The presence of abnormal septal motion on echocardiography is a predictor of abnormal cardiac magnetic resonance in systemic sclerosis.

OBJECTIVES: We aimed to perform a comprehensive analysis of the ECG, two-dimensional echocardiography (2DE) and cardiac MRI (CMR) findings in patients with systemic sclerosis (SSc), and also to investigate correlations between CMR findings and some ECG and echocardiography (ECHO) results. METHODS: We retrospectively analysed data from patients with SSc who were regularly seen at our outpatient referral centre, all assessed with ECG, Doppler ECHO and CMR. RESULTS: Ninety-three patients were included; mean (s.d.) age of 48.5 (10.3) years, 86% female, 52% diffuse SSc. Eighty-four (90%) of the patients had sinus rhythm. The most common ECG finding was the left anterior fascicular block, recorded in 26 patients (28%). The abnormal septal motion (ASM) was found in 43 (46%) patients on ECHO. Myocardial involvement (inflammation or fibrosis), as assessed by multiparametric CMR, was present in >50% of our patients. The age- and sex-adjusted model showed that ASM on ECHO increased significantly the odds of increased extracellular volume [odds ratio (OR) 4.43, 95% CI 1.73, 11.38], increased T1 Relaxation time (OR 2.67, 95% CI 1.09, 6.54), increased T2 Relaxation time (OR 2.56, 95% CI 1.05, 6.22), increased signal intensity ratio in T2-weighted imaging (OR 2.56, 95% CI 1.05, 6.22), presence of late gadolinium enhancement (OR 3.85, 95% CI 1.52, 9.76) and mid-wall fibrosis (OR 3.64, 95% CI 1.48, 8.96). CONCLUSION: This study indicates that the presence of ASM on ECHO is a predictor of abnormal CMR in SSc patients, and a precise assessment of ASM may serve as an important point for selecting the patients that should be evaluated by CMR for early detection of myocardial involvement.

Post COVID-19 neuropsychiatric complications and therapeutic role for TNF-α inhibitors: a case series study.

Background: The post-COVID syndrome is the various physical and neuropsychiatric symptoms after the acute phase of COVID-19. The understanding of pathophysiology of this syndrome and its treatment need to further studies. This study aimed to present three cases of neuropsychiatric symptoms after COVID-19 and effective treatments in these patients. Case presentation: Three patients with new or progressively neuropsychiatric symptoms such as seizures, attention difficulties, insomnia, confusion and etc., were referred to our clinic about 8 months after severe COVID-19 infection. The patients were assessed with extensive workup includes a neurological exam, brain MRI, LORETA scan, and biochemical and levels of inflammatory serum markers. All patients had elevated levels of TNF-α, poor neurological exam, and abnormal reports of MRI or LORETA scan. Diagnosis of post- COVID neuropsychiatric complications was made for the patients.TNF inhibition with Adalimumab (40 mg/weekly for a month) was initiated for the patients and led to a dramatic improvement of all symptoms. Conclusions: To our knowledge, this report is the first case series study that suggests TNF inhibitors in the treatment of post-COVID-19 syndrome, especially neuropsychological complications. However, future studies should evaluate the best therapeutic options for this syndrome.

The effect of probiotic cheese consumption on inflammatory and anti-inflammatory markers, disease severity, and symptoms in patients with rheumatoid arthritis: study protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: In recent decades, several studies have shown changes in the intestinal microflora among patients with rheumatoid arthritis (RA). Therapeutic measures using probiotics have shown favorable effects on the recovery of these patients. However, most studies have used probiotic supplements. In this study, we aimed to investigate the effect of probiotic cheese consumption on inflammatory and anti-inflammatory factors, disease severity, and symptoms in these patients. METHODS: This study is a randomized, double-blind clinical trial, in which forty patients with mild to moderate severity of RA will be randomly allocated to receive either 30 g/day probiotic cheese (n = 20) or only low-salt and low-fat cheese without any added probiotic (n = 20) for 12 weeks. Assessment of anthropometric measures and biochemical indicators, including serum concentrations of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10), will be done at the study baseline and end of the trial. In addition, disease severity and disability will be assessed by DAS-28 and the HAQ-DI questionnaire, respectively. DISCUSSION: Diet is the leading environmental factor affecting the gut microbiota. A prebiotic-rich diet and probiotics might be beneficial in this regard. To the best of our knowledge, the effect of probiotic supplements on inflammation in these patients has widely been assessed; however, there is only one study that examined the effect of probiotic-containing food in these patients. Further studies are needed to investigate the effect of probiotic-containing foods on inflammatory markers and symptoms in patients with RA. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20201120049449N1 . Registered on 14 February 2021.

Upregulation of Unfolded Protein Response and ER Stress-Related IL-23 Production in M1 Macrophages from Ankylosing Spondylitis Patients.

The inflammatory interleukin (IL)-23/IL-17 axis plays an important role in the pathogenesis of ankylosing spondylitis (AS), but with an unknown regulatory mechanism. This study aimed to investigate the role of endoplasmic reticulum (ER) stress and autophagy pathway in the expression of IL-23 in peripheral blood-derived macrophages in AS patients. Peripheral blood samples were obtained from 15 AS and 15 healthy control subjects. MACS was used to isolate monocytes from PBMCs. Then, M-CSF was used to differentiate monocytes to M2 macrophages. IFN-γ and/or LPS were used to activate macrophages and M2 polarization towards M1 macrophages. Thapsigargin was used to induce ER stress and 3-MA to inhibit autophagy. The purity of extracted monocytes and macrophage markers was evaluated by flow cytometry. mRNA expression of HLA-B and-B27, ER stress-related genes, autophagy-related genes, and IL-23p19 was performed using RT-qPCR. Soluble levels of IL-23p19 were measured using ELISA. Significant increase in mRNA expression of HLA-B, HLA-B27, BiP, XBP1, CHOP, and PERK mRNAs was observed in macrophages of AS patients before and after stimulation with IFN-γ and LPS. No significant change in autophagy gene expression was detected. mRNA and soluble levels of IL-23p19 demonstrated a significant increase in macrophages of AS patients compared to healthy subjects. ER stress induction led to a significant increase in IL-23p19 in macrophages. Inhibition of autophagy did not affect IL-23 expression. ER stress, unlike autophagy, is associated with increased IL-23 levels in macrophages of AS patients.Key Messages ER stress in macrophages from AS patients plays a role in the increased production of IL-23. The autophagy pathway is not involved in the modulation of IL-23 production by AS macrophages.

Cervical cancer screening and Pap test non-adherence risk factors in systemic sclerosis patients.

Systemic sclerosis is a rare autoimmune disorder that potentially affects nearly every organ of the body. Malignancies are one of the most common non-systemic sclerosis related cause of mortality. There are controversial findings regarding the cervical cancer rate among these patients, but prolonged immunosuppressive medication makes them more susceptible to cervical cancer. In the present study, we have aimed to investigate the cervical cancer screening result and the Pap test non-adherence risk factors among systemic sclerosis patients. This cross-sectional study was conducted on 100 systemic sclerosis patients. The clinicodemographic variables in addition to cervical cancer risk factors were obtained from the patients. Pap test performed using the liquid-based method. The non-adherence risk factors were determined by univariate and multivariate logistic regression analysis. Benign inflammatory and atrophic changes were reported in 26 and 5%, respectively. None of the cases had abnormal cytological finding. Twenty-two percent of the participants were a routine Pap test performer. According to the multivariate model, higher age was associated with Pap test non-adherence [odds ratio (95% confidence interval): 1.058 (1.010-1.108) and P-value: 0.018]. In the present study, we have shown that compliance with Pap test performing is extremely low among Iranian systemic sclerosis patients. In addition, we have demonstrated that older age is a risk factor for non-adherence. These findings highlighted the crucial role of the physicians in motivating the patients toward cancer screening.

Bundle Branch Blocks and Fragmented QRS Complex in Iranian Patients with Systemic Sclerosis.

Background: Cardiac involvement, as one of the life-threatening manifestations of systemic sclerosis (SSc), is chiefly caused by collagen fiber deposition in the myocardium, which subsequently leads to conduction abnormalities. In the present study, we aimed to investigate the prevalence and clinical significance of bundle branch blocks (BBBs) and the fragmented QRS complex (fQRS) in Iranian patients with SSc. Methods: Forty-one patients with SSc were enrolled from the outpatient SSc clinic of Shariati Hospital, Tehran University of Medical Sciences, between October 2016 and February 2017. Twelve-lead ECG was obtained and interpreted for BBBs and the fQRS. To adjust for the confounding effects of non-SSc-related cardiovascular risk factors, we calculated the Framingham risk score to estimate the risk of cardiovascular diseases. The associations between the studied conduction abnormalities and SSc cutaneous subtypes; disease duration; and the Medsger SSc severity scale of cutaneous, pulmonary, and vascular involvements were also analyzed. Results: The study population consisted of 41 Iranian patients with SSc at a mean age of 47.48±11.57 years (82.9% female). The prevalence of BBBs and the fQRS was 26.8% and 36.6%, respectively. The fQRS was associated with the limited cutaneous SSc subtype (OR: 0.100, 95%CI: 0.018-0.553, and P=0.028). BBBs and the fQRS were not associated with either the Framingham risk score or the rest of the clinicodemographic variables. Conclusion: BBBs and the fQRS were more prevalent in our patients with SSc, without any association with the involvement of the other organs. These findings may suggest the independent pathophysiology of cardiac involvement in SSc.

The safety and efficacy of Guluronic acid (G2013) in ankylosing spondylitis: A randomized controlled parallel clinical trial.

BACKGROUND: To assess the therapeutic efficacy, safety and tolerability of Guluronic acid (G2013) in patients with ankylosing spondylitis (AS) patients. METHODS: This investigation was a 12-week randomized, placebo-controlled, phase I/II clinical trial involving 75 AS patients that were randomly divided into 3 groups: 25 as placebo, 25 Guluronic acid and 25 naproxen groups. Patients who had AS with active disease at baseline according to the modified New York criteria were considered for this trial. The primary consequence measure was the Appraisement of Spondyloarthritis International Society (ASAS) 20 response-rate at week 12. RESULTS: There were no statistically significant differences between groups at the entry. ASAS20 response at week 12 was achieved (60.8%) in patients receiving Guluronic acid compared with - (68.4% of) - patients in the naproxen group (p > 0.05) and (21.0%) of patients in the placebo group. In comparison with the placebo group from the baseline to week 12, patients who received Guluronic acid and naproxen showed significantly greater improvement in all secondary endpoints. Moreover, Guluronic acid decreased some inflammatory parameters more dramatically than naproxen and placebo group. Patients in the naproxen group had more incidence of gastrointestinal and others adverse events in comparison with Guluronic acid and placebo groups. CONCLUSION: The present research indicated that Guluronic acid and naproxen are similar in terms of efficacy. However, Guluronic acid had more notable safety characteristics identifying information than naproxen. Accordingly, it is proposed that Guluronic acid could be appropriate for management of AS. Clinical trial identifier; IRCT2016091813739N4.

Effect of food intake and ambient air pollution exposure on ankylosing spondylitis disease activity.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by axial arthritis. The genetic-environmental factors seem to be involved in the pathogenesis of the disease and the disease debilitates patients during the most productive stages of their lives. The aim of this study was to examine the relationships between two environmental factors, diet and air pollution with disease activity and functional impairment in AS. METHODS: A case-control study was carried out. Thirty patients with AS and 30 age and sex-matched healthy controls were included. Disease scores including BASMI, BASDAI, BASFI, and BASG were calculated by means of the international Ankylosing Spondylitis Assessment working group consensus recommendations. The food intake was evaluated by semi-quantitative food frequency questionnaire (147 items FFQ). Level of air pollution indices, PM10 and PM2.5 information was obtained from the Tehran air quality control network. RESULTS: Total energy and fat intake, some vitamins (A, B1, B2, C) and mineral intake (potassium, calcium, iron, phosphorus, magnesium, zinc, copper and selenium) were significantly higher in patients with AS compared to controls. Fat component consumption especially Saturated Fat of Food was moderately correlated with BASFI score. PM2.5 long term exposure was strongly correlated with BASMI, BASFI and BASDAI scores of patients. CONCLUSION: High-fat diet and long term exposure to air pollution are associated with worse disease outcomes reported in patients with AS. This is an interesting area of investigation in AS pathogenesis and management.

A randomized clinical trial for the assessment of the efficacy and safety of guluronic acid (G2013) in patients with rheumatoid arthritis.

Objective: To evaluate the safety, efficacy and tolerability of guluronic acid (G2013) in order to treat the rheumatoid arthritis patients who had inadequate response to conventional drugs. Methods: A randomized, 12-week clinical trial with two treatment arms: guluronic acid (G2013) and conventional treatment was performed. The diagnosed RA patients according to the ACR/European League against Rheumatism 2010 classification criteria, with an active disease at baseline that had inadequate response to conventional therapy were considered for the study. G2013 was administered orally twice a day with capsules of 500 mg during a period of 12 weeks and the patients were followed up for the safety and efficacy. Results: Our data showed that, the mean changes in the G2013 and control groups were -7.54 and -2.5 for tender joint count; -7.59 and -3.59 for swollen joint count; -30 and -0.9 for physician global assessment; -23.18 and -1.81 for patient global assessment; -14.45 and -1.45 for erythrocyte sedimentation rate, respectively. Improvements seen with G2013 were significantly greater than those with conventional drugs. In total, in 15.3% of G2013-treated patients and 69.2% of conventional-treated patients adverse events (AEs) occurred in this study. Conclusion: These data from routine rheumatology clinical practice highlight the effectivenessof G2013 in combination with conventional therapy with more desirable safety profile compared to the conventional-treated patients. Therefore, G2013 therapy could be an appropriate choice in order to manage the RA disease. (Clinical trial identifier: IRCT2016092813739N5).

Comparison of the clinical phenotype of systemic sclerosis patients in Iran and France in two university centers.

Objectives: Systemic sclerosis is a severe and rare chronic auto-immune multisystem disorder characterized by vasculopathy and skin stiffness. Ethnic and geographical origin can influence the outcomes. In this study, we compared the phenotypic characteristics of Iranian and French patients. Methods: This cross-sectional study was performed on 200 Iranian and 268 French systemic sclerosis patients. Iranian patients collected from the Iranian systemic sclerosis cohort of the Rheumatology Research Center, Shariati hospital, Tehran University of Medical Sciences. The French population was monocentric, and it was constituted by the patients included locally in the EUSTAR database in December 2016. Results: The mean age at onset was significantly lower in Iranian patients (35.58 ± 11.68 vs 47.06 ± 13.54, p-value < 0.001). The female-to-male ratio was approximately 5.2:1 and was not different in the two populations. The prevalence of diffuse cutaneous systemic sclerosis was significantly higher in Iranian patients (60.2% vs 42.85%, p-value < 0.001). Calcinosis cutis and joint synovitis were more prevalent in French patients (p-value = 0.013, <0.001). The positivity of anti-topoisomerase antibody was higher in Iranian patients, whereas the anti-centromere antibody predominated in French cases (p-value < 0.001). Restrictive pattern of pulmonary function test was more common in Iranian patients (p-value < 0.001), while estimated pulmonary arterial pressure by echocardiography was higher in French patients (p-value < 0.001). Conclusion: It seems that systemic sclerosis occurred in younger ages among Iranian female with the predominance of diffuse cutaneous subtype. In addition, lung interstitial disease appeared to be more prevalent and severe in Iranians than French patients.

Nailfold videocapillaroscopy changes in Takayasu arteritis and their association with disease activity and subclavian artery involvement.

INTRODUCTION: Takayasu arteritis (TA) is a large vessel vasculitis characterized by the involvement of the aorta and its branches. In the present study, the nailfold videocapillaroscopy (NVC) findings of the TA patients were evaluated and compared to healthy individuals. Additionally, the association of NVC abnormalities with disease activity and subclavian artery involvement was also investigated. METHOD: In the present study, NVC changes of 15 TA patients and 15 age- and sex-matched healthy controls were compared. The frequency of hypertension, dyslipidemia, and smoking status was not different between the case and control group. Capillary density, avascular area, tortuosity, micro-hemorrhages, and ramification were investigated. Among capillaries' diameters; capillary length and width, arterial and venous limbs diameters were also compared between two groups. RESULTS: The capillary length and venous limb diameter were lower in TA patients compared to control cases (P-value: 0.026 and 0.049, respectively). Moreover, TA patients have more tortuous capillaries (P-value: 0.035). Among TA patients; capillary length, width, arterial and venous limbs diameter was lower in hands with subclavian involvement (P-value: 0.014, 0.034, 0.009 and 0.022, respectively). Furthermore, the arterial and venous limbs diameter were lower in TA patients with active disease compared to patients with inactive disease (P-value: 0.018 and 0.049, respectively). CONCLUSION: In the present study, we have shown that the hands with subclavian artery involvement have short, thin and tortuous capillaries which could be secondary to hypoperfusion. To the best of our knowledge, this is the first report describing NVC changes in TA.

Effect of food intake and ambient air pollution exposure on ankylosing spondylitis disease activity

Abstract Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by axial arthritis. The genetic-environmental factors seem to be involved in the pathogenesis of the disease and the disease debilitates patients during the most productive stages of their lives. The aim of this study was to examine the relationships between two environmental factors, diet and air pollution with disease activity and functional impairment in AS. Methods: A case-control study was carried out. Thirty patients with AS and 30 age and sex-matched healthy controls were included. Disease scores including BASMI, BASDAI, BASFI, and BASG were calculated by means of the international Ankylosing Spondylitis Assessment working group consensus recommendations. The food intake was evaluated by semiquantitative food frequency questionnaire (147 items FFQ). Level of air pollution indices, PM10 and PM2.5 information was obtained from the Tehran air quality control network. Results: Total energy and fat intake, some vitamins (A, B1, B2, C) and mineral intake (potassium, calcium, iron, phosphorus, magnesium, zinc, copper and selenium) were significantly higher in patients with AS compared to controls. Fat component consumption especially Saturated Fat of Food was moderately correlated with BASFI score. PM2.5 long term exposure was strongly correlated with BASMI, BASFI and BASDAI scores of patients. Conclusion: High-fat diet and long term exposure to air pollution are associated with worse disease outcomes reported in patients with AS. This is an interesting area of investigation in AS pathogenesis and management.

Estimation and Prediction of Avoidable Health Care Costs of Cardiovascular Diseases and Type 2 Diabetes Through Adequate Dairy Food Consumption: A Systematic Review and Micro Simulation Modeling Study.

BACKGROUND: Recent evidence from prospective cohort studies show a relationship between consumption of dairy foods and cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM). This association highlights the importance of dairy foods consumption in prevention of these diseases and also reduction of associated healthcare costs. The aim of this study was to estimate avoidable healthcare costs of CVD and T2D through adequate dairy foods consumption in Iran. METHODS: This was a multistage modelling study. We conducted a systematic literature review in PubMed and EMBASE to identify any association between incidence of CVD and T2DM and dairy foods intake, and also associated relative risks. We obtained age- and sex-specific dairy foods consumption level and healthcare expenditures from national surveys and studies. Patient level simulation Markov models were constructed to predict the disease incidence, patient population size and associated healthcare costs for current and optimal dairy foods consumption at different time horizons (1, 5, 10 and 20 years). All parameters including costs and transition probabilities were defined as statistical distributions in the models, and all analyses were conducted by accounting for first and second order uncertainty. RESULTS: The systematic review results indicated that dairy foods consumption was inversely associated with incidence of T2DM, coronary heart disease (CHD) and stroke. We estimated that the introduction of a diet containing 3 servings of dairy foods per day may produce a $0.43 saving in annual per capita healthcare costs in Iran in the first year due to saving in cost of CVD and T2DM treatment. The estimated savings in per capita healthcare costs were $8.42, $39.97 and $190.25 in 5, 10 and 20-years' time, respectively. Corresponding total aggregated avoidable costs for the entire Iranian population within the study time horizons were $33.83, $661.31, $3,138.21 and $14,934.63 million, respectively. CONCLUSION: Our analysis demonstrated that increasing dairy foods consumption to recommended levels would be associated with reductions in healthcare costs. Further randomized trial studies are required to investigate the effect of dairy foods intake on cost of CVD and T2DM in the population.

A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of ß-D-mannuronic acid in rheumatoid arthritis patients.

BACKGROUND: Following the potent efficacy of ß-D-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy. METHOD: The study was a 12-week randomized, controlled, phase I/II clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study. M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfilling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety. RESULTS: There were no statistically significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient's adverse events occurred during this study. CONCLUSION: Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.

The effects of ß-D-mannuronic acid (M2000), as a novel NSAID, on COX1 and COX2 activities and gene expression in ankylosing spondylitis patients and the murine monocyte/macrophage, J774 cell line.

Ankylosing spondylitis (AS) is a debilitating chronic inflammatory disease with genetic predisposition, which is characterized by the involvement of spine and sacroiliac joints. Due to the relatively unsuccessful treatments, we designed ß-D-mannuronic (M2000) with the beneficial effects in various experimental models as a novel non-steroidal anti-inflammatory drug (NSAID). The aims of our present study were: first, to compare the therapeutic effects of M2000, as a novel designed NSAID, with naproxen and placebo in Iranian patients with AS during 12 weeks; second, to evaluate the effect of M2000 on gene expression of cyclooxygenase enzyme (COX-1/COX-2), a key enzyme in the initiation of inflammatory pathways in AS patients; and third, to assess the activity of COX-1 and COX-2 enzymes in the presence/absence of M2000 at the different doses in the murine macrophage, J774 cell line. This was a sub-study of phase II, randomized, placebo-controlled trial with three treatment arms: M2000, naproxen, and placebo. The outcome measures were the mean changes from baseline to week 12. The gene expression was assessed by real-time PCR. The COX-1 and COX-2 activities were evaluated by ELISA in J774 cell line induced by LPS and arachidonic acid (AA). Our findings demonstrated that M2000 had beneficial therapeutic effects on pain, stiffness, and inflammation, whereas no adverse effects were observed following the use of M2000 after 12 weeks. The analysis of gene expression showed that M2000 could effectively reduce the expression levels of COX-1 and COX-2 in comparison with untreated patients. In addition, the enzymatic activities in the presence of M2000 were significantly less than LPS- and AA-treated groups. Our results indicate that M2000, as a novel designed NSAID with immunosuppressive properties, can be considered as one of the therapeutic options for the treatment of inflammatory diseases without adverse events. Clinical trial identifier IRCT2013062213739N1/ http://www.IRCT.ir .

Targeting of circulating Th17 cells by ß-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis.

OBJECTIVE: This study aimed at investigating the inhibitory effect of ß-D-mannuronic acid (M2000) on the Th17 circulating levels and IL-17 a related cytokine in rheumatoid arthritis (RA) patients. METHODS: The study included 27 patients with RA who had failed response to treatment. All patients were treated orally by M2000 at a dose of 500 mg twice daily for 12 weeks (Clinical trial identifier: IRCT2014011213739N2). The patients based on anti-tumor necrosis factor alpha (TNFα) blocker treatment were classified into two groups (conventional group and etanercept group). They were then allowed to continue their treatment excluding non-steroidal anti-inflammatory drugs (NSAIDs). The frequency of circulating Th17 cells and IL-17 serum level were determined before and 12 weeks after M2000 therapy and were compared to the healthy controls by using flow cytometry analysis and ELISA method, respectively. RESULTS: At baseline, higher circulating Th17 and IL-17 serum levels were significantly observed in both groups of RA patients than in the healthy controls (all P < 0.001). The frequency of Th17 cells significantly decreased in the conventional group as well as in the etanercept group after M2000 therapy but the level of reduction was higher in the conventional group compared to the etanercept group (P < 0.03 and P < 0.04, respectively). The IL-17 serum level significantly decreased in both groups after M2000 therapy (P < 0.01 and P < 0.02, respectively). Furthermore, the frequency of Th17 cells was positively correlated with Disease Activity Score (DAS28) (r = 0.34, P = 0.02). CONCLUSION: M2000 shows the inhibitory effect on the frequency of circulating Th17 cells as well as in the production of IL-17 in RA patients.

Evaluation of the efficacy and safety of ß-d-mannuronic acid in patients with ankylosing spondylitis: A 12-week randomized, placebo-controlled, phase I/II clinical trial.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of ß-d-mannuronic acid (M2000) in the treatment of ankylosing spondylitis (AS). METHODS: The study was a 12-week randomized, double-blind, placebo-controlled, phase I/II clinical trial with 3 treatment arms: placebo, ß-d-mannuronic acid and naproxen. Patients who had AS according to the modified New York criteria, with active disease at baseline were eligible for study. Primary outcome measure was the Assessment of SpondyloArthritis international Society (ASAS) 20 response rate at week 12. RESULTS: Of the 85 randomized patients, 27 were allocated to receive placebo, 28 naproxen, and 30 ß-d-mannuronic acid. There were no statistically significant differences between treatment groups at baseline. Of the patients receiving ß-d-mannuronic acid, 57.7% achieved an ASAS20 response at week 12, compared with 59% of the patients in the naproxen group (P>0.05) and 19% of the patients in the placebo group (P=0.007). In comparison with patients receiving placebo over the 12-week treatment period, those receiving ß-d-mannuronic acid and naproxen demonstrated statistically significantly greater improvement in all secondary endpoints. Interestingly, ß-d-mannuronic acid reduced some parameters associated with inflammation more effectively than naproxen and placebo. The incidence of gastrointestinal and other adverse events were higher on naproxen than on ß-d-mannuronic acid and placebo. CONCLUSION: The present study demonstrated similar efficacy, but with a more favorable safety profile for ß-d-mannuronic acid than naproxen and, therefore, suggest that ß-d-mannuronic acid is suitable for the management of AS. TRIAL REGISTRATION: Iranian registry of clinical trials; www.irct.ir; IRCT2013062213739N1.

Hematological Improvement of Patients with Active Rheumatoid Arthritis by ß-D-Mannuronic Acid (M2000) as a Novel NSAID with Immunosuppressive Property.

The aim of this study was to investigate the effect of ß-D-mannuronic acid (M2000) on hematological parameters in patients with active rheumatoid arthritis. This study was conducted on 25 patients with active rheumatoid arthritis (RA) (identifier: IRCT2014011213739N2). M2000 was administered orally for anemic and non-anemic RA patients at a dose of 500 mg twice daily for 12 weeks. The patients were permitted to continue the conventional treatments excluding NSAIDs. Blood samples were collected at baseline, 4 and 12 weeks after drug administration and were tested for hematological parameters. Moreover, serum levels of TNF-α and IL-6 were analysed before and after M2000 therapy compared to healthy controls using enzyme linked immunosorbent assay method. We found a significant increase in the count of red blood cells and also hemoglobin (Hb) concentration (0.9 g/dL) in anemic patients after 12 weeks of M2000 therapy (p<0.02 and p<0.01, respectively). Furthermore, our results showed an improvement in Hb level (0.45 g/dL) even in non-anemic patients who were treated by M2000 (p<0.04). The leukocytosis in RA patients, significantly decreased in both anemic and non-anemic patients after 12 weeks of M2000 therapy (p<0.02 and p<0.03, respectively). The percent of neutrophils significantly increased in anemic patients (p<0.01) while in non-anemic patients it significantly decreased after 12 weeks of M2000 therapy (p<0.01). The serum levels of IL-6 and TNF-α significantly decreased after 12 weeks of M2000 therapy (p<0.01 and p<0.04, respectively). M2000 improves hematological parameters in RA patients by its potent inhibitory effect on serum levels of TNF-α and IL-6.

Downregulation of Aquaporin3 in Systemic Sclerosis Dermal Fibroblasts.

Skin dryness and thickening are hallmarks of systemic sclerosis (SSc) disease. Aquaporins (AQPs) are plasma membrane proteins that transport glycerol and water, resulting in water retention and skin hydration. Expression of AQPs has been evaluated in human normal skin. However, expression of these proteins in SSc dermal fibroblasts has not yet been reported. The aim of this study was to assess the expression profile of AQPs in dermal fibroblasts of SSc patients. Fibroblast cells were extracted from SSc and healthy skin biopsies and characterized using fibroblast surface protein antibody. The SYBR Green Real-time PCR was used to evaluate the mRNA expression of AQP1, 3, 5, 7, 9, and 10 in dermal fibroblasts. Immunoblotting was performed to confirm the results of Real-time PCR. Our data demonstrated that only AQP1, AQP3, and AQP9 were expressed in human skin fibroblasts. Moreover, the expression of AQP3 mRNA and protein were significantly decreased in SSc dermal fibroblasts compare to healthy fibroblasts. AQP3, which involves in skin hydration and wound healing through water and glycerol transmission, is downregulated in SSc fibroblasts. Based on previous studies and our results, it seems that SSc manifestations like skin dryness, abnormal wound healing, and fibrotic lesions may be related to downregulation of AQP3 in SSc fibroblasts. Therefore, induction of AQP3 expression can be a potential treatment to relieve SSc skin thickness in the future.

A Multidisciplinary Workplace Intervention for Chronic Low Back Pain among Nursing Assistants in Iran.

STUDY DESIGN: Interventional research with a 6-month follow-up period. PURPOSE: We aimed to establish the effectiveness of a multidisciplinary workplace intervention on reduction of work-related low back pain (WRLBP), using ergonomic posture training coupled with an educational program based on social cognitive theory. OVERVIEW OF LITERATURE: WRLBP is a major occupational problem among healthcare workers, who are often required to lift heavy loads. Patient handling is a particular requirement of nurse aides, and has been reported as the main cause of chronic WRLBP. METHODS: We included 125 nursing assistants from two hospitals affiliated to Qom University of Medical Sciences from May to December 2015. There was an intervention hospital with a number of 63 nursing assistants who received four multidisciplinary educational sessions for 2 hours each plus ergonomic posture training over two days and a control hospital with a number of 62 nursing assistants who didn't receive educational intervention about low back pain. The outcomes of interest were reductions in WRLBP intensity and disability from baseline to the follow up at 6 months, which were measured using a visual analog scale and the Quebec Disability Scale. Descriptive and analytical statistics were used to analyze the data. RESULTS: The comparison tests showed significant change from baseline in reduction of WRLBP intensity following the multidisciplinary program, with scores of 5.01±1.97 to 3.42±2.53 after 6 months on the visual analog scale in the intervention group (p<0.001) and no significant change in control groups. There was no significant difference in the disability scores between the two groups (p=0.07). CONCLUSIONS: We showed that our multidisciplinary intervention could reduce the intensity of WRLBP among nurse aides, making them suitable for implementation in programs to improve WRLBP among nursing assistants working in hospitals.