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author:("bahrami, S")
1.  Asymptomatic Uterine Torsion in a Pregnant Woman 
The Indian Journal of Surgery  2013;76(4):321-322.
Some degree rotation of the gravid uterus in the third trimester of pregnancy is not an abnormal finding. However, extreme uterine torsion of 180° around its cervical junction is a relatively rare event in obstetrical practice. We report here such a case that detected at laparotomy for an emergency cesarean section due to rapture of amniotic membrane.
PMCID: PMC4175681  PMID: 25278659
Uterine torsion; Pregnancy; Caesarean; Uterus
2.  The neuroendocrine phenotype of gastric myofibroblasts and its loss with cancer progression 
Carcinogenesis  2014;35(8):1798-1806.
Gastric myofibroblasts normally exhibit a neuroendocrine-like phenotype characterized by calcium-dependent regulated exocytosis, dense-cored secretory vesicles and expression of neuroendocrine markers such as secretogranin-II and proenkephalin. This phenotype is lost in myofibroblasts from advanced gastric cancer.
Stromal cells influence cancer progression. Myofibroblasts are an important stromal cell type, which influence the tumour microenvironment by release of extracellular matrix (ECM) proteins, proteases, cytokines and chemokines. The mechanisms of secretion are poorly understood. Here, we describe the secretion of marker proteins in gastric cancer and control myofibroblasts in response to insulin-like growth factor (IGF) stimulation and, using functional genomic approaches, we identify proteins influencing the secretory response. IGF rapidly increased myofibroblast secretion of an ECM protein, TGFβig-h3. The secretory response was not blocked by inhibition of protein synthesis and was partially mediated by increased intracellular calcium (Ca2+). The capacity for evoked secretion was associated with the presence of dense-core secretory vesicles and was lost in cells from patients with advanced gastric cancer. In cells responding to IGF-II, the expression of neuroendocrine marker proteins, including secretogranin-II and proenkephalin, was identified by gene array and LC-MS/MS respectively, and verified experimentally. The expression of proenkephalin was decreased in cancers from patients with advanced disease. Inhibition of secretogranin-II expression decreased the secretory response to IGF, and its over-expression recovered the secretory response consistent with a role in secretory vesicle biogenesis. We conclude that normal and some gastric cancer myofibroblasts have a neuroendocrine-like phenotype characterized by Ca2+-dependent regulated secretion, dense-core secretory vesicles and expression of neuroendocrine marker proteins; loss of the phenotype is associated with advanced cancer. A failure to regulate myofibroblast protein secretion may contribute to cancer progression.
PMCID: PMC4123646  PMID: 24710625
3.  Polymorphisms of asparaginase pathway and asparaginase-related complications in children with acute lymphoblastic leukemia 
Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia (ALL), but it is also associated with several toxicities.
Experimental design
We recently reported the results of an association study between asparaginase pathway genes and event free survival (EFS) in childhood ALL patients. The same polymorphisms were interrogated here in relation to allergies, pancreatitis and thrombotic events following treatment with E.coli asparaginase.
Among patients of discovery group, allergies and pancreatitis were more frequent in individuals who are homozygous for the triple repeat allele (3R) of asparagine synthetase ASNS gene, resulting in remarkably higher risk of these toxicities associated with 3R3R genotype (OR for allergies =14.6, 95% CI= 3.6–58.7, p<0.0005 and OR for pancreatitis = 8.6, 95% CI= 2.0–37.3, p=0.01). In contrast, the ASNS haplotype *1 harbouring double repeat (2R) allele had protective effect against these adverse reactions (p≤0.01). The same haplotype was previously reported to confer reduction in EFS. The risk effect of 3R3R genotype was not replicated in validation cohort, whereas the protective effect of haplotype *1 against allergies was maintained (p≤0.002). Analysis with additional polymorphisms in ASNS locus in lymphoblastoid cell lines showed that haplotype *1 is diversified in several subtypes of which one was associated with reduced in vitro sensitivity to asparaginase (rs10486009p=0.01) possibly explaining an association seen in clinical setting.
This finding might have implication for treatment individualization in ALL and other cancers employing asparagine depletion strategies.
PMCID: PMC4258187  PMID: 24907114
asparaginase; polymorphisms; pharmacogenetics; childhood leukemia; treatment; adverse reactions
4.  Enteric neuromodulators and mucus discharge in a fish infected with the intestinal helminth Pomphorhynchus laevis 
Parasites & Vectors  2015;8:359.
In vertebrates, the presence of enteric worms can induce structural changes to the alimentary canal impacting on the neuroendocrine system, altering the proper functioning of the gastrointestinal tract and affecting the occurrence and relative density of endocrine cells (ECs). This account represents the first immunohistochemistry and ultrastructure-based study which documents the intimate relationship between the intestinal mucous cells and ECs in a fish-helminth system, investigating the potential effects of enteric neuromodulators on gut mucus secretion/discharge.
A modified dual immunohisto- and histochemical staining technique was applied on intestinal sections from both infected and uninfected fish. Sections were incubated in antisera to a range of neuromodulators (i.e. leu-enkephalin, met-enkephalin, galanin and serotonin) and the glycoconjugate histochemistry of the mucous cells was determined using a subsequent alcian blue – periodic acid Schiff staining step. Dual fluorescent staining on sections prepared for confocal laser scanning microscopy and transmission electron microscopy were also used to document the relationship between ECs and mucous cells.
From a total of 26 specimens of Squalius cephalus sampled from the River Paglia, 16 (i.e. 62 %) specimens were found to harbour an infection of the acanthocephalan Pomphorhynchus laevis (average intensity of infection 9.2 ± 0.8 parasites host−1, mean ± standard error). When acanthocephalans were present, the numbers of mucous cells (most notably those containing acidic or mixed glycoconjugates) and ECs secreting leu-enkephalin, met-enkephalin, galanin, serotonin were significantly higher than those seen on sections from uninfected fish. The relationship between met-enkephalin-like or serotonin-like ECs and lectin DBA positive mucous cells was demonstrated through a dual fluorescent staining. The presence of tight connections and desmosomes between mucous and ECs in transmission electron micrographs provides further evidence of this intimate relationship.
The presence of P. laevis induces an increase in the number of enteric ECs that are immunoreactive to leu- and met-enkephalin, galanin, and serotonin anti-sera. The mucous cells hyperplasia and enhanced mucus secretion in the helminth-infected intestines could be elicited by the increase in the number of ECs which release these regulatory substances.
PMCID: PMC4495775  PMID: 26152567
Mucous cells; Enteroendocrine cells; Immunohistochemistry; Transmission electron microscopy; Confocal laser scanning microscopy; Acanthocephalan; Pomphorhynchus laevis; Host immunity; Infected intestine
5.  Inferring interaction type in gene regulatory networks using co-expression data 
Knowledge of interaction types in biological networks is important for understanding the functional organization of the cell. Currently information-based approaches are widely used for inferring gene regulatory interactions from genomics data, such as gene expression profiles; however, these approaches do not provide evidence about the regulation type (positive or negative sign) of the interaction.
This paper describes a novel algorithm, “Signing of Regulatory Networks” (SIREN), which can infer the regulatory type of interactions in a known gene regulatory network (GRN) given corresponding genome-wide gene expression data. To assess our new approach, we applied it to three different benchmark gene regulatory networks, including Escherichia coli, prostate cancer, and an in silico constructed network. Our new method has approximately 68, 70, and 100 percent accuracy, respectively, for these networks. To showcase the utility of SIREN algorithm, we used it to predict previously unknown regulation types for 454 interactions related to the prostate cancer GRN.
SIREN is an efficient algorithm with low computational complexity; hence, it is applicable to large biological networks. It can serve as a complementary approach for a wide range of network reconstruction methods that do not provide information about the interaction type.
Electronic supplementary material
The online version of this article (doi:10.1186/s13015-015-0054-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4495944  PMID: 26157474
Gene expression data; Information-based approach; Interaction type; Regulatory interaction
6.  Genome-wide survey of Alternative Splicing in Sorghum Bicolor 
Sorghum bicolor is a member of grass family which is an attractive model plant for genome study due to interesting genome features like low genome size. In this research, we performed comprehensive investigation of Alternative Splicing and ontology aspects of genes those have undergone these events in sorghum bicolor. We used homology based alignments between gene rich transcripts, represented by tentative consensus (TC) transcript sequences, and genomic scaffolds to deduce the structure of genes and identify alternatively spliced transcripts in sorghum. Using homology mapping of assembled expressed sequence tags with genomics data, we identified 2,137 Alternative Splicing events in S. bicolor. Our study showed that complex events and intron retention are the main types of Alternative Splicing events in S. bicolor and highlights the prevalence of splicing site recognition for definition of introns in this plant. Annotations of the alternatively spliced genes revealed that they represent diverse biological process and molecular functions, suggesting a fundamental role for Alternative Splicing in affecting the development and physiology of S. bicolor.
PMCID: PMC4101146  PMID: 25049459
Alternative splicing; Ontology; Complex events; Intron retention
7.  Effect of Intravenous Intraoperative Esmolol on Pain Management Following Lower Limb Orthopedic Surgery 
The Korean Journal of Pain  2015;28(3):198-202.
Lack of proper control of acute postoperative pain often leads to lingering or chronic pain. Several studies have emphasized the role of beta-blockers in reducing postoperative pain. Esmolol is a selective short-acting beta-blocker that produces few side effects. The purpose of this study was to examine the effect of intravenous intraoperative esmolol on postoperative pain reduction following orthopedic leg fracture surgery.
In a clinical trial, 82 patients between 20-65 years of age with tibia fractures and American Society of Anesthesiologists (ASA) physical status I & II who underwent surgery were divided into two groups. Group A received esmolol and group B received normal saline. Postoperative pain was measured at three time points: entering the recovery unit, and at 3 h and 6 h following surgery, using the Visual Analogue Scale (VAS). A P value of < 0.05 was considered significant.
Mean VAS scores at all three time points were significantly different between the two test groups (P = 0.02, P = 0.0001, and P = 0.0001, respectively). The consumption of pethidine was lower in group A than in group B (P = 0.004) and the duration of its effect was significantly longer in time (P = 0.026).
Intravenous intraoperative esmolol is effective in the reduction of postoperative pain following leg fracture surgery. It reduced opioid consumption following surgery and delayed patient requests for analgesics.
PMCID: PMC4500784  PMID: 26175880
Esmolol; Meperidine; Orthopedic surgery; Pain management; Pain measurement; Postoperative pain; Tibial fractures; Visual analog scale
8.  Effect of Superparamagnetic Iron Oxide Nanoparticles-Labeling on Mouse Embryonic Stem Cells 
Cell Journal (Yakhteh)  2015;17(2):221-230.
Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label mammalian cells and to monitor their fate in vivo using magnetic resonance imaging (MRI). However, the effectiveness of phenotype of labeled cells by SPIONs is still a matter of question. The aim of this study was to investigate the efficiency and biological effects of labeled mouse embryonic stem cells (mESCs) using ferumoxide- protamine sulfate complex.
Materials and Methods
In an experimental study, undifferentiated mESCs, C571 line, a generous gift of Stem Cell Technology Company, were cultured on gelatin-coated flasks. The proliferation and viability of SPION-labeled cells were compared with control. ESCs and embryoid bodies (EBs) derived from differentiated hematopoietic stem cells (HSCs) were analyzed for stage-specific cell surface markers using fluorescence-activated cell sorting (FACS).
Our observations showed that SPIONs have no effect on the self-renewal ability of mESCs. Reverse microscopic observations and prussian blue staining revealed 100% of cells were labeled with iron particles. SPION-labeled mESCs did not significantly alter cell viability and proliferation activity. Furthermore, labeling did not alter expression of representative surface phenotypic markers such as stage-specific embryonic antigen 1 (SSEA1) and cluster of differentiation 117 (CD117) on undifferentiated ESC and CD34, CD38 on HSCs, as measured by flowcytometry.
According to the results of the present study, SPIONs-labeling method as MRI agents in mESCs has no negative effects on growth, morphology, viability, proliferation and differentiation that can be monitored in vivo, noninvasively. Noninvasive cell tracking methods are considered as new perspectives in cell therapy for clinical use and as an easy method for evaluating the placement of stem cells after transplantation.
PMCID: PMC4503836  PMID: 26199901
Iron Oxide; Mouse Embryonic Stem Cells; Cell Tracking
9.  Evaluation of Oxidative Metabolism in Child and Adolescent Patients with Attention Deficit Hyperactivity Disorder 
Psychiatry Investigation  2015;12(3):361-366.
Oxidative metabolism is impaired in several medical conditions including psychiatric disorders, and this imbalance may be involved in the etiology of these diseases. The present study evaluated oxidative balance in pediatric and adolescent patients with attention deficit hyperactivity disorder (ADHD).
The study included 48 children and adolescents (34 male, 14 female) with ADHD who had no neurological, systemic, or comorbid psychiatric disorders, with the exception of oppositional defiant disorder (ODD), and 24 sex- and age-matched healthy controls (17 male and seven female).
TAS was significantly lower, and TOS and OSI were significantly higher in patients with ADHD than in healthy controls. Total antioxidant levels were lower in patients with comorbid ODD than in those with no comorbidity. No difference was found in TOS or OSI among the ADHD subtypes; however, TAS was higher in the attention-deficient subtype.
Our findings demonstrated that oxidative balance is impaired and oxidative stress is increased in children and adolescents with ADHD. This results are consistent with those of previous studies.
PMCID: PMC4504919  PMID: 26207130
Attention deficit hyperactivity disorder; Oxidative stress; Total oxidant status; Total antioxidant status; Oxidative imbalance; Child and adolescent
10.  Higher order aberration comparison between two aspherical intraocular lenses: MC6125AS and Akreos advanced optics 
To compare higher order aberrations in two aspherical intraocular lenses (IOLs): Akreos advanced optics (AO) and Dr. Schmidt Microcrystalline 6125 aspheric anterior surface (MC6125AS) with each other.
Forty eyes of 39 patients underwent phacoemulsification and Akreos AO and MC6125AS were implanted in their eyes in a random manner. Three months post-operatively, higher order aberrations including spherical aberration, coma aberration, and total aberrations were measured and compared.
The total aberration was 0.24±0.17 in eyes with Dr. Schmidt and 0.20±0.01 in eyes with Akreos AO (P=0.361). The mean of coma aberration was 0.17±0.21 and 0.09±0.86 in Dr. Schmidt and Akreos lenses, respectively (P=0.825). Total spherical aberration was almost the same in both groups (Mean: 0.05, P=0.933). Best corrected visual acuity in Akreos AO (0.10±0.68) and Dr. Schmidt (0.09±0.67) did not differ significantly (P=0.700).
There is no statistically significant difference in the higher order aberrations between these two aspherical lenses.
PMCID: PMC4458664  PMID: 26086009
aspherical lenses; higher order aberrations; cataract; intraocular lens
11.  Neonatal blood stream infections in tertiary referral hospitals in Kurdistan, Iran 
Bloodstream infection (BSI) is one of the most common causes of nosocomial infection in neonatal intensive care units (NICU). The aim of the present study was to determine bacterial agents and their susceptibility patterns to antibiotics and to investigate the risk factors associated with BSI.
This was a nested case–control study carried out from September 2009 to June 2010 in the NICU wards in Sanandaj hospitals western Iran. Cases were patients with BSI and controls were other patients who had negative blood culture. Bacteriologic diagnosis and antibiotic susceptibility pattern was performed based on the Edward & Ewings and the National Committee of Clinical Laboratory (NCCL) Standards.
Of 472 patients who hospitalized in NICU, 6.4% had BSI (n = 30) including 17girls (56.7%) and 13 boys (43.3%). Enterobacter SPP was the predominant isolated bacteria from blood culture (36.7%). The maximum antibiotic resistance and sensitivity were observed by Tetracycline and Ciprofloxacin respectively. Risk factors associated with BSI were age ≤ 7 days (p = 0.001), previous antibiotic consumption (p = 0.013), and low birth weight (LBW), (p = 0.001).
Gram negative bacteria and Entrobacter in particular are the most common pathogens. Improving prenatal health care, standards of infection control and choosing accurate antibiotics are recommended to avoid BSI in neonatal intensive care units.
PMCID: PMC4470359  PMID: 26051617
Bloodstream Infections (BSI); Neonatal Intensive Care Unit (NICU); Sanandaj
12.  Toward Standardization of BK Virus Monitoring: Evaluation of the BK Virus R-gene Kit for Quantification of BK Viral Load in Urine, Whole-Blood, and Plasma Specimens 
Journal of Clinical Microbiology  2014;52(12):4298-4304.
Screening of BK virus (BKV) replication is recommended to identify patients at increased risk of BKV-associated diseases. However, the heterogeneity of molecular techniques hinders the establishment of universal guidelines for BKV monitoring. Here we aimed to compare the performance of the CE-marked BK virus R-gene kit (R-gene) to the performance of our in-house assay for quantification of BKV DNA loads (BKVL). A 12-specimen panel from the Quality Control for Molecular Diagnostics (QCMD) organization, 163 urine samples, and 88 paired specimens of plasma and whole blood (WB) from transplant recipients were tested. Both the R-gene and in-house assays showed a good correlation within the QCMD panel (r = 0.995 and r = 0.989, respectively). BKVL were highly correlated between assays, although positive biases were observed with the in-house assay in analysis of urine (0.72 ± 0.83 log10 copies/ml), plasma (1.17 ± 0.63 log10 copies/ml), and WB (1.28 ± 0.37 log10 copies/ml). Recalibration with a common calibrator significantly reduced the bias in comparisons between assays. In contrast, BKVL was underestimated with the in-house PCR in eight samples containing BKV genotype II, presenting point mutations at primer-annealing sites. Using the R-gene assay, plasma and WB specimens were found to be equally suitable for quantification of BKVL, as indicated by the high correlation coefficient (r = 0.965, P < 0.0001). In conclusion, the R-gene assay demonstrated reliable performance and higher accuracy than the in-house assay for quantification of BKVL in urine and blood specimens. Screening of BKV replication by a well-validated commercial kit may enable clinical laboratories to assess viral loads with greater reproducibility and precision.
PMCID: PMC4313301  PMID: 25297334
13.  Short Term Outcome of Neonates Born With Abnormal Umbilical Cord Arterial Blood Gases 
Iranian Journal of Pediatrics  2015;25(3):e174.
Umbilical arterial blood gas (UABG) analysis is more objective than other methods for predicting neonatal outcome. Acidemic neonates may be at risk for unfavorable outcome after birth, but all neonates with abnormal arterial blood gas (ABG) analysis do not always have poor outcome.
This study was carried out to determine the short term outcome of the neonates born with an abnormal ABG.
Patients and Methods:
In a cohort prospective study 120 high risk mother-neonate pairs were enrolled and UABG was taken immediately after birth. All neonates with an umbilical cord pH less than 7.2 were considered as case group and more than 7.2 as controls. Outcomes like need to resuscitation, admission to newborn services and/or NICU), seizure occurrence, hypoxic ischemic encephalopathy (HIE), delayed initiation of oral feeding and length of hospital stay were recorded and compared between the two groups. P value less than 0.05 was considered as being significant.
Comparison of short term outcomes between normal and abnormal ABG groups were as the fallowing: need for advanced resuscitation 4 vs. 0 (P = 0.001), NICU admission 16 vs. 4 (P = 0.001), convulsion 2 vs. 0 (P = 0.496), HIE 17 vs. 4 (P = 0.002), delay to start oral feeding 16 vs. 4 (P = 0.001), mean hospital stay 4 vs. 3 days (P = 0.001). None of the neonates died in study groups.
An umbilical cord PH less than 7.2 immediately after birth can be used as a prognostic factor for unfavorable short term outcome in newborns.
PMCID: PMC4505982  PMID: 26199700
Umbilical Arterial Blood Gas; pH; Propionic Acidemia; Assessment Patient Outcome
14.  Isolation of toxigenic Clostridium difficile from ready-to-eat salads by multiplex polymerase chain reaction in Isfahan, Iran 
Since 2003, the incidence of community associated Clostridium difficile infection (CA-CDI) has increased; different types of food have been supposed to be the vectors of C. difficile strains. The purpose of this study is to investigate the occurrence of C. difficile strains in ready-to-eat salads distributed in food services.
Materials and Methods:
A total of 106 ready-made salad specimens were sampled from different restaurants and food services located in Isfahan, in the center of Iran. Positive isolates of C. difficile were identified and confirmed for the existence of three genes including tpi, tcdA and tcdB by multiplex PCR.
A total of six (5.66%) samples were positive for C. difficile strains. Of which, one strain (16.6%) was positive for A and B toxins.
The existence of toxigenic C. difficile in ready-made salads could be a caution for public health. Further investigation is required to assess the relationship between the isolated strains in our study and those from diarrheic patients through molecular typing.
PMCID: PMC4434448  PMID: 26015913
Clostridium difficile; multiplex PCR; prevalence; salad; vegetable
15.  Horizons in Sjögren’s Syndrome Genetics 
Sjögren’s syndrome (SS) is a complex polygenic autoimmune disorder. A few major genetic effects have been identified. Historically, HLA and non-HLA genetic associations have been reported. Recently, the HLA region continued to reveal association findings. A new susceptibility region has been suggested by a study of a D6S349 microsatellite marker. Among non-HLA studies, recent association of immunoglobulin κ chain allotype KM1 with anti-La autoantibodies in primary Sjögren’s syndrome confirms findings in a study from two decades ago. Meanwhile, mouse models have been employed to study the genetic contribution to salivary lymphadenitis or dry eyes and mouth. Gene transfer exploration in mouse models shows promise. The authors review the HLA and non-HLA association studies and the mouse model work that has been reported. Newly developed genomic capacity will provide, in the future, a much closer approximation of the true picture of the genetic architecture of Sjögren’s syndrome.
PMCID: PMC4420170  PMID: 17963047
Sjögren’s syndrome; Genetics; HLA; Histocompatibility
16.  Accuracy of Prognostic and Predictive Markers in Core Needle Breast Biopsies Compared with Excisional Specimens 
Breast Care  2014;9(2):107-110.
Core needle biopsy (CNB) is widely accepted for preoperative diagnosis of breast cancer and sometimes can be the only way of providing a suitable specimen for prognostic and predictive marker studies prior to neoadjuvant treatment. The purpose of this study was to evaluate the accuracy of CNB by comparing histological tumor type and grade as well as estrogen receptor (ER), progesterone receptor (PR), p53, and HER2/ neu status by immunohistochemistry in CNB and excisional surgical specimens.
Patients and Methods
During a 2.5-year study period, we identified 30 patients with breast cancer, who underwent CNB and definitive surgery. To evaluate the accuracy of CNB, tumor grade, ER, PR, HER2, and p53 status were immunohistochemically determined in both the CNB and the surgical specimens, and concordance of results between the 2 specimens was assessed.
The concordance rate was 100% for histological type, 66.6% for histological grade, and 96.7, 90, 76.7 and 93.3% for ER, PR, p53 and HER2/neu, respectively.
Our study showed that CNB has an excellent accuracy for tumor type, ER, and HER2/ neu; however, it should be used cautiously for tumor grade, PR, and p53 status. Thus, excisional biopsy is recommended for the determination of these factors.
PMCID: PMC4038314  PMID: 24944553
Prognostic factors; Breast cancer; Core needle biopsy
17.  Coupled Segmentation of Nuclear and Membrane-bound Macromolecules through Voting and Multiphase Level Set 
Pattern recognition  2014;48(3):882-893.
Membrane-bound macromolecules play an important role in tissue architecture and cell-cell communication, and is regulated by almost one-third of the genome. At the optical scale, one group of membrane proteins expresses themselves as linear structures along the cell surface boundaries, while others are sequestered; and this paper targets the former group. Segmentation of these membrane proteins on a cell-by-cell basis enables the quantitative assessment of localization for comparative analysis. However, such membrane proteins typically lack continuity, and their intensity distributions are often very heterogeneous; moreover, nuclei can form large clump, which further impedes the quantification of membrane signals on a cell-by-cell basis. To tackle these problems, we introduce a three-step process to (i) regularize the membrane signal through iterative tangential voting, (ii) constrain the location of surface proteins by nuclear features, where clumps of nuclei are segmented through a delaunay triangulation approach, and (iii) assign membrane-bound macromolecules to individual cells through an application of multi-phase geodesic level-set. We have validated our method using both synthetic data and a dataset of 200 images, and are able to demonstrate the efficacy of our approach with superior performance.
PMCID: PMC4269261  PMID: 25530633
Segmentation of membrane-bound macromolecules; perceptual grouping; multi-phase level set; nuclear segmentation; tissue architecture
19.  Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates 
Viruses  2015;7(5):2308-2320.
Among Herpesviruses, Human Cytomegalovirus (HCMV or HHV-5) represents a major threat during congenital or neonatal infections, which may lead to encephalitis with serious neurological consequences. However, as opposed to other less prevalent pathogens, the mechanisms and genetic susceptibility factors for CMV encephalitis are poorly understood. This lack of information considerably reduces the prognostic and/or therapeutic possibilities. To easily monitor the effects of genetic defects on brain dissemination following CMV infection we used a recently developed in vivo mouse model based on the neonatal inoculation of a MCMV genetically engineered to express Luciferase. Here, we further validate this protocol for live imaging, and demonstrate increased lethality associated with viral infection and encephalitis in mutant mice lacking Dicer activity. Our data indicate that miRNAs are important players in the control of MCMV pathogenesis and suggest that miRNA-based endothelial functions and integrity are crucial for CMV encephalitis.
PMCID: PMC4452907  PMID: 25955106
Murine Cytomegalovirus; Dicer; encephalitis; imaging
20.  Comparing the Effect of Topical Anesthesia and Retrobulbar Block With Intravenous Sedation on Hemodynamic Changes and Satisfaction in Patients Undergoing Cataract Surgery (Phaco Method) 
Cataract is one of the most common surgical procedures in the elderly. In most cases, the elderly have cardiac ischemia or chronic coronary diseases, which would lead to more ischemic events during general anesthesia. Therefore, surgeons and anesthetists prefer regional aesthesia to the general one owing to its more advantages and less complications.
Therefore, this study aimed to compare topical method and retrobulbar block for pain intensity, patient’s satisfaction, hemodynamic changes and intra and postoperative complications.
Patients and Methods:
In a single-blinded clinical trial, 114 patients scheduled for cataract surgery, aged 50 to 90 years with ASA physical status of I-III, were randomly assigned to two groups under monitored anesthesia care as topical anesthesia and retrobulbar block. After the injection of intravenous sedation, which was the combination of midazolam 0.5-1 mg with fentanyl 0.5-1 µ/kg, patients received retro bulbar block or topical anesthesia. During the operation, heart rate, systolic and diastolic blood pressure, mean arterial blood pressure and arterial saturation of O2were measured every five minutes. In addition, pain (VAS) and satisfaction (ISAS) scores were recorded every 15 minutes, then at recovery and one hour after the ending of operation in the ward. Findings were statistically analyzed using SPSS 16.
In this study, no significant association was found between age, gender, education and physical condition of patients in both topical and retro bulbar block groups. Comparison of pain based on VAS, satisfaction based on ISAS score and MAP in the studied periods had no significant differences between the two groups of patients undergoing cataract surgery. However, significant differences were found between the two groups (P = 0.045, 0.02, 0.042 and P < 0.05) regarding heart rate, systolic and diastolic blood pressure and arterial oxygen saturation percentage after 20-30 minutes of the operation.
Both methods, topical and retro bulbar block had similar impression in cataract surgery regarding analgesia and patient satisfaction. However, in non-complicated cataract surgeries with short duration, topical anesthesia may be the preferable method, because of non-invasiveness, appropriate analgesia, patient satisfaction and hemodynamic stability.
PMCID: PMC4377165  PMID: 25918686
Cataract; Retro Bulbar Block; Topical; Anesthesia; Hemodynamics; Variables; Pain; Satisfaction
21.  Optical Data Compression in Time Stretch Imaging 
PLoS ONE  2015;10(4):e0125106.
Time stretch imaging offers real-time image acquisition at millions of frames per second and subnanosecond shutter speed, and has enabled detection of rare cancer cells in blood with record throughput and specificity. An unintended consequence of high throughput image acquisition is the massive amount of digital data generated by the instrument. Here we report the first experimental demonstration of real-time optical image compression applied to time stretch imaging. By exploiting the sparsity of the image, we reduce the number of samples and the amount of data generated by the time stretch camera in our proof-of-concept experiments by about three times. Optical data compression addresses the big data predicament in such systems.
PMCID: PMC4408077  PMID: 25906244
22.  The effect of exercise therapy on cognitive functions in multiple sclerosis patients: A pilot study 
Background: The positive impacts of exercise therapy on patients’ cognitive problems still remain unknown. This study was a pilot intervention to examine the effects of combined exercise on the cognitive problems of patients with multiple sclerosis (MS) in Iranian MS Society over 2012 to 2013.
Methods: This quasi-experimental research was carried out in the form of a pretest/posttest study. Forty two patients with MS were selected from those visiting the rehabilitation center of Iranian MS Society, using non-probability convenience sampling. The Expanded Disability Status Scale (EDSS) of each patient was recorded before the intervention and Brief Repeatable Battery of Neuropsychological (BRB-N) test was administered before and after the intervention. The data were analyzed using the analytical tests such as Wilcoxon test.
Results: Of 21 participants, 17 subjects (82%, n=14) female with mean (±SD) age of 37 (±9.98) years and mean (±SD) EDSS of 2.35 (±0.90) completed all stages of the study. Changes in long-term storage and permanent long-term retrieval of information after the intervention were statistically significant (p<0.001). In addition, the change in the average of total delay after the intervention was also significant by 1.11 (p<0.001).
Conclusion: Our study confirmed the possibility of change in the cognitive abilities of MS patients through physical interventions. This finding emphasizes the necessity of more clinical examinations and increases the hopes for new rehabilitation methods for the disorder.
PMCID: PMC4476225  PMID: 26157723
Exercise Therapy; Cognitive Functions; Multiple Sclerosis
23.  Molecular deconstruction, detection, and computational prediction of microenvironment-modulated cellular responses to cancer therapeutics 
The field of bioengineering has pioneered the application of new precision fabrication technologies to model the different geometric, physical or molecular components of tissue microenvironments on solid-state substrata. Tissue engineering approaches building on these advances are used to assemble multicellular mimetic-tissues where cells reside within defined spatial contexts. The functional responses of cells in fabricated microenvironments has revealed a rich interplay between the genome and extracellular effectors in determining cellular phenotypes, and in a number of cases has revealed the dominance of microenvironment over genotype. Precision bioengineered substrata are limited to a few aspects, whereas cell/tissue-derived microenvironments have many undefined components. Thus introducing a computational module may serve to integrate these types of platforms to create reasonable models of drug responses in human tissues. This review discusses how combinatorial microenvironment microarrays and other biomimetic microenvironments have revealed emergent properties of cells in particular microenvironmental contexts, the platforms that can measure phenotypic changes within those contexts, and the computational tools that can unify the microenvironment-imposed functional phenotypes with underlying constellations of proteins and genes. Ultimately we propose that a merger of these technologies will enable more accurate pre-clinical drug discovery.
PMCID: PMC4019691  PMID: 24582543
24.  Histopathology and the inflammatory response of European perch, Perca fluviatilis muscle infected with Eustrongylides sp. (Nematoda) 
Parasites & Vectors  2015;8:227.
The European perch, Perca fluviatilis L. is a common paratenic host of dioctophymatid nematodes belonging to the genus Eustrongylides. In this host, once infected oligochaetes, which serve as the first intermediate host, are ingested, Eustrongylides migrates through the intestine and is frequently encountered within the musculature, free within the body cavity, or encapsulated on the viscera. The current study details the first Italian record of Eustrongylides sp. with larvae reported in the muscle of P. fluviatilis.
Uninfected and nematode-infected muscle tissues of perch were fixed and prepared for histological evaluation and electron microscopy. Some sections were subjected to an indirect immunohistochemical method using anti-PCNA, anti-piscidin 3 and anti-piscidin 4 antibodies.
A total of 510 P. fluviatilis (TL range 15–25 cm) from Lake Trasimeno, Perugia were post-mortemed; 31 individuals had encysted nematode larvae within their musculature (1–2 worms fish−1). Histologically, larvae were surrounded by a capsule with an evident acute inflammatory reaction. Muscle degeneration and necrosis extending throughout the sarcoplasm, sarcolemmal basal lamina, endomysial connective tissue cells and capillaries was frequently observed. Within the encapsulating reaction, macrophage aggregates (MAs) were seen. Immunohistochemical staining with the proliferating cell nuclear antigen (PCNA) revealed numerous PCNA-positive cells within the thickness of the capsule and in the immediate vicinity surrounding Eustrongylides sp. larvae (i.e. fibroblasts and satellite cells), suggesting a host response had been initiated to repair the nematode-damaged muscle. Mast cells (MCs) staining positively for piscidin 3, were demonstrated for the first time in response to a muscle-infecting nematode. The piscidin 3 positive MC’s were seen principally in the periphery of the capsule surrounding the Eustrongylides sp. larva.
A host tissue response to Eustrongylides sp. larvae infecting the musculature of P. fluviatilis was observed. Numerous fibroblasts, MAs and MCs were seen throughout the thick fibroconnectival layer of the capsule enclosing larvae. PCNA positive cells within the capsule suggest that host repair of nematode damaged muscle does occur, while the presence of the antimicrobial peptide piscidin 3 is shown for the first time. This is first report of Eustrongylides sp. in an Italian population of P. fluviatilis.
PMCID: PMC4404125  PMID: 25889096
Nematode larvae; Piscidin 3; PCNA; Macrophage aggregates; Mast cells; Fibroblasts
25.  Anti-Ganglioside Antibodies in Amyotrophic Lateral Sclerosis Revisited 
PLoS ONE  2015;10(4):e0125339.
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder with typical onset in the 5th- 6th decade of life. The hypothesis of an autoimmune origin of ALS receives less attention today, but immunological phenomena still seem to be involved and mechanisms such as protective autoimmunity may be important. Detection of antibodies against a variety of gangliosides has been repeatedly described in ALS-patients by several authors, but widely differing frequencies and titres have been reported. Therefore, we investigated the presence of six common antibodies with a commercially available test panel for GA1, GM1, GM2, GD1a, GD1b and GQ1b in a large group of clinically well-characterized ALS patients and compared them to a collective of 200 healthy blood donors.
IgG and IgM antibodies to the six gangliosides asialoGM1 (GA1), GM1, GM2, GD1a, GD1b, GQ1b were determined by GanglioCombi ELISA in sera of 84 ALS patients. Results were expressed as a %-ratio of a highly positive control and categorized as negative (<30%), borderline (30–50%), moderately (50–100%) and strongly positive (>100%). The values obtained from 200 Swiss blood donors served as a reference group.
In twenty-two (26.2%) ALS-patients elevated anti-ganglioside antibodies could be detected: Taking all subspecific antibodies together, IgG antibodies were found in 9/84 (10.7%) and IgM in 15/84 (17.9%) patients. There was no correlation between age, gender, site of onset or survival and anti-ganglioside-positive/-negative titres in ALS-patients. No statistically significant difference in the frequency of anti-ganglioside antibodies compared to the group of healthy blood donors was found.
Even with this more comprehensive approach, anti-ganglioside antibody frequencies and patterns in our ALS cohort closely resembled the values measured in healthy controls. In accordance with other studies, we did not observe any association of a distinct ALS phenotype with elevated anti-ganglioside antibodies or an impact on survival.
PMCID: PMC4397083  PMID: 25875836

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