Complications leading to hospitalization due to consumption of anti-TB drugs in patients with tuberculosis in Gorgan, Iran (2007-12)

Background and Objective: Anti tuberculosis drugs therapy is the most effective method for controling the tuberculosis (TB). Early detection and appropriate treatment can prevent the TB-drug resistance. This study was carried out to determine the complications leading to hospitalization due to consumption of anti-TB drugs in patients with tuberculosis. Methods: In this descriptive-analytic study, 1550 records of patients with TB in urban and rural health centers of Gorgan, north of Iran were assessed during 2007-12. Checklist consists of demographic and clinical data for each patient was recorded in a questionare. Results: 44 cases experienced the complications of anti-TB drugs. 27 (61.4%) of cases with complications were women. 77.3% and 22.7% of patients affected with pulmonary and extra pulmonary tuberculosis,respectively. 38.6% of patients were diabetic. The hepatic complication was seen in 37 cases (84.1%). Skin and other complications were seen in 5 and 2 cases, respectively. There was not any relationship between drug complications and other disases. Conclusion: Hepatic damage is the most common complication leading to hospitalization in tuberculosis patients using anti-TB drugs. Keywords: Tuberculosis, Anti-TB drug, Live

A space-time pseudospectral discretization method for solving diffusion optimal control problems with two-sided fractional derivatives

We propose a direct numerical method for the solution of an optimal control problem governed by a two-side space-fractional diffusion equation. The presented method contains two main steps. In the first step, the space variable is discretized by using the Jacobi-Gauss pseudospectral discretization and, in this way, the original problem is transformed into a classical integer-order optimal control problem. The main challenge, which we faced in this step, is to derive the left and right fractional differentiation matrices. In this respect, novel techniques for derivation of these matrices are presented. In the second step, the Legendre-Gauss-Radau pseudospectral method is employed. With these two steps, the original problem is converted into a convex quadratic optimization problem, which can be solved efficiently by available methods. Our approach can be easily implemented and extended to cover fractional optimal control problems with state constraints. Five test examples are provided to demonstrate the efficiency and validity of the presented method. The results show that our method reaches the solutions with good accuracy and a low CPU time.Comment: This is a preprint of a paper whose final and definite form is with 'Journal of Vibration and Control', available from [http://journals.sagepub.com/home/jvc]. Submitted 02-June-2018; Revised 03-Sept-2018; Accepted 12-Oct-201

Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation

Resistance to temozolomide (TMZ) is the main cause of death in glioblastoma multiforme (GBM). The use of nanocarriers for drug delivery applications is one of the known approaches to overcome drug resistance. This study aimed to investigate the possible effect of selenium-chitosan nanoparticles loaded with TMZ on the efficacy of TMZ on the expression of MGMT, E2F6, and RELA genes and the rate of apoptosis in the C6 cell line. Selenium nanoparticles (SNPs) were loaded with TMZ and then they were coated by Eudragit(R) RS100 (Eud) and chitosan (C-S) to prepare Se@TMZ/Eud-Cs. Physicochemical properties were determined by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDAX), thermal gravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) methods. Se@TMZ/Eud-Cs was evaluated for loading and release of TMZ by spectrophotometric method. Subsequently, SNPs loaded with curcumin (as a fluorophore) were analyzed for in vitro uptake by C6 cells. Cytotoxicity and apoptosis assay were measured by MTT assay and Annexin-PI methods. Finally, real-time PCR was utilized to determine the expression of MGMT, E2F6, and RELA genes. Se@TMZ/Eud-Cs was prepared with an average size of 200 nm as confirmed by the DLS and microscopical methods. Se@TMZ/Eud-Cs presented 82.77 +/- 5.30 loading efficiency with slow and pH-sensitive release kinetics. SNPs loaded with curcumin showed a better uptake performance by C6 cells compared with free curcumin (p-value < 0.01). Coated nanoparticles loaded with TMZ showed higher cytotoxicity, apoptosis (p-value < 0.0001), and down-regulation of MGMT, E2F6, and RELA and lower IC50 value (p-value < 0.0001) than free TMZ and control (p-value < 0.0001) groups. Using Cs as a targeting agent in Se@TMZ/Eud-Cs system improved the possibility for targeted drug delivery to C6 cells. This drug delivery system enhanced the apoptosis rate and decreased the expression of genes related to TMZ resistance. In conclusion, Se@TMZ/Eud-Cs may be an option for the enhancement of TMZ efficiency in GBM treatment

Association between (GT)n repeats in heme oxygenase-1 gene promoter and 3-year survival of patients with acute leukemia: A controlled, cross-sectional study

Background: Acute leukemia is a common pediatric cancer. Novel strategies for treatment of acute leukemia have been developed, but treatment resistance is remained as the most problematic issue. It is hypothesized that the HO-1 gene up-regulation is responsible for tumor resistance to chemotherapy or radiotherapy-induced apoptosis. HO-1 expression levels are related to (GT)n microsatellite polymorphisms in the location of its promoter.This study designed to compare allelic frequencies of (GT)n microsatellite polymorphisms in HO-1 gene between acute leukemia patients and healthy controls. Indeed, 3-year disease-free survival was also evaluated. Materials and Methods: Sixty-three patients with acute leukemia and 70 healthy infants were included in this study. We used patient�s medical records to collect data about survival after chemotherapy. The number of GT repeats in HO-1 promoter was determined by an ABI 3100 sequencer. Results: The HO-1 GT repeats ranged from 14 to 34 with peaks at 27 repeats in both cases and controls. Children with longer alleles ((GT)n � 27) had enhanced 3-year survival rate after treatment with chemotherapy or radiotherapy (P&lt;0.05). Conclusion: Although no significant differences were observed between leukemia patients and controls regarding allelic frequency, we found elevated frequency of �LL� genotype in leukemia patients with good prognosis and 3-year surveillance. Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with subsequent increased resistance of leukemia patients to therapy. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved

Association between (GT)n repeats in heme oxygenase-1 gene promoter and 3-year survival of patients with acute leukemia: A controlled, cross-sectional study

Background: Acute leukemia is a common pediatric cancer. Novel strategies for treatment of acute leukemia have been developed, but treatment resistance is remained as the most problematic issue. It is hypothesized that the HO-1 gene up-regulation is responsible for tumor resistance to chemotherapy or radiotherapy-induced apoptosis. HO-1 expression levels are related to (GT)n microsatellite polymorphisms in the location of its promoter.This study designed to compare allelic frequencies of (GT)n microsatellite polymorphisms in HO-1 gene between acute leukemia patients and healthy controls. Indeed, 3-year disease-free survival was also evaluated. Materials and Methods: Sixty-three patients with acute leukemia and 70 healthy infants were included in this study. We used patient�s medical records to collect data about survival after chemotherapy. The number of GT repeats in HO-1 promoter was determined by an ABI 3100 sequencer. Results: The HO-1 GT repeats ranged from 14 to 34 with peaks at 27 repeats in both cases and controls. Children with longer alleles ((GT)n � 27) had enhanced 3-year survival rate after treatment with chemotherapy or radiotherapy (P&lt;0.05). Conclusion: Although no significant differences were observed between leukemia patients and controls regarding allelic frequency, we found elevated frequency of �LL� genotype in leukemia patients with good prognosis and 3-year surveillance. Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with subsequent increased resistance of leukemia patients to therapy. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved

Association between (GT)n repeats in heme oxygenase-1 gene promoter and 3-year survival of patients with acute leukemia: A controlled, cross-sectional study

Background: Acute leukemia is a common pediatric cancer. Novel strategies for treatment of acute leukemia have been developed, but treatment resistance is remained as the most problematic issue. It is hypothesized that the HO-1 gene up-regulation is responsible for tumor resistance to chemotherapy or radiotherapy-induced apoptosis. HO-1 expression levels are related to (GT)n microsatellite polymorphisms in the location of its promoter.This study designed to compare allelic frequencies of (GT)n microsatellite polymorphisms in HO-1 gene between acute leukemia patients and healthy controls. Indeed, 3-year disease-free survival was also evaluated. Materials and Methods: Sixty-three patients with acute leukemia and 70 healthy infants were included in this study. We used patient�s medical records to collect data about survival after chemotherapy. The number of GT repeats in HO-1 promoter was determined by an ABI 3100 sequencer. Results: The HO-1 GT repeats ranged from 14 to 34 with peaks at 27 repeats in both cases and controls. Children with longer alleles ((GT)n � 27) had enhanced 3-year survival rate after treatment with chemotherapy or radiotherapy (P&lt;0.05). Conclusion: Although no significant differences were observed between leukemia patients and controls regarding allelic frequency, we found elevated frequency of �LL� genotype in leukemia patients with good prognosis and 3-year surveillance. Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with subsequent increased resistance of leukemia patients to therapy. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved

A numerical study of fractional relaxation–oscillation equations involving ψ-Caputo fractional derivative

We provide a numerical method to solve a certain class of fractional differential equations involving ψ -Caputo fractional derivative. The considered class includes as particular case fractional relaxation–oscillation equations. Our approach is based on operational matrix of fractional integration of a new type of orthogonal polynomials. More precisely, we introduce ψ -shifted Legendre polynomial basis, and we derive an explicit formula for the ψ -fractional integral of ψ -shifted Legendre polynomials. Next, via an orthogonal projection on this polynomial basis, the problem is reduced to an algebraic equation that can be easily solved. The convergence of the method is justified rigorously and confirmed by some numerical experiments.publishe

Nutrition state of science and dementia prevention: Recommendations of the Nutrition for Dementia Prevention Working Group

Observational studies suggest that nutritional factors have a potential cognitive benefit. However, systematic reviews of randomised trials of dietary and nutritional supplements have reported largely null effects on cognitive outcomes and have highlighted study inconsistencies and other limitations. In this Personal View, the Nutrition for Dementia Prevention Working Group presents what we consider to be limitations in the existing nutrition clinical trials for dementia prevention. On the basis of this evidence, we propose recommendations for incorporating dietary patterns and the use of genetic, and nutrition assessment tools, biomarkers, and novel clinical trial designs to guide future trial developments. Nutrition-based research has unique challenges that could require testing both more personalised interventions in targeted risk subgroups, identified by nutritional and other biomarkers, and large-scale and pragmatic study designs for more generalisable public health interventions across diverse populations

A Comparison Between Full-COLD PCR/HRM and PCR Sequencing for Detection of Mutations in Exon 9 of PIK3CA in Breast Cancer Patients

One of the most common somatic mutations in breast cancer is found in PIK3CA with a prevalence rate of 18�45. Different variants of this gene are considered as resistance markers for treatment with HER2-targeted medicines. Conventional molecular methods such as Sanger sequencing are not able to detect mutations with low abundance in a mixture of wild-type DNA, especially in the early stages of cancer development. In this study, two methods of co-amplification at lower denaturation temperature PCR (COLD-PCR) and high-resolution melting (HRM) were combined for detection of mutations in exon 9 of PIK3CA; DNA, therefore, was extracted from MCF-7 and BT-474 as mutant and wild-type cell lines respectively. Thereafter, serial dilutions of extracted DNA were used to determine sensitivity of full-COLD PCR/HRM in comparison with conventional PCR sequencing as the gold standard method. Cell line experiments resulted in almost 30 fold increase in sensitivity by use of full-COLD PCR/HRM. In addition, 40 patients with primary breast cancer were investigated with the mentioned methods. As a result of this part of study, four mutations were detected by conventional PCR sequencing including E542K and E545K mutations in three and one samples respectively. Whereas, full-COLD PCR/HRM was able to detect one E542K mutation more than gold standard method which caused the percentage of sensitivity to get improved by 2.5 (10 to 12.5). Our results clearly demonstrated that full-COLD PCR/HRM could detect lower levels of mutations in wild-type background as a sensitive method with simple and cost-effective procedure; therefore, it can prospectively be used in screening of patients with early-stage breast cancers. © 2018, Springer Science+Business Media, LLC, part of Springer Nature