bluuebunny/crossref_metadata_2025 huggingface dataset:
Shoulder Pain in the Community: An Examination of Associative Factors Using a Longitudinal Cohort Study
Authors: Gill T. K. , Shanahan E. M. , Taylor A. W. , Buchbinder R. , Hill C. L.
Published: August 2013

Objective

To determine factors that are predictive of incident, recurrent, or resolved shoulder pain in a community‐based sample from the general population.

Methods

This study used data from the North West Adelaide Health Study, a cohort study located in the northwestern suburbs of Adelaide, South Australia. Data were obtained between 2004 and 2006 and between 2008 and 2010, with time between measurements ranging from 2–6 years (median 4 years), using a computer‐assisted telephone interview, a clinical assessment, and a self‐completed questionnaire. Multivariate logistic regression was used to examine the factors associated with shoulder pain.

Results

Overall, 14.6% (95% confidence interval [95% CI] 12.7–16.7) of 2,337 eligible participants reported that they had developed (or had incident) shoulder pain between 2 time points of the cohort study, 8.8% (95% CI 7.5–10.3) reported recurrent shoulder pain, and 8.7% (95% CI 7.0–10.6) had resolved shoulder pain. Incident shoulder pain was significantly associated with physically heavier occupational activities and pain in other joints after adjustment for age, sex, and body mass index. Recurrent shoulder pain was also associated with pain in other joints, but also with depressive symptoms, smoking, and decreased shoulder range of movement. Resolved shoulder pain was associated with being female, other areas of pain, and decreased shoulder range of movement, but higher grip strength.

Conclusion

Different factors were associated with incident, recurrent, or resolved shoulder pain in a longitudinal cohort study. Consideration of all of these factors may assist in the prevention and management of shoulder pain and the possible identification of those at risk of long‐term shoulder problems.
Improvement in Health‐Related Quality of Life for Children With Juvenile Idiopathic Arthritis After Start of Treatment With Etanercept
Authors: Klotsche Jens , Minden Kirsten , Thon Angelika , Ganser Gerd , Urban Andreas , Horneff Gerd
Published: August 2013

Objective

Improvement in health‐related quality of life (HRQOL) is an important therapy goal in the treatment of patients with juvenile idiopathic arthritis (JIA). We investigated the 12‐month course of HRQOL in patients with JIA after the start of therapy with etanercept and identified its determining factors.

Methods

Children with JIA were enrolled in the BiKer (Biologics in Pediatric Rheumatology) registry at the start of etanercept treatment. Children were prospectively followed in the first year of treatment and completed the Pediatric Quality of Life Inventory (PedsQL) at each occasion. The change in HRQOL was investigated by random‐effect regression models. The time‐varying variables pain and inactive disease were used for predicting the change in HRQOL. Inactive disease was defined by the Wallace et al criteria and pain was assessed on a visual analog scale (range 0–100).

Results

The children (n = 61) had a mean age of 10.6 years and a mean disease duration of 3.4 years at the start of etanercept. The mean PedsQL total score was 75. The PedsQL total score increased at a rate of 2.8 units per month (P < 0.001) in the first 6 months of treatment, up to a level of 89.7. A low HRQOL score was significantly highly associated with the number of tender joints, functional restrictions, pain, disease activity, and the existence of a comorbid condition at baseline. Inactive disease and reduced pain predicted better HRQOL under etanercept treatment.

Conclusion

HRQOL was dramatically improved in children who started etanercept treatment. Inactive disease and lower pain were important predictors for improvement of HRQOL over time.
Utility of the Ultrasound Examination of the Hand and Wrist Joints in the Management of Established Rheumatoid Arthritis
Authors: Ceponis Arnoldas , Onishi Maika , Bluestein Harry G. , Kalunian Kenneth , Townsend Jeanne , Kavanaugh Arthur
Published: August 2013

Objective

To investigate the usefulness of point‐of‐care hand and wrist joint ultrasound (US) examination in patients with established rheumatoid arthritis (RA).

Methods

Fifty‐one RA patients were evaluated using clinical disease activity measures and gray‐scale and power Doppler (PD) US. Agreement between US and clinical findings and its impact on physicians' confidence and clinical decision were assessed.

Results

Agreement between intraarticular PD signal and joint swelling (JS) was moderate (82%; κ = 0.44). Agreement between PD signal and joint tenderness to palpation (TTP) was fair (75%; κ = 0.24). The greatest agreement between PD signal and clinical findings was seen in the 5th metacarpophalangeal (MCP) joint (96% JS, 88% TTP) and the poorest agreement was seen in the wrist (69% JS, 65% TTP) and 2nd (75% JS, 72% TTP) and 3rd (82% JS, 72% TTP) MCP joints. The presence of PD signal in nonswollen and/or nontender joints accounted for most of the disagreement in the wrists, while the opposite was true for the 2nd/3rd MCP joints. Agreement between sonographic synovial thickening and clinical findings was poor. Total sonographic synovial hypertrophy or PD score correlated significantly with physician‐recorded, but not patient‐recorded, clinical outcomes. US increased both physicians' confidence in their clinical decision (P < 0.0005, irrespective of Clinical Disease Activity Index score) and patients' confidence in physicians' medical decisions (88.4% of the cases). US modified biologic agent and/or disease‐modifying antirheumatic drug (DMARD) use in 7 individual cases, but it did not affect the overall treatment plan (P > 0.15) or DMARD (P < 0.062) or biologic agent (P > 1.0) use in this group of RA patients.

Conclusion

PD examination of the wrist and 2nd/3rd MCP joints might be feasible and clinically meaningful in evaluation of disease activity in patients with established RA. US examination of the hand/wrist joints in RA increases physicians' confidence in their clinical decision and can help to individualize DMARD and biologic agent use.
Survival and Predictors of Mortality in Systemic Sclerosis‐Associated Pulmonary Arterial Hypertension: Outcomes From the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry
Authors: Chung Lorinda , Domsic Robyn T. , Lingala Bharathi , Alkassab Firas , Bolster Marcy , Csuka M. E. , Derk Chris , Fischer Aryeh , Frech Tracy , Furst Daniel E. , Gomberg‐Maitland Mardi , Hinchcliff Monique , Hsu Vivien , Hummers Laura K. , Khanna Dinesh , Medsger Thomas A. , Molitor Jerry A. , Preston Ioana R. , Schiopu Elena , Shapiro Lee , Silver Richard , Simms Robert , Varga John , Gordon Jessica K. , Steen Virginia D.
Published: August 2013

Objective

To assess cumulative survival rates and identify independent predictors of mortality in patients with incident systemic sclerosis (SSc)–associated pulmonary arterial hypertension (PAH) who had undergone routine screening for PAH at SSc centers in the US.

Methods

The Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma registry is a prospective registry of SSc patients at high risk for PAH or with definite pulmonary hypertension diagnosed by right‐sided heart catheterization within 6 months of enrollment. Only patients with World Health Organization group I PAH (mean pulmonary artery pressure ≥25 mm Hg and pulmonary capillary wedge pressure ≤15 mm Hg without significant interstitial lung disease) were included in these analyses.

Results

In total, 131 SSc patients with incident PAH were followed for a mean ± SD of 2.0 ± 1.4 years. The 1‐, 2‐, and 3‐year cumulative survival rates were 93%, 88%, and 75%, respectively. On multivariate analysis, age >60 years (hazard ratio [HR] 3.0, 95% confidence interval [95% CI] 1.1–8.4), male sex (HR 3.9, 95% CI 1.1–13.9), functional class (FC) IV status (HR 6.5, 95% CI 1.8–22.8), and diffusing capacity for carbon monoxide (DLco) <39% predicted (HR 4.2, 95% CI 1.3–13.8) were significant predictors of mortality.

Conclusion

This is the largest study describing survival in patients with incident SSc‐associated PAH followed up at multiple SSc centers in the US who had undergone routine screening for PAH. The survival rates were better than those reported in other recently described SSc‐associated PAH cohorts. Severely reduced DLco and FC IV status at the time of PAH diagnosis portended a poor prognosis in these patients.
Lifetime Risk of Total Knee Replacement and Temporal Trends in Incidence by Health Care Setting, Socioeconomic Status, and Geographic Location
Authors: Bohensky Megan A. , Ackerman Ilana , DeSteiger Richard , Gorelik Alexandra , Brand Caroline A.
Published: August 2013

Objective

To estimate the lifetime risk of total knee replacement (TKR) and examine temporal trends in TKR incidence in the state of Victoria, Australia.

Methods

We performed a retrospective analysis of a population‐based longitudinal cohort of patients (ages ≥40 years) who received a primary TKR in Victoria from 1999–2008. Hospital separations and life tables were used to estimate lifetime risk. Temporal changes in TKR incidence were examined according to health care setting (public versus private), socioeconomic status (SES), and geographic location (regional versus metropolitan).

Results

There were 43,570 incidents of primary TKRs identified over the study period. In 2008, the lifetime risk of surgery was 10.4% (95% confidence interval [95% CI] 10.13–10.64%) for men and 11.9% (95% CI 11.63–12.13%) for women. TKRs increased steadily over the study period in private hospitals (overall increase of 90%) with a smaller growth in procedure numbers for public hospitals (overall increase of 40%). From 2002–2003 onward, the low SES tertile showed a lower incidence of TKR compared to the middle and high SES groups, with incidence rates of 1.09 (95% CI 1.04–1.15), 1.22 (95% CI 1.17–1.28), and 1.20 (95% CI 1.16–1.25) per 1,000 population, respectively (based on 2007–2008 figures). Increased numbers of TKRs were also found to be occurring among people residing in regional areas of Victoria (from 1.12 [95% CI 1.04–1.31] to 1.84 [95% CI 1.72–2.02] per 1,000 population).

Conclusion

Increases in lifetime risk of TKR were evident. Although improved access to TKR for those living in regional areas was observed, sustained disparities relating to health care setting and SES warrant further investigation.
Measurement Properties of the German Michigan Hand Outcomes Questionnaire in Patients With Trapeziometacarpal Osteoarthritis
Authors: Marks Miriam , Audigé Laurent , Herren Daniel B. , Schindele Stephan , Nelissen Rob G. H. H. , Vliet Vlieland Thea P. M.
Published: August 2013

Objective

To investigate the reliability, validity, and responsiveness of the Michigan Hand Outcomes Questionnaire (MHQ) in patients with trapeziometacarpal (TMC) joint osteoarthritis (OA).

Methods

In this prospective observational study, patients diagnosed with TMC joint OA who received either conservative or surgical treatment were included. At baseline and at 1 year following the beginning of treatment, we measured key pinch strength and the patients filled out the MHQ, the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, and the Short Form 12 health survey. Patients also completed these questionnaires 2–11 days after the last study visit. In order to analyze the measurement properties of the MHQ, we calculated test–retest reliability (intraclass correlation coefficient [ICC]), internal consistency (Cronbach's alpha for the 6 subscales), construct validity (Pearson's correlation coefficient [r]), responsiveness (effect sizes), and the minimum important change (MIC).

Results

We included 177 patients, of whom 109 were scheduled for surgery. The mean ± SD MHQ total score for surgical patients increased from 48 ± 14 at baseline to 75 ± 18 at 1 year (P ≤ 0.001). In contrast, no treatment effect was observed in the conservative group (P = 0.74). The MHQ total score showed excellent test–retest reliability (ICC 0.95) and correlated strongly with the DASH (r = −0.77). Internal consistency of the MHQ subscales ranged between 0.77 and 0.89. A large effect size of 1.7 was found for the surgical patients, with an MIC of 17 points.

Conclusion

The MHQ demonstrated good reliability, validity, and responsiveness in patients with TMC joint OA and can be recommended as a suitable assessment instrument in this population.
Performance of the Assessment of Quality of Life Measure in People With Hip and Knee Joint Disease and Implications for Research and Clinical Use
Authors: Ackerman Ilana N. , Busija Lucy , Tacey Mark A. , Bohensky Megan A. , Ademi Zanfina , Brand Caroline A. , Liew Danny
Published: August 2013

Objective

To comprehensively evaluate the performance of the Assessment of Quality of Life (AQoL) instrument for measuring health‐related quality of life (HRQOL) in people with hip and knee joint disease (arthritis or osteoarthritis).

Methods

Data from 237 individuals were available for analysis from a national cross‐sectional, population‐based study of hip and knee joint disease in Australia. AQoL‐4D data were evaluated using Rasch analysis. A range of measurement properties was explored, including model and item fit, threshold ordering, differential item functioning, and targeting.

Results

Good overall fit of the AQoL with the Rasch model was demonstrated across a range of tests, supporting internal validity. Only 1 item (relating to hearing) showed evidence of misfit. Most AQoL items showed logical sequencing of response option categories, with threshold disordering evident for only 2 of the 12 items (items 4 and 9). Minor issues with potential clinical and research implications include limited options for reporting pain and some evidence of measurement bias between demographic subgroups (including age and sex). Participants' HRQOL was generally better than that represented by the AQoL items (mean ± SD for person abilities −2.15 ± 1.39, mean ± SD for item difficulties 0.00 ± 0.67), indicating ceiling effects that could impact the instrument's ability to detect HRQOL improvement in population‐based studies.

Conclusion

The AQoL is a competent tool for assessing HRQOL in people with hip and knee joint disease, although researchers and clinicians should consider the caveats identified when selecting appropriate HRQOL measures for future outcome assessment involving this patient group.
Generation of Monodisperse, Shape‐Controlled Single and Hybrid Core–Shell Nanoparticles via a Simple One‐Step Process
Authors: Kim Jong‐Seon , Jeon Hwan‐Jin , Yoo Hae‐Wook , Baek Youn‐Kyoung , Kim Kyoung Hwan , Kim Dae Woo , Jung Hee‐Tae
Published: August 2013

In nano‐biotechnology, optoelectronics, and energy research areas, various fabrication methods have been developed for hybrid nanoparticles. A method is developed here for fabricating highly monodisperse three‐dimensional hybrid nanoparticles using a unique top‐down method based on secondary sputtering lithography. Nanostructures that have been formed on a PEDOT sacrificial layer are transferred from the substrate to an aqueous solution in a process that could be used to successfully disperse a variety of nanoparticle shapes and hybrid nanoparticles. By this method, a fluorescent dye could be encapsulated within the fabricated hybrid nanoparticles for use in bio‐sensing and drug‐delivery applications
Platinum‐Catalyzed Divergent Reactivity of α‐Hydroxyallenes: Synthesis of Dihydrofurans and α,β‐Unsaturated Ketones
Authors: Alcaide Benito , Almendros Pedro , Fernández Israel , Campo Teresa Martínez del , Naranjo Teresa
Published: August 2013

α‐Allenols were catalytically transformed into dihydrofurans in the presence of platinum dichloride. Notably, using platinum dichloride along with silver triflate as the catalytic system, α,β‐unsaturated ketones were obtained. Therefore, the role of the silver salt may not just consist in the activation of the platinum precatalyst.

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NH2SO3H–SiO2 as a new water‐compatible, recyclable heterogeneous catalyst for the synthesis of novel (α,β‐unsaturated) β‐amino ketones via aza‐Michael reaction
Authors: Siddiqui Zeba N. , Ahmed Nayeem
Published: August 2013

NH2SO3H–SiO2/water as a novel catalytic system was used for the synthesis of (α,β‐unsaturated) β‐amino ketones via aza‐Michael reaction at reflux conditions. The methodology was of general applicability and the catalyst exhibited activity up to five cycles. The catalyst was characterized for the first time using FT‐IR, X‐ray diffraction and scanning electron microscopic–energy dispersion analytical X‐ray. The stability of the catalyst was evaluated by differential scanning calorimetry and TGA/differential thermal analysis. High efficiency of the catalyst along with its recycling ability and the rather low loading demonstrated in reactions are the merits of the presented protocol. Copyright © 2013 John Wiley & Sons, Ltd.
Amine‐bridged bis(phenol) ligands for efficient Pd‐catalyzed aqueous C‐C coupling reactions
Authors: Zhou Zhonggao , Liu Minyan , Wu Xiaoli , Yu Hongwei , Xu Guohai , Xie Yongrong
Published: August 2013

The influence of ring size (5 or 6), chain length (1, 2 or 3) and bulkiness of N‐aryl substituents in amine‐bridged bis(phenol) ligands (1, 2, 3) on palladium‐catalyzed aqueous C‐C coupling reactions were revealed. The homocoupling of arylboronic acid can be completed in neat water with the aid of a catalytic amount of p‐toluenesulfonyl chloride (TsCl) in a very short time under anaerobic or aerobic conditions. Interestingly, the same catalytic system was efficient for Suzuki–Miyaura reaction in aqueous acetone under aerobic conditions in the absence of TsCl. The crystal structures of ligand 1 and three unsymmetrical fluorine‐substituted biaryl derivatives were also reported. Copyright © 2013 John Wiley & Sons, Ltd.
Studies on Organophosphorus Compounds. Part 1: Synthesis and In Vitro Antimicrobial Activity of Some New Pyrimido[5′,4′:5,6]pyrano[2,3‐d][1,3,2]thiazaphosphinine Compounds
Authors: Younes Sabry H. H. , Mohamed Shaaban K. , Albayati Mustafa R.
Published: August 2013

2,4‐Bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane‐2,4‐disulfide (Lawesson's reagent, LR) reacted with pyrano[2,3‐d]pyrimidine‐2,4‐(1H,3H)‐dione derivatives in boiling acetonitrile to afford various pyrimido[5′,4′:5,6]pyrano[2,3‐d][1,3,2]thiazaphosphinine derivatives. The structures of the target compounds were characterized by elemental analysis and spectral data. The biological activities of all synthesized compounds were tested against various microorganisms by the disk diffusion method. In general, the newly synthesized compounds showed good inhibitory effects against most of the applied microorganisms.
Brief Report: Anti–Tumor Necrosis Factor α Targets Protein Kinase B/c‐Akt–Induced Resistance of Effector Cells to Suppression in Juvenile Idiopathic Arthritis
Authors: Wehrens Ellen J. , Vastert Sebastiaan J. , Mijnheer Gerdien , Meerding Jenny , Klein Mark , Wulffraat Nico M. , Prakken Berent J. , van Wijk Femke
Published: August 2013

Objective

To determine whether therapeutic strategies that block interleukin‐6 (IL‐6) or tumor necrosis factor α (TNFα) can improve the responsiveness of Teff cells to suppression in patients with juvenile idiopathic arthritis (JIA).

Methods

Synovial fluid mononuclear cells (SFMCs) from the inflamed joints of patients with JIA were cultured in the presence of etanercept or anti–IL‐6 in vitro, and protein kinase B (PKB)/c‐Akt activation and responsiveness to suppression were measured. In addition, the in vivo effects of TNFα blockade were investigated using peripheral blood mononuclear cells obtained from patients before and after the start of etanercept therapy.

Results

In vitro treatment of SFMCs with anti–IL‐6 led to improved Treg cell–mediated suppression of cell proliferation in some but not all patients. Blocking TNFα with etanercept, however, clearly enhanced suppression, especially that of CD8+ T cells. In the presence of etanercept, PKB/c‐Akt activation of Teff cells was reduced, and cells became more susceptible to transforming growth factor β–mediated suppression, indicating that anti‐TNFα directly targets resistant Teff cells.

Conclusion

This study is the first to show that anti‐TNFα targets the resistance of Teff cells to suppression, resulting in improved regulation of inflammatory effector cells.
Increased Intracellular Oxygen Radical Production in Neutrophils During Febrile Episodes of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome
Authors: Sundqvist Martina , Wekell Per , Osla Veronica , Bylund Johan , Christenson Karin , Sävman Karin , Foell Dirk , Cabral David A. , Fasth Anders , Berg Stefan , Brown Kelly L. , Karlsson Anna
Published: August 2013

Objective

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease of unknown etiology that primarily affects preschool‐aged children. PFAPA syndrome is characterized by recurrent attacks of fever and symptoms of inflammation consistent with the disease acronym. Since autoinflammatory diseases are, by definition, mediated by cells of the innate immune system, the aim of this study was to evaluate the functional features of neutrophils, the most abundant innate immune cell in the circulation, in children with PFAPA syndrome.

Methods

Blood polymorphonuclear leukocytes (PMNs), obtained from patients with PFAPA syndrome during both febrile and asymptomatic, afebrile phases of the disease, as well as from healthy children (afebrile controls) and children with fever and abdominal pain (febrile controls), were analyzed for 3 key neutrophil characteristics: 1) apoptosis (measured by annexin V/7‐aminoactinomycin D staining), 2) production of reactive oxygen species (ROS) (measured by luminol/isoluminol‐amplified chemiluminescence), and 3) priming status (measured as responsiveness to galectin‐3 and up‐regulation of CD11b).

Results

Compared to PMNs obtained from patients with PFAPA syndrome during an afebrile interval and those from febrile controls, PMNs obtained from patients during a PFAPA syndrome flare produced elevated levels of intracellular NADPH oxidase–derived ROS, had significantly diminished rates of spontaneous apoptosis, and displayed signatures of priming. In contrast, PMNs from afebrile patients with PFAPA syndrome had a significantly elevated rate of spontaneous apoptosis compared to PMNs from afebrile controls.

Conclusion

These findings demonstrate that 3 key aspects of neutrophil innate immune function, namely, apoptosis, priming, and generation of an intracellular oxidative burst, are altered, most prominently during febrile attacks, in children with PFAPA syndrome.
Brief Report: A Regulatory Variant in CCR6 Is Associated With Susceptibility to Antitopoisomerase‐Positive Systemic Sclerosis
Authors: Koumakis Eugénie , Bouaziz Matthieu , Dieudé Philippe , Ruiz Barbara , Riemekasten Gabriella , Airo Paolo , Müller‐Nurasyid Martina , Cusi Daniele , Matucci‐Cerinic Marco , Melchers Inga , Salvi Erika , Strauch Konstantin , Peters Annette , Cuomo Giovanna , Hachulla Eric , Diot Elisabeth , Hunzelmann Nicolas , Caramaschi Paola , Riccieri Valeria , Distler Jörg H. W. , Tarner Ingo , Avouac Jérôme , Letenneur Luc , Amouyel Philippe , Lambert Jean‐Charles , Chiocchia Gilles , Boileau Catherine , Allanore Yannick
Published: August 2013

Objective

Recognition of the well‐known pleiotropism of autoimmune genes supports the concept of a shared pathogenesis across autoimmune diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). Studies have reproducibly demonstrated an association between susceptibility to RA and polymorphisms of the CCR6 gene, a surface marker for Th17 cells, and the causal variant was recently identified. The present study was thus undertaken to investigate whether CCR6 polymorphisms could also be associated with susceptibility to SSc.

Methods

Twelve tag single‐nucleotide polymorphisms (SNPs) of CCR6, including the known RA‐associated SNP rs3093023, were genotyped in a total of 2,411 SSc patients and 7,084 healthy individuals from 3 European populations (France, Italy, and Germany). Meta‐analyses of the data were performed to assess whether an association exists between CCR6 polymorphisms and susceptibility to SSc or its main subtypes. Direct sequencing of DNA was performed to ascertain whether the functional dinucleotide polymorphism of CCR6 previously identified in RA (CCR6DNP) was also present in SSc.

Results

Combined analyses revealed an association between the rs10946216 SNP and SSc susceptibility (odds ratio [OR] 1.13, 95% confidence interval [95% CI] 1.05–1.21, adjusted P [Padj] = 0.026). The rs3093023 A allele and rs10946216 T allele were in high linkage disequilibrium, and both were found to confer disease susceptibility in the antitopoisomerase‐positive subset of SSc patients (OR 1.27, 95% CI 1.13–1.42, Padj = 1.5 × 10−3 and OR 1.32, 95% CI 1.17–1.48, Padj = 9.0 × 10−5, respectively, relative to healthy controls). Direct sequencing of the DNA of 78 individuals supported the hypothesis that the regulatory dinucleotide CCR6DNP could be the causal variant in SSc.

Conclusion

The results of this study establish CCR6 as a new susceptibility factor for antitopoisomerase‐positive SSc, as demonstrated in 3 European Caucasian populations, confirming the notion that SSc and RA could conceivably share autoimmune risk alleles. The results also suggest a potential role of the interleukin‐17 pathway in SSc.
9G4+ Autoantibodies Are an Important Source of Apoptotic Cell Reactivity Associated With High Levels of Disease Activity in Systemic Lupus Erythematosus
Authors: Jenks Scott A. , Palmer Elise M. , Marin Elides Y. , Hartson Louise , Chida Asiya Seema , Richardson Christopher , Sanz Ignacio
Published: August 2013

Objective

To determine the prevalence of anti–apoptotic cell (anti‐AC) antibodies with the 9G4 idiotype (9G4+) and the relationship between this and other known 9G4+ specificities and disease activity in patients with systemic lupus erythematosus (SLE).

Methods

Serum samples from 60 SLE patients and 40 healthy donors were incubated with apoptotic Jurkat cells and assayed by flow cytometry for the binding of 9G4+ antibodies. The samples were also tested for 9G4+ reactivity against naive B cells and total IgG and IgM anti‐AC antibody reactivity.

Results

The 9G4+ antibodies bound late ACs in sera from a majority of the SLE patients (60%) but in sera from only 2 healthy control subjects. Among samples with global IgM or IgG anti‐AC antibodies, those with 9G4+ anti‐AC antibodies predominated. Patients with high levels of 9G4+ anti‐AC antibodies were more likely to have active disease. This was the case even in patients with IgG anti‐AC antibodies or anti–double‐stranded DNA antibodies. Patients with lupus nephritis were also more likely to have 9G4+ anti‐AC antibodies. While 9G4+ reactivity to ACs often coincided with anti–B cell reactivity, some samples had distinct anti–AC or anti–B cell reactivity.

Conclusion

The 9G4+ antibody represents a major species of anti‐AC antibody in SLE serum, and this autoreactivity is associated with disease activity. The anti‐AC reactivity of 9G4+ antibodies can be separated from the germline VH4–34–encoded anti–B cell autoreactivity. Our results indicate that ACs are an important antigenic source in SLE that positively selects B cells with intrinsic autoreactivity against other self antigens. This selection of 9G4+ B cells by ACs may represent an important step in disease progression.
Overlapping Structural and Functional Brain Changes in Patients With Long‐Term Exposure to Fibromyalgia Pain
Authors: Jensen Karin B. , Srinivasan Priti , Spaeth Rosa , Tan Ying , Kosek Eva , Petzke Frank , Carville Serena , Fransson Peter , Marcus Hanke , Williams Steven C. R. , Choy Ernest , Vitton Olivier , Gracely Richard , Ingvar Martin , Kong Jian
Published: August 2013

Objective

There is vast evidence to support the presence of brain aberrations in patients with fibromyalgia (FM), and it is possible that central plasticity is critical for the transition from acute to chronic pain. The aim of the present study was to investigate the relationship between brain structure and function in patients with FM.

Methods

Functional connectivity of the brain during application of intermittent pressure–pain stimuli and measures of brain structure were compared between 26 patients with FM and 13 age‐ and sex‐matched healthy controls. Magnetic resonance imaging (MRI) was performed to obtain high‐resolution anatomic images and functional MRI scans of the brain, which were used for measurements of pain‐evoked brain activity.

Results

FM patients displayed a distinct overlap between decreased cortical thickness, decreased brain volumes, and decreased functional regional coherence in the rostral anterior cingulate cortex. The morphometric changes were more pronounced with longer exposure to FM pain. In addition, there was evidence of an association between structural and functional changes in the mesolimbic areas of the brain and the severity of comorbid depression symptoms in FM patients.

Conclusion

The combined integration of structural and functional measures allowed for a unique characterization of the impact of FM pain on the brain. These data may lead to the identification of early structural and functional brain alterations in response to pain, which could be used to develop markers for predicting the development of FM and other pain disorders.
Thieno–Pyrrole‐Fused BODIPY Intermediate as a Platform to Multifunctional NIR Agents
Authors: Awuah Samuel G. , Das Sushanta K. , D'Souza Francis , You Youngjae
Published: August 2013

We report the synthesis, photophysical and electrochemical properties, and in vivo fluorescence imaging of a series of new thieno–pyrrole‐fused near‐infrared (NIR) BODIPY agents by using a versatile intermediate as a building block. The versatile thieno–pyrrole‐fused BODIPY intermediate was rationally designed to bear bromo‐substituents and absorb in the mid‐red region (635 nm) to act as an organic electrophile for the development of NIR multifunctional agents. The use of subsequent palladium‐catalyzed and nucleophilic substitution reactions afforded highly conjugated NIR BODIPYs. The novel BODIPYs exhibit long‐wavelength absorptions in the NIR region (650–840 nm). The agents produce sharp fluorescence bands, and most of them display respectable quantum yields of fluorescence (0.05–0.87) useful for biomedical imaging, as demonstrated by in vivo imaging with SBDPiR740. Interestingly, a number of agents in the series that are non‐halogenated were reactive to O2 at the triplet photo‐excited state coupled with a favorable redox potential and decent fluorescence, and hence could be potential candidates for use as photosensitizers in fluorescence‐guided photodynamic therapy. Furthermore, the synthetic approach allows further functionalization of the highly conjugated NIR BODIPYs to tune the excited states (PET, ICT) and to conjugate targeting moieties for enhanced biological applications.
Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment
Authors: Craveiro Vinicius , Yang‐Hartwich Yang , Holmberg Jennie C. , Sumi Natalia J. , Pizzonia John , Griffin Brian , Gill Sabrina K. , Silasi Dan‐Arin , Azodi Masoud , Rutherford Thomas , Alvero Ayesha B. , Mor Gil
Published: August 2013

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite initial responsiveness, 80% of EOC patients recur and present with chemoresistant and a more aggressive disease. This suggests an underlying biology that results in a modified recurrent disease, which is distinct from the primary tumor. Unfortunately, the management of recurrent EOC is similar to primary disease and does not parallel the molecular changes that may have occurred during the process of rebuilding the tumor. We describe the characterization of unique in vitro and in vivo ovarian cancer models to study the process of recurrence. The in vitro model consists of GFP+/CD44+/MyD88+ EOC stem cells and mCherry+/CD44−/MyD88− EOC cells. The in vivo model consists of mCherry+/CD44+/MyD88+ EOC cells injected intraperitoneally. Animals received four doses of Paclitaxel and response to treatment was monitored by in vivo imaging. Phenotype of primary and recurrent disease was characterized by quantitative polymerase chain reaction (qPCR) and Western blot analysis. Using the in vivo and in vitro models, we confirmed that chemotherapy enriched for CD44+/MyD88+ EOC stem cells. However, we observed that the surviving CD44+/MyD88+ EOC stem cells acquire a more aggressive phenotype characterized by chemoresistance and migratory potential. Our results highlight the mechanisms that may explain the phenotypic heterogeneity of recurrent EOC and emphasize the significant plasticity of ovarian cancer stem cells. The significance of our findings is the possibility of developing new venues to target the surviving CD44+/MyD88+ EOC stem cells as part of maintenance therapy and therefore preventing recurrence and metastasis, which are the main causes of mortality in patients with ovarian cancer.
Borderline trend towards long‐term mortality benefit from drug eluting stents implantation in ST‐elevation myocardial infarction patients in Poland—data from NRDES registry
Authors: Siudak Zbigniew , Dziewierz Artur , Rakowski Tomasz , Żmudka Krzysztof , Legutko Jacek , Bartuś Stanisław , Dragan Jacek , Zasada Wojciech , Tokarek Tomasz , Kułaga Tomasz , Partyka Łukasz , Dudek Dariusz
Published: August 2013

Objectives

To analyze long‐term outcome of ST‐Elevation Myocardial Infarction (STEMI) and non‐STEMI (NSTEMI) patients treated with Drug Eluting Stents (DES) stents with regard to mortality and stent thrombosis rates based on the national Polish PCI registry database.

Background

Only a few studies suggested potential trend towards lower mortality in STEMI patients treated with DES. Current European Society of Cardiology STEMI guidelines recommend DES use only with one restriction to suspected patient poor compliance or contraindication to dual antiplatelet therapy.

Methods

Thirteen high‐volume interventional cardiology centers in Poland enrolled patients in National Registry of Drug Eluting Stents (NRDES) Registry from October 2010 till October 2011.

Results

There were 2686 patients enrolled in NRDES Registry. Eighty five patients (3%) had both DES and BMS implanted at index PCI procedure and were excluded from further analysis. A subpopulation of STEMI (1709; 66%) and NSTEMI (892; 34%) patients was selected for BMS vs DES comparison. A significant difference in favor of DES group for 1‐year mortality was found in STEMI subgroup (P < 0.0001—unadjusted and P = 0.0497 after propensity score adjustment). No such differences were noticed for NSTEMI subgroup or stent thrombosis comparisons.

Conclusions

A strong selection bias for DES stents was observed with regard to demographic and angiographic characteristics in both STEMI and NSTEMI. DES implantation was associated with similar ischemic outcome to BMS at 1‐year follow‐up. STEMI patients with DES presented a trend towards lower long‐term mortality at 1 year in comparison to BMS. © 2013 Wiley Periodicals, Inc.
Transseptal strategy in retrograde transcatheter valve‐in‐valve implantation for failed surgical aortic bioprosthesis
Authors: Chi Lam Simon Cheung , Bertog Stefan , Sievert Horst
Published: August 2013

We report a challenging case of transcatheter aortic valve‐in‐valve implantation in an elderly patient with failed surgical bioprosthesis. The transthoracic echocardiogram demonstrated a severe stenosis with a peak gradient of 142 mm Hg. The patient was a high‐risk candidate for reoperative valve replacement; therefore, transfemoral implantation of a CoreValve (Medtronic Inc, Minneapolis, MN) was decided. During the procedure, we were unable to introduce the delivery catheter system across the bioprosthesis due to its poor alignment with the aortic annulus and the severity of the stenosis. With strategies involving transseptal puncture and externalization of a guidewire in an antegrade manner, the CoreValve was successfully positioned and deployed. This case illustrated the utility of transseptal strategies in challenging retrograde transcatheter aortic valve‐in‐valve implantation. © 2013 Wiley Periodicals, Inc.
Long‐term clinical outcomes following drug‐eluting stent implantation for unprotected distal trifurcation left main disease: The Milan‐New Tokyo (MITO) registry
Authors: Ielasi Alfonso , Takagi Kensuke , Latib Azeem , Basavarajaiah Sandeep , Figini Filippo , Carlino Mauro , Montorfano Matteo , Chieffo Alaide , Nakamura Sunao , Colombo Antonio
Published: August 2013

Background

Unprotected distal left main trifurcation (ULMT) lesion represents a challenge for interventional cardiologists with the potential for peri‐procedural complications and adverse events at follow‐up especially when the main branch and the side branches are concomitantly diseased.

Methods

A retrospective cohort analysis was performed on consecutive patients with ULMT stenosis who electively underwent percutaneous coronary intervention (PCI) with drug‐eluting stent (DES) implantation in order to assess the technical feasibility and long‐term outcomes according to the disease distribution in the trifurcation branches (true vs. non‐true ULMT). Primary endpoint of the study was a composite of major adverse cardiovascular events (MACE) defined as cardiac‐death, myocardial infarction (MI), and target lesion revascularization (TLR) during follow‐up.

Results

Eighty‐four patients underwent PCI with DES for ULMT disease during the study period (40 true trifurcation and 44 non‐true trifurcation). Angiographic and procedural success were obtained in 94% and 92.8% of cases. At 3‐years follow‐up, the occurrence of MACE was significantly higher in patients with true ULMT than in those with non‐true ULMT (HR 2.801 [confidence interval; CI 1.164–7.896], P = 0.025) due to a higher TLR rate (HR 3.032 [CI 1.164–7.896], P = 0.023). No episodes of late and very late definite/probable stent thrombosis (ST) occurred. On multivariable analysis, a true‐ULMT lesion was the only independent predictor of MACE (HR 2.344 [C.I. 1.006–5.461], P = 0.049).

Conclusions

PCI with DES for ULMT stenosis is feasible with a high procedural success rate and no definite/probable ST reported at follow‐up. A true trifurcation lesion is associated with enhanced risk of MACE mainly driven by TLR. © 2013 Wiley Periodicals, Inc.
Paravalvular leak closure after transcatheter aortic valve replacement with a self‐expanding prosthesis
Authors: Gafoor Sameer , Franke Jennifer , Piayda Kerstin , Lam Simon , Bertog Stefan , Vaskelyte Laura , Hofmann Ilona , Sievert Horst
Published: August 2013

Introduction

Paravalvular leak (PVL) after percutaneous transcatheter aortic valve replacement (TAVR) is associated with significant morbidity and mortality. Percutaneous PVL closure has been reported for balloon‐expandable valves but not self‐expandable valves.

Methods

We conducted a review of cases at our center where patients who received TAVR with self‐expandable valves and went on to develop severe PVL underwent percutaneous closure. Baseline demographic, TAVR procedural, PVL procedural, and follow‐up data were collected.

Results

A total of five patients with severe PVL after TAVR with a self‐expanding valve underwent percutaneous PVL closure. Four of five patients had a trial of balloon postdilatation after valve deployment and had significant persistent PVL. In all five patients, PVL went from moderate‐severe to mild‐moderate PVL. There were no adverse events.

Conclusion

Percutaneous PVL closure for severe PVL self‐expanding valve for TAVR is a safe and efficacious procedure. Procedural technique involves transesophageal guidance, a high approach through the valve struts, deployment of an appropriate size device, and careful monitoring. This method may be part of the algorithm for severe PVL after TAVR. © 2013 Wiley Periodicals, Inc.
Photocatalytic Hydrogen Production with Copper Photosensitizer–Titanium Dioxide Composites
Authors: Karnahl Michael , Mejía Esteban , Rockstroh Nils , Tschierlei Stefanie , Luo Shu‐Ping , Grabow Kathleen , Kruth Angela , Brüser Volker , Junge Henrik , Lochbrunner Stefan , Beller Matthias
Published: August 2013

A series of heteroleptic copper photosensitizers [($\widehat{PP}$)Cu($\widehat{NN}$(SO3Na)2)]+ containing sulfonate anchor groups is described. In the presence of titanium dioxide they form composites, which are active photosensitizers in the light driven reduction of protons. Further stabilization of these systems is achieved by encapsulation within a plasma‐polymerized allylamine (PPAAm) layer. The resulting PPAAm‐CuPS‐TiO2‐composites exhibit a strong absorption in the visible region of the light. Photocatalytic hydrogen production is performed by using only non‐noble metals. In the presence of an iron reduction catalyst a maximum turnover number of 2452 is obtained.
Controlled Heterocyclization/Cross‐Coupling Domino Reaction of β,γ‐Allendiols and α‐Allenic Esters: Method and Mechanistic Insight for the Preparation of Functionalized Buta‐1,3‐dienyl Dihydropyrans
Authors: Alcaide Benito , Almendros Pedro , Martínez del Campo Teresa , Quirós M. Teresa , Soriano Elena , Marco‐Contelles José L.
Published: August 2013

Starting from β,γ‐allendiols and α‐allenic acetates, a chemo‐ and regiocontrolled palladium‐catalyzed methodology has provided access to enantiopure 3,6‐dihydropyrans that bear a buta‐1,3‐dienyl moiety. Thus, it has been demonstrated for the first time that the preparation of six‐membered heterocycles through cross‐coupling reactions of two different allenes can be accomplished. These heterocyclization/cross‐coupling reactions have been developed experimentally and their mechanisms have additionally been investigated by a computational study.
Estimating the Adoption of Transcatheter Aortic Valve Replacement By US Interventional Cardiologists and Clinical Trialists
Authors: Stolker Joshua M. , Patel Akshar Y. , Lim Michael J. , Hauptman Paul J.
Published: August 2013

Background

Despite extensive attention dedicated to transcatheter aortic valve replacement (TAVR) in both the medical literature and lay press, little is known about the anticipated utilization of TAVR by the US cardiology community.

Hypothesis

TAVR use is likely to outstrip its initial clinical indications.

Methods

Four days after approval of the first TAVR device in November 2011 by the US Food and Drug Administration, we emailed an online questionnaire to 201 authors of major TAVR clinical trials (trialists) and 461 recent members of an interventional cardiology professional society (clinicians). Responses were compared using χ2, t tests, and analysis of variance.

Results

Of 205 surveys received (response rate 31%; 114 clinicians, 91 trialists), the majority of respondents were interventionalists (86%) working in academic practices (72%). Although most physicians anticipated referring <25% of their patients with severe aortic stenosis for TAVR, 68% believed that TAVR is equally efficacious as open‐heart surgery, and 11% believed that moderate‐surgical risk patients should also be considered for TAVR. More clinicians (98%) than trialists (81%) expected to routinely refer patients for TAVR (P < 0.001). Furthermore, the clinicians were anticipating less operator training and lower annual volume requirements for performing TAVR, when compared with the trialists (P ≤ 0.001).

Conclusions

Our findings suggest optimism for TAVR acceptance in the United States., with more conservative expectations regarding training, procedural volume requirements, and anticipated referral patterns among TAVR trialists than clinical interventionalists.
The design of MACs (minimal actin cortices)
Authors: Vogel Sven K. , Heinemann Fabian , Chwastek Grzegorz , Schwille Petra
Published: August 2013

The actin cell cortex in eukaryotic cells is a key player in controlling and maintaining the shape of cells, and in driving major shape changes such as in cytokinesis. It is thereby constantly being remodeled. Cell shape changes require forces acting on membranes that are generated by the interplay of membrane coupled actin filaments and assemblies of myosin motors. Little is known about how their interaction regulates actin cell cortex remodeling and cell shape changes. Because of the vital importance of actin, myosin motors and the cell membrane, selective in vivo experiments and manipulations are often difficult to perform or not feasible. Thus, the intelligent design of minimal in vitro systems for actin‐myosin‐membrane interactions could pave a way for investigating actin cell cortex mechanics in a detailed and quantitative manner. Here, we present and discuss the design of several bottom‐up in vitro systems accomplishing the coupling of actin filaments to artificial membranes, where key parameters such as actin densities and membrane properties can be varied in a controlled manner. Insights gained from these in vitro systems may help to uncover fundamental principles of how exactly actin‐myosin‐membrane interactions govern actin cortex remodeling and membrane properties for cell shape changes. © 2013 Wiley Periodicals, Inc.
Structural Elaboration of a Natural Product: Identification of 3,3′‐Diindolylmethane Aminophosphonate and Urea Derivatives as Potent Anticancer Agents
Authors: Kandekar Somnath , Preet Ranjan , Kashyap Maneesh , M. U. Renu Prasad , Mohapatra Purusottam , Das Dipon , Satapathy Shakti Ranjan , Siddharth Sumit , Jain Vaibhav , Choudhuri Maitrayee , Kundu Chanakya N. , Guchhait Sankar K. , Bharatam Prasad V.
Published: August 2013

An approach involving rational structural elaboration of the biologically active natural product diindolylmethane (DIM) with the incorporation of aminophosphonate and urea moieties toward the discovery of potent anticancer agents was considered. A four‐step approach for the synthesis of DIM aminophosphonate and urea derivatives was established. These novel compounds showed potent anticancer activities in two representative kidney and colon cancer cell lines, low toxicity to normal cells, higher potency than the parent natural product DIM and etoposide, and potent inhibition of cancer cell migration. Biophysical and immunological studies, including DAPI nuclear staining, western blot analysis with apoptotic protein markers, flow cytometry, immunocytochemistry, and comet assays of the two most potent compounds revealed good efficacies in apoptosis and DNA damage. It was found that down‐regulation of nuclear factor κB (NF‐κB p65) could be an important mode of action in apoptosis, and the two most potent derivatives were found to be more potent than parent compound DIM in the down‐regulation of NF‐κB. Our results show the importance of structural elaboration of DIM by rational incorporation of aminophosphonate and urea moieties to produce potent anticancer agents; they also suggest that this approach using other structurally simple bioactive natural products as scaffolds holds promise for future drug discovery and development.
Precipitation and characterization of hollow calcite nanoparticles
Authors: Kontrec Jasminka , Ukrainczyk Marko , Džakula Branka Njegić , Kralj Damir
Published: August 2013

A method for preparation of significant amount of hollow rhombohedral calcite nanoparticles, based on carbonation of calcium hydroxide suspension, is described. The mineralogical and morphological analyses of the precipitate confirmed the existence of exclusively stable polymorphic modification, calcite, with the mean particle size of about 100 nm and the diameter of the holes observed at the surfaces that are about 50 nm. The analysis of carbonation kinetics pointed out to a complex mechanism of hollow particles formation at high initial supersaturation, that assumed nucleation of amorphous precursor calcium carbonate phase and its solution mediated transformation into nanosized crystalline calcite. The holes obtained at the calcite surfaces are most probably the imprints remained after the dissolution of amorphous calcium carbonate particles.