Efficacy and safety of intraarticular corticosteroid injections in adolescents with juvenile idiopathic arthritis in the temporomandibular joint: a Norwegian 2-year prospective multicenter pilot study

Background Intraarticular corticosteroids (IACs) have been used to treat temporomandibular joint (TMJ) arthritis. However, prospective clinical studies with magnetic resonance imaging (MRI) scoring are lacking. The aim of this study was to examine efficacy and safety of a single IAC in the TMJ in adolescents with juvenile idiopathic arthritis (JIA) in a clinical setting. Methods In this Norwegian prospective multicenter pilot study 15 patients with JIA (mostly persistent oligoarthritis or RF negative polyarthritis categories) and a clinically and MRI-verified diagnosis of TMJ arthritis were treated with IACs and followed for 2 years. Demographics, systemic medication, general disease activity and outcome measures were recorded including a pain-index score and maximal incisal opening (MIO). Inflammation and bone damage scores were assessed, using two recently published MRI scoring systems with masked radiological evaluation. Results Among the 15 patients, 13 received a single IAC (5 bilateral), and 2 repeated IACs once unilaterally. Thus, the total number of IACs was 22. Median age was 15 years and the majority had an age not thought of as critical regarding mandibular growth retardation due to steroid injection. During the 2-year observation period systemic medication with disease modifying antirheumatic drugs (DMARDs) including biologics was initiated or adjusted in 10/15 (67%) patients. At the 2-months study visit after injection we observed a minimal improvement in MIO from median 44 (1st, 3rd quartiles; 36, 48) mm to 45 (43, 47) mm, p = 0.045 and decreased MRI mean additive inflammatory score from 4.4 ± 1.8 standard deviations (SD) to 3.4 ± 2.0, p = 0.040. From baseline to the 2-months follow-up pain improved in 6/11 patients but pain scores were not significantly improved. MRI-assessed damage increased in two patients with repeated IACs, and decreased in 3 patients but most of the patients were stable over the 2-year follow-up. Intra-rater repeatability of the MRI scoring system domains varied from poor to excellent. Conclusions In this pilot study of predominately single IACs to the TMJ in combination with systemic treatment we observed improvement in MRI-assessed inflammation, mostly stable condylar bone conditions and minimal clinical improvement in adolescents with JIA and TMJ arthritis. No severe side effects were seen.publishedVersio

Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study

Background: The oral microbiota has been connected to the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. The objective of this study was to characterize the salivary oral microbiome associated with juvenile idiopathic arthritis (JIA), and correlate it with the disease activity including gingival inflammation. Methods: Fifty-nine patients with JIA (mean age, 12.6 ± 2.7 years) and 34 healthy controls (HC; mean age 12.3 ± 3.0 years) were consecutively recruited in this Norwegian cross-sectional study. Information about demographics, disease activity, medication history, frequency of tooth brushing and a modified version of the gingival bleeding index (GBI) and the simplified oral hygiene index (OHI-S) was obtained. Microbiome profiling of saliva samples was performed by sequencing of the V1-V3 region of the 16S rRNA gene, coupled with a species-level taxonomy assignment algorithm; QIIME, LEfSe and R-package for Spearman correlation matrix were used for downstream analysis. Results: There were no significant differences between JIA and HC in alpha- and beta-diversity. However, differential abundance analysis revealed several taxa to be associated with JIA: TM7-G1, Solobacterium and Mogibacterium at the genus level; and Leptotrichia oral taxon 417, TM7-G1 oral taxon 352 and Capnocytophaga oral taxon 864 among others, at the species level. Haemophilus species, Leptotrichia oral taxon 223, and Bacillus subtilis, were associated with healthy controls. Gemella morbillorum, Leptotrichia sp. oral taxon 498 and Alloprevotella oral taxon 914 correlated positively with the composite juvenile arthritis 10-joint disease activity score (JADAS10), while Campylobacter oral taxon 44 among others, correlated with the number of active joints. Of all microbial markers identified, only Bacillus subtilis and Campylobacter oral taxon 44 maintained false discovery rate (FDR) Conclusions: In this exploratory study of salivary oral microbiome we found similar alpha- and beta-diversity among children with JIA and healthy. Several taxa associated with chronic inflammation were found to be associated with JIA and disease activity, which warrants further investigation

The World Social Situation: Development Challenges at the Outset of a New Century

World social development has arrived at a critical turning point. Economically advanced nations have made significant progress toward meeting the basic needs of their populations; however, the majority of developing countries have not. Problems of rapid population growth, failing economies, famine, environmental devastation, majority-minority group conflicts, increasing militarization, among others, are pushing many developing nations toward the brink of social chaos. This paper focuses on worldwide development trends for the 40-year period 1970-2009. Particular attention is given to the disparities in development that exist between the world’s “rich” and “poor” countries as well as the global forces that sustain these disparities. The paper also discusses more recent positive trends occurring within the world’s “socially least developed countries” (SLDCs), especially those located in Africa and Asia, in reducing poverty and in promoting improved quality of life for increasing numbers of their populations

Cardiovascular adaptation in pregnancy - Effects of angiotensin II, transverse aorta constriction and high-intensity interval training on pregnant rats

Objectives: To investigate how cardiac function, remodeling and gene expression are affected in pregnancy in response to cardiovascular stress, to detect possible adverse effects on the fetus, and to evaluate if coronary endothelial function is influenced by pregnancy and increased cardiac afterload. Methods: Pregnant and non-pregnant rats were subjected to chronic AngII-infusion, transverse aortic constriction (TAC) or high-intensity interval training (HIIT) in three separate studies. Echocardiography was used to evaluate maternal heart function. Doppler signals from the left coronary artery was used to asses coronary flow reserve (CFR) using 3.5% inhaled isoflurane as a vasodilating agent. Blood pressure and left ventricle (LV) pressure and volume were measured invasively using a conductance catheter placed in the LV. Histological sections of the maternal LV were used to determine collagen content, vessel density and myocyte size. RT-PCR was used to quantify the gene expression in maternal myocardium and fetuses. Level of oxidative stress was measured in fetal tissue in the HIIT-study. Results: Chronic AngII infusion resulted in increased myocardial collagen content, and pregnancy reduced this effect. A decrease in LV vessel density following AngII infusion was less severe in pregnant rats. Calculated stroke work in pregnant TAC rats was double compared to pregnant shams, whereas it was not significantly increased in non-pregnant TAC rats compared to non-pregnant shams. The ratio of β-MHC to α-MHC expression was higher in pregnant compared to non-pregnant TAC. HIIT did not alter maternal cardiac structure or function, fetal growth or level of oxidative stress in the placenta or fetuses. There were no differences in CFR between rats with increased afterload (AngII or TAC) and controls. CFR was lower in pregnant compared to non-pregnant rats. Main conclusions: Pregnancy was protective against fibrosis and preserved angiogenesis in AngII infused rats. Increased afterload following TAC was less tolerated in pregnancy. CFR is reduced in late pregnancy. HIIT is feasible and well tolerated by pregnant rats and did not induce significant changes in the fetus

Det enkle er ikke alltid det beste

På slutten av 1950-tallet ble et nytt medikament introdusert på verdensmarkedet. Thalidomid ble raskt erklært som en mirakelmedisin. Stoffet virket beroligende, smertestillende og søvndyssende, og det skulle knapt ha bivirkninger. Den gode effekten på morgenkvalme gjorde at thalidomid ble særlig populært blant gravide. Konsekvensen ble katastrofal

Uveitis in Juvenile Idiopathic Arthritis 18-Year Outcome in the Population-based Nordic Cohort Study

Purpose: To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA). Design: Population-based, multicenter, prospective JIA cohort, with a cross-sectional assessment of JIA-associated uveitis (JIA-U) 18 years after the onset of JIA. Participants: A total of 434 patients with JIA, of whom 96 had uveitis, from defined geographic areas of Denmark, Finland, Norway, and Sweden. Methods: Patients with onset of JIA between January 1997 and June 2000 were prospectively followed for 18 years. Pediatric rheumatologists and ophthalmologists collected clinical and laboratory data. Main Outcome Measures: Cumulative incidence of uveitis and clinical characteristics, JIA and uveitis disease activity, ocular complications, visual outcome, and risk factors associated with the development of uveitis-related complications. Results: Uveitis developed in 96 (22.1%) of 434 patients with JIA. In 12 patients (2.8%), uveitis was diagnosed between 8 and 18 years of follow-up. Systemic immunosuppressive medication was more common among patients with uveitis (47/96 [49.0%]) compared with patients without uveitis (78/338 [23.1 %]). Active uveitis was present in 19 of 78 patients (24.4%) at the 18-year visit. Ocular complications occurred in 31 of 80 patients (38.8%). Short duration between the onset of JIA and the diagnosis of uveitis was a risk factor for developing ocular complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8). Patients with a diagnosis of uveitis before the onset of JIA all developed cataract and had an OR for development of glaucoma of 31.5 (95% CI, 3.6-274). Presence of antinuclear antibodies (ANAs) was also a risk factor for developing 1 or more ocular complications (OR, 3.0; 95% CI, 1.2-7.7). Decreased visual acuity (VA) Conclusions: Our results suggest that uveitis screening should start immediately when the diagnosis of JIA is suspected or confirmed and be continued for more than 8 years after the diagnosis of JIA. Timely systemic immunosuppressive treatment in patients with a high risk of developing ocular complications must be considered early in the disease course to gain rapid control of ocular inflammation. (C) 2020 by the American Academy of Ophthalmology.Peer reviewe

Coronary flow reserve in pregnant rats with increased left ventricular afterload

Background Coronary flow reserve (CFR) is used as a measure of coronary endothelial function. We investigated the effect of increased afterload on CFR of pregnant and non-pregnant rats. Methods Afterload increase in Wister rats (both pregnant and non-pregnant) was achieved by the infusion of angiotensin II (Ang II) for ~10 days or by subjecting them to transverse aortic constriction (TAC) for ~14 days. Control groups were infused with 0.9% NaCl or had sham surgery, respectively. In pregnant rats, the experiments were performed close to term gestation. Doppler velocity waveforms of the left main coronary artery were recorded using a high resolution ultrasound imaging system (Vevo 770, VisualSonics, Canada) at baseline while the animals were anesthetized with 1.5% inhaled isoflurane, and during maximal coronary dilatation obtained by the inhalation of 3.5% of isoflurane. CFR was calculated as the ratio between the peak coronary flow velocities (CFRpeak) and the velocity-time integrals (CFRVTI) recorded at hyperemia and at baseline. Results CFR could be calculated in 60 of 75 (80%) animals. There were no differences in CFR between intervention and control groups irrespective of whether afterload was increased by Ang II or TAC. In the TAC-study CFRpeak (1.54±0.07 vs 1.85±0.17; p = 0.03) was decreased in pregnant compared to non-pregnant shams. When sham animals from both studies were pooled together both CFRpeak (1.42±0.07 vs 1.86±0.16; p = 0.005) as well as CFRVTI (1.45±0.07 vs 1.78±0.12; p = 0.03) were significantly lower in pregnant rats compared to non-pregnant. Conclusions CFR can be measured non-invasively in rats using Doppler echocardiography and high concentrations of inhaled isoflurane as a coronary vasodilator. In pregnant rats, CFR is reduced close to term. CFR is not affected by increased left ventricular afterload caused by chronic Ang II infusion or TAC

Effect of Transverse Aortic Constriction on Cardiac Structure, Function and Gene Expression in Pregnant Rats

Background: There is an increased risk of heart failure and pulmonary edema in pregnancies complicated by hypertensive disorders. However, in a previous study we found that pregnancy protects against fibrosis and preserves angiogenesis in a rat model of angiotensin II induced cardiac hypertrophy. In this study we test the hypothesis that pregnancy protects against negative effects of increased afterload. Methods: Pregnant (gestational day 5.5–8.5) and non-pregnant Wistar rats were randomized to transverse aortic constriction (TAC) or sham surgery. After 14.260.14 days echocardiography was performed. Aortic blood pressure and left ventricular (LV) pressure-volume loops were obtained using a conductance catheter. LV collagen content and cardiomyocyte circumference were measured. Myocardial gene expression was assessed by real-time polymerase chain reaction. Results: Heart weight was increased by TAC (p,0.001) but not by pregnancy. Cardiac myocyte circumference was larger in pregnant compared to non-pregnant rats independent of TAC (p = 0.01), however TAC per se did not affect this parameter. Collagen content in LV myocardium was not affected by pregnancy or TAC. TAC increased stroke work more in pregnant rats (34.162.4 vs 17.562.4 mmHg/mL, p,0.001) than in non-pregnant (28.261.7 vs 20.961.5 mmHg/mL, p = 0.06). However, it did not lead to overt heart failure in any group. In pregnant rats, a-MHC gene expression was reduced by TAC. Increased in the expression of b-MHC gene was higher in pregnant (5-fold) compared to non-pregnant rats (2-fold) after TAC (p = 0.001). Nine out of the 19 genes related to cardiac remodeling were affected by pregnancy independent of TAC. Conclusions: This study did not support the hypothesis that pregnancy is cardioprotective against the negative effects of increased afterload. Some differences in cardiac structure, function and gene expression between pregnant and nonpregnant rats following TAC indicated that afterload increase is less tolerated in pregnancy

Uveitis in Juvenile Idiopathic Arthritis 18-Year Outcome in the Population-based Nordic Cohort Study

Purpose To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA). Design Population-based, multicenter, prospective JIA cohort, with a cross-sectional assessment of JIA-associated uveitis (JIA-U) 18 years after the onset of JIA. Participants A total of 434 patients with JIA, of whom 96 had uveitis, from defined geographic areas of Denmark, Finland, Norway, and Sweden. Methods Patients with onset of JIA between January 1997 and June 2000 were prospectively followed for 18 years. Pediatric rheumatologists and ophthalmologists collected clinical and laboratory data. Main Outcome Measures Cumulative incidence of uveitis and clinical characteristics, JIA and uveitis disease activity, ocular complications, visual outcome, and risk factors associated with the development of uveitis-related complications. Results Uveitis developed in 96 (22.1%) of 434 patients with JIA. In 12 patients (2.8%), uveitis was diagnosed between 8 and 18 years of follow-up. Systemic immunosuppressive medication was more common among patients with uveitis (47/96 [49.0%]) compared with patients without uveitis (78/338 [23.1%]). Active uveitis was present in 19 of 78 patients (24.4%) at the 18-year visit. Ocular complications occurred in 31 of 80 patients (38.8%). Short duration between the onset of JIA and the diagnosis of uveitis was a risk factor for developing ocular complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1–1.8). Patients with a diagnosis of uveitis before the onset of JIA all developed cataract and had an OR for development of glaucoma of 31.5 (95% CI, 3.6–274). Presence of antinuclear antibodies (ANAs) was also a risk factor for developing 1 or more ocular complications (OR, 3.0; 95% CI, 1.2–7.7). Decreased visual acuity (VA) <6/12 was found in 12 of 135 eyes (8.9%) with uveitis, and 4 of 80 patients (5.0%) with JIA-U had binocular decreased VA <6/12. Conclusions Our results suggest that uveitis screening should start immediately when the diagnosis of JIA is suspected or confirmed and be continued for more than 8 years after the diagnosis of JIA. Timely systemic immunosuppressive treatment in patients with a high risk of developing ocular complications must be considered early in the disease course to gain rapid control of ocular inflammation

Effects of high intensity interval training on pregnant rats, and the placenta, heart and liver of their fetuses.

Objective To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Methods Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Results Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Conclusions Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated