Osteoarthritic cartilage chondrocytes alter subchondral bone osteoblast differentiation via MAPK signalling pathway involving ERK1/2

Osteoarthritic subchondral bone is characterized by abnormal bone density and enhanced production of bone turnover markers, an indication of osteoblast dysfunction. Several studies have proposed that pathological changes in articular cartilage influence the subchondral bone changes, which are typical of the progression of osteoarthritis; however, direct evidence of this has yet to be reported. The aim of the present study was to investigate what effects articular cartilage cells, isolated from normal and osteoarthritic joints, may have on the subchondral bone osteoblast phenotype, and also the potential involvement of the mitogen activated protein kinase (MAPK) signalling pathway during this process. Our results suggest that chondrocytes isolated from a normal joint inhibited osteoblast differentiation, whereas chondrocytes isolated from an osteoarthritic joint enhanced osteoblast differentiation, both via a direct and indirect cell interaction mechanisms. Furthermore, the interaction of subchondral bone osteoblasts with osteoarthritic chondrocyte conditioned media appeared to significantly activate ERK1/2 phosphorylation. On the other hand, conditioned media from normal articular chondrocytes did not affect ERK1/2 phosphorylation. Inhibition of the MAPK–ERK1/2 pathways reversed the phenotype changes of subchondral bone osteoblast, which would otherwise be induced by the conditioned media from osteoarthritic chondrocytes. In conclusion, our findings provide evidence that osteoarthritic chondrocytes affect subchondral bone osteoblast metabolism via an ERK1/2 dependent pathway.

Mechanisms of change in negative thinking and urinary monoamines in depressed patients during acute treatment with group cognitive behavior therapy and antidepressant medication

This naturalistic study investigated the mechanisms of change in measures of negative thinking and in 24-h urinary metabolites of noradrenaline (norepinephrine), dopamine and serotonin in a sample of 43 depressed hospital patients attending an eight-session group cognitive behavior therapy program. Most participants (91%) were taking antidepressant medication throughout the therapy period according to their treating Psychiatrists' prescriptions. The sample was divided into outcome categories (19 Responders and 24 Non-responders) on the basis of a clinically reliable change index [Jacobson, N.S., & Truax, P., 1991. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12–19.] applied to the Beck Depression Inventory scores at the end of the therapy. Results of repeated measures analysis of variance [ANOVA] analyses of variance indicated that all measures of negative thinking improved significantly during therapy, and significantly more so in the Responders as expected. The treatment had a significant impact on urinary adrenaline and metadrenaline excretion however, these changes occurred in both Responders and Non-responders. Acute treatment did not significantly influence the six other monoamine metabolites. In summary, changes in urinary monoamine levels during combined treatment for depression were not associated with self-reported changes in mood symptoms.

Capital access of nonprofit organisations

This paper draws on a recently completed report for the National Roundtable of Nonprofit Organisations (Lyons, North-Samardzic and Young, 2007) to determine the extent and dimensions of problems nonprofit organisations have in accessing the capital they need.

Soil carbon saturation : evaluation and corroboration by long-term incubations

Although current assessments of agricultural management practices on soil organic C (SOC) dynamics are usually conducted without any explicit consideration of limits to soil C storage, it has been hypothesized that the SOC pool has an upper, or saturation limit with respect to C input levels at steady state. Agricultural management practices that increase C input levels over time produce a new equilibrium soil C content. However, multiple C input level treatments that produce no increase in SOC stocks at equilibrium show that soils have become saturated with respect to C inputs. SOC storage of added C input is a function of how far a soil is from saturation level (saturation deficit) as well as C input level. We tested experimentally if C saturation deficit and varying C input levels influenced soil C stabilization of added C-13 in soils varying in SOC content and physiochemical characteristics. We incubated for 2.5 years soil samples from seven agricultural sites that were closer to (i.e., A-horizon) or further from (i.e., C-horizon) their C saturation limit. At the initiation of the incubations, samples received low or high C input levels of 13 C-labeled wheat straw. We also tested the effect of Ca addition and residue quality on a subset of these soils. We hypothesized that the proportion of C stabilized would be greater in samples with larger C Saturation deficits (i.e., the C- versus A-horizon samples) and that the relative stabilization efficiency (i.e., Delta SCC/Delta C input) would decrease as C input level increased. We found that C saturation deficit influenced the stabilization of added residue at six out of the seven sites and C addition level affected the stabilization of added residue in four sites, corroborating both hypotheses. Increasing Ca availability or decreasing residue quality had no effect on the stabilization of added residue. The amount of new C stabilized was significantly related to C saturation deficit, supporting the hypothesis that C saturation influenced C stabilization at all our sites. Our results suggest that soils with low C contents and degraded lands may have the greatest potential and efficiency to store added C because they are further from their saturation level. (c) 2008 Elsevier Ltd. All rights reserved.

Differentially Expressed Protein Profile of Human Dental Pulp Cells in the Early Process of Odontoblast-like Differentiation In Vitro

Dental pulp cells (DPCs) are capable of differentiating into odontoblasts that secrete reparative dentin after pulp injury. The molecular mechanisms governing reparative dentinogenesis are yet to be fully understood. Here we investigated the differential protein profile of human DPCs undergoing odontogenic induction for 7 days. Using two-dimensional differential gel electrophoresis coupled with matrix-assisted laser adsorption ionization time of flight mass spectrometry, 2 3 protein spots related to the early odontogenic differentiation were identified. These proteins included cytoskeleton proteins, nuclear proteins, cell membrane-bound molecules, proteins involved in matrix synthesis, and metabolic enzymes. The expression of four identified proteins, which were heteronuclear ribonuclear proteins C, annexin VI, collagen type VI, and matrilin-2, was confirmed by Western blot and real-time realtime polymerase chain reaction analyses. This study generated a proteome reference map during odontoblast- like differentiation of human DPCs, which will be valuable to better understand the underlying molecular mechanisms in odontoblast-like differentiation.

Repair and regeneration of osteochondral defects in the articular joints

People suffering from pain due to osteoarthritic or rheumatoidal changes in the joints are still waiting for a better treatment. Although some studies have achieved success in repairing small cartilage defects, there is no widely accepted method for complete repair of osteochondral defects. Also joint replacements have not yet succeeded in replacing of natural cartilage without complications. Therefore, there is room for a new medical approach, which outperforms currently used methods. The aim of this study is to show potential of using a tissue engineering approach for regeneration of osteochondral defects. The critical review of currently used methods for treatment of osteochondral defects is also provided. In this study, two kinds of hybrid scaffolds developed in Hutmacher's group have been analysed. The first biphasic scaffold consists of fibrin and PCL. The fibrin serves as a cartilage phase while the porous PCL scaffold acts as the subchondral phase. The second system comprises of PCL and PCL-TCP. The scaffolds were fabricated via fused deposition modeling which is a rapid prototyping system. Bone marrow-derived mesenchymal cells were isolated from New Zealand White rabbits, cultured in vitro and seeded into the scaffolds. Bone regenerations of the subchondral phases were quantified via micro CT analysis and the results demonstrated the potential of the porous PCL and PCL-TCP scaffolds in promoting bone healing. Fibrin was found to be lacking in this aspect as it degrades rapidly. On the other hand, the porous PCL scaffold degrades slowly hence it provides an effective mechanical support. This study shows that in the field of cartilage repair or replacement, tissue engineering may have big impact in the future. In vivo bone and cartilage engineering via combining a novel composite, biphasic scaffold technology with a MSC has been shown a high potential in the knee defect regeneration in the animal models. However, the clinical application of tissue engineering requires the future research work due to several problems, such as scaffold design, cellular delivery and implantation strategies.

Metallic glass fiber-reinforced Zr-based bulk metallic glass

A novel Zr-based bulk metallic glass composite was fabricated using stainless steel capillaries as the reinforcement. Large plasticity (14%) was achieved in the composite with a reinforcement volume fraction of 38%. The high plasticity observed can be attributed to the formation of small glass fibers encapsulated by the steel capillaries, which promotes multiple shear bands in both metallic glass matrix and the fibers themselves. A new parameter was also proposed to approximately evaluate the reinforcement efficiency.

Axial elongation following prolonged near work in myopes and emmetropes

Background/aims: To investigate the influence of a period of sustained near work upon axial length in groups of emmetropes and myopes. Methods: Forty young adult subjects (20 myopes and 20 emmetropes) were recruited for the study. Myopes were further classified as either early onset (EOM), late onset (LOM), stable (SM) or progressing (PM) subgroups. Axial length was measured with the IOLMaster instrument before, immediately after and then again 10 minutes after a continuous 30 minute near task of 5 D accommodation demand. Measures of distance objective refraction were also collected. Results: Significant changes in axial length were observed immediately following the near task. EOM axial length elongated on average by 0.027 ± 0.021 mm, LOM by 0.014 ± 0.020 mm, EMM by 0.010 ± 0.015 mm, PM by 0.031 ± 0.022 mm, and SM by 0.014 ± 0.018 mm. At the conclusion of the 10 minute regression period, axial length measures were not significantly different from baseline values. Conclusion: Axial elongation was observed following a prolonged near task. Both EOM and PM groups showed increases in axial length that were significantly greater than emmetropes

Cigarette smoking in young adults : the influence of the HTR2A T102C polymorphism and punishment sensitivity

Background: The C allele of a common polymorphism of the serotonin 2A receptor (HTR2A) gene, T102C, results in reduced synthesis of 5-HT2A receptors and has been associated with current smoking status in adults. The -1438A/G polymorphism, located in the regulatory region of this gene, is in linkage disequilibrium with T102C, and the A allele is associated with increased promoter activity and with smoking in adult males. We investigated the contributions of the HTR2A gene, chronic psychological stress, and impulsivity to the prediction of cigarette smoking status and dependence in young adults. Methods: T102C and -1438A/G genotyping was conducted on 132 healthy Caucasian young adults (47 smokers) who completed self-report measures of chronic stress, depressive symptoms, impulsive personality and cigarette use. Results: A logistic regression analysis of current cigarette smoker user status, after adjusting for gender, depressive symptom severity and chronic stress, indicated that the T102C TT genotype relative to the CC genotype (OR = 7.53), and lower punishment sensitivity (OR = 0.91) were each significant predictive risk factors. However, for number of cigarettes smoked, only lower punishment sensitivity was a significant predictor (OR = 0.81). Conclusions: These data indicate the importance of the T102C polymorphism to tobacco use but not number of cigarettes smoked for Caucasian young adults. Future studies should examine whether this is explained by effects of nicotine on the serotonin system. Lower punishment sensitivity increased risk of both smoking and of greater consumption, perhaps via a reduced sensitivity to cigarette health warnings and negative physiological effects.

Strengthening of circular hollow steel tubular sections using high modulus CFRP sheets

This paper describes the behaviour of very high strength (VHS) circular steel tubes strengthened by carbon fibre reinforced polymer (CFRP) and subjected to axial tension. A series of tests were conducted with different bond lengths and number of layers. The distribution of strain through the thickness of CFRP layers and along CFRP bond length was studied. The strain was found to generally decrease along the CFRP bond length far from the joint. The strain through the thickness of the CFRP layers was also found to decrease from bottom to top layer. The effective bond length for high modulus CFRP was established. Finally empirical models were developed to estimate the maximum load for a given CFRP arrangement.

Less food for thought : impact of attentional instructions on intrusive thoughts about snack foods

Intrusive thoughts about food may play a role in unhealthy eating behaviours. Food-related thoughts that capture attention can lead to craving and further intrusive thoughts (Kavanagh, Andrade, & May, 2005). We tested whether diverting attention to mental images or bodily sensations would reduce the incidence of intrusive thoughts about snack foods. In two experiments, participants reported their thoughts in response to probes during three 10 min periods. In the Baseline and Post-task period, participants were asked to let their mind wander. In the middle, Experimental, period, participants followed mind wandering (Control), thought diversion, or Thought Suppression instructions. Self-directed or Guided Imagery, Mindfulness-based Body Scanning, and Thought Suppression all reduced the proportion of thoughts about food, compared to Baseline. Following Body Scanning and Thought Suppression, food thoughts returned to Baseline frequencies Post-task, rather than rebounding. There were no effects of the interventions upon craving, although overall, craving and thought frequency were correlated. Thought control tasks may help people to ignore thoughts about food and thereby reduce their temptation to snack.

Structure of selected basic zinc/copper (II) phosphate minerals based upon near-infrared spectroscopy : implications for hydrogen bonding

The NIR spectra of reichenbachite, scholzite and parascholzite have been studied at 298 K. The spectra of the minerals are different, in line with composition and crystal structural variations. Cation substitution effects are significant in their electronic spectra and three distinctly different electronic transition bands are observed in the near-infrared spectra at high wavenumbers in the 12000-7600 cm-1 spectral region. Reichenbachite electronic spectrum is characterised by Cu(II) transition bands at 9755 and 7520 cm-1. A broad spectral feature observed for ferrous ion in the 12000-9000 cm-1 region both in scholzite and parascholzite. Some what similarities in the vibrational spectra of the three phosphate minerals are observed particularly in the OH stretching region. The observation of strong band at 5090 cm-1 indicates strong hydrogen bonding in the structure of the dimorphs, scholzite and parascholzite. The three phosphates exhibit overlapping bands in the 4800-4000 cm-1 region resulting from the combinations of vibrational modes of (PO4)3- units.

An enriched radial point interpolation method (e-RPIM) for analysis of crack tip fields

In this paper, an enriched radial point interpolation method (e-RPIM) is developed the for the determination of crack tip fields. In e-RPIM, the conventional RBF interpolation is novelly augmented by the suitable trigonometric basis functions to reflect the properties of stresses for the crack tip fields. The performance of the enriched RBF meshfree shape functions is firstly investigated to fit different surfaces. The surface fitting results have proven that, comparing with the conventional RBF shape function, the enriched RBF shape function has: (1) a similar accuracy to fit a polynomial surface; (2) a much better accuracy to fit a trigonometric surface; and (3) a similar interpolation stability without increase of the condition number of the RBF interpolation matrix. Therefore, it has proven that the enriched RBF shape function will not only possess all advantages of the conventional RBF shape function, but also can accurately reflect the properties of stresses for the crack tip fields. The system of equations for the crack analysis is then derived based on the enriched RBF meshfree shape function and the meshfree weak-form. Several problems of linear fracture mechanics are simulated using this newlydeveloped e-RPIM method. It has demonstrated that the present e-RPIM is very accurate and stable, and it has a good potential to develop a practical simulation tool for fracture mechanics problems.

Dysbindin (DTNBP1) : a role in psychotic depression?

Previous studies yielded evidence for dysbindin (DTNBP1) to impact the pathogenesis of schizophrenia on the one hand and affective disorders such as bipolar or major depressive disorder (MDD) on the other. Thus, in the present study we investigated whether DTNBP1 variation was associated with psychotic depression as a severe clinical manifestation of MDD possibly constituting an overlapping phenotype between affective disorders and schizophrenia. A sample of 243 Caucasian inpatients with MDD (SCID-I) was genotyped for 12 SNPs spanning 92% of the DTNBP1 gene region. Differences in DTNBP1 genotype distributions across diagnostic subgroups of psychotic (N = 131) vs. non-psychotic depression were estimated by Pearson Chi2 test and logistic regression analyses adjusted for age, gender, Beck Depression Inventory (BDI) and the Global Assessment of Functioning Scale (GAF). Overall, patients with psychotic depression presented with higher BDI and lower GAF scores expressing a higher severity of the illness as compared to depressed patients without psychotic features. Four DTNBP1 SNPs, particularly rs1997679 and rs9370822, and the corresponding haplotypes, respectively, were found to be significantly associated with the risk of psychotic depression in an allele-dose fashion. In summary, the present results provide preliminary support for dysbindin (DTNBP1) gene variation, particularly SNPs rs1997679 and rs9370822, to be associated with the clinical phenotype of psychotic depression suggesting a possible neurobiological mechanism for an intermediate trait on the continuum between affective disorders and schizophrenia.

The effects of ambulance ramping on Emergency Department length of stay and mortality

Background: Ambulance ramping within the Emergency Department (ED) is a common problem both internationally and in Australia. Previous research has focused on various issues associated with ambulance ramping such as access block, ED overcrowding and ambulance bypass. However, limited research has been conducted on ambulance ramping and its effects on patient outcomes. ----- ----- Methods: A case-control design was used to describe, compare and predict patient outcomes of 619 ramped (cases) vs. 1238 non-ramped (control) patients arriving to one ED via ambulance from 1 June 2007 to 31 August 2007. Cases and controls were matched (on a 1:2 basis) on age, gender and presenting problem. Outcome measures included ED length of stay and in-hospital mortality. ----- ----- Results: The median ramp time for all 1857 patients was 11 (IQR 6—21) min. Compared to nonramped patients, ramped patients had significantly longer wait time to be triaged (10 min vs. 4 min). Ramped patients also comprised significantly higher proportions of those access blocked (43% vs. 34%). No significant difference in the proportion of in-hospital deaths was identified (2%vs. 3%). Multivariate analysis revealed that the likelihood of having an ED length of stay greater than eight hours was 34% higher among patients who were ramped (OR 1.34, 95% CI 1.06—1.70, p = 0.014). In relation to in-hospital mortality age was the only significant independent predictor of mortality (p < 0.0001). ----- ----- Conclusion: Ambulance ramping is one factor that contributes to prolonged ED length of stay and adds additional strain on ED service provision. The potential for adverse patient outcomes that may occur as a result of ramping warrants close attention by health care service providers.