Demography, baseline disease characteristics and treatment history of patients with psoriasis enrolled in a multicentre, prospective, disease-based registry (PSOLAR)*

Summary Background: Psoriasis is associated with several comorbidities and behavioural risk factors. Objectives: To evaluate demographic and disease characteristics in patients enrolled in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods: PSOLAR is a global, prospective, longitudinal, disease-based registry that includes a postmarketing commitment to evaluate safety in patients with psoriasis. Enrolled patients had to be receiving, or be eligible to receive, conventional systemic or biological agents. Demographic/disease characteristics, medical histories, lifestyle risk factors and previous treatments are collected at enrolment. Efficacy and safety data are collected every 6 months for 8 years, and data are extracted annually. Selected parameters are evaluated by age quartile using post hoc analyses. Results: As of 23 August 2012, 11 900 patients were enrolled at 301 sites in North America, Europe and Latin America. Over half of the PSOLAR population (54·7%) is male, with a mean age of 48·6 years and mean body mass index of 30·9 kg m−2 at enrolment. Mean duration of disease at enrolment was 17·5 years, and mean Physician's Global Assessment score was 2·0. Psoriatic arthritis (35·5%) and cardiovascular diseases (38·2%) were highly prevalent. Diabetes mellitus type II was reported in 11·4% of patients. Depression and anxiety were noted in 14·7% and 11·1% of patients, respectively; 79·0% reported any alcohol use and 56·7% reported smoking or a history of smoking. The occurrence of most comorbidities, including cardiovascular disease and risk factors, increased with age. Conclusions: In the PSOLAR population, multiple and age-appropriate comorbidities are associated with psoriasis and may affect the selection of psoriasis treatments. What's already known about this topic? Psoriasis is a complicated disorder, often accompanied by multiple comorbidities. Demographic and disease characteristics of patients with psoriasis reported from large claims datasets may be affected by misclassification bias or coding errors. In clinical trials, many patients are excluded owing to strict inclusion criteria. What does this study add? Data collected by the Psoriasis Longitudinal Assessment and Registry reveal that the demographics and disease characteristics of patients with psoriasis who are receiving, or are candidates for, systemic therapy in actual clinical care resemble those reported in clinical trials. Most comorbidities occur more frequently in older patients, who, in turn, may require more comprehensive overall medical care

Regulation of expression of the rat orthologue of mouse double minute 2 (MDM2) by H2O2-induced oxidative stress in neonatal rat cardiac myocytes.

The Mdm2 ubiquitin ligase is an important regulator of p53 abundance and p53-dependent apoptosis. Mdm2 expression is frequently regulated by a p53 Mdm2 autoregulatory loop whereby p53 stimulates Mdm2 expression and hence its own degradation. Although extensively studied in cell lines, relatively little is known about Mdm2 expression in heart where oxidative stress (exacerbated during ischemia-reperfusion) is an important pro-apoptotic stimulus. We demonstrate that Mdm2 transcript and protein expression are induced by oxidative stress (0.2 mm H(2)O(2)) in neonatal rat cardiac myocytes. In other cells, constitutive Mdm2 expression is regulated by the P1 promoter (5' to exon 1), with inducible expression regulated by the P2 promoter (in intron 1). In myocytes, H(2)O(2) increased Mdm2 expression from the P2 promoter, which contains two p53-response elements (REs), one AP-1 RE, and two Ets REs. H(2)O(2) did not detectably increase expression of p53 mRNA or protein but did increase expression of several AP-1 transcription factors. H(2)O(2) increased binding of AP-1 proteins (c-Jun, JunB, JunD, c-Fos, FosB, and Fra-1) to an Mdm2 AP-1 oligodeoxynucleotide probe, and chromatin immunoprecipitation assays showed it increased binding of c-Jun or JunB to the P2 AP-1 RE. Finally, antisense oligonucleotide-mediated reduction of H(2)O(2)-induced Mdm2 expression increased caspase 3 activation. Thus, increased Mdm2 expression is associated with transactivation at the P2 AP-1 RE (rather than the p53 or Ets REs), and Mdm2 induction potentially represents a cardioprotective response to oxidative stress

A randomized, double-blind, placebo-controlled investigation of BCc1 nanomedicine effect on survival and quality of life in metastatic and non-metastatic gastric cancer patients

Background: Currently, the main goal of cancer research is to increase longevity of patients suffering malignant cancers. The promising results of BCc1 in vitro and vivo experiments made us look into the effect of BCc1 nanomedicine on patients with cancer in a clinical trial. Methods: The present investigation was a randomized, double-blind, placebo-controlled, parallel, and multicenter study in which 123 patients (30-to-85-year-old men and women) with metastatic and non-metastatic gastric cancer, in two separate groups of BCc1 nanomedicine or placebo, were selected using a permuted block randomization method. For metastatic and non-metastatic patients, a daily dose of 3000 and 1500 mg was prescribed, respectively. Overall survival (OS) as the primary endpoint and quality of life (measured using QLQ-STO22) and adverse effects as the secondary endpoints were studied. Results: In metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (174 days 95% confidence interval (CI) 82.37-265.62) than in placebo (62 days 95% CI 0-153.42); hazard ratio (HR): 0.5 95% CI 0.25-0.98; p = 0.046. In non-metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (529 days 95% CI 393.245-664.75) than in placebo (345 days 95% CI 134.85-555.14); HR: 0.324 95% CI 0.97-1.07; p = 0.066. The QLQ-STO22 assessment showed a mean difference improvement of 3.25 and 2.29 (p value > 0.05) in BCc1 nanomedicine and a mean difference deterioration of - 4.42 and - 3 (p-value < 0.05) in placebo with metastatic and non-metastatic patients, respectively. No adverse effects were observed. Conclusion: The findings of this trial has provided evidence for the potential capacity of BCc1 nanomedicine for treatment of cancer. Trial registration IRCTID, IRCT2017101935423N1. Registered on 19 October 2017, http://www.irct.ir/ IRCT2017101935423N1 © 2019 The Author(s)

Comparison of neutral anolyte solution and malachite green efficiency on fungal contamination control of rainbow trout (Oncorhynchus mykiss) eggs in incubation stage

One of the important problems in Rainbow trout production industry is egg fungal infection especially saprolegniasis which is the most important mortality factor in Rainbow trout hatcheries. Controlling saprolegniasis in hatcheries was done using green malachite in the past years, which is a very effective fungicide. Nowadays, due to the prohibition of using green malachite, effort is done to replace it with other materials as an effective fungicide. Some of the most important materials which have been examined are formalin, sodium chloride and hydrogen peroxide etc. The aim of this study was to evaluate the effects of neutral anolyte on the mortality percent of rainbow trout eggs and produced larvae in point of view of growth indices and survival until yolk sac absorption and larvae active feeding in incubation phase comparing with green malachite to be able to introduce a suitable alternative. This study was carried out in a complete randomly plan with 7 treatments and 3 replications (21 troughs in general), in 20*35*70 cm (length*width*depth) Californian troughs containing an incubator. Treatments included anolyte solutions constant bathing with 0.5 and 0.25 ppm concentrations and periodic anolyte treatments with 2 ppm concentrations (every 2 days), positive control infected with fungus without any disinfectant and negative control without any infection or disinfectant. 300 grams of newly propagated green eggs of rainbow trout which were provided from one of the fish hatcheries in Haraz Road and acclimated with the trough’s water temperature, were distributed in one layer at the bottom of the trough basket. All treatments, except negative control, were infected with saprolegnia, taken from infected eggs of rainbow trout which were previously provided from one of the fish hatcheries of 2000 Road in Tonekabon. The treatments took one month to complete. The studied variables included hatching percent, percent of eyed eggs, abnormality percent and percent of unfertilized eggs, from which percent of eyed eggs was calculated and recorded in the middle and the rest of the variables at the end of the test. In this study Paired-sample T-student test, Levene’s test, one-way ANOVA and Bonferroni’s test was used. For examining egg abnormality, hatching, fungus infection and eyed eggs, first the percent of the variables were specified and then for comparing the rate of abnormality in one of the anolyte treatments (which had the least abnormality) and green malachite, Mann-Whitney test was carried out. This comparison was done to analyze the rate of hatching, fungus infections, eyed eggs, resulting from the materials used in different treatments, using one-way ANOVA Bonferroni’s tests. Results showed that in lower anolyte concentrations (0.5 and 0.25 ppm), the number of fungal colonies of hatchery water and the percent of egg fungus infection were significantly higher than higher concentrations of anolyte (100 ppm and 30 ppm) and green malachite. In other words with concentration increase, the fungicidal effect has also increased. In evaluating the percent of eyed eggs, statistical results showed that eyed eggs percent in 0.25 ppm treatment and green malachite treatment were significantly higher than the other three anolyte treatments. This result can explain egg hatching in 0.25 ppm concentrations and not seeing hatching in the (other) remaining three doses. Between the treatments of 0.25 ppm and green malachite, the group of 0.25 ppm anolyte can be a better disinfectant for rainbow trout eggs compared to green malachite, for fish farmers, due to the high percent of eyed eggs and the low total count of fungus. The results of this study showed that the amount of abnormality in 0.25 ppm treatment has been higher compared to the green malachite group. Because this study was the first research on using anolyte as a fungicide in rainbow trout hatcheries, therefore for more specific study of the concentrations, the timing of usage and the factors affecting these two, more vast and general research is needed

Reliability and Convergent Validity of Two Outcome Instruments for Pemphigus

A major obstacle in performing multicenter controlled trials for pemphigus is the lack of a validated disease activity scoring system. Here we assess the reliability and convergent validity of the PDAI (pemphigus disease area index). A group of 10 dermatologists scored 15 patients with pemphigus to estimate the inter- and intra-rater reliability of the PDAI and the recently described ABSIS (autoimmune bullous skin disorder intensity score) instrument. To assess convergent validity, these tools were also correlated with the Physician’s Global Assessment (PGA). Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.76 [95% CI = 0.61–0.91] for the PDAI and 0.77 [0.63–0.91] for the ABSIS. The tools differed most in reliability of assessing skin activity, with an ICC of 0.39 [0.17–0.60] for the ABSIS and 0.86 [0.76–0.95] for the PDAI. Intra-rater test-retest reliability demonstrated an ICC of 0.98 [0.96–1.0] for the PDAI and 0.80 [0.65–0.96] for the ABSIS. The PDAI also correlated more closely with the PGA. We conclude that the PDAI is more reproducible and correlates better with physician impression of extent. Subset analysis suggests that for this population of mild to moderate disease activity, the PDAI captures more variability in cutaneous disease than the ABSIS

The First Survey for Abilities of Wavelets in Solving Optimal Control Problems by Embedding Methods

By a brief review on the applications of wavelets in solving optimal control problems, a multiresolution analysis for two dimensional Sobolev spaces and the square spline wavelets are considered. Regarding the density and approximation properties of these wavelets, for the first time, they are employed for solving optimal control problems by embedding method. Existence and the determination way for the solution are also discussed. Finally, the abilities of the new approach are explained by a numerical example and some comparison

DIBc, a nanochelating-based nano metal-organic framework, shows anti-diabetic effects in high-fat diet and streptozotocin-induced diabetic rats

Saideh Fakharzadeh,1&ndash;3 Somayeh Kalanaky,2 Maryam Hafizi,2 Mohammad Hassan Nazaran,2 Homeira Zardooz1,3 1Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 3Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Aims: Despite daily increase in diabetic patients in the world, currently approved medications for this disease, at best, only reduce its progression speed. Using novel technologies is a solution for synthetizing more efficient medicines. In the present study, we evaluated anti-diabetic effects of DIBc, a nano metal&ndash;organic framework, which is synthetized based on nanochelating technology.Methods: High-fat diet and streptozotocin-induced diabetic rats were treated by DIBc or metformin for 6 weeks.Results: DIBc decreased plasma glucose, triglyceride, cholesterol, high-density lipoprotein, and low-density lipoprotein compared with diabetic and metformin groups. In DIBc-treated rats, significant homeostasis model assessment of insulin resistance index, malondialdehyde, and tumor necrosis factor-&alpha; decrease was observed. H&amp;E staining showed increased islet number and area in DIBc-treated rats compared with diabetic controls.Conclusion: The results showed anti-diabetic effects of nanochelating-based framework. So DIBc, as a nano structure, has the capacity to be evaluated in future studies as a novel anti-diabetic agent. Keywords: DIBc, nanochelating technology, metal organic framework, diabetes, streptozotocin, high-fat diet &nbsp