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author:("bahrami, S")
1.  Protein Complex Discovery by Interaction Filtering from Protein Interaction Networks Using Mutual Rank Coexpression and Sequence Similarity 
BioMed Research International  2015;2015:165186.
The evaluation of the biological networks is considered the essential key to understanding the complex biological systems. Meanwhile, the graph clustering algorithms are mostly used in the protein-protein interaction (PPI) network analysis. The complexes introduced by the clustering algorithms include noise proteins. The error rate of the noise proteins in the PPI network researches is about 40–90%. However, only 30–40% of the existing interactions in the PPI databases depend on the specific biological function. It is essential to eliminate the noise proteins and the interactions from the complexes created via clustering methods. We have introduced new methods of weighting interactions in protein clusters and the splicing of noise interactions and proteins-based interactions on their weights. The coexpression and the sequence similarity of each pair of proteins are considered the edge weight of the proteins in the network. The results showed that the edge filtering based on the amount of coexpression acts similar to the node filtering via graph-based characteristics. Regarding the removal of the noise edges, the edge filtering has a significant advantage over the graph-based method. The edge filtering based on the amount of sequence similarity has the ability to remove the noise proteins and the noise interactions.
doi:10.1155/2015/165186
PMCID: PMC4322317
2.  Lupus risk variants in the PXK locus alter B-cell receptor internalization 
Frontiers in Genetics  2015;5:450.
Genome wide association studies have identified variants in PXK that confer risk for humoral autoimmune diseases, including systemic lupus erythematosus (SLE or lupus), rheumatoid arthritis and more recently systemic sclerosis. While PXK is involved in trafficking of epidermal growth factor Receptor (EGFR) in COS-7 cells, mechanisms linking PXK to lupus pathophysiology have remained undefined. In an effort to uncover the mechanism at this locus that increases lupus-risk, we undertook a fine-mapping analysis in a large multi-ancestral study of lupus patients and controls. We define a large (257kb) common haplotype marking a single causal variant that confers lupus risk detected only in European ancestral populations and spans the promoter through the 3′ UTR of PXK. The strongest association was found at rs6445972 with P < 4.62 × 10−10, OR 0.81 (0.75–0.86). Using stepwise logistic regression analysis, we demonstrate that one signal drives the genetic association in the region. Bayesian analysis confirms our results, identifying a 95% credible set consisting of 172 variants spanning 202 kb. Functionally, we found that PXK operates on the B-cell antigen receptor (BCR); we confirmed that PXK influenced the rate of BCR internalization. Furthermore, we demonstrate that individuals carrying the risk haplotype exhibited a decreased rate of BCR internalization, a process known to impact B cell survival and cell fate. Taken together, these data define a new candidate mechanism for the genetic association of variants around PXK with lupus risk and highlight the regulation of intracellular trafficking as a genetically regulated pathway mediating human autoimmunity.
doi:10.3389/fgene.2014.00450
PMCID: PMC4288052  PMID: 25620976
lupus; PXK; fine-mapping; B cells; BCR
3.  Cloning and Expression of TNF Related Apoptosis Inducing Ligand in Nicotiana tabacum 
Molecular farming has been considered as a secure and economical approach for production of biopharmaceuticals. Human TNF Related Apoptosis Inducing Ligand (TRAIL) as a promising biopharmaceutical candidate has been produced in different expression hosts. However, little attention has been paid to molecular farming of the TRAIL in spite of numerous advantages of plant expression systems. Therefore, in this study the cytoplasmic production of the TRAIL was tackled in Nicotiana tabacum using Agrobacterium tumefaciens LBA 4404. Initially, the desired coding sequence was obtained using PCR technique on the constructed human cDNA library. Afterward, the necessary requirements for expression of the TRAIL in plant cell system were provided through sub-cloning into 35S-CaMV (Cauliflower Mosaic Virus) helper and final 0179-pGreen expression vectors. Then, the final TRAIL-pGreen expression vector was cloned into A. tumefaciens LBA 4404. Subsequently, the N. tabacum cells were transformed through co-culture method and expression of the TRAIL was confirmed by western blot analysis. Finally, the recombinant TRAIL was extracted through chromatographic technique and biological activity was evaluated through MTT assay (Methylthiazol Tetrazolium Assay). The result of western blot analysis indicated that only monomer and oxidized dimer forms of the TRAIL can be extracted from the N. tabacum cells. Moreover, the lack of trimeric assembly of the extracted TRAIL diminished its biological activity in sensitive A549 cell line. In conclusion, although N. tabacum cells can successfully produce the TRAIL, proper assembly and functionality of the TRAIL were unfavorable.
PMCID: PMC4277632  PMID: 25561925
Recombinant protein; TRAIL; Molecular Farming; Nicotiana tabacum; Agrobacterium tumefaciens
4.  Exploring possible causes of fatal burns in 2007 using Haddon’s Matrix: a qualitative study 
Abstract:
Background:
Burns are a major factor in injury mortality. The aim of this study was to explore the possible causes of fatal burns using Haddon’s Matrix.
Methods:
This is a qualitative study using a phenomenological approach. We collected elicitation interview data using nine corroborators who were the most knowledgeable about the index burn event. Immediately after recording, the data was verbatim. Each event was analyzed using Haddon’s Matrix.
Results:
Interviewees provided detailed information about 11 burn cases. Overall, 202 burn-related factors were extracted. Using Haddon’s Matrix, 43 risk factors were identified. The most common included the lack of basic knowledge of burn care, the use of unsafe appliances including kerosene heaters and stoves in hazardous environments such kitchens and bathrooms, poor burn care delivery system in hospitals, poor and unsafe living conditions, financial issues, and other factors detailed in the article.
Conclusions:
Our findings suggest burn related prevention efforts should focus on improving human living conditions, promoting the use of safe heating appliances, providing public burn-safety precautions education, and improving the quality of care in burn centers and hospitals. The use of Haddon’s Matrix in future injury research is discussed.
doi:10.5249/jivr.v7i1.501
PMCID: PMC4288289  PMID: 24879079
Fatal burns ; Haddon’s Matrix ; Injury; Qualitative study
5.  Classification of Histology Sections via Multispectral Convolutional Sparse Coding* 
Image-based classification of histology sections plays an important role in predicting clinical outcomes. However this task is very challenging due to the presence of large technical variations (e.g., fixation, staining) and biological heterogeneities (e.g., cell type, cell state). In the field of biomedical imaging, for the purposes of visualization and/or quantification, different stains are typically used for different targets of interest (e.g., cellular/subcellular events), which generates multi-spectrum data (images) through various types of microscopes and, as a result, provides the possibility of learning biological-component-specific features by exploiting multispectral information. We propose a multispectral feature learning model that automatically learns a set of convolution filter banks from separate spectra to efficiently discover the intrinsic tissue morphometric signatures, based on convolutional sparse coding (CSC). The learned feature representations are then aggregated through the spatial pyramid matching framework (SPM) and finally classified using a linear SVM. The proposed system has been evaluated using two large-scale tumor cohorts, collected from The Cancer Genome Atlas (TCGA). Experimental results show that the proposed model 1) outperforms systems utilizing sparse coding for unsupervised feature learning (e.g., PSD-SPM [5]); 2) is competitive with systems built upon features with biological prior knowledge (e.g., SMLSPM [4]).
doi:10.1109/CVPR.2014.394
PMCID: PMC4279924  PMID: 25554749
6.  The Effect of Inversion at 8p23 on BLK Association with Lupus in Caucasian Population 
PLoS ONE  2014;9(12):e115614.
To explore the potential influence of the polymorphic 8p23.1 inversion on known autoimmune susceptibility risk at or near BLK locus, we validated a new bioinformatics method that utilizes SNP data to enable accurate, high-throughput genotyping of the 8p23.1 inversion in a Caucasian population. Methods: Principal components analysis (PCA) was performed using markers inside the inversion territory followed by k-means cluster analyses on 7416 European derived and 267 HapMaP CEU and TSI samples. A logistic regression conditional analysis was performed. Results: Three subgroups have been identified; inversion homozygous, heterozygous and non-inversion homozygous. The status of inversion was further validated using HapMap samples that had previously undergone Fluorescence in situ hybridization (FISH) assays with a concordance rate of above 98%. Conditional analyses based on the status of inversion were performed. We found that overall association signals in the BLK region remain significant after controlling for inversion status. The proportion of lupus cases and controls (cases/controls) in each subgroup was determined to be 0.97 for the inverted homozygous group (1067 cases and 1095 controls), 1.12 for the inverted heterozygous group (1935 cases 1717 controls) and 1.36 for non-inverted subgroups (924 cases and 678 controls). After calculating the linkage disequilibrium between inversion status and lupus risk haplotype we found that the lupus risk haplotype tends to reside on non-inversion background. As a result, a new association effect between non-inversion status and lupus phenotype has been identified ((p = 8.18×10−7, OR = 1.18, 95%CI = 1.10–1.26). Conclusion: Our results demonstrate that both known lupus risk haplotype and inversion status act additively in the pathogenesis of lupus. Since inversion regulates expression of many genes in its territory, altered expression of other genes might also be involved in the development of lupus.
doi:10.1371/journal.pone.0115614
PMCID: PMC4278715  PMID: 25545785
7.  Imputation and quality control steps for combining multiple genome-wide datasets 
Frontiers in Genetics  2014;5:370.
The electronic MEdical Records and GEnomics (eMERGE) network brings together DNA biobanks linked to electronic health records (EHRs) from multiple institutions. Approximately 51,000 DNA samples from distinct individuals have been genotyped using genome-wide SNP arrays across the nine sites of the network. The eMERGE Coordinating Center and the Genomics Workgroup developed a pipeline to impute and merge genomic data across the different SNP arrays to maximize sample size and power to detect associations with a variety of clinical endpoints. The 1000 Genomes cosmopolitan reference panel was used for imputation. Imputation results were evaluated using the following metrics: accuracy of imputation, allelic R2 (estimated correlation between the imputed and true genotypes), and the relationship between allelic R2 and minor allele frequency. Computation time and memory resources required by two different software packages (BEAGLE and IMPUTE2) were also evaluated. A number of challenges were encountered due to the complexity of using two different imputation software packages, multiple ancestral populations, and many different genotyping platforms. We present lessons learned and describe the pipeline implemented here to impute and merge genomic data sets. The eMERGE imputed dataset will serve as a valuable resource for discovery, leveraging the clinical data that can be mined from the EHR.
doi:10.3389/fgene.2014.00370
PMCID: PMC4263197  PMID: 25566314
imputation; genome-wide association; eMERGE; electronic health records
8.  Efficient prediction of human protein-protein interactions at a global scale 
BMC Bioinformatics  2014;15(1):383.
Background
Our knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods.
Results
On the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network within 3 months. With a recall of 23% at a precision of 82.1%, we predicted 172,132 putative PPIs. We demonstrate the usefulness of these predictions through a range of experiments.
Conclusions
The speed and accuracy associated with MP-PIPE can make this a potential tool to study individual human PPI networks (from genomic sequences alone) for personalized medicine.
Electronic supplementary material
The online version of this article (doi:10.1186/s12859-014-0383-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12859-014-0383-1
PMCID: PMC4272565  PMID: 25492630
Protein-protein interactions; Computational prediction; Human proteome; Massively parallel computing; Personalized medicine; Interactome; Network analysis
9.  Renal function in a rat model of neurogenic bladder, effect of statins and phosphodiesterase-5 inhibitors 
European Spine Journal  2013;22(12):2766-2769.
Purpose
Neurogenic bladder is a common complication of several central nervous system injuries. Statins and phosphodiesterase-5 (PDE-5) inhibitors are reportedly beneficial in neural injuries and urinary system dysfunction. The effect of simvastatin, sildenafil and tadalafil on several renal function indices of an animal model of neurogenic bladder was investigated.
Methods
Forty male rats were assessed in five equal groups. Dura mater and the cord were injured with an aneurysmal clamp at the level of T9–T10 in all rats except in sham group. The sham and control groups (treated by normal saline), simvastatin (4 mg/kg), sildenafil (5 mg/kg), and tadalafil (2 mg/kg) groups received treatment (i.p.) for seven consecutive days following injury. Renal system and motor functions were assessed at day 28 following injury. Data were analyzed by analysis of variance followed by the Student–Newman–Keuls post hoc test.
Results
Simvastatin improved both the renal and the motor function compared with the control group. However, sildenafil and tadalafil could only improve the motor function but could not make any significant differences in renal indices in comparison with the control group.
Conclusion
Statins can effectively improve the motor and renal functions in a condition of renal dysfunction in a rat model of neurogenic bladder. PDE-5 inhibitors could help to improve motor function, but are not helpful in renal function, at least in short time.
doi:10.1007/s00586-013-2927-x
PMCID: PMC3843790  PMID: 23903999
Neurogenic bladder; Phosphodiesterase-5 inhibitors; Statins
10.  Protein-protein interaction networks (PPI) and complex diseases 
The physical interaction of proteins which lead to compiling them into large densely connected networks is a noticeable subject to investigation. Protein interaction networks are useful because of making basic scientific abstraction and improving biological and biomedical applications. Based on principle roles of proteins in biological function, their interactions determine molecular and cellular mechanisms, which control healthy and diseased states in organisms. Therefore, such networks facilitate the understanding of pathogenic (and physiologic) mechanisms that trigger the onset and progression of diseases. Consequently, this knowledge can be translated into effective diagnostic and therapeutic strategies. Furthermore, the results of several studies have proved that the structure and dynamics of protein networks are disturbed in complex diseases such as cancer and autoimmune disorders. Based on such relationship, a novel paradigm is suggested in order to confirm that the protein interaction networks can be the target of therapy for treatment of complex multi-genic diseases rather than individual molecules with disrespect the network.
PMCID: PMC4017556  PMID: 25436094
PPI; Complex diseases; Networks
11.  The effects of short term intravenous infusion of a soybean based lipid emulsion on some blood constituents in sheep: A preliminary study 
To evaluate the effect of intravenous infusion of a soybean based lipid emulsion (Lipovenoes 10%) on some blood constituents in sheep, a replicated 2 × 2 Latin square design experiment was conducted in four clinically healthy ewes. Lipid emulsion (LE group) or normal saline (NS group) was infused intravenously at a rate of 0.025 mL kg-1 per min for 6 hr and the concentrations of blood triglyceride, glucose, insulin, calcium, magnesium, phosphorous, sodium and potassium were measured before (baseline) and then at timepoints 2, 4, 6, 12 and 24 hr after infusion. Compared to the baseline values and/or NS infusion, LE infusion resulted in a significant increase in the concentrations of triglyceride (p < 0.001), glucose (p < 0.01), calcium (p < 0.05), phosphorous (p < 0.01) and a significant decrease in insulin (p < 0.001) and magnesium (p < 0.05) concentrations. Compared to the baseline value, the homeostasis model of insulin resistance (HOMA-IR) index increased (p < 0.001) at timepoints 2 and 4 hr and abruptly decreased at timepoint six hr (p < 0.01) following LE infusion. In LE group, HOMA-IR values were significantly (p < 0.001) higher than those for NS group at timepoints 2 and 4 hr after infusion. Neither treatment nor time influenced serum sodium and potassium concentrations (p > 0.05). In conclusion, intravenous infusion of Lipovenoes temporarily influenced some blood constituents. Increased triglyceride concentrations were associated with an increase in HOMA-IR values indicating a state of insulin resistance. No remarkable adverse effect was observed following LE infusion and lipid based emulsions can be safely used in ruminants not suffering from extensive lipid mobilization.
PMCID: PMC4279665  PMID: 25568690
Blood constituents; Insulin resistance; Lipid emulsion; Sheep
12.  Digitally synthesized beat frequency-multiplexed fluorescence lifetime spectroscopy 
Biomedical Optics Express  2014;5(12):4428-4436.
Frequency domain fluorescence lifetime imaging is a powerful technique that enables the observation of subtle changes in the molecular environment of a fluorescent probe. This technique works by measuring the phase delay between the optical emission and excitation of fluorophores as a function of modulation frequency. However, high-resolution measurements are time consuming, as the excitation modulation frequency must be swept, and faster low-resolution measurements at a single frequency are prone to large errors. Here, we present a low cost optical system for applications in real-time confocal lifetime imaging, which measures the phase vs. frequency spectrum without sweeping. Deemed Lifetime Imaging using Frequency-multiplexed Excitation (LIFE), this technique uses a digitally-synthesized radio frequency comb to drive an acousto-optic deflector, operated in a cat’s-eye configuration, to produce a single laser excitation beam modulated at multiple beat frequencies. We demonstrate simultaneous fluorescence lifetime measurements at 10 frequencies over a bandwidth of 48 MHz, enabling high speed frequency domain lifetime analysis of single- and multi-component sample mixtures.
doi:10.1364/BOE.5.004428
PMCID: PMC4285616  PMID: 25574449
(170.3650) Lifetime-based sensing; (170.2520) Fluorescence microscopy; (170.1065) Acousto-optics; (170.1790) Confocal microscopy
13.  Does disk space degeneration according to Los Angeles and Modic scales have relation with recurrent disk herniation? 
Background:
After single disk herniation operation, about 5–20% recurrences may occur. Different etiology may affect the prevalence of recurrence. Disk degeneration according to Modic and Los Angles scales could affect recurrence rate. This study wants to show the relationship between disk space degeneration according to these scales on severity, time, and prevalence of disk herniation recurrence.
Materials and Methods:
Thirty-four patients presented with radicular pain (with or without back pain) and history of lumbar disk surgery was included in this prospective study. Pre- and postoperative T2-weighted sagittal magnetic resonance imaging (MRI) compared for Modic and Los Angeles disk degeneration grading, then, data analysis on SPSS (version 20) software, paired t-test, and others.
Results:
The result of study shows for first operation that grade (II) Los Angeles is the most common, but, for second procedure grade (IV) was less common and the mostly decreased (from 14.7 to 9.2%). In addition, Wilcoxon test shows no change of Los Angeles grading for both first and second surgery (P = 0.06). Whereas; based on Modic criteria grading was different from first operation, in other words, grade (I) (41.2%) in first operation was changed to 20.6% in second operation (P = 0.007).
Conclusion:
Our study showed that the Los Angeles criterion is more practical and useful for prediction of recurrence and in the patients with Los Angles grade III and IV and grade II and III on Modic scale, the chance of recurrence is less than patients with lower grades.
doi:10.4103/2277-9175.145125
PMCID: PMC4260280  PMID: 25538906
Disk herniation recurrence; disc space degeneration; Los Angeles scale; Modic scale
14.  Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eosinophilic Esophagitis 
Frontiers in Genetics  2014;5:401.
Objective: We report the first pediatric specific Phenome-Wide Association Study (PheWAS) using electronic medical records (EMRs). Given the early success of PheWAS in adult populations, we investigated the feasibility of this approach in pediatric cohorts in which associations between a previously known genetic variant and a wide range of clinical or physiological traits were evaluated. Although computationally intensive, this approach has potential to reveal disease mechanistic relationships between a variant and a network of phenotypes.
Method: Data on 5049 samples of European ancestry were obtained from the EMRs of two large academic centers in five different genotyped cohorts. Recently, these samples have undergone whole genome imputation. After standard quality controls, removing missing data and outliers based on principal components analyses (PCA), 4268 samples were used for the PheWAS study. We scanned for associations between 2476 single-nucleotide polymorphisms (SNP) with available genotyping data from previously published GWAS studies and 539 EMR-derived phenotypes. The false discovery rate was calculated and, for any new PheWAS findings, a permutation approach (with up to 1,000,000 trials) was implemented.
Results: This PheWAS found a variety of common variants (MAF > 10%) with prior GWAS associations in our pediatric cohorts including Juvenile Rheumatoid Arthritis (JRA), Asthma, Autism and Pervasive Developmental Disorder (PDD) and Type 1 Diabetes with a false discovery rate < 0.05 and power of study above 80%. In addition, several new PheWAS findings were identified including a cluster of association near the NDFIP1 gene for mental retardation (best SNP rs10057309, p = 4.33 × 10−7, OR = 1.70, 95%CI = 1.38 − 2.09); association near PLCL1 gene for developmental delays and speech disorder [best SNP rs1595825, p = 1.13 × 10−8, OR = 0.65(0.57 − 0.76)]; a cluster of associations in the IL5-IL13 region with Eosinophilic Esophagitis (EoE) [best at rs12653750, p = 3.03 × 10−9, OR = 1.73 95%CI = (1.44 − 2.07)], previously implicated in asthma, allergy, and eosinophilia; and association of variants in GCKR and JAZF1 with allergic rhinitis in our pediatric cohorts [best SNP rs780093, p = 2.18 × 10−5, OR = 1.39, 95%CI = (1.19 − 1.61)], previously demonstrated in metabolic disease and diabetes in adults.
Conclusion: The PheWAS approach with re-mapping ICD-9 structured codes for our European-origin pediatric cohorts, as with the previous adult studies, finds many previously reported associations as well as presents the discovery of associations with potentially important clinical implications.
doi:10.3389/fgene.2014.00401
PMCID: PMC4235428  PMID: 25477900
PheWAS; ICD-9 code; genetic polymorphism
15.  A multiple logistic regression analysis of complications following microsurgical breast reconstruction 
Gland Surgery  2014;3(4):226-231.
Background
Although we practice in an era of high flap success rates following microsurgical breast reconstruction, complications can still occur. Several studies have evaluated the impact of risk factors on microvascular outcomes in the setting of a particular type of patient or with a particular type of flap. However, few studies that have evaluated a consecutive series of high-risk patients will all types of microvascular breast reconstruction. Our goal was to gain a better understanding of the relationship between risk factors and complications in order to provide useful information for patients and surgeons considering free flap breast reconstruction in high-risk patients.
Methods
We performed a retrospective review of all patients who underwent microsurgical breast reconstruction by the senior author (M.Y.N) from July 2005 July 2010. Patient records were analyzed for risk factors (age, BMI, smoking history, medical history, adjunct therapies, timing of reconstruction, type of reconstruction), and complications (hematoma, seroma, infection, wound dehiscence, pulmonary embolism (PE), deep venous thrombosis (DVT), pneumonia, fat necrosis, leech use, partial flap loss, total flap loss). Statistical methods were employed to determine statistically significant relationships.
Results
A total of 352 patients underwent 490 microvascular breast reconstructions during the study period. Active smoking was found to be a statistically significant risk factor for seroma [P<0.0001; odds ratio (OR) =36; 95% confidence interval (CI), 5.9-193.9], infection (P=0.0081; OR =4.3; 95% CI, 1.3-14.1), and pneumonia (P<0.0001; OR =17.1; 95% CI, 3.3-89.9). Unilateral reconstruction was found to be a statistically significant factor for fat necrosis (P=0.0083; OR =4; 95% CI, 1.4-11.4). Additionally, BMI was found to be a statistically significant risk factor for infection (P<0.00001).
Conclusions
This study corroborates findings from previous studies. Tobacco use was demonstrated to be a significant risk factor for infection, seroma, and pneumonia. Obesity was demonstrated to be a significant risk factor for infection. Unilateral reconstruction was demonstrated to pose additional risk for fat necrosis compared to bilateral reconstruction. Patients who choose to have microsurgical breast reconstruction should be informed of the complication profile associated with certain risk factors.
doi:10.3978/j.issn.2227-684X.2014.10.03
PMCID: PMC4244511  PMID: 25493253
Breast reconstruction; microsurgery; complications; radiation therapy; tobacco
16.  Interleukin-28B (rs12979860) gene variation and treatment outcome after peginterferon plus ribavirin therapy in patients with genotype 1 of hepatitis C virus 
Background:
The success of treatment of chronic hepatitis C (CHC) with pegylated interferon-α (PEG-IFN-α) and ribavirin (RBV) is affected by several host, viral, and treatment factors. This study was designed to describe the association of interleukin (IL) 28B genotypes for rs12979860 with sustained virologic response (SVR) in patients with genotype 1 CHC infection treated with PEG-IFN α-2 and RBV.
Materials and Methods:
Interleukin-28B genotype in 100 studied patients was detected by tagman real-time polymerase chain reaction. Before treatment blood samples were obtained, then patients were treated for 48-week with a combination therapy using of the PEG-IFN α-2 and RBV. SVR evaluated 6 months after stopping therapy, and was defined as undetectable plasma hepatitis C virus-RNA.
Results:
Among studied patients, 65% were IL-28B CT, 27% CC, and 8% TT. In all studied patients, SVR was 58.3%, relapse 15.6%, and null virological response 26.1%. SVR rates were 76.9% in IL-28B-CC, 56.4% in IL-28B-CT, and 12.5% in IL-28B-TT patients. Relapse rates were 7.7% in IL-28B-CC, 12.9% in IL-28B-CT, and 62.5% in IL-28B-TT patients. There was a significant difference between response to treatment in patients IL-28B-CC, CT, and TT (P = 0.003). IL-28B genotype CC, (odds ratio = 0.053, 95% confidence interval; 0.005-0.54, P = 0.03), was the independent predicting factor.
Conclusion:
Interleukin-28B was an important predictor of CHC treatment outcome with Peg-IFN-α and RBV. IL-28B-CC seems to be more important than IL-28B-CT/TT in predicting positive treatment response.
PMCID: PMC4310080  PMID: 25657752
Chronic hepatitis C; interleukin-28B; pegylated interferon-α; ribavirin
17.  Terbinafin 1% Cream and Ketoconazole 2% Cream in the Treatment of Pityriasis Versicolor: A randomized comparative clinical trial 
Pakistan Journal of Medical Sciences  2014;30(6):1273-1276.
Objective: To make a comparison between terbinafine 1% cream and ketoconazole 2% cream in the treatment of pityriasis versicolor.
Methods: This randomized single blind study included 110 patients with clinical diagnosis of pityriasis versicolor and positive mycological test for Malassezia furfur. The patients were randomly assigned to two groups. Group 1 used terbinafine cream and group 2 applied ketoconazole cream on the skin lesions for two weeks. Each group consisted of 55 patients. Clinical and mycological examinations were performed at baseline, at the end of the 2nd, 4th and 8th week of starting the treatment regimens.
Results: At the end of the 2nd week we achieved cure rates of 72% and 64.3% for group 1 and group 2 respectively. At the end of the 4th week the respective cure rates for group 1 and group 2 were 81.2% and 69%, and at the end of the 8th week 70.8% of the patients in group 1 and 61.9% of the patients in group 2 were cured.
Conclusion: The results of this study showed no significant statistical differences between the two groups in regard to cure and recurrence rates. But the numbers of cured patients were higher and recurrent cases were lower in group 1.
doi:10.12669/pjms.306.5509
PMCID: PMC4320714
Terbinafine cream; Ketoconazole cream; Pityriasis versicolor; Cure rate
18.  MiR-30a-3p Negatively Regulates BAFF Synthesis in Systemic Sclerosis and Rheumatoid Arthritis Fibroblasts 
PLoS ONE  2014;9(10):e111266.
We evaluated micro (mi) RNA-mediated regulation of BAFF expression in fibroblasts using two concomitant models: (i) synovial fibroblasts (FLS) isolated from healthy controls (N) or Rheumatoid Arthritis (RA) patients; (ii) human dermal fibroblasts (HDF) isolated from healthy controls (N) or Systemic Sclerosis (SSc) patients. Using RT-qPCR and ELISA, we first showed that SScHDF synthesized and released BAFF in response to Poly(I:C) or IFN-γ treatment, as previously observed in RAFLS, whereas NHDF released BAFF preferentially in response to IFN-γ. Next, we demonstrated that miR-30a-3p expression was down regulated in RAFLS and SScHDF stimulated with Poly(I:C) or IFN-γ. Moreover, we demonstrated that transfecting miR-30a-3p mimic in Poly(I:C)- and IFN-γ-activated RAFLS and SScHDF showed a strong decrease on BAFF synthesis and release and thus B cells survival in our model. Interestingly, FLS and HDF isolated from healthy subjects express higher levels of miR-30a-3p and lower levels of BAFF than RAFLS and SScHDF. Transfection of miR-30a-3p antisense in Poly(I:C)- and IFN-γ-activated NFLS and NHDF upregulated BAFF secretion, confirming that this microRNA is a basal repressors of BAFF expression in cells from healthy donors. Our data suggest a critical role of miR-30a-3p in the regulation of BAFF expression, which could have a major impact in the regulation of the autoimmune responses occurring in RA and SSc.
doi:10.1371/journal.pone.0111266
PMCID: PMC4216016  PMID: 25360821
19.  Microbiologic spectrum of acute and chronic dacryocystitis 
AIM
To report the microbiological spectrum of acute and chronic dacrocystitis.
METHODS
Retrospective study on 100 patients who presented to the ophthalmic plastic clinic of a tertiary eye care center from May 2011 and April 2013 with acute and chronic dacryocystitis was reviewed for demographic and microbiological profile. The culture results and organisms isolated were recorded.
RESULTS
Sixty patients had acute onset and the remaining 40 patients had chronic onset dacryocystitis. The female to male ratio was 1.78. The mean age of patients was 44y. Gram-positive organisms were the most commonly isolated accounting for 54%, and the commonest species isolated was S. aureus in 26%. Percentage of gram positive cultures was higher in chronic dacryocystitis than acute ones (82% vs 48% of positive cultures; P=0.003). Also in culture positive acute dacryocystitis, gram negative species were found in 52% of eyes but only in 18% of chronic dacryocystitis.
CONCLUSION
Gram negative bacteria, culture negative samples, unusual and more virulent organisms are more common in acute dacryocystitis than chronic ones. The results of this study have significant bearing on the treatment of patients with dacrocystitis.
doi:10.3980/j.issn.2222-3959.2014.05.23
PMCID: PMC4206896  PMID: 25349808
epiphora; dacrocystitis; acute; chronic; bacteriology
20.  Predicting Difficulty Score for Spinal Anesthesia in Transurethral Lithotripsy Surgery 
Background:
Spinal anesthesia (SA) is the most common regional anesthesia (RA) conducted for many surgical procedures.
Objectives:
The current study aimed to predict the difficulty score of SA, by which to reduce the complications and ultimately improve the anesthesia quality.
Materials and Methods:
Transurethral Lithotripsy (TUL) surgery candidates were enrolled in this observational study from 2010 to 2011. Before SA, the patient`s demographic information along with the Body Mass Index (BMI), lumbar spinous process status, spinal deformity, radiological signs of lumbar vertebrae, and a history of spinal surgery or difficult SA were recorded, then the patients underwent SA in L3-L4 interspinous process space. Information about Cerebrospinal Fluid (CSF) visibility at the first attempt (easy SA) and the times of trying with shifting in that space or trying the second space (moderate SA) and the third space (difficult SA) were recorded. Multinominal regression and relative operating characteristic (ROC) curve were used for statistical analysis.
Results:
Hundred and one patients were enrolled. Of these patients, 50 (49.5%) underwent SA by the first attempt of the first space, in 36 patients (35.6%) it was moderate and in 15 patients (14.9%) it was difficult. There was no significant relationship between difficulty score of SA and gender, age, height, and history of previous difficult SA. But there was a significant relationship between difficulty score of SA and lumbar spinous process status (P =0.0001), radiological profile of the lumbar spine (P = 0.0001), the status of lumbar deformity (P = 0.007), and BMI (P = 0.006). Then using the ROC curve to predict the difficult SA, the cutoff point was 8.5 with 86.7% and 86% sensitivity and specificity, respectively.
Conclusions:
It seems that considering the clinical examination of patients before SA focusing on lumbar spinous process status, presence of lumbar deformity, calculation of BMI and radiological signs of lumbar vertebrae can be helpful in predicting SA difficulty.
doi:10.5812/aapm.16244
PMCID: PMC4199214  PMID: 25337470
Spinal Anesthesia; Lithotripsy; Severity Score
21.  Comparing the Effects of Morphine Sulfate and Diclofenac Suppositories on Postoperative Pain in Coronary Artery Bypass Graft Patients 
Background:
Simple and efficient way of pain management after Coronary Artery Bypass Graft (CABG) surgery is an important aspect of patients' care.
Objectives:
This study aimed to compare the effects of morphine and diclofenac suppositories on postoperative pain management.
Patients and Methods:
In this double-blinded clinical trial study, 120 patients aged 30-65 years old, undergone CABG, were equally divided into two groups of A (morphine) and B (diclofenac). All patients were anesthetized with intravenous fentanyl 10 μg/kg, etomidate 0.2 mg/kg and cisatracurium 0.2 mg/kg. Anesthesia was maintained with oxygen 50% and air 50%, propofol 50 μg/kg/min, fentanyl 1-2 μg/kg/h and atracurium 0.6 mg/kg/h. Analgesics were administered after the operation at intensive care unit (ICU) and Visual Analogue Score (VAS) was evaluated in both groups in 4-hour intervals after extubation for 24 hours. After extubation in case of VAS > 3, morphine suppository 10 mg (group A) or diclofenac suppository 50 mg (group B) was administered for patients.
Results:
No significant statistical relationship was found between the two groups regarding gender, age, BMI, paracetamol consumption, length of operation time, cardiopulmonary bypass pump (CPB) time, and stay time at ICU (P Value ≥ 0.05). Total dosage of used morphine was 22 ± 8.3 mg in each patient and total dosage of used diclofenac was 94 ± 32.01 mg. Average variation of VAS at measured intervals was significant (P Value ≤ 0.0001), but these variations were not significantly different when comparing the two groups (P Value = 0.023).
Conclusions:
Both morphine and diclofenac suppositories reduced pain significantly and similarly after CABG surgery.
doi:10.5812/aapm.19423
PMCID: PMC4205802  PMID: 25346897
Cardiac Surgery; Pain; Morphine; Diclofenac
22.  Mixed field reactions in ABO and Rh typing chimerism likely resulting from twin haematopoiesis 
Blood Transfusion  2014;12(4):608-610.
doi:10.2450/2014.0261-13
PMCID: PMC4212043  PMID: 24887220
mixed field reactions; chimerism; ABO
23.  Visual Acuity Changes during Pregnancy and Postpartum: A Cross-Sectional Study in Iran 
Journal of Pregnancy  2014;2014:675792.
In this research, we represent the changes in visual acuity during pregnancy and after delivery. Changes as myopic shift start during second trimester and will be stopped after delivery; however it is obtained that women will have the same refractive error as what they had in the first trimester, after postpartum. So, any change in their spectacle prescription during this period is forbidden. As a result, not only changing in hormones can cause myopic shift in vision, but also overweight has its retributive role. What we are trying to do is to notify gynecologists and optometrists to be aware of these changes, so as to leave spectacle prescription writing to the session after postpartum period.
doi:10.1155/2014/675792
PMCID: PMC4195258  PMID: 25328705
24.  Effects of Obesity on Bone Mass and Quality in Ovariectomized Female Zucker Rats 
Journal of Obesity  2014;2014:690123.
Obesity and osteoporosis are two chronic conditions that have been increasing in prevalence. Despite prior data supporting the positive relationship between body weight and bone mineral density (BMD), recent findings show excess body weight to be detrimental to bone mass, strength, and quality. To evaluate whether obesity would further exacerbate the effects of ovariectomy on bone, we examined the tibiae and fourth lumbar (L4) vertebrae from leptin receptor-deficient female (Leprfa/fa) Zucker rats and their heterozygous lean controls (Leprfa/+) that were either sham-operated or ovariectomized (Ovx). BMD of L4 vertebra was measured using dual-energy X-ray absorptiometry, and microcomputed tomography was used to assess the microstructural properties of the tibiae. Ovariectomy significantly (P < 0.001) decreased the BMD of L4 vertebrae in lean and obese Zucker rats. Lower trabecular number and greater trabecular separation (P < 0.001) were also observed in the tibiae of lean- and obese-Ovx rats when compared to sham rats. However, only the obese-Ovx rats had lower trabecular thickness (Tb.Th) (P < 0.005) than the other groups. These findings demonstrated that ovarian hormone deficiency adversely affected bone mass and quality in lean and obese rats while obesity only affected Tb.Th in Ovx-female Zucker rats.
doi:10.1155/2014/690123
PMCID: PMC4189520  PMID: 25309751
25.  The inhibitory effect of Acyclovir loaded nano-niosomes against herpes simplex virus type-1 in cell culture 
Background: Wide distribution and low half-life of acyclovir has led to a high dose consumption of the drug. Recent studies have shown that encapsulation of acyclovir in nano-carriers can increase effectiveness and decrease its side effects. We investigated the inhibitory effect of acyclovir loaded nano-niosomes against herpes simplex virus type-1 (HSV-1) in cell culture.
Methods: In-vitro cytotoxicity study of empty niosomes (E-N), acyclovir loaded niosomes (ACV-N) and ACV as a free drug against HeLa cell line was performed by MTT assay and the viral titers was tested by TCID50 assay.
Results: The results indicated that a significant higher antiviral activity for acyclovir loaded nano-niosomes of about 3 times in comparison with free drug.
Conclusion: The results of this study revealed ACV-N have a higher antiviral activity compared with free drug; it could be a suitable carrier for delivery of acyclovir in the treatment of HSV-1 infections.
PMCID: PMC4301255  PMID: 25664300
Nano-niosomes; Herpes simplex virus; Cytotoxicity

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