bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Smoking With Cutaneous Manifestations in Systemic Lupus Erythematosus
Authors: Bourré‐Tessier Josiane , Peschken Christine A. , Bernatsky Sasha , Joseph Lawrence , Clarke Ann E. , Fortin Paul R. , Hitchon Carol , Mittoo Shikha , Smith C. Douglas , Zummer Michel , Pope Janet , Tucker Lori , Hudson Marie , Arbillaga Hector , Esdaile John , Silverman Earl , Chédeville Gaelle , Huber Adam M. , Belisle Patrick ,   The Canadian Network for Improved Outcomes in Systemic Lupus Erythematosus 1000 Canadian Faces of Lupus Investigators, Pineau Christian A.
Published: February 2013

Objective

To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE).

Methods

We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data.

Results

In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials.

Conclusion

Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.
Does C‐Reactive Protein Predict the Long‐Term Progression of Interstitial Lung Disease and Survival in Patients With Early Systemic Sclerosis?
Authors: Liu Xiaochun , Mayes Maureen D. , Pedroza Claudia , Draeger Hilda T. , Gonzalez Emilio B. , Harper Brock E. , Reveille John D. , Assassi Shervin
Published: February 2013

Objective

There are no identified clinical markers that reliably predict long‐term progression of interstitial lung disease (ILD) in systemic sclerosis (SSc; scleroderma). Elevated C‐reactive protein (CRP) levels have been reported in SSc patients. We examined the predictive significance of CRP level for long‐term ILD progression in a large early SSc cohort.

Methods

First, the CRP levels were compared between baseline samples of 266 SSc patients enrolled in the Genetics Versus Environment in Scleroderma Outcome Study cohort and 97 unaffected matched controls. Subsequently, the correlation between CRP levels and concomitantly obtained markers of disease severity was assessed. Serially obtained % predicted forced vital capacity (FVC) was used to examine the long‐term ILD progression. The predictive significance of CRP level was investigated by a joint analysis of longitudinal measurements (serial FVCs up to 13 years) and survival data. This approach allowed inclusion of all 1,016 FVC measurements and accounted for survival dependency.

Results

We confirmed that baseline CRP levels were higher in SSc patients than controls. CRP levels were associated with absence of anticentromere antibodies and correlated with the concomitant severity of lung, skin, and joint involvement. More importantly, higher baseline CRP levels were associated with shorter survival (P < 0.001) and predicted the long‐term decline in FVC independent of potential confounders (age at baseline, sex, ethnicity, disease type, current smoking, body mass index, topoisomerase status, and treatment with immunosuppressive agents) in the multivariable model (P = 0.006).

Conclusion

Baseline CRP levels are predictive of long‐term ILD progression. CRP level might aid clinicians in identifying patients that require more intensive monitoring and treatment.
Influence of Patients' Gender on Informed Decision Making Regarding Total Knee Arthroplasty
Authors: Borkhoff Cornelia M. , Hawker Gillian A. , Kreder Hans J. , Glazier Richard H. , Mahomed Nizar N. , Wright James G.
Published: February 2013

Objective

To investigate the effect of patient gender on patient–physician communication in the process of recommendation for total knee arthroplasty (TKA).

Methods

Seventy‐one physicians (38 family physicians and 33 orthopedic surgeons) in Ontario performed blinded assessments of 2 standardized patients (1 man and 1 woman) with moderate knee osteoarthritis and otherwise identical scenarios. Four surgeons did not consent to including their data. Standardized patients and accompanying mock family members recorded elements of informed decision making (IDM) as present/absent in the patient–physician discussion and rated the physicians' interpersonal skills.

Results

Overall, the completeness of IDM was low, but was lower still for the woman. Only 57% (38 of 67) and 15% (10 of 67) of physicians discussed the nature of the decision and elicited the patient's preference while consulting with the man and woman, respectively. Even after adjusting for physicians' recommendations regarding TKA, when interacting with the woman, physicians included fewer IDM elements (adjusted mean difference in IDM score 1.2 [95% confidence interval (95% CI) 0.6, 1.8]; P < 0.001) and had poorer interpersonal skills (adjusted mean difference 14.1 [95% CI 9.0, 19.2]; P < 0.001) compared with their consultation with the man.

Conclusion

Physicians provided less medical information and less encouragement to participate in the decision to undergo TKA to a woman compared with a man, irrespective of their recommendation regarding TKA. Our findings suggest that in addition to directly influencing physicians' clinical decision making, gender bias may also influence physicians' interpersonal behavior.
Ambient Air Pollution Exposures and Risk of Rheumatoid Arthritis
Authors: Hart Jaime E. , Källberg Henrik , Laden Francine , Costenbader Karen H. , Yanosky Jeff D. , Klareskog Lars , Alfredsson Lars , Karlson Elizabeth W.
Published: February 2013

Objective

Environmental factors may play a role in the development of rheumatoid arthritis (RA). We previously observed increased RA risk among women living closer to major roads (a source of air pollution). Herein, we examined whether long‐term exposures to specific air pollutants were associated with RA risk among women in the Nurses' Health Study (NHS).

Methods

The NHS is a large US cohort of female nurses followed up prospectively every 2 years since 1976. We studied 111,425 NHS participants with information on air pollution exposures as well as data concerning other lifestyle and behavioral exposures and disease outcomes. Outdoor levels of different size fractions of particulate matter (PM10 and PM2.5) and gaseous pollutants (SO2 and NO2) were predicted for all available residential addresses using monitoring data from the US Environmental Protection Agency. We examined the association of time‐varying exposures 6 and 10 years before each questionnaire cycle and cumulative average exposure with the risk of RA, seronegative (rheumatoid factor and anti–citrullinated peptide antibody negative) RA, and seropositive RA.

Results

Over the 3,019,424 person‐years of followup, 858 incident RA cases were validated by medical record review by 2 board‐certified rheumatologists. Overall, we found no evidence of increased risk of RA, seronegative RA, or seropositive RA with exposure to the different pollutants and little evidence of effect modification by socioeconomic status or smoking status, geographic region, or calendar period.

Conclusion

In this group of socioeconomically advantaged middle‐aged and elderly women, adult exposures to air pollution were not associated with an increased RA risk.
Modest Association of Joint Hypermobility With Disabling and Limiting Musculoskeletal Pain: Results From a Large‐Scale General Population–Based Survey
Authors: Mulvey Matthew R. , Macfarlane Gary J. , Beasley Marcus , Symmons Deborah P. M. , Lovell Karina , Keeley Philip , Woby Steve , McBeth John
Published: February 2013

Objective

To determine the population prevalence of joint hypermobility (JH) and to test the hypothesis that JH would be associated with reporting musculoskeletal pain.

Methods

We conducted a cross‐sectional population survey in Aberdeen and Cheshire. A total of 45,949 questionnaires were mailed that assessed JH and the presence, distribution, duration, and severity of musculoskeletal pain. Based on their pain reports, participants were classified as having chronic widespread pain (CWP), some pain, or no pain. Multinominal logistic regression tested the relationship between JH and pain status. Associations were adjusted for age, sex, and other putative confounders. Participants with no pain were the referent category.

Results

A total of 12,853 participants (28.0%) returned a questionnaire with complete data; 2,354 participants (18.3%) were classified as hypermobile. A total of 2,094 participants (16.3%) had CWP, 5,801 participants (45.1%) had some pain, and 4,958 participants (38.6%) reported no pain. JH participants were significantly more likely to report CWP than non‐JH participants (18.5% versus 15.8%; P < 0.001). After adjusting for age and sex, hypermobile participants were 40% more likely to report the most severe CWP (relative risk ratio [RRR] 1.4, 95% confidence interval [95% CI] 1.1–1.7; P < 0.00). After further adjustments for employment status, smoking, alcohol, and physical activity, JH remained significantly associated with the most severe CWP (RRR 1.6, 95% CI 1.3–2.1; P < 0.000) and some pain (RRR 1.3, 95% CI 1.02–1.6; P = 0.03).

Conclusion

JH was associated with severe pain; however, this relationship was not specific to CWP. The relationship was relatively modest and may be explained by unmeasured confounding factors such as psychological distress.
Effect of Moderate to Vigorous Physical Activity on Long‐Term Clinical Outcomes and Pain Severity in Fibromyalgia
Authors: Kaleth Anthony S. , Saha Chandan K. , Jensen Mark P. , Slaven James E. , Ang Dennis C.
Published: February 2013

Objective

To evaluate the relationship between long‐term maintenance of moderate to vigorous physical activity (MVPA) and clinical outcomes in fibromyalgia (FM).

Methods

Patients with FM (n = 170) received individualized exercise prescriptions and completed baseline and followup physical activity assessments using the Community Health Activities Model Program for Seniors questionnaire at weeks 12, 24, and 36. The primary outcome was the change in the Fibromyalgia Impact Questionnaire‐Physical Impairment (FIQ‐PI) score. The secondary outcomes included improvements in overall well‐being (FIQ total score), pain severity ratings, and depression.

Results

Using a threshold increase in MVPA of ≥10 metabolic equivalent hours/week above usual activities, 27 subjects (15.9%) increased and sustained (SUS‐PA), 68 (40%) increased but then declined (UNSUS‐PA), and 75 (44.1%) did not achieve (LO‐PA) this benchmark. Compared to LO‐PA subjects, both SUS‐PA and UNSUS‐PA subjects reported greater improvement in FIQ‐PI (P < 0.01) and FIQ total score (P < 0.05). Additionally, the SUS‐PA group reported greater improvement in pain severity compared to the LO‐PA group (P < 0.05). However, there were no significant group differences between SUS‐PA and UNSUS‐PA for any primary or secondary outcome measure.

Conclusion

Increased participation in MVPA for at least 12 weeks improved physical function and overall well‐being in patients with FM. Although sustained physical activity was not associated with greater clinical benefit compared with unsustained physical activity, these findings also suggest that performing greater volumes of physical activity is not associated with worsening pain in FM. Future research is needed to determine the relationship between sustained MVPA participation and subsequent improvement in patient outcomes.
Pregnancy Outcomes Among Patients With Vasculitis
Authors: Clowse Megan E. B. , Richeson Rachel L. , Pieper Carl , Merkel Peter A. ,   For The Vasculitis Clinical Research Consortium
Published: February 2013

Objective

Pregnancy outcomes of patients with vasculitis are unknown, but are of great concern to patients and physicians. Through an online survey, this study assessed pregnancy outcomes among patients with vasculitis.

Methods

Participants in the Vasculitis Clinical Research Consortium Patient Contact Registry were invited to respond to an anonymous, internet‐based survey that included questions about pregnancy outcomes, the timing of pregnancy relative to a diagnosis of vasculitis, and medication use.

Results

A total of 350 women and 113 men completed the survey. After a diagnosis of vasculitis, 74 pregnancies were reported by women and 18 conceptions were reported by men. The rate of pregnancy loss was higher among women who conceived after a diagnosis of vasculitis compared to those who conceived prior to diagnosis (33.8% versus 22.4%; P = 0.04). Among women, the rate of preterm births increased significantly for pregnancies conceived after a diagnosis of vasculitis relative to those conceived before diagnosis (23.3% versus 11.4%; P = 0.03). Only 18% of women reported worsening of vasculitis during pregnancy, but those who experienced increased vasculitis activity were more likely to deliver preterm. Exposure to cyclophosphamide or prednisone did not appear to impact pregnancy outcomes; however, the number of pregnancies among women taking these medications was small. Among the pregnancies conceived by men with vasculitis, the timing of diagnosis had no significant effect on the rate of pregnancy loss.

Conclusion

Women who conceived after a diagnosis of vasculitis had a higher rate of pregnancy loss than those who conceived prior to diagnosis. Vasculitis did not worsen during the majority of pregnancies conceived after diagnosis.
Convergence and stability analysis of a digital automatic gain control
Authors: Mingyang Zhang , Zhugang Wang , Weiming Xiong
Published: February 2013

This paper is dedicated to the theoretical analysis of a digital automatic gain control (AGC), which feedbacks according to the desired output direct current (DC). First, we mathematically model the AGC, with the input signal interfered by AWGN. As it turns out, the loop model is a first‐order varying‐coefficient stochastic difference equation, and its solution consists of two parts, that is, the transient state and the steady state, which respectively explain the convergence and stability of the AGC. As is shown in the paper, the properties of convergence and stability of AGC are mutually contradictory, and both are determined by a key parameter in the loop, and the parameter is defined as the feedback sensitivity of the loop. The results of the paper are validated by numerical simulation, and they are of theoretical guide for practical digital AGC implementation on Application Specific Integrated Chips (ASICs) or Field Programmable Gate Arrays (FPGAs). Copyright © 2013 John Wiley & Sons, Ltd.
Theoretical modeling coupled with experimental study on the preparation and characterization comparison of fluorinated copolymers: Effect of chain structure on copolymer properties
Authors: Zhou Yin‐Ning , Luo Zheng‐Hong , Chen Jian‐Hua
Published: February 2013

Theoretical modeling coupled with an experimental study is presented for the preparation and characterization comparison of the amphiphilic copolymers of 2, 2, 3, 3, 4, 4, 4‐heptafluorobutyl methacrylate (HFBMA) and 2‐hydroxyethyl methacrylate (HEMA) to achieve a multiscale generalization of the polymeric system. A series of amphiphilic copolymers having different chain structures with HFBMA as the hydrophobic component and HEMA as the hydrophilic component was first synthesized through atom transfer radical copolymerization (ATRcoP) or model‐based semibatch ATRcoP. Theoretical modeling is used to optimize the macromolecular structure and experimental approaches that are used to prepare copolymers of HFBMA and HEMA with some tailor‐made polymer properties. Furthermore, a systematic comparison of major properties (i.e., thermal, micellization, and surface properties) of these fluorinated copolymers (i.e., random, block, linear gradient, and inverse linear gradient copolymers) was carried out. The results show that these fluorinated copolymers with different chain structures have dissimilar properties. The results also demonstrate that the approach of coupling theoretical modeling with an experimental study can be used to guide a multiscale generalization of the polymeric system for practical application. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3019–3033, 2013
Evaluating mixture adsorption models using molecular simulation
Authors: Swisher Joseph A. , Lin Li‐Chiang , Kim Jihan , Smit Berend
Published: February 2013

The design of adsorption‐based separation processes using novel adsorbents requires reliable data for the adsorption of fluid mixtures on candidate adsorbents. Due to the difficulty of generating sufficient data across possible operating conditions, process designs generally rely on interpolation of pure‐component data using a model, most commonly ideal adsorbed solution theory (IAST), and related theories. There are many cases where IAST fails to provide an adequate description of mixture adsorption, usually due to the fact that practical adsorbents do not have uniform surfaces. We have evaluated the use of a segregated version of IAST, where competition is assumed to occur at isolated adsorption sites. This simple modification can provide the correct description of adsorption across a large range of pressures using ideal isotherm models. We also demonstrate the importance of identifying multiple sites even for weakly adsorbing components to provide the correct behavior at high pressure. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3054–3064, 2013
Thinnest uniform liquid films formed at the highest speeds with reverse roll coating
Authors: Benkreira H. , Shibata Y. , Ito K.
Published: February 2013

Reverse roll coating is probably the most widely used coating operation, much less investigated than its counterpart and inherently unstable forward roll coating. A new data to complement earlier work which was limited to large gaps and thus “thick” films is presented. The intention is to assess the feasibility of reverse roll coating to yield very thin films (<10 μm) at high speeds (>1 m/s) for application in the newer technologies, such as the production of solar cells and plastic electronics. The data obtained demonstrate this is possible but at the lowest permissible gap (25–50 μm) with low‐viscosity fluids (∼7 mPa s). The study also developed a new understanding of how instabilities are controlled. It was seen that the size of the inertia forces generated by the applicator roller in relation to surface tension, as expressed by the Weber number and not the applicator Capillary number (viscous forces/surface tension) which is the critical parameter. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3083–3091, 2013
Anti–amyloid β autoantibodies in cerebral amyloid angiopathy–related inflammation: Implications for amyloid‐modifying therapies
Authors: Piazza Fabrizio , Greenberg Steven M. , Savoiardo Mario , Gardinetti Margherita , Chiapparini Luisa , Raicher Irina , Nitrini Ricardo , Sakaguchi Hideya , Brioschi Monica , Billo Giuseppe , Colombo Antonio , Lanzani Francesca , Piscosquito Giuseppe , Carriero Maria Rita , Giaccone Giorgio , Tagliavini Fabrizio , Ferrarese Carlo , DiFrancesco Jacopo C.
Published: February 2013

Objective

Cerebral amyloid angiopathy–related inflammation (CAA‐ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid‐related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti–amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA‐ri.

Methods

We used a novel ultrasensitive technique on patients from a retrospective multicenter case–control study, and evaluated the anti‐Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA‐ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P‐181 tau, and APOE genotype were also investigated.

Results

During the acute phase of CAA‐ri, anti‐Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P‐181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel.

Interpretation

Our data support the hypothesis that the pathogenesis of CAA‐ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti‐Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA‐ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti‐Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid‐modifying therapies for the treatment of AD and CAA. Ann Neurol 2013;73:449–458
Clinical correlates in an experimental model of repetitive mild brain injury
Authors: Mannix Rebekah , Meehan William P. , Mandeville Joseph , Grant Patricia E. , Gray Tory , Berglass Jacqueline , Zhang Jimmy , Bryant John , Rezaie Shervin , Chung Joon Yong , Peters Nicholas V. , Lee Christopher , Tien Lee W. , Kaplan David L. , Feany Mel , Whalen Michael
Published: February 2013

Objective

Although there is growing awareness of the long‐term cognitive effects of repetitive mild traumatic brain injury (rmTBI; eg, sports concussions), whether repeated concussions cause long‐term cognitive deficits remains controversial. Moreover, whether cognitive deficits depend on increased amyloid β deposition and tau phosphorylation or are worsened by the apolipoprotein E4 allele remains unknown. Here, we use an experimental model of rmTBI to address these clinical controversies.

Methods

A weight drop rmTBI model was used that results in cognitive deficits without loss of consciousness, seizures, or gross or microscopic evidence of brain damage. Cognitive function was assessed using a Morris water maze (MWM) paradigm. Immunostaining and enzyme‐linked immunosorbent assay (ELISA) were used to assess amyloid β deposition and tau hyperphosphorylation. Brain volume and white matter integrity were assessed by magnetic resonance imaging (MRI).

Results

Mice subjected to rmTBI daily or weekly but not biweekly or monthly had persistent cognitive deficits as long as 1 year after injuries. Long‐term cognitive deficits were associated with increased astrocytosis but not tau phosphorylation or amyloid β (by ELISA); plaques or tangles (by immunohistochemistry); or brain volume loss or changes in white matter integrity (by MRI). APOE4 was not associated with worse MWM performance after rmTBI.

Interpretation

Within the vulnerable time period between injuries, rmTBI produces long‐term cognitive deficits independent of increased amyloid β or tau phosphorylation. In this model, cognitive outcome is not influenced by APOE4 status. The data have implications for the long‐term mental health of athletes who suffer multiple concussions. Ann Neurol 2013;74:65–75
Nonconvulsive seizures after subarachnoid hemorrhage: Multimodal detection and outcomes
Authors: Claassen Jan , Perotte Adler , Albers David , Kleinberg Samantha , Schmidt J. Michael , Tu Bin , Badjatia Neeraj , Lantigua Hector , Hirsch Lawrence J. , Mayer Stephan A. , Connolly E. Sander , Hripcsak George
Published: February 2013

Objective

Seizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood.

Methods

We analyzed intracortical electroencephalographic (EEG) and multimodality physiological recordings in 48 comatose subarachnoid hemorrhage patients to better characterize the physiological response to seizures after acute brain injury.

Results

Intracortical seizures were seen in 38% of patients, and 8% had surface seizures. Intracortical seizures were accompanied by elevated heart rate (p= 0.001), blood pressure (p< 0.001), and respiratory rate (p< 0.001). There were trends for rising cerebral perfusion pressure (p= 0.03) and intracranial pressure (p= 0.06) seen after seizure onset. Intracortical seizure–associated increases in global brain metabolism, partial brain tissue oxygenation, and regional cerebral blood flow (rCBF) did not reach significance, but a trend for a pronounced delayed rCBF rise was seen for surface seizures (p= 0.08). Functional outcome was very poor for patients with severe background attenuation without seizures and best for those without severe attenuation or seizures (77% vs 0% dead or severely disabled, respectively). Outcome was intermediate for those with seizures independent of the background EEG and worse for those with intracortical only seizures when compared to those with intracortical and scalp seizures (50% and 25% death or severe disability, respectively).

Interpretation

We replicated in humans complex physiologic processes associated with seizures after acute brain injury previously described in laboratory experiments and illustrated differences such as the delayed increase in rCBF. These real world physiologic observations may permit more successful translation of laboratory research to the bedside. Ann Neurol 2013;74:53–64
Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR‐124 and reduced AMPA receptors
Authors: Dutta Ranjan , Chomyk Anthony M. , Chang Ansi , Ribaudo Michael V. , Deckard Sadie A. , Doud Mary K. , Edberg Dale D. , Bai Brian , Li Michael , Baranzini Sergio E. , Fox Robert J. , Staugaitis Susan M. , Macklin Wendy B. , Trapp Bruce D.
Published: February 2013

Objective

Hippocampal demyelination, a common feature of postmortem multiple sclerosis (MS) brains, reduces neuronal gene expression and is a likely contributor to the memory impairment that is found in >40% of individuals with MS. How demyelination alters neuronal gene expression is unknown.

Methods

To explore whether loss of hippocampal myelin alters expression of neuronal microRNAs (miRNAs), we compared miRNA profiles from myelinated and demyelinated hippocampi from postmortem MS brains and performed validation studies.

Results

A network‐based interaction analysis depicts a correlation between increased neuronal miRNAs and decreased neuronal genes identified in our previous study. The neuronal miRNA miR‐124 was increased in demyelinated MS hippocampi and targets mRNAs encoding 26 neuronal proteins that were decreased in demyelinated hippocampus, including the ionotrophic glutamate receptors AMPA2 and AMPA3. Hippocampal demyelination in mice also increased miR‐124, reduced expression of AMPA receptors, and decreased memory performance in water maze tests. Remyelination of the mouse hippocampus reversed these changes.

Interpretation

We establish here that myelin alters neuronal gene expression and function by modulating the levels of the neuronal miRNA miR‐124. Inhibition of miR‐124 in hippocampal neurons may provide a therapeutic approach to improve memory performance in MS patients. Ann Neurol 2013;73:637–645
Improved outcomes with earlier surgery for intractable frontal lobe epilepsy
Authors: Simasathien Thitiwan , Vadera Sumeet , Najm Imad , Gupta Ajay , Bingaman William , Jehi Lara
Published: February 2013

Objective

To explore the prognostic implications of epilepsy duration and age at surgery for seizure outcomes after frontal lobe epilepsy (FLE) surgery.

Methods

We reviewed 158 patients who underwent FLE surgery from 1995 to 2010. The primary outcome was seizure freedom at last follow‐up (Engel class IA). Analyses employed Cox proportional and multiphase hazard modeling.

Results

The mean age at surgery was 20.4 years, and mean epilepsy duration was 12.0 years. The estimated chance of seizure freedom was 66% (95% confidence interval [CI] = 62–68) at 1 postoperative year, 52% (95% CI = 48–56) at 2 years, and 44% (95% CI = 39–49) at 5 years and beyond. Seventy‐five percent of recurrences occurred within 6 postoperative months. Both younger age at surgery (<18 years) and shorter epilepsy duration (<5 years) correlated with better seizure outcomes on univariate analysis, but only epilepsy duration remained statistically significant after multivariate modeling. Independent poor prognostic indicators included left‐sided resections and acute postoperative seizures (APOSs; whole model log‐rank test p < 0.0001). APOSs were particularly predictive of early epilepsy recurrence, starting within 6 postoperative months (adjusted risk ratio [RR] = 4.42, p < 0.0001), whereas long epilepsy duration correlated with late recurrences (RR = 6.25, p < 0.0001). Worse outcomes were seen with longer epilepsy duration for duration cutoffs of 2, 5, and 10 years independently for adults and children, although statistical significance was only achieved in children (66% seizure free at 5 postoperative years if operated on within 5 years of epilepsy onset vs 31% if later; p = 0.01).

Interpretation

Early resection may improve seizure outcomes of FLE surgery, particularly in children. Ann Neurol 2013;73:646–654
Pathological correlates of magnetic resonance imaging texture heterogeneity in multiple sclerosis
Authors: Zhang Yunyan , Moore G. R. Wayne , Laule Cornelia , Bjarnason Thorarin A. , Kozlowski Piotr , Traboulsee Anthony , Li David K. B.
Published: February 2013

Objective

To analyze the texture of T2‐weighted magnetic resonance imaging (MRI) of postmortem multiple sclerosis (MS) brain, and to determine whether and how MRI texture correlates with tissue pathology.

Methods

Ten brain samples from 3 subjects with MS were examined. Areas of complete, partial, or no loss of Luxol fast blue (myelin) and Bielschowsky (axons) staining were marked on histological images, and matched on corresponding MRI as lesions, diffusely abnormal white matter (DAWM), and normal‐appearing white matter (NAWM). The number of CD45+ cells (inflammation) was also counted. MRI texture was computed using polar Stockwell transform and compared to histology.

Results

Thirty‐four lesions, 17 DAWM regions, and 36 NAWM regions were identified. After mixed effects modeling, MRI texture heterogeneity was greater in lesions than in DAWM (p < 0.001) and NAWM (p < 0.001), and was greater in DAWM than in NAWM (p < 0.001); the number of CD45+ cells was greater in both lesions (p < 0.001) and DAWM (p = 0.005) than in NAWM. In MRI, a gradient of texture heterogeneity was detected in lesions, with gradual tapering toward perilesional NAWM. Moreover, besides univariate correlation with histological markers, texture heterogeneity correlated independently with normalized myelin density (p < 0.01) when random effects were considered. Within sample, MRI texture correlated with myelin and axonal density in 7 of 10 samples (p < 0.01).

Interpretation

Texture analysis performed on routine clinical magnetic resonance images may be a potential measure of tissue integrity. Tissues with more severe myelin and axonal pathology are associated with greater texture heterogeneity. Ann Neurol 2013;74:91–99
G protein–coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation‐induced sensitization to excitotoxic neurodegeneration
Authors: Degos Vincent , Peineau Stéphane , Nijboer Cora , Kaindl Angela M. , Sigaut Stéphanie , Favrais Géraldine , Plaisant Frank , Teissier Natacha , Gouadon Elodie , Lombet Alain , Saliba Elie , Collingridge Graham L. , Maze Mervyn , Nicoletti Ferdinando , Heijnen Cobi , Mantz Jean , Kavelaars Annemieke , Gressens Pierre
Published: February 2013

Objective

The concept of inflammation‐induced sensitization is emerging in the field of perinatal brain injury, stroke, Alzheimer disease, and multiple sclerosis. However, mechanisms underpinning this process remain unidentified.

Methods

We combined in vivo systemic lipopolysaccharide‐induced or interleukin (IL)−1β–induced sensitization of neonatal and adult rodent cortical neurons to excitotoxic neurodegeneration with in vitro IL‐1β sensitization of human and rodent neurons to excitotoxic neurodegeneration. Within these inflammation‐induced sensitization models, we assessed metabotropic glutamate receptors (mGluR) signaling and regulation.

Results

We demonstrate for the first time that group I mGluRs mediate inflammation‐induced sensitization to neuronal excitotoxicity in neonatal and adult neurons across species. Inflammation‐induced G protein–coupled receptor kinase 2 (GRK2) downregulation and genetic deletion of GRK2 mimicked the sensitizing effect of inflammation on excitotoxic neurodegeneration. Thus, we identify GRK2 as a potential molecular link between inflammation and mGluR‐mediated sensitization.

Interpretation

Collectively, our findings indicate that inflammation‐induced sensitization is universal across species and ages and that group I mGluRs and GRK2 represent new avenues for neuroprotection in perinatal and adult neurological disorders. Ann Neurol 2013;73:667–678
Stable isotope ratios of egg albumen of three waterbird species nesting in the Colorado River Delta indicate differences in foraging ground and isotopic niche breadth
Authors: Herzka Sharon Z. , Mellink Eric , Talley Drew M. , Huxel Gary R. , Dayton Paul K.
Published: February 2013

The Colorado River Delta is one of the most impacted wetland systems in the world and has experienced massive habitat loss owing to severe restrictions in freshwater inflow as a result of dam construction and diversion of water for irrigation. However, the delta still offers nesting and foraging habitats for waterbirds, although the habitats available are highly fragmented and limited.

Stable isotope ratio (SIR) analysis was used to assess quantitatively isotopic niche width of gull‐billed terns (Gelochelidon nilotica), laughing gulls (Leucophaeus atricilla) and snowy egrets (Egreta thula) that nest at an inland and coastal location.

The variance in carbon and nitrogen SIR of egg albumen indicated that inland colonies have a much broader isotope niche width (range 2.9 to 23.9) than coastal colonies (<0.1 to 1.4).

Species‐specific mean albumen δ13C values from inland nests were significantly more depleted in 13C than coastal colonies (−19.5 to −23.1‰ and −10.4 to −14.9‰, respectively). Comparison of albumen δ13C values corrected for trophic fractionation with those of potential prey and primary producers collected at 10 potential foraging grounds indicates that females of the three species that nest in inland colonies did not feed in habitats located in the vicinity of their nesting site, while coastal colonies had distinct isotopic signatures reflecting marine primary production. Inland colonies probably forage in a variety of habitats and for different prey, relying on food webs based mostly on C3 terrestrial plants.

Differences in the isotopic composition of eggs from species nesting in the same area and between conspecifics nesting in different habitats indicate that foraging habitats vary substantially, suggesting that feeding varies as a function of local resource availability.

These results suggest that a variety of habitat types fulfill the foraging needs of this suite of nesting waterbird species, especially in inland colonies. Since the specific feeding areas of nesting females from the inland colonies have not been identified, protection of the remaining wetlands within the Colorado River Delta is warranted.

Copyright © 2013 John Wiley & Sons, Ltd.
Geoarchaeological Context of the Motilla de la Vega Site (Spain) Based on Electrical Resistivity Tomography
Authors: Teixidó T. , Artigot E. G. , Peña J. A. , Molina F. , Nájera T. , Carrión F.
Published: February 2013

During the Bronze Age, the region of La Mancha Occidental (Spain) was occupied by prehistoric settlements in which the protection of basic resources was a primary concern. The structure of these settlements comprised several concentric walls that surrounded conical mounds around 4–10 m high. The Motilla de la Vega is an unexcavated site next to the Azuer River, and is only 4 km from another Bronze Age village, called Motilla del Azuer, which has been subject to systematic archaeological excavations and is the paradigmatic reference for these settlements. As Motilla del Azuer had a well inside its walls and this fort is located in a similar geological setting, it is logical to ask whether Motilla de la Vega also had a well inside its walls, and to determine whether it is possible to extend similar architectonic and social patterns to other settlements that occupied the river valleys of this region. In this study, we used the electrical resistivity tomography (ERT) method to detect the possible location of a well in Motilla de la Vega. In order to plan appropriate data acquisition, and to evaluate the optimal parameters for processing the field data, we performed a numerical modelling exercise to simulate the likely ERT responses based on the geological information and on the constructive scheme of the excavated well in Motilla del Azuer. Afterwards, we carried out five ERT profiles over the levelled Motilla de la Vega site and some of them have resistive anomalies similar to those that synthetic models predict for a well. Consequently, we propose the existence of a well placed in the eastern side of Motilla de la Vega, with the same relative position as the well of Motilla del Azuer. This has implications for the understanding of other sites in the region. Copyright © 2013 John Wiley & Sons, Ltd.
Brief Report: Attention Deficit and Hyperactivity Disorder Scores Are Elevated and Respond to N‐Acetylcysteine Treatment in Patients With Systemic Lupus Erythematosus
Authors: Garcia Ricardo J. , Francis Lisa , Dawood Maha , Lai Zhi‐Wei , Faraone Stephen V. , Perl Andras
Published: February 2013

Objective

To investigate whether attention deficit hyperactivity disorder (ADHD) may serve as a marker of neuropsychiatric disease and as a target for N‐acetylcysteine (NAC) treatment in patients with systemic lupus erythematosus (SLE).

Methods

The ADHD Self‐Report Scale (ASRS) was used to assess 49 patients with SLE and 46 matched healthy control subjects. Twenty‐four of the patients with SLE were randomized to receive either placebo, NAC at a dosage of 2.4 gm/day, or NAC at a dosage of 4.8 gm/day. Disease activity was evaluated monthly using the British Isles Lupus Assessment Group (BILAG) index, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the Fatigue Assessment Scale (FAS), and the ASRS, before and during the 3‐month treatment period and after a 1‐month washout period.

Results

The cognitive/inattentive (ASRS part A), hyperactivity/impulsive (ASRS part B), and combined (total) ASRS scores were increased in patients with SLE compared with control subjects (mean ± SEM 17.37 ± 1.03 [P = 3 × 10−7], 14.51 ± 0.89 [P = 2 × 10−4], and 31.92 ± 1.74 [P = 8 × 10−7], respectively, versus 10.41 ± 1.02, 9.61 ± 1.21, and 20.02 ± 1.98, respectively. ASRS part A scores correlated with SLEDAI (r = 0.53, P < 0.0001) and BILAG scores (r = 0.36, P = 0.011). ASRS total scores also correlated with SLEDAI (r = 0.45, P = 0.0009) and BILAG scores (r = 0.31, P = 0.025). ASRS part A (r = 0.73, P < 0.0001), ASRS part B (r = 0.47, P = 0.0006), and ASRS total scores (r = 0.67, P < 0.0001) correlated with the FAS score. Relative to the scores in placebo‐treated patients, ASRS total scores were reduced in SLE patients treated with NAC dosages of 2.4 gm/day and 4.8 gm/day combined (P = 0.037). ASRS part A scores were reduced by NAC dosages of 2.4 gm/day (P = 0.001) and 4.8 gm/day (P < 0.0001) as well as by NAC at dosages of 2.4 gm/day and 4.8 gm/day combined (P = 0.001).

Conclusion

In patients with SLE, elevated ASRS scores reveal previously unrecognized and clinically significant symptoms of ADHD that respond to NAC treatment.
Adoptive Transfer of Human Gingiva‐Derived Mesenchymal Stem Cells Ameliorates Collagen‐Induced Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of Regulatory T Cell Differentiation
Authors: Chen Maogen , Su Wenru , Lin Xiaohong , Guo Zhiyong , Wang Julie , Zhang Qunzhou , Brand David , Ryffel Bernhard , Huang Jiefu , Liu Zhongmin , He Xiaoshun , Le Anh D. , Zheng Song Guo
Published: February 2013

Objective

Current approaches offer no cures for rheumatoid arthritis (RA). Accumulating evidence has revealed that manipulation of bone marrow–derived mesenchymal stem cells (BM‐MSCs) may have the potential to control or even prevent RA, but BM‐MSC–based therapy faces many challenges, such as limited cell availability and reduced clinical feasibility. This study in mice with established collagen‐induced arthritis (CIA) was undertaken to determine whether substitution of human gingiva‐derived mesenchymal stem cells (G‐MSCs) would significantly improve the therapeutic effects.

Methods

CIA was induced in DBA/1J mice by immunization with type II collagen and Freund's complete adjuvant. G‐MSCs were injected intravenously into the mice on day 14 after immunization. In some experiments, intraperitoneal injection of PC61 (anti‐CD25 antibody) was used to deplete Treg cells in arthritic mice.

Results

Infusion of G‐MSCs in DBA/1J mice with CIA significantly reduced the severity of arthritis, decreased the histopathology scores, and down‐regulated the production of inflammatory cytokines (interferon‐γ and interleukin‐17A). Infusion of G‐MSCs also resulted in increased levels of CD4+CD39+FoxP3+ cells in arthritic mice. These increases were noted early after infusion in the spleens and lymph nodes, and later after infusion in the synovial fluid. The FoxP3+ Treg cells that were increased in frequency mainly consisted of Helios‐negative cells. When Treg cells were depleted, infusion of G‐MSCs partially interfered with the progression of CIA. Pretreatment of G‐MSCs with a CD39 or CD73 inhibitor significantly reversed the protective effect of G‐MSCs on CIA.

Conclusion

The role of G‐MSCs in controlling the development and severity of CIA mostly depends on CD39/CD73 signals and partially depends on the induction of CD4+CD39+FoxP3+ Treg cells. G‐MSCs provide a promising approach for the treatment of autoimmune diseases.
Brief Report: Shortened Telomere Length in Patients With Systemic Lupus Erythematosus
Authors: Haque Sahena , Rakieh Chadi , Marriage Fiona , Ho Pauline , Gorodkin Rachel , Teh Lee Suan , Snowden Neil , Day Philip J. R. , Bruce Ian N.
Published: February 2013

Objective

Patients with systemic lupus erythematosus (SLE) have a higher rate of premature death compared to the general population, suggesting a phenotype of premature senescence in SLE. Telomere length can be used to assess overall biologic aging. This study was undertaken to address the hypothesis that patients with SLE have reduced telomere length.

Methods

Telomere length was measured cross‐sectionally in whole blood from SLE patients and age‐matched healthy female controls, using real‐time quantitative polymerase chain reaction. SLE‐related and cardiovascular risk factors were assessed.

Results

We compared telomere length in 63 SLE patients and 63 matched controls with a median age of 50.8 years (interquartile range [IQR] 37–59 years) and 49.9 years (IQR 32–60 years), respectively. The median relative telomere length in SLE patients was 0.97 (IQR 0.47–1.57), compared to 1.53 (IQR 0.82–2.29) in controls (P = 0.0008). We then extended our cohort to measure telomere length in 164 SLE patients. Shorter telomere length was associated with Ro antibodies (β ± SE −0.36 ± 0.16; P = 0.023), and longer telomere length was associated with steroid therapy (0.29 ± 0.14; P = 0.046). We also noted an association of longer telomere length with increasing body mass index (β ± SE 0.07 ± 0.01; P < 0.0001) and tobacco smoking (0.64 ± 0.26; P = 0.016), as well as with the presence of carotid plaque (0.203 ± 0.177; P = 0.032).

Conclusion

Telomere length is shortened in SLE patients compared to controls and does not appear to be a reflection of disease activity or immune cell turnover. Subsets of patients such as those positive for Ro antibodies may be particularly susceptible to premature biologic aging. The predictive value of telomere length as a biomarker of future risk of damage/mortality in SLE requires longitudinal evaluation.
Future GHG emissions more efficiently controlled by land‐use policies than by bioenergy sustainability criteria
Authors: Böttcher Hannes , Frank Stefan , Havlík Petr , Elbersen Berien
Published: February 2013

The EU Renewable Energy Directive (RED) targets, implemented to achieve climate change mitigation, affect the level of agricultural production in the EU and in the rest of the world. This article presents an impact assessment of increased biomass supply under different sustainability constraints on land use and resulting total GHG emissions at global and EU level. We apply GLOBIOM, a global partial equilibrium model integrating the agricultural, livestock, bioenergy and forestry sectors based on geographically explicit modeling of supply under prescribed demand. According to the model, global greenhouse gas (GHG) emissions from agriculture and land‐use change (LUC) are anticipated to rise significantly up to 2030 due to various drivers (among others: GDP and population, diet shifts, and also bioenergy demand) despite basic sustainability criteria implemented by the RED (Reference scenario). Applying additional criteria, mainly protecting biodiversity outside the EU, overall GHG emissions can be reduced by 5% in 2030 compared to the Reference. Deforestation area decreases in this scenario slightly due to exclusion of high biodiversity forests but also due to increasing demand for energy wood that makes forests more valuable. If, however, in addition, deforestation is prevented through effective land‐use policies, global GHG emissions can be reduced by 20% (compared to the Reference scenario). We conclude that sustainability criteria applied to biofuel production and imports only, do not mitigate potential negative impacts on total GHG emissions effectively. Unsustainable biomass production in sectors not covered by the bioenergy criteria can be best avoided by targeting deforestation and biodiversity loss directly. © 2013 Society of Chemical Industry and John Wiley & Sons, Ltd