Assess efficacy, pharmacokinetics (PK), and safety of intravenous (IV) golimumab in patients with polyarticular-course juvenile idiopathic arthritis (pc-JIA).
 
  Children aged 2 to < 18 years with active pc-JIA despite methotrexate therapy for ≥2 months received 80 mg/m2 golimumab at Weeks 0, 4, then every 8 weeks through week 52 plus methotrexate weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at Weeks 28 and 52, respectively. JIA American College of Rheumatology (ACR) response and safety were also assessed.
 
  In total, 127 children were treated with IV golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70%, and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg·day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to IV golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including 1 death due to septic shock.
 
  Body surface area-based dosing of IV golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA.ClinicalTrials.gov number NCT02277444.
 Body surface area-based dosing of IV golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA.ClinicalTrials.gov number NCT02277444.
  The aims of this study were to examine the longitudinal and bi-directional associations between pain and fatigue with sedentary, standing and stepping time in Rheumatoid Arthritis (RA).
 
  People living with RA undertook identical assessments at baseline (T1 [n = 104]) and 6-month follow-up (T2 [n = 54]). Participants completed physical measures (e.g. height, weight, body-mass index) and routine clinical assessments to characterise RA disease activity (Disease Activity Score-28). Participants also completed questionnaires to assess physical function (Health Assessment Questionnaire), pain (McGill Pain Questionnaire) and fatigue (Multidimensional Assessment of Fatigue Scale). Participants' free-living sedentary, standing and stepping time (min/day) were assessed over 7 days using the activPAL3µTM. Statistical analysis Hierarchical regression analysis was employed to inform the construction of path models, which were subsequently used to examine bi-directional associations between pain and fatigue with sedentae with change in sedentary time. Path analysis supported the hypothesised bi-directionality of associations between change in pain and fatigue with change in sedentary time (pain, ß = 0.38; fatigue, ß = 0.44) and standing time (pain, ß = -0.39; fatigue, ß = -0.50).
 
  Findings suggest pain and fatigue are longitudinally and bi-directionally associated with sedentary and standing time in RA.
 Findings suggest pain and fatigue are longitudinally and bi-directionally associated with sedentary and standing time in RA.We review the exciting potential (and challenges) of quantitative nailfold capillaroscopy, focusing on its role in systemic sclerosis. Quantifying abnormality, including automated analysis of nailfold images, overcomes the subjectivity of qualitative/descriptive image interpretation. First we consider the rationale for quantitative analysis, including the potential for precise discrimination between normal and abnormal capillaries and for reliable measurement of disease progression and treatment response. We discuss nailfold image acquisition and interpretation, and describe how early work on semi-quantitative and quantitative analysis paved the way for semi-automated and automated analysis. Measurement of red blood cell velocity is described briefly. Finally we give a personal view on 'next steps'. From a clinical perspective, increased uptake of nailfold capillaroscopy by general rheumatologists could be achieved via low-cost hand-held devices with cloud-based automated analysis. From a research perspective, automated analysis could facilitate large-scale prospective studies using capillaroscopic parameters as possible biomarkers of systemic sclerosis-spectrum disorders.Little is known about how the health professions organize in low- and middle-income countries (LMICs). Recent strikes among health workers in many LMICs have directed interest toward measuring their impacts and understanding their causes. Yet, much of this literature belies a technical understanding of a social problem. By drawing on theoretical developments in organizational studies, this article proposes health sector movements be understood through attendant social processes of sensemaking as organizations seek to expand pragmatic, moral, and cognitive forms of legitimacy. Kenya, a lower middle-income country in sub-Saharan Africa, is an interesting case for such research. The intersubjective construction of meaning among medical doctors fashions narratives to order institutional change in the Kenyan health sector. This analysis shows how the strong legacy of colonial biomedicine shaped medical professionalism and inherent tensions with a deteriorating state following independence. In 2010, a new constitution and devolution of health services caused a fractured medical community to divide and pursue industrial action in its quest for organizational legitimacy. In this way, strike behavior, as a form of legitimation among union doctors in Kenya, is a risky path to universal health coverage.Auxin and cytokinin are two kinds of important phytohormones that mediate outgrowth of axillary buds in plants. How nitric oxide and its regulator of S-nitrosoglutathione reductase (GSNOR) taking part in auxin and cytokinin signaling for controlling axillary buds outgrowth remains elusive. We explained roles of GSNOR during tomato axillary buds outgrowth by physiological, biochemical and genetic approach. GSNOR negatively regulated NO homeostasis. Suppression of GSNOR promoted axillary buds outgrowth via inhibiting the expression of FZY in both apical and axillary buds.  https://www.selleckchem.com/products/sndx-5613.html  Meanwhile, AUX1 and PIN1 were down-regulated in apical buds but up-regulated in axillary buds in GSNOR-suppressed plants. Thus, reduced IAA accumulation was shown in both apical buds and axillary buds of GSNOR-suppressed plants. GSNOR-mediated changes of NO and auxin affected cytokinin biosynthesis, transport, and signaling. And a decreased ratio of auxin cytokinin was shown in axillary buds of GSNOR-suppressed plants, leading to buds dormancy breaking.