bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Reliability, Validity and Practical Utility of Measuring Supports using the I‐CAN Instrument: Part II
Authors: Riches Vivienne C. , Parmenter Trevor R. , Llewellyn Gwynnyth , Hindmarsh Gabrielle , Chan Jeff 
Published: November 2008

Background  There is an urgent need for developing reliable, valid and practical instruments that assess and classify the support needed by persons with disability to function in their chosen living, working and social environments. I‐CAN is an instrument that addresses the frequency and level of support needed (not individual skills or deficits) for each individual with a disability.Method  Studies were conducted to assess the test–retest reliability and inter‐rater reliability. Concurrent validity was investigated by exploring the relationship between the I‐CAN domain scales and the Inventory for Client and Agency Planning (ICAP) (Bruininks et al. 1986) and the Quality of Life Questionnaire (QOL‐Q) (Schalock & Keith 1993). Predictive validity studies were undertaken using day‐ and night‐time support hours. Regression analyses were run using these measures with I‐CAN domain scales. Two independent studies were also conducted to ascertain the practical utility of the instrument.Results  The I‐CAN instrument demonstrated excellent inter‐rater and test–retest reliability in the Activities and Participation domains. Low‐to‐moderate test–retest results in Physical Health, Mental Emotional Health and Behaviour domains were tracked to actual change in support needs in these areas. Validity proved acceptable. The relationships between I‐CAN domain scales and adaptive behaviour were mixed but in the expected direction. Low‐to‐moderate correlation coefficients were evident between the I‐CAN scales and the QOL‐Q Total, but greater support needed in certain domains was associated with less empowerment and independence, and less community integration and social belonging. Attempts to explain current support hours against the I‐CAN scales were disappointing and suggest that a number of other factors apart from individual support need to play a significant role. There was general satisfaction with the assessment process from stakeholders and participant groups.Conclusions  I‐CAN is a reliable, valid and user‐friendly instrument for assessing the support needs of people with disabilities. It uses a process that involves the persons with disability, their family and friends and staff as appropriate. It is also apparent that the current provision of paid support hours by agencies is a complex phenomenon that is not based solely on individual support needs. Further research is warranted on the influence of the environment and the perceptions of need for support based on negotiable and non‐negotiable support needs.
Exercise‐induced metacarpophalangeal joint adaptation in the Thoroughbred racehorse
Authors: Muir P. , Peterson A. L. , Sample S. J. , Scollay M. C. , Markel M. D. , Kalscheur V. L. 
Published: November 2008

AbstractRepetitive bone injury and development of stress fracture is a common problem in humans and animals. The Thoroughbred racehorse is a model in which adaptive failure and associated development of stress fracture is common. We performed a histologic study of the distal end of the third metacarpal bone in two groups of horses: young Thoroughbreds that were actively racing (n = 10) and a group of non‐athletic horses (n = 8). The purpose of this study was to determine whether development of articular microcracks was associated with specific alterations to subchondral plate osteocytes. Morphometric measurements were made in five regions of the joint surface: lateral condyle, lateral condylar groove, sagittal ridge, medial condylar groove, and medial condyle. The following variables were quantified: hyaline cartilage width; calcified cartilage width; the number of tidemarks; microcrack density at the articular surface; blood vessel density entering articular cartilage; the presence of atypical bone matrix in the subchondral plate; bone volume fraction; and osteocyte density. Adaptation of articular cartilage was similar in both groups of horses. Vascularization of articular cartilage was increased in the group of non‐athletic horses. Microcracks, which typically had an oblique orientation to the joint surface, were co‐localized with blood vessels, and resorption spaces. Microcracking was increased in the condylar grooves of athletic horses compared with the other joint regions and was also increased compared with the condylar groove regions of non‐athletic horses. Coalescence of microcracks also led to development of an intracortical articular condylar stress fracture in some joints and targeted remodeling of affected subchondral plate. The subchondral plate of the condyles in athletic horses was sclerotic, and contained atypically stained bone matrix with increased numbers of osteocytes with atypical morphology. However, osteocyte numbers were not significantly different between groups. We conclude that differences in site‐specific microdamage accumulation and associated targeted remodeling between athletic and non‐athletic horses are much greater than differences in subchondral osteocyte morphology. However, the presence of atypical subchondral bone matrix in athletic horses was associated with extensive osteocyte loss. Although osteocyte mechanotransduction is considered important for functional adaptation, in this model, adaptation is likely regulated by multiple mechanotransduction pathways.
Age‐related increase in the immunoproteasome content in rat hippocampus: molecular and functional aspects
Authors: Gavilán M. Paz , Castaño Angélica , Torres Manuel , Portavella Manuel , Caballero Cristina , Jiménez Sebastián , García‐Martínez Ana , Parrado Juan , Vitorica Javier , Ruano Diego 
Published: November 2008

AbstractAlterations in the proteasome activity in the CNS have been described during aging. However, a detailed study of all proteasome subunits is actually lacking. We have analyzed, in vivo, the age‐related modifications in the molecular composition of hippocampal proteasomes. We found that the immunoproteasome/proteasome ratio was increased in aged hippocampus. The processing of the low‐molecular‐mass protein (LMP)7/β5i subunit, practically absent in young hippocampus, was increased in aged animals. Among the potential factors underlying these modifications we evaluated the neuroinflammation and the transcription factor Zif268. Lipopolysaccharide (LPS)‐induced neuroinflammation in young rats, up‐regulated the expression of immunoproteasome subunits and increased the processing of the LMP7/β5i protein. Moreover, the hydrophobicity of cellular peptides, analyzed by liquid chromatography, increased in both, young LPS‐injected animals and aged rats, suggesting that immunoproteasomes including the LMP7/β5i subunit could, at least in part, account for this modification. Also, the mRNA expression of the transcription factor Zif268, which down‐regulates the immunoproteasome subunit LMP7/β5i by binding to sequences within the promoter regions, was decreased in both, aged hippocampus and young LPS‐injected animals. Finally, we found that spatial memory training in young animals, a situation in which the expression of Zif268 is increased, modified the mRNA expression of the constitutive and catalytic subunits in an opposite manner. Based on present data, we propose that the age‐related increases in the content of hippocampal immunoproteasome is mostly because of neuroinflammatory processes associated to aging.
A novel mechanism of methylglyoxal cytotoxicity in neuroglial cells
Authors: Lee Hyun Kyoung , Seo In Ae , Suh Duk Joon , Lee Hye Jeong , Park Hwan Tae 
Published: November 2008

AbstractMethylglyoxal (MGO) is an endogenous dicarbonyl compound that is highly produced in hyperglycemic conditions. It forms advanced glycation endproducts that are believed to contribute, as etiological factors, to the pathophysiology of diabetic complications. In addition, MGO suppresses cell viability through the induction of apoptosis in vitro. In this study, we have, for the first time, demonstrated the effect of MGO on the gp130 cytokine‐induced signal transducer and activator of transcription 3 (STAT3) responses in RT4 schwannoma, PC12 pheochromocytoma and U87MG glioma cells. At dose that very mildly affects cell viability, MGO rapidly induces endocytotic degradation of gp130, which involves the di‐leucine internalization motif in the cytoplasmic domain of gp130, without affecting other growth factor receptors. Concomitant inhibition of basal and interleukin‐6‐induced STAT3 activation was observed following pre‐treatment with MGO. The inhibitory effect of MGO on the gp130/STAT3 signaling was prevented by the pre‐treatment with an advanced glycation endproduct scavenger aminoguanidine. Finally, these deleterious effects of MGO on STAT3 signaling led to down‐regulation of a STAT3 target gene, Bcl‐2, and sensitized cellular toxicity induced by H2O2 and etoposide. Our data indicate that MGO affects cell viability via desensitization of gp130/STAT3 signaling, which is the key signaling pathway for cell survival, and thereby promotes cytotoxicity.
Developmental and daily expression of the Pax4 and Pax6 homeobox genes in the rat retina: localization of Pax4 in photoreceptor cells
Authors: Rath Martin F. , Bailey Michael J. , Kim Jong‐So , Coon Steven L. , Klein David C. , Møller Morten 
Published: November 2008

Abstract Pax4 is a homeobox gene encoding Pax4, a transcription factor that is essential for embryonic development of the endocrine pancreas. In the pancreas, Pax4 counters the effects of the related transcription factor, Pax6, which is known to be essential for eye morphogenesis. In this study, we have discovered that Pax4 is strongly expressed in retinal photoreceptors of the rat. Pax4 expression is not detectable in the foetal eye; however, postnatal Pax4 transcript levels rapidly increase. In contrast, Pax6 exhibits an inverse developmental pattern of expression being more strongly expressed in the foetal eye. Histological analysis revealed that Pax4 mRNA is exclusively expressed in the retinal photoreceptors, whereas Pax6 mRNA and protein are present in the inner nuclear layer and in the ganglion cell layer of the mature retina. In the adult retina, Pax4 transcripts exhibit a diurnal rhythm with maximal levels occurring during the light period, whereas retinal Pax6 transcript levels do not change throughout the day. The daily changes in Pax4 expression may contribute to daily changes in function in the differentiated retinal photoreceptor.
Behavioral stress accelerates plaque pathogenesis in the brain of Tg2576 mice via generation of metabolic oxidative stress
Authors: Lee Kang‐Woo , Kim Jung‐Bin , Seo Ji‐Seon , Kim Tae‐Kyung , Im Joo‐Young , Baek In‐Sun , Kim Kyoung‐Shim , Lee Ja‐Kyeong , Han Pyung‐Lim 
Published: November 2008

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disease caused by genetic and non‐genetic factors. Most AD cases may be triggered and promoted by non‐genetic environmental factors. Clinical studies have reported that patients with AD show enhanced baseline levels of stress hormones in the blood, but their physiological significance with respect to the pathophysiology of AD is not clearly understood. Here we report that AD mouse models exposed to restraints for 2 h daily on 16 consecutive days show increased levels of β‐amyloid (Aβ) plaque deposition and commensurable enhancements in Aβ(1–42), tau hyperphosphorylation, and neuritic atrophy of cortical neurons. Repeated restraints in Tg2576 mice markedly increased metabolic oxidative stress and down‐regulated the expression of MMP‐2, a potent Aβ‐degrading enzyme, in the brain. These stress effects were reversed by blocking the activation of the hypothalamus‐pituitary‐adrenal gland axis with the corticotropin‐releasing factor receptor antagonist NBI 27914, further suggesting that over‐activation of the hypothalamic‐pituitary‐adrenal axis is required for stress‐enhanced AD‐like pathogenesis. Consistent with these findings, corticosteroid treatments to cultured primary cortical neurons increased metabolic oxidative stress and down‐regulated MMP‐2 expression, and MMP‐2 down‐regulation was reversed by inhibition of oxidative stress. These results suggest that behavioral stress aggravates AD pathology via generation of metabolic oxidative stress and MMP‐2 down‐regulation.
Building capacity for the children's workforce: findings from the knowledge review of the higher education response
Authors: Taylor Imogen , Sharland Elaine , Whiting Russell 
Published: November 2008

AbstractIn the UK, there is rapid and far‐reaching policy change designed to provide integrated services to children, young people and their families, linking education, social care, health, youth and community, criminal justice and other professions. Higher education institutions must play a significant role in this process given the large proportion of its graduates who will join the Children's Workforce. In 2007, a University of Sussex team was commissioned by the Higher Education Academy Subject Centres for Social Policy and Social Work; Education; Health Sciences and Practice; Medicine, Dentistry and Veterinary Science; and Psychology, in collaboration with the Children's Workforce Development Council and the Children's Workforce Network to undertake a Knowledge Review of integrated children's services in higher education. In this paper, the authors explore the policy context for integrated children's services and its interaction with the educational and workforce agenda. They set out the process of the Knowledge Review and examine its findings thematically, drawing on activity theory. They suggest that to advance the integrated children's services agenda in higher education, four crucial issues need to be addressed: stakeholders need to provide a clear‐cut business case for investment; universities and regulators must address disciplinary and associated cultural barriers to change at all levels; funders must invest in supporting pilot initiatives and their evaluation; and finally, academics need to find ways to engage and sustain children, young people and their families in the development process.
‘A welcome home for identity’: a learning network between children's charities and a university
Authors: Coughlan Tony 
Published: November 2008

AbstractAcross Britain, universities and employers are being encouraged to form partnerships for the development and delivery of workforce development programmes. In the social care sector, discussion about workforce development programmes usually focuses on large employers such as local authorities and children's trusts, overlooking the charities that comprise a significant sector of the workforce.This paper explores an alternative dispersed model of workforce development that encourages voluntary & community sector children's agencies to share learning and development among volunteers, employees and employers within a learning network created by two children's charities (National Council for Voluntary Child Care Organizations and Barnardo's) and a university (the UK's Open University). This learning network – the Children's Workforce Learning Network (CWLN) – operates through communities of practice, distance learning courses and e‐learning.Employer and student feedback suggests that a learning network developed through a partnership between children's charities and a university can be effective, particularly in meeting the needs of ‘hard to reach’ learners who are not well served by existing provision. However, it also appears that e‐learning may not yet be a solution to the barriers to learning often faced by isolated, part‐time and volunteer workers.
Effects of lamotrigine compared with levetiracetam on anger, hostility, and total mood in patients with partial epilepsy
Authors: Labiner David M. , Ettinger Alan B. , Fakhoury Toufic A. , Chung Steve S. , Shneker Bassel , Tatum IV William O. , Mitchell Miller J. , Vuong Alain , Hammer Anne E. , Messenheimer John A. 
Published: November 2008

SummaryPurpose:  To assess anger/hostility during treatment with lamotrigine adjunctive therapy versus levetiracetam adjunctive therapy in patients with partial seizures.Methods:  This randomized, double‐blind, parallel‐group study in adults with partial seizures included an 8‐week escalation phase, during which adjunctive lamotrigine (n = 132) or adjunctive levetiracetam (n = 136) was titrated to a target dose, and a 12‐week, double‐blind maintenance phase, during which dosages of study medication and concomitant antiepileptic drugs were maintained. The primary endpoint was change from baseline to the end of the maintenance phase (week 20) in the Anger‐Hostility subscale score of the Profile of Mood States (POMS).Results:  Improvement with lamotrigine relative to levetiracetam was observed for mean ± SD (standard deviation) change from baseline to the end of the maintenance phase (week 20) on the Anger‐Hostility subscale (lamotrigine −2.0 ± 8.2, levetiracetam −0.3 ± 8.4; p = 0.024) (the primary endpoint); the Anger‐Hostility subscale on weeks 5, 6, 7, 8, 9, 11, 12, 14, 16, 18, and 19; and the Total Mood Disturbance score on weeks 6, 7, 8, 9, 11, 12, 17, 19, and 20. Improvement (p < 0.05) with lamotrigine relative to levetiracetam was also observed on the POMS subscales Depression‐Dejection, Vigor‐Activity, Fatigue‐Inertia, and Confusion‐Bewilderment. No difference in seizure frequency was observed between groups. The most common adverse events with both medications were headache and dizziness.Discussion:  Adjunctive lamotrigine significantly improved Anger‐Hostility subscale scores relative to adjunctive levetiracetam in patients with partial seizures at the end of 20 weeks. This difference was consistently observed throughout the treatment period. Similar improvement with lamotrigine versus levetiracetam was observed for other mood symptoms.
Does the effectiveness of the ketogenic diet in different epilepsies yield insights into its mechanisms?
Authors: Hartman Adam L. 
Published: November 2008

Summary The ketogenic diet (KD) has been used successfully in a variety of epilepsy syndromes. This includes syndromes with multiple etiologies, including Lennox–Gastaut syndrome and infantile spasms; developmental syndromes of unknown etiology, such as Landau–Kleffner syndrome; and idiopathic epilepsies, such as myoclonic‐astatic (Doose) epilepsy. It also includes syndromes where genetics play a major role, such as Dravet syndrome, tuberous sclerosis, and Rett syndrome. Study of the KD in humans and animals harboring various genetic mutations may yield insights into the diet's mechanisms. Comparison of the diet's effectiveness with other treatments in specific syndromes may be another useful tool for mechanistic studies. The diet's utility in epilepsy syndromes of various etiologies and in some neurodegenerative disorders suggests it may have multiple mechanisms of action.
Mouse models: The ketogenic diet and polyunsaturated fatty acids
Authors: Borges Karin 
Published: November 2008

SummaryLiterature on the anticonvulsant effects of the ketogenic diet (KD) in mouse seizure models is summarized. Recent data show that a KD balanced in vitamin, mineral, and antioxidant content is anticonvulsant in mice, confirming that the KD's effect in mice can be attributed to the composition of the diet and not other dietary factors. Given that the anticonvulsant mechanism of the KD is still unknown, the anticonvulsant profile of the diet in different seizure models may help to decipher this mechanism. The implications of the findings that the KD is anticonvulsant in electrical seizure models are indicated. Further, the potential involvement of polyunsaturated fatty acids (PUFA) in the KD's anticonvulsant mechanism is discussed.
Peroxisome proliferator‐activated receptor alpha and the ketogenic diet
Authors: Cullingford Tim 
Published: November 2008

Summary Peroxisome proliferator‐activated receptor alpha (PPARα) is a drug/fatty acid‐activated trans cription factor involved in the starvation response, and is thus relevant to the ketogenic diet (KD). This article summarizes research indicating the role of PPARα in central and peripheral nervous system function with particular reference to downstream targets relevant to anticonvulsant action.
Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet
Authors: Bough Kristopher 
Published: November 2008

Summary The efficacy of the ketogenic diet (KD) develops gradually over a period of 1–3 weeks, suggesting that adaptive changes in gene expression are involved in its anticonvulsant effects. Previously, microarrays were employed to define patterns of gene expression in the hippocampus of rats maintained on either a KD or a control diet for 3 weeks. The density of mitochondria in hippocampal tissue was assessed by electron microscopy. Levels of selected energy metabolites, enzyme activities, and the effect of low glucose on synaptic transmission were also investigated in hippocampal tissue taken from either KD‐ or control‐fed animals. We found a coordinated up‐regulation of transcripts encoding energy metabolism enzymes and a dramatic 46% increase in the density of mitochondria observed in neuronal processes. These changes were accompanied by an increased phosphocreatine (PCr):creatine (Cr) energy‐store ratio. Consistent with heightened energy reserves, hippocampal synaptic transmission in KD‐fed animals was maintained ∼50% longer compared to controls after exposure to a mild metabolic stressor. Taken together, several lines of evidence indicate that the KD enhances energy production in the brain. As a consequence, brain tissue appears to become more resistant to metabolic stress. It is proposed . . . that the observed KD‐induced enhancements in energy metabolism help to compensate for the metabolic deficits exhibited (interictally) within epileptic foci and transient failures of gamma‐aminobutyric acid (GABA) ergic inhibition, which would otherwise favor the initiation and propagation of seizure activity.
Seizure suppression via glycolysis inhibition with 2‐deoxy‐D‐glucose (2DG)
Authors: Stafstrom Carl E. , Roopra Avtar , Sutula Thomas P. 
Published: November 2008

Summary Metabolic regulation of neuronal excitability is increasingly recognized as a factor in seizure pathogenesis and control. Inhibiting or bypassing glycolysis may be one way through which the ketogenic diet provides an anticonvulsant effect. 2‐deoxy‐D‐glucose (2DG), a nonmetabolizable glucose analog that partially inhibits glycolysis, was tested in several acute and chronic seizure models. Acutely, 2DG decreases the frequency of high‐K+‐, bicuculline‐ and 4‐aminopyridine‐induced interictal bursts in the CA3 region of hippocampal slices; 2DG also exerts anticonvulsant effects in vivo against perforant path kindling in rats. Chronically, 2DG has novel antiepileptic effects by retarding the progression of kindled seizures. Finally, 2DG has a favorable preliminary toxicity profile. These factors support the possibility that 2DG or other modifiers of glycolysis can be used as novel treatments for epilepsy.
Diet, ketones, and neurotrauma
Authors: Prins Mayumi 
Published: November 2008

Summary The annual incidence of traumatic brain injury far exceeds the rates of any other disease in the United States, yet progress toward age‐relevant therapies, attention to patients needs, and research funding have all been minimal. Cerebral metabolism of glucose has been shown to be altered after head injury, and increasing cerebral metabolism of alternative substrates (ketones) has been shown to be neuroprotective in several models of traumatic brain injury. This altered dietary approach may have tremendous therapeutic potential for both the pediatric and adult head‐injured populations.