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In vivo selective inhibition of mitogen-activated protein kinase kinase 1/2 in rabbit experimental osteoarthritis is associated with a reduction in the development of structural changes

ARTHRITIS & RHEUMATISM, Issue 6 2003
Jean-Pierre Pelletier
Objective The primary aim of this study was to investigate, using an experimental rabbit model of osteoarthritis (OA), the effect of a selective mitogen-activated protein kinase kinase 1/2 (MEK-1/2) inhibitor, PD 198306, on the development of structural changes. Additional aims were to assess the effects of the inhibitor on levels of phosphorylated extracellular signal,regulated kinase 1/2 (phospho,ERK-1/2) and matrix metalloproteinase 1 (MMP-1; collagenase 1) in OA chondrocytes. Methods After surgical sectioning of the anterior cruciate ligament of the right knee joint, rabbits with OA were separated into 3 experimental groups: oral treatment with placebo or with PD 198306 at a therapeutic concentration of 10 mg/kg/day or 30 mg/kg/day. Each treatment started immediately after surgery. The animals were killed 8 weeks after surgery. Macroscopic and histologic studies were performed on the cartilage and synovial membrane. The levels of phospho,ERK-1/2 and MMP-1 in OA cartilage chondrocytes were evaluated by immunohistochemistry. Normal, untreated rabbits were used as controls. Results OA rabbits treated with the highest dosage of MEK-1/2 inhibitor showed decreases in the surface area (size) of cartilage macroscopic lesions (P < 0.002) and in osteophyte width on the lateral condyles (P = 0.05). Histologically, the severity of synovial inflammation (villous hyperplasia) was also reduced (P < 0.02). In cartilage from placebo-treated OA rabbits, a significantly higher percentage of chondrocytes in the superficial layer stained positive for phospho,ERK-1/2 and MMP-1 compared with normal controls. Rabbits treated with the highest dosage of PD 198306 demonstrated a significant and dose-dependent reduction in the level of phospho,ERK-1/2 and a lower level of MMP-1. Conclusion This study demonstrates that, in vivo, PD 198306, a selective inhibitor of MEK-1/2, can partially decrease the development of some of the structural changes in experimental OA. This effect was associated with a reduction in the level of phospho,ERK-1/2 in OA chondrocytes, which probably explains the action of the drug. [source]


The prevalence of depressive symptoms in a white European and South Asian population with impaired glucose regulation and screen-detected Type 2 diabetes mellitus: a comparison of two screening tools

DIABETIC MEDICINE, Issue 8 2010
N. Aujla
Diabet. Med. 27, 896,905 (2010) Abstract Aims, To compare the identification of prevalent depressive symptoms by the World Health Organization-5 Wellbeing Index (WHO-5) and Centre for Epidemiological Studies Depression Scale (CES-D) for South Asian and white European people, male and female, attending a diabetes screening programme, and to explore the adequacy of the screening tools for this population. An additional aim was to further explore associations of depressive symptoms with impaired glucose regulation (IGR) and Type 2 diabetes mellitus (Type2 DM). Methods, Eight hundred and sixty-four white European (40,75 years old) and 290 South Asian people (25,75 years old) underwent an oral glucose tolerance test (OGTT), detailed history and anthropometric measurements and completed the WHO-5 and CES-D. Depressive symptoms were defined by a WHO-5 score , 13, and CES-D score , 16. Results, Unadjusted prevalence of depressive symptoms with the WHO-5, for people with Type2 DM was 42.3% (47.4% in white European; 28.6% in South Asian) and for IGR 30.7% (26% in white European; 45.8% in South Asian). With the CES-D, the prevalence in Type2 DM was 27.2% (25.4% in white European; 31.8% in South Asian) and for IGR 30.7% (27.8% in white European; 40.7% in South Asian). Statistically significant differences in the prevalence of depressive symptoms for sex or ethnicity were not identified. Odds ratios adjusted for age, sex and ethnicity showed no significant association of depression with Type2 DM or IGR, with either WHO-5 or CES-D. Agreement was moderate (, = 0.48, 95% confidence intervals 0.42,0.54), and reduced when identifying depressive symptoms in people with Type2 DM. For this group, a WHO-5 cut-point of , 10 was optimal. Conclusions, Depressive symptoms, identified by WHO-5 or CES-D, were not significantly more prevalent in people with Type2 DM or IGR. The WHO-5 and CES-D differed in their identification of depressive symptoms in people with Type2 DM, though discrepancies between sex and ethnicity were not identified. [source]


Benthic metabolism in two turbid dryland rivers

FRESHWATER BIOLOGY, Issue 2 2009
CHRISTINE S. FELLOWS
Summary 1.,Australian dryland rivers have among the most variable discharge of any rivers worldwide and are characterized by extended periods of no flow during which aquatic habitat contracts into isolated waterholes. Despite naturally high turbidity, benthic primary production is known to be the main source of carbon to waterhole food webs. The objective of this study was to quantify rates of benthic metabolism and identify factors influencing these rates in two Australian dryland rivers, the Cooper Creek and the Warrego River. 2.,Both rivers have similar variable hydrology and high levels of turbidity (photic depths < 0.4 m), but fish abundance in Cooper Creek is 10 times than that of the Warrego River. Therefore, an additional aim of the study was to determine if fish abundances reflected underlying differences in benthic primary production. 3.,Benthic gross primary production (GPP), benthic respiration, nutrient concentrations and light penetration were measured immediately after flow had ceased (,post-flow') and after at least 2 months of zero flow (,no-flow') in 15 waterholes from each river. A subset of four waterholes from each river was sampled on two additional occasions to determine if patterns were consistent over time. 4. Cooper Creek generally had higher rates of GPP and a more autotrophic benthic zone than the Warrego River. As a result, the expected positive relationship between fish abundance and GPP was generally observed at a broad catchment scale. 4.,Light was the major control in benthic GPP in both rivers, as nutrient concentrations were high on all sampling occasions. However, for similar values of photic depth, GPP was greater in Cooper Creek than in the Warrego River. This suggests that more frequent disturbance of the littoral zone may inhibit biofilm development in waterholes of the Warrego River. 5.,Although flow variability in dryland rivers is extreme compared with other rivers worldwide, cycles of expansion and contraction of aquatic habitat in these two rivers were associated with a shift in the dominance of regional scale (subcatchments contributing to river flow) versus local scale (waterhole morphology) influences on ecosystem functioning, similar to floodplain rivers in tropical and temperate regions. [source]


Anomalies and stock returns: Australian evidence

ACCOUNTING & FINANCE, Issue 3 2009
Philip Gharghori
G12; G14 Abstract Prior research has identified the existence of several cross-sectional patterns in equity returns, commonly referred to as effects. This paper tests for the existence of a number of well-known effects using data from the Australian equities market. Specifically, we investigate the size effect, book-to-market effect, earnings-to-price effect, cashflow-to-price effect, leverage effect and the liquidity effect. An additional aim of this paper is to investigate the capability of the Fama,French model in explaining any observed effects. We document a size, book-to-market, earnings-to-price and cashflow-to-price effect but fail to find evidence of a leverage or liquidity effect. Although our findings indicate that the Fama,French model can partially explain some of the observed effects, we conclude that its performance is less than satisfactory in Australia. [source]


A miniaturized assay for influenza neuraminidase-inhibiting antibodies utilizing reverse genetics-derived antigens

INFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 5 2009
Matthew R. Sandbulte
Background, Antibodies to neuraminidase (NA) contribute to protection during influenza virus infection, but NA inhibition (NI) titers are not routinely analyzed in vaccine trials. One reason is the cumbersome nature of the conventional thiobarbituric acid (TBA) NI assay, which uses chemical methods to quantify free sialic acid following incubation of NA with substrate in the presence of serum. In addition, the assay is complicated by the need to use virus of a hemagglutinin (HA) subtype novel to the host to detect NA-specific antibodies only. Objectives, Our primary objectives were to miniaturize the colorimetric NI assay to a format suitable for quantitative analysis of large numbers of samples, and validate the specificity and sensitivity of the miniaturized format with ferret and human sera. An additional aim was to use reverse genetics to construct HA-mismatched viral reagents bearing NA of recent influenza A vaccine strains and H6 HA. Results, Analysis of ferret antisera by the miniaturized assay demonstrated sensitivity and specificity comparable with the conventional assay. Similar increases in the NI titers in sera from vaccinated human volunteers were measured in miniaturized and conventional assays. Inactivated and live-attenuated vaccines increased NI titers against a given subtype at approximately the same rate. Conclusions, The reagents and miniaturized format of the TBA method described here provide a platform for practical serological monitoring of functional antibodies against NA. [source]


Implementation of oral health recommendations into two residential aged care facilities in a regional Australian city

INTERNATIONAL JOURNAL OF EVIDENCE BASED HEALTHCARE, Issue 3 2006
Tony Fallon BAppSc(Hons) PhD
Abstract Background, Residents of aged care facilities usually have a large number of oral health problems. Residents who suffer from dementia are at particular risk. A systematic review of the best available evidence with regard to maintaining the oral health of older people with dementia in residential aged care facilities provided a number of recommendations. Objectives, The aim of the implementation project was to introduce evidence-based oral hygiene practices for patients with dementia in two publicly funded residential aged care facilities and monitor for changes in nursing awareness, knowledge, documentation and practice to improve patient outcomes and ensure appropriate accreditation standards were met. An additional aim was to identify barriers and strategies to overcome barriers to implementation of evidence-based recommendations. Methods, Two facilities, a 40-bed facility and a 71-bed facility in the health service district of the regional Australian city of Toowoomba, provided the setting. A quality improvement approach was taken, using a number of strategies from the National Health and Medical Research Council guidelines for implementation studies. The implementation involved a number of stages, including project development, interactive oral health education, oral audits of residents, changes to oral hygiene practice via care plans and critical reflection. Results, The multidisciplinary approach to improving oral healthcare appeared to improve knowledge and awareness and move oral health practices in facilities closer to best practice. Specialised training in oral health was provided to a Clinical Nurse Consultant. Regular oral audits were introduced and facility staff were trained in the use of the oral audit tool. Care plans at one facility were of better quality and more comprehensive than before the intervention. Comments made during critical reflection suggested improvements in the oral health of residents, increased use of oral swabs and saliva substitutes, improved care of dentures and mention of the use of mouth props in resident care plans. There was also some evidence that changes brought about by the implementation are sustainable. Conclusion, The majority of recommendations provided in the systematic review of oral healthcare for dementia patients were applicable to the applied context. The importance of day-to-day leaders was highlighted by the apparently varied outcomes across target facilities. The quality improvement approach would appear to have considerable advantages when applied to improving practice in residential aged care. [source]


Medication usage among young adult women: A comparison between Sweden, the USA, and Greece

NURSING & HEALTH SCIENCES, Issue 1 2008
Evy Lidell rn
Abstract This study evaluated whether or not medication usage among young adult women differed across three countries. An additional aim was to evaluate the association between medication use and sociodemographic factors and exercise habits. A sample of 1098 young adult women were selected in Sweden, the USA, and Greece. Consistent medication usage by young adult women in the three countries related to oral contraceptives and vitamins; nevertheless, there were differences. The main differences were found in the use of laxatives, iron supplements, analgesics, antidepressants, and antacid medication. The most outstanding differences were the frequent use of laxatives in Sweden and vitamins in the USA. Different association patterns were found between medication use and culture, sociodemographic factors, and exercise. The assessment of medication use among young adult women can be performed very easily and provides an immediate indication of their well-being and needs for preventative care. [source]


Quambalaria species associated with plantation and native eucalypts in Australia

PLANT PATHOLOGY, Issue 4 2008
G. S. Pegg
This study aimed to determine which species of Quambalaria are associated with shoot blight symptoms on Corymbia spp. An additional aim was to determine the presence and impact of quambalaria shoot blight on Eucalyptus species used in plantation development in subtropical and tropical regions of eastern Australia. Surveys identified three Quambalaria spp. ,Q. pitereka, Q. eucalypti and Q. cyanescens, from native and plantation eucalypts, as well as amenity plantings, including the first confirmed report of Q. eucalypti from Eucalyptus plantations in Australia. Symptom descriptions and morphological studies were coupled with phylogenetic studies using ITS rDNA sequence data. Quambalaria pitereka was the causal agent of blight symptoms on species and hybrids in the Corymbia complex. Quambalaria eucalypti was identified from Eucalyptus species and a single Corymbia hybrid. Quambalaria cyanescens was detected from native and plantation Corymbia spp. [source]


Case Management Relationships and a Recovery Orientation: A Consumer Survey of Class Members in the Arnold Case

AMERICAN JOURNAL OF ORTHOPSYCHIATRY, Issue 3 2010
José B. Ashford
The purpose of this study was to examine the relative contributions of the working alliance in predicting a recovery orientation. An additional aim was to determine whether a measure of case management fairness contributed any additional proportion of explained variance in a recovery orientation beyond what is accounted for by the working alliance. The study blended structured interview and clinical judgment measures with survey research methods to obtain data about consumer relationships with their case managers, as well as their recovery attitudes. The sample consisted of (N = 167) priority-class members involved in the Arnold v. Arizona Department of Health Services class-action lawsuit in Maricopa County, Arizona. The results showed that the working alliance and case management fairness variables accounted for more of the explained variance in a recovery orientation, than any of the other known correlates of recovery. The results also provided some preliminary support for the inclusion of case management fairness as a predictor variable of a recovery orientation, in that the study's measure of case management fairness contributed a small proportion of additional variance beyond what was explained by the working alliance in predicting a dimension of a recovery orientation. The implications of the study's findings for practice and future research are discussed. [source]


Human thiopurine methyltransferase activity varies with red blood cell age

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2001
L. Lennard
Aims, Inherited differences in thiopurine methyltransferase (TPMT) activity are an important factor in the wide interindividual variations observed in the clinical response to thiopurine chemotherapy. The aim of this study was to establish a population range for red blood cell (RBC) TPMT activity in children with acute lymphoblastic leukaemia (ALL) at disease diagnosis. An additional aim was to investigate factors that can influence TPMT activity within the RBC. Methods,Blood samples were collected from children with ALL at disease diagnosis, prior to any blood transfusions, as part of the nationwide UK MRC ALL97 therapeutic trial. RBC TPMT activity was measured by h.p.l.c. RBCs were age-fractionated on Percoll density gradients. Results,Pretreatment blood samples were received from 570 children within 3 days of venepuncture. TPMT activities at disease diagnosis ranged from 1.6 to 23.6 units/ml RBCs (median 7.9) compared with 0.654,18.8 units (median 12.9), in 111 healthy control children (median difference 4.5 units, 95% CI 3.9, 5.1 units, P < 0.001). A TPMT quality control sample, aliquots of which were assayed in 60 analytical runs over a 12 month period, contained a median of 11.98 units with a CV of 11.6%. Seven children had their RBCs age-fractionated on density gradients. TPMT activities in the top gradient (young cells) ranged from 4.2 to 14.1 units (median 7.5) and in the bottom gradient (old cells) 1.5,12.6 units (median 4.7 units), median difference 2.3 units, 95% CI 0.7, 4.1, P = 0.035. Conclusions,Circulating RBCs do not constitute a homogeneous population. They have a life span of around 120 days and during that time undergo a progressive ageing process. The anaemia of ALL is due to deficient RBC production. The results of this study indicate that RBC TPMT activities are significantly lower in children with ALL at disease diagnosis. This may be due, at least in part, to a relative excess of older RBCs. [source]


Children and Mothers in War: An Outcome Study of a Psychosocial Intervention Program

CHILD DEVELOPMENT, Issue 4 2001
Ragnhild Dybdahl
The present study was designed to evaluate the effects on children (age: M=5.5 years) in war-torn Bosnia and Herzegovina of a psychosocial intervention program consisting of weekly group meetings for mothers for 5 months. An additional aim was to investigate the children's psychosocial functioning and the mental health of their mothers. Internally displaced mother , child dyads were randomly assigned to an intervention group receiving psychosocial support and basic medical care (n=42) or to a control group receiving medical care only (n=45). Participants took part in interviews and tests to provide information about war exposure, mental health, psychosocial functioning, intellectual abilities, and physical health. Results showed that although all participants were exposed to severe trauma, their manifestations of distress varied considerably. The intervention program had a positive effect on mothers' mental health, children's weight gain, and several measures of children's psychosocial functioning and mental health, whereas there was no difference between the two groups on other measures. The findings have implications for policy. [source]