Validating an ontology-based algorithm to identify patients with Type 2 Diabetes Mellitus in Electronic Health Records

BackgroundImproving healthcare for people with chronic conditions requires clinical information systems that support integrated care and information exchange, emphasizing a semantic approach to support multiple and disparate Electronic Health Records (EHRs). Using a literature review, the Australian National Guidelines for Type 2 Diabetes Mellitus (T2DM), SNOMED-CT-AU and input from health professionals, we developed a Diabetes Mellitus Ontology (DMO) to diagnose and manage patients with diabetes. This paper describes the manual validation of the DMO-based approach using real world EHR data from a general practice (n = 908 active patients) participating in the electronic Practice Based Research Network (ePBRN).MethodThe DMO-based algorithm to query, using Semantic Protocol and RDF Query Language (SPARQL), the structured fields in the ePBRN data repository were iteratively tested and refined. The accuracy of the final DMO-based algorithm was validated with a manual audit of the general practice EHR. Contingency tables were prepared and Sensitivity and Specificity (accuracy) of the algorithm to diagnose T2DM measured, using the T2DM cases found by manual EHR audit as the gold standard. Accuracy was determined with three attributes – reason for visit (RFV), medication (Rx) and pathology (path) – singly and in combination.ResultsThe Sensitivity and Specificity of the algorithm were 100% and 99.88% with RFV; 96.55% and 98.97% with Rx; and 15.6% and 98.92% with Path. This suggests that Rx and Path data were not as complete or correct as the RFV for this general practice, which kept its RFV information complete and current for diabetes. However, the completeness is good enough for this purpose as confirmed by the very small relative deterioration of the accuracy (Sensitivity and Specificity of 97.67% and 99.18%) when calculated for the combination of RFV, Rx and Path. The manual EHR audit suggested that the accuracy of the algorithm was influenced by data quality such as incorrect data due to mistaken units of measurement and unavailable data due to non-documentation or documented in the wrong place or progress notes, problems with data extraction, encryption and data management errors.ConclusionThis DMO-based algorithm is sufficiently accurate to support a semantic approach, using the RFV, Rx and Path to define patients with T2DM from EHR data. However, the accuracy can be compromised by incomplete or incorrect data. The extent of compromise requires further study, using ontology-based and other approaches.     

Tolerogenic dendritic cell vaccines to treat autoimmune diseases: Can the unattainable dream turn into reality?

Autoimmune diseases affect about one in 15 individuals in developed countries and are characterized by a breakdown in immune tolerance. Current therapeutic approaches against destructive immune responses in autoimmune diseases are based on non-specific agents systemically suppressing the function of many immune effector cells. This indiscriminate immunosuppression, however, often causes serious and sometimes life-threatening side effects. Therefore, the need for more specific treatments resulting in lower toxicity and longer-term solutions is high. Because of the established role of dendritic cells (DCs) in maintaining the balance between immunity and tolerance, tolerogenic (tol)DCs might be novel therapeutic targets to prevent undesirable (auto-)immune responses. The idea behind tolDC therapy is that it is a highly targeted, antigen-specific treatment that only affects the auto-reactive inflammatory response. The therapeutic potential of tolDCs has already been proven in experimental animal models of different autoimmune disorders as well as with in vitro experiments using ex vivo generated human tolDCs, thus the challenge remains in bringing tolDC therapy to the clinic, although first clinical trials have been conducted. In this review, we will extensively discuss the use of tolDCs for induction of antigen-specific tolerance in several autoimmune disease settings, from bench to bedside, including currently applied strategies to generate tolDCs as well as technical difficulties and challenges in the field.     

Ameliorative effect of Yokukansan on social isolation-induced aggressive behavior of zinc-deficient young mice

Yokukansan, a traditional Japanese medicine has been used to cure neuropsychological disorders. In the present study, the effect of Yokukansan on social isolation-induced aggressive behavior was examined in zinc-deficient mice, which were fed a zinc-deficient diet and a drinking water containing Yokukansan for 2 weeks. In the resident–intruder test, the rate of mice that exhibited aggressive behavior in zinc-deficient mice, which was significantly higher than that in the control mice, was significantly decreased by administration of Yokukansan. The basal level of serum glucocorticoid, which was significantly higher in zinc-deficient mice, was lowered by administration of Yokukansan. On the other hand, serum glucocorticoid levels after the resident–intruder test were almost the same between the control and zinc-deficient mice. However, administration of Yokukansan to zinc-deficient mice significantly increased serum glucocorticoid level after the resident–intruder test and the significant difference in the rate of serum corticosterone level after the test to the basal level between the control and zinc-deficient mice was abolished. Dietary zinc deficiency increases the basal levels of serum glucocorticoid, while may insufficiently increase serum glucocorticoid levels in the resident–intruder test. The concentrations of glutamate and GABA (γ-aminobutyric acid) in the brain were significantly higher in zinc-deficient mice, while Yokukansan ameliorated the significant increases. These results indicate that Yokukansan ameliorates social isolation-induced aggressive behavior of zinc-deficient mice, probably via amelioration of abnormal glucocorticoid secretion. The ameliorative effect seems to be linked to the modification of glutamatergic neuron activity after administration of Yokukansan.     

TNF-α基因rs1800629多态性与中国人群宫颈癌的易感性

  目的  探讨肿瘤坏死因子-α(tumor necrosis factor α,TNF-α)基因位点rs1800629单核苷酸多态性与宫颈癌发生的关系。  方法  选择经组织学确诊的汉族552例新发宫颈癌患者作为病例组,与病例组人群不存在生物学相关的654例正常人群作为对照组,利用Taqman实时荧光定量聚合酶链式反应(polymerase chain reaction,PCR)技术检测基因型,Logistic回归模型计算基因型与人群罹患宫颈癌的风险比(odds ratio,OR)及其95%的可信区间(95%CI);Stata 11.0软件对中国人群rs1800629多态性与宫颈癌的关系进行Meta分析。  结果  与TNF-α rs1800629野生型GG基因型的相比,个体携带rs1800629 GA、AA及GA/AA基因型的个体罹患宫颈癌的风险差异无统计学意义(均有P>0.05);对该位点多态性与宫颈癌关系的Meta分析发现,TNF-α rs1800629遗传变异与中国人群宫颈癌的发生无明显相关性。  结论  TNF-α基因rs1800629位点多态性可能与中国人群宫颈癌发生无关。     

Neuroprotective effects of Caralluma tuberculata on ameliorating cognitive impairment in a d-galactose-induced mouse model

Cognitive deficiency and oxidative stress have been well documented in aging disorders including Alzheimer’s disease. The aim of this study was to investigate the therapeutic efficacy of Caralluma tuberculata methanolic extract (CTME) on cognitive impairment in mice induced with d-galactose. In this study we assessed the therapeutic efficacy of CTME on cognitive impairment in mice induced with d-galactose by conduction of behavioral and cognitive performance tests. In order to explore the possible role of CTME against d-galactose-induced oxidative damages, various biochemical indicators were assessed. Chronic administration of d-galactose (150 mg/kg d, s.c.) for 7 weeks significantly impaired cognitive performance (in step-through passive, active avoidance test, Hole-Board test, Novel object recognition task and Morris water maze) and oxidative defense as compared to the control group. The results revealed that CTME treatment for two weeks (100, 200 and 300 mg/kg p.o) significantly ameliorated cognitive performance and oxidative defense. All groups of CTME enhanced the learning and memory ability in step-through passive, active avoidance test, Hole-Board test Novel object recognition task and Morris water maze. Furthermore, high and middle level of CTME (300 and 200 mg/kg p.o) significantly increased Total antioxidative capacity (T-AOC), Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity, neprilysin (NEP), and β-site AβPP cleaving enzyme 1 (BACE1) expression while Nitric Oxide (NO), Nitric Oxide Synthase (NOS) activity and Malondialdehyde (MDA) concentration, and the level of Aβ1-42 and presenilin 1 (PS1) were decreased. The present study showed that CTME have a significant relieving effect on learning, memory and spontaneous activities in d-galactose-induced mice model, and ameliorates cognitive impairment and biochemical dysfunction in mice.     

IL-7R在成人急性淋巴细胞白血病中的突变及其临床意义

目的:白介素7(IL-7)及其受体(IL-7R)在正常T细胞发育和稳态中至关重要。本研究旨在探究IL-7R在成人急性淋巴细胞白血病(ALL),特别是T细胞ALL(T-ALL)中的突变特征和临床意义。方法:对144例成人ALL患者的IL-7R的外显子进行扩增、克隆和测序,研究IL-7R的突变率,发生位点,突变类型及与临床的相关性。结果:本研究结果显示,IL-7R突变在成人T-ALL和B-ALL中的发生率分别为7.3%和1.1%,分别位于exon 6和exon 5。此外,IL-7R突变患者临床预后差。同时,本研究还观察到IL-7R突变与NOTCH1和/或PHF6突变共存。结论:IL-7R突变及其涉及的信号通路可能在T-ALL的发病机制中起重要作用。     

The impact of short-term hyperglycemia and obesity on biventricular and biatrial myocardial function assessed by speckle tracking echocardiography in a population of women with gestational diabetes mellitus

Background and aimsTo compare biventricular and biatrial myocardial strain indices assessed by two-dimensional speckle tracking echocardiography (2D-STE) in women with gestational diabetes mellitus (GDM) and those with uncomplicated pregnancy at the third trimester of pregnancy and in post-partum.Methods and results30 consecutive GDM women and 30 age-, ethnicity- and gestational week-matched controls without any comorbidity were examined in this prospective case–control study. All women underwent obstetric visit, blood tests and transthoracic echocardiography (TTE) implemented with 2D-STE analysis of all cardiac chambers at 36–38 weeks’ gestation. TTE and 2D-STE were repeated at 6–10 weeks after delivery.At 36–38 weeks’ gestation, GDM women, compared to controls, had significantly higher body mass index (BMI), blood pressure values and inflammatory markers. TTE showed increased left ventricular (LV) mass and impaired LV diastolic function in GDM women, whereas there was no significant difference between the groups in ejection fraction. 2D-STE revealed that biventricular global longitudinal strain (GLS) and biatrial reservoir strain indices were significantly lower in GDM women than controls. Third trimester BMI was inversely correlated with LV-GLS (r = ?0.86) and was independently associated with reduced LV-GLS (less negative than ?20%) in GDM women in post-partum (OR 1.81, 95%CI 1.14–2.89). A BMI value ≥ 30 kg/m² had 100% sensitivity and 99.5% specificity for identifying GDM women with impaired LV-GLS in post-partum (AUC = 0.97).ConclusionWomen with GDM, compared to women with uncomplicated pregnancy, have significantly lower biventricular and biatrial myocardial deformation indices. These abnormalities may be persistent in post-partum in GDM women with obesity.     

压力控制通气方式的肺复张手法减轻家兔重复去复张相关肺损伤

目的：研究应用压力控制通气（pressure control ventilation,PCV）方式的肺复张手法（recruitment maneuvers,RM）对家兔重复去复张相关肺损伤的影响。方法：生理盐水肺泡灌洗法复制急性呼吸窘迫综合征（acute respiratory distress syndrome,ARDS）家兔模型,分为3组。分别为：（1）肺保护性通气组（LP组）：潮气量（tidal volume,Vt）6mL／kg,呼气末正压（positive end—expiratory pressure,PEEP）根据静态压力一容积曲线低位转折点水平（lower inflection point in static pressure-volume curve,LIP）设定;（2）去复张组（DR组）：通气条件同LP组,在3h机械通气期间每10min将呼吸机管路脱开1min实施去复张;（3）去复张＋压力控制组（PCV组）：去复张后用PCV法给予RM,具体方法为：将呼吸机模式调整为压力控制通气,吸气压力设定为30cmH2O、PEEP水平设定为UP水平、I：E=1：2,维持90s。机械通气期间监测动脉血气分析及呼吸力学,机械通气3h处死动物,测定肺湿／干重比（W／D）及肺组织病理损伤评分。结果：去复张后1,2和3h时,DR组动脉氧分压（PaO2）均显著低于同时间点的LP与PCV组（P均〈0．05）,在LP与PCV两组间同时间点PaO2比较无显著性差异（P均〉0．05）;DR组静态肺顺应性（Cst）与气道平台压力（Pplat）与同时间点IJP、SI与PCV组比较差异不显著（P均〉0．05）;DR组肺W／D与LP与PCV组比较也无显著性差异（P〉0．05）;机械通气3h时DR组肺组织病理损伤评分为（10．9±0．8）,显著高于LP与PCV组（P均〈0．05）,LP与PCV组间比较无显著性差异（P均〉0．05）。结论：重复去复张明显恶化氧合,加重ARDS肺组织损伤,PCV方式的RM可以改善氧合,减轻组织损伤。     

溶血磷脂酸与血管平滑肌细胞表型转化

2003年人类基因组计划的完成开辟了人类遗传学、人类病理学等研究领域的新时代,然而近年来解析人类基因组意义过程中遇到一系列的难题使人们认识到DNA序列本身并不能解释所有关于遗传信息传递、人类疾病生物学基础等问题.随着研究的深入,人们逐渐认识到不仅蛋白编码序列,而且非编码序列、表观遗传机制等也是影响遗传信息传递、疾病发生等过程中的重要因素.     

二甲双胍与消渴热清丸合用对模型大鼠胰岛素抵抗的影响

目的:研究二甲双胍与消渴热清丸合用对模型大鼠胰岛素抵抗的影响。方法:选取体重180～200g的雄性Wistar大鼠60只,随机均分为正常对照、模型、二甲双胍、消渴热清丸和二甲双胍+消渴热清丸组。各组大鼠给药第6周后,取血分别检测空腹血糖(FBG)、血清胰岛素(FIns)、血清游离脂肪酸(FFA)、血清肿瘤坏死因子-α(TNF-α)水平与胰岛素敏感性指数(ISI)。结果:经10%果糖水喂养5周后,模型组大鼠FBG、FIns、FFA、TNF-α均较正常对照组显著增高(P<0.01),ISI较正常对照组显著降低(P<0.01),大鼠有明显的胰岛素抵抗;各给药组大鼠上述各项指标与模型组比较显著降低(P<0.01或P<0.05),胰岛素敏感指数显著升高(P<0.01);且二甲双胍+消渴热清丸组比单独给予二甲双胍的大鼠效果更好。结论:二甲双胍与中药复方消渴热清丸合用有明显的协同作用,并且能在剂量上降低西药二甲双胍的用量,从而减轻二甲双胍的毒副作用。