bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Physical Impairment, Functional, and Psychosocial Measures Based on Fear of Reinjury/Lack of Confidence and Return-to-Sport Status After ACL Reconstruction
Authors: Lentz Trevor A. , Zeppieri Giorgio , George Steven Z. , Tillman Susan M. , Moser Michael W. , Farmer Kevin W. , Chmielewski Terese L. 
Published: December 2014

Background: Fear of reinjury and lack of confidence influence return-to-sport outcomes after anterior cruciate ligament (ACL) reconstruction. The physical, psychosocial, and functional recovery of patients reporting fear of reinjury or lack of confidence as their primary barrier to resuming sports participation is unknown. Purpose: To compare physical impairment, functional, and psychosocial measures between subgroups based on return-to-sport status and fear of reinjury/lack of confidence in the return-to-sport stage and to determine the association of physical impairment and psychosocial measures with function for each subgroup at 6 months and 1 year after surgery. Study Design: Case-control study; Level of evidence, 3. Methods: Physical impairment (quadriceps index [QI], quadriceps strength/body weight [QSBW], hamstring:quadriceps strength ratio [HQ ratio], pain intensity), self-report of function (International Knee Documentation Committee [IKDC]), and psychosocial (Tampa Scale for Kinesiophobia–shortened form [TSK-11]) measures were collected at 6 months and 1 year after surgery in 73 patients with ACL reconstruction. At 1 year, subjects were divided into “return-to-sport” (YRTS) or “not return-to-sport” (NRTS) subgroups based on their self-reported return to preinjury sport status. Patients in the NRTS subgroup were subcategorized as NRTS-Fear/Confidence if fear of reinjury/lack of confidence was the primary reason for not returning to sports, and all others were categorized as NRTS-Other. Results: A total of 46 subjects were assigned to YRTS, 13 to NRTS-Other, and 14 to NRTS-Fear/Confidence. Compared with the YRTS subgroup, the NRTS-Fear/Confidence subgroup was older and had lower QSBW, lower IKDC score, and higher TSK-11 score at 6 months and 1 year; however, they had similar pain levels. In the NRTS-Fear/Confidence subgroup, the IKDC score was associated with QSBW and pain at 6 months and QSBW, QI, pain, and TSK-11 scores at 1 year. Conclusion: Elevated pain-related fear of movement/reinjury, quadriceps weakness, and reduced IKDC score distinguish patients who are unable to return to preinjury sports participation because of fear of reinjury/lack of confidence. Despite low average pain ratings, fear of pain may influence function in this subgroup. Assessment of fear of reinjury, quadriceps strength, and self-reported function at 6 months may help identify patients at risk for not returning to sports at 1 year and should be considered for inclusion in return-to-sport guidelines.
WIC Peer Counselors’ Perceptions of Breastfeeding in African American Women with Lower Incomes
Authors: Gross Tyra T. , Powell Rachel , Anderson Alex K. , Hall Jori , Davis Marsha , Hilyard Karen 
Published: December 2014

Background: African American women have the lowest breastfeeding rates among all racial/ethnic groups in the United States. Peer counseling is an effective intervention in improving breastfeeding in this population. However, little is known on peer counselors’ perceptions of breastfeeding in African American women. Objective: As part of a larger qualitative study, the goal of this study was to understand the contextual factors influencing breastfeeding decisions of low-income African American women from the perspective of breastfeeding peer counselors (PCs). Methods: Three focus groups were conducted with 23 PCs from the Women, Infants, and Children program in a southeastern state. All focus group discussions were audio-recorded, professionally transcribed, and analyzed using thematic analysis. Bronfenbrenner’s socioecological model was used to group categories into themes. Results: Of the sample, 47.8% were African American, 78.2% were married, and 56.5% had some college education. Five main themes emerged to describe factors at multiple levels influencing breastfeeding in PCs’ low-income African American clients: individual, microsystem, exosystem, macrosystem, and chronosystem. Novel findings included (1) having breast pumps may give African American women a “sense of security,” (2) cultural pressures to be a “strong black woman” can impede breastfeeding support, and (3) breastfeeding “generational gaps” have resulted from American “slavery” and when formula was “a sign of wealth.” Conclusion: As PCs described, low-income African American women’s breastfeeding decisions are affected by numerous contextual factors. Findings from this study suggest a need to broaden the public health approach to breastfeeding promotion in this population by moving beyond individual characteristics to examining historical and sociocultural factors underlying breastfeeding practices in African American women.
Stem cell therapy in cats with chronic enteropathy: a proof-of-concept study
Authors: Webb Tracy L , Webb Craig B 
Published: December 2014

Objectives The current treatment of cats with chronic enteropathy frequently includes use of a prescription diet and daily medication administration, with the potential for side effects or problems with owner compliance, and may still result in treatment failure in some cases. The objective of this study was to determine if stem cell therapy was a safe and viable treatment in cases of feline chronic enteropathy. Methods Allogeneic adipose-derived feline mesenchymal stem cells (fMSC) were used to treat seven cats with diarrhea of no less than 3 months’ duration, while four cats with a similar clinical condition received placebo, in a blinded manner. Three additional cats were treated with an identical fMSC protocol, but owners were not blinded to the treatment. Owners completed a questionnaire characterizing clinical signs both before entering the study and 2 weeks following the second of two fMSC or placebo treatments. Owners were also surveyed for similar input by email 1–2 months later before being unblinded to their cat’s study group. Besides the fMSC or placebo treatment, no other changes were made in diet, supplement or medication administration during the study. Results No adverse reactions or side effects were attributed to the fMSC therapy in any of the cats. Owners of 5/7 fMSC-treated cats reported significant improvement or complete resolution of clinical signs, while the owner of the remaining two cats reported modest but persistent improvement. Owners of placebo-treated cats reported no change or worsening of clinical signs. Of the owners not blinded to the treatment, one reported marked improvement, one reported no change and one was lost to follow-up. Conclusions and relevance Although allogeneic adipose-derived fMSC therapy appears to be a safe and potentially effective treatment for cats suffering from chronic enteropathy, these preliminary results require significant follow-up study.
Quantitative Measurement of tissue damage and recovery within new T2w lesions in pediatric- and adult-onset multiple sclerosis
Authors: Ghassemi Rezwan , Brown Robert , Banwell Brenda , Narayanan Sridar , Arnold Douglas L. ,   on behalf of the Canadian Pediatric Demyelinating Disease Study Group
Published: December 2014

Background: Children and adolescents with relapsing–remitting multiple sclerosis (RRMS) have a similar T2 lesion burden as adults matched for disease duration. However, it is unknown whether the degree of tissue destruction within lesions is also similar. Persistent reduced T1-weighted signal intensity within lesions indicates loss of tissue integrity. Objective: We aimed to compare change over a 2-year period in T1 intensity within new T2 lesions, from pre-lesion levels to chronic post-lesion levels, between pediatric and adult-onset MS. Methods: A two-point intensity-normalization method was used to generate normalized T1-weighted (NT1) images from T1-weighted data in 29 pediatric MS patients (age(mean±SD, years), disease duration (years)=15.7±2.4, 3.9±2.6) and 24 adult MS patients (36.7±8.9, 6.9±4.8). Subjects were imaged at three consecutive timepoints, 1 year apart. For each subject, a ‘new-T2’ lesion mask was created and the NT1 intensities ‘pre-lesion’, ‘peri-lesion’ and ‘post-lesion’ were determined. A longitudinal model was used to capture NT1 changes. Results: The NT1 in both groups failed to recover to pre-lesion values by 1 year post-lesion ( p=0.0002), with children showing significantly better recovery than adults ( p=0.0089). Conclusions: Both groups showed a significant chronic reduction of T1 intensity within new T2 lesions. However, children showed a significantly greater recovery of T1 intensity, suggesting that MS lesions in the pediatric MS population are less destructive, or that pediatric patients have greater reparative capacity.
The role of cerebellar abnormalities in neuromyelitis optica – a comparison with multiple sclerosis and healthy controls
Authors: Weier Katrin , Eshaghi Arman , Magon Stefano , Andelova Michaela , Radue Ernst-Wilhelm , Kappos Ludwig , Azimi Amir Reza , Sahraian Mohammad Ali , Sprenger Till 
Published: December 2014

Background: In relapsing–remitting multiple sclerosis (RRMS), the cerebellum is a known predilection site for atrophy. Neuromyelitis optica (NMO) is characterized by extensive lesions in the spinal cord and optic nerve; however, cerebellar involvement has been less studied. Secondary degeneration of the spinocerebellar tract could impact the cerebellum in NMO. Objective: We aimed to investigate whether spinal cord and cerebellar volume measures differ between patients with NMO and RRMS. Methods: Volumetric analyses of the cerebellum (TCV), the upper cervical cord (UCV) as well as the whole brain (NBV) of age- and gender-matched patients with NMO ( n=30; 56% AQP4 +ve) and RRMS ( n=25) were performed on 3T brain magnetic resonance imaging (MRI) and compared with 34 healthy controls (HC). Results: UCV was significantly reduced in NMO patients (6.3 cm3) as compared with HC (6.7 cm3), while patients with MS had reduced brain volumes compared with HC (NBV=1482 cm3; p<0.001; TCV=188 cm3; p=0.042), but UCV close to normal values. Patients with RRMS and NMO differed in NBV ( p=0.001; lower in RRMS) and by trend (towards reduction in RRMS) in cerebellar volume ( p=0.06). Conclusions: While atrophy seems to be diffuse in MS patients, a rather focussed pattern with predominant involvement of the UCV was observed in NMO patients.
Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing–remitting multiple sclerosis
Authors: Kalincik Tomas , Jokubaitis Vilija , Izquierdo Guillermo , Duquette Pierre , Girard Marc , Grammond Pierre , Lugaresi Alessandra , Oreja-Guevara Celia , Bergamaschi Roberto , Hupperts Raymond , Grand’Maison Francois , Pucci Eugenio , Van Pesch Vincent , Boz Cavit , Iuliano Gerardo , Fernandez-Bolanos Ricardo , Flechter Shlomo , Spitaleri Daniele , Cristiano Edgardo , Verheul Freek , Lechner-Scott Jeannette , Amato Maria Pia , Cabrera-Gomez Jose Antonio , Saladino Maria Laura , Slee Mark , Moore Fraser , Gray Orla , Paine Mark , Barnett Michael , Havrdova Eva , Horakova Dana , Spelman Timothy , Trojano Maria , Butzkueven Helmut ,   On behalf of the MSBase Study Group, Roullet Etienne , Rozsa Csilla , Kasa Krisztian , Sirbu Carmen-Adella , Shaw Cameron , Vucic Steve , Petkovska-Boskova Tatjana , Herbert Joseph , Kister Ilya , Singhal Bhim , Alroughani Raed , Bacile Elizabeth Alejandra Bacile , Arruda Walter Oleschko , Roger Elaine , Despault Pierre , Marriott Mark , Van der Walt Anneke , King John , Byron Jill , Morgan Lisa , Hinson Eloise , Haartsen Jodi , Mechati Samir , Bianchi Erich , Bulla Alexandre , Corageoud Matthieu , De Luca Giovanna , Di Tommaso Valeria , Travaglini Daniela , Pietrolongo Erika , di Ioia Maria , Farina Deborah , Mancinelli Luca , Rojas Juan Ignacio , Patrucco Liliana , Elisabetta  
Published: December 2014

Background: The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed. Objective: We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators. Methods: Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted. Results: Of the 3326 included patients, 345–1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b ( p≤0.001). No differences in 12-month confirmed progression of disability were observed. Conclusion: Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely.
Decreased Dicer expression is linked to increased expression of co-stimulatory molecule CD80 on B cells in multiple sclerosis
Authors: Aung Latt Latt , Balashov Konstantin E 
Published: December 2014

Background: Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system. B cells have been strongly implicated in disease pathogenesis based on clinical trials with B-cell ablation. There is a growing body of evidence linking microRNAs with regulation of the immune system. Dicer, a key enzyme involved in microRNA biogenesis, is necessary for normal B-cell function. Objective: We aimed to determine whether Dicer expression is impaired in B cells and is linked to increased expression co-stimulatory molecules in patients with MS. Methods: B cells were separated from blood samples of MS patients and healthy subjects. Expression of Dicer and co-stimulatory molecules CD80 and CD86 was tested. The effect of Dicer modulation on CD80 and CD86 expression in B cells was studied. Results: Dicer expression was decreased in B cells but not in monocytes of patients with MS compared with healthy subjects. CD80 and CD86 expression was increased on B cells of MS patients compared with healthy subjects. Inhibition of Dicer expression in B cells by small interfering RNA led to increased expression of CD80. Conclusion: Dicer expression is decreased and is mechanistically linked to increased expression of co-stimulatory molecule CD80 in B cells of patients with MS. This may contribute to activation of immune responses in MS.
The neutralizing antibody GNbAC1 abrogates HERV-W envelope protein-mediated oligodendroglial maturation blockade
Authors: Kremer David , Förster Moritz , Schichel Tanja , Göttle Peter , Hartung Hans-Peter , Perron Hervé , Küry Patrick 
Published: December 2014

Background: The envelope protein (ENV) of the human endogenous retrovirus type W is implicated in inflammatory reactions in multiple sclerosis (MS) but also interferes with oligodendroglial maturation. A neutralizing antibody GNbAC1 has been developed and successfully been tested in clinical trials. Objectives and methods: We stimulated primary oligodendroglial cells with ENV upon preincubation with GNbAC1 and assessed for nitrosative stress and myelin expression. Results: Neutralization of ENV by GNbAC1 reduces its ability to induce stress reactions resulting in a rescue of myelin expression. Conclusions: Beyond immune cell modulation, this monoclonal antibody may therefore help to overcome the oligodendroglial differentiation blockade in MS.
Corpus callosum atrophy is strongly associated with cognitive impairment in multiple sclerosis: Results of a 17-year longitudinal study
Authors: Granberg Tobias , Martola Juha , Bergendal Gösta , Shams Sara , Damangir Soheil , Aspelin Peter , Fredrikson Sten , Kristoffersen-Wiberg Maria 
Published: December 2014

Background: Cognitive impairment is common in multiple sclerosis (MS) and may be subtle. The corpus callosum is essential for connectivity-demanding cognitive tasks and is significantly affected in MS, therefore it may serve as a marker for cognitive function. Objective: The objective of this paper is to longitudinally study the normalized corpus callosum area (nCCA) as a marker of cognitive function and disability in MS. Methods: Thirty-seven MS patients were followed from 1996 with follow-ups in 2004 and 2013. A healthy matched control group was recruited. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed. The nCCA was measured on T2-weighted images. Volumetry was performed with FreeSurfer. Results: Disease duration spanned five decades (1.6–46 years). Annual corpus callosal atrophy rate decreased with disease duration. nCCA was strongly correlated with SDMT ( r = 0.793, p < 0.001) and moderately correlated with EDSS ( r = −0.545, p < 0.001) after adjusting for disease duration, age and sex. The correlations of brain parenchymal fraction, white matter fraction, gray matter fraction and normalized lesion volume were less strong. Conclusions: The nCCA correlates well with physical and cognitive disability in time perspectives close to two decades, outperforming volumetric measurements. The nCCA is fast and could be feasible for clinical implementation where it may help identify patients in need of neuropsychological evaluation.
A new cognitive rehabilitation programme for patients with multiple sclerosis: the ‘MS-line! Project’
Authors: Gich Jordi , Freixenet Jordi , Garcia Rafael , Vilanova Joan Carles , Genís David , Silva Yolanda , Montalban Xavier , Ramió-Torrentà Lluís 
Published: December 2014

Background: Cognitive rehabilitation is often delayed in multiple sclerosis (MS). Objective: To develop a free and specific cognitive rehabilitation programme for MS patients to be used from early stages that does not interfere with daily living activities. Methods: MS-line!, cognitive rehabilitation materials consisting of written, manipulative and computer-based materials with difficulty levels developed by a multidisciplinary team. Results: Mathematical, problem-solving and word-based exercises were designed. Physical materials included spatial, coordination and reasoning games. Computer-based material included logic and reasoning, working memory and processing speed games. Conclusions: Cognitive rehabilitation exercises that are specific for MS patients have been successfully developed.
Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis
Authors: Checa Antonio , Khademi Mohsen , Sar Daniel G , Haeggström Jesper Z , Lundberg Jon O , Piehl Fredrik , Olsson Tomas , Wheelock Craig E 
Published: December 2014

Background: Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS). Objectives: We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression. Methods: Using liquid chromatography tandem mass spectrometry, we analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing–remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart. Results: Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS ( p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND ( p<0.001), iOND ( p<0.05) and EarlyMS ( p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies ( p=0.048; p=0.027). Conclusion: HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.
Interferon-beta affects mitochondrial activity in CD4+ lymphocytes: Implications for mechanism of action in multiple sclerosis
Authors: Haghikia Aiden , Faissner Simon , Pappas Derek , Pula Bartosz , Akkad Denis A , Arning Larissa , Ruhrmann Sabrina , Duscha Alexander , Gold Ralf , Baranzini Sergio E , Malhotra Sunny , Montalban Xavier , Comabella Manuel , Chan Andrew 
Published: December 2014

Background: Whereas cellular immune function depends on energy supply and mitochondrial function, little is known on the impact of immunotherapies on cellular energy metabolism. Objective: The objective of this paper is to assess the effects of interferon-beta (IFN-β) on mitochondrial function of CD4+ T cells. Methods: Intracellular adenosine triphosphate (iATP) in phytohemagglutinin (PHA)-stimulated CD4+ cells of multiple sclerosis (MS) patients treated with IFN-β and controls were analyzed in a luciferase-based assay. Mitochondrial-transmembrane potential (ΔΨm) in IFN-β-treated peripheral blood mononuclear cells (PBMCs) was investigated by flow cytometry. Expression of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) in CD4+ cells of IFN-β-treated individuals and correlations between genetic variants in the key metabolism regulator PGC-1α and IFN-β response in MS were analyzed. Results: IFN-β-treated MS patients exhibited a dose-dependent reduction of iATP levels in CD4+ T cells compared to controls ( p < 0.001). Mitochondrial effects were reflected by depolarization of ΔΨm. Expression data revealed changes in the transcription of OXPHOS-genes. iATP levels in IFN-β-responders were reduced compared to non-responders ( p < 0.05), and the major T allele of the SNP rs7665116 of PGC-1α correlated with iATP-levels. Conclusion: Reduced iATP-synthesis ex vivo and differential expression of OXPHOS-genes in CD4+ T cells point to unknown IFN-β effects on mitochondrial energy metabolism, adding to potential pleiotropic mechanisms of action.
The Charcot Lecture | Beating MS: A story of B cells, with twists and turns
Authors: Hauser Stephen L 
Published: December 2014

Autoimmune B cells play a major role in mediating tissue damage in multiple sclerosis (MS). In MS, B cells are believed to cross the blood-brain barrier and undergo stimulation, antigen-driven affinity maturation and clonal expansion within the supportive CNS environment. These highly restricted populations of clonally expanded B cells and plasma cells can be detected in MS lesions, in cerebrospinal fluid, and also in peripheral blood. In phase II trials in relapsing MS, monoclonal antibodies that target circulating CD20-positive B lymphocytes dramatically reduced disease activity. These beneficial effects occurred within weeks of treatment, indicating that a direct effect on B cells—and likely not on putative autoantibodies—was responsible. The discovery that depletion of B cells has an impact on MS biology enabled a paradigm shift in understanding how the inflammatory phase of MS develops, and will hopefully lead to development of increasingly selective therapies against culprit B cells and related humoral immune system pathways. More broadly, these studies illustrate how lessons learned from the bedside have unique power to inform translational research. They highlight the essential role of clinician scientists, currently endangered, who navigate the rocky and often unpredictable terrain between the worlds of clinical medicine and biomedical research.