Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after shortterm treatment with intravitreous bevacizumab

OBJECTIVE: Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits. METHODS: Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test. RESULTS: No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group. CONCLUSIONS: Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eyes

PReS-FINAL-2177: Safety and lack of autoantibody production following influenza H1N1 vaccination in patients with juvenile idiopathic arthritis (JIA)

Introduction Vaccination is an effective tool against several infectious agents including influenza. In 2010, the Advisory Committee on Immunization Practices (ACIP) recommended influenza A H1N1/2009 immunization for high risk groups, including juvenile idiopathic arthritis (JIA) patients and more recently the EULAR task force reinforced the importance of vaccination in immunosuppressed pediatric rheumatologic patients. We have recently shown that Influenza A H1N1/2009 vaccination generated protective antibody production with short-term safety profile among 93 JIA patients, but the possible impact of the vaccine in autoimmune response in JIA have not been studied. Therefore, we aimed to assess the production of some autoantibodies generated following influenza H1N1 vaccination in JIA patients. Objectives To assess the autoimmune response and H1N1 serology following influenza H1N1 vaccination in patients with JIA. Methods Cepa A/California/7/2009 (NYMC X-179A) anti-H1N1 was used to vaccinate JIA patients: 1 dose of immunization was given to all participants and those <9yrs of age received a second booster 3 weeks apart. Sera were analyzed before and 3 weeks following complete vaccination. Serology against H1N1 virus was performed by hemagglutination inhibition antibody assay, rheumatoid factor (RF) by latex fixation test, antinuclear antibodies (ANA) by IIF, IgM and IgG anticardiolipin (aCL) by ELISA.Results Among 98 JIA patients that were vaccinated, 58 sera were available for this study. Mean age of 58 JIA patients was 23.9 ± 9.5 yrs, 38 were females and 20 males with mean disease duration of 14.7 ± 10.1 yrs. JIA subtypes were: 33 (57%) poliarticular, 10 (17%) oligoarticular, 6 (10%) systemic and 9 (16%) other. Sixteen patients were off drugs while 42 (72%) were under different pharmacotherapy: 32 (55%) were on 1 DMARD/IS, 10 (17%) on 2 DMARDs/IS, 19 (33%) antimalarials, 29 (50%) MTX, 8(14%) sulfasalazine, 6 (10%) anti-TNFs, 4 (7%) abatacept; no patient was using prednisone >0.5 mg/kg/d. Seroprotection rates against H1N1 influenza increased from 23 to 83% and seroconversion rates were achieved in 78% JIA. Prior to vaccination, 31(53.4%) JIA patients were ANA+, 6(10.3%) RF+, and 4 (7%) IgM + IgG aCL+. After complete H1N1 vaccination, positivity for ANA remained the same whereas 1 patient became negative for IgG aCL, and another for RF, IgM and IgG aCL. One (1.7%) patient turned low titer IgG aCL+. Conclusion Vaccination of JIA patients against pandemic influenza A (H1N1) generated successful protective antibody production without the induction of autoantibody production, except for 1 patient that became positive for low titer IgG aCL, supporting its safety.

PReS-FINAL-2170: Work disability in adult patients with juvenile idiopathic arthritis (JIA)

Introduction Approximately 20% JIA patients enters adulthood with clinically active disease and disabled, therefore work condition may be affected. Objectives To assess the prevalence of work disability among adult patients with JIA regularly attending a tertiary heumatology center and to determine possible associated risk factors. Methods This was a cross-sectional study that enrolled 43 JIA patients according to 2004 revised ILAR criteria. A questionnaire was developed in order to evaluate working status and labor activity: occupation, current/previous work, employment status and withdrawal rate were actively searched. Demographic data, JIA characteristics, clinical activity (DAS28>2.6), therapeutic intervention, comorbidities, physical activity, sedentarism (WHO definitions), functional class (1991 ACR criteria), HAQ and SF-36 were recorded. The prevalence of work disability was calculated using 95% confidence interval, and compared to all parameters; qualitative variables were analyzed using tests of association (chi-square test) and quantitative variables by Mann-Whitney or student test. Results Patients' mean age was 29+7.4 yrs (range 19-41) with mean JIA duration = 17.2+12.3 yrs (range 3-33); 63% were males and 37% females. JIA subtypes were 64% polyarticular, 11% oligoarticular, 9% systemic, 9% ERA, 2% extended oligoarticular, 2% psoriatic arthritis; 7% had uveitis. Serum RF was positive in 21% and ANA in 21%. The majority (72%, n = 31) of JIA patients were employed, whereas 28% (n = 12) were currently not working. In the latter group, 83% (10/12) were retired due to JIA related disability. Further analysis comparing those currently working vs. Those not working revealed similar age (25,3 yrs vs.29,5 yrs, p = 0,09). Although not significantly, most patients currently working had Poly onset JIA (22 vs. 6 p = 0,37), higher frequencies of good education level >12 yrs of school (31 vs.9, p = 0,38), functional class I (p = 0,96), practiced regular physical activity (9 vs. 0, p = 0,89), were singles (26 vs. 8, p = 0,15). Both groups had comparable HAQ and DAS 28 scores (0,62 vs. 0.59, p = 0,47 and 2,51 vs.2,07, p = 0,64) and similar arthroplasty rate (8 vs. 4, p = 0,427). Frequencies of hypertension (3 vs.1, p = 0,999), dyslipidemia (1 vs. 1, p = 0,125), diabetes (1 vs. 0 p = 0,999), depression (1 vs. 0, p = 0,999) and smokers (3 vs. 1, p = 0,99) were alike in both groups. Remarkably, employed patients had higher SF 36 mental health component (84.0 vs. 70.42, P = 0.01). Conclusion High prevalence of almost 1/3 work disability and of retirement due to disease related incapacity remain major problems for adult JIA individuals. We also identified worse mental health in employed patients indicating that further research is needed, in addition to intense affirmative disability actions in order to remove possible disabling barriers and to adapt restrictive environments for these patients. Moreover, enhanced strategies and policy for inclusion of JIA patients in the job market is urged.

The juvenile three-spined stickleback : model organism for the study of estrogenic and androgenic endocrine disruption in laboratory and field

Industrial and domestic sewage effluents have been found to cause reproductive disorders in wild fish, often as a result of the interference of compounds in the effluents with the endocrine system. This thesis describes laboratory-based exposure experiments and a field survey that were conducted with juveniles of the three-spined stickleback, Gasterosteus aculeatus. This small teleost is a common fish in Swedish coastal waters and was chosen as an alternative to non-native test species commonly used in endocrine disruption studies, which allows the comparison of field data with results from laboratory experiments. The aim of this thesis was to elucidate 1) if genetic sex determination and differentiation can be disturbed by natural and synthetic steroid hormones and 2) whether this provides an endpoint for the detection of endocrine disruption, 3) to evaluate the applicability of specific estrogen- and androgen-inducible marker proteins in juvenile three-spined sticklebacks, 4) to investigate whether estrogenic and/or androgenic endocrine disrupting activity can be detected in effluents from Swedish pulp mills and domestic sewage treatment plants and 5) whether such activity can be detected in coastal waters receiving these effluents. Laboratory exposure experiments found juvenile three-spined sticklebacks to be sensitive to water-borne estrogenic and androgenic steroid substances. Intersex – the co-occurrence of ovarian and testicular tissue in gonads – was induced by 17β-estradiol (E2), 17α-ethinylestradiol (EE2), 17α-methyltestosterone (MT) and 5α-dihydrotestosterone (DHT). The first two weeks after hatching was the phase of highest sensitivity. MT was ambivalent by simultaneously eliciting masculinizing and feminizing effects. When applying a DNA-based method for genetic sex identification, it was found that application of MT only during the first two weeks after hatching caused total and apparently irreversible development of testis in genetic females. E2 caused gonad type reversal from male to female. E2 and EE2 induced vitellogenin - the estrogen-responsive yolk precursor protein, while DHT and MT induced spiggin – the androgen-responsive glue protein of the stickleback. None of the effluents from two pulp mills and two domestic sewage treatment plants had any estrogenic or androgenic activity. Juvenile three-spined sticklebacks were collected during four subsequent summers at the Swedish Baltic Sea coast in recipients of effluents from pulp mills and a domestic sewage treatment plant as well as remote reference sites. No sings of endocrine disruption were observed at any site, when studying gonad development or marker proteins, except for a deviation of sex ratios at a reference site. The three-spined stickleback – with focus on the juvenile stage – was found to be a sensitive species suitable for the study of estrogenic and androgenic endocrine disruption.

Effects of dietary mannan oligosaccharides (MOS) on European sea bass (Dicentrarchus labrax) juvenile culture

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Setting up interpretation criteria for juvenile and adult European anchovy otoliths from Canary Islands

Máster en Gestión Sostenible de Recursos Pesqueros

Coronal plane segmental flexibility in thoracic adolescent idiopathic scoliosis assessed by fulcrum-bending radiographs

Knowledge about segmental flexibility in adolescent idiopathic scoliosis is crucial for a better biomechanical understanding, particularly for the development of fusionless, growth-guiding techniques. Currently, there is lack of data in this field. The objective of this study was, therefore, to compute segmental flexibility indices (standing angle minus corrected angle/standing angle). We compared segmental disc angles in 76 preoperative sets of standing and fulcrum-bending radiographs of thoracic curves (paired, two-tailed t tests, p < 0.05). The mean standing Cobb angle was 59.7 degrees (range 41.3 degrees -95 degrees ) and the flexibility index of the curve was 48.6\% (range 16.6-78.8\%). The disc angles showed symmetric periapical distribution with significant decrease (all p values <0.0001) for every cephalad (+) and caudad (-) level change. The periapical levels +1 and -1 wedged at 8.3 degrees and 8.7 degrees (range 3.5 degrees -14.8 degrees ), respectively. All angles were significantly smaller on the-bending views (p values <0.0001). We noted mean periapical flexibility indices of 46\% (+1), 49\% (-1), 57\% (+2) and 81\% (-2), which were significantly less (p < 0.001) than for the group of remote levels 105\% (+3), 149\% (-3), 231\% (+4) and 300\% (-4). The discal and bony wedging was 60 and 40\%, respectively, and mean values 35 degrees and 24 degrees (p < 0.0001). Their relationship with the Cobb angle showed a moderate correlation (r = 0.56 and 0.45). Functional, radiographic analysis of idiopathic thoracic scoliosis revealed significant, homogenous segmental tethering confined to four periapical levels. Future research will aim at in vivo segmental measurements in three planes under defined load to provide in-depth data for novel therapeutic strategies.

Scoliosis surgery: correction not correlated with instrumentation, quality of life not correlated with correction or instrumentation

The authors conducted a retrospective study on 24 consecutive adolescent scoliosis patients, 11 of whom were instrumented with hooks and 13 with hooks and screws (hybrid technique). The mean preoperative Cobb angle was 62.2 degrees (range: 48 degrees-96 degrees). The mean correction of the primary curve was 56.6% at followup after +/- 1.18 years ; there was no statistically significant difference between groups. Special attention was given to the postoperative quality of life (QOL) by means of the following scores: COMI patient self-assessment, SF-36, ODI, and VAS. Again, there was no statistical difference between groups but, interestingly, there was no correlation between QOL and degree of correction, after a follow-up period of +/- 2.1 years. Nevertheless, on the COMI patient self-assessment, there was a high level of satisfaction with treatment. Further studies should concentrate on how to achieve a high QOL, and abandon the best possible correction as a primary endpoint of success.