Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study

IntroductionUse of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada.MethodsA cohort of new-onset RA patients was identified from Quebec’s physician billing and hospitalization databases from 2002–2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity.ResultsDuring follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95 % confidence interval, 95 % CI 0.93-0.97) or other DMARDs (HR = 0.97, 95 % CI 0.95-0.99) was associated with longer time to joint replacement.ConclusionsOur results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0713-3) contains supplementary material, which is available to authorized users.     

Crocodilian phylogeny inferred from twelve mitochondrial protein-coding genes, with new complete mitochondrial genomic sequences for Crocodylus acutus and Crocodylus novaeguineae

We report complete mitochondrial genomic sequences for Crocodylus acutus and Crocodylus novaeguineae, whose gene orders match those of other crocodilians. Phylogenetic analyses based on the sequences of 12 mitochondrial protein-coding genes support monophyly of two crocodilian taxonomic families, Alligatoridae (genera Alligator, Caiman, and Paleosuchus) and Crocodylidae (genera Crocodylus, Gavialis, Mecistops, Osteolaemus, and Tomistoma). Our results are consistent with monophyly of all crocodilian genera. Within Alligatoridae, genus Alligator is the sister taxon of a clade comprising Caiman and Paleosuchus. Within Crocodylidae, the basal phylogenetic split separates a clade comprising Gavialis and Tomistoma from a clade comprising Crocodylus, Mecistops, and Osteolaemus. Mecistops and Osteolaemus form the sister taxon to Crocodylus. Within Crocodylus, we sampled five Indopacific species, whose phylogenetic ordering is ((C. mindorensis, C. novaeguineae), (C. porosus, (C. siamensis, C. palustris))). The African species C. niloticus and New World species C. acutus form the sister taxon to the Indopacific species, although our sampling lacks three other New World species and an Australian species of Crocodylus.     

Baculiferins A–O,O-sulfated pyrrole alkaloids with anti-HIV-1 activity,from the Chinese marine sponge Iotrochota baculifera

Fifteen new DOPA-derived pyrrole alkaloids, named baculiferins A–O (2–16), were isolated from the Chinese marine sponge Iotrochota baculifera, together with the known alkaloids purpurone (1) and ningalin A (17). Most of the new compounds contain one to three O-sulfate units. Their structures were determined by extensive spectroscopic analysis including ¹H and ¹³C NMR (COSY, HMQC, HMBC) and ESIMS data. A possible pathway for the biosynthetic origin of the isolated alkaloids is proposed, in which DOPA is assumed to be a joint biogenetic precursor. Baculiferins C, E–H, and K–N (4, 6–9, 12–15) were found to be potent inhibitors against the HIV-1 IIIB virus in both, MT4 and MAGI cells. Additional bioassay revealed that baculiferins could dramatically bind to the HIV-1 target proteins Vif, APOBEC3G, and gp41, for which structure–activity relationships are discussed.     

普通番茄叶肉原生质体和多毛番茄茎尖原生质体的电融合

普通番茄叶肉原生质体和多毛番茄茎尖原生质体在一交变电场中(正弦波;1mHz,200v/cm)可发生双向电泳而随机排列成串。再附加单个直流方波脉冲,可诱导相邻原生质体的融合,适宜的融合脉宽为40μs,电压幅度为3000v/cm。最高融合率可达57%。培养经电融合处理的原生质体,观察到了少数原生质体的第1次分裂。     

An optimized human resource management model for cloud-edge computing in the internet of things

The use of cloud-edge technology creates significant potential for cost reduction, efficiency and resource management. These features have encouraged users and organizations to use intelligence federated cloud-edge paradigm in Internet of Things (IoT). Human Resource Management (HRM) is one of the important challenges in federated cloud-edge computing. Since hardware and software resources in the edge environment are allocated for responding human requests, selecting optimal resources based on Quality of Service (QoS) factors is a critical and important issue in the IoT environments. The HRM can be considered as an NP-problem in a way that with proper selection, allocation and monitoring resource, system efficiency increases and response time decreases. In this study, an optimization model is presented for the HRM problem using Whale Optimization Algorithm (WOA) in cloud-edge computing. Experimental results show that the proposed model was able to improve minimum response time, cost of allocation and increasing number of allocated human resources in two different scenarios compared to the other meta-heuristic algorithms.

     

Characterization and site-directed mutagenesis of the putative novel acyl carrier protein Rv0033 and Rv1344 from Mycobacterium tuberculosis

Mycolic acids are generated in Mycobacterium tuberculosis as a result of the interaction of two fatty acid biosynthetic systems: type I fatty acid synthase (FAS) and type II fatty acid synthase. Acyl carrier protein (ACP) is a small, acidic protein in type II FAS systems. It plays a central role in mycolic acid biosynthesis by transferring the acyl groups from one enzyme to another for the completion of the fatty acid synthesis cycle. The nature of the proper recognition between ACPs and its many interactive proteins is not understood. Here, we report the over-expression, purification, and characterization of two putative ACPs: Rv0033 and Rv1344 in M. tuberculosis. In order to study the role of the conserved residues and the conformation of whole protein, some site-directed mutations of recombinant Acp1344 were made and the 3D structure of Acp1344 was modeled.     

山地视觉景观的GIS评价--以广东南昆山国家森林公园为例

视觉景观评价是指某一特定区域具有视觉价值的景观的量化评价。山地是旅游开发的重要区域,山地景观是山地资源价值和山地生态环境的重要体现之一。以广东南昆山为例,将视野总面积、水域空阔度、景观层作为七仙湖环湖地区视觉景观评价的三大因子。以基础地理数据结合DEM作为数据基础,借助ArcGIS软件作为具体实现平台,设计景观层分析和视通性分析模型,对最佳坡度、最佳坡向、水文、交通条件叠加分析后过滤的62个样地进行视觉景观定量分析,确定评价标准,最后得到8号、23号、50号、55号样地较其他样地在整体视野\,能见水域开阔和景观层次有明显优势。以此验证了将GIS空间分析技术应用于视觉景观评价的可行性,并为旅游观景点与度假村开发提供了科学依据。     

Construction and analysis of the abnormal lncRNA–miRNA–mRNA network in hypoxic pulmonary hypertension

The incidence of hypoxic pulmonary hypertension (HPH) is increasing. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in HPH, but the functions and mechanism have yet to be fully elucidated. In the present study, we established a HPH rat model with 8 h of hypoxia exposure (10% O₂) per day for 21 days. High-throughput sequencing identified 60 differentially expressed (DE) lncRNAs, 20 DE miRNAs and 695 DE mRNAs in rat lung tissue. qRT-PCR verified the accuracy of the results. The DE mRNAs were significantly enriched in immune response, inflammatory response, leukocyte migration, cell cycle, cellular response to interleukin-1, IL-17 signalling pathway, cytokine–cytokine receptor interaction and Toll-like receptor signalling pathway. According to the theory of competing endogenous RNA (ceRNA) networks, lncRNA–miRNA–mRNA network was constructed by Cytoscape software, 16 miRNAs and 144 mRNAs. The results suggested that seven DE lncRNAs (Ly6l, AABR07038849.2, AABR07069008.2, AABR07064873.1, AABR07001382.1, AABR07068161.1 and AABR07060341.2) may serve as molecular sponges of the corresponding miRNAs and play a major role in HPH.     

林分因子对成都绕城高速路域不同人工林群落物种多样性的影响

【目的】为探究林分因子对不同路域人工林群落物种多样性的影响,为成都路域人工林营造与管理提供参考。【方法】研究采用典型样地法对成都绕城高速路域现种植的5种不同人工林群落（Ⅰ,加杨纯林;Ⅱ,樟树、加杨混交林;Ⅲ,樟树纯林;Ⅳ,樟树、巨桉混交林;Ⅴ,巨桉纯林）进行全面踏查,调查林分因子及林下植被物种多样性。【结果】（1）研究区共记录植物184种,隶属于72科132属。5种不同人工林群落乔-灌-草三层的植物科属种数量均为草本层＞灌木层＞乔木层,其中樟树纯林记录到的林下物种数最多。（2）构树（Broussonetia papyrifera）和葎草（Humulus scandens）重要值占比大,分别占据不同人工林群落灌木层与草本层的优势地位。（3）在5种不同人工林群落中,樟树纯林的灌木物种丰富度指数D显著高于其他群落（P<0.05）;草本层的Shannon-Wiener指数H、Simpson指数H′和D大小变化趋势一致,表现为群落Ⅲ>Ⅳ>I>I>V,其中樟树纯林的H显著高于樟树、巨桉混交林外其他群落（P<0.05）。（4）冗余分析结果表明：乔木层平均冠幅与灌木层的D和H、草本层的H、H''、D、Jsw均呈显著正相关（P<0.01）,与灌木层的H''和Jsw均呈显著负相关（P<0.01）;乔木层平均枝下高与灌木层的H、H''、D、Jsw均呈显著正相关（P<0.01）。【结论】乔木层的树种组成、平均枝下高和平均冠幅显著影响路域人工林群落的物种多样性,选择合适树种并定期修枝管理,将有利于路域人工林良好乔灌草群落结构形成和林下植被物种多样性维持。 关键词 林分因子;路域人工林;林下植被;物种多样性