Perceived barriers of migrants and refugees to vaccinate their children against Measles and polio: a study in Iran.

BACKGROUND: This study examined the perceived barriers of migrants and refugees to vaccinating their children against measles and polio in Iran. METHODS: First, an instrument was developed and validated through several steps. Next, 1,067 parents who had not vaccinated their children against polio and measles or had delayed receiving any dose of these two vaccines until the age of 15 were selected from 16 provinces and completed the instrument. Finally, the data were analyzed. RESULTS: The results of the explanatory factor analysis showed that the perceived barriers affecting vaccination against polio and measles vaccines were categorized into five factors: low knowledge, negative attitude, communication challenges, lack of participation in vaccination programs, and problems related to migration and refugees. Additionally, the results indicated a significant difference in the mean score of perceived barriers based on participants' level of education, economic status, and nationality. CONCLUSION: The identified barriers may provide a perspective for developing effective efforts in this area. Interventions should focus on parents with low education and poor economic status.

An intermolecular G-quadruplex as the basis for GTP recognition in the class V-GTP aptamer.

Many naturally occurring or artificially created RNAs are capable of binding to guanine or guanine derivatives with high affinity and selectivity. They bind their ligands using very different recognition modes involving a diverse set of hydrogen bonding and stacking interactions. Apparently, the potential structural diversity for guanine, guanosine, and guanine nucleotide binding motifs is far from being fully explored. Szostak and coworkers have derived a large set of different GTP-binding aptamer families differing widely in sequence, secondary structure, and ligand specificity. The so-called class V-GTP aptamer from this set binds GTP with very high affinity and has a complex secondary structure. Here we use solution NMR spectroscopy to demonstrate that the class V aptamer binds GTP through the formation of an intermolecular two-layered G-quadruplex structure that directly incorporates the ligand and folds only upon ligand addition. Ligand binding and G-quadruplex formation depend strongly on the identity of monovalent cations present with a clear preference for potassium ions. GTP binding through direct insertion into an intermolecular G-quadruplex is a previously unobserved structural variation for ligand-binding RNA motifs and rationalizes the previously observed specificity pattern of the class V aptamer for GTP analogs.

Comparing Therapeutic Efficacy and Safety of Epoetin Beta and Epoetin Alfa in the Treatment of Anemia in End-Stage Renal Disease Hemodialysis Patients.

BACKGROUND: Anemia is one of the most prevalent complications in patients with chronic kidney disease, which is believed to be caused by the insufficient synthesis of erythropoietin by the kidney. This phase III study aimed to compare the efficacy and safety of CinnaPoietin® (epoetin beta, CinnaGen) with Eprex® (epoetin alfa, Janssen Cilag) in the treatment of anemia in ESRD hemodialysis patients. METHODS: In this randomized, active-controlled, double-blind, parallel, and non-inferiority trial, patients were randomized to receive either CinnaPoietin® or Eprex® for a 26-week period. The primary endpoints of this study were to assess the mean hemoglobin (Hb) change during the last 4 weeks of treatment from baseline along with the evaluation of the mean weekly epoetin dosage per kilogram of body weight that was necessary to maintain the Hb level within 10-12 g/dL during the last 4 weeks of treatment. As the secondary objective, safety was assessed along with other efficacy endpoints. RESULTS: A total of 156 patients were included in this clinical trial. There was no statistically significant difference between treatment groups regarding the mean Hb change (p = 0.21). In addition, the mean weekly epoetin dosage per kg of body weight for maintaining the Hb level within 10-12 g/dL showed no statistically significant difference between treatment arms (p = 0.63). Moreover, both products had comparable safety profiles. However, the incidence of Hb levels above 13 g/dL was significantly lower in the CinnaPoietin® group. CONCLUSION: CinnaPoietin® was proved to be non-inferior to Eprex® in the treatment of anemia in ESRD hemodialysis patients. The trial was registered in Clinicaltrials.gov (NCT03408639).

Polymerase assays for lead discovery: An overall review of methodologies and approaches.

Polymerases represent an attractive molecular target for antibacterial drug development, antiviral intervention and cancer therapy. Over the past decade, academic groups and scientists from pharmaceutical industry have developed a large plethora of different functional assays to monitor the enzymatic reaction catalyzed by polymerases. These assays were used to enable high-throughput screening (HTS) for lead discovery purposes, as well as hit-to-lead (H2L) drug profiling activities. In both cases the choice of the assay technology is critical and to the best of our knowledge, there is no review available to help scientists to choose the most suitable assay. This review summarizes the most common functional assays developed to monitor the enzymatic activity of polymerases and discusses the advantages and disadvantages of each assay. Assays are presented and evaluated in term of cost, ease of use, high-throughput screening compatibility and liability towards delivering false positives and false negatives.

A Stably Protonated Adenine Nucleotide with a Highly Shifted pKa Value Stabilizes the Tertiary Structure of a GTP-Binding RNA Aptamer.

RNA tertiary structure motifs are stabilized by a wide variety of hydrogen-bonding interactions. Protonated A and C nucleotides are normally not considered to be suitable building blocks for such motifs since their pKa values are far from physiological pH. Here, we report the NMR solution structure of an in vitro selected GTP-binding RNA aptamer bound to GTP with an intricate tertiary structure. It contains a novel kind of base quartet stabilized by a protonated A residue. Owing to its unique structural environment in the base quartet, the pKa value for the protonation of this A residue in the complex is shifted by more than 5 pH units compared to the pKa for A nucleotides in single-stranded RNA. This is the largest pKa shift for an A residue in structured nucleic acids reported so far, and similar in size to the largest pKa shifts observed for amino acid side chains in proteins. Both RNA pre-folding and ligand binding contribute to the pKa shift.

Evaluation of Safety in Horizontal Curves of Roads Using a Multi-Body Dynamic Simulation Process.

Road transportation poses one of the significant public health risks. Several contributors and factors strongly link public health and road safety. The design and advancement of higher-quality roads can significantly contribute to safer roads and save lives. In this article, the safety aspect of the roads' horizontal curves under the standard of the American Association of State Highway Transportation Officials (AASHTO) is evaluated. Several factors, including vehicle weight, vehicle dimensions, longitudinal grades, and vehicle speed in the geometric design of the horizontal curves, are investigated through a multi-body dynamic simulation process. According to the AASHTO, a combination of simple circular and clothoid transition curves with various longitudinal upgrades and downgrades was designed. Three vehicles were used in this simulation, including a sedan, a bus, and a 3-axle truck. The analysis was based on the lateral friction between the tire and the pavement and also the safety margin parameter. The results showed that designers must differentiate between light and heavy vehicles, especially in curves with a high radius. Evaluation of longitudinal grade impacts indicated that the safety margin decreases when the vehicle is entering the curve. Safety margin reduction on the clothoid curve takes place with a lower grade toward the simple circular curve. By increasing the speed, the difference between lateral friction demand obtained from simulation and lateral friction demand proposed by AASHTO grows. The proposed novel methodology can be used for evaluating road safety.

Comparison of overall obesity and abdominal adiposity in predicting chronic kidney disease incidence among adults.

OBJECTIVE: Epidemiological data on the association between different aspects of adiposity and the risk for chronic kidney disease (CKD) in a cohort are limited. We compared the independent power of waist circumference (WC), waist-to-hip ratio (WHR), and body mass index (BMI) in predicting CKD in a large cohort of adults. DESIGN: This was a population-based cohort study. SETTING, PARTICIPANTS, AND MEASUREMENTS: A representative sample of 3107 subjects (1309 men and 1798 women), aged over 20 years, and free of CKD at baseline, was followed for 7 years. METHODS: We estimated glomerular filtration rate (GFR) by using the abbreviated equation from the Modification of Diet in Renal Disease Study, and defined CKD as an estimated GFR of less than 60 mL/min/1.73 m(2). Adjusted relative hazards of CKD were modeled using Cox proportional hazards regression, including BMI, WC, and WHR as risk factors. RESULTS: During the 7-year follow-up (median of 2183 days), 13.5% of participants (n = 419) developed CKD. The WC was positively related to risk of CKD, after multivariable adjustment for age, sex, smoking, menopause, physical activity, blood pressure, prevalent and incident diabetes, and change in WC during study period: Hazard ratios for CKD incidence were 1.00 (reference), 1.60 (95% CI: 1.06, 2.42), 1.86 (0.95 CI: 1.21, 2.85), and 1.88 (0.95 CI: 1.17, 3.01) for WC categories 1 to 4, respectively (P for trend < .02). The WHR was not independently associated with CKD. The rate of GFR decline (measured in mL/min/1.73 m(2)/year) was associated with baseline waist categories: regression coefficient for 1 SD increase in WC = -0.18 (0.95 CI:-0.28, -0.07). Based on Harrell's measure of concordance statistics, baseline WC was a better predictor of CKD than WHR (P < .05) and BMI (P < .05). CONCLUSIONS: Abdominal adiposity measured with WC, irrespective of general adiposity, is a more important determinant of CKD risk in adults than are WHR and BMI.

NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family.

Erythropoietin-producing hepatocellular (EPH) receptors are transmembrane receptor tyrosine kinases. Their extracellular domains bind specifically to ephrin A/B ligands, and this binding modulates intracellular kinase activity. EPHs are key players in bidirectional intercellular signaling, controlling cell morphology, adhesion, and migration. They are increasingly recognized as cancer drug targets. We analyzed the binding of NVP-BHG712 (NVP) to EPHA2 and EPHB4. Unexpectedly, all tested commercially available NVP samples turned out to be a regioisomer (NVPiso) of the inhibitor, initially described in a Novartis patent application. They only differ by the localization of a single methyl group on either one of two adjacent nitrogen atoms. The two compounds of identical mass revealed different binding modes. Furthermore, both in vitro and in vivo experiments showed that the isomers differ in their kinase affinity and selectivity.

NMR resonance assignments for the class II GTP binding RNA aptamer in complex with GTP.

The structures of RNA-aptamer-ligand complexes solved in the last two decades were instrumental in realizing the amazing potential of RNA for forming complex tertiary structures and for molecular recognition of small molecules. For GTP as ligand the sequences and secondary structures for multiple families of aptamers were reported which differ widely in their structural complexity, ligand affinity and ligand functional groups involved in RNA-binding. However, for only one of these families the structure of the GTP-RNA complex was solved. In order to gain further insights into the variability of ligand recognition modes we are currently determining the structure of another GTP-aptamer--the so-called class II aptamer--bound to GTP using NMR-spectroscopy in solution. As a prerequisite for a full structure determination, we report here (1)H, (13)C, (15)N and partial (31)P-NMR resonance assignments for the class II GTP-aptamer bound to GTP.

Comparison of half-dose and full-dose triple therapy regimens for Helicobacter pylori eradication in patients with end-stage renal disease.

AIM: The aim of this study was to compare the half-dose and full-dose triple therapy regimens for Helicobacter pylori (Hp) eradication in patients with end-stage renal disease. BACKGROUND: H. Pylori is one the most important causes of dyspepsia in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS: Sixty-six patients with ESRD were enrolled in the study with Hp infection and peptic disease with a need of Hp eradication. Patients were randomly assigned to full-dose (A=35 patients) or half-dose group (B=31 patients). Patients received clarithromycin 500 mg, amoxicillin 1000 mg and omeprazole 20 mg twice daily in group A and clarithromycin 250 mg and amoxicillin 500 mg twice daily and omeprazole 20 mg once daily in group B for two weeks. Patients provided stool samples 4 weeks of completing study to assess the success of Hp eradication by Hp-specific stool antigen. Finally, the rate of eradication and complications were compared between two groups. RESULTS: The successful Hp eradication was achieved in 26 patients (74%) in group A and in 22 patients (74%) in group B. The difference between 2 groups was not statistically significant (p=0.973) (per protocol analysis). CONCLUSION: Half-dose triple-therapy with clarithromycin, amoxicillin and omeprazole is as effective as full-dose triple-therapy to eradicate the Hp in patients with ESRD. According to lower toxicity level, complications and cost in half-dose regimen in this subset of patients, this protocol is advised.

Incidence of chronic kidney disease and its risk factors, results of over 10 year follow up in an Iranian cohort.

To examine, the predictors of incident chronic kidney disease (CKD) in a community-based cohort of Middle East population, during a mean follow-up of 9.9 years. In a sample of 3313 non-CKD Iranian adults ≥20 years the estimated glomerular filtration rate (eGFR) was calculated at baseline and at three year intervals during three consecutive phases. The eGFR <60 mL/min/1.73 m2 was defined as CKD. Multivariate Logistic regression analysis was used to determine the independent variables associated with incident CKD. The incidence density rates of CKD were 285.3 and 132.6 per 10,000 person-year, among women and men, respectively. Female gender per se was associated with higher risk of CKD, compared with males. Among women, age, eGFR, known diabetes, being single or divorced/widowed, hypertension (marginally significant) and current smoking were independent risk factors for CKD; however the intermediate degree of education and family history of diabetes decreased the risk by 40% (P<0.05). Among male subjects, independent predictors of developing CKD included aging and hypertension (with significantly higher risk than in women, P for interaction<0.05), eGFR, new diagnosed diabetes, high normal blood pressure; abdominal obesity decreased the risk of CKD about 30% which was marginally significant. In the Iranian population,>2% of individuals develops CKD each year. Our findings confirmed that sex- specific risk predictors should be considered in primary prevention for incident CKD.

Acute effects of hemodialysis on pulmonary function in patients with end-stage renal disease.

INTRODUCTION: Despite many beneficial effects, hemodialysis may cause pulmonary dysfunction. On the other hand, patients with end-stage renal disease are potentially prone to lung edema and respiratory dysfunction. This study was conducted to evaluate the alterations of pulmonary function indicators after hemodialysis, measured by spirometry. MATERIALS AND METHODS: A total of 26 patients on hemodialysis for at least 3 months were studied. They were all older than 18 years old. None of the patients was a current or recent smoker, and none of them had a history of respiratory diseases, current or recent respiratory infections, musculoskeletal disorders, or tuberculosis. All of the patients underwent the spirometry test before and after a 4-hour hemodialysis session, and the forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), vital capacity (VC), and FEV1/FVC ratio were measured. RESULTS: After hemodialysis, the FVC significantly increased (P = .02), while no significant improvement in the FEV1, VC, and FEV1/FVC ratio were observed. Gender was related to the changes in VC, with better results in women (P < .001). There was no association between the changes in spirometry parameters and age, body mass index, cause of kidney failure, type of anion used for hemodialysis, and weight changes. CONCLUSIONS: According to our results, pulmonary function, especially the FVC, improves after a session of hemodialysis.