Incidence of pressure ulcers in intensive care units and direct costs of treatment: Evidence from Iran

Background and objective

Pressure ulcer (PU) is one of the important and frequent complications of hospitalization, associated with high treatment costs. The present study was conducted to determine the incidence of PU and its direct treatment costs for patients in intensive care unit (ICU) in Iran.

Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α⁺ isoform but not the α⁻ isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.     

3D-CRT 低剂量区 V5体积的大小对非小细胞肺癌患者肺功能的影响

目的：探讨3D-CRT 低剂量区 V5体积的大小对非小细胞肺癌患者肺功能的影响。方法：收集我院肿瘤科2014年4月～2015年10月收治的46例首次行三维适形放射治疗且顺利完成治疗的非小细胞肺癌患者，对每例患者分别在治疗前以及治疗后的1、3个月进行肺功能检测，分析3D-CRT 低剂量区 V5体积的大小与肺功能变化之间的关系。结果：放疗后1个月的 FEV1％、FVC％值明显高于放疗前且差异均具有显著性。放疗后1个月、3个月的 DLCO％值明显低于放疗前，且放疗前的与放疗后3个月的差异具有显著性；V5≦45％、45％55％三组放疗前后的 FEV1％值和 FVC％值比较差异均不具有显著性。V5≦45％、45％55％三组放疗前后的 DLCO％值均呈逐渐下降趋势，且 V5>55％组的放疗前后 DLCO％值比较差异具有显著性。而 V5≦45％组和45％55％时，DLCO％值降低的趋势更加显著。     

Reference set for performance testing of pediatric vaccine safety signal detection methods and systems

BackgroundSafety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources.MethodsThe study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement.ResultsWe selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC.ConclusionA reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.     

Specific alterations in plasma proteins during depressed,manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.     

Marr and Reductionism

David Marr's three-level method for completely understanding a cognitive system and the importance he attaches to the computational level are so familiar as to scarcely need repeating. Fewer seem to recognize that Marr defends his famous method by criticizing the “reductionistic approach.” This sets up a more interesting relationship between Marr and reductionism than is usually acknowledged. I argue that Marr was correct in his criticism of the reductionists of his time—they were only describing (cellular activity), not explaining (cognitive functions). But a careful metascientific account of reductionistic neuroscience over the past two decades reveals that Marr's criticisms no longer have force. Contemporary neuroscience now explains cognition directly, although in a fashion—causal-mechanistically—quite different than Marr recommended. So while Marr was correct to reject the reductionism of his day and offer an alternative method for genuinely explaining cognition, contemporary cognitive scientists now owe us a new defense of Marr's famous method and the advantages of its explanations over the type now pursued successfully in current reductionist neuroscience. There are familiar reasons for thinking that this debt will not be paid easily.     

AuNP flares-capped mesoporous silica nanoplatform for MTH1 detection and inhibition

The human mutT homologue MTH1, a nucleotide pool sanitizing enzyme, represents a vulnerability factor and an attractive target for anticancer therapy. However, there is currently a lack of selective and effective platforms for the detection and inhibition of MTH1 in cells. Here, we demonstrate for the first time a gold nanoparticle (AuNP) flares-capped mesoporous silica nanoparticle (MSN) nanoplatform that is capable of detecting MTH1 mRNA and simultaneously suppressing MTH1 activity. The AuNP flares are made from AuNPs that are functionalized with a dense shell of MTH1 recognition sequences hybridized to short cyanine (Cy5)-labeled reporter sequences and employed to seal the pores of MSN to prevent the premature MTH1 inhibitors (S-crizotinib) release. Just like the pyrotechnic flares that produce brilliant light when activated, the resulting AuNP flares@MSN (S-crizotinib) undergo a significant burst of red fluorescence enhancement upon MTH1 mRNA binding. This hybridization event subsequently induces the opening of the pores and the release of S-crizotinib in an mRNA-dependent manner, leading to significant cytotoxicity in cancer cells and improved therapeutic response in mouse xenograft models. We anticipate that this nanoplatform may be an important step toward the development of MTH1-targeting theranostics and also be a useful tool for cancer phenotypic lethal anticancer therapy.     

死亡结构域相关蛋白及其在宫颈病变中的研究进展

宫颈癌对妇女健康构成严重威胁,人乳头瘤病毒感染与宫颈病变及宫颈癌的发生密切相关。关于宫颈癌发生发展的机制仍在研究中。近年研究发现一种多功能核蛋白,即死亡结构域相关蛋白(death domain associated protein,Daxx),其与细胞内蛋白或病毒蛋白相互作用,参与调节细胞凋亡、转录调控、抗病毒等细胞活动,在不同途径中发挥不同的生理或病理作用。通过对Daxx功能及其作用机制的研究有助于进一步阐明宫颈癌发生发展的机制,有助于发现新的预防和治疗方法。综述Daxx的一般特性和研究现况及其在宫颈病变的研究进展。