bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for lower extremity fatigue among assembly plant workers
Authors: Gell Nancy , Werner Robert A. , Hartigan Anne , Wiggermann Neal , Keyserling W. Monroe 
Published: October 2010

AbstractBackgroundWork‐related fatigue of the lower extremities is a known cause of lost productivity and significant employer costs. Common workplace solutions to reduce fatigue levels include anti‐fatigue matting, shoe orthoses, or sit/stand work stations. However, assessment of these anti‐fatigue measures within the workplace has been limited.MethodsThis was a cross sectional study in an automotive assembly plant on employees with at least 6 months tenure. Subject data were collected via questionnaires including Likert‐scale questions to define fatigue severity. Jobs were evaluated for lower extremity ergonomic exposures via videotaping, pedometers, interviews, and industrial engineering records.ResultsLower extremity fatigue at the end of the work day was associated with a higher prevalence of smoking, rheumatoid arthritis, job dissatisfaction, use of shoes with firmer outsoles, and increased time on the job spent standing or walking. Supervisor support and increased time spent on carpet were protective. Lower extremity fatigue that interfered with activities outside of work had additional risk factors including higher BMI, prior diagnosis of osteoarthritis, and increased hours per week spent working.ConclusionsWhile these results identify carpet as being protective against lower extremity fatigue, no similar relationship was identified for anti‐fatigue mats. No adverse relationship was found between hard surfaces such as concrete and lower extremity fatigue. Given the high costs associated with work‐related fatigue, future areas for potential intervention include smoking cessation, specific shoe recommendations, and enhancing psychosocial aspects of work such as supervisor support. Am. J. Ind. Med. 54:216–223, 2011. © 2010 Wiley‐Liss, Inc.
Intragenic deletions of IL1RAPL1: Report of two cases and review of the literature
Authors: Behnecke Anne , Hinderhofer Katrin , Bartsch Oliver , Nümann Astrid , Ipach Marie‐Luise , Damatova Natalja , Haaf Thomas , Dufke Andreas , Riess Olaf , Moog Ute 
Published: October 2010

AbstractIL1RAPL1 (interleukin‐1 receptor accessory protein‐like 1) located at Xp21.3‐22.1 has repeatedly been shown to be deleted in patients with a contiguous gene syndrome also affecting neighboring genes, in particular DMD (dystrophin), DAX‐1 (NR0B1, nuclear receptor subfamily 0, group B, member 1), and GK (glycerol kinase). In contrast, intragenic deletions of IL1RAPL1 or other mutations or cytogenetic aberrations affecting IL1RAPL1 have only rarely been identified. Up to date, they have mostly been associated with nonspecific mental retardation (MRX). We report on two nonrelated patients with MR and additional dysmorphic features who both show intragenic deletions of IL1RAPL1, one of them being de novo (exon 2) and the other one being inherited from his mother (exons 3–5). Deletions were identified by microarray‐based chromosome analysis and confirmed by multiplex PCR and FISH, respectively. These data, along with recent functional studies indicating its role in neuronal development, provide further evidence for the relevance of IL1RAPL1 in the pathogenesis of X‐linked MR and add knowledge to the phenotypic spectrum of IL1RAPL1 mutations. © 2010 Wiley‐Liss, Inc.
Brain biopsy in children with primary small‐vessel central nervous system vasculitis
Authors: Elbers Jorina , Halliday William , Hawkins Cynthia , Hutchinson Clare , Benseler Susanne M. 
Published: October 2010

AbstractObjective::Primary angiitis of the central nervous system in childhood (cPACNS) is an immune‐mediated inflammatory process directed toward blood vessels in the central nervous system. It has been associated with variable clinical and radiological presentations, and devastating consequences without treatment. Brain biopsy is required for definitive diagnosis. The objective of this study was to characterize the clinical and histopathological features of brain biopsies in small‐vessel cPACNS (SVcPACNS).Methods::A single‐center prospective cohort study of children diagnosed with cPACNS from 1998 to 2008 was performed. All patients with negative cerebral angiography and brain biopsy were included. Patient data were reviewed for clinical, laboratory, and radiological characteristics at presentation. Standardized brain biopsy review protocols were established, with independent analysis by 2 neuropathologists. Histopathology was correlated with collected clinical data.Results::A total of 13 SVcPACNS patients were included. Ages ranged from 5 to 17 years. Presenting features included seizures (85%), headache (62%), and cognitive decline (54%). Brain biopsy confirmed SVcPACNS in 11 patients with intramural lymphocytic infiltrate. Two had nonspecific perivascular inflammation only. All 6 nonlesional biopsies yielded a diagnosis of SVcPACNS. Lack of specific histological features correlated with prolonged time to biopsy, prior steroid treatment, and inadequate specimen sampling.Interpretation::In children presenting with new onset severe headaches, seizures, or cognitive decline, SVcPACNS and brain biopsy should be considered. Lesional biopsies are preferred; however, nonlesional biopsies may succeed in yielding the diagnosis. Steroid treatment prior to biopsy and inadequate biopsy sampling may obscure the diagnosis in true cases of SVcPACNS. ANN NEUROL 2010;68:602–610
Recurrent ischemic events in young adults after first‐ever ischemic stroke
Authors: Putaala Jukka , Haapaniemi Elena , Metso Antti J. , Metso Tiina M. , Artto Ville , Kaste Markku , Tatlisumak Turgut 
Published: October 2010

AbstractObjective::Data on recurrence of vascular events and their prognostic factors in young (<50 years of age) stroke patients are not well defined.Methods::We assessed the occurrence of arterial thrombotic events in consecutive first‐ever ischemic stroke patients aged 15 to 49 years entered into the Helsinki Young Stroke Registry (January 1994–October 2004) within 5‐year follow‐up. Follow‐up was conducted with a structured telephone interview or letter, and review of all patient records; mortality data came from Statistics Finland. Primary outcomes were (1) nonfatal or fatal recurrent ischemic stroke; (2) nonfatal or fatal myocardial infarct, other arterial thrombotic event, or revascularization procedure; and (3) any combination of these, whichever occurred first (composite endpoint). We used Kaplan‐Meier analysis to estimate cumulative risks and Cox proportional hazard model—adjusted for age, gender, relevant risk factors, and stroke subtype—for identifying predictors of recurrence.Results::In the 807 patients followed (mean age, 41.5 ± 7.4 years; 62.9% male), cumulative 5‐year recurrence rate was 9.4% (95% confidence interval [CI], 7.3–11.5%) for nonfatal or fatal ischemic stroke, 2.4% (95% CI, 1.3‐3.5%) for nonfatal or fatal myocardial infarct or other arterial endpoint, and 11.5% (95% CI, 9.2‐13.7%) for the composite endpoint. Independent predictors of the composite endpoint were type 1 diabetes mellitus (hazard ratio [HR], 4.39; 95% CI, 2.28‐8.45), large‐artery atherosclerosis underlying the index stroke (HR, 2.82; 95% CI, 1.36‐5.83), heart failure (HR, 2.96; 95% CI, 1.17‐7.50), previous transient ischemic attack (HR, 2.33; 95% CI, 1.40‐3.88), and increasing age (HR, 1.05; 95% CI, 1.01‐1.10).Interpretation::Despite their young age, these individuals were at marked risk of recurrent arterial events, predicted by mostly modifiable baseline factors.ANN NEUROL 2010;68:661–671
Caffeine and brain development in very preterm infants
Authors: Doyle Lex W. , Cheong Jeanie , Hunt Rod W. , Lee Katherine J. , Thompson Deanne K. , Davis Peter G. , Rees Sandra , Anderson Peter J. , Inder Terrie E. 
Published: October 2010

AbstractObjective:Caffeine improves neurological outcome in very preterm infants, but the mechanisms responsible for this neurological benefit are unknown. The objective of this study was to assess whether caffeine influenced brain macro‐ or microstructural development in preterm infants.Methods:Seventy preterm infants <1,251 g birthweight randomly allocated to either caffeine (n = 33) or placebo (n = 37) underwent brain magnetic resonance imaging (MRI) at term‐equivalent age; white and gray matter abnormalities were qualitatively scored, global and regional brain volumes were measured, and white matter microstructure was evaluated using diffusion‐weighted imaging.Results:There were no significant differences between the groups in the extent of white matter or gray matter abnormality, or in global or regional brain volumes. In contrast, although only available in 28 children, caffeine exposure was associated with reductions in the apparent diffusion coefficient, and radial and axial diffusivity with the greatest impact in the superior brain regions. The alterations in diffusion measures were not mediated by lowering the rate of lung injury, known as bronchopulmonary dysplasia.Interpretation:These diffusion changes are consistent with improved white matter microstructural development in preterm infants who received caffeine. ANN NEUROL 2010;68:734–742
Recombinant osteopontin in cerebral vasospasm after subarachnoid hemorrhage
Authors: Suzuki Hidenori , Hasegawa Yu , Chen Wanqiu , Kanamaru Kenji , Zhang John H. 
Published: October 2010

AbstractObjective:Osteopontin (OPN), a pleiotropic extracellular matrix glycoprotein, has been reported to be protective against ischemic lesions, but effects of OPN on vascular functions have not been investigated. The aim of this study was to assess whether recombinant OPN (r‐OPN) could prevent cerebral vasospasm after subarachnoid hemorrhage (SAH) in rats.Methods:r‐OPN was administered intraventricularly to rats undergoing SAH by endovascular perforation, and its protective effects were evaluated by measuring the diameter of cerebral arteries and neurobehavioral testing. Western blotting and immunofluorescence were performed to explore the underlying mechanisms. An integrin receptor antagonist GRGDSP or mitogen‐activated protein kinase (MAPK) phosphatase (MKP)‐1 small interfering RNA (siRNA) was also administered to r‐OPN‐treated SAH rats, and those effects were evaluated.Results:Pre‐SAH administration of r‐OPN prevented vasospasm and neurological impairments at 24–72 hours post‐SAH. r‐OPN enhanced an endogenous MAPK inhibitor, MKP‐1, and suppressed the phosphorylation of MAPKs, caldesmon, and heat shock protein 27 in the spastic cerebral arteries at 24 hours post‐SAH. Immunofluorescence revealed that MKP‐1 was induced in the arterial smooth muscle layer. GRGDSP prevented r‐OPN‐induced MKP‐1 upregulation, and MKP‐1 siRNA abolished both MAPK inactivation and anti‐vasospastic effects by r‐OPN. Post‐SAH r‐OPN treatment also prevented vasospasm.Interpretation:r‐OPN induced MKP‐1 in the spastic cerebral arteries via binding to L‐arginyl‐glycyl‐L‐aspartate‐dependent integrin receptors and prevented vasospasm after SAH. Therapeutic induction of MKP‐1 may be a novel approach for the prevention and treatment of cerebral vasospasm. ANN NEUROL 2010;68:650–660
Glycogen hyperphosphorylation underlies lafora body formation
Authors: Turnbull Julie , Wang Peixiang , Girard Jean‐Marie , Ruggieri Alessandra , Wang Tony J. , Draginov Arman G. , Kameka Alexander P. , Pencea Nela , Zhao Xiaochu , Ackerley Cameron A. , Minassian Berge A. 
Published: October 2010

AbstractObjective:Glycogen, the largest cytosolic macromolecule, acquires solubility, essential to its function, through extreme branching. Lafora bodies are aggregates of polyglucosan, a long, linear, poorly branched, and insoluble form of glycogen. Lafora bodies occupy vast numbers of neuronal dendrites and perikarya in Lafora disease in time‐dependent fashion, leading to intractable and fatal progressive myoclonus epilepsy. Lafora disease is caused by deficiency of either the laforin glycogen phosphatase or the malin E3 ubiquitin ligase. The 2 leading hypotheses of Lafora body formation are: (1) increased glycogen synthase activity extends glycogen strands too rapidly to allow adequate branching, resulting in polyglucosans; and (2) increased glycogen phosphate leads to glycogen conformational change, unfolding, precipitation, and conversion to polyglucosan. Recently, it was shown that in the laforin phosphatase‐deficient form of Lafora disease, there is no increase in glycogen synthase, but there is a dramatic increase in glycogen phosphate, with subsequent conversion of glycogen to polyglucosan. Here, we determine whether Lafora bodies in the malin ubiquitin ligase‐deficient form of the disease are due to increased glycogen synthase or increased glycogen phosphate.Methods:We generated malin‐deficient mice and tested the 2 hypotheses.Results:Malin‐deficient mice precisely replicate the pathology of Lafora disease with Lafora body formation in skeletal muscle, liver, and brain, and in the latter in the pathognomonic perikaryal and dendritic locations. Glycogen synthase quantity and activity are unchanged. There is a highly significant increase in glycogen phosphate.Interpretation:We identify a single common modification, glycogen hyperphosphorylation, as the root cause of Lafora body pathogenesis. ANN NEUROL, 2010
Signatures of cardioembolic and large‐vessel ischemic stroke
Authors: Jickling Glen C. , Xu Huichun , Stamova Boryana , Ander Bradley P. , Zhan Xinhua , Tian Yingfang , Liu Dazhi , Turner Renée J. , Mesias Matthew , Verro Piero , Khoury Jane , Jauch Edward C. , Pancioli Arthur , Broderick Joseph P. , Sharp Frank R. 
Published: October 2010

AbstractObjective:The cause of stroke remains unknown or cryptogenic in many patients. We sought to determine whether gene expression signatures in blood can distinguish between cardioembolic and large‐vessel causes of stroke, and whether these profiles can predict stroke etiology in the cryptogenic group.Methods:A total of 194 samples from 76 acute ischemic stroke patients were analyzed. RNA was isolated from blood and run on Affymetrix U133 Plus2.0 microarrays. Genes that distinguish large‐vessel from cardioembolic stroke were determined at 3, 5, and 24 hours following stroke onset. Predictors were evaluated using cross‐validation and a separate set of patients with known stroke subtype. The cause of cryptogenic stroke was predicted based on a model developed from strokes of known cause and identified predictors.Results:A 40‐gene profile differentiated cardioembolic stroke from large‐vessel stroke with >95% sensitivity and specificity. A separate 37‐gene profile differentiated cardioembolic stroke due to atrial fibrillation from nonatrial fibrillation causes with >90% sensitivity and specificity. The identified genes elucidate differences in inflammation between stroke subtypes. When applied to patients with cryptogenic stroke, 17% are predicted to be large‐vessel and 41% to be cardioembolic stroke. Of the cryptogenic strokes predicted to be cardioembolic, 27% were predicted to have atrial fibrillation.Interpretation:Gene expression signatures distinguish cardioembolic from large‐vessel causes of ischemic stroke. These gene profiles may add valuable diagnostic information in the management of patients with stroke of unknown etiology though they need to be validated in future independent, large studies. Ann Neurol 2010;68:681–692
Imaging the future of stroke: II. Hemorrhage
Authors: Liebeskind David S. 
Published: October 2010

AbstractBleeding into the brain or adjacent structures is one of the most devastating neurological conditions, incurring tremendous emotional, financial, and societal costs. Imaging is essential to differentiate variants of hemorrhage, as the clinical features may be insufficient. A comprehensive approach to hemorrhage therefore relies on imaging to disclose pathophysiology, elucidate mechanisms, and thereby open further avenues to effective treatment. Hemorrhage patterns from superficial to deep locations in the brain are surveyed in this work, noting myriad potential causes and the influential pathophysiology of arterial ischemia, venous hypertension, and microvascular dysfunction. Recent progress of imaging studies and novel techniques to evaluate hemorrhage are explored. For decades, only computed tomography was available to define a hematoma without corroborating evidence of other pathology whereas multimodal computed tomography and magnetic resonance imaging, including noninvasive imaging of brain tissue, vessels, and perfusion, have now radically altered clinical practice. Imaging of the blood‐brain barrier, cerebral microbleeds, coexistent ischemia, associated vascular lesions, and markers of hemorrhage expansion is possible with routine protocols akin to diagnostic strategies for ischemic stroke. Imaging applications for hemorrhagic transformation, venous thrombosis, and microvascular disorders are considered with a perspective that balances concern for hemorrhage with prevention of ischemia as these processes are often intertwined and clinical conundrums arise. Imminent imaging advances are anticipated with increased use of detailed imaging for hemorrhage and overlap with cerebral ischemia. Numerous questions abound regarding optimal management of hemorrhage and definitive treatments are lacking, yet imaging of pivotal pathophysiology offers tremendous opportunity for future progress in combating this debilitating condition. Ann Neurol 2010;68:581–592
Immune regulation of multiple sclerosis by transdermally applied myelin peptides
Authors: Juryńczyk Maciej , Walczak Agata , Jurewicz Anna , Jesionek‐Kupnicka Dorota , Szczepanik Marian , Selmaj Krzysztof 
Published: October 2010

AbstractObjective:Antigen‐specific therapy targeting selective inhibition of autoreactive responses holds promise for controlling multiple sclerosis (MS) without disturbing homeostasis of the whole immune system. Key autoantigens in MS include myelin proteins, such as myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG). In this study, we examined the effect of transdermal therapy with myelin peptides on immune responses in the skin, lymph nodes, and peripheral blood immune cells of MS patients.Methods:In a 1‐year placebo‐controlled study, 30 patients with relapsing‐remitting MS were treated transdermally with a mixture of 3 myelin peptides: MBP85‐99, PLP139‐151, and MOG35‐55, or placebo. The phenotype of immune cells in the skin was assessed using immunohistochemistry. Cell populations in lymph nodes were analyzed using flow cytometry. In peripheral blood immune cells, cytokine production was measured by enzyme‐linked immunosorbent assay, and myelin‐specific proliferation was examined by carboxyfluorescein succinimidyl ester‐based assay.Results:We found that myelin peptides applied transdermally to MS patients activated dendritic Langerhans cells in the skin at the site of immunization and induced a unique population of granular dendritic cells in local lymph nodes. In the periphery, transdermal immunization with myelin peptides resulted in the generation of type 1, interleukin‐10–producing regulatory T cells, suppression of specific autoreactive proliferative responses, and suppression of interferon‐γ and transforming growth factor‐β production.Interpretation:We demonstrate for the first time the immunoregulatory potential of transdermal immunization with myelin peptides in MS patients. Ann Neurol 2010;68:593–601
Elevated plasma YKL‐40 levels and ischemic stroke in the general population
Authors: Kjaergaard Alisa D. , Bojesen Stig E. , Johansen Julia S. , Nordestgaard Børge G. 
Published: October 2010

AbstractObjective:We hypothesized that elevated plasma YKL‐40 levels are associated with increased risk of ischemic cardiovascular disease in the general population. In contrast to C‐reactive protein (CRP) produced in the liver in response to inflammation, YKL‐40 is produced by lipid‐laden macrophages inside the vessel wall.Methods:We measured plasma YKL‐40 in 8,899 21‐ to 93‐year‐old participants of the Copenhagen City Heart Study 1991–1994 examination, and followed them for up to 18 years. Endpoints were ischemic stroke, ischemic cerebrovascular disease, myocardial infarction, and ischemic heart disease. Hazard ratios were calculated for plasma YKL‐40 levels in 10‐year age percentile categories of 34 to 66%, 67 to 90%, and 91 to 100% versus 0 to 33%.Results:Multifactorially and CRP‐adjusted hazard ratios for ischemic stroke were 1.2 (95% confidence interval, 0.9–1.6) for 33 to 66%, 1.8 (1.3–2.4) for 67 to 90%, and 2.3 (1.5–3.3) for 91 to 100% versus the 0 to 33% percentile category (p‐trend < 0.001). Corresponding hazard ratios for ischemic cerebrovascular disease were 1.2 (0.9–1.5), 1.6 (1.2–2.0), and 2.2 (1.6–3.2) (p‐trend < 0.001). Hazard ratios for myocardial infarction were not significant, whereas corresponding hazard ratios for ischemic heart disease were 1.0 (0.8–1.2), 1.2 (1.0–1.5), and 1.3 (1.0–1.6) (p‐trend = 0.01). Stratifying for CRP or other risk factors gave similar results. A doubling in plasma YKL‐40 was associated with multifactorially and CRP‐adjusted increased risk of 20% (95% confidence interval, 11%–30%) for ischemic stroke, 16% (8%–24%) for ischemic cerebrovascular disease, 3% (‐5%–11%) for myocardial infarction, and 7% (1%–12%) for ischemic heart disease.Interpretation:In the general population, elevated plasma YKL‐40 levels are associated with increased risk of ischemic stroke and ischemic cerebrovascular disease, independent of plasma CRP levels.Ann Neurol 2010;68:672–680
Sustained alpha‐sarcoglycan gene expression after gene transfer in limb‐girdle muscular dystrophy, type 2D
Authors: Mendell Jerry R. , Rodino‐Klapac Louise R. , Rosales Xiomara Q. , Coley Brian D. , Galloway Gloria , Lewis Sarah , Malik Vinod , Shilling Chris , Byrne Barry J. , Conlon Thomas , Campbell Katherine J. , Bremer William G. , Taylor Laura E. , Flanigan Kevin M. , Gastier‐Foster Julie M. , Astbury Caroline , Kota Janaiah , Sahenk Zarife , Walker Christopher M. , Clark K. Reed 
Published: October 2010

AbstractObjective:The aim of this study was to attain long‐lasting alpha‐sarcoglycan gene expression in limb‐girdle muscular dystrophy, type 2D (LGMD2D) subjects mediated by adeno‐associated virus (AAV) gene transfer under control of a muscle specific promoter (tMCK).Methods:rAAV1.tMCK.hSGCA (3.25 × 1011 vector genomes) was delivered to the extensor digitorum brevis muscle of 3 subjects with documented SGCA mutations via a double‐blind, randomized, placebo controlled trial. Control sides received saline. The blind was not broken until the study was completed at 6 months and all results were reported to the oversight committee.Results:Persistent alpha‐sarcoglycan gene expression was achieved for 6 months in 2 of 3 LGMD2D subjects. Markers for muscle fiber transduction other than alpha‐sarcoglycan included expression of major histocompatibility complex I, increase in muscle fiber size, and restoration of the full sarcoglycan complex. Mononuclear inflammatory cells recruited to the site of gene transfer appeared to undergo programmed cell death, demonstrated by terminal deoxynucleotide transferase–mediated deoxyuridine triphosphate nick‐end labeling and caspase‐3 staining. A patient failing gene transfer demonstrated an early rise in neutralizing antibody titers and T‐cell immunity to AAV, validated by enzyme‐linked immunospot on the second day after gene injection. This was in clear distinction to other participants with satisfactory gene expression.Interpretation:The findings of this gene replacement study in LGMD2D subjects have important implications not previously demonstrated in muscular dystrophy. Long‐term, sustainable gene expression of alpha‐sarcoglycan was observed following gene transfer mediated by AAV. The merit of a muscle‐specific tMCK promoter, not previously used in a clinical trial, was evident, and the potential for reversal of disease was displayed. ANN NEUROL 2010;68:629–638