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OBJECTIVE Patient-Reported Outcomes Measurement Information System® (PROMIS® ) measures can be administered via computerized adaptive testing (CAT) or fixed short forms (FSF), but the empirical benefits of CAT versus FSF are unknown in juvenile myositis (JM). This study assesses if PROMIS CAT is feasible, precise, correlated with FSF, and less prone to respondent burden and floor/ceiling effects than FSF in JM. METHODS Patients 8-17 yo (self-report and parent proxy) and parents of patients 5-7 yo (only parent proxy) completed PROMIS Fatigue, Pain Interference, Upper Extremity Function, Mobility, Anxiety and Depressive Symptoms measures. Pearson correlations, paired t-tests, and Cohen's D were calculated between PROMIS CAT and FSF. McNemar test assessed floor/ceiling effects between CAT and FSF. Precision and respondent burden were examined across the T-score range. RESULTS Data from 67 patient-parent dyads were analyzed. CAT and FSF mean scores did not significantly differ except in parent proxy Anxiety and Fatigue (effect size: 0.23 and 0.19, respectively). CAT had less pronounced floor/ceiling effects at the less symptomatic extreme in all domains except self-report Anxiety. Increased item burden and higher standard errors were seen in less symptomatic scorers for CAT. Modified stopping rules limiting CAT item administration did not decrease precision. CONCLUSION PROMIS CAT appears to be feasible and correlated with FSF. CAT had less pronounced floor/ceiling effects, allowing detection of individual differences in less symptomatic patients. Modified stopping rules for CAT may decrease respondent burden. CAT can be considered for long-term follow-up of JM patients.

Cartilage does not naturally heal, and cartilage lesions from trauma and wear-and-tear can lead to eventual osteoarthritis. To address long-term repair, tissue engineering of functional biologic implants to treat cartilage lesions is desirable, but the development of such implants is hindered by several limitations, including (1) donor tissue scarcity due to the presence of diseased tissues in joints, (2) dedifferentiation of chondrocytes during expansion, and (3) differences in functional output of cells dependent on donor age. Toward overcoming these challenges, (1) costal cartilage has been explored as a donor tissue, and (2) methods have been developed to rejuvenate the chondrogenic phenotype of passaged chondrocytes for generating self-assembled neocartilage. However, it remains unclear how the rejuvenation processes are influenced by donor age and, thus, how to develop strategies that specifically target age-related differences. Using histological, biochemical, proteomic, and mechanical assays, this study sought to determine the differences among neocartilage generated from neonatal, juvenile, and adult donors using the Yucatan minipig, a clinically relevant large animal model. Based on the literature, a relatively young adult population of animals was chosen due to a reduction in functional output of human articular chondrocytes after 40 years of age. After isolation, costal chondrocytes were expanded, rejuvenated, and self-assembled, and the neocartilages were assessed. The aggregate modulus values of neonatal constructs were at least 1.65-fold of those from the juvenile or adult constructs. Poisson's ratio also significantly differed among all groups, with neonatal constructs exhibiting values 49% higher than adult constructs. Surprisingly, other functional properties such as tensile modulus and glycosaminoglycan content did not significantly differ among groups. Total collagen content was slightly elevated in the adult constructs compared to neonatal and juvenile constructs. A more nuanced view using bottom-up mass spectrometry showed that Col2a1 protein was not significantly different among groups, but protein content of several other collagen subtypes (i.e., Col1a1, Col9a1, Col11a2, and Col12a1) was modulated by donor age. For example, Col12a1 protein content in adult constructs was found to be 102.9% higher than neonatal-derived constructs. Despite these differences, this study shows that different aged donors can be used to generate neocartilages of similar functional properties. IMPACT STATEMENT: Tissue-engineered neocartilage can be generated with functional properties that mimic native cartilage tissue. However, cell sourcing challenges hinder clinical translation of tissue-engineered cartilage. Chondrocytes can be expanded and rejuvenated for the generation of functional self-assembled cartilage, making an allogeneic approach feasible. However, it is currently unclear if donor age impacts functional properties. In this study, using the Yucatan minipig as a clinically relevant large animal model, we demonstrate that functional properties of self-assembled neocartilage are relatively consistent regardless of donor age, suggesting that a wider range of donor ages may be used for cartilage tissue engineering than previously expected.

To describe high-dose biologic use when treating juvenile idiopathic arthritis (JIA).Patients with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry and treated with a biologic after enrollment were eligible. We described the frequency of high-dose biologic use and characteristics of patients receiving high-dose biologics. We used regression modeling to compare 6-month outcomes (using disease activity measures) between those who increased their biologic from standard to high dose (high-dose group) to those who initiated and remained on standard dosing (no-change group), and to those who switched biologic agents (biologic-switch group). We also compared serious adverse events (SAEs) between groups.A total of 5,352 patients with JIA were treated with biologics following enrollment; 1,080 (20%) had ever received a high-dose biologic. There were no significant differences in outcomes between the high-dose group and the biologic-switch group; both improved disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score 10 (-3.53 and -3.95, respectively; P = 0.68). Although the SAE rates in the high-dose group and the biologic-switch group were numerically higher than the no-change group, the event rates were similar, and neither rate was significantly higher than in the no-change group (unadjusted incident rate ratio 2.5 [95% confidence interval (95% CI) 0.7-8.5] and 1.8 [95% CI 0.7-4.6], respectively).Dosing escalation appears to be a reasonable choice to improve disease control, but large, prospective, randomized studies evaluating specific biologic agents are needed.

BACKGROUND Disease activity in Juvenile Idiopathic Arthritis (JIA) commonly persists into adulthood. Transfer of JIA patients to adult healthcare services can be challenging, with prior studies showing poor rates of success. AIMS This audit sought to examine characteristics of patients undergoing transfer of care within the rheumatology unit at the Royal Children's Hospital (RCH) in Melbourne, with the aim of identifying areas for improvement. Specifically, we sought to determine the rate at which confirmation of established care with an adult service (confirmed transfer of care) was documented in the patient chart. METHODS Patients with a diagnosis of JIA who turned 18 years of age between 2012-2019 were identified. A chart review was undertaken to collect relevant data. RESULTS 177 patients were identified. 64% (114/177) were referred for adult care. The commonest JIA subtypes referred were seronegative polyarticular (35/114 or 30.7%) and oligoarticular JIA (22/114 or 19.3%). Documentation of confirmed transfer of care occurred in 62.3% (71/114), with correspondence received from adult services in 49.1% (56/114). There was no difference in rate of return correspondence from public versus private providers (45% vs. 53.8%, p=0.38). The use of 'backstop appointments' was more likely in those with confirmed transfer of care (66% vs. 30%, p=0.0002). CONCLUSIONS Lack of confirmed transfer of care for JIA patients is common and carries a risk of suboptimal outcomes. Strategies to improve communication with adult services, the routine use of 'backstop' appointments and vigilance regarding potential loss to follow-up at the time of transfer would minimise this risk. This article is protected by copyright. All rights reserved.

BACKGROUND: Vibration training can affect strength improvement. However, the role of the vibration frequency, in terms of knee muscle strength, is unclear. OBJECTIVE: To evaluate the effect of vibration training with the same amplitude and different frequencies on the isokinetic muscle strength of the knee in juvenile football players. METHODS: Juvenile football players were divided into four groups: low frequency (n= 13, 25 Hz), medium frequency (n= 14, 40 Hz), high frequency (n= 14, 50 Hz), and control (n= 13). The frequency groups completed 12 weeks of weight-free vibration training (three times/week) with the same amplitude (3 mm) but different frequency. RESULTS: Compared with baseline, the peak extension torque of the knee at 60∘/s and 240∘/s increased by 8.4% and 12.9%, respectively, in the medium-frequency group, and by 8.9% and 15.5%, respectively, in the high-frequency group. The extensor endurance (the ability of joint muscle groups to maintain a force output over time) of the knee in the high-frequency group increased by 4.3%. At 12 weeks, the high-frequency group had greater knee extensor endurance than the low- and medium-frequency groups. CONCLUSION: In juvenile football players, weight-free vibration training at 40 Hz and 50 Hz improves peak torque of the knee extensors at 60∘/s and 240∘/s, while training at 50 Hz improves endurance of the knee extensors.

In recent years, high-fat diet (HFD) has been widely applied in aquaculture, which reduces the intestinal health of cultured fish. The current study evaluated the protective effects of nano-selenium (nano-Se) on intestinal health of juvenile grass carp (Ctenopharyngodon idella) fed with HFD. A total of 135 experimental fish were fed with a regular diet (Con), a HFD (HFD) and a HFD containing nano-Se at 0.6 mg/kg (HSe) for 10 weeks. The results showed that dietary nano-Se significantly improved the survival rate and feed efficiency which were reduced by HFD in juvenile grass carp (P

While growing awareness of the unmet mental health needs of LGBTQ youth populations has prompted calls for greater emphasis on health equity, efforts have largely overlooked glaring inequities affecting LGBTQ youth who become involved with the justice system. The disproportionality of juvenile justice system involvement for LGTBQ youth is a public health concern that merits focused attention and advocacy from child and adolescent mental health professionals. The proportion of incarcerated youth in the juvenile justice system who are LGBTQ is twice that of LGBTQ youth in the general adolescent population.1 Disparities are even more pronounced for girls-40% of incarcerated girls identify as LGB and/or report same-sex attraction.2 Furthermore, gender and sexuality dimensions intersect with racial and ethnic identities for many youth involved in the justice system. In fact, 85%-90% of incarcerated LGBTQ youth are from ethnic or racial minority backgrounds.2,3 Thus, we call for attentiveness to the intersectional inequities facing LGBTQ youth involved in the justice system and offer solutions for improving their mental health outcomes. Child and adolescent mental health professionals can change trajectories of LGBTQ youth through clinical work that addresses modifiable risk factors facing LGBTQ youth, targeted research efforts on the experiences of LGBTQ youth in justice settings as well as intervention studies, and legislative advocacy that provides protective and appropriate services to LGBTQ youth across various justice system touchpoints.

Стаття присвячена ювенільному ревматоїдному артриту (ЮРА) — одному з найбільш поширених ревматичних захворювань у дітей. У статті викладені сучасні погляди на етіологію, імунопатогенез ЮРА. Розглядаються термінологічні та класифікаційні питання, діагностичні критерії ЮРА, що є предметом наукових дискусій вже протягом останнього століття. Незважаючи на значні досягнення в питаннях діагностики та лікування ЮРА, етіологія і патогенез цього захворювання багато в чому залишаються неясними. Сприятливі фактори, що мають тропізм до тканин суглобів, здатні тривалий час у них персистувати, викликаючи імунне запалення. До них належать артротропні персистуючі віруси (ретровіруси, онкорнавіруси, парвовіруси), здатні тривалий час «не діяти» і тільки в разі їх ініціації будь-якими провокуючими факторами — здійснювати пошкодження на рівні геному клітини. Віруси Коксакі, Епштейна — Барр, цитомегаловірус, віруси герпесу, парвовіруси можуть викликати хронічну вірусну інфекцію на тлі імунологічних дефектів. Ініціаторами розвитку запалення можуть бути часті гострі респіраторні вірусні інфекції, переохолодження, інсоляція, профілактичні щеплення, гормональний дисбаланс, травми суглобів, несприятливі екологічні фактори, хронічні психоемоційні стреси. Важливу роль у виникненні та розвитку ЮРА відіграють генетична схильність і особливості імунної системи. Як маркери ризику розвитку ЮРА називають гени гістосумісності HLA А2, В27, А28, В35, DR5, DR8, DR1. Протективний (захисний) ефект справляють DR2 і DR7, що майже не зустрічаються у хворих на ЮРА. При активному запаленні у дітей з різними варіантами ЮРА характерним є залучення практично всіх ланок імунної системи, активація клітинної і гуморальної ланки імунітету. Основу патогенезу становлять дефекти Т- і В-клітинних імунних реакцій, що призводять до гіперпродукції прозапальних цитокінів та широкого спектра органоспецифічних автоантитіл, що індукують запалення і деструкцію суглобів та інших тканин організму. ЮРА є багатофакторним захворюванням, що розвивається в результаті поєднання генетичної схильності, особливостей імунної системи і впливу факторів зовнішнього середовища. В основі патогенезу імунозапальних ревматичних захворювань лежить поєднання генетично детермінованих (система HLA, поліморфізм генів цитокінів) і придбаних дефектів (дисбаланс) імунорегуляторних механізмів, що обмежують патологічну активацію імунної системи у відповідь на потенційно патогенні фактори зовнішнього середовища, такі як інфекції, порушення мікробіоти кишечника, переохолодження, інсоляція.

Major variations in venom composition can occur between juvenile and adult venomous snakes. However, due to logistical constraints, antivenoms are produced using adult venoms in immunising mixtures, possibly resulting in limited neutralisation of juvenile snake venoms. Daboia russelii is one of the leading causes of snakebite death across South Asia. Its venom is potently procoagulant, causing stroke in prey animals but causing in humans consumptive coagulopathy—a net anticoagulant state—and sometimes death resulting from hemorrhage. In this in vitro study, we compared the venom activity of—and antivenom efficacy against—six 2-week-old D. russelii relative to that of their parents. Using a coagulation analyser, we quantified the relative coagulotoxicity of these venoms in human, avian, and amphibian plasma. The overall potency on human plasma was similar across all adult and neonate venoms, and SII (Serum Institute of India) antivenom was equipotent in neutralising these coagulotoxic effects. In addition, all venoms were also similar in their action upon avian plasma. In contrast, the neonate venoms were more potent on amphibian plasma, suggesting amphibians make up a larger proportion of neonate diet than adult diet. A similar venom potency in human and avian plasmas but varying selectivity for amphibian plasma suggests ontogenetic differences in toxin isoforms within the factor X or factor V activating classes, thereby providing a testable hypothesis for future transcriptomics work. By providing insights into the functional venom differences between adult and neonate D. russelii venoms, we hope to inform clinical treatment of patients envenomated by this deadly species and to shed new light on the natural history of these extremely medically important snakes.

Aggressiveness is one of the most basic behaviors, characterized by targeted intentional actions oriented to cause harm. The reactive type of aggression is regulated mostly by the brain’s prefrontal cortex; however, the molecular changes underlying aggressiveness in adults have not been fully characterized. Here we used an RNA-seq approach to investigate differential gene expression in the prefrontal cortex of bovines from the aggressive Lidia breed at different age stages: young three-year old and adult four-year-old bulls. A total of 50 up and 193 down-regulated genes in the adult group were identified. Furthermore, a cross-species comparative analysis retrieved 29 genes in common with previous studies on aggressive behaviors, representing an above-chance overlap with the differentially expressed genes in adult bulls.Particularly, we detected changes in the regulation of networks such as synaptogenesis, involved in maintenance and refinement of synapses, and the glutamate receptor pathway, which acts as excitatory driver in aggressive responses. Our results provide insights into candidate genes and networks involved in the molecular mechanisms leading to the maturation of the brain. The reduced reactive aggression typical of domestication has been proposed to form part of a retention of juvenile traits as adults (neoteny). The significant age-associated differential expression of genes implicated in aggressive behaviors and concomitant increase in Lidia cattle aggression validates this species as a novel model comparator to explore the impact of behavioral neoteny under domestication.

Aim of the work To evaluate the demographic, clinical presentation, and laboratory findings of the juvenile idiopathic arthritis (JIA) subtypes in Sudanese patients attending the Pediatric Rheumatology Clinic. Patients and methods This single-center study was conducted at the Rheumatology Clinic of Ahmed Gasim Hospital, Khartoum North. A specially designed data collection form was used. Full medical history and physical examination of patients was done. The initial investigation was collected from the patients' records. Results Eighty-one patients were enrolled in the study. Females were 54 and 27 males (F: M was 2:1). The mean age of the patients was 10.8 ± 3.6 years, 58% were above 10 years; disease duration 5.8 ± 2.4 years and age at onset 9 ± 3.8 years, the commonest age at onset was between 5 and 10 years. Half of the patients were from rural areas. There was a positive family history in 7.4%. Morning stiffness was the commonest presenting symptom (98.8%) and uveitis was present in 8.6%. The knee was the most affected joint (82.7%). The polyarticular subtype was found in 51 (63%), systemic-onset in 18 (22.2%), oligo articular in 10 (12.3%) and spondyloarthritis in 2 (2.5%). Seven patients (8.6%) had uveitis. Rheumatoid factor (RF) and antinuclear antibody (ANA) were positive among 30.9% and 46.9% of the participants respectively. Conclusion Females predominate and half of the patients are from rural areas. Polyarticular is the commonest subtype. Morning stiffness is the presenting symptom. The knee joint was the most affected. Positive RF was found in one-third of patients, ANA in about half of them.

We present the case of a 17-year-old Asian man diagnosed with pachydermodactyly, a rare digital fibromatosis. Although this is a non-inflammatory periarticular soft tissue disorder, the clinical appearance can mimic inflammatory arthritis. The patient had a 2-year history of fusiform swelling of multiple proximal interphalangeal joints. He was initially diagnosed with juvenile idiopathic arthritis and treated with methotrexate, but a lack of clinical response led to the diagnosis of pachydermodactyly. Recognising this rare condition can prevent unnecessary and potentially harmful treatment.

To define the prevalence and clinical phenotype of anti-cortactin autoantibodies in adult and juvenile myositis.In this longitudinal cohort study, anti-cortactin autoantibody titers were assessed by enzyme-linked immunosorbent assay in 670 adult myositis patients and 343 juvenile myositis patients as well as in 202 adult healthy controls and 90 juvenile healthy controls. The prevalence of anti-cortactin autoantibodies was compared among groups. Clinical features of patients with and those without anti-cortactin autoantibodies were also compared.Anti-cortactin autoantibodies were more common in adult dermatomyositis (DM) patients (15%; P = 0.005), particularly those with coexisting anti-Mi-2 autoantibodies (24%; P = 0.03) or anti-NXP-2 autoantibodies (23%; P = 0.04). In adult myositis, anti-cortactin was associated with DM skin involvement (62% of patients with anti-cortactin versus 38% of patients without anti-cortactin; P = 0.03), dysphagia (36% versus 17%; P = 0.02) and coexisting anti-Ro 52 autoantibodies (47% versus 26%; P = 0.001) or anti-NT5c1a autoantibodies (59% versus 33%; P = 0.001). Moreover, the titers of anti-cortactin antibodies were higher in patients with interstitial lung disease (0.15 versus 0.12 arbitrary units; P = 0.03). The prevalence of anti-cortactin autoantibodies was not different in juvenile myositis patients (2%) or in any juvenile myositis subgroup compared to juvenile healthy controls (4%). Nonetheless, juvenile myositis patients with these autoantibodies had a higher prevalence of "mechanic's hands" (25% versus 7%; P = 0.03), a higher number of hospitalizations (2.9 versus 1.3; P = 0.04), and lower peak creatine kinase values (368 versus 818 IU/liter; P = 0.02) than those without anti-cortactin.The prevalence of anti-cortactin autoantibodies is increased in adult DM patients with coexisting anti-Mi-2 or anti-NXP-2 autoantibodies. In adults, anti-cortactin autoantibodies are associated with dysphagia and interstitial lung disease.

Key Points A total of 137 patients with JMML were analyzed using DREAM.We developed a robust DNA methylation test that is highly consistent with the array-based international consensus definition for JMML., Visual Abstract, Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm that develops during infancy and early childhood. The array-based international consensus definition of DNA methylation has recently classified patients with JMML into the following 3 groups: high (HM), intermediate (IM), and low methylation (LM). To develop a simple and robust methylation clinical test, 137 patients with JMML were analyzed using the Digital Restriction Enzyme Analysis of Methylation (DREAM), which is a next-generation sequencing–based methylation analysis. Unsupervised consensus clustering of the discovery cohort (n = 99) using DREAM data identified HM (HM_DREAM; n = 35) and LM subgroups (LM_DREAM; n = 64). Of the 98 cases that could be compared with the international consensus classification, 90 HM (n = 30) and LM (n = 60) cases had 100% concordance with DREAM clustering results. Of the remaining 8 cases comprising the IM group, 4 were classified as belonging to the HM_DREAM group and 4 to the LM_DREAM group. A machine-learning classifier was successfully constructed using a support vector machine (SVM), which divided the validation cohort (n = 38) into HM (HM_SVM, n = 18) and LM (LM_SVM; n = 20) groups. Patients with the HM_SVM profile had a significantly poorer 5-year overall survival rate than those with the LM_SVM profile. In conclusion, we developed a robust methylation test using DREAM for patients with JMML. This simple and straightforward test can be easily incorporated into diagnosis to generate a methylation classification for patients so they can receive risk-adapted treatment in the context of future clinical trials.

Background We encountered a 12-year-old girl with Takayasu arteritis (TA) who developed acute heart failure at onset. There have been few reports of specific treatment for acute heart failure (AHF) in TA. We successfully treated her with intravenous methylprednisolone and tocilizumab. Case presentation The patient developed palpitations and shortness of breath 3 weeks before admission. Her symptoms exacerbated rapidly and she finally entered our hospital intensive care unit due to respiratory distress and tachycardia. Blood pressure values measured on the left arm and bilateral legs were paradoxically lower than values taken on the right arm. Chest X-ray revealed a severely enlarged heart. Contrast computed tomography showed an expanded aorta, aortic aneurysm, meandering, and irregular diameter of the aorta. The left ventricular ejection fraction (LVEF) was 20% on cardiac ultrasound. Laboratory examination suggested acute inflammation and positivity of HLA-B52. Her medical condition was finally diagnosed as TA with AHF. Along with inotropes and diuretics, methylprednisolone pulse therapy was administered for 3 days on the 2nd and 12th hospital day followed by oral prednisolone. Cardiac function was slightly improved. As intravenous cyclophosphamide therapy requires hydration and may exacerbate AHF, we started weekly subcutaneous tocilizumab treatment (162 mg/week) from the 20th hospital day. Inotropes were discontinued on the 51st hospital day and her LVEF had improved to 37.5% on the 63rd day when she was discharged. Conclusions Tocilizumab could be a significant treatment option for acute heart failure in juvenile TA.

The severe course of chronic pancreatitis (CP) in children is rare. More often it is caused by hereditary factors and abnormalities of the bile and pancreatic ducts. Cases of the development of pancreatitis against the background of systemic inflammatory diseases are described. Therapy of a systemic disease can aggravate the course of pancreatitis, and the general serious condition of the patient does not allow for the necessary surgical treatment. The article describes the clinical case report of a complicated course of CP against the background of juvenile idiopathic arthritis in a 17-year-old girl. The effectiveness of intraluminal endoscopic methods of treatment (wirsungotomy and stenting of the main pancreatic duct) for relieving exacerbation and complications of CP has been demonstrated.

TNF-α inhibitors are used in the treatment of non-systemic variants of juvenile idiopathic arthritis (JIA) in case of ineffectiveness or intolerance to methotrexate. Despite 20 years of experience of using of etanercept in pediatric rheumatology, a long-term study of the efficacy and safety of the drug in real clinical practice remains necessary. Objective of the study: to study the efficacy and safety of etanercept for treatment of various non-systemic JIA subtypes in real clinical practice. Materials and methods of research: data from the case histories of 375 patients (242 girls and 133 boys) with articular forms of JIA for 2010–2020 were included in a retrospective, open, uncontrolled, nonrandomized, continuous multicenter cohort study. The age of debut was 6.3 (2.9; 10.7) years. Demographic characteristics, subtypes of arthritis, indicators of laboratory activity of inflammation, and outcomes were estimated: achievement of remission, exacerbation, and switching from etanercept to another genetically engineered biological drug (GEBD) were assessed. Results: remission was recorded in 78.9% on average after 6 months. The factors that determine the likelihood of achieving remission were the absence of previous therapy with GEBD (p=0.001) and compliance with therapy – OR=2.5 (95% CI: 1.3; 4.7), p=0.006. Exacerbations were recorded in 29.5% and were associated with the presence of the HLA B27 antigen – OR=2.6 (95% CI: 1.1; 6.0), p=0.028, antinuclear factor seropositivity (p=0.060). Change of etanercept to another GEBD was made in 17.4% of children and was associated with a failure to achieve remission – OR=7.7 (95% CI: 4.0–14.3), p=0.000001, with previous exacerbations – OR=14,8 (5.3; 41.2), p=0.0000001 and the development of de novo uveitis – OR=2.4 (95% CI: 1.1–5.3), p=0.038. The arthritis subtype and the presence of concomitant methotrexate therapy did not significantly affect treatment outcomes. Conclusion: achievement of remission, compliance with therapy, history of previous therapy with GEBD, exacerbation of JIA and development of de novo uveitis determined the main outcomes of etanercept therapy. The JIA subtype, as well as concomitant therapy with methotrexate, did not significantly affect the outcomes of the disease, which makes it possible to consider etanercept therapy a very effective and safe method of treating JIA as a genetically engineered first-line therapy of any variants of articular forms of JIA, even in monotherapy with ineffectiveness or intolerance to methotrexate.

We continued direct morphological studies of the canid coxofemoral joint, considering early-life spatial relationships around the locus of the proximocaudal joint capsule insertion. Our primary goal was to elucidate the postnatal developmental gross anatomy of the proximocaudal femur, among juveniles across Canidae. From an original database of 267 independent (museum) specimens from 11 canid taxa and 1 hybrid taxon, we identified 29 ancient or modern candidate juvenile specimens (nine taxa and one hybrid taxon). Based on optimal ability to recognize landmarks, the best photographic data were categorized into five groups of four each (n = 20). The data groups approximated early juvenile, early-mid juvenile, mid-juvenile, mid-late juvenile; and young adult stages. In this descriptive photographic essay, we demonstrate the developmental spatial proximity among (a) the dorsal meeting of the respective lateral and medial extensions from the growth centers of the femoral head and greater trochanter; (b) the caudodorsal aspect of the coxofemoral joint capsule attachment; (c) a segment of the proximocaudal femoral shaft physis; and (d) an eventual associated mineralized prominence. The latter occurs frequently but not universally, suggesting natural population variability across taxa. Across taxa and juvenile age categories, the morphology thus supports developmental conservation among ancient and modern Canidae. The biomechanical and biological cause-effect implications are not yet clear. For zoological purposes, we apply the term postdevelopmental mineralized prominence to the residual caudolateral surface feature. We extend the original anatomical work of Morgan in zoological and phylogenic arenas, using direct observation of cleared skeletal specimens.

Antagonist and long-lasting environmental manipulations (EM) have successfully induced or reduced the stress responses and quality of life of zebrafish. For instance, environmental enrichment (EE) generally reduces anxiety-related behaviours and improves immunity, while unpredictable chronic stress (UCS) and aquarium-related stressors generate the opposite effects. However, there is an absence of consistency in outcomes for some EM, such as acute exposure to stressors, social enrichment and some items of structural enrichment. Therefore, considering intraspecies variation (sex, personality, and strain), increasing intervention complexity while improving standardisation of protocols and contemplating the possibility that EE may act as a mild stressor on a spectrum between too much (UCS) and too little (standard conditions) stress intensity or stimulation, would reduce the inconsistencies of these outcomes. It would also help explore the mechanism behind stress resilience and to standardise EM protocols. Thus, this review critically analyses and compares knowledge existing over the last decade concerning environmental manipulations for zebrafish and the influences that sex, strain, and personality may have on behavioural, physiological, and fitness-related responses.

Treatment of juvenile hallux valgus can be challenging. Initial treatment with conservative measures is appropriate until exhausted. Surgical treatment should be delayed until after skeletal maturity when possible. Before any intervention, a thorough understanding of the whole patient and any underlying systemic contributors to their hallux valgus, in addition to the radiographic foot parameters, is imperative. Careful and individualized surgical planning should be done to optimize results and decrease the risk for recurrence.

Background. Vaccination is the most effective method for reducing morbidity, disability, mortality from of various infections. However, there was a view for a long time that vaccines are ineffective and unsafe to use in people with rheumatological diseases, including juvenile idiopathic arthritis (JIA). Objective.The aim of the study is to analyze literature data on safety and efficacy of vaccination for JIA patients with live and non-live vaccines.Methods: literature analysis was based on data from medical databases PubMed and Google Scholar.Results. Both live and non-live vaccines are safe and immunogenic enough for children with JIA. Most studies confirm vaccination efficacy in patients with JIA when using glucocorticosteroids (GCS) and methotrexate, while therapy with disease-modifying antirheumatic drugs (DMARD) can reduce antibody titers over time. In general, antibodies levels preservation in previously vaccinated children with JIA is less than in global population. This indicates the need to administer booster doses for such patients. No adverse effects on the course of primary disease after vaccination and no post-vaccine complications were revealed.Conclusion. Vaccination of patients with JIA should be performed with reference to the therapy that the patient already receives, under the control of antibodies level. Booster doses should be implemented in case of titers decrease below the protective levels.

El pejelagarto es una especie carnívora, en la que se ha demostrado una mejora en el crecimiento durante el larvicultivo al incluir almidón de maíz en su dieta, así como una eficiencia en la ruta de la gluconeogénesis al utilizar hasta 23% de carbohidratos en sus dietas. El objetivo de esta investigación fue determinar si el uso de almidón de maíz en el larvicultivo puede producir un afecto de programación metabólica, determinado mediante la bioquímica sanguínea durante la etapa juvenil. Los peces fueron divididos en 3 grupos, los cuales se alimentaron durante 73 días con las dietas experimentales, que tenían diferente porcentaje de inclusión de almidón de maíz (13.8, 22.5 y 28.9 % de carbohidratos). Posteriormente, los peces de los 3 grupos fueron sometidos a una prueba de tolerancia a la glucosa y se midió la concentración de glucosa, triglicéridos y colesterol a las 0, 1.5, 3 y 5 h después de aplicar una descarga de dextrosa intraperitonealmente. Los resultados demuestran que la concentración de carbohidratos y lípidos suministrada mediante la dieta durante la etapa temprana de crianza puede modificar de forma permanente las concentraciones de glucosa y triglicéridos en plasma de los pejelagartos juveniles.

Background There is a knowledge gap about how equine medial femoral condyle (MFC) subchondral radiolucencies (SR) arise and evolve. Osteoclasts are believed to have a role, but have not been studied in situ. Objectives To measure and compare osteoclast density and the percentage of chondroclasts in healthy and MFC SR specimens from juvenile Thoroughbreds. Study design Cadaveric study. Methods Medial femoral condyles from a tissue bank of equine stifles were studied. Inclusion criteria were MFCs (≤8 months old) with a computed tomography SR lesion and histological focal failure of endochondral ossification (L group). Contralateral, lesion-free, MFCs were a control group (CC). Osteochondral slabs were cut through the lesion (L), a healthy site immediately caudal to the lesion, (internal control; IC) and the contralateral, site - matched controls (CC). Histological sections were immunostained with Cathepsin K for osteoclast counting. Osteoclasts in contact with the growth cartilage (chondroclasts) were also counted. The sections were segmented into regions of interest (ROI) at different depths in the subchondral bone: ROI1 (0-1mm), ROI2 (1-3mm) and ROI3 (3-6mm). Osteoclasts were counted and the bone area measured in each ROI to calculate their density. Chondroclasts were counted in ROI1 . Results Sections were studied from L and IC (n=6) and CC sites (n=5). Osteoclast density was significantly higher in ROI1 when compared with ROI3 in all groups. Although higher osteoclast density was measured in ROI1 in the L group, no significant differences were detected when compared with control ROIs. The proportion of chondroclasts in ROI1 was lower in the L sections when compared with controls but no significant differences was detected. Main limitations Limited sample size. Conclusions Osteoclasts are important actors in MFC subchondral bone development, digesting both growth cartilage (chondroclasts) and bone, but the pathophysiology of early MFC SRs cannot be explained solely by an increased osteoclast presence in the subchondral bone.