Leptin concentration in children with juvenile idiopathic arthritis

  Wstęp: Leptyna reguluje odpowiedź immunologiczną organizmów. Młodzieńcze idiopatyczne zapalenie stawów (MIZS) jest przewlekłą chorobą stawów u dzieci prowadzącą do przewlekłych zmian w narządach układu ruchu. Materiał i metody: U dzieci z MIZS (n = 42) i zdrowych osobników (n = 28) analizowano następujące parametry: stężenie leptyny (LEP), wskaźnik masy ciała (BMI), hematokryt (HTC), zawartość hemoglobiny (HB), liczba elementów morfotycznych krwi (WBC, LYMPH), odczyn OB i obecność przeciwciał ANA Hep-2. Grupę MIZS podzielono na: dzieci dłużej chorujące (51–148 miesięcy) n = 22 (IA) i krócej chorujące (2–18 miesięcy) n = 20 (IB). Wyniki: Tylko u 58,3% dzieci grupy IA i 50% dzieci grupy IB potwierdzono obecność przeciwciał przeciwjądrowych ANA Hep-2. U chorych dzieci wykazano wyższe poziomy LYMPH i OB oraz większe zróżnicowanie wyników, w porównaniu do dzieci zdrowych. Najwyższe stężenie LEP dla grupy IA wynosiło 37,50 ng/cm3, (Me 5,85) dla IB 40,10 ng/cm3, (Me2,46), w porównaniu z IC, gdzie wynosiło odpowiednio 3,74 ng/cm3 (Me 2,85). Średnia wartość BMI dla grupy IA wynosiła 16,61 kg/m2, dla IC 18,91 kg/m2, a mediana dla IB 15,89 kg/m2 . U dzieci z BMI < 23 kg/m2, grupy IA i IB, stwierdzono niższe stężenia leptyny w porównaniu z grupą kontrolną (p = 0,04). Stwierdzono wpływ schorzenia na zróżnicowanie stężenia leptyny w przeliczeniu na BMI w obu grupach dzieci chorych. U chorych dzieci, z krótszym czasem trwania choroby, wykazano większe zróżnicowanie wartości stężenia leptyny w przeliczeniu na BMI, niż u zdrowych. Wnioski: Dzieci z młodzieńczym idiopatycznym zapaleniem stawów z BMI<23 kg/m2 mają niższe stężenie leptyny niż dzieci grupy kontrolnej. Dzieci z MIZS z krótszym czasem trwania choroby, charakteryzują się większym zróżnicowaniem stężenia leptyny w przeliczeniu na jednostkę BMI, w porównaniu ze zdrowymi dziećmi. (Endokrynol Pol 2015; 66 (5): 417–421)  Introduction: Leptin regulates the organism’s immune response. Juvenile idiopathic arthritis (JIA) is a chronic joint disease in children, leading to chronic changes in motor organs. Material and methods: In children with JIA (n = 42) and healthy subjects (n = 28), leptin concentration (LEP), body mass index (BMI), haematocrit (HTC), haemoglobin (HB), morphotic elements (WBC,LYMPH), erythrocyte sedimentation rate (ESR), and ANA Hep-2 antibodies were analysed. JIA group was divided into: children with a longer (51–148 months) (IA) n = 22 and a shorter disease period (2–18 months) (IB) n = 20. Results: Only 58.3% of the IA and 50% of the IB group had ANA Hep-2 confirmed. The ill children had higher and more diversified LYMPH and ESR levels compared to the healthy children. The highest LEP for the IA group was 37.5 ng/cm3, (Me 5.85), for IB — 40.10 ng/cm3, (Me 2.46) as compared to the IC — 3.74 ng/cm3 (Me 2.85), respectively. The average BMI value for the IA group was 16.61 kg/m2, for IC it was 18.91 kg/m2, and the median for IB was 15.89 kg/m2. Children with BMI values < 23 kg/m2 from the IA and IB group had a reduction in LEP as compared to control group (p = 0.04). The relationship between the illness and LEP diversification per BMI unit was found in both groups. Children with a shorter illness period had higher LEP differentiation per BMI unit compared to the healthy children. Conclusions: Children with juvenile idiopathic arthritis with BMI < 23 kg/m2 had lower leptin concentrations than healthy subjects. Ill children with a shorter-term disease had a higher diversification of leptin concentration per BMI unit as compared to healthy controls. (Endokrynol Pol 2015; 66 (5): 417–421)

Transformative Agreements: Overview, Case Studies, and Legal Analysis

The aim of the report „Transformative Agreements: Overview, Case Studies, and Legal Analysis” is to present the current situation regarding ‘transformative agreements’ understood as a means of transitioning from a subscription-based model of scientific publishing to full and immediate open access. In chapter one, the authors present transformative agreements in the context of Plan S; in chapter two, they outline the current state of negotiations and agreements between scientific institutions and publishers in various countries; in chapter three, they provide legal analysis of the agreements from the ESAC Transformative Agreement Registry. Chapter four consists of three case studies (Germany, Norway, Sweden); finally, chapter five is devoted to recommendations

Introducing the FAIR Principles for research software

Research software is a fundamental and vital part of research, yet significant challenges to discoverability, productivity, quality, reproducibility, and sustainability exist. Improving the practice of scholarship is a common goal of the open science, open source, and FAIR (Findable, Accessible, Interoperable and Reusable) communities and research software is now being understood as a type of digital object to which FAIR should be applied. This emergence reflects a maturation of the research community to better understand the crucial role of FAIR research software in maximising research value. The FAIR for Research Software (FAIR4RS) Working Group has adapted the FAIR Guiding Principles to create the FAIR Principles for Research Software (FAIR4RS Principles). The contents and context of the FAIR4RS Principles are summarised here to provide the basis for discussion of their adoption. Examples of implementation by organisations are provided to share information on how to maximise the value of research outputs, and to encourage others to amplify the importance and impact of this work

Genetically determined telomere length and multiple myeloma risk and outcome

This work was partially supported by intramural funds of Univerity of Pisa and DKFZ; by Fondo de Investigaciones Sanitarias (Madrid, Spain) [PI12/02688 to J. S., PI17/02276 to J.S.]; by Instituto de Salud Carlos III, co-funded by FEDER funds —a way to build Europe—[PI14-00613 to V.M.] and by Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Barcelona, Spain) [2017SGR723 to V.M.]. Open Access funding enabled and organized by Projekt DEAL.Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the "teloscore" in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36-2.11; P = 2.97 x 10(-6) for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86-0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.Univerity of PisaHelmholtz AssociationInstituto de Salud Carlos III PI12/02688 PI17/02276Instituto de Salud Carlos IIIEuropean CommissionFEDER funds-a way to build Europe PI14-00613Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Barcelona, Spain) 2017SGR723Projekt DEA

Association of Circulating COMP and YKL-40 as Markers of Metabolic Changes of Cartilage with Adipocytokines in Juvenile Idiopathic Arthritis

The aim of this study was to evaluate the association of circulating cartilage oligomeric matrix protein (COMP) and human cartilage glycoprotein-39 (YKL-40) as markers of metabolic changes of cartilage, with leptin, adiponectin, and resistin in juvenile idiopathic arthritis (JIA) patients before and after treatment. A significant decrease of COMP and an increase of YKL-4 were found in blood of untreated patients. JIA treatment leading to clinical improvement resulted in normalization of COMP levels only. Concentrations of both markers in treated patients, while showing no clinical improvement, differed from those in controls and patients with remission. The leptin level decreased (p < 0.05) in untreated patients; however, concentrations of adiponectin and resistin increased (p < 0.05) as compared to controls. JIA treatment resulted in normalization of adipocytokine levels in remissive patients but not those with active JIA. Untreated patients showed a correlation between COMP and leptin, adiponectin, and body mass index (BMI) and between YKL-40 and leptin, adiponectin, BMI, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). In inactive JIA, a correlation between YKL-40 and leptin was shown. Treated patients with an active JIA demonstrated a correlation between COMP and adiponectin and between YKL-40 and leptin, adiponectin, BMI, CRP, and ESR. The results of this work indicate that leptin and adiponectin but not resistin may be involved in the development and progression of joint dysfunction in JIA. Additionally, we suggest that YKL-40 may be a useful biomarker of disease activity and may be used to assess treatment towards remission, as compared to COMP

Association of Circulating COMP and YKL-40 as Markers of Metabolic Changes of Cartilage with Adipocytokines in Juvenile Idiopathic Arthritis

The aim of this study was to evaluate the association of circulating cartilage oligomeric matrix protein (COMP) and human cartilage glycoprotein-39 (YKL-40) as markers of metabolic changes of cartilage, with leptin, adiponectin, and resistin in juvenile idiopathic arthritis (JIA) patients before and after treatment. A significant decrease of COMP and an increase of YKL-4 were found in blood of untreated patients. JIA treatment leading to clinical improvement resulted in normalization of COMP levels only. Concentrations of both markers in treated patients, while showing no clinical improvement, differed from those in controls and patients with remission. The leptin level decreased (p &lt; 0.05) in untreated patients; however, concentrations of adiponectin and resistin increased (p &lt; 0.05) as compared to controls. JIA treatment resulted in normalization of adipocytokine levels in remissive patients but not those with active JIA. Untreated patients showed a correlation between COMP and leptin, adiponectin, and body mass index (BMI) and between YKL-40 and leptin, adiponectin, BMI, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). In inactive JIA, a correlation between YKL-40 and leptin was shown. Treated patients with an active JIA demonstrated a correlation between COMP and adiponectin and between YKL-40 and leptin, adiponectin, BMI, CRP, and ESR. The results of this work indicate that leptin and adiponectin but not resistin may be involved in the development and progression of joint dysfunction in JIA. Additionally, we suggest that YKL-40 may be a useful biomarker of disease activity and may be used to assess treatment towards remission, as compared to COMP.</jats:p

Influence of etanercept on leptin and ghrelin secretion in children with juvenile idiopathic arthritis

Objective To assess possible changes in leptin and ghrelin secretion due to etanercept in juvenile idiopathic arthritis (JIA). Methods 50 patients with JIA and 16 age-matched controls were enrolled into this prospective, cross-sectional study. Serum leptin, total and acyl ghrelin were measured in addition to white blood cell (WBC) and lymphocyte counts. Results 25 patients received etanercept and 25 conventional therapies (including methotrexate) for JIA. There was no difference between treatment and control groups in leptin or ghrelin levels and no evidence of a relationship between leptin and ghrelin in patients with JIA. In all children with JIA there was a correlation between leptin and body mass index (BMI). However, compared with children in the conventional treatment group, children in the etanercept group showed a positive correlation between total ghrelin and BMI and those with a low BMI showed a negative correlation between acyl ghrelin and BMI. Conclusion No differences in leptin and ghrelin concentrations were found when patients with JIA and controls were compared or when patients who received etanercept were compared with those who received conventional treatment for JIA. </jats:sec

Investigation of Glycosaminoglycans in Urine and Their Alteration in Patients with Juvenile Idiopathic Arthritis

(1) Background: In this study, we evaluated the modulation of urine glycosaminoglycans (GAGs), which resulted from etanercept (ETA) therapy in patients with juvenile idiopathic arthritis (JIA) in whom methotrexate therapy failed to improve their clinical condition. (2) Methods: The sulfated GAGs (sGAGs, by complexation with blue 1,9-dimethylmethylene), including chondroitin&ndash;dermatan sulfate (CS/DS) and heparan sulfate (HS), as well as non-sulfated hyaluronic acid (HA, using the immunoenzymatic method), were determined in the blood of 89 children, i.e., 30 healthy children and 59 patients with JIA both before and during two years of ETA treatment. (3) Results: We confirmed the remodeling of the urinary glycan profile of JIA patients. The decrease in the excretion of sGAGs (p &lt; 0.05), resulting from a decrease in the concentration of the dominant fraction in the urine, i.e., CS/DS (p &lt; 0.05), not compensated by an increase in the concentration of HS (p &lt; 0.000005) and HA (p &lt; 0.0005) in the urine of patients with the active disease, was found. The applied biological therapy, leading to clinical improvement in patients, at the same time, did not contribute to normalization of the concentration of sGAGs (p &lt; 0.01) in the urine of patients, as well as CS/DS (p &lt; 0.05) in the urine of sick girls, while it promoted equalization of HS and HA concentrations. These results indicate an inhibition of the destruction of connective tissue structures but do not indicate their complete regeneration. (4) Conclusions: The metabolisms of glycans during JIA, reflected in their urine profile, depend on the patient&rsquo;s sex and the severity of the inflammatory process. The remodeling pattern of urinary glycans observed in patients with JIA indicates the different roles of individual types of GAGs in the pathogenesis of osteoarticular disorders in sick children. Furthermore, the lack of normalization of urinary GAG levels in treated patients suggests the need for continued therapy and continuous monitoring of its effectiveness, which will contribute to the complete regeneration of the ECM components of the connective tissue and thus protect the patient against possible disability