are needed to elucidate the functional impact of LRP6 expression and activity in NSCLC.     

Surgical treatment of jaw osteonecrosis in “Krokodil” drug addicted patients

Retrospective study of jaw osteonecrosis treatment in patients using the “Krokodil” drug from 2009 to 2013.On the territory of the former USSR countries there is widespread use of a self-produced drug called “Krokodil”. Codeine containing analgesics (“Sedalgin”, “Pentalgin” etc), red phosphorus (from match boxes) and other easily acquired chemical components are used for synthesis of this drug, which used intravenously. Jaw osteonecrosis develops as a complication in patients who use “Krokodil”. The main feature of this disease is jawbone exposure in the oral cavity. Surgery is the main method for the treatment of jaw osteonecrosis in patients using “Krokodil”.40 “Krokodil” drug addict patients with jaw osteonecrosis were treated. Involvement of maxilla was found in 11 patients (27.5%), mandible in 21 (52.5%), both jaws in 8 (20%) patients. 35 Lesions were found in 29 mandibles and 21 lesions in 19 maxillas. Main factors of treatment success are: cessation of “Krokodil” use in the pre- (minimum 1 month) and postoperative period and osteonecrosis area resection of a minimum of 0.5 cm beyond the visible borders of osteonecrosis towards the healthy tissues. Surgery was not delayed until sequestrum formation. In the mandible marginal or segmental resection (with or without TMJ exarticulation) was performed. After surgery recurrence of disease was seen in 8 (23%) cases in the mandible, with no cases of recurrence in the maxilla.According to our experience in this case series, surgery is the main method for the treatment of jaw osteonecrosis in patients using “Krokodil”. Cessation of drug use and jaw resection minimize the rate of recurrences in such patients.     

Plasma hydrogenated cationic detonation nanodiamonds efficiently deliver to human cells in culture functional siRNA targeting the Ewing sarcoma junction oncogene

The expression of a defective gene can lead to major cell dysfunctions among which cell proliferation and tumor formation. One promising therapeutic strategy consists in silencing the defective gene using small interfering RNA (siRNA). In previous publications we showed that diamond nanocrystals (ND) of primary size 35 nm, rendered cationic by polyethyleneimine-coating, can efficiently deliver siRNA into cell, which further block the expression of EWS/FLI-1 oncogene in a Ewing sarcoma disease model. However, a therapeutic application of such nanodiamonds requires their elimination by the organism, particularly in urine, which is impossible for 35 nm particles. Here, we report that hydrogenated cationic nanodiamonds of primary size 7 nm (ND-H) have also a high affinity for siRNA and are capable of delivering them in cells. With siRNA/ND-H complexes, we measured a high inhibition efficacy of EWS/FLI-1 gene expression in Ewing sarcoma cell line. Electron microscopy investigations showed ND-H in endocytosis compartments, and especially in macropinosomes from which they can escape before siRNA degradation occurred. In addition, the association of EWS/FLI-1 silencing by the siRNA/ND-H complex with a vincristine treatment yielded a potentiation of the toxic effect of this chemotherapeutic drug. Therefore ND-H appears as a promising delivery agent in anti-tumoral gene therapy.