The Prevalence of the Genetic Polymorphism of GSTM1, GSTT1 and GSTP1 and Its Relationship with Clinical Criteria of Multiple Sclerosis (MS) Patients in Tehran

BACKGROUND AND OBJECTIVE: Multiple Sclerosis is the chronic inflammation of central nervous system with demyelinated lesions in the brain and spinal cord. The genetic polymorphisms associated with glutathione S-transferase enzymes involved in antioxidant defense in Iranian patients have not been investigated. Therefore, in the present study, the prevalence of the genetic polymorphism of glutathione S-transferase M1, P1 and T1 and its relationship with clinical criteria of MS patients with has been examined. METHODS: In this case-control study, 69 patients who referred to Sina Hospital in Tehran and had no panic attack within the last three months and 74 healthy subjects were interviewed. After examination by neurologist and blood sampling, DNA extraction was performed using Roche kit. Then, the genotypic variations of the samples were evaluated using RFLP-PCR and its prevalence was analyzed in relation with age, birth weight, malignancy (EDSS) and gender using GraphPad Prism software. FINDINGS: Most malignancies were observed in men (3.1±5.9) and the highest incidence rate was observed in those born in May (30%). Although the results of genotyping between the studied groups and their gender did not show any significant difference (OR: 2-4, p>0.05), patients with GSTM1 deficiency developed the disease at a lower age (32.8±2.6 years) compared with other patients (29.5±8.9 years) (CI-95%: 20.3–26.4, p=0.009). In addition, people with a rare GSTM1 allele who smoked cigarette had higher EDSS (CI-95%: 2.1–3.7, p=0.03). CONCLUSION: Based on the results of this study, the effect of GSTM1 on malignancy is indicative of its role in detoxification of tobacco products and can be used as an agent for early diagnosis of disease in people who are susceptible to this disease

KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancer

The association between kidney disease and cancer is multifaceted and complex. Persons with chronic kidney disease (CKD) have an increased incidence of cancer, and both cancer and cancer treatments can cause impaired kidney function. Renal issues in the setting of malignancy can worsen patient outcomes and diminish the adequacy of anticancer treatments. In addition, the oncology treatment landscape is changing rapidly, and data on tolerability of novel therapies in patients with CKD are often lacking. Caring for oncology patients has become more specialized and interdisciplinary, currently requiring collaboration among specialists in nephrology, medical oncology, critical care, clinical pharmacology/pharmacy, and palliative care, in addition to surgeons and urologists. To identify key management issues in nephrology relevant to patients with malignancy, KDIGO (Kidney Disease: Improving Global Outcomes) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology in December 2018. This report covers issues related to kidney impairment and solid organ malignancies as well as management and treatment of kidney cancer. Knowledge gaps, areas of controversy, and research priorities are described

Helicobacter pylori and cancer among adults in Uganda

Data from Africa on infection with Helicobacter pylori (H. pylori) are sparse. Therefore, as part of an epidemiological study of cancer in Uganda, we investigated the prevalence and determinants of antibodies against H. pylori among 854 people with different cancer types and benign tumours. Patients were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against H. pylori. In all patients combined, excluding those with stomach cancer (which has been associated with H. pylori infection), the prevalence of antibodies was 87% (723/833) overall, but declined with increasing age (p = 0.02) and was lower among people who were HIV seropositive compared to seronegative (p <0.001). Otherwise, there were few consistent epidemiological associations. Among those with stomach cancer, 18/21 (86%) had anti-H. pylori antibodies (odds ratio 0.8, 95% confidence intervals 0.2–2.9, p = 0.7; estimated using all other patients as controls, with adjustment for age, sex and HIV serostatus). No other cancer site or type was significantly associated with anti-H. pylori antibodies. The prevalence of H. pylori reported here is broadly in accord with results from other developing countries, although the determinants of infection and its' role in the aetiology of gastric cancer in Uganda remain unclear

Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research

Relationship between plasma sialic acid and fibrinogen concentration and incident micro- and macrovascular complications in type 1 diabetes. The EURODIAB Prospective Complications Study (PCS)

AIMS/HYPOTHESIS: Type 1 diabetes is associated with an increased risk of vascular complications. This increased risk could be explained by sialic acid and/or fibrinogen. It is also not clear what explains the abolition of sex-related differences affecting risk of CHD in the presence of type 1 diabetes. Therefore, we examined whether fibrinogen and sialic acid are related to incident micro- and macrovascular complications in patients with type 1 diabetes. METHODS: A subset (n=2329) of the EURODIAB Prospective Complications Study was analysed. Sialic acid and fibrinogen concentrations were measured at baseline. The main outcomes after 7 years were development of albuminuria, retinopathy, neuropathy and CHD. RESULTS: Univariable and multivariable models using Cox proportional survival analyses showed that an SD unit increase in sialic acid and fibrinogen levels was significantly associated with CHD in men only. Adjusted standardised hazard ratios (sHRs) were 1.50 (95% CI 1.05-2.15) and 1.40 (95% CI 1.06-1.86) for sialic acid and fibrinogen, respectively. Initial associations between (1) sialic acid and incident retinopathy [standardised odds ratio (sOR) men 1.68, 95% CI 1.10-2.57], (2) fibrinogen and retinopathy (sOR women 1.37, 95% CI 1.06-1.78) and (3) sialic acid and neuropathy (sOR men 1.37, 95% CI 1.06-1.77) were shown, but became non-significant in multivariable models. CONCLUSIONS/INTERPRETATION: Sialic acid and fibrinogen are strong predictors of CHD in men with type 1 diabetes, beyond the effect of established risk factors. The associations found with microvascular complications were not independent of other risk factors

Imputation strategies for missing binary outcomes in cluster randomized trials

<p>Abstract</p> <p>Background</p> <p>Attrition, which leads to missing data, is a common problem in cluster randomized trials (CRTs), where groups of patients rather than individuals are randomized. Standard multiple imputation (MI) strategies may not be appropriate to impute missing data from CRTs since they assume independent data. In this paper, under the assumption of missing completely at random and covariate dependent missing, we compared six MI strategies which account for the intra-cluster correlation for missing binary outcomes in CRTs with the standard imputation strategies and complete case analysis approach using a simulation study.</p> <p>Method</p> <p>We considered three within-cluster and three across-cluster MI strategies for missing binary outcomes in CRTs. The three within-cluster MI strategies are logistic regression method, propensity score method, and Markov chain Monte Carlo (MCMC) method, which apply standard MI strategies within each cluster. The three across-cluster MI strategies are propensity score method, random-effects (RE) logistic regression approach, and logistic regression with cluster as a fixed effect. Based on the community hypertension assessment trial (CHAT) which has complete data, we designed a simulation study to investigate the performance of above MI strategies.</p> <p>Results</p> <p>The estimated treatment effect and its 95% confidence interval (CI) from generalized estimating equations (GEE) model based on the CHAT complete dataset are 1.14 (0.76 1.70). When 30% of binary outcome are missing completely at random, a simulation study shows that the estimated treatment effects and the corresponding 95% CIs from GEE model are 1.15 (0.76 1.75) if complete case analysis is used, 1.12 (0.72 1.73) if within-cluster MCMC method is used, 1.21 (0.80 1.81) if across-cluster RE logistic regression is used, and 1.16 (0.82 1.64) if standard logistic regression which does not account for clustering is used.</p> <p>Conclusion</p> <p>When the percentage of missing data is low or intra-cluster correlation coefficient is small, different approaches for handling missing binary outcome data generate quite similar results. When the percentage of missing data is large, standard MI strategies, which do not take into account the intra-cluster correlation, underestimate the variance of the treatment effect. Within-cluster and across-cluster MI strategies (except for random-effects logistic regression MI strategy), which take the intra-cluster correlation into account, seem to be more appropriate to handle the missing outcome from CRTs. Under the same imputation strategy and percentage of missingness, the estimates of the treatment effect from GEE and RE logistic regression models are similar.</p

Effect of particle size, coupling agent and DDGS additions on Paulownia wood polypropylene composites

Studies aimed at improving the tensile, flexural, impact, thermal, and physical characteristics of wood–plastic composites composed of Paulownia wood flour derived from 36-month-old trees blended with polypropylene were conducted. Composites of 25% and 40% w/w of Paulownia wood were produced by twin-screw compounding and injection molding. Composites containing 0–10% by weight of maleated polypropylene were evaluated and an optimum maleated polypropylene concentration determined, i.e., 5%. The particle size distribution of Paulownia wood filler is shown to have an effect on the tensile and flexural properties of the composites. Novel combination composites of dried distiller’s grain with solubles mixed with Paulownia wood (up to 40% w/w) were produced and their properties evaluated. Depending on the composite tested, soaking composites for 872 h alters mechanical properties and causes weight gain

NT-proBNP and Circulating Inflammation Markers in Prediction of a Normal Myocardial Scintigraphy in Patients with Symptoms of Coronary Artery Disease

Myocardial perfusion imaging (MPI) can detect myocardial perfusion abnormalities but many examinations are without pathological findings. This study examines whether circulating biomarkers can be used as screening modality prior to MPI.243 patients with an intermediate risk of CAD or with known CAD with renewed suspicion of ischemia were referred to MPI. Blood samples were analyzed for N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), YKL-40, IL-6, matrix metalloproteinase 9 (MMP-9) and high sensitive C-reactive protein (hsCRP). Patients with myocardial perfusion defects had elevated levels of NT-proBNP (p<0.0001), YKL-40 (p = 0.03) and IL-6 (p = 0.03) but not of hsCRP (p = 0.58) nor of MMP-9 (p = 0.14). The NT-proBNP increase was observed in both genders (p<0.0001), whereas YKL-40 (p = 0.005) and IL-6 (p = 0.02) were elevated only in men. A NT-proBNP cut off-concentration at 25 ng/l predicted a normal MPI with a negative predictive value >95% regardless of existing CAD.20-25% of patients suspected of CAD could have been spared a MPI by using a NT-proBNP cut-off concentration at 25 ng/l with a negative predictive value >95%. NT-proBNP has the potential use of being a screening marker of CAD before referral of the patient to MPI