Sensory neuronal sensitisation occurs through HMGB-1/RAGE and TRPV1 in high glucose conditions

Many potential causes for painful diabetic neuropathy have been proposed including actions of cytokines and growth factors. High mobility group protein B1 (HMGB1) is a RAGE agonist, increased in diabetes, that contributes to pain by modulating peripheral inflammatory responses. HMGB1 enhances nociceptive behaviour in naïve animals through an unknown mechanism. We tested the hypothesis that HMGB1 causes pain through direct neuronal activation of RAGE and alteration of nociceptive neuronal responsiveness. HMGB1 and RAGE expression were increased in skin and primary sensory (DRG) neurons of diabetic rats at times when pain behaviour was enhanced. Agonist-evoked TRPV1-mediated calcium responses increased in cultured DRG neurons from diabetic rats and in neurons from naïve rats exposed to high glucose concentrations. HMGB1-mediated increases in TRPV1-evoked calcium responses in DRG neurons were RAGE and PKC-dependent, and this was blocked by co-administration of the growth factor splice variant, VEGF-A165b. Pain behaviour and DRG RAGE expression increases were blocked by VEGF-A 165 b treatment of diabetic rats in vivo. HMGB-1-RAGE activation sensitizes DRG neurons in vitro. VEGF-A165b blocks HMGB-1/RAGE DRG activation, which may contribute to its analgesic properties in vivo

A Development Environment for Visual Physics Analysis

The Visual Physics Analysis (VISPA) project integrates different aspects of physics analyses into a graphical development environment. It addresses the typical development cycle of (re-)designing, executing and verifying an analysis. The project provides an extendable plug-in mechanism and includes plug-ins for designing the analysis flow, for running the analysis on batch systems, and for browsing the data content. The corresponding plug-ins are based on an object-oriented toolkit for modular data analysis. We introduce the main concepts of the project, describe the technical realization and demonstrate the functionality in example applications

Understanding Face and Shame: A Servant-Leadership and Face Management Model

Clergy can have a negative impact on churches and other individuals when they knowingly or unknowingly attempt to save face, that is, try to protect their standing or reputation. The desire to gain face and the fear of losing face and feeling ashamed will likely permeate clergy’s decision-making processes without even being noticed. This study explores the essence of face and face management and the relationship between face management and two characteristics of servant-leadership—awareness and healing—in both Chinese and American churches through the methodology of hermeneutic phenomenology. Prior to this study, to my knowledge, no hermeneutic phenomenological research of face management has been conducted in a church setting. Through a review of the literature, four areas are explored: face and shame, face management, servant-leadership, and face, shame, and face management within the church. This study obtained approval from the Institutional Review Board and informed consent from the participants. Three Chinese and three American Christian ministers were chosen to complete a question sheet and participate in two semi-structured interview sessions. A first cycle of open coding and second cycle of pattern coding were used during data analysis. Face experiences are discussed in light of eight major themes: body, triggers, becoming, face concepts, strategies, emotions, servant-leadership, and the church. Findings from the study help build a servant-leadership and face management model, which can offer an anchored approach for clergy and pastoral counselors to address face and shame and to develop therapeutic interventions

A variational method based on weighted graph states

In a recent article [Phys. Rev. Lett. 97 (2006), 107206], we have presented a class of states which is suitable as a variational set to find ground states in spin systems of arbitrary spatial dimension and with long-range entanglement. Here, we continue the exposition of our technique, extend from spin 1/2 to higher spins and use the boson Hubbard model as a non-trivial example to demonstrate our scheme.Comment: 36 pages, 13 figure

Identification of new susceptibility loci for osteoarthritis (arcOGEN):a genome-wide association study

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.Arthritis Research UK 1803

Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients manuscript id: 8962091628764582

BACKGROUND: The inactivation of the tumour suppressor gene and activation of the proto-oncogene are the key steps in the development of the human cancer. The p53 and c-erbB-2 are the best examples of it. In the present study, our aim was to determine the role of these genes in the carcinogenesis of gallbladder by immunohistochemistry. METHODS: In all 78 consecutive patients of gall bladder diseases were studied for p53 and c-erbB-2 expression immunohistochemically and their expression was correlated with the age, grades and stages of the disease and presence of stone. An informed consent was obtained in each case. Chi square and z test were applied to see the association of p53 and c-erbB-2 over expression with other clinicopathological factors. RESULTS: Eight (20%) patients of gall bladder cancer were positive for p53 expression and 10 (25%) patients for c-erbB-2. The p53 positivity increased with increasing grade while cerbB-2 positivity decreased with increasing grade of gall bladder cancer. Mean age in cerbB-2 positive cases were lesser as compared to negative cases while p53 did not show such association with age. CONCLUSION: Only one case of gall bladder cancer co-expressed the p53 and c-erbB-2, thereby suggesting that p53 and c-erbB-2 may have independent role in carcinogenesis of gall bladder cancer. c-erbB-2 over expression in adenoma and younger age group indicates its role as an early event in carcinogenesis of gallbladder. However study of larger sample is required to further validate the results

‘Where we stayed was very bad …’: migrant children’s perspectives on life in informal rented accommodation in two southern African cities

Most research and initiatives relating to children's experiences of urban space have focused on the physical environment. Housing policies in Third World countries have also emphas- ised the provision of physical infrastructure and buildings, and urban aesthetics. In this paper the authors draw on the voices of young informants from Maseru (Lesotho), and Blantyre (Malawi), who, in discussions concerning moving house, chose to talk about social and economic aspects of life in the informal sector rented accommodation that is increasingly characteristic of these and many other African cities. The children offer insight into the peopling of urban space, mapping unruly environments characterised by disorder, gossip, and social contestation, far removed from the hard technocratic spaces imagined by planners. Their observations are important not only because children represent a very large and relatively neglected proportion of African urban dwellers but also because they offer a unique insight into the dynamic character of urban environments. As close observers of adult decisionmaking processes, children are informed commentators on motivations for moving house as well as the impacts of urban environments on their own lives. Not only do the children highlight the inadequacies of the informal private rental sector but they also offer a window onto why it is inadequate

Inducing mineral precipitation in groundwater by addition of phosphate

<p>Abstract</p> <p>Background</p> <p>Induced precipitation of phosphate minerals to scavenge trace elements from groundwater is a potential remediation approach for contaminated aquifers. The success of engineered precipitation schemes depends on the particular phases generated, their rates of formation, and their long term stability. The purpose of this study was to examine the precipitation of calcium phosphate minerals under conditions representative of a natural groundwater. Because microorganisms are present in groundwater, and because some proposed schemes for phosphate mineral precipitation rely on stimulation of native microbial populations, we also tested the effect of bacterial cells (initial densities of 10⁵and 10⁷mL^-1) added to the precipitation medium. In addition, we tested the effect of a trace mixture of propionic, isovaleric, formic and butyric acids (total concentration 0.035 mM).</p> <p>Results</p> <p>The general progression of mineral precipitation was similar under all of the study conditions, with initial formation of amorphous calcium phosphate, and transformation to poorly crystalline hydroxylapatite (HAP) within one week. The presence of the bacterial cells appeared to delay precipitation, although by the end of the experiments the overall extent of precipitation was similar for all treatments. The stoichiometry of the final precipitates as well as Rietveld structure refinement using x-ray diffraction data indicated that the presence of organic acids and bacterial cells resulted in an increasing <it>a </it>and decreasing <it>c </it>lattice parameter, with the higher concentration of cells resulting in the greatest distortion. Uptake of Sr into the solids was decreased in the treatments with cells and organic acids, compared to the control.</p> <p>Conclusions</p> <p>Our results suggest that the minerals formed initially during an engineered precipitation application for trace element sequestration may not be the ones that control long-term immobilization of the contaminants. In addition, the presence of bacterial cells appears to be associated with delayed HAP precipitation, changes in the lattice parameters, and reduced incorporation of trace elements as compared to cell-free systems. Schemes to remediate groundwater contaminated with trace metals that are based on enhanced phosphate mineral precipitation may need to account for these phenomena, particularly if the remediation approach relies on enhancement of <it>in situ </it>microbial populations.</p

Using motivational techniques to reduce cardiometabolic risk factors in long term psychiatric inpatients: A naturalistic interventional study

Background People with severe mental illness have markedly reduced life expectancy; cardiometabolic disease is a major cause. Psychiatric hospital inpatients have elevated levels of cardiometabolic risk factors and are to a high degree dependent of the routines and facilities of the institutions. Studies of lifestyle interventions to reduce cardiometabolic risk in psychiatric inpatients are few. The current study aimed at assessing the feasibility and effects of a lifestyle intervention including Motivational Interviewing (MI) on physical activity levels, cardiometabolic risk status and mental health status in psychotic disorder inpatients. Methods Prospective naturalistic intervention study of 83 patients at long term inpatient psychosis treatment wards in South-Eastern Norway. Patients were assessed 3–6 months prior to, at start and 6 months after a life-style intervention program including training of staff in MI, simple changes in routines and improvements of facilities for physical exercise. Assessments were done by clinical staff and included level of physical activity, motivation, life satisfaction, symptom levels (MADRS, AES-C, PANSS, and GAF) as well as anthropometric and biochemical markers of cardiometabolic risk. A mixed model was applied to analyze change over time. Results A total of 88% of patients received MI interventions, with a mean of 2.5 MI interventions per week per patient. The physical activity level was not increased, but activity level was positively associated with motivation and negatively associated with positive symptoms. Triglyceride levels and number of smokers were significantly reduced and a significant decrease in symptom levels was observed. Conclusions The current results suggest that a simple, low cost life-style intervention program focusing on motivational change is feasible and may reduce symptoms and improve lifestyle habits in psychosis patients in long term treatment facilities. Similar programs may easily be implemented in other psychiatric hospitals.submittedVersio