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Yi-Hsing Chen,1 Hellen MDS de Carvalho,2 Umut Kalyoncu,3 Lyndon John Q Llamado,4 Gaston Solano,5 Ron Pedersen,6 Galina Lukina,7 Juan J Lichauco,8 Radu S Vasilescu9 1Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung City, Taiwan; 2Unidade de Reumatologia, Hospital de Base do Distrito Federal, Brasilia, Brazil; 3Department of Internal Medicine, Faculty of Medicine, Division of Rheumatology, Hacettepe University, Ankara, Turkey; 4Pfizer, Makati City, Philippines; 5Pfizer, San Jose, Costa Rica; 6Pfizer, Collegeville, PA, USA; 7Moscow Clinical Scientific Center, Moscow, Russia; 8Section of Rheumatology, Department of Medicine, St. Luke’s Medical Center, Quezon City, Manila, Philippines; 9Pfizer, Brussels, Belgium Abstract: Tumor necrosis factor-α (TNF-α) inhibitors are increasingly becoming the standard of care for treating a number of inflammatory diseases. However, treatment with TNF-α inhibitors carries an inherent risk of compromising the immune system, resulting in an increased susceptibility to infections and malignancies. This increased risk of infection is of particular concern in Asia, Eastern Europe, and Latin America where tuberculosis (TB) and viral hepatitis are endemic. In this brief review, we examine the literature and review the impact of TNF-α inhibitors on the incidence and the reactivation of latent disease with respect to TB, hepatitis C infection, and hepatitis B infection. Our findings show that TNF-α inhibitors are generally safe, if used with caution. Patients should be screened prior to the initiation of TNF-α inhibitor treatment and given prophylactic treatment if needed. In addition, patients should be monitored during treatment with TNF-α inhibitors and after treatment has stopped to ensure that infections, if detected, are treated promptly and effectively. Our analysis is consistent with other reports and guidelines. Keywords: tuberculosis, hepatitis C, hepatitis B, tumor necrosis factor inhibitors, reactivation, risk

Growth patterns and biological milestones in youth sports are key to interpreting the development of young athletes. However, there is no analysis of longitudinal meta-analysis describing the growth of young female athletes. This longitudinal meta-analysis estimated growth curves and age at peak height velocity (PHV) in young female athletes based on anthropometric data from longitudinal studies found in the literature. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies with repeated measurements in young female athletes were identified from searches of four databases (MEDLINE, Web of Science, SCOPUS, and SPORTDiscus) without date restrictions through August 2023. We adapted our bias assessment criteria using the Cochrane risk of bias tool for randomized controlled trials as a reference. Bayesian multilevel modeling was used to perform a longitudinal meta-analysis to extract stature growth curves and age at PHV. Fourteen studies met our eligibility criteria. Twenty-one independent samples could be included in the analysis. Conditional on the data and models, the predicted mean age at PHV for female athletes was 11.18 years (90% CI: 8.62; 12.94). When studies were aggregated by sport in the models, the models could not capture sport-specific growth curves for stature and estimate a corresponding age at PHV. We provide the first longitudinal meta-analytic summary of pubertal growth and derive age at PHV in young female athletes. The meta-analysis predicted that age at PHV occurs at similar ages to those in the general pediatric population. The data pool was limited in sports and geographic distribution, emphasizing the need to promote longitudinal research in females across different youth sports contexts., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Lima et al.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The present study examined the influence of the specialization onset on the magnitude and patterns of changes in basketball-specific physical fitness within a competitive season and developmental fitness trends between 11 and 17 years in young basketball players. Repeated measures of 181 young basketball players (female, n  = 40; male, n  = 141) were examined. Anthropometry, age, estimated maturity status, and basketball-specific physical fitness (assessed with the countermovement jump, line drill, and yo-yo intermittent recovery level-1 and fitness score) were considered. Players were grouped by the onset of specialization as related to biological maturation milestones (pre-puberty, mid-puberty, and late-puberty specialization). The within-season and developmental changes in physical fitness were fitted using multilevel modeling in a fully Bayesian framework. The fitness outcomes were similar between-player and within-player changes when grouped by specialization across a season. Fitness improvements across a season were apparent for female players, while male players maintained their performance levels. There was no variation in the patterns of physical fitness development between 11 and 17 years associated with the onset of specialization. Conditional on our data and models, the assumption that early sport specialization provides a physical fitness advantage for future athletic success does not hold., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Soares, Lima, Miguel, Galvão, Leonardi, Paes, Gonçalves and Carvalho.)

Background: Currently, there is no standard treatment for Autism Spectrum Disorders (ASD), but there are many ways to minimize the symptoms and maximize abilities. Some studies suggest that exercise and other physical activities with children with ASD may be beneficial. In this study, we hypothesized that a physical exercise program (48-week exercise-intervention) could improve symptomatology dyad among children and adolescents with ASD. Our main aim was to examine the effects of physical activity on the primary clinical symptoms and associated comorbidities in children and adolescents with ASD., Methods: We allocated 229 children with ASD, ranging in age from 2.3-17.3 years ( M = 7.8, SD = 3.2), into three groups: (a) exercise- intervention group, (b) control group from the same institution, and (c) control group from another institution. The exercise program was performed at moderate intensity in a 30 min section twice a week for 48 weeks. We used Bayesian multilevel regression modeling to examine participant outcomes and responses to the exercise-intervention., Results: Our results showed that a 48-week exercise-intervention substantially decreased ASD social interaction problems, attention deficit, emotional reactivity, stereotypical verbal and motor behavior, and sleep disturbances. However, physical exercise did not affect eye contact and food selectivity. We also observed that ASD severity and socioeconomic status influence eye contact, attention deficit, and sleep disturbance responses., Conclusion: In conclusion, children and adolescents with ASD exposed to a 48-week physical exercise-intervention program had important improvements in ASD symptoms. This study highlights that structured exercise programs can be a powerful complementary therapy for the ASD population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Toscano, Ferreira, Quinaud, Silva, Carvalho and Gaspar.)

Constructivism is used as a powerful theoretical outlook to support teaching, learning, and curriculum in physical education and sport. The Constructivist Teaching Practices Inventory in Elementary Physical Education (CTPI-EPE) is a valid instrument for assessing in-service teachers. However, there is a need to translate constructivist teaching practices for PE into other languages. This study examined the validity of the Portuguese version of the adapted CTPI-EPE for Brazilian physical education preservice teachers (PST). The sample comprised of 869 physical education PSTs from Brazil. Data were collected through an online form. Aiken's V was used to examine content validity, and Bayesian methods used for exploratory and confirmatory factor analysis. The results showed adequate content and internal structure of the translated and adapted questionnaire. This study highlighted the validity of the Portuguese version of the CTPI-EPE, which could be considered an important instrument for self-reflection by PSTs, and provide information for improved training in higher education toward constructivist teaching.

Background: Joint pain in the absence or with little synovitis is observed in a large percentage of HTLV-1 infected subjects. As the virus infect CD4 + and CD8 + positive, macrophages and B cells an exaggerated production of pro-inflammatory cytokines is detected in these patients. However, the possible association of HTLV-1 infection with autoimmune diseases has not been documented definitively and the clinical characteristics of HTLV-1 associated arthropathy has not been defined. The objective this study is to describe clinic and radiographic features in HTLV-1-infected individuals with complaints of joint pain., Methods: Cross-sectional study enrolling HTLV-1-infected individuals with chronic joint pain, aged up to 75 years, both genders and seronegative controls with osteoarthritis. All participants underwent conventional radiography of the hips, knees and ankles., Results: Eighty-one HTLV-1 infected patients and 30 subjects with osteoarthritis participated in the study. Polyarticular and symmetrical arthritis prevailed in the HTLV-1 positive group (54%), while oligoarticular and asymmetrical (44%) were more common in controls (p < 0.05). The frequency of enthesophytes (90%) in HTLV-1-infected patients was greater than in the control group (73%) (p < 0.05). Radiographic features were similar in HTLV-1 carriers and in patients with probable or definite HTLV-1 associated myelopathy. The presence of enthesophytes in the absence of joint space reduction or osteophytes was only observed in HTLV-1-infected individuals (p < 0.001). Magnetic resonance imaging of the ankles of five HTLV-1-infected patients and five controls demonstrated a higher frequency of enthesitis, bursitis and osteitis in the HTLV-1 infected group., Conclusion: HTLV-1-associated arthropathy is clinically characterized by symmetrical polyarthralgia and the main radiological finding is the presence of enthesophytes in the absence of osteophytes and joint space narrowing., (© 2022. The Author(s).)

Background: Applied research using the phase angle (PhA) in children and adolescents has increased notably. Using multilevel modeling in a fully Bayesian framework, we examined the relationships between PhA, age, sex, biological maturity status, and body size in 10-16-year-old adolescents., Methods: The sample comprised 519 adolescents (women, n = 241; men, n = 278) from Campinas, São Paulo, Brazil. Biological maturity status was assessed with self-examination of pubertal development for sexual maturity and maturity offset protocol to estimate age at peak height velocity (PHV) for somatic maturity status. Stature and body mass were measured by anthropometry. Phase angle was calculated based on raw resistance and reactance values (50 kHz frequency) obtained by bioelectrical impedance with the foot-to-hand technology., Results: The multilevel regression analysis revealed that boys had significantly higher values of phase angle than girls, adjusting for age group and sexual maturity status. Overall, older and more mature adolescents had higher values of phase angle. When considering aligning variation in the phase angle by distance to estimated PHV (maturity offset), there was a higher association between the phase angle and time before and after predicted age at PHV for boys ( r = 0.31, 90% CI: 0.23 to 0.39) than girls ( r = 0.2, 90% CI: 0.11 to 0.28). When including body mass in the multilevel models, corresponding changes in the overall body mass mediate most of the influence of the maturity status and age group on the phase angle., Conclusion: The present study demonstrated that the variability in phase angle is related to inter-individual variation in sex, age, and maturity status, as well as differences in body size. Research with adolescents considering phase angle should use multilevel modeling with standardized parameters as default to adjust for the concurrent influence of sex, age, maturity status, and body size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de Moraes, Quinaud, Ferreira, Lima, Carvalho and Guerra-Júnior.)

Background: Reliable assessment and understanding of student-athletes' motivation for dual careers are crucial to support their career development and transitions. The purpose of this research was to examine the validity and usefulness of the student-athletes' motivation toward sport and academics questionnaire (SAMSAQ-PT) in the Brazilian higher education context. Four studies were performed., Methods: In study one, conceptually and semantic translation of the questionnaire and Bayesian exploratory factor analysis were conducted. In study two, a Bayesian confirmatory factor analysis with an independent sample was performed. In study three, Bayesian multilevel modeling was applied to examine the construct validity of the questionnaire in a cross-sectional sample. In study four, the SAMSAQ-PT sensitiveness was examined in a longitudinal sample, and the results were interpreted based on multilevel regression and poststratification., Results: Altogether the results provided evidence validity and usefulness of the SAMSAQ-PT in Brazilian student-athletes. The Brazilian student-athletes' motivation scores were sensitive to the influence of sex, sport level, and type of university on career and sport motivation. SAMSAQ-PT estimate scores across an academic year showed a trend of stability in the scores, adjusting for sex, sport level, type of university, and student-athlete status., Conclusion: The SAMSAQ-PT proved to be a robust and valuable questionnaire, which could be used in Portuguese-speaking countries. The findings of the cross-sectional and longitudinal surveys urge to consider individual and contextual characteristics when investigating motivation of dual-career of athletes, also concerning the sex-related opportunities in university sports. Furthermore, there is a need for a call for action to promote and nurture the student-athletes motivation to remain engaged in both sports and educational commitments., Competing Interests: The authors declare there are no competing interests., (©2021 Quinaud et al.)

Background: Large-scale health surveys often consider sociodemographic characteristics and several health indicators influencing physical activity that often vary across subpopulations. Data in a survey for some small subpopulations are often not representative of the larger population., Objective: We developed a multilevel regression and poststratification (MRP) model to estimate leisure-time physical activity across Brazilian state capitals and evaluated whether the MRP outperforms single-level regression estimates based on the Brazilian cross-sectional national survey VIGITEL (2018)., Methods: We used various approaches to compare the MRP and single-level model (complete-pooling) estimates, including cross-validation with various subsample proportions tested., Results: MRP consistently had predictions closer to the estimation target than single-level regression estimations. The mean absolute errors were smaller for the MRP estimates than single-level regression estimates with smaller sample sizes. MRP presented substantially smaller uncertainty estimates compared to single-level regression estimates. Overall, the MRP was superior to single-level regression estimates, particularly with smaller sample sizes, yielding smaller errors and more accurate estimates., Conclusion: The MRP is a promising strategy to predict subpopulations' physical activity indicators from large surveys. The observations present in this study highlight the need for further research, which could, potentially, incorporate more information in the models to better interpret interactions and types of activities across target populations.

Brazil has been the benchmark for volleyball performance for at least two decades, providing a unique context to examine expertise development. This study examined the variation in body size, functional capacities, motivation for achievement, competitiveness, and deliberate practice of youth volleyball players associated with differences in biological maturity status, chronological age, and accumulated deliberate volleyball practice, adopting a Bayesian multilevel modeling approach. We considered 68 female and 94 male adolescent players (14.2 years, 90% confidence interval: 12.7 to 16.0). Players were grouped by the onset of deliberate volleyball practice as related to biologic maturation milestones [pre-puberty deliberate practice onset (12% of the sample), mid-puberty deliberate practice onset (51% of the sample), and late-puberty deliberate practice onset (37% of the sample). There was substantial variation in body dimensions and functional performance by gender. There was no variation by gender for motivation for deliberate practice and motivation for achievement and competitiveness. The young volleyball players appeared to be highly motivated and committed to deliberate practice, achievement, and competitiveness. Alignment of chronological age, biological maturation, and accumulated training experience allow more in-depth insights into young volleyball players' development, providing sounder support for coaches´ decisions., Competing Interests: The authors have declared that no competing interests exist.

Relative age effect (RAE) is considered to bias the selection of young athletes and a cause of exclusion of many participants. The goal of the study was to unveil the effects of the birth quarter on physical performances and a set of psychological constructs in the age groups corresponding to the specialization years. A set of surveys with cross-sectional data collected from 2015 to 2019 in youth basketball was used. Three hundred and twenty-seven Brazilian players (127 females, 100 males), mean age 14.0 years, participated in the study. Counter-movement jump, line-drill, yoyo intermittent test, achievement goals, motivation for deliberate practice, and enjoyment were measured. Bayesian multilevel regression was performed. RAE was observed but its advantages did not persist and did not differentiate the players in the variables under scrutiny. The only predictor of athletic and psychological outcomes was chronological age. The initial advantage that triggered the coaches' decision to select individual players disappears during the specialization years. Coaches must overcome the superficial observation of young athletes based only on age groups and actual performances, avoiding hasty decisions that, unlike RAE, last in time and cannot be reversed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gonçalves and Carvalho.)

Background: Early sport specialization has increased its popularity mostly based on the deliberate practice theory premises. In this study, we examined the influence of the age of onset of deliberate basketball practice on body size, functional performance (countermovement jump, line drill and yo-yo intermittent recovery level 1), motivation for achievement and competitiveness, motivation for deliberate practice and sources of enjoyment among young Brazilian basketball players. In addition, we adjusted for the influence of gender, age group, maturity status and state basketball federation on the outcomes., Methods: The sample included 120 female and 201 male adolescent basketball players aged 14.0 (1.7) years, on average. We grouped players by the age of onset of deliberate basketball practice as related to biologic maturation milestones (pre-puberty deliberate practice onset, mid-puberty deliberate practice onset and late-puberty deliberate practice onset)., Results: There was no substantial variation among contrasting players by the onset of deliberate practice in all of the outcomes. Adjusting for gender, male players with late-puberty deliberate practice onset had better functional performance than players with pre- and mid-puberty onset of practice. Females players with late-puberty deliberate practice onset had slightly worst functional performance than players with pre- and mid-puberty onset of practice., Conclusions: Early deliberate basketball practice does not appear to provide an advantage for the development of physiological functions. Likewise, enjoyment, motivation for deliberate practice and motivation for achievement and competition do not appear to be negatively influenced by early deliberate basketball practice. The debate about the relationship between time spent in deliberate practice and performance development in young athletes will need to emphasize the coaching pedagogical quality and the training environment and account for informal practice and deliberate play.

Objective: This study examined the growth status and physical development of Brazilian children with autism spectrum disorders from 4 to 15 years of age. Furthermore, it was examined whether variation in growth patterns and weight status was influenced by the use of psychotropic medications., Methods: One-hundred and twenty children aged 3.6-12.1 years at baseline (average=7.2 years, SD=2.3 years) diagnosed with autism spectrum disorders were measured on three repeated occasions across a 4-year period. Stature, body mass, and body mass index were considered. Bayesian multilevel modeling was used to describe the individual growth patterns., Results: Growth in stature was comparable to the age-specific 50th percentile for Centers for Disease Control and Prevention reference data until approximately 8 years, but a substantial decrease in growth rate was observed thereafter, reaching the age-specific 5th percentile at 15 years of age. Both body mass and body mass index values were, on average, higher than both the Brazilian and Centers for Disease Control and Prevention age-specific 95th percentile reference until 8 years, but below the 50th specific-age percentile at the age of 15 years., Conclusions: Brazilian boys with autism spectrum disorders between 4 and 15 years appear to have impaired growth in stature after 8-9 years of age, likely impacting pubertal growth. A high prevalence of overweight and obesity was observed in early childhood, although a trend of substantial decrease in body mass and body mass index was apparent when children with autism spectrum disorders entered the years of pubertal development., (Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

B ackground and O bjectives : Recent studies have shown the existence of a positive relationship between physical exercise, symptomatic improvement, and reduction of damage caused by comorbidities associated with autistic spectrum disorder (ASD) in children, adolescents, and adults. The aim of this systematic review with meta-analysis (SRM) was to estimate the effects of physical exercise (PE) on the stereotyped behaviors of children with a diagnosis of ASD in intervention studies. Material s and Methods : The design followed the PRISMA guidelines and the TREND statement to assess the quality of information in each study. Nine non-randomized intervention trial studies with low, moderate, and vigorous physical exercise, with a duration varying from 8 to 48 weeks and a frequency of 3 times a week, were included in the SRM. The dependent variable episodes of stereotypical behaviors was analyzed in all studies and assessed as the number of episodes demonstrated by the child in pre- versus post-exercise intervention conditions. Results : The eight studies included a total 129 children (115 males and 14 females) with an average age of 8.93 ± 1.69 years. Children with ASD showed a reduction of 1.1 in the number of occurrences of stereotypical behaviors after intervention with physical exercise. Conclusion : Evidence was found to support physical exercise as an effective tool in reducing the number of episodes of stereotypical behaviors in children diagnosed with ASD.

Background and O bjectives: This study considered the use of a generalized additive multilevel model to describe the joint-angle-specific functional hamstring to quadriceps ratio (H:Q ratio) in the knee, using all of the available truly isokinetic data within the range. Materials and Methods: Thirty healthy male basketball players aged 15.0 (1.4) years (average stature = 180.0 cm, SD = 11.1 cm; average body mass = 71.2, SD = 14.9 kg) years were considered. All players considered had no history of lower extremity musculoskeletal injury at the time of testing or during the 6 months before testing, and had been engaged in formal basketball training and competition for 5.9 (2.4) years. Moments of force of the reciprocal concentric and eccentric muscular actions for the knee extensors and flexors assessed by isokinetic dynamometry at 60°∙s -1 were used. Results: Maximum moments of force were attained at different angle positions for knee extension. For knee flexion, it was apparent that there was an ability to maintain high levels of moment of force between 30° and 60° in the concentric muscular action, corresponding to the concentric action of the hamstrings. However, for the eccentric knee flexion, corresponding to the quadriceps action, there was a marked peak of moment of force at about 55°. The functional H:Q ratio for the knee extension was non-linear, remaining higher than 1.0 (i.e., point of equality) from the beginning of the extension until approximately 40° of the knee extension, leveling off below the point of equality thereafter. On average, the functional H:Q ratio for the knee flexion did not attain 1.0 across the range of motion. The functional H:Q ratio for the knee in the present sample peaked at 20° and 80°, declining between these angle positions to below 0.50 at about 0.54. Conclusions: Estimating the form of the non-linear relationship on-the-fly using a generalized additive multilevel model provides joint-angle-specific curves and joint-angle-specific functional H:Q ratio patterns, allowing the identification and monitoring of strength development, with potential implications for injury and performance., Competing Interests: The authors declare that they have no conflicts of interest.

In this study, we examined the probability of coaches' survival in the top Brazilian professional football championship considering variation across the competitive seasons between 2012 and 2017, considering a multilevel framework. We also considered whether previous coaching experience in the top Brazilian professional football championship would change the probability of coaches' survival across the season. The data considered 4,560 games from the top professional Brazilian football league (Campeonato Brasileiro Série A) between the 2012 and 2017 seasons. At the start of each season, the coach from each team was followed, being recorded at the time the event occurred, i.e., the coach being sacked. A total survival of 120 coaches was considered between the seasons of 2012 and 2017, i.e., 20 coaches at the beginning of each season. Coaches were assigned as novice (no previous experience as head coach in the top Brazilian championship) or experienced (with at least some previous experience as head coach in the top Brazilian championship). Data were available and extracted from the official website of the Brazilian Football Confederation. On average and considering un-pooled observations, the median life of a coach was about 16.5 rounds. Considering variation between 2012 and 2017 seasons, only about 26.3% (95% CI: 18.2-36.1) of the coaches ended a season without being sacked. By mid-season, at round 19, the probability of coaches' survival was 0.42 (95% CI: 0.32-0.53). Variation between season on survival estimates per round was substantial (between-season standard deviation = 0.48, 95% credible intervals: 0.25-0.95; corresponding to an inverse logit = 0.62, 95% CI: 0.56-0.72). There was no substantial variation between novice and experienced coaches' survival probability. The present results expose the vulnerability of the coaching context in Brazilian football, potentially highlighting an excessive emphasis on short-term results to mediate club management decisions.

Background: The interpretation of young athletes' performance during pubertal years is important to support coaches' decisions, as performance may be erroneously interpreted due to the misalignment between chronological age (CA), biological age (BA) and sport age (SA). Aim: Using a Bayesian multilevel approach, the variation in longitudinal changes in performance was examined considering the influence of CA, BA (age at menarche), SA, body size, and exposure to training among female basketball players. Method: The study had a mixed-longitudinal design. Thirty eight female basketball players (aged 13.38 ± 1.25 years at baseline) were measured three times per season. CA, BA and SA were obtained. Anthropometric and functional measures: countermovement jump, Line drill (LD), Yo-Yo (Yo-Yo IR1). Based on the sum of the z-scores, an index of overall performance was estimated. The effects of training on longitudinal changes in performance were modeled. Results: A decrease in the rate of improvements was apparent at about 14 years of age. When aligned for BA, the slowing of the rate of improvements is apparent about 2 years after menarche for LD. For countermovement jump longitudinal changes, when performance was aligned for BA improvements became linear. For Yo-Yo IR1 and performance index, both indicators showed a linear trend of improvement when aligned for CA and BA, separately. Older players showed higher rates of improvement for Yo-Yo IR1 and performance index from pre-season to end-season. When considering performance changes aligned for BA it was apparent an improvement of performance as players became biologically mature. Conclusions and Implications: The alignment of CA with BA and SA provides important information for coaches. Human growth follows a genetically determined pattern, despite variation in both tempo and timing. When the effects of maturation reach their end, all the girls went through the same process. Hence, there is no need to artificially manipulate youth competitions in order to accelerate gains that sooner or later reach their peak and tend to flat their improvement curve.

Physical exercise has shown positive effects on symptomatology and on the reduction of comorbidities in population with autism spectrum disorder (ASD). However, there is still no consensus about the most appropriate exercise intervention model for children with ASD. The physical exercise program for children with autism (PEP-Aut) protocol designed allow us to (i) examine the multivariate associations between ASD symptoms, metabolic profile, physical activity level, physical fitness, and health-related quality of life of children with ASD; (ii) assess the effects of a 40-week exercise program on all these aspects of children with ASD. The impact of the exercise program will be assessed based on the sequence of the two phases. Phase 1 is a 12-week cross-sectional study assessing the symptomatology, metabolic profile, physical fitness and physical activity levels, socioeconomic status profile, and health-related quality of life of participants. This phase is the baseline of the following phase. Phase 2 is a 48-week intervention study with a 40-week intervention with exercise that will take place in a specialized center for children with ASD in the city of Maceió-Alagoas, Brazil. The primary outcomes will be change in the symptomatic profile and the level of physical activity of children. Secondary outcomes will be anthropometric and metabolic profiles, aerobic function, grip strength, socioeconomic status, and health-related quality of life. The study will provide critical information on the efficacy of exercise for children with ASD and help guide design and delivery of future programs.

Backgrounds/Objectives:The activity of brown/beige adipose tissue (B/BAT) is inversely proportional to body adiposity. Studies have shown that obese subjects submitted to distinct approaches aimed at reducing body mass present an increase of B/BAT activation. However, it is unknown if this beneficial effect of body mass reduction applies to patients with type 2 diabetes mellitus. In this study, we evaluated the impact of massive body mass reduction obtained as a consequence of bariatric surgery in the cold-induced activation of B/BAT in obese non-diabetic (OND) and obese diabetic (OD) subjects., Subjects/methods: This is an observational study. Fourteen OND, 14 OD and 11 subjects were included in the study. All obese subjects were submitted to Roux-in-Y gastric bypass and measurements were performed before and 8 months after surgery. B/BAT was evaluated by ( 18 F)-FDG-PET/CT scan and determination of signature transcript expression in specimens obtained in biopsies., Results: Before surgery, mean B/BAT activity and the expression of signature transcripts were similar between OND and OD groups. Eight months after surgery, body mass reduction was similar between the obese groups. Nevertheless, the activity of B/BAT was increased in OND and unchanged in OD subjects. This effect was correlated with a more pronounced improvement of insulin resistance, as evaluated by the hyperinsulinemic, euglycemic clamp, in OND subjects as compared with OD subjects., Conclusions: Body mass reduction has a more efficient effect to induce the activation of B/BAT in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in B/BAT of non-diabetic than in diabetic subjects.

Objective: To analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA)., Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire., Results: The mean ASQoL score was 7.74 (+5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p=0.014) and African-Brazilian ethnicity (p<0.001). The analysis of the clinical symptoms showed that buttock pain (p=0.032), cervical pain (p<0.001) and hip pain (p=0.001) were statistically associated with worse scores of ASQoL. Continuous use of nonsteroidal anti-inflammatory drugs (p<0.001) and biologic agents (p=0.044) were associated with higher scores of ASQoL, while the other medications did not interfere with the ASQoL scores., Conclusion: In this large series of patients with SpA, female gender and African-Brazilian ethnicity, as well as predominant axial symptoms, were associated with impaired quality of life., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)

The aim of this paper was to outline a multilevel modeling approach to fit individual angle-specific torque curves describing concentric knee extension and flexion isokinetic muscular actions in Master athletes. The potential of the analytical approach to examine between individual differences across the angle-specific torque curves was illustrated including between-individuals variation due to gender differences at a higher level. Torques in concentric muscular actions of knee extension and knee extension at 60º·s(-1) were considered within a range of motion between 5º and 85º (only torques "truly" isokinetic). Multilevel time series models with autoregressive covariance structures with standard multilevel models were superior fits compared with standard multilevel models for repeated measures to fit angle-specific torque curves. Third and fourth order polynomial models were the best fits to describe angle-specific torque curves of isokinetic knee flexion and extension concentric actions, respectively. The fixed exponents allow interpretations for initial acceleration, the angle at peak torque and the decrement of torque after peak torque. Also, the multilevel models were flexible to illustrate the influence of gender differences on the shape of torque throughout the range of motion and in the shape of the curves. The presented multilevel regression models may afford a general framework to examine angle-specific moment curves by isokinetic dynamometry, and add to the understanding mechanisms of strength development, particularly the force-length relationship, both related to performance and injury prevention.

In the United States, Shiga toxin (Stx)-producing Escherichia coli (STEC) is the most frequent infectious cause of hemorrhagic colitis. Hemolytic uremic syndrome (HUS) is a serious sequela that may develop after STEC infection that can lead to renal failure and death in up to 10% of cases. STEC can produce one or more types of Stx, Stx1 and/or Stx2, and Stx1 and Stx2 are responsible for HUS-mediated kidney damage. We previously generated two monoclonal antibodies (MAbs) that neutralize the toxicity of Stx1 or Stx2. In this study, we evaluated the protective efficacy of human/mouse chimeric versions of those monoclonal antibodies, named cαStx1 and cαStx2. Mice given an otherwise lethal dose of Stx1 were protected from death when injected with cαStx1 either 1 h before or 1 h after toxin injection. Additionally, streptomycin-treated mice fed the mouse-lethal STEC strain B2F1 that produces the Stx2 variant Stx2d were protected when given a dose of 0.1 mg of cαStx2/kg of body weight administered up to 72 h post-oral bacterial challenge. Since many STEC strains produce both Stx1 and Stx2 and since either toxin may lead to the HUS, we also assessed the protective efficacy of the combined MAbs. We found that both antibodies were required to protect mice from the presence of both Stx1 and Stx2. Pharmacokinetic studies indicated that cαStx1 and cαStx2 had serum half-lives (t1/2) of about 50 and 145 h, respectively. We propose that cαStx1 and cαStx2, both of which have been tested for safety in humans, could be used therapeutically for prevention or treatment early in the development of HUS., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Objective: To analyze the results of the application of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in a large series of Brazilian patients with the diagnosis of SpA and establish its correlations with specific variables into the group., Methods: A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyoarthropathies Study Group (ESSG), attended at 29 referral centers of Rheumatology in Brazil. Clinical and demographic variables, and disease indices (BASDAI, Basfi, Basri, Mases, ASQol) were applicated. The total values of BASDAI were compared to the presence of the different variables., Results: The mean score of BASDAI was 4.20 ± 2.38. The mean scores of BASDAI were higher in patients with the combined (axial + peripheral + entheseal) (4.54 ± 2.38) clinical presentation, compared to the pure axial (3.78 ± 2.27) or pure peripheral (4.00 ± 2.38) clinical presentations (p<0.001). BASDAI also presented higher scores associated with the female gender (p<0.001) and patients who did not practice exercises (p < 0.001). Regarding the axial component, higher values of BASDAI were significantly associated with inflammatory low back pain (p<0.049), alternating buttock pain (p<0.001), cervical pain (p<0.001) and hip involvement (p<0.001). There was also statistical association between BASDAI scores and the peripheral involvement, related to the lower (p=0.004) and upper limbs (p=0.025). The presence of enthesitis was also associated to higher scores of BASDAI (p=0.040). Positive HLA-B27 and the presence of cutaneous psoriasis, inflammatory bowel disease, uveitis and urethritis were not correlated with the mean scores of BASDAI. Lower scores of BASDAI were associated with the use of biologic agents (p<0.001)., Conclusion: In this heterogeneous Brazilian series of SpA patients, BASDAI was able to demonstrate "disease activity" in patients with axial as well as peripheral disease., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

Background: The Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist is used worldwide to drive quality improvement in laboratories in developing countries and to assess the effectiveness of interventions such as the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme. However, the paper-based format of the checklist makes administration cumbersome and limits timely analysis and communication of results., Development of E-Tool: In early 2012, the SLMTA team in Vietnam developed an electronic SLIPTA checklist tool. The e-Tool was pilot tested in Vietnam in mid-2012 and revised. It was used during SLMTA implementation in Vietnam and Cambodia in 2012 and 2013 and further revised based on auditors' feedback about usability., Outcomes: The SLIPTA e-Tool enabled rapid turn-around of audit results, reduced workload and language barriers and facilitated analysis of national results. Benefits of the e-Tool will be magnified with in-country scale-up of laboratory quality improvement efforts and potential expansion to other countries., Competing Interests: The authors declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article.

Cutaneous metastasis is an uncommon manifestation of visceral malignancy. It occurs late in the course of the disease but can be a sign of an unknown neoplasm. A case of local cutaneous metastasis by contiguity with breast adenocarcinoma is reported. It presented as initial manifestation and main complaint of a 68-year-old woman, with no family history and negative screening tests for the disease. Biopsies of ulcers which do not heal, persistent hardened erythema and cutaneous nodules of unknown cause must be performed, since the evidence of cutaneous metastasis can be of extreme importance for the diagnosis, staging and prognosis of an internal cancer. In this scenario, the dermatologist plays a fundamental role and should be always attentive to this diagnostic possibility.

Objective: To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients., Patients and Methods: Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE - Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group)., Results: Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA-B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index - BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult-onset SpA., Conclusions: Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

The objectives of the study were to analyze the deliberate practice variables in three different youth competitive sport settings; to analyze the effects of a season-long exposure on deliberate practice variables. The study explores three contexts in two different sports, soccer and volleyball, and at two competitive levels. The athletes fulfilled the questionnaire at the beginning and at the end of the season. A multilevel analysis was performed. Forty eight boys aged 15-17 years (14 from a volleyball club; 14 from an elite volleyball centre; 20 from a professional soccer club) participated in the study. The measure was an adapted version for soccer and volleyball of the Deliberate Practice Motivation Questionnaire, which assesses two dimensions: the will to compete and the will to excel. Fewer people in the volleyball group showed a will to excel, the soccer group showed an increase in the scores. In will to compete, the three teams showed a decrease in their means. The decrease is more pronounced in the will to excel but the context effect is not significant. The biggest decrease is shown by the elite volleyball team, followed by the club teams. The findings raise questions for managers and coaches who look for physical and technical gifted young athletes and aim to develop their qualities through a careful planned training programme. The insertion in programmes that are believed to foster expertise seems to have unexpected consequences. Sport participation cannot rely exclusively on an orientation toward expertise, forgetting the autonomy of young people to set their goals. Key PointsThe need for the adolescents to focus on game performance can be a deterrent for their own perspectives of a career or just to have fun.The crucial factor to influence the players' answers seems to be the perspective of a rewarding professional career in sport.It is possible that young athletes, after a hard season, re-evaluate their priorities and think that their dedication to sport did not fit their initial expectations.Managers and coaches should be aware of important pedagogical implications, and the effectiveness of sport participation cannot rely exclusively on an orientation toward expertise.

Introduction: Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA)., Methods: A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ)., Results: At least one DMD was used by 73.6% of patients: MTX by 29.2% and SSZ by 21.7%, while 22.7% used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001)., Conclusion: The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

Unlabelled: Inflammatory bowel diseases (Crohn's disease and ulcerative rectocolitis) have extraintestinal manifestations 25% of the patients, with the most common one being the enteropathic arthritis., Methods: Prospective, observational, multicenter study with patients from 29 reference centers participating in the Brazilian Registry of Spondyloarthritis (RBE), which incorporates the RESPONDIA (Ibero-American Registry of Spondyloarthritis) group. Demographic and clinical data were collected from 1472 patients and standardized questionnaires for the assessment of axial mobility, quality of life, enthesitic involvement, disease activity and functional capacity were applied. Laboratory and radiographic examinations were performed. The aim of this study is to compare the clinical, epidemiological, genetic, imaging, treatment and prognosis characteristics of patients with enteropathic arthritis with other types of spondyloarthritis in a large Brazilian cohort., Results: A total of 3.2% of patients were classified as having enteroarthritis, 2.5% had spondylitis and 0.7%, arthritis (peripheral predominance). The subgroup of individuals with enteroarthritis had a higher prevalence in women (P < 0.001), lower incidence of inflammatory axial pain (P < 0.001) and enthesitis (P = 0.004). HLA-B27 was less frequent in the group with enteroarthritis (P = 0.001), even when considering only those with the pure axial form. There was a lower prevalence of radiographic sacroiliitis (P = 0.009) and lower radiographic score (BASRI) (P = 0.006) when compared to patients with other types of spondyloarthritis. They also used more corticosteroids (P < 0.001) and sulfasalazine (P < 0.001) and less non-steroidal anti-inflammatory drugs (P < 0.001) and methotrexate (P = 0.001)., Conclusion: There were differences between patients with enteroarthritis and other types of spondyloarthritis, especially higher prevalence of females, lower frequency of HLA-B27, associated with less severe axial involvement.

Background: Multidisciplinary intervention is an alternative for the treatment of children and adolescent obese. However, the influence of age and menarcheal status in the pattern of metabolic response of obese girls has not been investigated. The following study examined the effects of a 12-week multidisciplinary intervention on metabolic health in overweight girls and the contribution of age and menarcheal status on the resulting changes., Methods: Eighty-eight overweight girls (10 - 16 years) were considered initially for this study and randomly assigned (intervention group: n = 58; control group: n = 30). Forty-six girls completed the intervention program and 16 girls completed the follow-up for the control group. The 12-week intervention included aerobic exercises (three times per week) and nutritional intervention. Anthropometrical measures (body mass, body mass index and waist circumference), menarcheal status and metabolic profiles including glucose, insulin, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed in the beginning and after of intervention. Additionally, were calculated homeostatic model assessment-insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)., Results: After 12-week, girls decreased significantly the body mass (76.6 ± 14.7 to 75.7 ± 14.6 kg) body mass index (30.1 ± 4.0 to 29.4 ± 4.0 kg/m2) and waist circumference (98.9 ± 10.9 to 96.5 ± 11.4 cm). There were differences in HDL-C (43.1 ± 8.2 to 50.3 ± 9.4 mg/dl), TG (120.9 ± 64.3 to 93.3 ± 47.9 mg/dl) and insulin (16.9 ± 7.6 to 15.6 ± 9.8 mg/dl). Relative contribution of age was significant only for within-subject variability in waist circumference., Conclusions: The multidisciplinary based on aerobic training intervention used in this study produced substantial benefits on metabolic health indicators in overweight girls. The changes observed were not related to inter-individual variability in age and maturity status.

The influence of body size and maturation on the responses in peak oxygen uptake (VO2) to a 12-week aerobic training and nutritional intervention in obese boys (n = 30; 10-16 years) was examined using multilevel allometric regressions. Anthropometry, sexual maturity status, peak VO2, and body composition were measured pre- and postintervention. Significant decrements for body mass, body mass index z-score, and waist circumference and increments for stature, fat-free mass, and peak oxygen uptake were observed after intervention. Partitioning body size on peak VO2, the responses of the individuals to training were positive (11.8% to 12.7% for body mass; 7.6% to 8.1% for fat-free mass). Body mass and fat-free mass were found as significant explanatory variables, with an additional positive effect for chronological. The allometric coefficients (k') in the initial models were k' = 0.883 and k' = 1.058 for body mass and fat-free mass, respectively. The coefficients decreased when age was considered (k' = 0.530 for body mass; k' = 0.860 for fat-free mass). Including maturity indicator in the models was not significant, thus the influence of variability in sexual maturity status in responses to exercise-based intervention in peak VO2 may be mediated by the changes in body dimensions.

Objectives: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients., Methods: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%)., Results: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups., Conclusions: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.

Objective: To describe the extra-articular manifestations (cardiac, renal, pulmonary, and neurological), usually not related to spondyloarthritis (SpA), in a large cohort of Brazilian patients., Materials and Methods: This retrospective study analyzed 1,472 patients diagnosed with SpA and cared for at 29 health care centers distributed in the five major geographic regions in the country, participating in the Brazilian Registry of Spondyloarthritis (BRS). All patients were assessed for the prevalence of major extra-articular manifestations (cardiac, renal, pulmonary, and neurological), classified according to the diagnosis [ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD), undifferentiated spondyloarthritis (uSpA), and juvenile SpA], and according to the clinical presentation (axial, peripheral, mixed, and enthesitis)., Results: Of the patients with SpA assessed, 963 had AS, 271 PsA, 49 ReA, 48 arthritis associated with IBD, 98 uSpA, and 43 juvenile SpA. Cardiac involvement was reported in 44 patients (3.0%), pulmonary involvement in 19 (1.3%), renal involvement in 17 (1.2%), and neurological involvement in 13 patients (0.9%). Most patients with visceral involvement had AS or PsA, and the mixed (axial + peripheral) and/or predominantly axial clinical form., Conclusion: Cardiac, renal, pulmonary, and neurological extra-articular manifestations are quite infrequent in SpA, ranging from 0.9% to 3% in this large Brazilian cohort, and affected predominantly patients with AS and PsA.

Excellent performance in sport has a strong positive relationship with the accumulated hours of practice. The specialization years are seen as a decisive moment to lift the skill level, athletic readiness and commitment but the selection and orientation of talent has been strongly dependent of biological and motor variables. The purpose of this study is to describe the achievement and motivation variables that can explain the belonging to an elite competitive level of young basketball players. Eighty-two basketball players under 16 years fulfilled the WOFO Questionnaire (Spence and Helmreich, 1983), and an adapted version of the DPMQ (De Bruin, Rikers and Schmidt, 2007). Forty players (mean age 15. 8 ± 0.96) were engaged in high performance centres and forty-two (mean age 15.6 ± 1.01) played in national level clubs. A decision tree and a random forest analysis between elite and national level players were performed. The most discriminant variable was Will to Excel, with 85,2% true positives in elite or national level. Mastery and competitiveness did not enter the final model. The will to reach excellence in performance can be considered as a condition to engage in more specialized and demanding practice. The assessment of the path to expertise only through motor variables or through the accumulated hours of deliberate practice is limited and can lead to mistaken identification or orientation of young sport talents. The use of a more comprehensive model is needed. Key pointsExcellent performance in sport has a strong positive relationship with the accumulated hours of practice.It seems reasonable that if the young athletes are better selected, have better training conditions and practice and compete more time with better teammates and opponents, the chance of becoming competent adult athletes is greater.A self orientation to excellence may play a crucial role in persistence in practice, in order to achieve higher standards in competition.The specific motivation that underpins participation at different levels and help the coaches to be sensitive to non-biological or non-functional variables, leading to a better knowledge and caring of the adolescents they teach.The assessment of the path to expertise only through motor variables or through the accumulated hours of deliberate practice is limited and can lead to mistaken identification or orientation of young sport talents.

Objectives: The present study aimed at describing the implementation process of a national registry in a developing country (Brazil) and at reporting the main preliminary results of the BiobadaBrasil registry., Material and Methods: Through a PANLAR agreement, the Biobadaser protocol was used as a model for implementing the new registry in our country. During the first two years of this effort, the original protocol was adapted, translated, and presented to all Brazilian rheumatologists. For ten months, data of 1,037 patients (750 subjects treated with biological drugs and 287 control subjects) from 15 centers were collected., Results: Most patients had rheumatoid arthritis (RA) (n = 723). Infliximab was the most frequently used anti-TNF agent, and the total exposure to biologic drugs was 2,101 patient-years. The most common reason for interrupting drug use was lack or loss of efficacy (50%), while 30% withdrew from the treatment arm due to adverse events. Three cases of tuberculosis were observed in the biologic group, with an incidence higher than that of the general Brazilian population. Infections were observed in 23% of the biologic group, and the upper respiratory tract was the most commonly affected site. Only one case of tuberculoid leprosy was observed. No deaths or malignancies attributed to drug effects were observed as of February 2010., Conclusions: The implementation of the BiobadaBrasil registry was successful, and, although recent, the registry has provided important data.

Background: The reproducibility of day-to-day testing of isokinetic concentric and eccentric muscular actions among adolescent basketball players aged 14 to 16 years and relationships of mean within-subject variation in two isokinetic testing sessions with chronological age, biological maturation (estimated age at peak height velocity), training experience, body size, lower-body morphology, and initial strength performance were evaluated., Material and Methods: The sample included 27 basketball players who completed replicate test sessions of 5 repetitions of reciprocal concentric and eccentric knee extensions and flexions at 60º s(-1). A randomly selected subsample of 8 players completed a third testing session to confirm reliability estimates., Results: Coefficients of variation (CV) between sessions 1 and 2 ranged from 8.1% to 17.4%, and intraclass coefficients (ICCs) ranged from 0.72 to 0.89. For sessions 1 and 3, CVs ranged from 3.9% to 6.0%, and ICCs ranged from 0.95 to 0.99. The initial level of strength of eccentric knee flexion (r=-0.43) and eccentric knee extension (r=-0.42) were correlated (P<0.05) with eccentric knee extension within-variation between two sessions. Training experience (r=-0.37, P<0.05) and initial values of concentric knee flexion (r=-0.62, P<0.01) were correlated with concentric knee flexion within-subject differences. Within-subject variation of eccentric knee extension was correlated (P<0.05) with chronologic age (r=0.41), estimated age at peak height velocity (r=-0.38), body size (r=0.41 to 0.47), and leg volume (r=0.39)., Conclusions: Familiarization sessions may improve the reliability of concentric and eccentric knee isokinetic strength testing at 60º s(-1) in adolescent basketball players. Age, maturity status, and training experience of young athletes should be considered when testing knee isokinetic strength at 60º s(-1).

Leprosy is associated with the occurrence of various skin lesions such as macules, papules, plaques, nodules, and even diffused infiltration, depending on the patient's immune response. Its clinical presentation is often different from the usual pattern, leading to confusion in diagnosis. The present article describes a rare case of leprosy simulating lichenoid eruption and explores different aspects of the clinical manifestations, diagnosis, and treatment of this nosologic entity.

Monoclonal antibody (MAb) 11E10 recognizes the Shiga toxin type 2 (Stx2) A(1) subunit. The binding of 11E10 to Stx2 neutralizes both the cytotoxic and lethal activities of Stx2, but the MAb does not bind to or neutralize Stx1 despite the 61% identity and 75% similarity in the amino acids of the A(1) fragments. In this study, we sought to identify the segment or segments on Stx2 that constitute the 11E10 epitope and to determine how recognition of that region by 11E10 leads to inactivation of the toxin. Toward those objectives, we generated a set of chimeric Stx1/Stx2 molecules and then evaluated the capacity of 11E10 to recognize those hybrid toxins by Western blot analyses and to neutralize them in Vero cell cytotoxicity assays. We also compared the amino acid sequences and crystal structures of Stx1 and Stx2 for stretches of dissimilarity that might predict a binding epitope on Stx2 for 11E10. Through these assessments, we concluded that the 11E10 epitope is comprised of three noncontiguous regions surrounding the Stx2 active site. To determine how 11E10 neutralizes Stx2, we examined the capacity of 11E10/Stx2 complexes to target ribosomes. We found that the binding of 11E10 to Stx2 prevented the toxin from inhibiting protein synthesis in an in vitro assay but also altered the overall cellular distribution of Stx2 in Vero cells. We propose that the binding of MAb 11E10 to Stx2 neutralizes the effects of the toxin by preventing the toxin from reaching and/or inactivating the ribosomes.

We sought to visualize the site of Bacillus anthracis spore germination in vivo. For that purpose, we constructed a reporter plasmid with the lux operon under control of the spore small acid-soluble protein B (sspB) promoter. In B. subtilis, sspB-driven synthesis of luciferase during sporulation results in incorporation of the enzyme in spores. We observed that B. anthracis Sterne transformed with our sspBp::lux plasmid was only luminescent during germination. In contrast, Sterne transformed with a similarly constructed plasmid with lux expression under control of the protective antigen promoter displayed luminescence only during vegetative growth. We then infected A/J mice intranasally with spores that harbored the germination reporter. Mice were monitored for up to 14 days with the Xenogen In Vivo Imaging System. While luminescence only became evident in live animals at 18 h, dissection after sacrificing infected mice at earlier time points revealed luminescence in lung tissue at 30 min after intranasal infection. Microscopic histochemical and immunofluorescence studies on luminescent lung sections and imprints revealed that macrophages were the first cells in contact with the B. anthracis spores. By 6 h after infection, polymorphonuclear leukocytes with intracellular spores were evident in the alveolar spaces. After 24 h, few free spores were observed in the alveolar spaces; most of the spores detected by immunofluorescence were in the cytoplasm of interstitial macrophages. In contrast, mediastinal lymph nodes remained nonluminescent throughout the infection. We conclude that in this animal system, the primary site of B. anthracis spore germination is the lungs.

Bacillus collagen-like protein of anthracis (BclA) is an immunodominant glycoprotein located on the exosporium of Bacillus anthracis. We hypothesized that antibodies to this spore surface antigen are largely responsible for the augmented immunity to anthrax that has been reported for animals vaccinated with inactivated spores and protective antigen (PA) compared to vaccination with PA alone. To test this theory, we first evaluated the capacity of recombinant, histidine-tagged, nonglycosylated BclA (rBclA) given with adjuvant to protect A/J mice against 10 times the 50% lethal dose of Sterne strain spores introduced subcutaneously. Although the animals elicited anti-rBclA antibodies and showed a slight but statistically significant prolongation in the mean time to death (MTD), none of the mice survived. Similarly, rabbit anti-rBclA immunoglobulin G (IgG) administered intraperitoneally to mice before spore inoculation increased the MTD statistically significantly but afforded protection to only 1 of 10 animals. However, all mice that received suboptimal amounts of recombinant PA and that then received rBclA 2 weeks later survived spore challenge. Additionally, anti-rBclA IgG, compared to anti-PA IgG, promoted a sevenfold-greater uptake of opsonized spores by mouse macrophages and markedly decreased intramacrophage spore germination. Since BclA has some sequence similarity to human collagen, we also tested the extent of binding of anti-rBclA antibodies to human collagen types I, III, and V and found no discernible cross-reactivity. Taken together, these results support the concept of rBclA as being a safe and effective boost for a PA-primed individual against anthrax and further suggest that such rBclA-enhanced protection occurs by the induction of spore-opsonizing and germination-inhibiting antibodies.

Cytotoxic necrotizing factor type 1 (CNF1) and CNF2 are highly homologous toxins that are produced by certain pathogenic strains of Escherichia coli. These 1,014-amino-acid toxins catalyze the deamidation of a specific glutamine residue in RhoA, Rac1, and Cdc42 and consist of a putative N-terminal binding domain, a transmembrane region, and a C-terminal catalytic domain. To define the regions of CNF1 that are responsible for binding of the toxin to its cellular receptor, the laminin receptor precursor protein (LRP), a series of CNF1 truncated toxins were characterized and assessed for toxin binding. In particular, three truncated toxins, DeltaN63, DeltaN545, and DeltaC469, retained conformational integrity and in vitro enzymatic activity and were immunologically reactive against a panel of anti-CNF1 monoclonal antibodies (MAbs). Based on a comparison of these truncated toxins with wild-type CNF1 and CNF2 in LRP and HEp-2 cell binding assays and in MAb and LRP competitive binding inhibition assays and based on the results of confocal microscopy, we concluded that CNF1 contains two major binding regions: one located within the N terminus, which contained amino acids 135 to 164, and one which resided in the C terminus and included amino acids 683 to 730. The data further indicate that CNF1 can bind to an additional receptor(s) on HEp-2 cells and that LRP can also serve as a cellular receptor for CNF2.

The 13C4 monoclonal antibody (MAb) recognizes the B subunit of Stx1 (StxB1) and neutralizes the cytotoxic and lethal activities of Stx1. However, this MAb does not bind to the B polypeptide of Stx2, despite the 73% amino acid sequence similarity between StxB1 and StxB2. When we compared the amino acid sequences of StxB1 and StxB2, we noted three regions of dissimilarity (amino acids 1 to 6, 25 to 32, and 54 to 61) located near each other on the crystal structure of StxB1. To identify the 13C4 epitope, we generated seven Stx1/Stx2 B chimeric polypeptides that contained one, two, or three of the dissimilar StxB1 regions. The 13C4 MAb reacted strongly with StxB1 and the triple-chimeric B subunit but not with the other chimeras. Mice immunized with the triple-chimeric B subunit survived a lethal challenge with Stx1 but not Stx2, substantiating the identified regions as the 13C4 MAb epitope and suggesting that the incorporation of this epitope into StxB2 altered sites necessary for anti-Stx2-neutralizing Ab production. Next, single amino acid substitutions were made in StxB1 to mimic Stx1d, a variant not recognized by the 13C4 MAb. The 13C4 MAb reacted strongly to StxB1 with the T1A or G25A mutations but not with the N55T change. Finally, we found that the 13C4 MAb blocked the binding of Stx1 to its receptor, globotriaosyl ceramide. Taken together, these results indicate that the 13C4 MAb prevents the interaction of Stx1 with its receptor by binding three nonlinear regions of the molecule that span receptor recognition sites on StxB1, one of which includes the essential residue 55N.

Cytotoxic necrotizing factor type 1 (CNF1), a toxin produced by many strains of uropathogenic Escherichia coli (UPEC), constitutively activates small GTPases of the Rho family by deamidating a single amino acid within these target proteins. Such activated GTPases not only stimulate actin polymerization within affected cells but also, as we previously reported, decrease membrane fluidity on mouse polymorphonuclear leukocytes (PMNs). In that same investigation we found that this diminished membrane movement impedes the clustering of the complement receptor CD11b/CD18 on PMNs and, in turn, decreases PMN phagocytic capacity and microbicidal activity on PMNs in direct contact with CNF1-expressing UPEC as well as on those in proximity to wild-type UPEC. The latter observation suggested to us that CNF1 is released from neighboring bacteria, although at the time of initiation of the study described here, no specific mechanism for export of CNF1 from UPEC had been described. Here we present evidence that CNF1 is released from the CNF1-expressing UPEC strain CP9 (serotype O4/H5/K54) in a complex with outer membrane vesicles (OMVs) and that these CNF1-bearing vesicles transfer biologically active CNF1 to PMNs and attenuate phagocyte function. Furthermore, we show that CNF1-bearing vesicles act in a dose-dependent fashion on PMNs to inhibit their chemotactic response to formyl-Met-Leu-Phe, while purified CNF1 does not. We conclude that OMVs provide a means for delivery of CNF1 from a UPEC strain to PMNs and thus negatively affect the efficacy of the acute inflammatory response to these organisms.

We sought to develop a practical and representative model to study the interactions of enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC, respectively) with human intestinal tissue. For this purpose, human intestinal epithelial HCT-8 cells were cultured under low-shear microgravity conditions in a rotating cell culture system. After 10 days, layered cell aggregates, or 'organoids', developed. Three lines of evidence indicated that these organoids exhibited traits characteristic of normal tissue. First, the organoids expressed normal intestinal tissue markers in patterns that suggested greater cellular differentiation in the organoids than conventionally grown monolayers. Second, the organoids produced higher levels of intestinally expressed disaccharidases and alkaline phosphatase on a cell basis than did conventionally cultured monolayers. Third, HCT-8 organoid tissue developed microvilli and desmosomes characteristic of normal tissue, as revealed by electron microscopy. Because the low-shear microgravity condition is proposed by modelling studies to more closely approximate conditions in the intestinal microvilli, we also tested the impact of microgravity of bacterial growth and virulence gene expression. No influence on growth rates was observed but intimin expression by EHEC was elevated during culture in microgravity as compared with normal gravity. That the responses of HCT-8 organoids to infection with wild-type EPEC or EHEC under microgravitational conditions approximated infection of normal tissue was demonstrated by the classical appearance of the resultant attaching and effacing lesions. We concluded that the low shear microgravity environment promoted growth of intestinal cell organoids with greater differentiation than was seen in HCT-8 cells maintained in conventional tissue culture and provided a reduced gravity environment for study of bacterial-host cell interactions.

The C-terminal third of intimin binds to its translocated receptor (Tir) to promote attaching and effacing lesion formation during infection with enteropathogenic Escherichia coli (EPEC). We observed that the adherence of EPEC strains to HEp-2 cells was reduced and that actin polymerization was blocked by antibody raised against the C-terminal third of intimin alpha.

The diseases and virulence genes associated with Shiga toxin-producing Escherichia coli (STEC) are characterized incompletely. We analyzed, by polymerase chain reaction, 82 STEC isolates collected prospectively in Montana and profiled associated illnesses by patient chart review. All E. coli O157:H7 contained stx2-group genes, as well as eae, iha, espA, and ehxA; 84% contained stx1. Non-O157:H7 STEC less frequently contained stx1 (P=.046), stx2 (P<.001), iha (P<.001), eae, and espA (P=.039 for both), were isolated less often from patients treated in emergency departments (P=.022), and tended to be associated less frequently with bloody diarrhea (P=.061). There were no significant associations between stx genotype and bloody diarrhea, but isolates containing stx2c or stx(2d-activatable) were recovered more often from patients who underwent diagnostic or therapeutic procedures (P=.033). Non-O157:H7 STEC are more heterogeneous and cause bloody diarrhea less frequently than do E. coli O157:H7. Bloody diarrhea cannot be attributed simply to the stx genotype of the infecting organism.