bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fall risk and gait in Parkinson's disease: The role of the LRRK2 G2019S mutation
Authors: Mirelman Anat , Heman Talia , Yasinovsky Kira , Thaler Avner , Gurevich Tanya , Marder Karen , Bressman Susan , Bar‐Shira Anat , Orr‐Urtreger Avi , Giladi Nir , Hausdorff Jeffrey M. ,   on behalf of the LRRK2 Ashkenazi Jewish Consortium
Published: October 2013

ABSTRACTPatients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine‐rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non‐carrier patients with PD to better understand the genotype‐phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non‐carriers were studied. An accelerometer quantified gait under three walking conditions: usual‐walking, dual‐tasking, and fast‐walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub‐types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P < 0.016). The PD carriers also took longer to complete the Timed Up and Go (P = 0.011) and were more likely to report having fallen in the previous year (P = 0.018). 64% of the PD carriers were classified as belonging to the postural‐instability‐gait‐difficulty (PIGD) sub‐type compared to only 17% of the PD non‐carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub‐type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation. © 2013 International Parkinson and Movement Disorder Society
Phase II safety, tolerability, and dose selection study of isradipine as a potential disease‐modifying intervention in early Parkinson's disease (STEADY‐PD)
Authors:   Parkinson Study Group
Published: October 2013

ABSTRACTIsradipine, a dihydropyridine calcium channel antagonist, has been shown to be neuroprotective in animal models of Parkinson's disease (PD). To establish a dosage of isradipine controlled‐release (CR) that is tolerable and demonstrates preliminary efficacy for use in a future pivotal efficacy trial a Phase 2, randomized, double‐blind, parallel group trial (Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease [STEADY‐PD]) was undertaken in subjects with early PD not requiring dopaminergic therapy (dopamine agonists or levodopa) randomized 1:1:1:1 to 5, 10, or 20 mg of isradipine CR or matching placebo daily. The primary outcome was tolerability defined as no more than a 30% difference in the proportion of patients completing the study on the originally assigned dosage between an active and placebo group. If more than one isradipine dosage was tolerable, then a 3‐point difference in total Unified Parkinson's Disease Rating Scale (UPDRS) change between baseline and week 52 (or time to sufficient disability to require dopaminergic therapy) was taken as a criterion for selection of the most desirable dosage for future study. STEADY‐PD enrolled 99 subjects. The tolerability of isradipine was dose dependent: placebo, 25 of 26 patients (96%); 5 mg, 19 of 23 patients (83%); 10 mg 19 of 26 patients (73%); and 20 mg 9 of 24 patients (37%). There was no difference in change in UPDRS among dosages. The most common adverse events were peripheral edema (30) and dizziness (24). Isradipine 10 mg daily was the maximal tolerable dosage in this study of early PD. A large placebo‐controlled trial will be necessary and is planned to assess efficacy of isradipine 10 mg daily to slow progression of PD disability. © 2013 International Parkinson and Movement Disorder Society.
Dementia in Parkinson's disease: Usefulness of the pill questionnaire
Authors: Martinez‐Martin Pablo 
Published: October 2013

ABSTRACTThe Level I algorithm for the diagnosis of dementia associated with Parkinson's disease (PD‐D) recommended by the Movement Disorder Society task force includes a Pill Questionnaire to determine the impact of cognitive decline on daily activities. The objective of this study was to test the performance of the Pill Questionnaire as a screening tool for the detection of dementia (all‐cause) in patients with PD and to test the performance of another functional scale substituting the Pill Questionnaire for the diagnosis of “probable PD‐D” (pPD‐D). Data were collected from 529 patients who had PD in Hoehn and Yahr stages 1 through 5. The measures used include the Scales for Outcomes in PD‐Motor (SCOPA‐Motor), scales for psychiatric complications, the Mini Mental State Examination, the Clinical Impression of Severity Index, and the Pill Questionnaire. The SCOPA‐Motor functional subscale score was categorized as “impact” or “no impact” of PD on daily activities. According to clinical judgment, 13.3% of patients had dementia. For detecting dementia, the Pill Questionnaire had 89% accuracy, although its positive predictive value was 55%. Performance was worse with the categorized SCOPA‐Motor subscale. According to the Movement Disorder Society task force criterion, 85 patients (16.1%) had pPD‐D. When the Pill Questionnaire was substituted by the categorized SCOPA‐Motor subscale, the modified algorithm showed sensitivity, specificity, and accuracy indexes over 90% but had positive predictive value of 66% for pPD‐D diagnosis. Although the Pill Questionnaire demonstrated acceptable basic properties as a screening tool for dementia, its positive predictive value was low. The SCOPA‐Motor subscale cannot be proposed as a substitute for the Pill Questionnaire. © 2013 International Parkinson and Movement Disorder Society
Defining optimal cutoff scores for cognitive impairment using Movement Disorder Society Task Force criteria for mild cognitive impairment in Parkinson's disease
Authors: Goldman Jennifer G. , Holden Samantha , Bernard Bryan , Ouyang Bichun , Goetz Christopher G. , Stebbins Glenn T. 
Published: October 2013

ABSTRACTThe recently proposed Movement Disorder Society (MDS) Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD‐MCI) represent a first step toward a uniform definition of PD‐MCI across multiple clinical and research settings. However, several questions regarding specific criteria remain unanswered, including optimal cutoff scores by which to define impairment on neuropsychological tests. Seventy‐six non‐demented PD patients underwent comprehensive neuropsychological assessment and were classified as PD‐MCI or PD with normal cognition (PD‐NC). The concordance of PD‐MCI diagnosis by MDS Task Force Level II criteria (comprehensive assessment), using a range of standard deviation (SD) cutoff scores, was compared with our consensus diagnosis of PD‐MCI or PD‐NC. Sensitivity, specificity, and positive and negative predictive values were examined for each cutoff score. PD‐MCI subtype classification and distribution of cognitive domains impaired were evaluated. Concordance for PD‐MCI diagnosis was greatest for defining impairment on neuropsychological tests using a 2 SD cutoff score below appropriate norms. This cutoff also provided the best discriminatory properties for separating PD‐MCI from PD‐NC compared with other cutoff scores. With the MDS PD‐MCI criteria, multiple domain impairment was more frequent than single domain impairment, with predominant executive function, memory, and visuospatial function deficits. Application of the MDS Task Force PD‐MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at a 2 SD cutoff score. The predominance of multiple domain impairment in PD‐MCI with the Level II criteria suggests not only influences of testing abnormality requirements, but also the widespread nature of cognitive deficits within PD‐MCI. © 2013 International Parkinson and Movement Disorder Society
Primary motor cortex long‐term plasticity in multiple system atrophy
Authors: Suppa Antonio , Marsili Luca , Di Stasio Flavio , Latorre Anna , Parvez AK. , Colosimo Carlo , Berardelli Alfredo 
Published: October 2013

ABSTRACTIn humans, intermittent and continuous theta‐burst stimulation (iTBS and cTBS) elicit long‐term changes in motor‐evoked potentials (MEPs) reflecting long‐term potentiation (LTP)‐ and depression (LTD)‐like plasticity in the primary motor cortex (M1). In this study, we used TBS to investigate M1 plasticity in patients with MSA. We also assessed whether responses to TBS reflect M1 excitability as tested by short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), short‐interval intracortical facilitation (SICF), and the input/output curves. We studied 20 patients with MSA and 20 healthy subjects (HS). Patients were clinically evaluated with the Unified Multiple System Atrophy Rating Scale. The left M1 was conditioned with TBS. Twenty MEPs were recorded from the right first dorsal interosseous muscle before TBS and 5, 15, and 30 minutes thereafter. In a subgroup of 10 patients, we also tested MEPs elicited by SICI, ICF, SICF, and input/output curves, before TBS. Between‐group analysis of variance showed that at all time points after iTBS MEPs increased, whereas after cTBS they decreased only in HS. In both subgroups tested, patients with predominant parkinsonian and cerebellar features, iTBS and cTBS left MEPs unchanged. MSA patients had reduced SICI, but normal ICF, SICF, and input/output curves. No correlation was found between patients' clinical features and responses to TBS and M1 excitability variables. These findings suggest impaired M1 plasticity in MSA. © 2013 International Parkinson and Movement Disorder Society
The unified huntington's disease rating scale for advanced patients: Validation and follow‐up study
Authors: Youssov Katia , Dolbeau Guillaume , Maison Patrick , Boissé Marie‐Françoise , de Langavant Laurent Cleret , Roos Raymund A. C. , Bachoud‐Lévi Anne‐Catherine 
Published: October 2013

ABSTRACTThe Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In patients with advanced HD, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS‐For Advanced Patients (UHDRS‐FAP) to improve longitudinal assessment of patients at the advanced disease stage. Sixty‐nine patients with a Total Functional Capacity score ≤ 5 were recruited in France and the Netherlands. Among them, 45 patients were followed longitudinally (mean ± standard deviation, 1.6 ± 1.2 years) with the UHDRS‐FAP; 30 patients also were assessed with the UHDRS. In cross‐sectional analyses, the psychometric properties and inter‐rater reliability of the scale were evaluated. Longitudinal analyses were used to evaluate the sensitivity to decline of the UHDRS‐FAP compared with the UHDRS. Internal consistency was higher for motor (0.84) and cognitive (0.91) scores than for somatic (0.70) and behavioral (0.49) scores. Inter‐rater reliability was ≥ 0.88 for all scores. The somatic score, which was specific to the UHDRS‐FAP, declined over time along with motor and cognitive performance on both scales. Although performance with the two scales was correlated, the UHDRS‐FAP appeared to be more sensitive to change and was the only scale that detected decline in patients with a Total Functional Capacity score ≤ 1. Neither scale detected a significant decline in behavioral scores. The results indicate that the UHDRS‐FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items that are relevant for daily care. Behavioral scores tended to decline, but this may reflect the decline in patients' communicative abilities. © 2013 International Parkinson and Movement Disorder Society
Cortical gyrification reductions and subcortical atrophy in Parkinson's disease
Authors: Zhang Yuanchao , Zhang Jiuqun , Xu Jinping , Wu Xiu , Zhang Yanling , Feng Hua , Wang Jian , Jiang Tianzi 
Published: October 2013

ABSTRACTBackgroundParkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non‐motor symptoms. Previous morphometric studies of PD were mainly conducted by measuring gray matter volume and cortical thickness, and little attention has been paid to the morphology of the cortical surface.MethodsUsing a surface‐based local gyrification index (lGI), this study compared the cortical gyrification patterns of 37 PD patients and 34 matched healthy controls. Volumetric analyses also were performed on the subcortical structures.ResultsCompared with the control group, patients with PD had significantly reduced cortical gyrification in multiple brain regions, which the authors speculated were associated with disruptions in white matter connectivity and suboptimal intracortical organization. In addition, subcortical volume atrophy was identified in the bilateral hippocampus and bilateral caudate of the patients with PD.ConclusionsFurther studies are needed to identify the clinical correlates of the structural abnormalities observed in PD. © 2013 International Parkinson and Movement Disorder Society
Impaired force control in writer's cramp showing a bilateral deficit in sensorimotor integration
Authors: Bleton Jean‐Pierre , Teremetz Maxime , Vidailhet Marie , Mesure Serge , Maier Marc A. , Lindberg Påvel G. 
Published: October 2013

ABSTRACTBackgroundAbnormal cortical processing of sensory inputs has been found bilaterally in writer's cramp (WC). This study tested the hypothesis that patients with WC have an impaired ability to adjust grip forces according to visual and somatosensory cues in both hands.MethodsA unimanual visuomotor force‐tracking task and a bimanual sense of effort force‐matching task were performed by WC patients and healthy controls.ResultsIn visuomotor tracking, WC patients showed increased error, greater variability, and longer release duration than controls. In the force‐matching task, patients underestimated, whereas controls overestimated, the force applied in the other hand. Visuomotor tracking and force matching were equally impaired in both the symptomatic and nonsymptomatic hand in WC patients.ConclusionsThis study provides evidence of bilaterally impaired grip‐force control in WC, when using visual or sense of effort cues. This suggests a generalized subclinical deficit in sensorimotor integration in WC. © 2013 International Parkinson and Movement Disorder Society
A segmented and weighted Adomian decomposition algorithm for boundary value problem of nonlinear groundwater equation
Authors: Yun Yin‐shan , Chaolu Temuer , Duan Jun‐sheng 
Published: October 2013

AbstractBased on Adomian decomposition method, a new algorithm for solving boundary value problem (BVP) of nonlinear partial differential equations on the rectangular area is proposed. The solutions obtained by the method precisely satisfy all boundary conditions, except the small pieces near the four corners of the rectangular area. A theorem on the boundary error is given. Hence, the Adomian decomposition method is more efficiently applied to BVPs for partial differential equations. Segmented and weighted analytical solutions with a high accuracy for the BVP of nonlinear groundwater equations on a rectangular area are obtained by the present algorithm. Copyright © 2013 John Wiley & Sons, Ltd.
Existence of positive solutions for nonlinear Kirchhoff type problems in with critical Sobolev exponent
Authors: Li Gongbao , Ye Hongyu 
Published: October 2013

AbstractIn this paper, we study the following nonlinear problem of Kirchhoff type with critical Sobolev exponent:
urn:x-wiley:01704214:media:mma3000:mma3000-math-0001 where a, b > 0 are constants. Under certain assumptions on the sign‐changing function f(x,u), we prove the existence of positive solutions by variational methods.Our main results can be viewed as a partial extension of a recent result of He and Zou in [Journal of Differential Equations, 2012] concerning the existence of positive solutions to the nonlinear Kirchhoff problem
urn:x-wiley:01704214:media:mma3000:mma3000-math-0002 where ϵ > 0 is a parameter, V (x) is a positive continuous potential, and with 4 < p < 6 and satisfies the Ambrosetti–Rabinowitz type condition. Copyright © 2013 John Wiley & Sons, Ltd.
Cocoa flavonoid epicatechin protects pancreatic beta cell viability and function against oxidative stress
Authors: Martín María Ángeles , Fernández‐Millán Elisa , Ramos Sonia , Bravo Laura , Goya Luis 
Published: October 2013

ScopeDiabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress‐induced degenerative and age‐related diseases. Flavonoids such as epicatechin (EC) constitute an important part of the human diet; they can be found in green tea, grapes, and cocoa and possess multiple biological activities. This study investigates the chemo‐protective effect of EC against oxidative stress induced by tert‐butylhydroperoxide (t‐BOOH) on Ins‐1E pancreatic beta cells.Methods and resultsCell viability, oxidative status, phosphorylated Jun kinase (p‐JNK) expression, and insulin secretion were evaluated. Ins‐1E cells treatment with 5–20 μM EC for 20 h evoked no cell damage and enhanced antioxidant enzymes and insulin secretion. Addition of 50 μM t‐BOOH for 2 h induced reactive oxygen species, p‐JNK, and carbonyl groups and decreased GSH and insulin secretion. Pretreatment of cells with EC prevented the t‐BOOH‐induced reactive oxygen species, carbonyl groups, p‐JNK expression and cell death, and recovered insulin secretion.ConclusionIns‐1E cells treated with EC showed a remarkable recovery of cell viability and insulin secretion damaged by t‐BOOH, indicating that integrity of secreting and surviving machineries in the EC‐treated cells was notably protected against the oxidative insult.
The chemopreventive action of bromelain, from pineapple stem (Ananas comosusL.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects
Authors: Romano Barbara , Fasolino Ines , Pagano Ester , Capasso Raffaele , Pace Simona , De Rosa Giuseppe , Milic Natasa , Orlando Pierangelo , Izzo Angelo A. , Borrelli Francesca 
Published: October 2013

ScopeColorectal cancer is an important health problem across the world. Here, we investigated the possible antiproliferative/proapoptotic effects of bromelain (from the pineapple stem Ananas comosus L., family Bromeliaceae) in a human colorectal carcinoma cell line and its potential chemopreventive effect in a murine model of colon cancer.Methods and resultsProliferation and apoptosis were evaluated in human colon adenocarcinoma (Caco‐2) cells by the 3H‐thymidine incorporation assay and caspase 3/7 activity measurement, respectively. Extracellular signal‐related kinase (ERK) and Akt expression were evaluated by Western blot analysis, reactive oxygen species production by a fluorimetric method. In vivo, bromelain was evaluated using the azoxymethane murine model of colon carcinogenesis. Bromelain reduced cell proliferation and promoted apoptosis in Caco‐2 cells. The effect of bromelain was associated to downregulation of pERK1/2/total, ERK, and pAkt/Akt expression as well as to reduction of reactive oxygen species production. In vivo, bromelain reduced the development of aberrant crypt foci, polyps, and tumors induced by azoxymethane.ConclusionBromelain exerts antiproliferative and proapoptotic effects in colorectal carcinoma cells and chemopreventive actions in colon carcinogenesis in vivo. Bromelain‐containing foods and/or bromelain itself may represent good candidates for colorectal cancer chemoprevention.
Sensitizing potential of enzymatically cross‐linked peanut proteins in a mouse model of peanut allergy
Authors: Radosavljevic Jelena , Nordlund Emilia , Mihajlovic Luka , Krstic Maja , Bohn Torsten , Buchert Johanna , Velickovic Tanja Cirkovic , Smit Joost 
Published: October 2013

ScopeThe cross‐linking of proteins by enzymes to form high‐molecular‐weight protein, aggregates can be used to tailor the technological or physiological functionality of food products. Aggregation of dietary proteins by food processing may promote allergic sensitization, but the effects of enzymatic cross‐linking of dietary proteins on the allergenic potential of food are not known. In this study, the bioavailability and the sensitizing or tolerizing potential of peanut proteins (PE) cross‐linked with microbial tyrosinase from Trichoderma reesei and mushroom tyrosinase from Agaricus bisporus, were investigated.Methods and resultsThe impact of cross‐linking of PE on the in vitro bioavailability of fluorescein isothiocyanate‐labeled peanut proteins was tested in a Caco‐2 cell monolayer and by competitive ELISA. The in vivo allergenicity or capacity to induce oral tolerance in mice were measured by serum levels of PE‐specific antibodies and T cell cytokine production after exposure to PE and cross‐linked PE.ConclusionEnzymatic processing of peanut proteins by the two tyrosinases increased the bioavailability of major peanut allergen Ara h 2, but did not significantly change the allergenic or tolerizing properties of peanut. Enzymatic treatment of peanut proteins yielded cross‐linked proteins with preserved molecular and immunological features of peanut allergens.
Plant polyphenol induced cell death in human cancer cells involves mobilization of intracellular copper ions and reactive oxygen species generation: A mechanism for cancer chemopreventive action
Authors: Khan Husain Yar , Zubair Haseeb , Faisal Mohd , Ullah Mohd Fahad , Farhan Mohd , Sarkar Fazlul H. , Ahmad Aamir , Hadi Sheikh Mumtaz 
Published: October 2013

ScopeAnticancer polyphenolic nutraceuticals from fruits, vegetables, and spices are generally recognized as antioxidants, but can be prooxidants in the presence of copper ions. We earlier proposed a mechanism for such activity of polyphenols and now we provide data in multiple cancer cell lines in support of our hypothesis.Methods and resultsThrough multiple assays, we show that polyphenols luteolin, apigenin, epigallocatechin‐3‐gallate, and resveratrol are able to inhibit cell proliferation and induce apoptosis in different cancer cell lines. Such cell death is prevented to a significant extent by cuprous chelator neocuproine and reactive oxygen species scavengers. We also show that normal breast epithelial cells, cultured in a medium supplemented with copper, become sensitized to polyphenol‐induced growth inhibition.ConclusionSince the concentration of copper is significantly elevated in cancer cells, our results strengthen the idea that an important anticancer mechanism of plant polyphenols is mediated through intracellular copper mobilization and reactive oxygen species generation leading to cancer cell death. Moreover, this prooxidant chemopreventive mechanism appears to be a mechanism common to several polyphenols with diverse chemical structures and explains the preferential cytotoxicity of these compounds toward cancer cells.