Role of viral RNA and lipid in the adverse events associated with the 2010 Southern Hemisphere trivalent influenza vaccine

In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in post-marketing adverse event reports of febrile seizures (FS) in children under 5 years of age shortly after vaccination with the CSL 2010 SH trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous CSL TIVs and other licensed 2010 SH TIVs. In an accompanying study, we described the contribution to these adverse events of the 2010 SH influenza strains as expressed in the CSL 2010 SH TIV using in vitro cytokine/chemokine secretion from whole blood cells and induction of NF-κB activation in HEK293 reporter cells. The aim of the present study was to identify the root cause components that elicited the elevated cytokine/chemokine and NF-κB signature. Our studies demonstrated that the pyrogenic signal was associated with a heat-labile, viral-derived component(s) in the CSL 2010 SH TIV. Further, it was found that viral lipid-mediated delivery of short, fragmented viral RNA was the key trigger for the increased cytokine/chemokine secretion and NF-κB activation. It is likely that the FS reported in children <5 years were due to a combination of the new influenza strains included in the 2010 SH TIV and the CSL standard method of manufacture preserving strain-specific viral components of the new influenza strains (particularly B/Brisbane/60/2008 and to a lesser extent H1N1 A/California/07/2009). These combined to heighten immune activation of innate immune cells, which in a small proportion of children <5 years of age is associated with the occurrence of FS. The data also demonstrates that CSL TIVs formulated with increased levels of splitting agent (TDOC) for the B/Brisbane/60/2008 strain can attenuate the pro-inflammatory signals in vitro, identifying a potential path forward for generating a CSL TIV indicated for use in children <5 years.     

Clinical phenotyping in selected national networks: demonstrating the need for high-throughput,portable, and computational methods

ObjectiveThe combination of phenomic data from electronic health records (EHR) and clinical data repositories with dense biological data has enabled genomic and pharmacogenomic discovery, a first step toward precision medicine. Computational methods for the identification of clinical phenotypes from EHR data will advance our understanding of disease risk and drug response, and support the practice of precision medicine on a national scale.MethodsBased on our experience within three national research networks, we summarize the broad approaches to clinical phenotyping and highlight the important role of these networks in the progression of high-throughput phenotyping and precision medicine. We provide supporting literature in the form of a non-systematic review.ResultsThe practice of clinical phenotyping is evolving to meet the growing demand for scalable, portable, and data driven methods and tools. The resources required for traditional phenotyping algorithms from expert defined rules are significant. In contrast, machine learning approaches that rely on data patterns will require fewer clinical domain experts and resources.ConclusionsMachine learning approaches that generate phenotype definitions from patient features and clinical profiles will result in truly computational phenotypes, derived from data rather than experts. Research networks and phenotype developers should cooperate to develop methods, collaboration platforms, and data standards that will enable computational phenotyping and truly modernize biomedical research and precision medicine.     

产时电子胎心监护减速区面积在新生儿酸中毒预测中的价值

目的:探讨产时胎心监护减速区面积在新生儿酸中毒预测中的价值。方法:分析2011年2月至2013年10月在北京大学第三医院住院分娩足月单胎孕产妇204例的分娩前30分钟的胎心监护图形的减速区面积,根据p H7.20和(或)碱剩余-12.00 mmol/L分为酸中毒组(26例)和对照组(178例),探讨胎心监护图形的减速区面积与新生儿脐动脉血气的关系,并绘制受试者工作特性曲线(ROC曲线),计算曲线下面积(AUC),预测酸中毒的敏感性和特异性。结果:酸中毒组减速区面积(18.00 cm~2)明显大于对照组(10.50 cm~2),差异有统计学意义(P0.05)。分娩前30分钟图形的减速区面积的AUC为0.663(95%CI 0.541~0.785),预测酸中毒的敏感性为61.5%,特异性为72.5%。结论:产时胎心监护减速区面积对预测新生儿酸中毒有一定价值,特异性较高,而敏感性欠佳,建议结合更多图形指标解读图形对新生儿酸中毒的预测。     

A closer look at nursing documentation on paper forms: Preparation for computerizing a nursing documentation system

A small scale documentation analysis was conducted to explore the medical and surgical nursing content of the patient record at a large teaching hospital affiliated with Partners Healthcare System (PHS), in preparation for a computerized documentation system. Through this study, we identified a number of problems associated with the paper record that require resolution in the new computerized system, including elimination of documentation redundancy, areas where more structure is needed to properly capture data on nursing practice, and various design considerations to support a more complete and accurate documentation of nursing care.     

Validation and utilisation of a digital version of the survey instrument for natural history,Aetiology and Prevalence of Patellofemoral pain studies (eSNAPPS)

ObjectiveThis study validated the newly adapted electronic SNAPPS (eSNAPPS) against the original paper SNAPPS. Subsequently, the study estimated the prevalence of PFP in running participants and spectators attending three mass-participant running events in the United Kingdom by using the eSNAPPS tool.DesignThis study had two parts. Firstly, a validation of the original paper version of the SNAPPS tool. Secondly, if validation was achieved, eSNAPPS was used in a prevalence study.ParticipantsA convenience sample of running participants and spectators aged 18–40 years attending the mass participation running events.Main outcome measureThe 12-month prevalence of PFP.Results: eSNAPPS was valid in identifying those with PFP (ICC 0.99 for Overall agreement, p < 0.0001). In the prevalence study, a total of 1080 running participants and spectators completed the eSNAPPS. The overall prevalence of PFP was 17.4% (95%CI: 15.2%, 19.8%); 20.5% of males (16.5, 24.9) and 15.7% of females (13.1, 18.7) had PFP. Prevalence was 17.4% (15.2, 19.8) in spectators and 16.7% in running participants (14.5, 19.0).ConclusionThe overall PFP prevalence in this study was slightly smaller than those previously reported in the literature. Findings also show that there were similar prevalence estimates in spectators and running participants.     

The quality of mother–child shared reading: its relations to child’s storytelling and home literacy environment

In the present study, we analysed the relations among the quality of mother–child shared reading, child’s storytelling and family literacy environment. The sample included 20 mother–child dyads, with 5-year-old children, who were recorded during shared reading. The quality of shared reading was assessed with the Scale for Observing Shared Reading while children’s storytelling was assessed with the textless book Frog Goes to Dinner. We found that the quality of mother–child shared reading was related to the coherence of children’s stories and to the factors of home literacy environment. Child’s age when parents started reading to him, the number of all books and children’s books in child’s home together explained 43.1% of the variance in the quality of shared reading. The findings give an insight into the process of the quality of the interactive reading between a child and an adult and emphasize the importance of shared reading for child’s storytelling.     

PDCA循环在输液室规范化管理中的应用

目的研究PDCA(计划—实施—检查—处理)循环管理模式在医院输液室规范化管理中的应用效果。方法分析影响输液室护理服务质量的原因,成立护理质量管理小组,提出切实可行的整改措施,并组织落实。每月科会讨论实施情况,每季小结一次,未解决的问题进入下一轮PDCA。结果比较输液室在实施PDCA循环前后,护患纠纷发生率及不良事件发生率比较,差异有高度统计学意义(P<0.01);满意度及护理部对输液室质量评分差异有统计学意义(P<0.05)。结论 PDCA循环是输液室规范化管理中的一项行之有效的管理模式。     

A set of interesting sequoiatones stereoisomers from a wetland soil-derived fungus Talaromyces flavus

Four interesting sequoiatones stereoisomers (1–4) were isolated from a wetland soil-derived fungus Talaromyces flavus by chiral HPLC. On the basis of comprehensive NMR and mass analyses, their planar structures were elucidated as the same as that of sequoiatone B. Among them, 1 and 3 (or 2 and 4) were a pair of enantiomers, and 1 and 2 (or 3 and 4) were a pair of stereoisomers with epimerization at C-12, which indicated that sequoiatione-type metabolites exist as enantiomers rather than as optically pure compounds in some strains. With the quantum chemical ECD calculations, the absolute configurations of C-8 in 1–4 were determined, which is the first report to establish the absolute configuration of C-8 in sequoiatones. However, the absolute configurations of C-12 in sequoiatones are still unsolved.     

籍名家影响推广期刊阅读的实践

介绍复旦大学医科图书馆“医学名家荐刊”系列活动,从荐刊内容与形式、初步成效等方面进行阐述,从此活动中得到启示,包括建设有特色的馆藏、加强文献传递服务、多渠道争取专家的支持等方面。     

In vivo and in vitro effects of 42-hydroxy-palytoxin on mouse skeletal muscle: Structural and functional impairment

Palytoxins (PLTXs) are known seafood contaminants and their entrance into the food chain raises concern about possible effects on human health. The increasing number of analogs being identified in edible marine organisms complicates the estimation of the real hazard associated with the presence of PLTX-like compounds. So far, 42-OH-PLTX is one of the few congeners available, and the study of its toxicity represents an important step toward a better comprehension of the mechanism of action of this family of compounds. From this perspective, the aim of this work was to investigate the in vivo and in vitro effect of 42-OH-PLTX on skeletal muscle, one of the most sensitive targets for PLTXs. Our results demonstrate that 42-OH-PLTX causes damage at the skeletal muscle level with a cytotoxic potency similar to that of PLTX. 42-OH-PLTX induces cytotoxicity and cell swelling in a Na⁺-dependent manner similar to the parent compound. However, the limited Ca²⁺-dependence of the toxic insult induced by 42-OH-PLTX suggests a specific mechanism of action for this analog. Our results also suggest an impaired response to the physiological agonist acetylcholine and altered cell elasticity.