bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of interleukin‐1β–induced matrix metalloproteinases 1 and 13 production in human osteoarthritic chondrocytes by prostaglandin D2
Authors: Zayed Nadia , Afif Hassan , Chabane Nadir , Mfuna‐Endam Leandra , Benderdour Mohamed , Martel‐Pelletier Johanne , Pelletier Jean‐Pierre , Motiani Rajender K. , Trebak Mohamed , Duval Nicolas , Fahmi Hassan
Published: October 2008

Objective

To investigate the effects of prostaglandin D2 (PGD2) on interleukin‐1β (IL‐1β)–induced matrix metalloproteinase 1 (MMP‐1) and MMP‐13 expression in human chondrocytes and the signaling pathways involved in these effects.

Methods

Chondrocytes were stimulated with IL‐1 in the presence or absence of PGD2, and expression of MMP‐1 and MMP‐13 proteins was evaluated by enzyme‐linked immunosorbent assay. Messenger RNA (mRNA) expression and promoter activity were analyzed by real‐time reverse transcription–polymerase chain reaction and transient transfections, respectively. The role of the PGD2 receptors D prostanoid receptor 1 (DP1) and chemoattractant receptor–like molecule expressed on Th2 cells (CRTH2) was evaluated using specific agonists and antibody‐blocking experiments. The contribution of the cAMP/protein kinase A (PKA) pathway was determined using cAMP‐elevating agents and PKA inhibitors.

Results

PGD2 decreased in a dose‐dependent manner IL‐1–induced MMP‐1 and MMP‐13 protein and mRNA expression as well as their promoter activation. DP1 and CRTH2 were expressed and functional in chondrocytes. The effect of PGD2 was mimicked by BW245C, a selective agonist of DP1, but not by 13,14‐dihydro‐15‐keto‐PGD2, a selective agonist of CRTH2. Furthermore, treatment with an anti‐DP1 antibody reversed the effect of PGD2, indicating that the inhibitory effect of PGD2 is mediated by DP1. The cAMP‐elevating agents 8‐Br‐cAMP and forskolin suppressed IL‐1–induced MMP‐1 and MMP‐13 expression, and the PKA inhibitors KT5720 and H89 reversed the inhibitory effect of PGD2, suggesting that the effect of PGD2 is mediated by the cAMP/PKA pathway.

Conclusion

PGD2 inhibits IL‐1–induced production of MMP‐1 and MMP‐13 by chondrocytes through the DP1/cAMP/PKA signaling pathway. These data also suggest that modulation of PGD2 levels in the joint may have therapeutic potential in the prevention of cartilage degradation.
Coculture of osteoclast precursors with rheumatoid synovial fibroblasts induces osteoclastogenesis via transforming growth factor β–mediated down‐regulation of osteoprotegerin
Authors: Hase Hidenori , Kanno Yumiko , Kojima Hidefumi , Sakurai Daisuke , Kobata Tetsuji
Published: October 2008

Objective

The mechanisms of osteoclast maturation and the role of rheumatoid arthritis (RA) synovial fibroblasts in the control of osteoclastogenesis remain unclear. The purpose of this study was to determine the humoral factors that influence osteoclast differentiation resulting from mutual interactions between osteoclast progenitor cells and synovial fibroblasts.

Methods

The cloned mouse macrophage cell line RAW 264.7 or isolated human CD14+ monocytes were cocultured with RA or osteoarthritis (OA) synovial fibroblasts in the presence of RANKL. Osteoclasts were visualized by staining for tartrate‐resistant acid phosphatase (TRAP), and their functions were evaluated by bone resorption assay. Transforming growth factor β (TGFβ) and osteoprotegerin (OPG) levels were measured by enzyme‐linked immunosorbent assay. Expression of pSmad2 and Smad7 was analyzed by Western blotting.

Results

RANKL‐mediated osteoclast formation was observed in cocultures of RAW cells with RA synovial cells, but not with OA synovial cells. This formation was inhibited by TGFβ receptor kinase inhibitor or neutralizing TGFβ antibody. Human CD14+ monocytes showed the same results with RAW 264.7, and bone resorption activity was consistent with osteoclast formation. RA synovial fibroblasts produced TGFβ in response to cell–cell contact with RAW cells in a RANKL‐dependent manner. TGFβ reduced OPG production by RA synovial fibroblasts, but dose‐dependently increased OPG secretion in OA synovial fibroblasts. TGFβ decreased the expression of pSmad2 and increased the expression of Smad7 in RA synovial fibroblasts, but not OA synovial fibroblasts.

Conclusion

Suppression of OPG production by down‐regulation of TGFβ/Smad2 signaling may contribute to RANKL‐mediated osteoclastogenesis from RA synovial fibroblasts.
Borrelia burgdorferi NapA–driven Th17 cell inflammation in lyme arthritis
Authors: Codolo Gaia , Amedei Amedeo , Steere Allen C. , Papinutto Elena , Cappon Andrea , Polenghi Alessandra , Benagiano Marisa , Paccani Silvia Rossi , Sambri Vittorio , Del Prete Gianfranco , Baldari Cosima Tatiana , Zanotti Giuseppe , Montecucco Cesare , D'Elios Mario Milco , de Bernard Marina
Published: October 2008

Objective

Human Lyme arthritis caused by Borrelia burgdorferi is characterized by an inflammatory infiltrate that consists mainly of neutrophils and T cells. This study was undertaken to evaluate the role of the innate and acquired immune responses elicited by the neutrophil‐activating protein A (NapA) of B burgdorferi in patients with Lyme arthritis.

Methods

Serum anti‐NapA antibodies were measured in 27 patients with Lyme arthritis and 30 healthy control subjects. The cytokine profile of synovial fluid T cells specific for NapA was investigated in 5 patients with Lyme arthritis. The cytokine profile induced by NapA in neutrophils and monocytes was also investigated.

Results

Serum anti‐NapA antibodies were found in 48% of the patients with Lyme arthritis but were undetectable in the healthy controls. T cells from the synovial fluid of patients with Lyme arthritis produced interleukin‐17 (IL‐17) in response to NapA. Moreover, NapA was able to induce the expression of IL‐23 in neutrophils and monocytes, as well as the expression of IL‐6, IL‐1β, and transforming growth factor β (TGFβ) in monocytes, via Toll‐like receptor 2.

Conclusion

These findings indicate that NapA of B burgdorferi is able to drive the expression of IL‐6, IL‐1β, IL‐23, and TGFβ by cells of the innate immune system and to elicit a synovial fluid Th17 cell response that might play a crucial role in the pathogenesis of Lyme arthritis.
Antiinflammatory effect of Rho kinase blockade via inhibition of NF‐κB activation in rheumatoid arthritis
Authors: He Ya , Xu Hanshi , Liang Liuqin , Zhan Zhongping , Yang Xiuyan , Yu Xueqing , Ye Yujin , Sun Lin
Published: October 2008

Objective

There is increasing evidence that the RhoA signaling pathway may play a critical role in the inflammatory response. This study was undertaken to examine the effects of RhoA and its downstream effector Rho kinase (ROK) in synovial inflammation in rheumatoid arthritis (RA).

Methods

RhoA activity was assessed by pull‐down assay. Fasudil and Y27632, both specific inhibitors of ROK, were used to examine the role of ROK in inflammatory responses in vivo and in vitro. Nuclear translocation of NF‐κB was measured by confocal fluorescence microscopy, and DNA binding activity was assessed with a sensitive multiwell colorimetric assay. Enzyme‐linked immunosorbent assay was used to detect cytokine production.

Results

Increased activation of RhoA was found in inflamed synovial membrane cells isolated from patients with RA and from rats with collagen‐induced arthritis (CIA). Intraperitoneal administration of fasudil in rats with CIA significantly reduced synovial inflammation and ROK activity. In vitro, treatment with fasudil or Y27632 decreased production of tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and IL‐6 by synovial membrane cells, peripheral blood mononuclear cells, and fibroblast‐like synoviocytes from patients with active RA. Inhibition of ROK by specific inhibitors or ROK small interfering RNA suppressed lipopolysaccharide‐ or TNFα‐induced NF‐κB nuclear translocation, DNA binding activity, luciferase reporter gene expression, and IκBα degradation.

Conclusion

The results of this study provide new evidence that blockade of ROK inhibits activation of NF‐κB and production of proinflammatory cytokines, suggesting a critical role of ROK in the synovial inflammation of RA. Specific inhibition of ROK may be a novel therapeutic approach in RA.
A CD40–CD154 interaction in tissue fibrosis
Authors: Kawai Masataka , Masuda Ayako , Kuwana Masataka
Published: October 2008

Objective

To examine the role of an interaction between fibroblasts and mononuclear infiltrates through CD40–CD154 engagement in the development of tissue fibrosis.

Methods

Cultured dermal fibroblasts derived from healthy skin were induced to express CD40 by adenoviral gene transfer, stimulated with soluble CD154, and evaluated for proliferation, gene expression, and protein expression in vitro. The skin of mice with bleomycin‐induced skin sclerosis, a model for systemic sclerosis (SSc), was assessed for CD40 and CD154 expression, in vivo fibroblast proliferation, and the expression of specific genes. The effects of an anti‐CD154 monoclonal antibody on bleomycin‐induced skin sclerosis were also examined.

Results

Upon stimulation with soluble CD154, cultured fibroblasts induced to express CD40 by adenoviral gene transfer proliferated and showed up‐regulation of the genes for intercellular adhesion molecule 1, interleukin‐6 (IL‐6), IL‐8, monocyte chemoattractant protein 1 (MCP‐1), and RANTES, as well as up‐regulation of their proteins. In the skin from bleomycin‐treated mice, dermal fibroblasts expressed CD40, and mast cells and CD4+ T cells expressed CD154. Electron microscopic analysis revealed fibroblasts attached to mast cells and T cells with primitive contacts. The proliferation of fibroblasts and the up‐regulated MCP‐1 gene expression preceded thickening of the dermis. Finally, the anti‐CD154 antibody inhibited the bleomycin‐induced skin sclerosis by suppressing fibroblast proliferation and down‐regulating MCP‐1 expression.

Conclusion

The interaction between fibroblasts and mast cells or T cells through CD40–CD154 signaling is critical for fibroblast activation early in the course of fibrosis. Blockade of the CD40–CD154 signal may be a novel therapeutic strategy for human fibrotic diseases, such as SSc.
Reduced limb length and worsened osteoarthritis in adult mice after genetic inhibition of p38 MAP kinase activity in cartilage
Authors: Namdari Surena , Wei Lei , Moore Douglas , Chen Qian
Published: October 2008

Objective

MAP kinase p38 is part of an intracellular signaling pathway activated by environmental stress and inflammatory factors. Since in vitro studies show that inhibiting p38 activity leads to a reduction in the release of degenerative metalloproteinase from chondrocytes, we speculated that inactivation of p38 in vivo may be chondroprotective. To test this hypothesis, we examined the morphology of adult mice that express a dominant‐negative (DN) p38 MAPK transgene in a cartilage‐specific manner.

Methods

The in vivo effects of the genetic inhibition of p38 MAPK activity in cartilage were investigated in 1‐year‐old heterozygous DN p38–transgenic mice (n = 10) using morphologic measurements, microfocal computed tomography scanning, biomechanical testing, and histologic analysis. Results were compared with those in wild‐type (WT) littermates (n = 9).

Results

Adult DN p38 MAPK+/−–transgenic mice exhibited 50% p38 MAPK activity in articular chondrocytes as compared with WT mice. They were significantly shorter in overall body length as well as in the femur and tibia lengths. There were no differences in bone material or mechanical properties between the transgenic and WT mice. Surprisingly, the transgenic mice had higher grades of osteoarthritis of the knee joint.

Conclusion

Genetic inhibition of p38 MAPK activity in cartilage results in shortened limb length and defects in the articular cartilage of the knee joints of adult mice. Our findings demonstrate that chronic life‐long reduction of p38 MAPK activity may be harmful to joint health and suggest that the timing of p38 inhibition for chondroprotection in vivo is an important variable that warrants further investigation.
Fibroblast growth factor 2 inhibits induction of aggrecanase activity in human articular cartilage
Authors: Sawaji Yasunobu , Hynes Judith , Vincent Tonia , Saklatvala Jeremy
Published: October 2008

Objective

Articular chondrocytes are surrounded by an extracellular pool of fibroblast growth factor 2 (FGF‐2). We undertook this study to investigate the possible role of FGF‐2 in aggrecan catabolism by aggrecanase in human articular cartilage.

Methods

Aggrecan catabolism was induced by interleukin‐1α (IL‐1α) in normal human articular cartilage and assessed by measuring the release of glycosaminoglycan (GAG) and aggrecanase‐dependent fragments by Western blotting with antibodies against neoepitopes. ADAMTS‐4 and ADAMTS‐5 messenger RNA (mRNA) expression was measured by quantitative real‐time reverse transcriptase–polymerase chain reaction. Production of matrix metalloproteinases (MMPs) 1, 3, and 13 and tissue inhibitors of metalloproteinases (TIMPs) 1 and 3 was measured by Western blotting. IL‐6 and IL‐8 were measured by enzyme‐linked immunosorbent assay. Proteoglycan synthesis was monitored by 35S‐sulfate incorporation.

Results

IL‐1α caused cleavage of aggrecan in cultured human articular cartilage explants, with release of GAG and aggrecan fragments containing ARGS and AGEG neoepitopes. This was inhibited by FGF‐2 (1–100 ng/ml). Tumor necrosis factor α and retinoic acid also stimulated release of neoepitope, and this was also suppressed by FGF‐2. IL‐1α induced ADAMTS‐4 and ADAMTS‐5 mRNA in primary human chondrocytes, and this was inhibited by FGF‐2. IL‐1α–induced aggrecan breakdown was inhibited by TIMP‐1 or by the N‐terminal portion of TIMP‐3, although FGF‐2 did not affect production of the inhibitors TIMP‐1 and TIMP‐3 when IL‐1α was present. FGF‐2 did not prevent IL‐1α suppression of proteoglycan synthesis and did not negate its ability to stimulate the production of IL‐6, IL‐8, and MMPs 1, 3, and 13.

Conclusion

Our findings suggest that FGF‐2 may play a chondroprotective role in human articular cartilage by controlling the expression and activity of the aggrecanases ADAMTS‐4 and ADAMTS‐5.
Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis
Authors: Dalrymple Judith M. , Stamp Lisa K. , O'Donnell John L. , Chapman Peter T. , Zhang Mei , Barclay Murray L.
Published: October 2008

Objective

There is evidence supporting a therapeutic range for methotrexate polyglutamate (MTXGlu) concentrations in the treatment of rheumatoid arthritis (RA). Knowledge of the pharmacokinetics of MTXGlu1–5 is required for optimal timing of blood sampling. The aim of this study was to determine the time to steady state and the half‐life of accumulation of red blood cell (RBC) MTXGlu1–5 in patients with RA commencing oral MTX, and the time for RBC MTXGlu1–5 to become undetectable and the half‐life of elimination of RBC MTXGlu1–5 in patients ceasing treatment with oral MTX.

Methods

Ten patients beginning treatment and 10 patients stopping treatment with low‐dose oral MTX were recruited. Blood samples were initially collected weekly, with gradual extension to monthly collection over the study period. RBC MTXGlu1–5 concentrations were assayed by high‐performance liquid chromatography. Results were analyzed using a first‐order exponential method.

Results

The median times to reach steady state in RBCs (defined as 90% of the maximum concentration) were 6.2, 10.6, 41.2, 149, and 139.8 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half‐life of accumulation for RBC MTXGlu1–5 ranged from 1.9 weeks to 45.2 weeks. The median times for MTXGlus to become undetectable in RBCs were 4.5, 5.5, 10, 6, and 4 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half‐life of elimination for RBC MTXGlu1–5 ranged from 1.2 weeks to 4.3 weeks.

Conclusion

There is wide interpatient variability of RBC MTXGlu1–5 accumulation and elimination in adults with RA. These data also suggest that after a dose change, >6 months are required for RBC MTXGlu1–5 to reach steady state. Such delays in achieving steady state suggest that more rapid dose escalation or subcutaneous administration from the outset should be considered.
Myotonic dystrophy type 2 found in two of sixty‐three persons diagnosed as having fibromyalgia
Authors: Auvinen Satu , Suominen Tiina , Hannonen Pekka , Bachinski Linda L. , Krahe Ralf , Udd Bjarne
Published: October 2008

Because of its high prevalence, fibromyalgia (FM) is a major general health issue. Myotonic dystrophy type 2 (DM2) is a recently described autosomal‐dominant multisystem disorder. Besides variable proximal muscle weakness, myotonia, and precocious cataracts, muscle pain and stiffness are prominent presenting features of DM2. After noting that several of our mutation‐positive DM2 patients had a previous diagnosis of FM, suggesting that DM2 may be misdiagnosed as FM, we invited 90 randomly selected patients diagnosed as having FM to undergo genetic testing for DM2. Of the 63 patients who agreed to participate, 2 (3.2%) tested positive for the DM2 mutation. Their cases are described herein. DM2 was not found in any of 200 asymptomatic controls. We therefore suggest that the presence of DM2 should be investigated in a large sample of subjects diagnosed as having FM, and clinicians should be aware of overlap in the clinical presentation of these 2 distinct disorders.
Prevalence and course of forefoot impairments and walking disability in the first eight years of rheumatoid arthritis
Authors: Leeden Marike Van Der , Steultjens Martijn P. M. , Ursum Jennie , Dahmen Rutger , Roorda Leo D. , Schaardenburg Dirkjan Van , Dekker Joost
Published: October 2008

Objective

To evaluate the prevalence and 8‐year course of forefoot impairments and walking disability in patients with rheumatoid arthritis (RA).

Methods

A total of 848 patients with recent‐onset RA from 1995 through the present were included. The patients were assessed annually. Pain and swelling of the metatarsophalangeal (MTP) joints, erosions and joint space narrowing of the MTP joints and first interphalangeal joints, and the Health Assessment Questionnaire walking subscale were analyzed using descriptive and correlational techniques.

Results

Pain and swelling of ≥1 MTP joint was present in 70% of patients at baseline, decreasing to ∼40–50% after 2 years. The forefoot erosion score was ≥1 in 19% of the patients at baseline, and the prevalence of forefoot erosion increased to ∼60% after 8 years, during which the mean forefoot erosion score increased from 1.3 to 7.9. At least mild walking disability was present in 57% of patients at baseline, stabilizing at ∼40% after 1 year.

Conclusion

The prevalence rates for pain and swelling of the MTP joints and walking disability are initially high and then stabilize, but the prevalence and severity of forefoot joint damage increase during an 8‐year course of RA. The findings of this study quantitatively emphasize the importance of forefoot involvement in patients with RA.
Gout and the risk of parkinson's disease: A cohort study
Authors: De Vera Mary , Rahman M. Mushfiqur , Rankin James , Kopec Jacek , Gao Xiang , Choi Hyon
Published: October 2008

Objective

Several studies have suggested that higher serum uric acid levels lead to a lower risk of Parkinson's disease (PD) because uric acid exerts antioxidant effects on neurons. Our objective was to examine the relationship between gout and the risk of PD in persons age ≥65 years.

Methods

We conducted a population‐based cohort study using the British Columbia Linked Health Database and PharmaCare data (i.e., prescription drug data for those age ≥65 years). We compared incidence rates of PD between 11,258 gout patients and 56,199 controls matched on age, sex, date of gout diagnosis, and length of medical record. Cox proportional hazards models were used to estimate the relative risk (RR) of PD, adjusting for age, sex, prior comorbid conditions, and use of diuretics and nonsteroidal antiinflammatory drugs.

Results

Over an 8‐year median followup, we identified 1,182 new cases of PD. Compared with individuals without gout, the multivariate RR of PD among those with gout was 0.70 (95% confidence interval [95% CI] 0.59–0.83). In subgroup analyses, the inverse association was similarly present in both sexes and was evident among those who did not use diuretics (RR 0.66, 95% CI 0.54–0.81), but not among diuretic users (RR 0.80, 95% CI 0.58–1.10, P for interaction 0.35).

Conclusion

Our population‐based data provide evidence for a protective effect of gout on the risk of PD and support the purported protective role of uric acid.
Vitamin E in the primary prevention of rheumatoid arthritis: The women's health study
Authors: Karlson Elizabeth W. , Shadick Nancy A. , Cook Nancy R. , Buring Julie E. , Lee I.‐min
Published: October 2008

Objective

Vitamin E supplements may reduce the risk of developing rheumatoid arthritis (RA) through antioxidant effects. Although previous observational studies have investigated this question, no randomized trial data are available.

Methods

The Women's Health Study is a randomized, double‐blind, placebo‐controlled trial designed to evaluate the benefits and risks of low‐dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health professionals age ≥45 years throughout the US, conducted between 1992 and 2004. After excluding women with self‐reported RA at baseline, 39,144 women were included in the present study. The primary end point, definite RA, was confirmed using a connective tissue disease screening questionnaire, followed by medical record review for American College of Rheumatology criteria.

Results

During an average followup of 10 years, 106 cases of definite RA occurred, 50 in the vitamin E group and 56 in the placebo group. Sixty‐four (60%) RA cases were rheumatoid factor positive and 42 (40%) were rheumatoid factor negative. There was no significant association between vitamin E and risk of definite RA (relative risk [RR] 0.89, 95% confidence interval [95% CI] 0.61–1.31). There were also no significant risk reductions for either seropositive RA (RR 0.64, 95% CI 0.39–1.06) or seronegative RA (RR 1.47, 95% CI 0.79–2.72).

Conclusion

Six hundred IU of vitamin E supplements taken every other day is not associated with a significant reduction in the risk of developing RA among women in a randomized, double‐blind, placebo‐controlled trial.
Isometric rate of force development, maximum voluntary contraction, and balance in women with and without joint hypermobility
Authors: Mebes Christine , Amstutz Astrid , Luder Gere , Ziswiler Hans‐Ruedi , Stettler Matthias , Villiger Peter M. , Radlinger Lorenz
Published: October 2008

Objective

To determine differences between hypermobile subjects and controls in terms of maximum strength, rate of force development, and balance.

Methods

We recruited 13 subjects with hypermobility and 18 controls. Rate of force development and maximal voluntary contraction (MVC) during single leg knee extension of the right knee were measured isometrically for each subject. Balance was tested twice on a force plate with 15‐second single‐leg stands on the right leg. Rate of force development (N/second) and MVC (N) were extracted from the force‐time curve as maximal rate of force development (= limit Δforce/Δtime) and the absolute maximal value, respectively.

Results

The hypermobile subjects showed a significantly higher value for rate of force development (15.2% higher; P = 0.038, P = 0.453, ϵ = 0.693) and rate of force development related to body weight (16.4% higher; P = 0.018, P = 0.601, ϵ = 0.834) than the controls. The groups did not differ significantly in MVC (P = 0.767, P = 0.136, ϵ = 0.065), and MVC related to body weight varied randomly between the groups (P = 0.921, P = 0.050, ϵ = 0.000). In balance testing, the mediolateral sway of the hypermobile subjects showed significantly higher values (11.6% higher; P = 0.034, P = 0.050, ϵ = 0.000) than that of controls, but there was no significant difference (4.9% difference; P = 0.953, P = 0.050, ϵ = 0.000) in anteroposterior sway between the 2 groups.

Conclusion

Hypermobile women without acute symptoms or limitations in activities of daily life have a higher rate of force development in the knee extensors and a higher mediolateral sway than controls with normal joint mobility.
A proof‐of‐concept study of the “employment and arthritis: Making it work” program
Authors: Lacaille Diane , White Margaret A. , Rogers Pam A. , Backman Catherine L. , Gignac Monique A. M. , Esdaile John M.
Published: October 2008

Objective

Work disability is a common outcome of inflammatory arthritis (IA), yet few services address employment. We conducted a proof‐of‐concept study of the “Employment and Arthritis: Making It Work” self‐management program aimed at preventing work disability and maintaining at‐work productivity in employed people with IA.

Methods

The program was developed using the precede‐proceed model and self‐management concepts. Program goals included modifying risk factors for work disability and enhancing self‐management of work problems due to IA, as identified in initial focus groups. The program included a self‐learning manual, 5 group sessions, and individual visits with an occupational therapist for an ergonomic assessment and a vocational rehabilitation counselor. It was pilot tested in 2 groups (n = 19) and evaluated over 12 months of followup.

Results

Participants consisted of 19 employed women with IA. Process evaluation demonstrated feasibility and excellent attendance and use of the self‐learning manual. By 1 year, 80% reported increased confidence in requesting job accommodations, 74% had requested an accommodation, and 71% of requested accommodations were implemented. The occupational therapist and vocational rehabilitation counselor visits resulted in recommendations for change in 100% and 74% of participants, respectively, with implementation of some recommended changes in 89% and 63%, respectively. Improvements were observed in self‐confidence in managing problems at work, fatigue interference with work, measures of limitations, and at‐work productivity.

Conclusion

We developed a novel intervention to prevent work disability in patients with IA, combining self‐management group sessions and professional assessments aimed at job retention, which resulted in people making changes to adapt their work to their arthritis, and improved fatigue, self‐efficacy, and at‐work productivity.
Assessing current outcomes of juvenile idiopathic arthritis: A cross‐sectional study in a tertiary center sample
Authors: Solari Nicoletta , Viola Stefania , Pistorio Angela , Magni‐Manzoni Silvia , Vitale Rosa , Ruperto Nicolino , Ullmann Nicola , Filocamo Giovanni , Martini Alberto , Ravelli Angelo
Published: October 2008

Objective

To investigate the disease outcomes of a cross‐sectional sample of children with longstanding juvenile idiopathic arthritis (JIA) seen between September 2002 and December 2006, and to provide a benchmarking of outcomes obtained with current treatment.

Methods

All consecutive patients were included if they met the following criteria: diagnosis of JIA, disease duration ≥5 years, and informed consent. Outcome assessments included disease activity, inactive disease, minimal disease activity, pain, physical function, health‐related quality of life (HRQOL), auxometric measurements, and articular and extraarticular damage.

Results

A total of 310 patients were included. At study visit, patients had on average a low level of disease activity. However, only 21.8% met the criteria for inactive disease, and less than 50% met the definition of minimal disease activity. Additionally, 19.2% had moderate to severe Childhood Health Assessment Questionnaire disability and 3.6% were in Steinbrocker class III–IV. Approximately 10% had major impairment in HRQOL. A total of 34.2% had damage in ≥1 joint or joint group and 26.1% showed extraarticular damage. Of the 125 patients who underwent a wrist radiograph, 35.2% had significant structural damage and 8.7% had growth retardation.

Conclusion

Our patients had on average a low level of disease activity, little or no physical disability, and a satisfactory HRQOL. However, a sizable proportion of patients had persistently active disease, impaired function, and damage. These findings underscore the critical need for treatments and treatment strategies that have the ability to better control disease activity and to reduce the development of disease‐related morbidities.
Feasibility of ultrasound‐guided sacroiliac joint injection considering sonoanatomic landmarks at two different levels in cadavers and patients
Authors: Klauser Andrea , De Zordo Tobias , Feuchtner Gudrun , Sögner Peter , Schirmer Michael , Gruber Johann , Sepp Norbert , Moriggl Bernhard
Published: October 2008

Objective

Sacroiliitis is often caused by rheumatic diseases, and besides other therapeutic options, treatment consists of intraarticular injection of corticosteroids. The purpose of this study was to assess the feasibility of ultrasound (US)‐guided sacroiliac joint (SI joint) injection at 2 different puncture levels in cadavers and patients when defined sonoanatomic landmarks were considered.

Methods

After defining sonoanatomic landmarks, US‐guided needle insertion was performed in 10 human cadavers (20 SI joints) at 2 different puncture sites. Upper level was defined at the level of the posterior sacral foramen 1 and lower level at the level of the posterior sacral foramen 2. In 10 patients with unilateral sacroiliitis, injection at the most feasible level was attempted.

Results

Computed tomography confirmed correct intraarticular needle placement in cadavers by showing the tip of the needle in the joint and intraarticular diffusion of contrast media in 16 (80%) of 20 SI joints (upper level 7 [70%] of 10; lower level 9 [90%] of 10). In all 4 cases in which needle insertion failed, intraarticular SI joint injection at the other level was successful. In patients, 100% of US‐guided injections were successful (8 lower level, 2 upper level), with a mean pain relief of 8.6 after 3 months.

Conclusion

US guidance of needle insertion into SI joints was feasible at both levels when defined sonoanatomic landmarks were used. If SI joint alterations do not allow for direct visualization of the dorsal joint space of the lower level, which is easier to access, the upper level might offer an appropriate alternative.
Active or passive pain coping strategies in hip and knee osteoarthritis? results of a national survey of 4,719 patients in a primary care setting
Authors: Perrot S. , Poiraudeau S. , Kabir M. , Bertin P. , Sichere P. , Serrie A. , Rannou F.
Published: October 2008

Objective

To study pain coping strategies in patients with hip and knee osteoarthritis (OA), and to assess the psychometric qualities of the French version of the Pain Coping Inventory (PCI).

Methods

We conducted a national, cross‐sectional survey in a primary care setting in France. A total of 1,811 general practitioners included 5,324 patients with hip and knee OA who completed several questionnaires, including the PCI, which assesses ability to cope with pain.

Results

The records of 4,719 (86.4%) patients were analyzed (knee 2,781; hip 1,553; hip and knee 385). Supporting the structure of the original questionnaire, we found that the 33 PCI questionnaire items could be grouped into 3 domains defining active coping strategies and 3 defining passive coping strategies. Acceptable convergent validity was found for the PCI (Cronbach's alpha coefficient for each domain >0.68). Coping strategy scores were significantly higher in patients with both knee and hip involvement (mean ± SD 2.3 ± 0.4) than for patients with OA at 1 site (mean ± SD 2.1 ± 0.4), and in women compared with men (P < 0.001). The use of passive pain coping strategies increased with OA duration, and was greater in older and overweight patients, in patients with no current physical activity or major impairment, in retired and nonworking patients, and in patients who were not married, and to a lesser extent in patients with higher pain intensity. Compared with previous data, patients with OA demonstrated lower active and higher passive strategies than patients with rheumatoid arthritis and other chronic painful conditions.

Conclusion

The PCI has good structural validity and is highly suitable for analyzing active and passive pain coping strategies in OA. In OA, active and passive coping strategies differ significantly as a function of age, body mass index, OA involvement, professional and marital status, sport activities, and OA duration, with pain intensity having a weaker effect.
Is health equity considered in systematic reviews of the cochrane musculoskeletal group?
Authors: Tugwell Peter , Maxwell Lara , Welch Vivian , Kristjansson Elizabeth , Petticrew Mark , Wells George , Buchbinder Rachelle , Suarez‐Almazor Maria E. , Nowlan Marie‐Andrée , Ueffing Erin , Khan Maryam , Shea Bev , Tsikata Setorme
Published: October 2008

Objective

To determine whether Cochrane Musculoskeletal Group (CMSG) systematic reviews and corresponding primary studies of rheumatoid arthritis interventions report and analyze the data needed to assess the effectiveness of interventions in reducing socioeconomic differences in health and/or improving the health of the poor.

Methods

We selected all CMSG reviews on rheumatoid arthritis published since issue 1, 2003. Fourteen reviews were identified; 147 of the 156 primary studies included in these reviews were obtained and assessed. We extracted data on whether the dimensions place of residence, race/ethnicity/culture, occupation, gender, religion, education, socioeconomic status, and social capital and networks (PROGRESS) were reported or analyzed, and whether any interventions were aimed at disadvantaged or low‐ and middle‐income country populations.

Results

Among the dimensions of PROGRESS reported at baseline in 147 primary studies, gender (89%) was the most commonly reported, followed by education (25%) and race/ethnicity (18%). Less than 50% of the systematic reviews reported dimensions of PROGRESS even when they had been reported in the primary study. Of 147 primary studies, 6 (5%) were aimed specifically at disadvantaged populations; another 6 reported on effectiveness by at least 1 dimension of PROGRESS.

Conclusion

Primary studies of interventions for rheumatoid arthritis generally reported few variables necessary to answer questions about health inequalities. Most CMSG systematic reviews failed to assess those variables even when described in the primary studies. The Cochrane Health Equity Field welcomes the opportunity to provide guidance to systematic review authors on incorporating equity considerations into their reviews.
Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28‐week, phase III, randomized, double‐blind, parallel‐group trial
Authors: Schumacher H. RALPH , Becker Michael A. , Wortmann Robert L. , MacDonald Patricia A. , Hunt Barbara , Streit Janet , Lademacher Christopher , Joseph‐Ridge Nancy
Published: October 2008

Objective

To compare the urate‐lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function.

Methods

Subjects (n = 1,072) with hyperuricemia (serum urate level ≥8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to ≤2.0 mg/dl) renal function were randomized to receive once‐daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks.

Results

Significantly (P ≤ 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol.

Conclusion

At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function.
Early and dynamic student achievement prediction in e‐learning courses using neural networks
Authors: Lykourentzou Ioanna , Giannoukos Ioannis , Mpardis George , Nikolopoulos Vassilis , Loumos Vassili
Published: October 2008

The increasing popularity of e‐learning has created a need for accurate student achievement prediction mechanisms, allowing instructors to improve the efficiency of their courses by addressing specific needs of their students at an early stage. In this paper, a student achievement prediction method applied to a 10‐week introductory level e‐learning course is presented. The proposed method uses multiple feed‐forward neural networks to dynamically predict students' final achievement and to cluster them in two virtual groups, according to their performance. Multiple‐choice test grades were used as the input data set of the networks. This form of test was preferred for its objectivity. Results showed that accurate prediction is possible at an early stage, more specifically at the third week of the 10‐week course. In addition, when students were clustered, low misplacement rates demonstrated the adequacy of the approach. The results of the proposed method were compared against those of linear regression and the neural‐network approach was found to be more effective in all prediction stages. The proposed methodology is expected to support instructors in providing better educational services as well as customized assistance according to students' predicted level of performance.
Die Wärmeübertragung in porösen Stoffen – Einfluss von Albedo und Extinktion
Authors: Zeitler Martin , Hencke Ernst‐Günter
Published: October 2008

Für die Harmonisierung des europäischen Marktes ist es von Bedeutung, die Eigenschaften von Bau‐ und Dämmstoffen mit möglichst geringen Messunsicherheiten zu ermitteln. Für die Dämmung von betriebstechnischen Anlagen in der Industrie und der technischen Gebäudeausrüstung ist die Wärmeleitfähigkeit für den geplanten Anwendungsbereich in Abhängigkeit von der Temperatur anzugeben. Die eingeführten Prüfmethoden für die Bestimmung der Wärmeleitfähigkeit sind jedoch nicht auf die Verhältnisse bei hohen Temperaturen abgestimmt. Mit prEN 15548‐1:2006 [4] ist eine technische Spezifikation erarbeitet worden, die den Erfordernissen für diese Messungen eher gerecht wird. Um Dämmstoffe unterschiedlicher Lieferformen vergleichen zu können, muss gewährleistet sein, dass die Messmethoden einerseits etwa gleiche Messunsicherheiten beinhalten; andererseits muss klar sein, welche Einflussgrößen sich durch die unterschiedlichen Messmethoden auswirken. Für bestimmte Produkte ist der Einfluss der Dicke wichtig. Er kann unterschiedliche Ursachen haben, wobei der Artikel insbesondere auf den so genannten “Dickeneffekt” eingeht.
Zur Durchstanzbemessung von ausmittig beanspruchten Stützenknoten und Einzelfundamenten nach Eurocode 2
Authors: Hegger Josef , Häusler Frank , Ricker Marcus
Published: October 2008

Die Bemessungsgleichungen gegen Durchstanzen für rotationssymmetrisch beanspruchte Innenstützen sind für die Bemessungspraxis allein nicht ausreichend. In der Praxis führen häufig die Einflüsse aus einer Momenten‐Querkraftinteraktion und die Bemessung von Einzelfundamenten zu Diskussionen. Die Momentenbeanspruchung eines Stützen‐Decken‐Knotens kann sowohl bei Randstützen durch die Randeinspannung der Platte in die Stütze als auch bei Innenstützen, z. B. infolge unterschiedlicher Stützweiten der angrenzenden Deckenfelder, auftreten. Eurocode 2 stellt für die Momenten‐Querkraftinteraktion und für die Fundamentbemessung von DIN 1045‐1 abweichende Bemessungsgleichungen zur Verfügung, die in diesem Beitrag vorgestellt und mit Versuchsergebnissen verglichen werden.
Konzepte des Verbundbaus für hohe Stanzlasten – Grundlagen und Anwendung
Authors: Fastabend Michael , Sauerborn Norbert , Neubauer Till , Doering Norbert
Published: October 2008

Die Tragfähigkeit von Flachdecken wird im Wesentlichen durch die Biegeverformungen und Durchstanzwiderstände beschränkt. Vermittels des Einsatzes von Stanzkreuzen auf der Basis von bauaufsichtlichen Zulassungen oder von Ingenieurmodellen des Verbundbaus lassen sich die ertragenen Durchstanzlasten erheblich steigern. Der vorliegende Beitrag beschreibt am Beispiel des Neubaus der Ernst‐August‐Galerie in Hannover den vorteilhaften Einsatz von Stanzkreuzen des Verbundbaus für höchste Stanzlasten in einer Flachdecke einer Abfangebene.
“Density equilibrium” method for the quantitative and rapid in situ determination of lipid, hydrocarbon, or biopolymer content in microorganisms
Authors: Eroglu Ela , Melis Anastasios
Published: October 2008

The work provides a simple method, based on a direct density equilibrium measurement, for the rapid in situ estimation of total lipid, hydrocarbon or biopolymer content in a variety of prokaryotic and eukaryotic samples. The method can be readily applied to live microalgae and photosynthetic bacteria, single‐celled or colonial microorganisms, as well as cellular fractions and isolated subcellular compartments or components. In this approach, the absolute lipid, hydrocarbon, or biopolymer content of the cells can be readily calculated. This method is especially useful for tracking the oil or polymer content of strains of microalgae and other microorganisms, whose lipid, hydrocarbon or biopolymer content may change with cultivation conditions and/or time, as the case would be in microorganism lipid‐induction industrial processes. The method is also useful for the direct in situ measurement of storage polymer accumulation in live cells, such as starch in microalgae and polyhydroxybutyrate, or other polyhydroxyalkanoates, in photosynthetic and non‐photosynthetic bacteria. Biotechnol. Bioeng. 2009;102: 1406–1415. © 2008 Wiley Periodicals, Inc.
Madness strikes back
Authors: Rose Diana
Published: October 2008

This commentary is concerned with the involvement of mental health service users in research. It will argue that research carried out by service users is one way of giving voice to a previously silenced group—the mad. It is one way in which ‘Madness Strikes Back’. The main theoretical model to be used is that of the early Foucault. I will not be concerned with what has become known as ‘Foucauldian discourse analysis’ since nowhere in Foucault's writing is there reference to conversation or talk. I will, however, be concerned with power as mental health service users are amongst the most disempowered of groups in all societies. I will also be concerned with Foucault's claim that, since the Enlightenment, madness has been positioned as the antithesis of reason, as ‘unreason’. This distinction can be argued to persist in the field of research. Copyright © 2008 John Wiley & Sons, Ltd.
Generalized minimum‐norm perspective shadow maps
Authors: Zhang Fan , Sun Hanqiu , Zhao Chong , Wang Lifeng
Published: October 2008

Shadow mapping has been extensively used for real‐time shadow rendering in 3D computer games, though it suffers from the inherent aliasing problems due to its image‐based nature. This paper presents an enhanced variant of light space perspective shadow maps to optimize perspective aliasing distribution in possible general cases where the light and view directions are not orthogonal. To be mathematically sound, the generalized representation of perspective aliasing errors has been derived in detail. Our experiments have shown the enhanced shadow quality using our algorithm in dynamic scenes. Copyright © 2008 John Wiley & Sons, Ltd.
Responsive listening behavior
Authors: Gillies M. , Pan X. , Slater M. , Shawe‐Taylor J.
Published: October 2008

Humans use their bodies in a highly expressive way during conversation, and animated characters that lack this form of non‐verbal expression can seem stiff and unemotional. An important aspect of non‐verbal expression is that people respond to each other's behavior and are highly attuned to picking up this type of response. This is particularly important for the feedback given while listening to some one speak. However, automatically generating this type of behavior is difficult as it is highly complex and subtle. This paper takes a data driven approach to generating interactive social behavior. Listening behavior is motion captured, together with the audio being listened to. These data are used to learn an animation model of the responses of one person to the other. This allows us to create characters that respond in real‐time during a conversation with a real human. Copyright ? 2008 John Wiley & Sons, Ltd.
Two‐Photon Fluorescent Probes for Biomembrane Imaging: Effect of Chain Length
Authors: Kim Hwan Myung , Kim Bo Ra , Choo Hyo‐Jung , Ko Young‐Gyu , Jeon Seung‐Joon , Kim Chul Hoon , Joo Taiha , Cho Bong Rae
Published: October 2008

Two‐photon fluorescent probes for the cellular membrane, derived from 6‐acyl‐2‐aminonaphthalene as the fluorophore and hexanoyl (CH), lauryl (CL), and stearyl (CS) groups as the receptor, have been synthesized. Their photophysical properties and utility as membrane probes were also studied. Whereas CH cannot be used as a membrane probe due to its high water solubility, CL and CS are useful two‐photon probes for membrane lateral heterogeneity, as they can easily stain cells, emit fluorescence with high sensitivity to the environment polarity, and are capable of imaging the membrane lateral heterogeneity in live cells. Moreover, CS is more likely to be located in the plasma membrane due to its negligible water solubility. Our results show that the liquid ordered‐like domain covers 31–35 % of the cellular surface.
Chemical and Genetic Wrappers for Improved Phage and RNA Display
Authors: Lamboy Jorge A. , Tam Phillip Y. , Lee Lucie S. , Jackson Pilgrim J. , Avrantinis Sara K. , Lee Hye J. , Corn Robert M. , Weiss Gregory A.
Published: October 2008

An Achilles heel inherent to all molecular display formats, background binding between target and display system introduces false positives into screens and selections. For example, the negatively charged surfaces of phage, mRNA, and ribosome display systems bind with unacceptably high nonspecificity to positively charged target molecules, which represent an estimated 35 % of proteins in the human proteome. Here we report the first systematic attempt to understand why a broad class of molecular display selections fail, and then solve the underlying problem for both phage and RNA display. Firstly, a genetic strategy was used to introduce a short, charge‐neutralizing peptide into the solvent‐exposed, negatively charged phage coat. The modified phage (KO7+) reduced or eliminated nonspecific binding to the problematic high‐pI proteins. In the second, chemical approach, nonspecific interactions were blocked by oligolysine wrappers in the cases of phage and total RNA. For phage display applications, the peptides Lysn (where n=16 to 24) emerged as optimal for wrapping the phage. Lys8, however, provided effective wrappers for RNA binding in assays against the RNA binding protein HIV‐1 Vif. The oligolysine peptides blocked nonspecific binding to allow successful selections, screens, and assays with five previously unworkable protein targets.