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Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance. Methods We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate. Results We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly. Conclusion The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.

Biofeedback is a well-known and effective treatment for patients with fecal evacuation disorder (FED). The main purpose of this study was to investigate the outcome and the effects of biofeedback therapy on physiological parameters as assessed by manometry in patients with FED. Data from 114 consecutive patients with FED who underwent biofeedback therapy in Sara Gastrointestinal clinic in Tehran, Iran during 2015–2018 were retrospectively reviewed and analyzed. All participants underwent a comprehensive evaluation of anorectal function that included anorectal manometry and a balloon expulsion test at the baseline and after biofeedback therapy. Maximum anal squeeze pressure and sustained anal squeeze pressure were improved up to 100% and 94.7% of normal values in the patients after biofeedback, respectively (P

Calcinosis, insoluble calcium compounds deposited in skin and other tissues, is a crippling sequela of dermatomyositis. Prolonged disease associated with ongoing inflammation, ischemia, repetitive trauma, and certain autoantibodies are associated with calcinosis. Herein, we describe potential pathogenic mechanisms including the role of mitochondrial calcification. There are no widely effective treatments for calcinosis. We review available pharmacologic therapies for calcinosis including those targeting calcium and phosphorus metabolism; immunosuppressive/anti-inflammatory therapies; and vasodilators. Mounting evidence supports the use of various formulations of sodium thiosulfate in the treatment of calcinosis. Although the early institution of aggressive immunosuppression may prevent calcinosis in juvenile dermatomyositis, only limited data support improvement once it has developed. Minocycline can be useful particularly for lesions associated with surrounding inflammation. Powerful vasodilators, such as prostacyclin analogs, may have promise in the treatment of calcinosis, but further studies are necessary. Surgical removal of lesions when amenable is our treatment of choice.

Objective Cigarette smoking is associated with immune-mediated disorders. We explored the contribution of smoking to polymyositis (PM) and dermatomyositis (DM) phenotypes and attempted to determine whether cigarette smoking effects differ by race and genotype. Methods Associations of tobacco smoking with disease features, autoantibodies, HLA types, and race were evaluated using multiple logistic regressions in 465 patients. Results Caucasian ever-smokers (n = 140) were more likely to have PM (adjusted OR = 2.24, 95% CI: 1.41\x963.57), anti-synthetase (adjusted OR = 1.93, 95% CI: 1.12\x963.34) and anti-Jo-1 autoantibodies (adjusted OR = 1.94, 95% CI: 1.08\x963.46) and less likely to have anti-p155/140 autoantibodies (adjusted OR = 0.36, 95% CI: 0.14\x960.92). In Caucasians, ever-smokers had a greater interstitial lung disease (ILD) frequency than never-smokers, while in African-Americans this relationship was inverted, but neither trend reached statistical significance. Pack-years of cigarette smoking showed significant positive associations with PM (adjusted OR = 1.02, 95% CI: 1.002\x961.04) and ILD (adjusted OR = 1.02, 95% CI: 1.001\x961.03) and was inversely associated with anti-p155/140 autoantibodies (adjusted OR = 0.93, 95% CI: 0.87\x960.99) in Caucasians. Caucasian heavy smokers (=20 pack-years) were more likely to have PM (adjusted OR = 2.52, 95% CI: 1.25\x965.09), ILD (adjusted OR = 2.48, 95% CI: 1.23\x965.00) and anti-Jo-1 autoantibodies (adjusted OR = 2.65, 95% CI: 1.16\x966.08) than never-smokers. In Caucasians, compared to never-smokers without HLA-DRB1*03:01 allele, ever-smokers with HLA-DRB1*03:01 allele had the highest odds of PM, ILD, ASA, and anti-Jo-1 autoantibodies. Risks for those with only one of these two factors were intermediate. An inverse pattern was observed regarding anti-p155/140 autoantibodies. Conclusion Tobacco smoking was associated with clinical and autoantibody phenotypes in Caucasians. Our findings also suggest possible interactions among HLA-DRB1*03:01 and smoking on the risk of PM and ILD, as well as, anti-synthetase, anti-Jo-1, and anti-p155/140 autoantibodies in Caucasians.

This paper discusses the drained static triaxial testing on granite ballast material with different amount of breakdown fouling and water content. Large-scale, 10 in., triaxial equipment was used for this testing program at the University of Massachusetts, Amherst. These tests were performed to study the effect of fouling and its inseparable associate, water content, on the strength properties and degradation characteristics of railroad ballasted track. Ballast with three different fouling percentages (defined as the ratio of dry weight material passing 3/8″ (9.5 mm) sieve to dry weight of the total ballast sample) from clean to highly fouled ballast (

Vitamin D deficiency, common in the population with irritable bowel syndrome (IBS), can induce the main factors that lead to IBS clinical symptoms, such as depression, anxiety, and inflammation. Serotonin (5-HT) plays an important role in the pathophysiology of IBS, and its production and secretion are increased from the lumen due to stress and inflammation. The aim of this study was to evaluate the effect of vitamin D3 supplementation on the pathogenesis of diarrhea-predominant IBS (IBS-D). Seventy-four IBS-D patients (age: 18-65 y) participated in a randomized, double-blind, placebo-controlled trial study from February 2017 to May 2018, at Rasoul-e-Akram Hospital, Tehran, Iran. Subjects were allocated into two groups receiving 50,000 IU/week of vitamin D3 or placebo for 9 weeks. IBS severity score system (IBS-SSS), IBS-quality of life questionnaire (QoL), hospital anxiety and depression Scale (HADs), visceral sensitivity index (VSI) and serum 25(OH) vitamin D3, serotonin, 5-hydroxy-indole acetic acid and ratio of 5-HIAA/5-HT were evaluated before and after the interventions. Symptoms severity, QoL, HADs-depression, and VSI score improved significantly in the vitamin D group as compared to the placebo group (P-values, EXCLI Journal;Vol. 19. 2020, p. 652-667

Supplementation with saffron helps improve antioxidant status. Oxidative stress plays an important role in ulcerative colitis (UC). The present study aimed to investigate the effect of saffron supplementation on disease severity and Oxidative/Antioxidant factors in patients with UC. This randomized double-blinded study was conducted on 80 mild to moderate UC patients. Participants were randomly divided into intervention (100 mg saffron/daily) and placebo (100 mg maltodextrin/daily) groups. Of all the participants, 75 completed the study. After 8 weeks, there were significantly increased in the mean score of simple clinical colitis activity index questionnaire (3.83 ± 1.78 to 3 ± 1.60, p =.004), the serum levels of total antioxidant capacity (2.68 ± 0.90 to 2.79 ± 0.87, p =.016), superoxide dismutase (60.69 ± 9.59 to 66.30 ± 10.79, p =.009) and glutathione peroxidase (22.05 ± 14.27 to 29.67 ± 17.97, p =.011) in patients received saffron compared to the placebo group. Whereas, there was no significant difference in serum levels of malondialdehyde between the two groups. Finally, dietary saffron as an alternative therapy may effective in improving antioxidant factors and reducing the severity of disease in UC patients. © 2020 John Wiley & Sons Ltd

Vitamin D deficiency, common in the population with irritable bowel syndrome (IBS), can induce the main factors that lead to IBS clinical symptoms, such as depression, anxiety, and inflammation. Serotonin (5-HT) plays an important role in the pathophysiology of IBS, and its production and secretion are increased from the lumen due to stress and inflammation. The aim of this study was to evaluate the effect of vitamin D3 supplementation on the pathogenesis of diarrhea-predominant IBS (IBS-D). Seventy-four IBS-D patients (age: 18-65 y) participated in a randomized, double-blind, placebo-controlled trial study from February 2017 to May 2018, at Rasoul-e-Akram Hospital, Tehran, Iran. Subjects were allocated into two groups receiving 50,000 IU/week of vitamin D3 or placebo for 9 weeks. IBS severity score system (IBS-SSS), IBS-quality of life questionnaire (QoL), hospital anxiety and depression Scale (HADs), visceral sensitivity index (VSI) and serum 25(OH) vitamin D3, serotonin, 5-hydroxy-indole acetic acid and ratio of 5-HIAA/5-HT were evaluated before and after the interventions. Symptoms severity, QoL, HADs-depression, and VSI score improved significantly in the vitamin D group as compared to the placebo group (P-values, EXCLI Journal; 19:Doc652; ISSN 1611-2156

The allowable speed limit of railroad tracks is dependent upon maintaining track conditions that will ensure the safety and ride quality. Settlement of railway tracks amplifies the dynamic loads of trains, which results in high maintenance costs and poor ride quality. Direct settlement measurement in the field is costly due to the requirement for installing many gauges along the many kilometers of track. Different datasets from the US passenger tracks consisting of more than 300 million elements were employed to propose a novel method for measuring the rate of settlement from the reported space curve. In this method, Cross Power Spectral Density (CPSD) was employed for determining the quality of data and choosing reliable observations for calculating the settlement. After calculating the rate of settlement for two railway tracks with a total length of 287 miles, its correlation with changes in different geometry indices was investigated. Equations were proposed for predicting the rate of settlement by changes in geometry indices. Results indicate that standard deviation index has the best correlation with the rate of settlement. Track quality index (TQI) is sensitive to high-frequency noise and does not yield highly accurate results when there is noise in the dataset.

Repeated loading of railroad track results in deformation of the track foundation materials. The degree of ballast fouling and the amount of moisture affect the rate and magnitude of both elastic and plastic deformation of the track. As train traffic accumulates, the track deforms to a point where maintenance is required. Studying the effects of fouled ballast in different moisture conditions under different loads leads to a better understanding of the risk factors and maintenance needs of the track. In this study, a large ballast testing box was used to simulate the degradation of fouled ballast at different moisture conditions under heavy axle loading and high traffic conditions. The ballast compression tests were conducted on ballast with different fouling and moisture conditions up to 2,500,000 cycles of repeated heavy loading. The ballast was also tested in saturated conditions that simulated heavy rainfall events. The laboratory results have been compared with an accepted settlement model and different measured field settlements. The ballast box test results show comparable results with field measurements and analytical modeling. This paper presents conclusions regarding the effects of various factors on the rate and magnitude of the plastic and elastic settlement.

Background Antisynthetase syndrome (ASSD) lacks of established clinico-serological classification criteria. A taskforce by EULAR and ACR is working on to develop and validate classification criteria for ASSD. Objectives To systematically upraise literature to retrieve the available definitions of ASSD and to evaluate their diagnostic performance. Methods This systematic review followed a pre-specified protocol. Two research questions (Q1: how is ASSD defined; Q2: what is the diagnostic performance of the definitions) were rephrased into PICOs terms to create search strategies. Studies on patients with suspect or confirmed ASSD, including a definition of the disease with any study design, excluding case-reports and narrative reviews, were eligible for inclusion. The diagnostic performance had to be tested against the reference standard of expert opinion. PubMed and Embase were searched from 01/01/1984 to 06/11/2018. Moreover, the ACR and EULAR congress abstracts (2017-2018) were hand searched. The titles and abstracts of the retrieved studies were screened by pairs of reviewers, the full-text of studies fulfilling the inclusion criteria was assessed to confirm eligibility. The references of the included studies were also evaluated in search of additional studies. Data from primary studies were extracted into a pre-specified extraction form and, if possible, 2x2 tables to assess diagnostic performance were completed. Sensitivities, specificities, positive and negative likelihood ratios (LR) were calculated for each study. If the diagnostic performance of a definition or variable was assessed in at least 4 studies, a meta-analysis of diagnostic performance was undertaken. The risk of bias (RoB) was assessed using the most appropriate tool depending on study design. Results After the exclusion of duplicates, the searches retrieved 4358 studies, of which 375 suitable for full-text review. Finally, 77 studies were included, along with 1 additional study from hand search and 3 congress abstracts. 72 studies were included in Q1 and 9 in both Q1 and 2. The presence of antisynthetase antibodies (70 studies), mainly anti-Jo1 (57 studies); myositis (51 studies), mainly defined clinically (32 studies); and interstitial lung disease (38 studies) were the variables most frequently used to define ASSD. Other variables, such as arthritis (19 studies), Raynaud’s phenomenon and skin manifestations (10 studies each) were included less frequently. Most commonly, ASSD was defined by a combination of clinical and serological variables. However, no study evaluated the diagnostic performance of such combined definitions. Most of the studies included in Q2 (6) evaluated specific variables of muscle biopsy, one evaluated MRI and 2 clinical variables, with a wide variability in the performance of each item. It was possible to meta-analyze data only to assess the performance of perifascicular necrosis/atrophy: pooled sensitivity (95%CI) was 0.53 (0.33,0.72) and specificity 0.63 (0.47,0.76), pooled LR+ 1.45 (0.72,2.89) and LR- 0.73 (0.40,1.34). Conclusion ASSD is defined according to a variety of combinations of serological, clinical and histological variables. The performance of these combined definitions however has not been tested, and from the limited evidence available single muscle biopsy variable (perifascicular necrosis/atrophy) seem to perform poorly. The systematic review confirms the need of data and consensus driven classification criteria for ASSD. Disclosure of Interests Giovanni Zanframundo: None declared, Sara Faghihi Kashani: None declared, Lorenzo Cavagna: None declared, Rohit Aggarwal: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Carlo Alberto Scire: None declared, Garifallia Sakellariou: None declared

Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. The aim of this study was to determine the frequency of HLA-DRB1 alleles in Iranian patients with AIH and investigate the association between HLA alleles and the different types of the disease. Fifty-four AIH patients and 100 age- and sex-matched healthy controls were subjected to low resolution HLA-DRB typing performed by polymerase chain reaction-sequence-specific primers (PCR-SSP) technique. The results revealed higher frequencies of HLA-DRB1(∗)03, and DRB1(∗)13 alleles in patients with AIH compared to controls. However, DRB1(∗)11 was less frequent in AIH patients. In type I AIH patients HLA-DRB1(∗)03, HLA-DRB1(∗)04, HLA-DRB1(∗)08, and HLA-DRB1(∗)13 were the most frequent alleles. While in type II, the most frequent alleles were HLA-DRB1(∗)07 and HLA-DRB1(∗)13. The seronegative patients showed more frequency of HLA-DRB1(∗)03 and HLA-DRB3. In contrary, the frequency of HLA-DRB1(∗)11, HLA-DRB1(∗)15 and HLA-DRB5 in type 1 was less than healthy individuals. These findings indicate the role of HLA-DRB haplotypes in AIH susceptibility and protection, in the Iranian population.

Needle insertion during electromyography (EMG) may cause varying levels of pain that could lead to inaccurate assessment and premature termination of the procedure. The aim of this study is to compare paracetamol 325 mg/tramadol 37.5 mg with placebo in relieving pain before EMG. This is a randomized, crossover, placebo-controlled, double-blind clinical trial; forty-four healthy individuals, including 27 males with a mean age of 35.3 years (range 18-59 years), entered this study. The needles were inserted unilaterally 2 h after administration of two analgesic tablets of paracetamol 325 mg/tramadol 37.5 mg or two placebo tablets. The pain was scored through a 100-mm visual analog scale (VAS) immediately and 2 h after the procedure. The side effects were also recorded. Within a week, the procedure was repeated on the other upper limb, changing the treatment and placebo. The immediate and 2-h VAS scores were notably lower after administration of treatment compared to placebo (immediate pain: 17.5 ± 12.8 vs. 32.1 ± 16.0, P

Background Curcumin (diferuloylmethane) has been associated with the inhibition of angiogenesis, as well as the prevention of cancers and inflammatory processes. The aim of this study was to assess the efficacy of curcumin in suppressing angiogenesis in the cultured endothelial cells of rat aortic rings. Methods Eight-week-old male Wistar rats were randomized into five groups each with a different treatment and cell culturing paradigm: controls cultured in the absence of VEGF (vascular endothelial growth factor) (C), controls cultured in the presence of VEGF (C-V), controls treated with curcumin and then cultured in media lacking VEGF (C-TC), diabetics cultured in media supplemented with VEGF (D-V) and diabetics treated with curcumin and then cultured in media supplemented with VEGF (D-V-TC). Each group consisted of 8 animals. Diabetes was induced in by streptozotocin (STZ; 60 mg/kg body weight, IV). After 8 weeks, animals were sacrificed and their aortas were excised. Ring-shaped explants were embedded in a 96-well culture plate. Angiogenesis response was measured by counting the number of primary microtubules in each well. Results Optic microscopy revealed that the D-V group had the highest number of microvessels, while angiogenesis was not observed in the C or C-TC groups. The number of primary microtubules was significantly lower in the D-V-TC group compared to the D-V group (P, Graphical abstract

Railway ballast is an important component of the track substructure that provides vertical, lateral, and longitudinal support, increases track resiliency, reduces stress applied to the subgrade, and facilitates the drainage of water away from the track. Ballast is typically composed of highly angular, uniformly graded crushed stone that provides high shear strength. However, the properties of ballast are continually changing under repeated loading from train traffic. Abrasion between ballast pieces often results in more rounded particles as corners are broken off. This process also contributes to fouling, or the introduction of finer grained particles into the ballast. Abraded material accounts for the majority of fouling, but it can also be introduced via other processes, such as infiltration from the subgrade or infiltration by windblown particles. While laboratory testing of ballast has been performed extensively over the past several decades, much of the testing is performed on fresh ballast with manufactured fouling materials. This study performs laboratory tests on naturally abraded ballast, taken from real track, and the naturally occurring fouling material which includes abraded and windblown material. This study builds on tests previously performed at the University of Massachusetts, Amherst which used fresh, highly angular ballast and fouling which originates from the same parent rock. Triaxial and box tests are performed on specimens, which are prepared to the same fouling and water contents as the previous testing so that the material properties and behaviors can be directly compared. The triaxial tests reveal similar strength properties, but significantly different volumetric strain behaviors. The box tests show similar results, with higher overall settlements from the abraded ballast, particularly under initial loading. This testing has also resulted in the first known basal failure of ballast in a box test. The results show that abraded ballast exhibits distinct behavioral differences, as well as reductions in performance when compared to highly angular ballast in the same conditions.

Railway ballast under repeated traffic loading deforms and deteriorates. Increases in the rate of settlement in ballast decreases its useful life and contributes to geometry roughness and poor ride quality. Based on laboratory and field studies, as well as mechanic-based models, the fouling condition of the ballast has been shown to have a profound effect on settlement and overall ballast life. Quantifying ballast settlement and the effect of maintenance at different stages of ballast life can define the State of Good Repair (SGR) for ballast. This paper presents an approach for predicting ballast life based on geotechnical principles and maintenance management philosophy. Over 200 revenue-service locations have been studied for developing this model for different tracks including mixed passenger and freight as well as only freight traffic. The approach presented in this paper can be used for optimizing ballast’s life-cycle costs through a maintenance management approach.

The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list. All patients and research investigators were blinded to treatment allocation. The primary outcome was survival, and event was defined to be death or mechanical ventilation dependency. Analysis was by intention-to-treat and included all patients who received at least one dose of study drug. A total of 54 patients were randomized to receive either nanocurcumin (n = 27) or placebo (n = 27). After 12 months, events occurred in 1 patient (3.7%) in the nanocurcumin group and in 6 patients (22.2%) in the placebo group. Kaplan–Meier analysis revealed a significant difference between the study groups regarding their survival curves (p = 0.036). No significant between-group differences were observed for any other outcome measures. No serious adverse events or treatment-related deaths were detected. No patients withdrew as a result of drug adverse events. The results suggest that nanocurcumin is safe and might improve the probability of survival as an add-on treatment in patients with ALS, especially in those with existing bulbar symptoms. Future studies with larger sample sizes and of longer duration are needed to confirm these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-018-0606-7) contains supplementary material, which is available to authorized users.

Background/Aims: This prospective study is aimed at examining the predictive value of high-sensitivity C-reactive protein (hs-CRP) for coronary heart disease (CHD) events and microvascular complications of type 2 diabetes mellitus (T2DM). Methods: A population-based study (NCT02958579) was conducted on 1,301 participants with T2DM (mean follow-up of 7.5 years). Risk assessment for vascular events was done at baseline, and serum hs-CRP was measured. End points of this study include CHD events, diabetic retinopathy, neuropathy, and diabetic kidney disease. Individuals with unavailable data or hs-CRP >20 mg/L were excluded. The discrimination and reclassification improvement of study end points were tested after addition of hs-CRP to traditional risk factors. Results: Median serum hs-CRP was 2.00 ranging from 0.1 to 17 mg/L. Hazards ratio of each SD increment in baseline hs-CRP was 1.028 (1.024–1.032) for CHD, 1.025 (1.021–1.029) for diabetic neuropathy, 1.037 (1.030–1.043) for diabetic retinopathy, and 1.035 (1.027–1.043) for diabetic kidney disease. The addition of hs-CRP to traditional risk factors of vascular complications of T2DM improved discrimination of all end points (p < 0.001). Net reclassification improvement ranged from 8% for diabetic neuropathy to 31% for diabetic kidney disease (p < 0.05). Conclusion: Baseline hs-CRP predicts both of CHD events and microvascular complications of patients with T2D.

To investigate in a pilot study the safety and efficacy of infliximab in patients with refractory dermatomyositis (DM) and polymyositis (PM).A randomized, double-blind, placebo-controlled trial including subjects with active DM or PM. Participants had stable doses of immunosuppressive medication and prednisone (≤0.5mg/kg/day), and exhibited clinical signs of muscle weakness for at least 4 weeks prior to study entry. Participants received infusions of either placebo or infliximab 5mg/kg at 0, 2, 6, and 14 weeks in blinded manner. The primary outcome was a ≥15% manual muscle strength (MMT) improvement at week 16 compared to week 0. The secondary outcome measures were improvement defined by the International Myositis Assessment and Clinical Studies Group (IMACS) criteria. At week 16, responders in each arm had the option of either continuing the same treatment or changing to the non-responder treatment for that study arm. Non-responders in the 5mg/kg infliximab arm were increased to infliximab 7.5mg/kg for weeks 22, 30, and 38. Non-responders in the placebo arm at week 16 received infliximab 5mg/kg at weeks 16, 18, 22, 30, and 38. Outcomes were reassessed at week 40.Twelve subjects completed the study to week 16. Six of the 12 subjects received infliximab treatment at the dose of 5mg/kg with only one subject meeting the responder criteria at that dose. Of the remaining five subjects on infliximab, three crossed over to the infliximab 7.5mg/kg dose. One of those three subjects responded. All six patients in the placebo arm crossed over to the 5mg/kg dosing regimen after week 16, and two of those responded to infliximab.Infliximab therapy for patients with refractory PM and DM was well tolerated and may benefit a subset of patients.

Epilepsy is one of the most common neurological disorders. Studies have demonstrated that genetic factors have a strong role in etiology of epilepsy. Mutations in genes encoding ion channels, neurotransmitters and other proteins involved in the neuronal biology have been recognized in different types of this disease. Moreover, some chromosomal aberration including ring chromosomes will result in epilepsy. In this review, we intend to highlight the role of molecular genetic in etiology of epilepsy syndromes, inspect the most recent classification of International League against Epilepsy and discuss the role of genetic counseling and genetic testing in management of epilepsy syndromes. Furthermore, we emphasize on collaboration of neurologists and geneticists to improve diagnosis and management.

Administration of filgrastim (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) (Neupogen) in healthy donors to mobilize hematopoietic stem cells (HSCs) is a widespread practice in adults. Application of peripheral blood stem cell (PBSC) collection in normal pediatric donors is scarce due to ethical issues. Hence, there are insufficient data on the long-term impact of PBSC procedure in healthy children. This retrospective study aimed to evaluate the early and late adverse effects of PBSC donation in pediatric donors. Bone marrow and PBSC procedures and known adverse events of each technique were completely explained to parents and when applicable to children and written informed consent was obtained. rhG-CSF was administered for 4 days. HSCs were collected on the fifth day through continuous-flow apheresis and donors were followed for 30 days. Manual chart review was performed to collect short-term complications. Donors' health status was assessed via a questionnaire. A total of 145 healthy pediatric donors with a median age of 10 years at the time of donation (2 to 15 years) were followed for a median of 4.8 years (range, 1.2 to 14.2 years). The most frequent symptoms of rhG-CSF administration were fatigue (5%) and headache (3%). Thirty-five (24%) donors experienced hypocalcaemia during apheresis procedure that quickly responded to treatment. Two pregnancies occurred after rhG-CSF administration that resulted in normal births. We did not encounter any serious adverse events, including neoplastic disorders and death in this study. rhG-CSF and leukophresis procedure were well-tolerated in this study and all children completed the donation process without interruption or reduction of rhG-CSF dosage. Our results suggest that rhG-CSF is a safe drug in healthy children for the purpose of HSC mobilization.

The performance of ballasted railway systems is commonly compromised by the infiltration of fine material into the voids of the ballast. This sand and finer grained materials in the ballast is known as fouling. Increased fouling can cause decreases in hydraulic conductivity and shear strength of the ballast, as well as reduce stiffness and resilient modulus of the overall track system. These problems can cause gradual deterioration of the track, which could eventually require maintenance. One of the largest source of fouling comes from ballast breakdown resulting from abrasion caused under repeated loading. This study aims to investigate the effects of fouling from ballast breakdown on the bearing capacity of the substructure that supports the rail superstructure. Previous investigations at the University of Massachusetts Amherst utilized large scale 10-inch (25.4 cm) diameter triaxial tests on granitic ballast with fouling from ballast breakdown. The tests were run with fouling contents of 0% (clean ballast), 15%, and 30% and at water contents varying from dry ballast to field capacity. Confining pressures of 5 psi (34.5 kPa), 10 psi (68.9 kPa) and 15 psi (103.4 kPa) were used in this series of tests. Using the results from these tests, the Mohr-Coulomb strength properties can be determined for each case. This study will make use of the strength properties obtained from the results of these tests and apply them using two commonly used bearing capacity analyses. The first model is the Meyerhof and Hanna Method which considers the track as a continuous footing over a layered system. This model considers two modes of failure; punching of an individual sleeper, and track system bearing. The second model applied is the slope stability method, which uses a two-dimensional limit equilibrium approach and the method of slices to determine a factor of safety against slope stability. This analysis is commonly performed using various software programs. In this study, SLOPE/W from the GeoStudio software package is utilized for analysis. The factors of safety resulting from the bearing capacity analysis using these two methods will be compared for each of the test configurations performed, which will help to confirm the results of the analyses. Since the Mohr-Coulomb strength properties change with the degree of fouling and the water content of the ballast, it is expected that this will have some effect on the bearing capacity of the track substructure. The results of these analyses showing the effects of water content and fouling of ballast on overall track substructure bearing capacity are presented in this paper.

Railroad ballast as a layer of track substructure performs important tasks such as increasing the bearing capacity of the sleepers, providing large voids for drainage and resisting the forces applied to the super-structure. Contamination of ballast as the result of ballast breakdown known as breakdown fouling can prevent ballast from performing its job and also affects the engineering properties of ballast. This paper discusses the drained static triaxial testing on granite ballast material with different amount of breakdown fouling and water content. Large-scale triaxial equipment was used for this testing program at the University of Massachusetts, Amherst. These tests were performed to study the effect of fouling and water content, on the strength properties and degradation characteristics of railroad ballasted track. Ballast with three different fouling percentages from clean to highly fouled ballast (