The effect of eucalyptus inhalation on pain and the quality of life in rheumatoid arthritis.

Problem considered: Pain is one of the most significant symptoms of rheumatoid arthritis that reduce the quality of life. The purpose of the study was to determine the effect of eucalyptus on pain and the quality of life in patients with rheumatoid arthritis. Methods: In this randomized clinical trial, 70 patients with rheumatoid arthritis were selected by random sampling. In the eucalyptus group, 1 mL of eucalyptus oil was inhaled for 5 min, 3 times a day, for one month. The control group received placebo inhalation. Both groups used routine treatments. Data were collected using a questionnaire of demographics, the numerical pain rating scale (NRS), and Quality of Life (SF-12). Statistical analysis was done using 19th edition SPSS software and applied on paired t-test, chi-square, Fisher's exact test, and analysis of covariance. Results: The mean score of pain severity in the eucalyptus group significantly decreased in comparison with the control group (P < 0.001). The severity of pain there was no statistical difference in both groups before, the first, and the second weeks after the intervention, (p > 0.05); however, in the third and fourth weeks after the intervention, the mean severity of pain in the eucalyptus group was lower than in the control group, and these differences were statistically significant between the two groups (p < 0.05). Also, the patients' quality of life in the eucalyptus group was increased significantly (P < 0.001). Conclusion: The eucalyptus leads to pain reduction, and consequently, improves the quality of life of patients with rheumatoid arthritis. Trial registration: IRCT20160110025929N15 Registration date: 2018-10-07; https://en.irct.ir/trial/33573.

Peripheral distributions of IL-4-producing CD4 + T cells and CD4 + CD25 + FoxP3 + T cells (Tregs) in rheumatoid arthritis patients with poor response to therapy are associated with HLA shared epitope alleles and ACPA status.

Specific profiling of CD4 + T cell subsets in the circulation and inflamed joints of rheumatoid arthritis (RA) patients may have therapeutic implications. This study aimed to evaluate the peripheral distributions of Th2 and Treg cells in relation to HLA-shared epitope (SE) alleles and anti-cyclic citrullinated peptide antibody (ACPAs) status in patients with good response (GR) and poor response (PR) to treatment. The frequencies of IL-4-producing CD4 + T cells (Th2) and CD4 + CD25 + Foxp3 + T cells (Tregs) were determined by flow cytometry in 167 RA patients including 114 GR and 53 PR cases. CD4 + T cell subsets were also analyzed based on HLA-SE and ACPAs statuses. One hundred nine of 167 patients were positives for HLA-SE, 63.4% for ACPAs, 43.7% for SE/ACPAs and 14.9% were negatives for SE/ACPAs. Higher frequencies of Th2 (P = 0.001) and Treg cells (P = 0.03) were found in the patients versus controls. Increased and decreased frequencies of Th2 and Tregs cells were observed in the PR versus GR patients respectively (P = 0.003 and P = 0.004). Higher proportions of Th2 cells were observed in the SE+RA versus SE-RA (P = 0.001), in ACPA+RA versus ACPA-RA (P = 0.005) and in the SE+ACPA+RA versus SE-ACPA-RA patients (P = 0.002). Treg cells frequencies decreased in the SE+RA versus SE-RA (P = 0.03) and in SE+ACPA+RA versus SE-ACPA-RA (P = 0.02). ACPA+GR and SE+PR patients showed higher proportions of Th2 cells than ACPA-GR and SE-PR patients respectively (P = 0.02 and P = 0.01). Analysis of the CD4 + T cell subsets profiles in conjunction with genetic background and autoantibodies patterns can be useful for precise therapeutic response monitoring in the RA patients.

Relevance of autoantibody profile with HLA-DRB1 and -DQB1 alleles in a group of Iranian systemic lupus erythematosus patients.

BACKGROUND: One of the most relevant genetic components in systemic lupus erythematosus (SLE) is human leukocyte antigen (HLA) gene complex which plays a central role in autoimmune responses. This study aimed to explore the associations of HLA-DRB1/-DQB1 alleles and haplotypes with SLE risk and the appearance of autoantibodies in SLE disease. METHODS: A total of 127 SLE patients and 153 ethnically matched healthy controls were enrolled. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP method and then HLA alleles and haplotypes frequencies were compared between two groups and among the patients in terms of autoantibodies spectrum. RESULTS: We found that HLA-DRB1*03 and HLA-DRB1*16 alleles were significantly associated with increased risk (P = 0.008, PC=0.05 and P = 0.002, PC=0.02 respectively) and DRB1*01 conferred a potential protective role for disease (P = 0.03, PC=0.13). Similar associations were observed at haplotype level; DRB1*03~DQB1*02 (OR1.91,P = 0.01, PC=0.08), DRB1*16~DQB1*05 (OR3.65,P = 0.004,PC=0.06) and DRB1*01~DQB1*05 (OR0.36,P = 0.04, PC=0.22). Remarkably, we observed significantly associations of DRB1*03 with the appearance of anti-SSA/Ro (PC=0.02), anti-SSB/La (PC=0.002) and anti-coagulant (P = 0.007), DRB1*15 with anti-SSA/Ro (PC=0.04), DRB1*16 with anti-Sm (PC=0.02), DRB1*04 with anti-ß2gpI (PC=3 * 10-5), anti-cardiolipin (P = 0.002) and rheumatoid factor (P = 0.004) and DRB1*13 with anti-Sm (PC=0.02) and anti-ß2gpI (PC=0.01) antibodies. Also, negative associations of DRB1*04 with anti-Sm, anti-SSA/Ro, DQB1*03 with anti-Sm and DRB1*11 with anti-Sm and anti-ß2gpI were observed. CONCLUSIONS: We identified DRB1*03 and DRB1*16 as risk alleles and DRB1*01 as a potential protective allele for SLE disease. More importantly, we found a close link between genetic susceptibility for SLE and autoantibodies status that was more evident for DRB1*03 allele.

Non-closed acoustic cloaking devices enabled by sequential-step linear coordinate transformations.

Hitherto acoustic cloaking devices, which conceal objects externally, depend on objects' characteristics. Despite previous works, we design cloaking devices placed adjacent to an arbitrary object and make it invisible without the need to make it enclosed. Applying sequential linear coordinate transformations leads to a non-closed acoustic cloak with homogeneous materials, creating an open invisible region. Firstly, we propose to design a non-closed carpet cloak to conceal objects on a reflecting plane. Numerical simulations verify the cloaking effect, which is completely independent of the geometry and material properties of the hidden object. Moreover, we extend this idea to achieve a directional acoustic cloak with homogeneous materials that can render arbitrary objects in free space invisible to incident radiation. To demonstrate the feasibility of the realization, a non-resonant meta-atom is utilized which dramatically facilitated the physical realization of our design. Due to the simple acoustic constitutive parameters of the presented structures, this work paves the way toward realization of non-closed acoustic devices, which could find applications in airborne sound manipulation and underwater demands.

Altered expression of microRNAs may predict therapeutic response in rheumatoid arthritis patients.

BACKGROUND: Epigenetic alternations of microRNAs (miRNAs) can contribute to the pathogenesis and progression of rheumatoid arthritis (RA). This study aimed to measure the expression level of peripheral blood miRNAs, as well as their target mRNAs, in RA patients and healthy controls (HCs), and to evaluate the potential of miRNAs as promising non-invasive biomarkers of treatment response. METHODS: The peripheral expression of miRNAs, including miR-146a, miR-146b, miR-150, miR-155, miR-125a-5p, miR-223, miR-26a, and miR-21, as well as their target mRNAs, was analyzed in 90 RA patients and 30 HCs via quantitative real-time polymerase chain reaction (RT-PCR) assay. We compared differences between the patients in terms of good response (GR; n = 55) and poor response (PR; n = 35) to the conventional therapeutic approach. RESULTS: All miRNAs were significantly overexpressed in RA patients. The expression of miR-155, miR-150, miR-146a, miR-146b, miR-125a-5p, and miR-223 increased in both groups of RA patients, compared to HCs, and miR-26a and miR-21 were the only upregulated miRNAs in the GR group versus HCs. Among the upregulated miRNAs, miR-125a-5p expression significantly changed in GR and PR patients (P = 0.047). The ROC curve analysis indicated the potential involvement of miR-125a-5p in the pathogenesis of RA. We also observed the downregulated expression of GATA3, RORC, FOXP3, TBX21, STAT1, and TRAF6 in RA patients versus HCs. CONCLUSION: Our findings indicated that different expression levels of miR-125a-5p in the GR and PR groups of patients may serve as a therapeutic response biomarker, which can be also used as a target for therapeutic interventions.

Circulating IFN-γ producing CD4+ T cells and IL-17A producing CD4+ T cells, HLA-shared epitope and ACPA may characterize the clinical response to therapy in rheumatoid arthritis patients.

This study analyzed the association between peripheral distributions of helper T cell subsets, HLA shared-epitope (SE), anti-cyclic citrullinated peptide antibody (ACPA) and clinical response to therapy in rheumatoid arthritis (RA) patients. Frequencies of IFN-γ-producing CD4+T (Th1) and IL-17A-producing CD4+T (Th17) cells were determined by flow cytometry in 167 patients (114 cases with good-response (GR) and 53 poor-response (PR) based on DAS28). HLA-DRB1 alleles for patients and 150 healthy controls were determined by PCR-SSP. We observed that 65.2% of RA patients were SE+, 63.4%ACPA+, 43.7%SE+ACPA+ and 14.9% were SE-ACPA-. Higher significantly proportions of Th1 and Th17 cells were found in RA patients than controls (P < 0.05) as well as in the SE+ or ACPA+RA patients compared to SE- and ACPA- patients. Increased frequencies of both Th subsets were found in SE+ACPA+ versus SE-ACPA- patients (P < 0.001) and in the PR versus GR group (P < 0.001). We showed significant differences for Th cells frequencies between SE+ and SE- patients in both groups, and between ACPA+ and ACPA- cases in the PR group. Our findings suggest a close link between Th1 and Th17 cells proportions and HLA-SE/ACPA in the RA patients and remarkably in the PR group which could be indicative for the importance of immune monitoring for evaluation of response to therapy.

Development and psychometric properties of a self-care behaviors scale (SCBS) among patients with rheumatoid arthritis.

BACKGROUND: The role of self-care behaviors in promoting physical function, pain management, health status and quality of life among patients with Rheumatoid Arthritis (RA) is well documented. However, there is no valid and reliable instrument in the literature to assess such behaviors among the patients. In the present study, we aimed to develop and assess the psychometric properties of a Self-care Behaviors Scale (SCBS) among patients with RA. METHODS: In 2017, applying a cross-sectional design, we recruited a convenient sample of 436 RA patients in Hamadan, Iran, to participate in the study. We developed the initial scale, including 30 items, after literature review, and having recommendations from an expert panel. Face, content, construct and convergent validity, as well as reliability of the scale were investigated. RESULTS: In Exploratory Factor Analysis, the optimal solution comprising 25 items and 7 factors was emerged, which explained 62.5% of all variances between the items. In Confirmatory Factor Analysis, the measurement model fit the data well, and all subscales were significant within an acceptable range (χ2 [233] = 428.654, p < 0.0001, comparative fit index = 0.942, normed fit index =0.907, Tucker-Lewis index =0.916, and root mean square error of approximation = 0.043[(0.037-0.05]). CONCLUSION: The Self-care Behaviors Scale was found with appropriate validity, reliability, functionality and simplicity. To our knowledge, this scale is the only valid and reliable RA specific self-care behavior scale in the literature. Healthcare providers and health practitioners may apply the English version of this suitable instrument to find more valid and reliable data on RA self-care behaviors during primary assessments of the behaviors in educational interventions for the patients.

A Pilot Study to Evaluate the Effects of Oral N-Acetyl Cysteine on Inflammatory and Oxidative Stress Biomarkers in Rheumatoid Arthritis.

BACKGROUND: Rheumatoid Arthritis (RA) is a common inflammatory disease of the joints. Due to the importance of inflammation and oxidative stress in the pathogenesis of RA, drugs that have anti-oxidant and anti-inflammatory properties, such as N-acetyl Cysteine (NAC), can be used as adjunctive therapy in patients with RA. AIMS: The aim of this study was to evaluate the effects of oral NAC on inflammatory cytokines and oxidative stress in patients with RA. METHODS: Adjunct to standard treatment, the NAC group (23 patients) received 600 mg of NAC twice daily and the placebo group (19 patients) received identical placebo twice daily for 12 weeks. Serum levels of Total Oxidant Status (TOS), Total Antioxidant Capacity (TAC), nitric oxide (NO), Total Thiol Groups (TTG), Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin- 6 (IL-6), C-reactive Protein (CRP), and Erythrocyte Sedimentation Rate (ESR) were measured at baseline and at the end of the study. RESULTS: Results showed that in the NAC group, the serum levels of MDA, NO, IL-6, TNF-α, ESR and CRP were significantly lower than the baseline. Also, the serum level of TAC and TTG, as antioxidant parameters, increased significantly. However, only NO, MDA and TTG showed a significant difference in the NAC group as compared to the placebo group at the end of study. CONCLUSION: According to the results of this study, oral NAC can significantly reduce the several oxidative stress factors and inflammatory cytokines. These results need to be confirmed in larger studies while considering clinical outcomes of RA patients.

Evaluating the Effect of Oral N-acetylcysteine as an Adjuvant Treatment on Clinical Outcomes of Patients with Rheumatoid Arthritis: A Randomized, Double Blind Clinical Trial.

OBJECTIVE: Oxidative stress and Overproduction of pro-inflammatory cytokines are contributed in Rheumatoid Arthritis (RA) pathogenesis. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent which demonstrated analgesic effects in some studies. This study is designed to assess the effects of oral NAC as an adjuvant therapy on the clinical outcomes of patients with active RA. METHODS: In this randomized clinical trial, 51 RA patients with active RA were studied in 2 groups: NAC group (27 patients) received standard treatment of RA and 600 mg NAC twice a day for 12 weeks, and placebo group (24 patients) received the standard treatment of RA and placebo. Disease activity score (DAS28) was used to assess the activity of RA, Visual Analog Scale (VAS) for the severity of pain, Health Assessment Questionnaire (HAQ) for the patients' physical performance, and Global Health (GH) parameter for the patients' assessment of their disease activity. The number of tender and swollen joints and Erythrocyte Sedimentation Rate (ESR) were also determined for each patient. Data were analyzed using SPSS version 16.0 (Chicago, IL, USA). RESULTS: After 12 weeks of intervention, there were no significant differences between two groups in DAS28 score and ESR (P values were 0.4 and 0.6, respectively). However, GH, VAS, and HAQ scores were improved significantly in the NAC group compared to the placebo group. CONCLUSION: Our findings indicate that oral administration of NAC may be associated with improving health status in RA patients and considered as an adjuvant therapy in these patients. Further studies with larger sample size, longer study duration and higher doses of NAC are needed to confirm the effects of oral NAC in RA patients.

Vitamin D3 inhibits the proliferation of T helper cells, downregulate CD4+ T cell cytokines and upregulate inhibitory markers.

1 α, 25-dihydroxyvitamin D3 (VitD3) has been suggested to have strong modulatory properties in the immune system. Researchers in the present study primarily aimed to understand the effect of VitD3 on human CD4+ T cell proliferation in antigen presenting cells (APCs) free condition in vitro. The effect of VitD3 on intracellular cytokine responses trend to Th1, Th2, Th17 and Th22 was evaluated using the flow cytometry. Moreover the effect of VitD3 on the expression of inhibitory markers such as PD1, PD-L1, and CTLA4 which are induced upon polyclonal T cell receptor (TCR) activation on CD4+ T cells, was assessed. We observed that the stimulation of CD4+ T cells with VitD3, suppressed proliferation capacity, enhanced the expression of PD1, PD-L1 and CTLA4 inhibitory markers on CD4+ T cells, and diminished the percentage of pro-inflammatory cytokines including, IFN-γ, IL-17, and IL-22 except IL-4 in CD4+ T cells. The data suggested a potential insight into the consideration of VitD3 in the prevention/control of pro-inflammatory immune response/autoimmune disorders.

Topical Effects of Artemisia Absinthium Ointment and Liniment in Comparison with Piroxicam Gel in Patients with Knee Joint Osteoarthritis: A Randomized Double-Blind Controlled Trial.

BACKGROUND: Pain alleviation and improvement of functional status are the main objectives in the treatment of osteoarthritis. Artemisia absinthium (AA) was used traditionally in reducing pain and inflammation. The aim of the present study was to compare the effects of topical formulations of AA and piroxicam gel (PG) among patients with knee osteoarthritis. METHODS: In total, 90 outpatients aged 30-70 years with the diagnosis of primary osteoarthritis in at least one knee were enrolled in a randomized double-blind clinical trial. The patients referred to the Rheumatology Clinic at Shahid Beheshti Hospital in Hamadan province during 2012-2013. The patients were randomly assigned into three groups, 30 patients per group, and respectively received AA ointment (AAO) 3%, AA liniment (AAL) 3%, and PG; three times daily (TID) for 4 weeks. The patients were visited at baseline, week 4, and week 6. The effectiveness criteria were pain severity which was assessed with a 10-point visual analog scale (VAS), the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) for total pain score (WTPS), total physical function score (WTPFS), and total stiffness score (WTSS). Repeated measure ANOVA, paired t test and post hoc were used to compare variables. Statistical analysis was performed using the SPSS software, version 13.0 (SPSS Inc., Chicago, Illinois). RESULTS: All groups had similar patient demographics. The administration of PG significantly improved all tested criteria with no recurrence after discontinuing the treatment protocol. AAO alleviated all tested factors except for WTSS. Alleviation was comparable to PG. AAL only reduced pain factors (VAS, WTPS) in week 4 with recurrence in week 6. CONCLUSION: Administration of Artemisia ointment may have beneficial effects in the treatment of osteoarthritis. Trial Registration Number: IRCT201202123109N3.

The hospital resource utilization associated with osteoporotic hip fractures in Kermanshah, Iran.

BACKGROUND: Hip fracture is the most serious complication of osteoporosis and imposes a significant financial burden on countries' economy. This study aimed to assess the hospitalization costs and length of stay associated with osteoporosis hip fractures and identify the major cost components in a referral hospital in Kermanshah city, Iran. METHODS: In a prospective study, from May 21 2007 to May 21 2008, all patients with osteoporotic hip fracture admitted to a referral hospital for operation were recruited as the study sample. For each patient, information such as age, gender, length of stay (LOS) in hospital and intensive care unit (ICU), medical and diagnostic procedures and cost of surgery and implant were collected both through interview with the patient or a family member and the patients' hospital records. RESULTS: A total of 103 patients (56 men and 47 women) were studied. The average hospital length of stay (LOS) for the patients was 9.7 days, ranging from 5 to 38 days. The average total hospitalization costs was 7,208,588 IRR (US$774). The main components of the costs were ward stay (16.3%), operative (54.6%), implant (26%) and medical and diagnostic procedures (3.1%). CONCLUSIONS: The results of this study demonstrate that the hospital resource burden associated with osteoporotic hip fractures in Iran is substantial and expected to rise with the projected increase of life expectancy and the number of elderly in Iran. Estimating the economic burden of osteoporotic hip fractures provide information that can be of importance in the planning and design of preventive strategies.

The prevalence of anticardiolipin antibody in patients with systemic lupus erythematosus and its association with clinical manifestations.

The central immunological disturbance in systemic lupus erythematosus (SLE) is autoantibody production. Some of these antibodies affecting components of the cell nucleus are the major characteristics of SLE. The present study was aimed to assess importance of anticardiolipin (ACL) antibody and its association with clinical state in SLE patients. A cross sectional study was performed on 100 patients with SLE referred to rheumatology outpatient clinic in Ekbatan hospital in Hamadan (Iran) between 2007 and 2008. Serum samples were extracted and screened for IgG and IgM using an ACL enzyme-linked immunosorbent assay. Up to 36% of patients were positive for ACL antibody that was more frequent in women than men (39.8% versus 8.3%). No association was revealed between ACL antibody and age. Clinical manifestations of antiphospholipid antibody syndrome were observed in 23.0% of patients that was more prevalent in ACL positive group compared with ACL negative group (41.7% versus 125%). The prevalence of other manifestations including pregnancy-related disorders (recurrent abortion), central nervous system defects, and deep vein thrombosis was 33.3%, 25.0%, and 30.6% in ACL positive group and was 9.4%, 7.8%, and 7.8% in ACL negative group that all were more frequent in the former group. The prevalence of thrombocytopenia was also higher in ACL positive group than another group (22.2% versus 15.6%). Among ACL positive patients with clinical manifestations of antiphospholipid antibody syndrome, 86.6% had medium to high titer of ACL. Our study emphasized value of (ACL) antibody to assess clinical status in SLE patients.

Effect of rheumatoid arthritis on periodontitis: a historical cohort study.

PURPOSE: Rheumatoid arthritis (RA) is a chronic multi-systemic disease that causes damage to the bone and connective tissues. This study was conducted in order to accurately measure the correlation between RA and periodontitis, and to obtain an unbiased estimate of the effect of RA on periodontal indices. METHODS: In this historical cohort study, which was conducted from February to May 2011 in Hamadan city, Iran, 53 exposed people (with RA) were compared with 53 unexposed people (without RA) in terms of clinical periodontal indices (the outcomes of interest) including 1) plaque index (PI), 2) bleeding on probing (BOP), and 3) clinical attachment loss (CAL). RESULTS: A sample of 106 volunteers were evaluated, 53 rheumatoid versus 53 non-rheumatoid subjects. There was a statistically significant correlation between RA and BOP (P<0.001) and between RA and CAL (P<0.001). However, there was no statistically significant correlation between RA and any of the periodontal indices. No correlation was seen between gender and any of the indices either. There was a strong positive correlation between age and all three periodontal indices (P<0.001). CONCLUSIONS: The present study indicated a potential effect of RA on periodontal indices. However, much more evidence based on a prospective cohort study is needed to support the cause and effect relationship between RA and periodontal indices.