The pathogenicity of genetic variants previously associated with left ventricular non-compaction

BACKGROUND: Left ventricular non‐compaction (LVNC) is a rare cardiomyopathy. Many genetic variants have been associated with LVNC. However, the number of the previous LVNC‐associated variants that are common in the background population remains unknown. The aim of this study was to provide an updated list of previously reported LVNC‐associated variants with biologic description and investigate the prevalence of LVNC variants in healthy general population to find false‐positive LVNC‐associated variants. METHODS AND RESULTS: The Human Gene Mutation Database and PubMed were systematically searched to identify all previously reported LVNC‐associated variants. Thereafter, the Exome Sequencing Project (ESP) and the Exome Aggregation Consortium (ExAC), that both represent the background population, was searched for all variants. Four in silico prediction tools were assessed to determine the functional effects of these variants. The prediction results of those identified in the ESP and ExAC and those not identified in the ESP and ExAC were compared. In 12 genes, 60 LVNC‐associated missense/nonsense variants were identified. MYH7 was the predominant gene, encompassing 24 of the 60 LVNC‐associated variants. The ESP only harbored nine and ExAC harbored 18 of the 60 LVNC‐associated variants. In total, eight out of nine ESP‐positive variants overlapped with the 18 variants identified in ExAC database. CONCLUSIONS: In this article, we identified 9 ESP‐positive and 18 ExAC‐positive variants of 60 previously reported LVNC‐associated variants, suggesting that these variants are not necessarily the monogenic cause of LVNC

Assessment and Prioritization of Alternative Gasoline Pricing Policies in Iran based on Economic, Social and Environmental Criteria

The main purpose of this study is to identify and prioritize different gasoline pricing policies in Iran based on sustainable development indicators using the Delphi method and Analytical Hierarchy Process (AHP). To this end, first, various types of gasoline pricing options along with evaluation indicators of these options were extracted separately in economic, social, and environmental terms by the Delphi method based on reviewing studies and interviews with specialists and experts. In this section, four pricing options for gasoline pricing were extracted entitled (i) “Double pricing of gasoline or continuation of the current trend; (ii) “Single rate gasoline price and cash payment of subsidies to cars; (iii) “Proportional pricing for gasoline consumption; (iv) “Single price of gasoline and allocation of quotas to people instead of cars. Then, these options were evaluated and prioritized in terms of economic, social, and environmental indicators in the framework of the AHP method. The results show that pricing commensurate with gasoline consumption or consumption tax (third option) is the best pricing option among the mentioned options. In this option, environmental and economic indicators are of great importance, and the price of gasoline between the quota price and FOB is determined in proportion to the consumption of individuals and sudden price changes do not occur for all consumers and the price of gasoline is completely dependent on the consumption behavior of individuals. Thus high consumption is always faced with higher taxes and allows for a fairer distribution of subsidies and reduced smuggling incentives for this fuel

A Case Report of a Successful Allergen Immunotherapy with Candida Albicans in Patient with Sever Atopic Dermatitis Sensitive to Candida Albicans

Introduction: Atopic dermatitis (AD) is an inflammatory, chronic, relapsing, itchy skin disease with an immunologic basis. This disease is associated with itchy skin lesions (pruritus), dry skin (xerosis) and plaques of eczema. The role of aeroallergens, such as house dust mite (HDM) and food allergens has been proven to exacerbate skin eczema lesions. Alongside drugs such as corticosteroids, topical emollients, antihistamines, tacrolimus, and immune suppressants, phototherapy and subcutaneous immunotherapy (SCIT) also done. SCIT is mostly using for sensitization to mite allergens.Case Presentation: We present a 30 y/o Iranian woman with severe atopic dermatitis and sensitization to Candida allergens. We initiated SCIT with candida allergen and the patient had obvious improvements in her signs and symptoms 3 months after starting SCIT.Conclusion: Although subcutaneous immunotherapy was only approved for mite sensitization in atopic dermatitis, it should be considered in other aeroallergen sensitizations

New population-based exome data question the pathogenicity of some genetic variants previously associated with Marfan syndrome

BACKGROUND: Marfan syndrome (MFS) is a rare autosomal dominantly inherited connective tissue disorder with an estimated prevalence of 1:5,000. More than 1000 variants have been previously reported to be associated with MFS. However, the disease-causing effect of these variants may be questionable as many of the original studies used low number of controls. To study whether there are possible false-positive variants associated with MFS, four in silico prediction tools (SIFT, Polyphen-2, Grantham score, and conservation across species) were used to predict the pathogenicity of these variant. RESULTS: Twenty-three out of 891 previously MFS-associated variants were identified in the ESP. These variants were distributed on 100 heterozygote carriers in 6494 screened individuals. This corresponds to a genotype prevalence of 1:65 for MFS. Using a more conservative approach (cutoff value of >2 carriers in the EPS), 10 variants affected a total of 82 individuals. This gives a genotype prevalence of 1:79 (82:6494) in the ESP. A significantly higher frequency of MFS-associated variants not present in the ESP were predicted to be pathogenic with the agreement of ≥3 prediction tools, compared to the variants present in the ESP (p = 3.5 × 10(−15)). CONCLUSIONS: This study showed a higher genotype prevalence of MFS than expected from the phenotype prevalence in the general population. The high genotype prevalence suggests that these variants are not the monogenic cause of MFS. Therefore, caution should be taken with regard to disease stratification based on these previously reported MFS-associated variants

Implicit Theories of Intelligence and Corrective Feedback Preferences

Considering the facilitative role of corrective feedback in language learning, the impact of learners’ noticing on its effectiveness, and the significant contributions of individual attributes in learners’ noticing the corrective feedback, this study is designed to examine how learners’ implicit theories of intelligence (Mindset), an individual attribute, predict their preferences for oral corrective feedback (henceforth, OCF). A total of 143 Iranian EFL learners participated in the study. The participants were assigned to groups of fixed mindset (N=26) and growth mindset (N=26) based on their scores on Language Mindset Inventory (LMI) scale. The data obtained from the questionnaires were analyzed quantitatively. The results indicated that there were significant differences between the fixed-mindset and the growth-mindset groups in their beliefs toward some aspects of OCF. All in all, it can be claimed that language mindset (henceforth, LM) has a significant role in EFL learners’ beliefs about OCF. Pedagogical implications for considering learners’ LM in providing OCF are also discussed

Evaluation of the Reliability and Validity of the Persian Version of Urticaria Control Test (UCT)

The urticaria control test (UCT) is a patient-reported outcome measure (PROM) for chronic urticaria (CU) patients. As a Persian version of the UCT was not available, the present research aimed to develop such a version, to test its reliability and validity as well as to evaluate urticaria control among Persian-speaking patients. This research was conducted at the Urticaria Centre of Reference and Excellence (UCARE) of Ghaem Hospital, Mashhad, Iran. In a first step, a linguistically validated Persian version of the UCT was developed through a structured forward and backward translation process and subsequent cognitive debriefing interviews. In a second step, the Persian version of the UCT was completed by 100 well-characterized CU patients together with two anchor instruments, the Chronic Urticaria Quality of life Questionnaire (CU-Q2oL) and the urticaria activity score (UAS), to obtain information on its internal consistency reliability and convergent validity. The Persian version of the UCT was found to have acceptable internal consistency reliability with a Cronbach's alpha coefficient of 0.68. In addition, the results obtained with the Persian UCT correlated with the CU-Q2oL total score (-0.48, p<0.001) and the UAS (-0.404, p< 0.001), suggesting convergent validity. Virtually all patients had poorly controlled CU (UCT<12). A Persian version of the UCT is now available and may help to improve the assessment and monitoring of disease control in Persian-speaking CU patients and to optimize treatment decisions

Stability of Circulating Blood-Based MicroRNAs - Pre-Analytic Methodological Considerations

Background and aim The potential of microRNAs (miRNA) as non-invasive diagnostic, prognostic, and predictive biomarkers, as well as therapeutic targets, has recently been recognized. Previous studies have highlighted the importance of consistency in the methodology used, but to our knowledge, no study has described the methodology of sample preparation and storage systematically with respect to miRNAs as blood biomarkers. The aim of this study was to investigate the stability of miRNAs in blood under various relevant clinical and research conditions: different collection tubes, storage at different temperatures, physical disturbance, as well as serial freeze-thaw cycles. Methods Blood samples were collected from 12 healthy donors into different collection tubes containing anticoagulants, including EDTA, citrate and lithium-heparin, as well as into serum collection tubes. MiRNA stability was evaluated by measuring expression changes of miR-1, miR21 and miR-29b at different conditions: varying processing time of whole blood (up to 72 hours (h)), long-term storage (9 months at -80 degrees C), physical disturbance (1 and 8 h), as well as in a series of freeze/thaw cycles (1 and 4 times). Results Different collection tubes revealed comparable concentrations of miR-1, miR-21 and miR-29b. Tubes with lithium-heparin were found unsuitable for miRNA quantification. MiRNA levels were stable for at least 24 h at room temperature in whole blood, while separated fractions did show alterations within 24 h. There were significant changes in the miR-21 and miR-29b levels after 72 h incubation of whole blood at room temperature (p< 0.01 for both). Both miR-1 and miR-21 showed decreased levels after physical disturbance for 8 h in separated plasma and miR-1 in serum whole blood, while after 1 h of disturbance no changes were observed. Storage of samples at -80 degrees C extended the miRNA stability remarkably, however, miRNA levels in long-term stored (9 months) whole blood samples were significantly changed, which is in contrast to the plasma samples, where miR-21 or miR-29b levels were found to be stable. Repetitive (n = 4) freeze-thaw cycles resulted in a significant reduction of miRNA concentration both in plasma and serum samples. Conclusion This study highlights the importance of proper and systematic sample collection and preparation when measuring circulating miRNAs, e.g., in context of clinical trials. We demonstrated that the type of collection tubes, preparation, handling and storage of samples should be standardized to avoid confounding variables influencing the results

"Effect of Aerobic Exercise Training on Pulmonary Function and Tolerance of Activity in Asthmatic Patients "

The aim of the present study was to examine the effects of a course of aerobic exercise on pulmonary function and tolerance of activity in asthmatic patients. Among the asthmatic patients, 36 patients (M= 16, F= 20) were chosen after clinical examinations, pulmonary function test, skin prick test (SPT) for aeroallergen and a six minute walk test (6MWT) on their own free will. A patient was said to have Exercise Induced Asthma (EIA) when he/she fulfilled the following criteria; (1) FEV1 < 80%, (2) 12% increase or more in FEV1 or PEF after short-acting ß2 agonist prescription and (3) 15% decrease in FEV1 or PEF after 6MWT with 70% or 80% of maximum heart rate. The patients were randomly put into two groups of case (M=8, F=10, Mean age=27) and control (M=8, F=10, Mean age=29). Case group participated in eight-week aerobic exercise plan, while control group had no plan of exercise. Pulmonary function tests were done before and after the course of exercise. There were significant changes in FEV1, FVC, PEF, FEF25-75%, MVV, RF and 6MWT between asthmatic patients of the two groups (P≤0.05), but FEV1/FVC showed no significant change. Mean of changes in FEV1, FVC, PEF, FEF25-75%, MVV, RF and 6MWT were –25.56, -17.19, 32.09, -27.93, -22.18, 5.63 and –307.5 in case group respectively while they were 6.2, 4.67, 1.96, 6.65, 15.56,-2.87 and 18.78 in the control group. This study shows that aerobic exercises in asthmatic patients lead to an improvement in pulmonary functions. Aerobic exercise rehabilitation can be a complement to medical treatment of asthma

Association of common genetic variants related to atrial fibrillation and the risk of ventricular fibrillation in the setting of first ST-elevation myocardial infarction

Background: Cohort studies have revealed an increased risk for ventricular fibrillation (VF) and sudden cardiac death (SCD) in patients with atrial fibrillation (AF). In this study, we hypothesized that single nucleotide polymorphisms (SNP) previously associated with AF may be associated with the risk of VF caused by first ST-segment elevation myocardial infarction (STEMI). Methods: We investigated association of 24 AF-associated SNPs with VF in the prospectively assembled case–control study among first STEMI-patients of Danish ancestry. Results: We included 257 cases (STEMI with VF) and 537 controls (STEMI without VF). The median age at index infarction was 60 years for the cases and 61 years for the controls (p = 0.100). Compared to the control group, the case group was more likely to be male (86% vs. 75%, p = 0.001), have a history of AF (7% vs. 2%, p = 0.006) or hypercholesterolemia (39% vs. 31%, p = 0.023), and a family history of sudden death (40% vs. 25%, p < 0.001). All 24 selected SNPs have previously been associated with AF. None of the 24 SNPs were associated with the risk of VF after adjustment for age and sex under additive genetic model of inheritance in the logistic regression model. Conclusion: In this study, we found that the 24 AF-associated SNPs may not be involved in increasing the risk of VF. Larger VF cohorts and use of new next generation sequencing and epigenetic may in future identify additional AF and VF risk loci and improve our understanding of genetic pathways behind the two arrhythmias