bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence and rehabilitation: toward second-generation virtual reality applications in neuropsychology
Authors: Riva Giuseppe , Mantovani Fabrizia , Gaggioli Andrea 
Published: January 2005

AbstractVirtual Reality (VR) offers a blend of attractive attributes for rehabilitation. The most exploited is its ability to create a 3D simulation of reality that can be explored by patients under the supervision of a therapist. In fact, VR can be defined as an advanced communication interface based on interactive 3D visualization, able to collect and integrate different inputs and data sets in a single real-like experience.However, "treatment is not just fixing what is broken; it is nurturing what is best" (Seligman & Csikszentmihalyi). For rehabilitators, this statement supports the growing interest in the influence of positive psychological state on objective health care outcomes.This paper introduces a bio-cultural theory of presence linking the state of optimal experience defined as "flow" to a virtual reality experience. This suggests the possibility of using VR for a new breed of rehabilitative applications focused on a strategy defined as transformation of flow. In this view, VR can be used to trigger a broad empowerment process within the flow experience induced by a high sense of presence.The link between its experiential and simulative capabilities may transform VR into the ultimate rehabilitative device. Nevertheless, further research is required to explore more in depth the link between cognitive processes, motor activities, presence and flow.
The involvement of survival signaling pathways in rubella-virus induced apoptosis
Authors: Cooray Samantha , Jin Li , Best Jennifer M 
Published: January 2005

AbstractRubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the development of such defects. Often the outcome of apoptotic stimuli is dependent on apoptotic, proliferative and survival signaling mechanisms in the cell. Therefore we investigated the role of phosphoinositide 3-kinase (PI3K)-Akt survival signaling and Ras-Raf-MEK-ERK proliferative signaling during RV-induced apoptosis in RK13 cells. Increasing levels of phosphorylated ERK, Akt and GSK3β were detected from 24–96 hours post-infection, concomitant with RV-induced apoptotic signals. Inhibition of PI3K-Akt signaling reduced cell viability, and increased the speed and magnitude of RV-induced apoptosis, suggesting that this pathway contributes to cell survival during RV infection. In contrast, inhibition of the Ras-Raf-MEK-ERK pathway impaired RV replication and growth and reduced RV-induced apoptosis, suggesting that the normal cellular growth is required for efficient virus production.
Homeostatic capabilities of the choroid plexus epithelium in Alzheimer's disease
Authors: Johanson Conrad , McMillan Paul , Tavares Rosemarie , Spangenberger Anthony , Duncan John , Silverberg Gerald , Stopa Edward 
Published: January 2005

AbstractAs the secretory source of vitamins, peptides and hormones for neurons, the choroid plexus (CP) epithelium critically provides substances for brain homeostasis. This distributive process of cerebrospinal fluid (CSF) volume transmission reaches many cellular targets in the CNS. In ageing and ageing-related dementias, the CP-CSF system is less able to regulate brain interstitial fluid. CP primarily generates CSF bulk flow, and so its malfunctioning exacerbates Alzheimers disease (AD). Considerable attention has been devoted to the blood-brain barrier in AD, but more insight is needed on regulatory systems at the human blood-CSF barrier in order to improve epithelial function in severe disease. Using autopsied CP specimens from AD patients, we immunocytochemically examined expression of heat shock proteins (HSP90 and GRP94), fibroblast growth factor receptors (FGFr) and a fluid-regulatory protein (NaK2Cl cotransporter isoform 1 or NKCC1). CP upregulated HSP90, FGFr and NKCC1, even in end-stage AD. These CP adjustments involve growth factors and neuropeptides that help to buffer perturbations in CNS water balance and metabolism. They shed light on CP-CSF system responses to ventriculomegaly and the altered intracranial pressure that occurs in AD and normal pressure hydrocephalus. The ability of injured CP to express key regulatory proteins even at Braak stage V/VI, points to plasticity and function that may be boosted by drug treatment to expedite CSF dynamics. The enhanced expression of human CP 'homeostatic proteins' in AD dementia is discussed in relation to brain deficits and pharmacology.
Australian primary care policy in 2004: two tiers or one for Medicare?
Authors: Swerissen Hal 
Published: January 2005

AbstractThe recent primary care policy debate in Australia has centred on access to primary medical (general practice) services. In Australia, access is heavily influenced by Commonwealth Government patient rebates that provide incentives for general practitioners not to charge copayments to patients (bulk billing). A steady decline in key access indicators (bulk billing) has led the Howard Government to introduce a set of changes that move Medicare from a universal scheme, to one increasingly targeted at providing services to more disadvantaged Australians. In doing so, another scene in the story of the contest between universal health care and selective provision in Australia has been written. This paper explores the immediate antecedents and consequences of the changes and sets them in the broader context of policy development for primary care in Australia.
Healthy children, healthy country: the use of governing instruments in shifting the policy paradigm
Authors: Leggat Sandra G 
Published: January 2005

AbstractThe evidence on early childhood strongly suggests the need to shift child health policy from the current focus on social welfare to a socio-ecologically based approach. This paper reviews three governing instruments, exhortation, expenditure and regulation, that have been used by governments in Australia and discusses the relative effectiveness of these approaches in shifting the child health policy paradigm.
The Australian Health Care Agreements 2003–2008
Authors: Duckett Stephen J 
Published: January 2005

AbstractThe Australian Health Care Agreements for the five years 1 July 2003 to 30 June 2008 were signed in August 2003 after vituperative debate and intransigence from the Commonwealth that vitiated the negotiation process. The new Agreements, which were not as generous as the Agreements they replaced, increase accountability on the States, requiring States to match increases in Commonwealth funding, and de-emphasise the prospects for further reform in Commonwealth-State relations during the course of the Agreements. This paper describes the new Australian Health Care Agreements and the process which led to them.
Australian health system restructuring – what problem is being solved?
Authors: Dwyer Judith M 
Published: January 2005

Abstract
Background
In recent years, Australian state and territory governments have reviewed and restructured the health systems they lead and regulate. This paper examines the outcomes of the most recent official published reviews of systems and structures; identifies the common themes; and addresses two questions: what problems are being addressed? And how would we know if the changes were successful?

Results
In all the broad, systemic reviews, the main health system problems identified were money, hospital utilisation and a weak primary health care system. The solutions are various, but there is a common trend towards centralisation of governance, often at state health authority level, and stronger accountability measures. Other common themes are hospital substitution (services to avoid the need for admission); calls for cooperation across the Commonwealth:state divide, or for its abolition; and the expected range of current efficiency and effectiveness measures (eg amalgamate pathology and support services) and ideas in good currency (eg call centres). The top-down nature of the public review process is noted, along with the political nature of the immediate catalysts for calling on a review.

Conclusion
The long-standing tension between the pull to centralisation of authority and the need for innovation in care models is heightened by recent changes, which may be counterproductive in an era dominated by the burden of chronic disease. I argue that the current reforms will not succeed in achieving the stated goals unless they make a difference for people with chronic illness. And if this is correct, the most useful focus for evaluation of the success of the reforms may be their impact on the system's ability to develop and deliver better models of care for this growing group of patients.
Microcirculation abnormalities in patients with fibromyalgia – measured by capillary microscopy and laser fluxmetry
Authors: Morf Susanne , Amann-Vesti Beatrice , Forster Adrian , Franzeck Ulrich K , Koppensteiner Renate , Uebelhart Daniel , Sprott Haiko 
Published: January 2005

AbstractThis unblinded preliminary case-control study was done to demonstrate functional and structural changes in the microcirculation of patients with primary fibromyalgia (FM). We studied 10 women (54.0 ± 3.7 years of age) with FM diagnosed in accordance with the classification criteria of the American College of Rheumatology, and controls in three groups (n = 10 in each group) – age-matched women who were healthy or who had rheumatoid arthritis or systemic scleroderma (SSc). All 40 subjects were tested within a 5-week period by the same investigators, using two noninvasive methods, laser fluxmetry and capillary microscopy. The FM patients were compared with the healthy controls (negative controls) and with rheumatoid arthritis patients and SSc patients (positive controls). FM patients had fewer capillaries in the nail fold (P < 0.001) and significantly more capillary dilatations (P < 0.05) and irregular formations (P < 0.01) than the healthy controls. Interestingly, the peripheral blood flow in FM patients was much less (P < 0.001) than in healthy controls but did not differ from that of SSc patients (P = 0.73). The data suggest that functional disturbances of microcirculation are present in FM patients and that morphological abnormalities may also influence their microcirculation.
Local expression of matrix metalloproteinases, cathepsins, and their inhibitors during the development of murine antigen-induced arthritis
Authors: Schurigt Uta , Stopfel Nadine , Hückel Marion , Pfirschke Christina , Wiederanders Bernd , Bräuer Rolf 
Published: January 2005

AbstractCartilage and bone degradation, observed in human rheumatoid arthritis (RA), are caused by aberrant expression of proteinases, resulting in an imbalance of these degrading enzymes and their inhibitors. However, the role of the individual proteinases in the pathogenesis of degradation is not yet completely understood. Murine antigen-induced arthritis (AIA) is a well-established animal model of RA. We investigated the time profiles of expression of matrix metalloproteinase (MMP), cathepsins, tissue inhibitors of matrix metalloproteinases (TIMP) and cystatins in AIA. For primary screening, we revealed the expression profile with Affymetrix oligonucleotide chips. Real-time polymerase chain reaction (PCR) analyses were performed for the validation of array results, for tests of more RNA samples and for the completion of the time profile. For the analyses at the protein level, we used an MMP fluorescence activity assay and zymography. By a combination of oligonucleotide chips, real-time PCR and zymography, we showed differential expressions of several MMPs, cathepsins and proteinase inhibitors in the course of AIA. The strongest dysregulation was observed on days 1 and 3 in the acute phase. Proteoglycan loss analysed by safranin O staining was also strongest on days 1 and 3. Expression of most of the proteinases followed the expression of pro-inflammatory cytokines. TIMP-3 showed an expression profile similar to that of anti-inflammatory interleukin-4. The present study indicates that MMPs and cathepsins are important in AIA and contribute to the degradation of cartilage and bone.
A2Badenosine receptor activity is reduced in neutrophils from patients with systemic sclerosis
Authors: Bazzichi Laura , Trincavelli Letizia , Rossi Alessandra , De Feo Francesca , Lucacchini Antonio , Bombardieri Stefano , Martini Claudia 
Published: January 2005

AbstractWe conducted the present study to investigate protein expression and functioning of A2A and A2B adenosine receptors (ARs) in neutrophils of patients affected by systemic sclerosis (SSc). The presence of A2A and A2B ARs was assessed by immunoblotting using specific antibodies. Equilibrium A2A and A2B ARs binding parameters were evaluated by radioligand binding assay. Functional studies were conducted to investigate coupling of the A2B AR to the adenylyl cyclase pathway. This is the first report of the use of Western blot analysis to confirm the presence of A2A and A2B ARs in human neutrophils. No significant changes in A2A AR binding parameters or expression levels were detected between SSc patients and healthy control individuals. A significant decrease (65%) in the maximum density of A2B AR binding sites occurred in SSc neutrophils, whereas no changes in the affinity constant values were found. Moreover, a decrease in A2B AR mediated adenylyl cyclase activity was observed in patients with SSc. Our findings demonstrate the occurrence of selective alterations in A2B AR density and signalling in SSc.
Gene expression profiling in murine autoimmune arthritis during the initiation and progression of joint inflammation
Authors: Adarichev Vyacheslav A , Vermes Csaba , Hanyecz Anita , Mikecz Katalin , Bremer Eric G , Glant Tibor T 
Published: January 2005

AbstractWe present here an extensive study of differential gene expression in the initiation, acute and chronic phases of murine autoimmune arthritis with the use of high-density oligonucleotide arrays interrogating the entire mouse genome. Arthritis was induced in severe combined immunodeficient mice by using adoptive transfer of lymphocytes from proteoglycan-immunized arthritic BALB/c mice. In this unique system only proteoglycan-specific lymphocytes are transferred from arthritic mice into syngeneic immunodeficient recipients that lack adaptive immunity but have intact innate immunity on an identical (BALB/c) genetic background.Differential gene expression in response to donor lymphocytes that migrated into the joint can therefore be monitored in a precisely timed manner, even before the onset of inflammation. The initiation phase of adoptively transferred disease (several days before the onset of joint swelling) was characterized by differential expression of 37 genes, mostly related to chemokines, interferon-γ and tumor necrosis factor-α signaling, and T cell functions. These were designated early arthritis 'signature' genes because they could distinguish between the naive and the pre-arthritic state. Acute joint inflammation was characterized by at least twofold overexpression of 256 genes and the downregulation of 21 genes, whereas in chronic arthritis a total of 418 genes with an equal proportion of upregulated and downregulated transcripts were expressed differentially.Hierarchical clustering and functional classification of inflammation-related and arthritis-related genes indicated that the most common biological activities were represented by genes encoding interleukins, chemokine receptors and ligands, and by those involved in antigen recognition and processing.
JNK1 is not essential for TNF-mediated joint disease
Authors: Köller Marcus , Hayer Silvia , Redlich Kurt , Ricci Romeo , David Jean-Pierre , Steiner Günter , Smolen Josef S , Wagner Erwin F , Schett Georg 
Published: January 2005

AbstractTumour necrosis factor (TNF) signalling molecules are considered as promising therapeutic targets of antirheumatic therapy. Among them, mitogen-activated protein kinases are thought to be of central importance. Herein, we investigate the role in vivo of TNF-α signalling through c-Jun N-terminal kinase (JNK)1 in destructive arthritis. Human TNF transgenic (hTNFtg) mice, which develop inflammatory arthritis, were intercrossed with JNK1-deficient (JNK1-/-) mice. Animals (n = 35) of all four genotypes (wild-type, JNK1-/-, hTNFtg, JNK1-/-hTNFtg) were assessed for clinical and histological signs of arthritis. Clinical features of arthritis (swelling and decreased grip strength) developed equally in hTNFtg and JNK1-/-hTNFtg mice. Histological analyses revealed no differences in the quantity of synovial inflammation and bone erosions or in the cellular composition of the synovial infiltrate. Bone destruction and osteoclast formation were observed to a similar degree in hTNFtg and JNK1-/-hTNFtg animals. Moreover, cartilage damage, as indicated by proteoglycan loss in the articular cartilage, was comparable in the two strains. Intact phosphorylation of JNK and c-Jun as well as expression of JNK2 in the synovial tissue of JNK1-/-hTNFtg mice suggests that signalling through JNK2 may compensate for the deficiency in JNK1. Thus, JNK1 activation does not seem to be essential for TNF-mediated arthritis.
Tapasin gene polymorphism in systemic onset juvenile rheumatoid arthritis: a family-based case–control study
Authors: Bukulmez Hulya , Fife Mark , Tsoras Monica , Thompson Susan D , Twine Natalie A , Woo Patricia , Olson Jane M , Elston Robert C , Glass David N , Colbert Robert A 
Published: January 2005

AbstractJuvenile rheumatoid arthritis (JRA) comprises a group of chronic systemic inflammatory disorders that primarily affect joints and can cause long-term disability. JRA is likely to be a complex genetic trait, or a series of such traits, with both genetic and environmental factors contributing to the risk for developing the disease and to its progression. The HLA region on the short arm of chromosome 6 has been intensively evaluated for genetic contributors to JRA, and multiple associations, and more recently linkage, has been detected. Other genes involved in innate and acquired immunity also map to near the HLA cluster on 6p, and it is possible that variation within these genes also confers risk for developing JRA. We examined the TPSN gene, which encodes tapasin, an endoplasmic reticulum chaperone that is involved in antigen processing, to elucidate its involvement, if any, in JRA. We employed both a case–control approach and the transmission disequilibrium test, and found linkage and association between the TPSN allele (Arg260) and the systemic onset subtype of JRA. Two independent JRA cohorts were used, one recruited from the Rheumatology Clinic at Cincinnati Children's Hospital Medical Center (82 simplex families) and one collected by the British Paediatric Rheumatology Group in London, England (74 simplex families). The transmission disequilibrium test for these cohorts combined was statistically significant (χ2 = 4.2, one degree of freedom; P = 0.04). Linkage disequilibrium testing between the HLA alleles that are known to be associated with systemic onset JRA did not reveal linkage disequilibrium with the Arg260 allele, either in the Cincinnati systemic onset JRA cohort or in 113 Caucasian healthy individuals. These results suggest that there is a weak association between systemic onset JRA and the TPSN polymorphism, possibly due to linkage disequilibrium with an as yet unknown susceptibility allele in the centromeric part of chromosome 6.
Membrane estrogen receptor-α levels in MCF-7 breast cancer cells predict cAMP and proliferation responses
Authors: Zivadinovic Dragoslava , Gametchu Bahiru , Watson Cheryl S 
Published: January 2005

Abstract
Introduction
17β-estradiol (E2) can rapidly induce cAMP production, but the conditions under which these cAMP levels are best measured and the signaling pathways responsible for the consequent proliferative effects on breast cancer cells are not fully understood. To help resolve these issues, we compared cAMP mechanistic responses in MCF-7 cell lines selected for low (mERlow) and high (mERhigh) expression of the membrane form of estrogen receptor (mER)-α, and thus addressed the receptor subform involved in cAMP signaling.

Methods
MCF-7 cells were immunopanned and subsequently separated by fluorescence activated cell sorting into mERhigh (mER-α-enriched) and mERlow (mER-α-depleted) populations. Unique (compared with previously reported) incubation conditions at 4°C were found to be optimal for demonstrating E2-induced cAMP production. Time-dependent and dose-dependent effects of E2 on cAMP production were determined for both cell subpopulations. The effects of forskolin, 8-CPT cAMP, protein kinase A inhibitor (H-89), and adenylyl cyclase inhibitor (SQ 22,536) on E2-induced cell proliferation were assessed using the crystal violet assay.

Results
We demonstrated a rapid and transient cAMP increase after 1 pmol/l E2 stimulation in mERhigh cells; at 4°C these responses were much more reliable and robust than at 37°C (the condition most often used). The loss of cAMP at 37°C was not due to export. 3-Isobutyl-1-methylxanthine (IBMX; 1 mmol/l) only partially preserved cAMP, suggesting that multiple phosphodiesterases modulate its level. The accumulated cAMP was consistently much higher in mERhigh cells than in mERlow cells, implicating mER-α levels in the process. ICI172,780 blocked the E2-induced response and 17α-estradiol did not elicit the response, also suggesting activity through an estrogen receptor. E2 dose-dependent cAMP production, although biphasic in both cell types, was responsive to 50-fold higher E2 concentrations in mERhigh cells. Proliferation of mERlow cells was stimulated over the whole range of E2concentrations, whereas the number of mERhigh cells was greatly decreased at concentrations above 1 nmol/l, suggesting that estrogen over-stimulation can lead to cell death, as has previously been reported, and that mER-α participates. E2-mediated activation of adenylyl cyclase and downstream participation of protein kinase A were shown to be involved in these responses.

Conclusion
Rapid mER-α-mediated nongenomic signaling cascades generate cAMP and downstream signaling events, which contribute to the regulation of breast cancer cell number.