bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood–brain barrier breakdown and repair by Src after thrombin‐induced injury
Authors: Liu Da‐Zhi , Ander Bradley P. , Xu Huichun , Shen Yan , Kaur Pali , Deng Wenbin , Sharp Frank R. 
Published: November 2009

AbstractObjectiveThrombin mediates the life‐threatening cerebral edema that occurs after intracerebral hemorrhage. Therefore, we examined the mechanisms of thrombin‐induced injury to the blood–brain barrier (BBB) and subsequent mechanisms of BBB repair.MethodsIntracerebroventricular injection of thrombin (20U) was used to model intraventricular hemorrhage in adult rats.ResultsThrombin reduced brain microvascular endothelial cell (BMVEC) and perivascular astrocyte immunoreactivity—indicating either cell injury or death—and functionally disrupted the BBB as measured by increased water content and extravasation of sodium fluorescein and Evans blue dyes 24 hours later. Administration of nonspecific Src family kinase inhibitor (PP2) immediately after thrombin injections blocked brain edema and BBB disruption. At 7 to 14 days after thrombin injections, newborn endothelial cells and astrocytes were observed around cerebral vessels at the time when BBB permeability and cerebral water content resolved. Delayed administration of PP2 on days 2 through 6 after thrombin injections prevented resolution of the edema and abnormal BBB permeability.InterpretationThrombin, via its protease‐activated receptors, is postulated to activate Src kinase phosphorylation of molecules that acutely injure the BBB and produce edema. Thus, acute administration of Src antagonists blocks edema. In contrast, Src blockade for 2 to 6 days after thrombin injections is postulated to prevent resolution of edema and abnormal BBB permeability in part because Src kinase proto‐oncogene members stimulate proliferation of newborn BMVECs and perivascular astrocytes in the neurovascular niche that repair the damaged BBB. Thus, Src kinases not only mediate acute BBB injury but also mediate chronic BBB repair after thrombin‐induced injury. ANN NEUROL 2010;67:526–533
Dysferlin overexpression in skeletal muscle produces a progressive myopathy
Authors: Glover Louise E. , Newton Kimberly , Krishnan Gomathi , Bronson Roderick , Boyle Alexandra , Krivickas Lisa S. , Brown Robert H. 
Published: November 2009

AbstractObjectiveThe dose–response effects of dysferlin transgenesis were analyzed to determine if the dysferlin‐deficient myopathies are good candidates for gene replacement therapy.MethodsWe have generated 3 lines of transgenic mice, expressing low, mid, and high levels of full‐length human dysferlin from a muscle‐specific promoter. Transgenic skeletal muscle was analyzed and scored for morphological and functional deficits.ResultsOverexpression of dysferlin in mice resulted in a striking phenotype of kyphosis, irregular gait, and reduced muscle mass and strength. Moreover, protein dosage correlated with phenotype severity. In contrast to dysferlin‐null skeletal muscle, no evidence of sarcolemmal impairment was revealed. Rather, increased levels of Ca2+‐regulated, dysferlin‐binding proteins and endoplasmic reticulum stress chaperone proteins were observed in muscle lysates from transgenic mice as compared with controls.InterpretationExpression levels of dysferlin are important for appropriate function without deleterious or cytotoxic effects. As a corollary, we propose that future endeavors in gene replacement for correction of dysferlinopathy should be tailored to take account of this. ANN NEUROL 2010;67:384–393
Organotin catalysts grafted onto cross‐linked polystyrene supports through polar spacers
Authors: Pinoie Vanja , Biesemans Monique , Willem Rudolph 
Published: November 2009

AbstractThe present study investigates the suitability of a HypoGel support bearing oligomeric poly(ethylene glycol) (PEG) chains to act as an insoluble carrier for grafted organotin catalysts. Through the introduction of polar spacers, an improved swelling and site accessibility in the polar media typically involved in transesterification reactions are targeted. Advanced structural investigation shows that quantitative conversion into the targeted HypoGel‐supported organotin trichloride is hampered by the existence of intra‐ and/or intermolecular donor‐acceptor O→Sn interactions caused by the presence of donor moieties in the PEG‐linker. Support is provided to the proposal that the latter interactions are at the origin of the moderate catalytic performance displayed by these HypoGel‐supported catalysts, achieving only 41% conversion after 2 hours in the transesterification of ethyl acetate and n‐octanol. In contrast with similar organotin catalysts supported by an alkyl spacer, the HypoGel‐supported materials appear to be poorly recyclable and display poor leaching resistance. Copyright © 2009 John Wiley & Sons, Ltd.
MCM‐41‐supported mercapto palladium(0) complex: an efficient and recyclable catalyst for the heterogeneous Stille coupling reaction
Authors: Zhao Hong , Zheng Guomin , Hao Wenyan , Cai Mingzhong 
Published: November 2009

AbstractThe Stille cross‐coupling reaction of organostannanes with aryl halides was achieved in the presence of a catalytic amount of MCM‐41‐supported mercapto palladium(0) complex (1 mol%) in DMFH2O (9:1) under air atmosphere in good to high yields. This MCM‐41‐supported palladium catalyst can be reused at least 10 times without any decrease in activity. Copyright © 2009 John Wiley & Sons, Ltd.
Can patellar tape reduce the patellar malalignment and pain associated with patellofemoral osteoarthritis?
Authors: Crossley Kay M. , Marino Giovanni P. , Macilquham Michael D. , Schache Anthony G. , Hinman Rana S. 
Published: November 2009

AbstractObjectivePatellar taping is a conservative treatment that may reduce patellar malalignment and pain in people with patellofemoral joint osteoarthritis (OA). This study aimed to compare patellar alignment in people with and without patellofemoral joint OA and to evaluate immediate effects of patellar taping on patellar alignment and pain in people with patellofemoral joint OA.MethodsPatellar malalignment was measured from magnetic resonance imaging (MRI; 15° knee flexion) in 28 individuals (14 with patellofemoral joint OA and 14 asymptomatic, age‐matched controls). In the patellofemoral joint OA group, MRI data were collected in 2 randomly allocated conditions (tape and no tape). Patellar alignment indices were measured from deidentified axial scans by 1 examiner. Pain during squatting was recorded in the 2 conditions (tape and no tape).ResultsPeople with patellofemoral joint OA exhibited greater lateral displacement and bisect offset compared with controls (P < 0.001). Lateral patellar tilt angle did not differ between groups. In the patellofemoral joint OA group, patellar tape resulted in a significant lessening of lateral alignment, with reduced lateral displacement (P = 0.028) and increased lateral patellar tilt angle (P < 0.001). Mean pain during squatting decreased with patellar tape by 15 mm on a 100‐mm scale (P = 0.045).ConclusionPatellar tape may reduce malalignment and pain associated with patellofemoral joint OA.
“Should I tell my employer and coworkers I have arthritis?” A longitudinal examination of self‐disclosure in the work place
Authors: Gignac Monique A.M. , Cao Xingshan 
Published: November 2009

AbstractObjectiveTo examine arthritis self‐disclosure at work, factors associated with disclosure, and prospective relationships of self‐disclosure and work place support with changes to work place interactions, work transitions, and work place stress.MethodsUsing a structured questionnaire, participants with osteoarthritis or inflammatory arthritis were interviewed at 4 time points, 18 months apart. At time 1, all participants (n = 490; 381 women, 109 men) were employed. Of the entire sample, 71% were retained throughout the study. Respondents were recruited using community advertising and from rheumatology and rehabilitation clinics. Self‐disclosure and perceived support from managers and coworkers was assessed, as well as demographic, illness, work‐context, and psychological variables. Generalized estimating equations modeled associations of disclosure and support on changes at work (e.g., job disruptions, work place stress).ResultsAt each time point, 70.6–76.6% of participants had self‐disclosed arthritis to their manager and 85.2–88.1% had told a coworker. Intraindividual variability in disclosure was considerable. Factors associated with self‐disclosure were often inconsistent over time, with the exception of variables assessing the need to self‐disclose (e.g., activity limitations) and perceived coworker support. Self‐disclosure was not associated with changes to work. However, coworker support was related to fewer job disruptions, help with work tasks, and being less likely to reduce hours. Perceived managerial support was associated with less work place stress.ConclusionGreater awareness is needed about issues related to self‐disclosing arthritis at work. This study emphasizes the importance of a supportive work place, especially supportive coworkers, in decisions to discuss arthritis at work and in changes to work that might enable people to remain employed.
Modeling the need for hip and knee replacement surgery. Part 1. A two‐stage cross‐cohort approach
Authors: Judge Andy , Welton Nicky J. , Sandhu Jat , Ben‐Shlomo Yoav 
Published: November 2009

AbstractObjectiveTo explore inequalities in the need for hip/knee replacement surgery using a 2‐stage cross‐cohort approach.MethodsIn the first stage, a small‐area population‐based survey, the Somerset and Avon Survey of Health, was used to provide a high‐quality measure of need for hip/knee replacement using the New Zealand (NZ) score. Receiver operating characteristic curve analyses were used to validate a simplified NZ score, excluding information from clinical examination. In the second stage, a nationally representative population‐based survey, the English Longitudinal Study of Ageing, was used to explore inequalities in need for hip/knee replacement using the simplified NZ score. Multilevel Poisson regression modeling was used to estimate rates of need for surgery. Exposures considered were age, sex, social class, ethnicity, obesity, Index of Multiple Deprivation 2004 deprivation quintiles, rurality, and ethnic mix of area.ResultsRates of need for hip/knee replacement increase with age and are lower in men than in women (rate ratio [RR] 0.7, 95% confidence interval [95% CI] 0.6–0.9 for hips; RR 0.8, 95% CI 0.7–1.0 for knees). Those of lowest social class have greater need. Need was greatest for people living in more deprived areas. Individual ethnic group did not predict the need for surgery. For hip replacement, there was no rurality effect; for knee replacement, those in town and fringe areas had greater need. Obesity was a strong predictor of need for surgery (RR 2.3, 95% CI 1.9–2.8 for hips; RR 2.4, 95% CI 2.0–2.8 for knees).ConclusionThis study provides evidence of greater variations of inequalities in need for hip/knee replacement than previous studies. Further research should explore geographic variation and produce small‐area estimates of need to inform local health planning. It is important to complement data on need with willingness to undergo surgery.
Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: A systematic review and meta‐analysis
Authors: Bannuru Raveendhara R. , Natov Nikola S. , Obadan Isi E. , Price Lori L. , Schmid Christopher H. , McAlindon Timothy E. 
Published: November 2009

AbstractObjectiveTo compare the efficacy of intraarticular hyaluronic acid with corticosteroids for knee osteoarthritis (OA).MethodsOur data sources were Medline, EMBASE, CINAHL, BIOSIS, and the Cochrane database, as well as hand‐ searched reviews, manuscripts, and supplements. For unpublished data we used author contacts. Randomized trials that reported effects of intraarticular hyaluronic acid versus corticosteroids on knee OA were selected based on inclusion criteria. Two reviewers extracted data independently. Using a random‐effects model, we computed effect sizes for pain change from baseline at 2, 4, 8, 12, and 26 weeks. We also performed multivariate analyses accounting for within and between‐study covariance. We performed sensitivity analyses for trials that reported intent‐to‐treat (ITT) analysis and blinding, and directly compared Hyalgan with methylprednisolone.ResultsThe 7 eligible trials included 606 participants. Five reported ITT analyses. At week 2 the effect size was −0.39 (95% confidence interval [95% CI], −0.65, −0.12) favoring corticosteroids; at week 4 it was −0.01 (95% CI −0.23, 0.21) suggesting equal efficacy. At week 8 the effect size was 0.22 (95% CI −0.05, 0.49) favoring hyaluronic acid, and at week 12 it was 0.35 (95% CI 0.03, 0.66) favoring hyaluronic acid. At week 26 the effect size was 0.39 (95% CI 0.18, 0.59), favoring hyaluronic acid. The multivariate analyses and sensitivity analyses generated consistent results.ConclusionFrom baseline to week 4, intraarticular corticosteroids appear to be relatively more effective for pain than intraarticular hyaluronic acid. By week 4, the 2 approaches have equal efficacy, but beyond week 8, hyaluronic acid has greater efficacy. Understanding this trend is useful to clinicians when treating knee OA.
Contribution of a haplotype in the HLA region to anti–cyclic citrullinated peptide antibody positivity in rheumatoid arthritis, independently of HLA–DRB1
Authors: Okada Yukinori , Yamada Ryo , Suzuki Akari , Kochi Yuta , Shimane Kenichi , Myouzen Keiko , Kubo Michiaki , Nakamura Yusuke , Yamamoto Kazuhiko 
Published: November 2009

AbstractObjectiveTo examine the risk of anti–cyclic citrullinated peptide (anti‐CCP) antibody positivity in rheumatoid arthritis (RA) patients carrying certain haplotypes in the HLA region.MethodsA total of 1,389 Japanese patients with RA were genotyped for 30 single‐nucleotide polymorphisms (SNPs) in the HLA region using commercial oligonucleotide arrays (from Perlegen or Affymetrix) as well as for HLA–DRB1 alleles using a sequence‐specific polymerase chain reaction method. Stepwise logistic regression was used to select from among the 30 SNPs the ones that represented a risk of anti‐CCP antibody positivity. Haplotypes of the selected SNPs were inferred using an expectation‐maximization algorithm. Associations of individual SNPs were evaluated with the Cochran‐Armitage test for trend. DRB1 alleles and haplotypes were evaluated with the chi‐square test. Heterogeneities of risks among the shared epitope (SE) and non‐SE HLA–DRB1 alleles were examined using the exact test. Haplotype associations that were independent of individual HLA–DRB1 alleles were evaluated using the likelihood ratio test.ResultsSignificant associations were found for 9 SNPs (smallest P value being 2.4 × 10−8) and in 4 HLA–DRB1 alleles (smallest P value being 2.0 × 10−10 in DRB1*0405). Stepwise logistic regression selected 4 SNPs (rs9262638, rs7775228, rs4713580, and rs9277359). Among the 16 inferred haplotypes of these 4 SNPs, 6 indicated significant associations (smallest P value being 1.9 × 10−11). Risks among SE and non‐SE alleles were significantly heterogeneous (P = 0.0095 and P = 9.8 × 10−9, respectively), indicating the importance of stratification with individual DRB1 alleles rather than SE alleles. Conditional analysis of the risk associated with individual DRB1 alleles identified a risk haplotype that was independent of DRB1 (odds ratio 2.00 [95% confidence interval 1.44–2.79], P = 2.6 × 10−5).ConclusionHeterogeneous risks of anti‐CCP antibody positivity were confirmed among SE and non‐SE alleles in our patient population. A risk haplotype in the HLA region that is independent of HLA–DRB1 was confirmed.
Clinical appropriateness and not race predicted referral for joint arthroplasty
Authors: Ang Dennis C. , James Golda , Stump Timothy E. 
Published: November 2009

AbstractObjectiveTo understand the reasons behind racial disparities in the use of total joint arthroplasty (TJA), we sought to examine the predictors of time to referral to orthopedic surgery for consideration of joint replacement.MethodsIn this prospective, longitudinal study of 676 primary care clinic patients with at least a moderately severe degree of hip or knee osteoarthritis (OA), we examined the effects of race, health beliefs (i.e., perceived benefits and risks) of TJA, and clinical appropriateness of TJA on referral to orthopedic surgery.ResultsThe sample included 255 African Americans (38%) and 421 whites (62%); 523 patients had knee OA (78%) and 153 had hip OA (22%). Subjects were 60% male, with a mean ± SD age of 64 ± 9 years, a mean ± SD body mass index of 33.6 ± 8 kg/m2, and a mean ± SD summary Western Ontario and McMaster Universities Osteoarthritis Index score of 56 ± 14, suggesting moderately severe OA. At baseline, African Americans perceived fewer benefits and greater risk from TJA than whites. There were no significant racial group differences in the proportions of cases deemed clinically appropriate for TJA. After controlling for potential confounders, clinical appropriateness (hazard ratio [HR] 1.95, 95% confidence interval [95% CI] 1.15–3.32; P = 0.01) predicted referral to orthopedic surgery. Neither race (HR 1.30, 95% CI 0.94–2.05; P = 0.1) nor health beliefs (HR 1.0, P = 0.5) were associated with referral status.ConclusionIn this sample of primary care clinic patients, African Americans and whites were equally likely to be referred by their physicians to orthopedic surgery. Clinical appropriateness predicted future referral to orthopedic surgery, and not race or TJA‐specific health beliefs.
Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: Evidence of possible gene–gene interaction and alterations in Th1/Th2 cytokines
Authors: Gourh Pravitt , Agarwal Sandeep K. , Divecha Dipal , Assassi Shervin , Paz Gene , Arora‐Singh Rajpreet K. , Reveille John D. , Shete Sanjay , Mayes Maureen D. , Arnett Frank C. , Tan Filemon K. 
Published: November 2009

AbstractObjectiveSystemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Dysregulation of the immune system, including the Th1/Th2 cytokine balance, is central to the pathogenesis of SSc. This study was undertaken to investigate the hypothesis that single‐nucleotide polymorphisms (SNPs) in TBX21 and STAT4, both of which are critical transcription factors that regulate the Th1/Th2 balance, are associated with SSc susceptibility.MethodsWe tested SNPs in TBX21 and STAT4 for association with SSc in 2 independent cohorts, the SSc Registry cohort (880 SSc cases and 507 controls) and the University of Texas SSc cohort (522 cases and 531 controls). Additional white control genotypes were obtained from public repositories. We also investigated for gene–gene interactions. Plasma cytokines and whole blood gene expression profiles were examined to determine functional effects of these SNPs.ResultsMultiple SNPs in TBX21 and STAT4 were found to be associated with SSc. In a combined analysis of 902 SSc patients and 4,745 controls, TT genotyping of the TBX21 rs11650354 variant revealed a recessive pattern for disease susceptibility (Pcorr = 1.4 × 10−15, odds ratio 3.37, 95% confidence interval 2.4–4.6). In an analysis of 1,039 SSc patients and 3,322 controls, the A allele of the STAT4 variant rs11889341 was associated with increased SSc susceptibility in a dominant pattern (Pcorr = 2.4 × 10−5, odds ratio 1.29, 95% confidence interval 1.2–1.5). Furthermore, we identified gene–gene interaction among the TBX21 and STAT4 variants, such that the STAT4 genotype increased the risk of SSc only in the TBX21 CC genotype group. SSc patients carrying the TBX21 CC genotype had higher interleukin‐6 (IL‐6) and tumor necrosis factor α levels, and those with the TT genotype had elevated IL‐2, IL‐5, IL‐4, and IL‐13 (Th2) levels, compared with controls. Whole blood expression profiles revealed dysregulation of type I interferon pathways in the CC group and T cell pathways in the TT group of the TBX21 SNP.ConclusionThe present results, from studies of 2 independent cohorts, indicate that SNPs in TBX21 and STAT4 contribute uniquely and interactively to SSc susceptibility, leading to altered cytokine balance and immune dysregulation.
Progressive multifocal leukoencephalopathy: A national estimate of frequency in systemic lupus erythematosus and other rheumatic diseases
Authors: Molloy Eamonn S. , Calabrese Leonard H. 
Published: November 2009

AbstractObjectiveProgressive multifocal leukoencephalopathy (PML) is a rare, typically fatal, central nervous system demyelinating disease that results from reactivation of the JC virus, which generally occurs in immunosuppressed hosts. The aim of this study was to generate a national estimate of the frequency of PML among patients with rheumatic diseases.MethodsData were obtained from the Nationwide Inpatient Sample database. This is a 20% sample of all hospital discharges, weighted to represent the entire US inpatient population. Data were analyzed for the years 1998–2005 inclusive, representing 297,797,180 hospital discharges. Cases of PML, systemic lupus erythematosus (SLE), and other rheumatic diseases were identified by diagnostic codes from the International Classification of Diseases, Ninth Revision, Clinical Modification.ResultsA total of 9,675 cases of PML were identified. The majority were associated with human immunodeficiency virus (HIV; 7,934 patients [82.00%]), hematologic cancers (813 patients [8.40%]), and solid cancers (274 patients [2.83%]). Among the rheumatic diseases, 43 cases of PML (0.44%) were associated with SLE, 24 (0.25%) with rheumatoid arthritis (RA), and 25 (0.26%) with other connective tissue diseases (CTDs). When patients with other potential risk factors for PML (HIV, malignancy, bone marrow or other organ transplantation) were excluded, the rates of PML per 100,000 discharges coded for SLE, RA, and other CTDs were 4, 0.4 and 2, respectively, compared with a rate of PML in the background population of 0.2/100,000 discharges.ConclusionThis study was confined to hospitalized patients with rheumatic diseases, and it was also limited by the lack of information regarding immunosuppressive therapy. Nevertheless, the findings suggest that, although rare overall, PML occurs more commonly in SLE than in other rheumatic diseases.