Haptoglobin Polymorphism and Association with Complications in Ghanaian Type 2 Diabetic Patients

There is scanty information on the role of genetic factors, especially those relating to haptoglobin (Hp) phenotypes in the expression of complications among diabetes mellitus patients in Ghana. In this study, we investigated whether there is any association between Hp phenotypes and diabetic complications and to determine if association of the Hp phenotypes with diabetic complications in Ghanaian diabetics differ from those in Caucasians. A total of 398 participants were randomly recruited into the study. These comprised diabetic patients numbering 290 attending a diabetes Clinic in Ghana and 108 non-diabetic controls from the same community. Analyses of the results indicate that most of the diabetics with complications were of the Hp 2–2 (35%) and Hp 2–1 (23.9%) phenotypes. Fewer diabetics were found to be of the Hp 2–1 M phenotype. The controls were mostly of Hp 1–1 and Hp 2–1 M phenotypes. The odds ratio of having complications in a diabetic with an Hp 2–2 phenotype was 18.27 times greater than that for Hp 0–0. Hp 2–2 phenotype with its poor antioxidant activity may therefore be a useful predictor for the propensity of an individual to develop diabetes complications.     

Association Between Urinary IgG and Relative Risk for Factors Affecting Proteinuria in Type 2 Diabetic Patients

Abnormal glomerular permeability is the primary step towards the glomerulosclerosis. The progression rate of glomerulosclerosis is proportionate to abundance and severity of lesions created at incipient stage, which is reflected as proteinuria even though eGFR remains in the normal range. Therefore, there is a current need to find out the association between relative risks for the factors leading to proteinuria. The relations could be more informative, if it is with respect to the macromolecules like “IgG” excretion in urine. Type 2 diabetic patients were selected for this study with eGFR > 75 ml/min/1.73 m² and grouped into four quartiles based on UIgGCR. The markers of key factors affecting progression of proteinuria were estimated through biochemical tests. The impact of these markers on proteinuria was accessed by applying multinomial logistic regression. The adjusted odds ratio for the UGAGCR was 1.186 (95 % CI: 1.061–1.327) P < 0.003 in highest quartiles of UIgGCR, followed by odds ratio for markers of collagen catabolism 1.051 (95 % CI: 1.025–1.079) P < 0.001, and USACR 1.044 (95 % CI: 1.013–1.077) P < 0.006 respectively. The marker of glycation, i.e., glycated hemoglobin showed the highest odds ratio 5.449 (95 % CI: 1.132–26.236) P < 0.035. In addition, odds for the systolic blood pressure was observed 1.387 (95 % CI: 1.124–1.712) P < 0.002. The higher odds inform and could help to discriminate the diabetic patients with fast progressive diabetic nephropathy. The study describes critical relationship between the urinary excretion of IgG and factors leading to proteinuria in type 2 diabetic patients.     

Estimated Creatinine Clearance, Homocysteine and High Sensitivity-C-Reactive Protein Levels Determination for Early Prediction of Nephropathy and Atherosclerosis Risk In Type 2 Diabetic Patients

Type 2 diabetes mellitus (T2D) patients are increased risk for cardiovascular disease (CVD) and chronic kidney disease (CKD). Many studies had demonstrated that CKD is significantly associated with CVD. We aim to indicate the using estimated creatinine clearance (eCrCl), homocysteine (tHcy), and high sensitivity-C-reactive protein (hs-CRP) levels, may have an impact on the interpretation risk for nephropathy and CVD. eCrCl was using the Cockroft-Gault formula, eCrCl levels were stratified according to the Kidney Disease Outcome Quality Initiative definition. We measured serum tHcy, hs-CRP, and the other biochemical variables in 54 T2D patients compared with 40 age matched healthy controls (NDM). T2D patients were significantly lower eCrCl than NDM (P < 0.05). T2D patients also showed significantly higher in tHcy, hs-CRP, and MDA levels than NDM subjects (P < 0.05). The eCrCl was significantly correlated with tHcy and hs-CRP levels in T2D patients (r = −0.504, P < 0.001; r = −0.282, P = 0.047). eCrCl had an impact on interpretation for CKD, especially in T2D patients. Decrease eCrCl concomitant with increased in tHcy, hs-CRP, and MDA levels may present a higher risk for future diabetic nephropathy and CVD.     

Study of Common Genetic Variant S447X in Lipoprotein Lipase and Its Association with Lipids and Lipoproteins in Type 2 Diabetic Patients

Elevated plasma triglyceride and non-esterified fatty acid concentrations may cause insulin resistance and type 2 diabetes mellitus. Lipoprotein lipase (LPL) is a rate-determining enzyme in lipid metabolism. A variant in the LPL gene has been identified which alters the penultimate amino acid Serine at 447 to a stop codon (S447X), and results in a truncated LPL molecule lacking the C-terminal dipeptide Ser–Gly. The present study was designed to evaluate the frequency of S447X variant in the LPL gene and its effect on the lipid and lipoprotein levels in type 2 diabetic subjects. The genotype frequency distributions of type 2 diabetes patients and controls were in Hardy–Weinberg equilibrium. Comparison of the genotype and allelic frequencies of S447X in subjects with type 2 diabetics compared to controls demonstrated no significant difference. In subjects with type 2 diabetics having hypertriglyceridemia (TG ≥ 150 mg/dl) compared to diabetics with TG level <150 mg/dl, significant difference in genotype frequency was found among these groups, while allelic frequency of X was significantly differed. Logistic regression analysis showed the negative association of LPL S447X variant with TG and VLDL cholesterol, while no association with total cholesterol, HDL cholesterol and LDL cholesterol was found. The lipid levels except for HDL cholesterol were found to be significantly lower in carriers for S447X than wild type in diabetes group. The decreased level of TG and TG rich lipoprotein in subjects with SNP S447X in LPL, predicts anti-atherogenic activity of carriers for S447X variant in general population as well as type 2 diabetic patients.     

A Comparative Study of Clinical Utility of Spot Urine Samples with 24-h Urine Albumin Excretion for Screening of Microalbuminuria in Type 2 Diabetic Patients

Twenty-four hour urinary albumin excretion (UAE) is considered as gold standard method for albuminuria measurement, but collection of 24-h urine is inconvenient. The aim of present study was to evaluate whether albumin: creatinine ratio (ACR) and urinary albumin concentration (UAC) in different spot urine samples correlate or not with 24-h UAE for screening of microalbuminuria in type 2 diabetic patients. We collected first morning void (FMV), random urine sample (RUS) and 24-h urine, separately on consecutive days from 104 type 2 diabetic patients. ACR and UAC in each spot urine sample compared with 24-h UAE with regard to Pearson correlation coefficient. Pearson’s correlation of albumin: creatinine ratio (ACR) with 24-h UAE was (r = 0.802 and 0.623) in first morning void (FMV) and random urine sample (RUS), respectively. Pearson’s correlation coefficient of urinary albumin concentration (UAC) compared with 24-h UAE was (r = 0.943 and 0.920), in FMV and RUS, respectively, P < 0.01. Results revealed that values in first morning void (FMV) were better correlated with 24-h urinary albumin excretion (UAE), than the values in random urine sample (RUS). We conclude that the first morning void (FMV) may be able to replace 24-h urine collection, preferably urinary albumin concentration (UAC) in the initial screening of microalbuminuria in diabetic patients.     

政治关联、创新基金与企业研发投入

为探索不同的政治关联方式、创新基金与研发投入三者之间的关系,以创业板上市公司2011-2014年的数据为样本进行研究,发现虽然从整体来衡量,政治关联对企业研发投入有显著的消极影响,但是不同的关联方式对研发投入具有不同的影响和作用机制.代表委员类政治关联对企业的研发投入有负向影响,而政府官员类政治关联有助于企业增加研发投入,并且创新基金在其中起到中介作用.     

Altered Kinetics Properties of Erythrocyte Lactate Dehydrogenase in Type II Diabetic Patients and Its Implications for Lactic Acidosis

Recent studies have been noted that the erythrocytes from Type II diabetic patients show significantly altered structural and functional characteristics along with the changed intracellular concentrations of glycolytic intermediates. More recent studies from our laboratory have shown that the activities of enzymes of glycolytic pathway changed significantly in RBCs from Type II diabetic patients. In particular the levels of lactate dehydrogenase (LDH) increased significantly. Lactic acidosis is an established feature of diabetes and LDH plays a crucial role in conversion of pyruvate to lactate and reportedly, the levels of lactate are significantly high which is consistent with our observation on increased levels of LDH. Owing to this background, we examined the role of erythrocyte LDH in lactic acidosis by studying its kinetics properties in Type II diabetic patients. Km, Vmax and apparent catalytic efficiency were determined using pyruvate and NADH as the substrates. With pyruvate as the substrate the Km values were comparable but Vmax increased significantly in the diabetic group. With NADH as the substrate the enzyme activity of the diabetic group resolved in two components as against a single component in the controls. The Apparent Kcat and Kcat/Km values for pyruvate increased in the diabetic group. The Ki for pyruvate increased by two fold for the enzyme from diabetic group with a marginal decrease in Ki for NADH. The observed changes in catalytic attributes are conducive to enable the enzyme to carry the reaction in forward direction towards conversion of pyruvate to lactate leading to lactic acidosis.     

p38 MAPK Inhibitor (SB203580) and Metformin Reduces Aortic Protein Carbonyl and Inflammation in Non-obese Type 2 Diabetic Rats

Microvascular and macrovascular diseases are the main causes of morbidity in type 2 diabetes patients through chronic hyperglycaemic condition via oxidative stress and inflammation. Reactive oxygen species (ROS) activate p38 MAPK phosphorylation and inflammation which enhances protein modification by carbonylation. The use of metformin and a p38 MAPK inhibitor is hypothesised to reduce ROS production and inflammation but effects of metformin and p38 MAPK inhibitor (SB203580) on ROS production and inflammation in vascular type 2 diabetes mellitus non-obese (T2DM) have not been investigated. The Goto-Kakizaki rat T2DM model was divided into three groups as T2DM, T2DM treated with 15 mg/kg bw metformin and T2DM treated with 2 mg/kg bw SB203580 for 4 weeks. Rat aortas were isolated and protein carbonyl (PC) contents were measured by spectrophotometric DNPH assay. Aortic IL-1ß level was determined by ELISA. Results showed that aortic PC contents in the T2DM group were significantly higher than in non-diabetic rats. Treatment with metformin or SB203580 significantly reduced PC contents while only metformin significantly reduced IL-1ß levels. Findings indicated that metformin reduced ROS production and inflammation in diabetic vessels and possibly reduce vascular complications in non-obese T2DM.     

基于模块化的物联网商业模式:结构、类型与构建

当前,理论界与实践界都认为企业需要构建恰当的物联网商业模式,从而有效地释放和获取物联网技术的商业价值。为此,运用模块化理论深入解析物联网商业模式的复杂结构、可能形态与构建路径。研究发现:用户企业物联网商业模式是由能够独立设计而又功能集成的技术模块和业务模块构成;按照用户企业处理看得见的设计规则可将物联网商业模式划分为封闭型、开放型与自适应型3种类型;用户企业通过模块整合构建物联网商业模式,包括技术模块整合、技术模块与业务模块整合、跨企业的模块整合3个层次。     

Diagnostic Laboratories in India: Investigating Quality Characteristics,Productivity and Time of Reporting

This is the result of a Survey of diagnostics laboratories in the Asia Pacific (APAC) region with perspectives on India, investigating the three key aspects that are central to the success of a laboratory: quality, cost and speed. This Survey provides a comparison in selected performance indicators in a large number of diagnostic laboratories in a broad range of countries in the APAC region. The Survey provides data on some key performance characteristics such as quality improvement activities, staff productivity and Turnaround Time (TAT). This Survey also demonstrates in India the common issues facing all the laboratories surveyed but also common solutions using a Quality Systems approach which involves Accreditation, customer responsiveness, greater use of IT, automation and Lean principles. Indian laboratories reported less automation and fewer laboratories have Laboratory Information Systems. The productivity by various measures in Indian laboratories was less than in other APAC laboratories. TAT was more commonly monitored in the Indian specimens though there were fewer laboratories compared with the APAC specimens where there were separate TATs for Short Turnaround Time and Routine specimens.     

Diabetic cardiomyopathy and reactive oxygen species (ROS) related parameters in male and female rats: A comparative study

Studies were carried out to examine and compare the effects of alloxan-diabetes on reactive oxygen species (ROS) related parameters in the heart from male and female rats. Effects of insulin treatment were also evaluated. The diabetic state severely compromised the ROS defense mechanism in the cardiac tissue and the effects were more pronounced in the female than in the male rats. There was several fold increase in the xanthine oxidase (XO) activity in general and the magnitude of increase was higher in the females; insulin treatment resulted in further increase in the XO activity. The glucose-6-phosphate dehydrogenase (G6PDH) and catalase activities decreased and the reduced glutathione (GSH) content in mitochondria was completely depleted in diabetic state with significant decrease in the GSH levels in the post-mitochondrial fraction; the effect was more pronounced in the females. The superoxide dismutase (SOD) and glutathione peroxidase (GPox) activities increased in the diabetic state to a greater extent in male rats. Insulin treatment had restorative action only on some parameters. In conclusion, our results suggest that diabetic state may further compromise the weak ROS defense systems in the heart thus initiating a lesion at the level of mitochondria which ultimately leads to cardiomyopathy and the effects are especially more pronounced in the females. Our results also pointed out that insulin treatment was ineffective in restoring ROS related parameters.     

Differential Expressions of p53, p53R2, hRRM2 and PBR in Chronic Lymphocytic Leukemia: A Correlation with Intracellular Cholesterol

Regulation of intracellular cholesterol homeostasis exists under balance between intracellular biosynthesis and uptake from extracellular origin by cell surface transport proteins. Expected role of cholesterol on either tumor suppressor gene and/or DNA synthesis has been aimed in the present study to explore intracellular cholesterol homeostasis in CLL subjects. Higher expressions of p53R2 (p53 dependent subunit of ribonucleotide reductase) and p53 were found in lymphocytes of chronic human lymphocytic leukemia as comparison to their normal counterparts. Inverse relation was found with p53 independent R2 subunit (in human hRRM2) of ribonucleotide reductase, which was found to be decreased from its control group. More expression of peripheral type benzodiazepine receptor, a cholesterol transporter, was noticed in isolated nuclear fraction with simultaneous increase of cholesterol concentration in cytoplasmic and nuclear compartments. A parallel increase of cholesterol in cell nucleus with increased p53R2 expression shows priority of the involvement of cholesterol in the process of cell replication.     

浅谈物理教学中布白艺术的现实依据、功能与创生策略

物理教学布白艺术是指在物理课堂教学中教师故意留给学生空间和余地,它的产生有深刻的文化经验、生活经验和心理经验基础。在物理教学中恰当运用布白艺术可以发展学生思维能力、激发学生求知欲、愉悦学生心灵。初中物理教学布白艺术创生策略包括:省略、质疑、停顿和暗示,教师在教学过程中灵活运用布白艺术创生策略,可以达到良好的教学效果。     

Role of Matrix Degradation,Oxidative Stress,Inflammation & Trace Elements in COVID-19 Patients: A Multivariate Study from India

The interrelationship between matrix degradation, oxidative stress, inflammation and trace elements can be speculated in COVID-19. The objective of the study was to evaluate the oxidative stress, inflammation and matrix degradation markers and trace elements in COVID-19 positive patients. A group of confirmed severe COVID-19 positive patients (n = 30) along with COVID-19 negative patients (n = 30) with similar symptoms were included. Both group of patients were assessed for oxidative stress markers, inflammatory cytokines, matrix metalloproteinase (MMP)s and their inhibitors along with trace elements in blood. All the data were subjected to univariate as well as multivariate analysis including PCA, PLS-DA, OPLS-DA. Diagnostic accuracy was tested by ROC curve analysis. Further relationship with Neutrophil/ lymphocyte (N/L) ratio was established if any. Increased oxidative stress, inflammation and matrix degradation is evidenced by significant rise in oxidative markers, inflammatory cytokines and MMP9/TIMP-1 ratio. Decreased Cu/Zn ratio is also observed in COVID-19 positive patients. Multivariate analysis identified SOD, Cu/Zn ratio, IL-6 and TOS, as effective discriminant among the two groups of patients. Further, accuracy was confirmed by ROC curves. Neutrophil/ lymphocyte (N/L) ratio, shows significant negative association with SOD (r= -0.75, p < 0.005) and Cu/Zn ratio (r = -0.88, p < 0.005). These data suggest the attributes of these biomarkers in disease severity. The potential use of these blood-based laboratory markers in disease prognosis seems promising and warrants further attention. Given by the symptoms and severity of the disease, it will be promising to monitor Cu/Zn ratio along with other prognostic indicators.     

大都市边缘区域耕地数量变化的时空特征及动力机制——以广州市花都区为例

土地利用/土地覆盖变化已成为全球变化研究的核心领域和热点问题之一，其中大都市边缘区域耕地变化研究意义尤为重大。本研究利用广州市花都区近30年来的普查、更新调查和逐年统计数据，结合卫星影像资料和实地调研，在深入分析耕地数量变化时空特征基础上，重点对耕地变化影响因子进行灰色关联分析，揭示出：工业化及产业结构调整、人口增长及城市化分别构成全区耕地减少的第一、二驱动因子，经济对外开放对耕地数量变化的影响力不断加强，土地政策、土地规划、经济政策和行政区划等制度因子亦对耕地数量周期性变化产生重要影响。研究认为综合运用耕地保护管制和经济调节手段、建立土地资源节约型产业结构体系、加强建设用地规划与整理整治、促进集约用地和内涵式发展等是大都市边缘区域耕地变化调控的主要路径。