Publications by authors named "Navid Manouchehri"

27 Publications

  • Page 1 of 1

Should ocrelizumab be used in non-active primary progressive multiple sclerosis? Time for a re-assessment.

Ther Adv Neurol Disord 2021 1;14:1756286421990500. Epub 2021 Feb 1.

Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Rd., Dallas, TX 75216, USA Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9036, USA.

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http://dx.doi.org/10.1177/1756286421990500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970673PMC
February 2021

CD11cCD88CD317 myeloid cells are critical mediators of persistent CNS autoimmunity.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390;

Natalizumab, a humanized monoclonal antibody (mAb) against α4-integrin, reduces the number of dendritic cells (DC) in cerebral perivascular spaces in multiple sclerosis (MS). Selective deletion of α4-integrin in CD11c cells should curtail their migration to the central nervous system (CNS) and ameliorate experimental autoimmune encephalomyelitis (EAE). We generated CD11c.Cre C57BL/6 mice to selectively delete α4-integrin in CD11c cells. Active immunization and adoptive transfer EAE models were employed and compared with WT controls. Multiparameter flow cytometry was utilized to immunophenotype leukocyte subsets. Single-cell RNA sequencing was used to profile individual cells. α4-Integrin expression by CD11c cells was significantly reduced in primary and secondary lymphoid organs in CD11c.Cre mice. In active EAE, a delayed disease onset was observed in CD11c.Cre mice, during which CD11cCD88 cells were sequestered in the blood. Upon clinical EAE onset, CD11cCD88 cells appeared in the CNS and expressed CD317 In adoptive transfer experiments, CD11c.Cre mice had ameliorated clinical disease phenotype associated with significantly diminished numbers of CNS CD11cCD88CD317 cells. In human cerebrospinal fluid from subjects with neuroinflammation, microglia-like cells display coincident expression of (CD11c), (CD88), and (CD317). In mice, we show that only activated, but not naïve microglia expressed CD11c, CD88, and CD317. Finally, anti-CD317 treatment prior to clinical EAE substantially enhanced recovery in mice.
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http://dx.doi.org/10.1073/pnas.2014492118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040603PMC
April 2021

The antioxidant MnTBAP does not effectively downregulate CD4 expression in T cells in vivo.

J Neuroimmunol 2021 May 8;354:577544. Epub 2021 Mar 8.

Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical School, Dallas, TX, USA; Neurology Section, VA North Texas Health Care System, Dallas, TX, USA. Electronic address:

The antioxidant MnTBAP was previously shown to down-regulate the surface expression of CD4 molecule in T cells. This observation obviously holds great potential impact in a number of pathological human conditions, including autoimmunity. Three different single doses of MnTBAP reduced the frequency of CD4 cells. However, the median florescent intensity (MFI) was not different. Initiation of in vivo pharmacotherapy or vehicle control was performed inC57BL/6 mice that were actively immunized for experimental autoimmune encephalomyelitis (EAE). In contrast to published reports, the mean frequency of CD4 cells, and the median fluorescent intensity (MFI) of CD4 was similar in both treatment groups. 25-day survival following active immunization among the MnTBAP treated animals compared to vehicle controls was16.6 ± 6.9 days vs 23.6 ± 2.7 days; (P value <0.05). We conclude that MnTBAP (Sack and Herzog, 2009 (Sack and Herzog, 2009)) does not effectively downregulate CD4 expression in T cells in vivo, probably due to extensive mechanism that distinguishes it from an in vitro model (Harding, 1993 (Harding, 1993)) possesses toxic properties that may limit its clinic use in possible doses that could deliver the immunomodulation through down regulation of CD4 expression, and (Saizawa et al., 1987 (Saizawa et al., 1987)) has limited availability in specific tissues, including the CNS.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577544DOI Listing
May 2021

Biological Significance of Anti-SARS-CoV-2 Antibodies: Lessons Learned From Progressive Multifocal Leukoencephalopathy.

Neurol Neuroimmunol Neuroinflamm 2021 03 24;8(2). Epub 2020 Dec 24.

From the Department of Neurology (N.M.), the University of Texas Southwestern Medical Center, Dallas; Departments of Pediatrics and Neurology and Neurological Sciences (L.S.), Stanford University, CA; and Neurology Section (O.S.), VA North Texas Health Care System, Medical Service Dallas, VA Medical Center.

Objective: To discuss the pathogenic and diagnostic relevance of cellular and humoral immune responses against severe acute respiratory syndrome novel coronavirus (SARS-COV-2) and pertinent observations made in progressive multifocal leukoencephalopathy (PML).

Methods: Review of pertinent literature RESULTS: There is at least 1 precedent for an antibody response against a viral pathogen that fails to provide host protection in the absence of immune-competent CD4 T cells. PML is an infection of the CNS caused by JC virus (JCV), which commonly occurs during treatment with the therapeutic monoclonal antibody natalizumab. In this context, the humoral immune response fails to prevent JCV reactivation, and elevated anti-JCV serum indices are associated with a higher PML incidence. The more relevant immune-competent cells in host defense against JCV appear to be T cells. T cell-mediated responses are also detectable in convalescing patients with SARS-COV-2 irrespective of the humoral immune response.

Conclusion: Based on pathogenic lessons learned from PML under natalizumab therapy, we suggest the incorporation of functional assays that determine neutralizing properties of SARS-CoV-2-specific antibodies. In addition, we outline the potential role of T-cell detection assays in determining herd immunity in a given population or in studying therapeutic responses to vaccines.
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http://dx.doi.org/10.1212/NXI.0000000000000935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768959PMC
March 2021

Reelin depletion protects against autoimmune encephalomyelitis by decreasing vascular adhesion of leukocytes.

Sci Transl Med 2020 08;12(556)

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Neuroinflammation as a result of immune cell recruitment into the central nervous system (CNS) is a key pathogenic mechanism of multiple sclerosis (MS). However, current anti-inflammatory interventions depleting immune cells or directly targeting their trafficking into the CNS can have serious side effects, highlighting a need for better immunomodulatory strategies. We detected increased Reelin concentrations in the serum of patients with MS, resulting in increased endothelial permeability to leukocytes through increased nuclear factor κB-mediated expression of vascular adhesion molecules. We thus investigated the prophylactic and therapeutic potential of Reelin immunodepletion in experimental autoimmune encephalomyelitis (EAE) and further validated the results in Reelin knockout mice. Removal of plasma Reelin by either approach protected against neuroinflammation and largely abolished the neurological consequences by reducing endothelial permeability and immune cell accumulation in the CNS. Our findings suggest Reelin depletion as a therapeutic approach with an inherent good safety margin for the treatment of MS and other diseases where leukocyte extravasation is a major driver of pathogenicity.
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http://dx.doi.org/10.1126/scitranslmed.aay7675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860587PMC
August 2020

Limitations of cell-lineage-specific non-dynamic gene recombination in CD11c.CreITGA4 mice.

J Neuroimmunol 2020 07 18;344:577245. Epub 2020 Apr 18.

Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, TX, USA; Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA. Electronic address:

Background: The Cre-lox system is a non-dynamic method of gene modification and characterization. Promoters thought to be relatively cell-specific are utilized for generation of cell-lineage-specific gene modifications.

Methods: CD11c.CreITGA4 mice were generated to abolish the expression of ITGA (α4-integrin) in CD11c cells. Ex vivo flow cytometry studies were used to assess the expression of cellular surface markers in different lymphoid compartments and leukocytes subsets after Cre-mediated recombination.

Results: A significant reduction of α4-integrin expression among CD11c cells was achieved in CD11c.CreITGA4 mice in primary and secondary lymphoid tissues. A similar reduction in the expression of α4-integrin was also observed in CD11c cells.

Conclusion: Cre-lox-mediated cell lineage-specific gene deletion is limited by the transient expression of recombination regulating sequences in hematopoietic cell lines. These methodological issues indicate the need to consider when to employ non-dynamic DNA recombination models in animal models of CNS autoimmunity. An experimental algorithm to address the biological complexities of non-dynamic gene recombination is provided.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577245DOI Listing
July 2020

The temporal and causal relationship between inflammation and neurodegeneration in multiple sclerosis.

Mult Scler 2020 07 4;26(8):876-886. Epub 2019 Nov 4.

Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, TX, USA/Neurology Section, Medical Service, VA North Texas Health Care System, Dallas, TX, USA/Department of Neurology, Klinikum rechts der Isar, Technische Universität München, München, Germany.

It is currently incompletely understood whether inflammation and neurodegeneration are causally related in multiple sclerosis (MS). The sequence of a potential causal relationship is also unknown. Inflammation is present in rather all clinical stages of MS. Its role in the pathogenesis of MS is supported by histopathological analyses, genetic data, and numerous animal models of MS. All approved disease-modifying therapies that reduce clinical relapses and diminish the accumulation of lesions on neuroimaging are anti-inflammatory. Axonal loss and accelerated brain volume loss can also be detected from clinical disease onset throughout all stages. The expression of neurofilament light chain in cerebrospinal fluid and serum, a scaffolding protein in axons and dendrites, is a biomarker of neuronal injury associated with clinical relapses and reflects neuronal loss during episodes of acute inflammation. The recent association of human endogenous retrovirus (HERV) and its envelope proteins with MS illustrates a pathogenic pathway that causally links central nervous system (CNS)-intrinsic proinflammatory effects and inhibition of myelin repair and neuroregeneration. A review of current data on the causal relationship between inflammation and neurodegeneration in MS identified numerous plausible pathomechanisms that link the two events. Observations from most experimental models appear to favor a pathogenesis in which inflammation precedes neurodegeneration.
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http://dx.doi.org/10.1177/1352458519886943DOI Listing
July 2020

Outcome of lesional epilepsy surgery: Report of the first comprehensive epilepsy program in Iran.

Neurol Clin Pract 2019 Aug;9(4):286-295

Kashani Comprehensive Epilepsy Center (JMH, MZ), Kashani Hospital, School of Medicine, Isfahan University of Medical Sciences; Departments of Neurology (JMH, SB, BZ, NM, MZ), Isfahan Neurosciences Research Center and Neurosurgery (HM), Department of Radiology (RB), Students' Research Center (SB, NM), and Department of Psychiatry (MB), Psychosomatic Research Center, School of Medicine, Isfahan University of Medical Sciences; Shefa Neuroscience Research Center (ER), Tehran, Iran; Students' Research Center (AMH), School of Medicine, Shahrekord University of Medical Sciences, Iran; Department of Neurology (PM), University of Tennessee Health Science Center, Memphis, TN; Department of Clinical Neurosciences (YA), University of Calgary, Calgary, Alberta, Canada; and Epilepsy Center (SA, SL), Neurological Institute, University Hospitals Cleveland Medical Center, Cleveland, OH.

Background: We investigated the utility of epilepsy surgery and postoperative outcome in patients with lesional epilepsy in Iran, a relatively resource-poor setting.

Methods: This prospective longitudinal study was conducted during 2007-2017 in Kashani Comprehensive Epilepsy Center, Isfahan, Iran. Patients with a diagnosis of intractable focal epilepsy, with MRI lesions, who underwent epilepsy surgery and were followed up ≥ 24 months, were included and evaluated for postoperative outcome.

Results: A total of 214 patients, with a mean age of 26.90 ± 9.82 years (59.8% men) were studied. Complex partial seizure was the most common type of seizure (85.9%), and 54.2% of the cases had auras. Temporal lobe lesions (75.2%) and mesial temporal sclerosis (48.1%) were the most frequent etiologies. With a mean follow-up of 62.17 ± 19.33 months, 81.8% of patients became seizure-free postoperatively. Anticonvulsants were reduced in 86% of the cases and discontinued in 40.7%. In keeping with previous studies, we found that seizure freedom rates were lower among patients with longer follow-up periods.

Conclusions: We found high rates of seizure freedom after surgery in lesional epilepsy patients despite limited facilities and infrastructure; antiepileptic medications were successfully tapered in almost half of the patients. Considering the favorable outcome of epilepsy surgery in our series, we believe that it is a major treatment option, even in less resource-intensive settings, and should be encouraged. Strategies to allow larger scale utility of epilepsy surgery in such settings in the developing world and dissemination of such knowledge may be considered an urgent clinical need, given the established mortality and morbidity in refractory epilepsy.
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http://dx.doi.org/10.1212/CPJ.0000000000000627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745744PMC
August 2019

Trials and therapies in secondary progressive MS, simplified.

Nat Rev Neurol 2019 Aug;15(8):431-432

Department of Neurology and Neurotherapeutics, the University of Texas Southwestern Medical Center, Dallas, TX, USA.

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http://dx.doi.org/10.1038/s41582-019-0233-xDOI Listing
August 2019

Clinical trials in multiple sclerosis: potential future trial designs.

Ther Adv Neurol Disord 2019 13;12:1756286419847095. Epub 2019 May 13.

Neurology Section, VA North Texas Health Care System, Medical Service, 500 South Lancaster Rd., Dallas, TX 75216, USA Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, TX Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Germany.

Clinical trials of new treatments in multiple sclerosis (MS) currently require large sample sizes and long durations in order to yield reliable results. The differential responses of an already heterogeneous population of MS patients to individual disease-modifying therapies (DMTs) will further complicate future trials. MS trials with smaller samples and faster outcomes are conceivable through the substitution of current clinical and MRI outcomes with objectively measureable genomic and proteomic biomarkers. Currently, biomarkers that could be utilized for diagnosis and monitoring of MS disease activity are in the early validation phase. The power of single biomarkers or multiple correlated biomarkers to predict prognosis and response to treatment could initially be compared with currently accepted methods. These prospectively validated disease biomarkers could then be used to subcategorize the spectrum of MS patients into a finite number of endophenotypes with demonstrable different molecular pathogeneses and DMT response profiles. Newly developed DMT could potentially be assessed within specific endophenotypes and compared with pharmacogenomically relevant active comparator DMT. This approach may increase the efficiency of MS trials through homogenization of patient population and minimization of nonresponders in study groups, providing the potential for the development of targeted therapies.
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http://dx.doi.org/10.1177/1756286419847095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535717PMC
May 2019

Evaluation of dual pathology among drug-resistant epileptic patients with hippocampal sclerosis.

Neurol Sci 2019 Mar 11;40(3):495-502. Epub 2018 Dec 11.

Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Purpose: Dual pathology (DP) is defined as simultaneous presence of hippocampal sclerosis (HS) and any other pathology in the brain. Since this is a less probed concept, we aimed to evaluate the frequency and characteristics of DP among drug-resistant epileptic patients with HS.

Methods: This is a cross-sectional study conducted during 2007-2016 in Kashani Comprehensive Epilepsy Center, Isfahan, Iran. Patients with diagnosis of drug-resistant epilepsy and HS were enrolled in the study, and demographic data, seizure semiology, EEG findings, and MRI findings were collected. We compared these variables between three groups of DP, unilateral HS, and bilateral HS.

Results: Of the 200 enrolled cases, 29 patients (14.5%) had DP and 21 patients (10.5%) had bilateral HS; the remaining patients had unilateral HS. The average age of patients with DP was 30.03, and 65.5% of them were male. Patients with DP had more EEG discharges from regional and multi-focal sites compared to unilateral HS (P value < 0.001). Also, complex partial seizure (CPS) was more commonly presented in patients with unilateral HS (96.8%). Comparison of disease characteristics between DP and bilateral HS showed no difference in most categories (P > 0.05).

Conclusions: We found DP among 14.5% of our drug-resistant epileptic patients with HS. DP patients mostly presented with CPS and had high proportion of ictal and interictal EEG discharges from regional and multi-focal areas. Gliosis and focal cortical dysplasia were the most common pathologies among DP patients. Patients with DP showed a similar behavior to bilateral HS in many features.
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http://dx.doi.org/10.1007/s10072-018-3677-7DOI Listing
March 2019

Neuromyelitis optica spectrum disorder and menstruation.

Rev Neurol (Paris) 2018 Dec 23;174(10):716-721. Epub 2018 Jul 23.

Isfahan Neurosciences Research Center, Alzahra Research Institute, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran; Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran. Electronic address:

Background: Gender issues and the female preponderance in neuromyelitis optica spectrum disorder (NMOSD) have been investigated before, yet the interplay between NMOSD and menstrual characteristics has remained unknown. Thus, the aim was to compare menstrual cycle patterns and their symptoms in NMOSD patients and healthy women.

Methods: This cross-sectional study was conducted during 2015-2016 in Isfahan, Iran, and included female patients aged>14years with a diagnosis of NMOSD and healthy subjects as controls. Data regarding age at menarche, menstrual characteristics, history of premenstrual syndrome (PMS) and possible perimenstrual symptoms were collected. Also, NMOSD patients were asked to report changes in their menstrual cycles after onset of the disorder.

Results: The final study population included 32 NMOSD and 33 healthy controls. These groups did not differ regarding their demographics (P>0.05), and age at menarche in the NMOSD and control groups was 13.31±1.49 years and 13.48±1.44 years, respectively (P=0.637). The controls experienced PMS more frequently (78.8% vs. 40.6% in the NMOSD patients; P=0.03), with no significant differences in other menstrual features between groups (P>0.05). However, changes in menstruation after NMOSD onset were reported by 43.8% of patients, with an increase in menstrual irregularities from 15.6% to 43.7% (P=0.012); other menstrual characteristics did not differ after disease onset (P>0.05).

Conclusion: Menstruation do not differ between healthy controls and NMOSD patients before the onset of disease whereas, after its onset, those affected experienced more irregularities in their menstrual cycles. This may be an effect of NMOSD and its underlying disorders on menstruation and suggests that further interventions may be required for affected women.
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http://dx.doi.org/10.1016/j.neurol.2018.01.373DOI Listing
December 2018

The interplay of multiple sclerosis and menstrual cycle: Which one affects the other one?

Mult Scler Relat Disord 2018 Apr 2;21:46-50. Epub 2018 Feb 2.

Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Background: Menstruation is suggested to affect multiple sclerosis (MS) symptoms, while the effect of MS on menstruation is not studied before. Here, we aimed to compare the pattern of menstrual cycle and its symptoms between MS patients and healthy controls.

Methods: This is a cross-sectional study conducted during 2015-2016 in MS clinic of Kashani hospital, Isfahan, Iran. We included female patients > 14 years with diagnosis of relapsing-remitting MS, and healthy subjects as the control group. We collected data regarding menarche age, menstrual characteristics, history of premenstrual syndrome, the amount of menstrual bleeding, and the possible perimenstrual symptoms from all subjects. Also, MS patients were asked to report changes in menstrual characteristics after MS occurrence.

Results: The final study population contained 181 MS patients and 202 healthy subjects. The mean age in MS and control group were 36.04 ± 9.86 and 35.16 ± 11.30, respectively (P-value = 0.426). Menarche age in MS patients and control group were not statistically different (13.59 ± 1.87 and 13.29 ± 1.53, respectively; P-value = 0.087). Changing menstrual characteristics was reported in 70 MS patients (38.7%). Irregular menstrual cycle increased from 21% to 40.3% after occurrence of MS (P-value < 0.001) and was reported 24.7% in the control group. MS patients versus controls reported more symptoms before, during, and after their menstrual period (P-values < 0.001).

Conclusion: We found no difference regarding menstrual characteristics in MS patients before onset of the disease and healthy controls. Irregular menstrual cycle was observed more after the disease occurrence while other menstrual characteristics did not change. Moreover, MS patients reported many more perimenstrual symptoms.
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http://dx.doi.org/10.1016/j.msard.2018.01.020DOI Listing
April 2018

Vitamin D Status in Small Vessel and Large Vessel Ischemic Stroke Patients: A Case-control Study.

Adv Biomed Res 2017 30;6:146. Epub 2017 Nov 30.

Isfahan Neurosciences Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Vitamin D insufficiency is a globally widespread issue. Recent studies have reported a high prevalence of Vitamin D deficiency in Middle-East countries. Studies have shown negative effects of Vitamin D deficiency on endothelium and related diseases such as ischemic brain stroke. Here, we assessed Vitamin D status in patients with different types of ischemic brain stroke and control group.

Materials And Methods: Seventy-five patients (49.3% small vessel, 50.7% large vessel) and 75 controls, matched for age (68.01 ± 10.94 vs. 67.64 ± 10.24) and sex (42 male and 33 female) were recruited. 25(OH) D levels were measured by Chemiluminescence immunoassay. 25(OH) D status was considered as severely, moderately, or mildly deficient and normal with 25(OH) D levels of less than 5, 5-10, 10-16, and >16 ng/ml, respectively.

Results: Mean ± standard error concentration of 25(OH) D in cases and controls were 17.7 ± 1.5 and 26.9 ± 1.6 ( = 0.0001), respectively. Mild, moderate, and severe Vitamin D deficiency were observed in 10.8%, 32.4%, 8.1% vs. 34.3%, 31.5%, 9.5% of small vessel and large vessel group, respectively. 21.7% of the controls were Vitamin D deficient. Vitamin D deficiency was significantly associated with higher risk for ischemic stroke, ( = 0.000, OR = 7.17, 95% confidence interval: 3.36-15.29). 25(OH) D levels were significantly higher in control group comparing to small vessel (26.9 ± 1.6 vs. 20.59 ± 2.6 < 0.05) and large vessel (26.9 ± 1.6 vs. 13.4 ± 1.3 < 0.001) stroke patients. Small vessel group had significantly higher levels of Vitamin D than large vessel ( < 0.05).

Conclusion: Vitamin D deficiency significantly increases the risk of ischemic stroke, favoring the types with the pathogenesis of large vessel strokes.
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http://dx.doi.org/10.4103/2277-9175.219411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735556PMC
November 2017

An Evaluation on Iran International Public Health Summer School in Relation to its Efficacy Based on Participants' Experience and Opinions.

Adv Biomed Res 2017 10;6:137. Epub 2017 Nov 10.

Center of Excellence in Teaching and Learning Clinical Skills, Medical Education Development Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: A serious challenge to educate health staff for public health is to appear encouraging enough to persuade them for learning issues on this field and implementing new educational methods and innovative ways. Iran International Public Health Summer School (IPHS) made an effort to provide medical sciences students with a fortune to get familiar with and involved in public health. This study intended to evaluate the efficacy of this event.

Materials And Methods: This cross-sectional study was performed in March-April 2015 by the help of an electronic self-administered questionnaire filled out by 49 Iranian participants 6 months after IPHS2014. The questionnaire assessed the main goals in seven main domains: Interest, activities, and general knowledge in the field of public health, general skills, educational methods, educational and executive schedules, and general satisfaction.

Results: Average scores of all domains were >3 (the mean), and all were statistically significant. The highest average score belonged to educational methods (3.92) and the lowest was calculated for the item regarding participants' activities on public health (3.5). No significant difference was found between positive answers of individuals who were interested or active in public health prior to the event and those who had no background.

Conclusions: We believe IPHS was a unique instance in Public Health Education in Iran. Considering the level of success of this program to reach its goals for both students' with or without any previous background on public health, it is recommended as a general model to be simulated in other developing countries.
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http://dx.doi.org/10.4103/2277-9175.218028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698976PMC
November 2017

Effects of Interferential Electrical Stimulation Plus Pelvic Floor Muscles Exercises on Functional Constipation in Children: A Randomized Clinical Trial.

Am J Gastroenterol 2018 02 19;113(2):295-302. Epub 2017 Dec 19.

Pediatric Gastroenterology and Hepatology Research Center, Pediatric Center of Excellence, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI).

Objectives: Functional constipation is a common condition in children. We assessed the effectiveness of combined interferential (IF) electrical stimulation and pelvic floor muscle (PFM) exercises on functional constipation in children.

Methods: We conducted a single-center, double-blind randomized clinical trial study during 2014-2017 in Tehran, Iran. Ninety children, aged 5-13 years, who fulfilled Rome III criteria were enrolled and randomly assigned into two treatment groups. Case group (n=45) underwent IF electrical stimulation and PFM exercises, whereas the control group (n=45) received PFM exercises plus sham stimulation. A complete bowel habit diary (with concerning data on the frequency of defecation per week, stool form, and the number of fecal soiling episodes), a constipation score questionnaire, and a visual pain score were recorded before, after the treatment and 6 months later for all participants. In addition, children in both groups were assessed with a constipation-related quality-of-life questionnaire before, after the end of treatment sessions, and 6 months after the treatment.

Results: Treatment success was achieved for 88.4% of children in the case group compared with 43.2% of children in the control group after the treatment (P<0.003). The median constipation score was reduced in both groups, with the cases having significantly lower scores after the treatment (4 vs. 8, P<0.000). Stool form normalized in 75.6% of the cases and 45.5% of the controls after the treatment (P<0.01).

Conclusions: Our results showed that using IF electrical stimulation as an adjuvant therapy to the medical and rehabilitation programs significantly boosts the effects of treatment among these patients.
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http://dx.doi.org/10.1038/ajg.2017.459DOI Listing
February 2018

Cutaneous anaplastic large cell lymphoma in a multiple sclerosis patient receiving Fingolimod.

Mult Scler Relat Disord 2018 Jan 22;19:121-123. Epub 2017 Nov 22.

Isfahan Neurosciences Research Center, Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Background: Previous reports of cutaneous neoplastic lesions secondary to Fingolimod treatment among multiple sclerosis patients.

Objective: Reporting a case of cutaneous large cell lymphoma in a multiple sclerosis patient during Fingolimod treatment.

Method: Case study.

Result: Our patient developed CD30+ cutaneous large cell lymphoma two years after initiation of Fingolimod treatment and her symptoms regressed following the cessation of treatment.

Conclusion: This report indicates that cutaneous lymphoid neoplasms should be considered a possible side effect among patients receiving Fingolimod.
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http://dx.doi.org/10.1016/j.msard.2017.11.012DOI Listing
January 2018

More evidence is needed to show any role of cytomegalovisrus and varicella zoster virus in pathogenesis of multiple sclerosis.

J Neuroimmunol 2017 12 18;313:123-124. Epub 2017 Sep 18.

Faculty of Medicine, Najafabad Branch, Islamic Azad University, Najafabad, Iran.

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http://dx.doi.org/10.1016/j.jneuroim.2017.09.006DOI Listing
December 2017

Attitudes Toward Cancer and Cancer Patients in an Urban Iranian Population.

Oncologist 2017 08 30;22(8):944-950. Epub 2017 May 30.

Cancer Education Center, Samsung Comprehensive Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Sungkyunkwan University, Seoul, Korea

Background: Because of the significant incidence and mortality of cancer in Iran, a Comprehensive National Cancer Control Program for the prevention and early detection of cancer was launched in 2007. However, cancer awareness and screening rates in Iran did not improve. This study aimed to evaluate public attitudes toward cancer and cancer patients in Iran.

Materials And Methods: We conducted a cross-sectional survey among 953 non-institutionalized individuals in Isfahan, Iran, from November 2014 to February 2015. We collected data on attitudes toward cancer in three domains (impossibility of recovery, cancer stereotypes, and discrimination), as well as questions on willingness to disclose a cancer diagnosis.

Results: Among all participants, 33.9% agreed that it is very difficult to regain one's health after a cancer diagnosis, 17.4% felt uncomfortable with a cancer patient, and 26.9% said that they would avoid marrying people whose family members had cancer. While 88.9% of study participants said that cancer patients deserve to be protected in society, 53.3% and 48.4% of participants agreed that they would not disclose a cancer diagnosis to neighbors and coworkers, respectively.

Conclusion: Negative attitudes with respect to impossibility of recovery and discrimination toward cancer and cancer patients were common among urban Iranians. Most people would not disclose a cancer diagnosis to others in spite of advancements in cancer diagnosis and treatment, reflecting unfavorable attitudes toward cancer and cancer patients in society. Successful implementation of cancer awareness and prevention programs in Iran may require social changes based on adequate information on cancer and cancer patients.

Implications For Practice: Public attitudes toward cancer and cancer patients are an important factor affecting cancer control programs as well as quality of life and recovery of cancer patients. The issue has not been studied in Iran and the surrounding countries in the Middle East. This is the first report presented on the subject. These findings can be used by health policy makers, health managers, and clinicians for better practice.
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http://dx.doi.org/10.1634/theoncologist.2017-0073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553964PMC
August 2017

The effect of gall extract on burn wound healing in rat.

Iran J Basic Med Sci 2016 Oct;19(10):1144-1150

Physiology Research Center, Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran.

Objectives: The aim of the present study was to evaluate the effect of galls extract on the rat skin burn wound healing.

Materials And Methods: Ethanol extract of the galls of was used to treat the induced burn wounds on the back of 32 Wistar rats divided into 4 groups. The groups were treated by placebo, 1%, 2% and 4% concentration gall extract gels for 14 days and the efficacy of treatment was assessed based on reduction of burn wound area, as well as histological and molecular characteristics.

Results: The mean wound surface in the 14 day, in all groups treated by gall extracts were larger than control group and the differences were statistically significant (=0.043). The mean histological wound healing scores were not statistically different. Analysis of nitric oxide and platelet derived growth factor concentration in wound fluids in the 5 day of study showed that there was not any significant difference between groups (=0.468 and 0.312 respectively). Fibroblast growth factor (bFGF) concentration in the wound fluids, was significantly higher in group treated with 1% gall extract gel in comparison to the control group (=0.026).

Conclusion: Our results could not prove the significant positive effect of galls extract on the burning wound healing. More studies with more groups treated with different doses of the extract are recommended.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110664PMC
October 2016

A comparative study of transcutaneous interferential electrical stimulation plus behavioral therapy and behavioral therapy alone on constipation in postoperative Hirschsprung disease children.

J Pediatr Surg 2017 Jan 27;52(1):177-183. Epub 2016 Jul 27.

Department of Pediatric Surgery, Pediatric Center Excellence, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI). Electronic address:

Purpose: We assessed the effectiveness of transcutaneous interferential (IF) electrical stimulation on constipation in postoperative Hirschsprung's disease (HD) patients.

Methods: Thirty HD children (18 boys and 12 girls) with constipation who had no surgical complication were enrolled and then randomly divided into two treatment groups. The control group underwent only behavioral therapy comprising high fiber diet, hydration, toilet training and pelvic floor muscles exercises while; the IF group underwent behavioral therapy plus IF electrical stimulation. Patients underwent anorectal manometry before and 6months after the treatment. In addition, a complete bowel diary with data on the frequency of defecation per week, stool form and the number of fecal soiling episodes, a constipation score and a visual pain score were obtained from all patients before, after treatment and 6months later.

Results: Constipation symptoms were improved in 10 (66%) and 4 (26.6%) patients in IF and control groups, respectively at 6months of follow up (P<0.03). Frequency of defecation per week significantly increased after the treatment in the IF group compared with control group at the 6months of follow up (5.4±2.1 vs. 3.3±1.8 per week, respectively; P<0.009). In addition, mean pain score was significantly decreased in IF group compared with controls after treatment (P<0.05).

Conclusion: IF electrical stimulation is an effective adjunct to behavioral therapy to overcome symptoms of constipation in postoperative HD patients.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.07.007DOI Listing
January 2017

Reliability and validity of the migraine disability assessment scale among migraine and tension type headache in Iranian patients.

Biomed Res Int 2014 16;2014:978064. Epub 2014 Jan 16.

Albert Einstein College of Medicine, Bronx, NY, USA ; Montefiore Medical Center, Bronx, NY, USA.

Introduction: MIDAS is a valid and reliable short questionnaire for assessment of headache related disability. Linguistic validation of Persian MIDAS and assessment of psychometric properties between tension type headache (TTH) and migraine were the aims of this study.

Methods: Patients with migraine or TTH were included. At the first visit, we administered a headache symptom questionnaire, MIDAS, and SF-36. Patients filled out MIDAS in second and third visit within three and eight weeks after base line visit. Internal consistency (Cronbach α ) and test-retest reproducibility (Spearman correlation coefficient) were used to assess reliability. Convergent validity and MIDAS capability to differentiate between chronic and episodic headaches (migraine and TTH) were also assessed.

Results: The 267 participants had episodic migraine (EM-64%), chronic migraine (CM-13.5%), episodic TTH (ETTH-13.5%), and chronic TTH (CTTH-9). Internal consistency reliability was 0.8 for the entire sample, 0.72 for TTH, and 0.82 for migraine. Test-retest reliability for all questions between visit 1 and visit 2 varied from 0.54 to 0.71. Convergent validity was assessed using SF-36 as an external referent. Patients with episodic headaches (EM and ETTH) had significantly lower MIDAS scores than chronic headaches (CM and CTTH).

Conclusion: Persian MIDAS is a valid and reliable questionnaire for migraine and TTH that can differentiate between episodic headache and chronic headache.
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http://dx.doi.org/10.1155/2014/978064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914354PMC
September 2014

Vitamin D status in migraine patients: a case-control study.

Biomed Res Int 2014 2;2014:514782. Epub 2014 Jan 2.

Physiology Research Center, Department of Physiology, Isfahan University of Medical Sciences, Isfahan 81745-319, Iran ; Department of Neurology and Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Hezarjarib Avenue, Isfahan 81745-319, Iran.

Background: There have been few studies on the relation between vitamin D and migraine. We investigated the prevalence of vitamin D deficiency in migraine patients and compared it with a control group. We also evaluated the relationship of vitamin D deficiency with severity of migraine.

Methods: 105 newly diagnosed migraine patients and 110 controls, matched for age, sex, socioeconomic status, education, and sun exposure, were enrolled during the spring of 2011. 25-Hydroxy vitamin D [25(OH)D] plasma levels were measured by chemiluminescence immunoassay.

Results: The mean ± SE concentration of 25(OH)D was 13.55 ± 0.91 ng/mL in cases and 13.19 ± 1.19 ng/mL in controls. There was no significant difference in 25(OH)D concentration between cases and controls. We found no relationship between severity of headache and 25(OH)D status.

Conclusions: We did not find any association between migraine and vitamin D status; also, severity of headaches was not related to 25(OH)D level. Further studies with larger sample sizes are required to confirm our results.
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http://dx.doi.org/10.1155/2014/514782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910019PMC
December 2014

Stroke in a patient with pulmonary arteriovenous fistula: A case report study.

Adv Biomed Res 2013 30;2:84. Epub 2013 Nov 30.

Medical students' research center, Isfahan University of medical sciences, Isfahan, Iran.

Pulmonary arteriovenous fistula (PAVF) is a venous malformation that permits right to left shunting of blood, bypassing the pulmonary capillary bed. Often PAVFs are seen in association with hereditary conditions. On the other hand, isolated PAVFs are rare and asymptomatic. There have been few reports of isolated PAVF related complications. A patient was referred to us with dysarthria and diplopia and history of surgically-treated PAVF. Further evaluations revealed a stroke in thalamic region. We found an open PAVF in a case of thalamic stroke.
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http://dx.doi.org/10.4103/2277-9175.122499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908485PMC
February 2014

Reliability and Validity of the Persian HIT-6 Questionnaire in Migraine and Tension-type Headache.

Pain Pract 2014 Sep 18;14(7):625-31. Epub 2013 Nov 18.

QualityMetric Inc., Lincoln, Rhode Island, U.S.A.

Objective: Headache Impact Test (HIT-6) measures the impact headaches in a 1-month period. We validated the Persian translation of HIT-6, compared the HIT-6 psychometric analysis between migraine and tension-type headache (TTH) patients, and evaluated the capability of HIT-6 to differentiate between TTH, chronic migraine, and episodic migraine.

Methods: Qualified participants, including 274 patients diagnosed with migraine or TTH, were required to complete HIT-6, SF-36v2, and a symptoms questionnaire on their first visit. At 3 and 8 weeks from first visit, participants completed HIT-6. Internal consistency (Cronbach's α) and test-retest reproducibility (Pearson's correlation coefficient) were used to assess reliability. Convergent validity was also assessed.

Results: Tension-type headache, episodic, and chronic migraines included 24.5%, 61.9%, and 13.6% of the participants, respectively. Internal consistency among all patients, TTH, and migraine in the first visit were 0.74, 0.77, and 0.73, respectively. Test-retest reliability for HIT-6 between visit 1 and 2 showed a moderate level of correlation (r = 0.50). Convergent validity and also item total correlation were acceptable. There was no significant difference in HIT-6 total score between TTH and migraine.

Conclusion: Persian HIT-6 is a valid and reliable questionnaire for the evaluation of headache. However, it cannot differentiate between chronic migraine, episodic migraine, and TTH in Iranian population.
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http://dx.doi.org/10.1111/papr.12120DOI Listing
September 2014

The psychometric properties of the persian migraine-specific quality of life questionnaire version 2.1 in episodic and chronic migraines.

ScientificWorldJournal 2013 27;2013:950245. Epub 2013 Aug 27.

Department of Physiology, Physiology Research Center, Isfahan University of Medical Sciences, Isfahan 81745-319, Iran ; Medical Student Research Center, Isfahan University of Medical Sciences, Isfahan 81745-319, Iran.

Background: Migraine-specific quality of life (MSQ) is a valid and reliable questionnaire. Linguistic validation of Persian MSQ questionnaire, analysis of psychometric properties between chronic and episodic migraine patients, and capability of MSQ to differentiate between chronic and episodic migraines were the aims of this study.

Method: Participants were selected from four different neurology clinics that were diagnosed as chronic or episodic migraine patients. Baseline data included information from MSQ v. 2.1, MIGSEV, SF-36, and symptoms questionnaire. At the third week from the baseline, participants filled out MSQ and MIGSEV. Internal consistency (Cronbach alpha) and test-retest reproducibility (intraclass correlation coefficients) were used to assess reliability. Convergent and discriminant validities were also assessed.

Results: A total of 106 participants were enrolled. Internal consistencies of MSQ among all patients, chronic and episodic migraines, were 0.92, 0.91, and 0.92, respectively. Test-retest correlation of MSQ dimensions between visits 1 and 2 varied from 0.41 to 0.50. Convergent, item discriminant, and discriminant validities were approved. In all visits MSQ scores were lower in chronic migraine than episodic migraine; however, the difference was not statistically significant.

Conclusion: Persian translation of MSQ is consistent with original version of MSQ in terms of psychometric properties in both chronic and episodic migraine patients.
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http://dx.doi.org/10.1155/2013/950245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771439PMC
April 2014

Recurrent acute pancreatitis and cholangitis in a patient with autosomal dominant polycystic kidney disease.

Int J Prev Med 2013 Feb;4(2):233-6

Department of Gastroenterology and Hepatology, Isfahan University of Medical Sciences, Isfahan, Iran ; Kurdistan Liver and Digestive Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder associated with multiple cyst formation in the different organs. Development of pancreatic cyst in ADPKD is often asymptomatic and is associated with no complication. A 38-year-old man with ADPKD was presented with six episodes of acute pancreatitis and two episodes of cholangitis in a period of 12 months. Various imaging studies revealed multiple renal, hepatic and pancreatic cysts, mild ectasia of pancreatic duct, dilation of biliary system and absence of biliary stone. He was managed with conservative treatment for each attack. ADPKD should be considered as a potential risk factor for recurrent acute and/or chronic pancreatitis and cholangitis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604858PMC
February 2013