Publications by authors named "Zahra Aryan"

38 Publications

Proximity to Major Roads and Risks of Childhood Recurrent Wheeze and Asthma in a Severe Bronchiolitis Cohort.

Int J Environ Res Public Health 2021 04 15;18(8). Epub 2021 Apr 15.

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Air pollution exposures have been suggested as risk factors for childhood respiratory diseases. We investigated proximity to major roads, an indicator of air pollution exposure, and its associations with childhood recurrent wheeze and asthma. We used data from a multicenter prospective cohort study of 921 infants hospitalized for bronchiolitis and recruited from 14 U.S. states. Primary exposure was residential proximity to the nearest major road at birth through age 3 years. Residential distance from nearest major road was divided into four categories: <100, 100-200, 201-300, and >300 m. Outcomes were parent-reported recurrent wheeze by age 3 years and asthma by age 5 years. Associations between residential proximity to major roads and respiratory outcomes were investigated using multivariable Cox proportional hazards modeling and logistic regression, adjusted for confounders. Out of 920 participants with home address data, pooled estimates identified 241 (26%) participants resided within 300 m of a major road, 296 (32%) developed recurrent wheeze by age 3, and 235 out of 858 participants (27%) developed asthma by 5 years. Participants who resided close to a major road had the highest risk of recurrent wheeze (adjusted hazards ratio for <100 m, 1.59, 95%CI: 1.08-2.33) and asthma (adjusted odds ratio for 201-300 m, 1.62, 95%CI: 1.16-2.25), compared to those residing >300 m from a major road. Proximity to major roads is associated with increased risks of recurrent wheeze and asthma in young children.
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http://dx.doi.org/10.3390/ijerph18084197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071463PMC
April 2021

Cell adhesion molecule IGPR-1 activates AMPK connecting cell adhesion to autophagy.

J Biol Chem 2020 12 25;295(49):16691-16699. Epub 2020 Sep 25.

Department of Pathology, School of Medicine, Boston University Medical Campus, Boston, Massachusetts, USA. Electronic address:

Autophagy plays critical roles in the maintenance of endothelial cells in response to cellular stress caused by blood flow. There is growing evidence that both cell adhesion and cell detachment can modulate autophagy, but the mechanisms responsible for this regulation remain unclear. Immunoglobulin and proline-rich receptor-1 (IGPR-1) is a cell adhesion molecule that regulates angiogenesis and endothelial barrier function. In this study, using various biochemical and cellular assays, we demonstrate that IGPR-1 is activated by autophagy-inducing stimuli, such as amino acid starvation, nutrient deprivation, rapamycin, and lipopolysaccharide. Manipulating the IκB kinase β activity coupled with and kinase assays demonstrated that IκB kinase β is a key serine/threonine kinase activated by autophagy stimuli and that it catalyzes phosphorylation of IGPR-1 at Ser The subsequent activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase, which leads to phosphorylation of the major pro-autophagy proteins ULK1 and Beclin-1 (BECN1), increased LC3-II levels, and accumulation of LC3 punctum. Thus, our data demonstrate that IGPR-1 is activated by autophagy-inducing stimuli and in response regulates autophagy, connecting cell adhesion to autophagy. These findings may have important significance for autophagy-driven pathologies such cardiovascular diseases and cancer and suggest that IGPR-1 may serve as a promising therapeutic target.
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http://dx.doi.org/10.1074/jbc.RA120.014790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864065PMC
December 2020

Moving Genomics to Routine Care: An Initial Pilot in Acute Cardiovascular Disease.

Circ Genom Precis Med 2020 10 26;13(5):406-416. Epub 2020 Aug 26.

Cardiovascular Medicine Division, Department of Medicine (Z.A., A.S., C.R., W.P., E.W., R.C.D., C.A.M., D.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Background: Whole-genome sequencing (WGS) costs are falling, yet, outside oncology, this information is seldom used in adult clinics. We piloted a rapid WGS (rWGS) workflow, focusing initially on estimating power for a feasibility study of introducing genome information into acute cardiovascular care.

Methods: A prospective implementation study was conducted to test the feasibility and clinical utility of rWGS in acute cardiovascular care. rWGS was performed on 50 adult patients with acute cardiovascular events and cardiac arrest survivors, testing for primary and secondary disease-causing variants, cardiovascular-related pharmacogenomics, and carrier status for recessive diseases. The impact of returning rWGS results on short-term clinical care of participants was investigated. The utility of polygenic risk scores to stratify coronary artery disease was also assessed.

Results: Pathogenic variants, typically secondary findings, were identified in 20% (95% CI, 11.7-34.3). About 60% (95% CI, 46.2-72.4) of participants were carriers for one or more recessive traits, most commonly in and genes. Although 64% (95% CI, 50.1-75.9) of participants carried at least one pharmacogenetic variant of cardiovascular relevance, these were actionable in only 14% (95% CI, 7-26.2). Coronary artery disease prevalence among participants at the 95th percentile of polygenic risk score was 88.2% (95% CI, 71.8-95.7).

Conclusions: We demonstrated the feasibility of rWGS integration into the inpatient management of adults with acute cardiovascular events. Our pilot identified pathogenic variants in one out of 5 acute vascular patients. Integrating rWGS in clinical care will progressively increase actionability.
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http://dx.doi.org/10.1161/CIRCGEN.120.002961DOI Listing
October 2020

Clinical and Mutation Description of the First Iranian Cohort of Infantile Inflammatory Bowel Disease: The Iranian Primary Immunodeficiency Registry (IPIDR).

Immunol Invest 2021 May 7;50(4):445-459. Epub 2020 Jul 7.

Research Center for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

We describe a cohort of 25 Iranian patients with infantile inflammatory bowel disease (IBD), 14 (56%) of whom had monogenic defects. After proper screening, patients were referred for whole exome sequencing (WES). Four patients had missense mutations in the , and one had a large deletion in the . Four patients had mutations in genes implicated in host:microbiome homeostasis, including deficiency, and two patients with novel mutations in the and . We found a novel homozygous mutation in the in a deceased patient and the heterozygous variant in his sibling with a milder phenotype. Three patients had combined immunodeficiency: one with ZAP-70 deficiency (TBNK), and two with atypical SCID due to mutations in and . One patient had a mutation without neutropenia. Eleven of the 14 patients with monogenic defects were results of consanguinity and only 4 of them were alive to this date.
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http://dx.doi.org/10.1080/08820139.2020.1776725DOI Listing
May 2021

Novel CYBA mutation in a family with BCGitis.

Acta Microbiol Immunol Hung 2019 Dec 18;67(1):56-60. Epub 2019 Dec 18.

Research Center for Immunodeficiencies (RCID), Children's Medical Center,Tehran University of Medical Sciences, Tehran,Iran.

Chronic granulomatous disease is a non-prevalent genetic disorder due to different structural gene mutations encoding components of nicotinamide adenine dinucleotide phosphate oxidase complex. Nicotinamide adenine dinucleotide phosphate oxidase is a complex made by a group of five proteins (subunit) and plays an important role in the innate immune system. Five structural genes are responsible for encoding each subunit, in which cytochrome b-245 alpha chain (also known as p22-phox) is encoded by CYBA gene. CYBA gene mutation leads to a group of autosomal dominant chronic granulomatous disease. Decreased level or lack of nicotinamide adenine dinucleotide phosphate oxidase leaves affected individuals vulnerable to many types of infections and excessive inflammation. In this study, a family affected by BCGitis caused by a novel intronic autosomal recessive CYBA mutation (88,713,158 C > T) has been described. The proband is a 5-year-old girl with chronic granulomatous disease who was referred to the clinic due to BCGitis. The culprit mutation was detected following whole genome sequencing and was confirmed among the family members by Sanger sequencing. Being symptom-free at the time of diagnosis, despite the proband's mother homozygosity, was a characteristic feature of this report. Remarkably, none of the CYBA-mutated members, as a known chronic granulomatous disease causing gene, has expressed symptoms other than regional lymph node enlargements. This might explain the gene mutation site importance in demonstrating different manifestations.
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http://dx.doi.org/10.1556/030.66.2019.043DOI Listing
December 2019

Hypomorphic DOCK8 deletion causes hypereosinophilic syndrome.

Pediatr Blood Cancer 2020 02 20;67(2):e28084. Epub 2019 Nov 20.

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1002/pbc.28084DOI Listing
February 2020

Association of non-alcoholic fatty liver disease with microvascular complications of type 2 diabetes.

Prim Care Diabetes 2019 12 1;13(6):505-514. Epub 2019 May 1.

Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Introduction: Non-alcoholic fatty liver disease (NAFLD) affects risks of type 2 diabetes (T2D), diabetes-related complications, and cardiovascular disease in a complex manner. This study is designed to clarify associations of sonographically-detected NAFLD and serum liver enzymes with diabetes-related microvascular complications.

Methods: A matched case-contorl study was designed for 440 patients with T2D and at least one of the chronic diabetes-related microvascular complications and 495 age- and gender-matched control patients with T2D.

Results: Considering pre-existing and newly developed chronic microvascular complications, diabetic peripheral neuropathy was found in 347 out of 935 (37.1%) study patients, diabetic retinopathy in 141/935 (15.1%), and diabetic nephropathy in 103/935 (11.0%). Diagnosis of diabetic retinopathy and diabetic nephropathy were inversely associated with the presence of NAFLD in the crude logistic regressions (OR [95% CI] = 0.18 [0.05-0.63], p value = 0.007; OR [95% CI] = 0.17 [0.04-0.59], p value = 0.011, respectively). The subgroup of NAFLD with elevated liver enzymes had lower odds of having diabetic peripheral neuropathy in the fully adjusted model (OR [95% CI] = 0.34 [0.12-0.98], p value = 0.048).

Conclusion: Diagnosis of NAFLD with or without elevated serum liver enzymes was inversely correlated with certain chronic diabetes microvascular complications. Possible explanations for this counter-intuitive and unexpected finding are discussed and center on reverse-causality, wherein sicker patients may develop beneficial compensatory physiological and behavioral adaptations. Diversity of studied patients, in particular with regards to the ethnic and racial differences among the Western and Asian populations may also partly account for contrasting findings of the relationship between NAFLD and microvascular complications of diabetes.
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http://dx.doi.org/10.1016/j.pcd.2019.03.009DOI Listing
December 2019

Immunomodulatory and Anti-Inflammatory Phytochemicals for the Treatment of Inflammatory Bowel Disease (IBD): - Turning Strong Rationale into Strong Evidence?

J Pharmacopuncture 2018 Dec 31;21(4):294-295. Epub 2018 Dec 31.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

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http://dx.doi.org/10.3831/KPI.2018.21.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333189PMC
December 2018

The prevalence, awareness, and treatment of lipid abnormalities in Iranian adults: Surveillance of risk factors of noncommunicable diseases in Iran 2016.

J Clin Lipidol 2018 Nov - Dec;12(6):1471-1481.e4. Epub 2018 Aug 10.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Hypercholesterolemia is one of the modifiable risk factors for atherosclerosis and cardiovascular diseases. Prevention and treatment of hypercholesterolemia and other lipid abnormalities require reliable data regarding the current prevalence of these abnormalities in the country.

Objective: This study aims to determine the current prevalence, awareness, and treatment of lipid abnormalities in Iran.

Methods: We planned to recruit 31,050 individuals who are 18 years old and above and take blood samples from individuals who are 25 years and above as representative sample at national and provincial levels in 2016. In practice, we recruited 21,293 Iranian adult aged more than 25 years through a systematic random sampling from 30 provinces of Iran. Sociodemographic, anthropometric, and lifestyle data and history of cardiometabolic diseases were gathered. Serum total cholesterol, high-density lipoprotein-cholesterol (HDL-C), triglyceride, low-density lipoprotein-cholesterol (LDL-C), and non-HDL-C were investigated. The prevalence of lipid abnormalities, awareness, treatment, and achievement to non-HDL-C and LDL-C goals were determined based on National Cholesterol Education Program Adult Treatment Panel III criteria.

Results: In this representative Iranian adult population, 80.0% had at least one lipid abnormality, 69.2% had low HDL-C, 39.5% had high non-HDL-C, 28.0% had hypertriglyceridemia, and 26.7% hypercholesterolemia. Of those with hypercholesterolemia, 74.2% were aware of their lipid abnormality. Only 22.0% and 36.5% of the study population met the desired level of non-HDL-C and LDL-C, respectively.

Conclusion: Low HDL-C is the main lipid abnormality in adult Iranian population. The majority of the population did not meet the desired level of non-HDL-C and LDL-C. Public health preventive policies should be made and implemented to better manage dyslipidemia.
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http://dx.doi.org/10.1016/j.jacl.2018.08.001DOI Listing
October 2019

Circadian Rhythm, Lifestyle and Health: A Narrative Review.

Iran J Public Health 2018 Aug;47(8):1068-1076

Genetics Clinic, Valli-e-Asr Sq., Tehran, Iran.

Background: The circadian rhythm regulation plays a crucial role in people's healthy lives affected by factors consisting of cosmic events related to the universe and earth, environmental factors (light, night and day duration, seasons) and lifestyles. These factors changes lead to disturbance of circadian rhythm and it causes increasing the incidence of mental diseases like depression and physiological problems like cancers, cardiovascular disease and diabetes.

Methods: The present review searched Elsevier, SID, Pub Med, Springer, and Google Scholar databases for relevant articles were published between 1996 and 2017. Keywords used included lifestyle, circadian rhythm, cancer, metabolic diseases and cosmic factors.

Results: Circadian rhythm can be affected by lifestyle, heredity, cosmos spin and seasonal factors. Two first factors have physically direct effects on circadian rhythm and health, while other factors influence on them mentally. After all, all of them lead to cancer, cardiovascular diseases and metabolic obesity.

Conclusion: Although environmental factors are universal events which are unrelated to human control but affect human's body and circadian rhythm. Other factors are manageable by human to prevent disturbance of circadian rhythm making physical disorders.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123576PMC
August 2018

Salt intake among Iranian population: the first national report on salt intake in Iran.

J Hypertens 2018 12;36(12):2380-2389

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute.

Objective: In Iran, there has been no national report on salt intake based on laboratory measurements so far. Therefore, this study was conducted to measure salt intake among Iranian population at the national level.

Methods: In stepwise approach to conduct a surveillance survey 2016, 18 624 Iranian adults (25 years old and above), as a representative sample of Iranian adult population at national and subnational levels, underwent urine sodium measurement and were included in this study. The participants were recruited through a systematic random sampling from 30 provinces of Iran. For each individual, through a computer-assisted interview, a questionnaire on lifestyle risk factors was completed, all anthropometric indices were measured, and data on sodium of spot urine sample for all individuals and 24-h urine sample for a subsample were collected. To estimate the 24-h salt intake, common equations were used.

Results: In total, 97.66% of the population consumed at least 5 g of salt per day. In addition, in 41.20% of the population, the level of salt intake was at least two times higher than the level recommended by the WHO for adults. The mean of salt intake among Iranian population was 9.52 g/day (95% confidence interval: 9.48-9.56).

Conclusion: The study showed that the consumption of salt among the Iranian population is higher than the level recommended by WHO. To reduce salt intake, it is necessary to adopt a combination of nationwide policies such as food reformulation and food labelling.
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http://dx.doi.org/10.1097/HJH.0000000000001836DOI Listing
December 2018

Baseline High-Sensitivity C-Reactive Protein Predicts Macrovascular and Microvascular Complications of Type 2 Diabetes: A Population-Based Study.

Ann Nutr Metab 2018 25;72(4):287-295. Epub 2018 Apr 25.

Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background/aims: This prospective study is aimed at examining the predictive value of high-sensitivity C-reactive protein (hs-CRP) for coronary heart disease (CHD) events and microvascular complications of type 2 diabetes mellitus (T2DM).

Methods: A population-based study (NCT02958579) was conducted on 1,301 participants with T2DM (mean follow-up of 7.5 years). Risk assessment for vascular events was done at baseline, and serum hs-CRP was measured. End points of this study include CHD events, diabetic retinopathy, neuropathy, and diabetic kidney disease. Individuals with unavailable data or hs-CRP >20 mg/L were excluded. The discrimination and reclassification improvement of study end points were tested after addition of hs-CRP to traditional risk factors.

Results: Median serum hs-CRP was 2.00 ranging from 0.1 to 17 mg/L. Hazards ratio of each SD increment in baseline hs-CRP was 1.028 (1.024-1.032) for CHD, 1.025 (1.021-1.029) for diabetic neuropathy, 1.037 (1.030-1.043) for diabetic retinopathy, and 1.035 (1.027-1.043) for diabetic kidney disease. The addition of hs-CRP to traditional risk factors of vascular complications of T2DM improved discrimination of all end points (p < 0.001). Net reclassification improvement ranged from 8% for diabetic neuropathy to 31% for diabetic kidney disease (p < 0.05).

Conclusion: Baseline hs-CRP predicts both of CHD events and microvascular complications of patients with T2D.
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http://dx.doi.org/10.1159/000488537DOI Listing
August 2019

Conflicting interactions of apolipoprotein A and high density lipoprotein cholesterol with microvascular complications of type 2 diabetes.

Diabetes Res Clin Pract 2017 Nov 1;133:131-141. Epub 2017 Sep 1.

Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. Electronic address:

Aims: This study is amid at investigating the associations, and interactions of serum lipid biomarkers with microvascular complications of type 2 diabetes (T2D).

Methods: A nested case-control study was conducted within an ongoing prospective study on patients with T2D. Microvascular complications of T2D including diabetic neuropathy, diabetic retinopathy and diabetic nephropathy were investigated. A total of 444 cases with at least one of the microvascular complications of T2D and 439 age- and gender-matched controls free of any of the chronic microvascular complications of T2D were included. The associations and interactions of a panel of serum lipid biomarkers with the microvascular complications of T2D were investigated.

Results: Serum triglyceride had the strongest association with microvascular complications of T2D (crude model: β=0.632, P value=0.045). Each standard deviation increment in serum TG was associated with 3.7 times increased frequency of microvascular complications. Despite high density lipoprotein cholesterol (HDL-C), serum apolipoprotein A1 (Apo A1) was positively associated with the presence of diabetic neuropathy. Each standard deviation increment in serum ApoA1 was associated with increased frequency of diabetic neuropathy (OR, 1.2, 95% CI, (1.1-1.3), P value=0.006). The frequency of diabetic neuropathy was higher in 2nd and 3rd quartiles of serum Lp(a) compared to diabetic patients in the first quartile (OR, 5.52, 95% (1.17-25.8), P value=0.047).

Conclusions: ApoA1 but not HDL-C is straightly associated with diabetic neuropathy. Even Slight rise in serum Lp(a) is associated with increased frequency of diabetic retinopathLipid variables could serve as specific predictors of vascular complications in diabetes.
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http://dx.doi.org/10.1016/j.diabres.2017.07.037DOI Listing
November 2017

Is there sufficient evidence to support the use of vitamin supplements in the asthmatic patient?

Expert Rev Respir Med 2017 11 26;11(11):851-853. Epub 2017 Sep 26.

d Research Center for Immunodeficiencies, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.

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http://dx.doi.org/10.1080/17476348.2017.1383897DOI Listing
November 2017

Vitamin D status, aeroallergen sensitization, and allergic rhinitis: A systematic review and meta-analysis.

Int Rev Immunol 2017 01 19;36(1):41-53. Epub 2017 Jan 19.

g Department of Emergency Medicine, and Division of Rheumatology, Allergy, and Immunology, Department of Medicine , Massachusetts General Hospital, Harvard Medical School , Boston , Massachusetts , USA.

Purpose: The role of vitamin D status in the etiology of allergic diseases is uncertain. The aim of this study was to investigate the association of vitamin D status with risk of two main outcomes: aeroallergen sensitization and allergic rhinitis (AR).

Methods: We performed a systematic review of Medline, Scopus, Science Citation Index, and Google Scholar databases. Studies were included if they reported on prevalent or incident cases of aeroallergen sensitization or AR according to vitamin D status. Quality assessment, data extraction and meta-analysis were performed.

Results: A total of 21 observational studies were included. Children with serum 25(OH)D ≥75 nmol/L had significantly reduced odds of aeroallergen sensitization, but neither vitamin D intake in pregnancy nor vitamin D supplementation in infancy were associated with risk of AR. Individuals with serum 25(OH)D ≥75 nmol/L had lower prevalence of AR compared to those with serum 25(OH)D <50 nmol/L (OR; 0.71, 95%CI; (0.56-0.89), p = 0.04). This association was mainly observed in adult men; prevalence of AR was lower in men with serum 25(OH)D ≥75 nmol/L compared to men with serum 25(OH)D <50 nmol/L, while this association was not observed in women.

Conclusions: The current literature suggests significant age- and sex-specific relations of vitamin D status to risk of aeroallergen sensitization and AR.
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http://dx.doi.org/10.1080/08830185.2016.1272600DOI Listing
January 2017

Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes.

Atherosclerosis 2016 11 9;254:42-51. Epub 2016 Sep 9.

Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background And Aims: We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes.

Methods: In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses.

Results: We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], p value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05).

Conclusions: Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure.
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http://dx.doi.org/10.1016/j.atherosclerosis.2016.09.009DOI Listing
November 2016

Comment on Sharif et al. HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes. Diabetes Care 2016;39:1424-1430.

Diabetes Care 2016 10;39(10):e189

Endocrinology and Metabolism Research Institute, Vali-e-Asr Hospital, School of Medicine, Tehran University of Medical Sciences and Health Services, Tehran, Iran

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http://dx.doi.org/10.2337/dc16-1211DOI Listing
October 2016

Positive Correlation of Serum Adiponectin with Lipid Profile in Patients with Type 2 Diabetes Mellitus is Affected by Metabolic Syndrome Status.

Arch Iran Med 2016 Apr;19(4):269-74

Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Type-2 diabetes mellitus (DM) and Metabolic syndrome (MetS) are both associated with dyslipidemia which may lead to development of vascular complications. Adiponectin is an anti-inflammatory protein synthesized by the adipose tissue. There is controversy regarding the association of adiponectin with lipid profile.

Aim: To evaluate the correlation between serum adiponectin concentration and metabolic profile in patients with type-2 DM.

Methods: A single center cross-sectional study was conducted on 173 patients with type-2 DM (82 males and 91 females). Plasma adiponectin concentration, lipid profile, glucose profile, and anthropometric features were investigated. Insulin resistance was determined using Homeostasis model assessment (HOMA). Correlation of serum adiponectin with lipid profile of patients with type-2 DM was assessed.

Results: Adiponectin was negatively correlated with waist circumference (r = -0.16, P = 0.06) and positively with HbA1c (r = 0.19, P = 0.032), total cholesterol (r = 0.23, P = 0.017), LDL (r = 0.30, P = 0.001), SD-LDL (r = 0.41, P < 0.001), and SD-LDL/LDL (r = 0.22, P = 0.023). We found a positive correlation between adiponectin and total cholesterol (r = 0.27, P = 0.055), LDL (r = 0.34, P = 0.026) and SD-LDL (r = 0.41, P = 0.006) in patients with at least 3 components of MetS criteria. Correlation of adiponectin with LDL and SD-LDL remained positively significant with increasing the number of MetS components. In patients with 5 components of MetS, serum adiponectin was significantly correlated with serum triglyceride (r = 0.89). Significant interaction was observed between adiponectin and metabolic syndrome in relation to serum lipid profile.

Conclusion: The results of the present study suggest that in patients with type-2 DM and MetS, lipid profile is strongly correlated with blood concentration of adiponectin. The strongest association was observed between serum adiponectin and LDL.
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http://dx.doi.org/0161904/AIM.008DOI Listing
April 2016

Recurrence of lymphangioleiomyomatosis: Nine years after a bilateral lung transplantation.

World J Transplant 2016 Mar;6(1):249-54

Khawaja S Zaki, Zahra Aryan, Atul C Mehta, Olufemi Akindipe, Marie Budev, Respiratory Institute, Cleveland Clinic, Cleveland, OH 44195, United States.

Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive lethal lung disease primary afflicting young women. LAM is characterized by proliferation of abnormal smooth muscle cells that target the lungs, causing cystic destruction and eventual respiratory failure leading to death. Recent ten year mortality due to end stage LAM has been reported to be approximately 10%-20%, but may vary. The decline in lung function in LAM is gradual, occurring at a rate of about 3% to 15% per year but can vary from patient to patient. But recently therapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus has shown promising results in the stabilization of lung function and reduction of chylous effusions in LAM. Lung transplantation is a viable option for patients who continue to have decline in lung function despite mTOR therapy. Unique issues that may occur post-transplant in a recipient with LAM include development of chylous effusion and a risk of recurrence. We describe a case of LAM recurrence in a bilateral lung transplant recipient who developed histological findings of LAM nine years after transplantation.
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http://dx.doi.org/10.5500/wjt.v6.i1.249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801802PMC
March 2016

Paediatric orphan lung diseases in Asia.

Lancet Respir Med 2016 Mar 2;4(3):174-5. Epub 2016 Mar 2.

Pediatric Pulmonary and Sleep Medicine Department, Children's Medical Center, Gharib St, Keshavarz Blvd, Tehran University of Medical Sciences, Tehran, Iran; Pediatric Respiratory Diseases Education and Research Network (PRDERN), Universal Scientific Education and Research Network (USERN), Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(16)00049-7DOI Listing
March 2016

Serum IL-33 Is Elevated in Children with Asthma and Is Associated with Disease Severity.

Int Arch Allergy Immunol 2015 21;168(3):193-6. Epub 2016 Jan 21.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: The role of IL-33, a member of the IL-1 family, in airway hyperresponsiveness and asthma has still to be fully understood.

Objectives: This study is aimed at investigating serum IL-33 in children with asthma and its association with asthma severity.

Methods: This age- and sex-matched case-control study comprised 61 children with asthma and 63 healthy controls. The mean age of the participants was 9.21 years (range: 6-14). Serum IL-33 was measured using ELISA and was compared between children with asthma and controls. In addition, the association of serum IL-33 with asthma severity was investigated.

Results: The level of serum IL-33 was significantly higher in children with asthma than in controls (15.17 ± 32.3 vs. 0.61 ± 2.16 pg/ml; p = 0.028). It was significantly increased proportionately to asthma severity, namely 9.92 ± 30.26 pg/ml in children with mild asthma, 13.68 ± 29.27 pg/ml in children with moderate asthma and 31.92 ± 41.45 pg/ml in children with severe asthma (p = 0.026).

Conclusion: Serum IL-33 is increased in children with asthma and is associated with disease severity.
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http://dx.doi.org/10.1159/000442413DOI Listing
June 2016

Toll-like receptors as targets for allergen immunotherapy.

Curr Opin Allergy Clin Immunol 2015 Dec;15(6):568-74

aStudents' Scientific Research Center bResearch Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center cDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences dUniversal Scientific Education and Research Network (USERN), Tehran, Iran.

Purpose Of Review: Toll-like receptors (TLRs) are novel and promising targets for allergen immunotherapy. Bench studies suggest that TLR agonists reduce Th2 responses and ameliorate airway hyper-responsiveness. In addition, clinical trials are at initial phases to evaluate the safety and efficacy of TLR agonists for the allergen immunotherapy of patients with allergic rhinitis and asthma. (Figure is included in full-text article.)

Recent Findings: To date, two allergy vaccine-containing TLR agonists have been investigated in clinical trials; Pollinex Quattro and AIC. The former contains monophosphoryl lipid, a TLR4 agonist and the latter contains, CpG motifs activating the TLR9 cascade. Preseasonal subcutaneous injection of both of these allergy vaccines has been safe and efficacious in control of nasal symptoms of patients with allergic rhinitis. CRX-675 (a TLR4 agonist), AZD8848 (a TLR7 agonist), VTX-1463 (a TLR8 agonist) and 1018 ISS and QbG10 (TLR9 agonists) are currently in clinical development for allergic rhinitis and asthma.

Summary: TLR agonists herald promising results for allergen immunotherapy of patients with allergic rhinitis and asthma. Future research should be directed at utilizing these agents for immunotherapy of food allergy (for instance, peanut allergy) as well.
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http://dx.doi.org/10.1097/ACI.0000000000000212DOI Listing
December 2015

Pharmacogenetic tests to predict the efficacy of aspirin desensitization in patients with aspirin-exacerbated respiratory diseases; HLA-DQB302.

Expert Rev Respir Med 2015 Oct 26;9(5):511-8. Epub 2015 Aug 26.

a 1 Department of Allergy and Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

This study is aimed at investigating the association of HLA-DRB1, HLA-DQA1, and HLA-DQB1 variability with the response to aspirin desensitization (AD). A total of 16 patients with aspirin-exacerbated respiratory diseases (AERD, 81.3% were female) with median age of 29 ± 4.3 years were included in this study. Following 6 months, Sino-Nasal Outcome Test-22 (SNOT-22), medication, symptom scores, and forced expiratory volume in 1 s (FEV1) (all p < 0.001) improved significantly. However, only seven patients (43.7%) had clinically significant improvement in all of the medication and symptom scores and FEV1, who were considered responders to AD. Responders to AD had significantly higher symptom scores compared with non-responders at baseline (20 ± 1.18 vs 10 ± 1.27; p = 0.003). HLADQB1*0302 was significantly lower in non-responders than in responders to AD (0.12 [0.02-0.76]; p = 0.022). Sensitivity and specificity of HLA-DQB1*0302 to predict response to AD was 71.4% (95% CI: 35.8-91.7) and 81.8% (95% CI: 52.3-94.8). This study introduces HLA-DQB1*0302 as a genetic marker for favorable response to AD.
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http://dx.doi.org/10.1586/17476348.2015.1081062DOI Listing
October 2015

Association between single nucleotide polymorphisms of the interleukin-4 gene and atopic dermatitis.

Acta Dermatovenerol Croat 2015 ;23(2):96-100

Nima Rezaei, MD, PhD, Research Center for Immunodeficiencies, Children's Medical Center Hospital, Dr Qarib St, Keshavarz Blvd, Tehran 14194, Iran;

Atopic dermatitis (AD) is an inflammatory skin disease in which both genetic and environmental factors seem to be involved. Several studies investigated the association of certain genetic factors with AD in different ethnic groups, but conflicting data were obtained. This study was performed to check the possible association between single nucleotide polymorphisms (SNPs) of interleukin 4 (IL-4) and the IL-4 receptor α chain (IL-4Rα) and AD in a group of Iranian patients. The allele and genotype frequencies of genes encoding for IL-4 and IL-4Rα were investigated in 89 patients with AD in comparison with 139 healthy controls, using methods based on polymerase chain reaction sequence-specific primers. The most frequent alleles of IL-4 in patients were T at -1098 (P<0.001, odds ratio (OR)=2.35), C at -590 (P<0.001, OR=4.84) and C at -33 (P=0.002, OR=2.08). The most frequent genotypes of IL-4 in patients were TT, CC, and CC at positions -1098 (P<0.001, OR=3.59), -590 (P<0.001, OR=31.25) and -33 (P<0.001, OR=3.46), respectively. We found a significant lower frequency of GT at -1098 GT, TC at -590, and TC at -33 in patients. There were no statistically significant differences in the frequency of alleles and genotypes of IL-4Rα gene at position +1902. A strong positive association was seen between TCC haplotype and AD (68% in patients vs. 23.4% in controls, P<0.001, OR=8.91). We detected a significantly lower frequency of TTC, GCC, and TTT haplotypes (P<0.001, OR=0.02, P<0.001, OR=0.40, P<0.001, OR=0.39, respectively) in patients compared to controls. A significant association between the polymorphisms of the IL-4 gene promoter at positions -1098, -590, and -33 and AD was detected in the Iranian population.
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January 2017

Drainage-related ultrasonography (DRUS): a novel technique for discriminating obstructive and nonobstructive hydroureters in children.

J Ultrasound 2015 Jun 11;18(2):117-25. Epub 2014 Oct 11.

Department of Urology, University Hospitals of Case Medical Center, Case Western Reserve University, Cleveland, OH 44106 USA.

Background: Despite advances in urologic imaging, the paucity of an optimal technique that accurately clarifies obstructive and nonobstructive hydroureter exists.

Objective: This study was conducted to introduce a novel and modified ultrasonographic technique, known as drainage-related ultrasonography (DRUS), discriminating obstructive and nonobstructive, nonrefluxing hydroureter.

Materials And Methods: A total of 358 children (mean age, 3.7 years) with 418 nonrefluxing hydroureter were included. These children were composed of two groups of obstructive nonrefluxing (141 children with 157 dilated ureters) and nonobstructive, nonrefluxing (217 children with 261 hydroureter). The definite diagnosis regarding the subtype of hydroureter was derived from appropriate investigation. The maximum diameter of the dilated ureter, which was observed on ultrasonography, was recorded before and after 3 h of catheterization, as D1 and D2, respectively. To assess the D ratio, a formula was developed, that is, [(|D1 - D2|)/D1] × 100. Values were recorded and cutoff points were set to discriminate between subtypes.

Results: Obstructive versus nonobstructive subtypes of nonrefluxing hydroureter were clarified with 78.5 % sensitivity and 83.4 % specificity, by setting a cutoff point of 22 % for the D ratio. Regardless of the cutoff point assigned to the reduction in D (D2 compared with D1), DRUS revealed 93.9 % sensitivity, 80.6 % specificity, 63.2 % positive predictive value, and 97.4 % negative predictive value in discriminating upper from lower obstruction.

Conclusion: DRUS affords favorable results in terms of differentiating between obstructive and nonobstructive, nonrefluxing hydroureter, as well as between upper and lower obstruction in obstructive cases. It has the potential to become an efficient imaging modality in the diagnostic algorithm of hydroureter.
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http://dx.doi.org/10.1007/s40477-014-0128-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504862PMC
June 2015

Aspirin desensitization for patients with aspirin-exacerbated respiratory disease: A randomized double-blind placebo-controlled trial.

Clin Immunol 2015 Oct 14;160(2):349-57. Epub 2015 Jun 14.

Department of Clinical Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The effect of aspirin desensitization (AD) on immunologic profile of patients with AERD has been poorly understood. This study is aimed at investigating the effect of AD on clinical and immunological markers of patients with AERD. This randomized double-blind placebo-controlled trial comprised 34 adult patients (67.6% female) with chronic rhinosinusitis, nasal polyps, and aspirin-intolerant asthma. The active group underwent AD over a 2-day period with increasing doses of aspirin (60, 125, 325, and 625 mg), followed by receiving aspirin 625 mg twice daily for 6 months. Symptom scores and medication needs of patients with AERD who have undergone AD were significantly lower compared to the placebo group after 6 months (7.5 ± 3.5 vs. 10.6 ± 3.8 and 9.3 ± 2.0 vs. 11.0 ± 3.1, respectively, all p < 0.05). However, no significant difference was observed in serum concentration of IL-10, IFN-γ, and TGF-β between two groups neither at baseline nor at the end of study.
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http://dx.doi.org/10.1016/j.clim.2015.05.012DOI Listing
October 2015

Innate lymphoid cells are pivotal actors in allergic, inflammatory and autoimmune diseases.

Expert Rev Clin Immunol 2015 25;11(8):885-95. Epub 2015 May 25.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Innate lymphoid cells (ILCs) are lymphoid cells that do not express V(D)J-rearranged receptors and play a role in the innate immune system. ILCs are categorized into three groups with respect to their function in the immune system. ILC1 induces production of IFN-γ via T-box expressed on T cells, ILC2 promotes production of type 2 cytokines via GATA-binding protein-3 and ILC3 promotes IL-17 and IL-22 production via retinoic acid receptor-related orphan receptor-γt. ILCs can maintain homeostasis in epithelial surfaces by responding to locally produced cytokines or direct recognition of danger patterns. Altered epithelial barrier function seems to be a key point in inappropriate activation of ILCs to promote inflammatory and allergic responses. ILCs play an essential role in initiation and maintenance of defense against infections as well as immune-mediated diseases. In this paper, we discuss the role of ILCs in inflammatory, allergic and autoimmune diseases.
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http://dx.doi.org/10.1586/1744666X.2015.1050382DOI Listing
June 2016

HLA-DRB and HLA-DQ genetic variability in patients with aspirin-exacerbated respiratory disease.

Am J Rhinol Allergy 2015 May-Jun;29(3):e63-9

Department of Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

Background: Major histocompatibility complex (MHC) class II is involved in T-cell activation, cytokine secretion, and induction of immune responses. Cytokines, staphylococcus super antigens, and eosinophil activation are proposed to play important roles in aspirin-exacerbated respiratory disease (AERD).

Objectives: This study is aimed at investigating the association of HLA-DRB and DQ genetic variabilities in patients with AERD.

Methods: A genetic association analysis in three different groups, including 33 patients with AERD, 17 patients with aspirin-tolerant asthma (ATA), and 100 healthy controls was performed. Oral aspirin challenge (OAC) test was performed to identify aspirin hypersensitivity. Pulmonary function test (PFT) was performed for all patients. Eosinophil percentage in nasal smear and peripheral blood and serum immunoglobin (Ig)E were investigated. HLA-DRB, HLA-DQA1, and HLA-DQB1 were genotyped using polymerase chain reaction.

Results: HLA-DQB1*0302 (OR, 5.49, 95% confidence interval [CI],(2.40-12.59)), HLA-DQA1*0301 (OR, 2.90, 95% CI, (1.49-5.67)), HLA-DRB4 (OR, 2.94, 95% CI, (1.61-5.36)), and HLA-DRB1*04 (OR, 3.19, 95% CI, (1.57-6.47)) were higher in patients with AERD compared with controls. In patients with AERD, HLA-DQB1*0301 (OR,0.22, 95% CI, (0.09-0.54)), HLA-DQA1*0501 (OR, 0.42, 95% CI, (0.21-0.81)), HLA-DRB1*11 (OR, 0.30, 95% CI, (0.12-0.73)), and HLA-DRB3 (OR, 0.38, 95% CI, (0.21-0.70)) were significantly lower compared with healthy controls. Patients with AERD had lower frequencies of HLA-DQB1*0301 (OR, 0.27, 95% CI, (0.08-0.86)), and HLA-DRB1*011 (OR, 0.27, 95% CI, (0.08-0.86)) compared with ATA. Haplotypes of HLA-DRB1*04/ DQA1*0301/ DQB1*0302 (OR, 4.25, 95% CI, (1.94-9.29)) and HLA-DRB1*07 /DQA1*0201/ DQB1*0201 (OR, 3.52, 95% CI, (1.54-8.06)) were higher in patients with AERD compared with controls (all p < 0.05).

Conclusions: Results of this study suggest that HLA-DQB1*0302 and HLA-DRB1*04 and their related haplotypes are genes involved in predisposing patients to AERD, whereas HLA-DQB1*0301 and HLA-DRB1*011 have negative association with AERD.
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http://dx.doi.org/10.2500/ajra.2015.29.4154DOI Listing
February 2016

Association of interleukin 10 and transforming growth factor β gene polymorphisms with chronic idiopathic urticaria.

Acta Dermatovenerol Croat 2014 ;22(4):239-45

Ali Akbar Amirzargar, PhD, Molecular Immunology Research Center, Children's Medical Center Hospital, Dr Qarib St, Keshavarz Blvd, Tehran 14194, Iran;

Transforming growth factor β (TGF-β) and interleukin 10 (IL-10) are two anti-inflammatory cytokines that are implicated in the pathogenesis of urticaria. The goal of this study was to examine the possible association of polymorphisms of TGF-β and IL-10 genes with susceptibility to chronic idiopathic urticaria (CIU). This study was conducted on 90 patients with CIU. Polymerase chain reaction (PCR) was done to determine the genotype at 5 polymorphic sites; TGF-β (codon10C/T and codon25G/C) and IL-10 (-1082G/A, -819C/T, and -592C/A). The C allele at codon 25 of TGF-β was more prevalent in CIU patients compared to controls (OR = 9.5, 95% CI = 5.4-16.8, P<0.001). Genotypes of CT and CG at 10 and 25 codons of TGF-β gene, respectively, and AG, CT, and CA for loci of -1082, -819, and -592 of IL-10 gene were significantly higher in CIU patients (P<0.001). In haplotype analysis, frequency of TGF-β haplotypes differed between patients with CIU and controls; CC haplotype was overrepresented, while CG and TG haplotypes were underrepresented (P<0.001). These results suggest that TGF-β and IL-10 genetic variability could contribute to susceptibility to CIU. Additionally, patients with CIU seem to have genotypes leading to high production of TGF-β and IL-10.
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October 2016

Glomus tumor of the trachea.

Clin Respir J 2016 Jul 26;10(4):537-9. Epub 2014 Nov 26.

Cleveland Clinic, Respiratory Institute, Cleveland, OH, USA.

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http://dx.doi.org/10.1111/crj.12238DOI Listing
July 2016