Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Persistent Chlamydia Pneumoniae serology is related to decline in lung function in women but not in men. Effect of persistent Chlamydia pneumoniae infection on lung function

<p>Abstract</p> <p>Background</p> <p><it>Chlamydia pneumoniae </it>(C pn) infection causes an acute inflammation in the respiratory system that may become persistent, but little is known about the long-term respiratory effects of C pn infections. Aim: To estimate the long term respiratory effects of C pn with change in forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) as a main outcome variable.</p> <p>Methods</p> <p>The study comprised of 1109 subjects (500 men and 609 women, mean age 28 ± 6 years) that participated in the Reykjavik Heart Study of the Young. Spirometry and blood samples for measurements of IgG antibodies for C pn were done at inclusion and at the end of the follow-up period (mean follow-up time 27 ± 4 years).</p> <p>Results</p> <p>Having IgG against C pn at both examinations was significantly associated to a larger decrease in FEV₁(6 mL/year) and FVC (7 mL/year) in women but not in men. In women the association between C pn and larger FEV₁decline was only found in women that smoked at baseline where having C pn IgG was associated with 10 mL/year decline compared to smokers without C pn IgG. These results were still significant after adjustment for age, smoking and change in body weight.</p> <p>Conclusion</p> <p>Our results indicate that persistent C pn serology is related to increased decline in lung function in women but not in men. This effect was, however, primarily found in smoking women. This study is a further indication that the pathophysiological process leading to lung impairment may differ between men and women.</p

Chlamydophila pneumoniae induces a sustained airway hyperresponsiveness and inflammation in mice

Background: It has been reported that Chlamydophila (C.) pneumoniae is involved in the initiation and promotion of asthma and chronic obstructive pulmonary diseases (COPD). Surprisingly, the effect of C. pneumoniae on airway function has never been investigated.Methods: In this study, mice were inoculated intranasally with C. pneumoniae (strain AR39) on day 0 and experiments were performed on day 2, 7, 14 and 21.Results: We found that from day 7, C. pneumoniae infection causes both a sustained airway hyperresponsiveness and an inflammation. Interferon-γ (IFN-γ) and macrophage inflammatory chemokine-2 (MIP-2) levels in bronchoalveolar lavage (BAL)-fluid were increased on all experimental days with exception of day 7 where MIP-2 concentrations dropped to control levels. In contrast, tumor necrosis factor-α (TNF-α) levels were only increased on day 7. From day 7 to 21 epithelial damage and secretory cell hypertrophy was observed. It is suggested that, the inflammatory cells/mediators, the epithelial damage and secretory cell hypertrophy contribute to initiation of airway hyperresponsiveness.Conclusion: Our study demonstrates for the first time that C. pneumoniae infection can modify bronchial responsiveness. This has clinical implications, since additional changes in airway responsiveness and inflammation-status induced by this bacterium may worsen and/or provoke breathlessness in asthma and COPD

Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP

Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure

Evidence for the adaptation of protein pH-dependence to subcellular pH

<p>Abstract</p> <p>Background</p> <p>The availability of genome sequences, and inferred protein coding genes, has led to several proteome-wide studies of isoelectric points. Generally, isoelectric points are distributed following variations on a biomodal theme that originates from the predominant acid and base amino acid sidechain pKas. The relative populations of the peaks in such distributions may correlate with environment, either for a whole organism or for subcellular compartments. There is also a tendency for isoelectric points averaged over a subcellular location to not coincide with the local pH, which could be related to solubility. We now calculate the correlation of other pH-dependent properties, calculated from 3D structure, with subcellular pH.</p> <p>Results</p> <p>For proteins with known structure and subcellular annotation, the predicted pH at which a protein is most stable, averaged over a location, gives a significantly better correlation with subcellular pH than does isoelectric point. This observation relates to the cumulative properties of proteins, since maximal stability for individual proteins follows the bimodal isoelectric point distribution. Histidine residue location underlies the correlation, a conclusion that is tested against a background of proteins randomised with respect to this feature, and for which the observed correlation drops substantially.</p> <p>Conclusion</p> <p>There exists a constraint on protein pH-dependence, in relation to the local pH, that is manifested in the pKa distribution of histidine sub-proteomes. This is discussed in terms of protein stability, pH homeostasis, and fluctuations in proton concentration.</p

A CLINICAL STUDY OF INHALANT ANAESTHESIA IN DOGS

A clinical trial was undertaken using three different inhalant anaesthetic agents and one intravenous anaesthetic agent in dogs undergoing routine desexing surgery. Healthy adult dogs undergoing either ovariohysterectomy or castration were assessed as to their demeanour, with the more excitable dogs being placed in groups receiving premedication with acepromazine and morphine. All dogs were then randomly assigned an anaesthetic agent for induction of general anaesthesia. The agents were the inhalants halothane, isoflurane and sevoflurane, and the intravenous agent propofol. Inhalant inductions were undertaken using a tight fitting mask attached to a standard anaesthetic machine with a rebreathing circuit, with the maximum dose of inhalant available from a standard vaporiser. Propofol inductions were undertaken via intravenous catheter. Dogs induced with propofol were randomly assigned one of the three inhalant agents for maintenance. Those induced by inhalant agent were maintained using the same agent. The surgical procedure was undertaken in standard fashion, as was recovery from anaesthesia. All dogs received the non-steroidal anti-inflammatory agent meloxicam. Data collection was divided into three stages: induction, maintenance, and recovery from anaesthesia. Variables measured at induction of anaesthesia were time to intubation, number of intubation attempts, tolerance of mask, quality of induction and quality of transfer to the maintenance stage. Standard variables for monitoring of anaesthesia were recorded throughout the maintenance of anaesthesia. Variables measured at recovery were time to righting, time to standing and quality of recovery. The mean time to intubation when using the newer inhalant sevoflurane (196.2 ± 14.8sec, mean ± SE) was not significantly different to that for halothane (221.4 ± 14.0sec) or isoflurane (172.4 ± 15.0sec). Time to intubation with isoflurane was significantly faster than with halothane. Mean time to intubation with propofol (85.4 ± 7.7sec) was significantly faster than that for any of the three inhalants. Choice of inhalant had no effect on quality of induction. The use of premedication significantly improved the quality of induction. The use of propofol for induction likewise significantly improved the quality of induction. Standard cardiorespiratory variables measured during the maintenance phase of anaesthesia remained within normal clinical ranges for all three inhalants, and were therefore not further analysed. Choice of inhalant agent had no significant effect on the time to righting or standing in recovery. The use of propofol for induction had no effect on these variables. Animals placed in groups receiving premedication had significantly longer times to righting and standing. The oesophageal temperature at the end of the procedure had a significant effect on times to righting and standing, with lower temperatures contributing to slower recoveries. Independent of procedure time, male dogs had shorter times to righting than female dogs

Time spent on work-related activities, social activities and time pressure as intermediary determinants of health disparities among elderly women and men in 5 European countries: a structural equation model

Background Psychosocial factors shape the health of older adults through complex inter-relating pathways. Besides socioeconomic factors, time use activities may explain gender inequality in self-reported health. This study investigated the role of work-related and social time use activities as determinants of health in old age. Specifically, we analysed whether the impact of stress in terms of time pressure on health mediated the relationship between work-related time use activities (i.e. housework and paid work) on self-reported health. Methods We applied structural equation models and a maximum-likelihood function to estimate the direct and indirect effects of psychosocial factors on health using pooled data from the Multinational Time Use Study on 11,168 men and 14,295 women aged 65+ from Italy, Spain, UK, France and the Netherlands. Results The fit indices for the conceptual model indicated an acceptable fit for both men and women. The results showed that socioeconomic status (SES), demographic factors, stress and work-related time use activities after retirement had a significant direct influence on self-reported health among the elderly, but the magnitude of the effects varied by gender. Social activities had a positive impact on self-reported health but had no significant impact on stress among older men and women. The indirect standardized effects of work-related activities on self-reported health was statistically significant for housework (β = − 0.006; P  0.05 among women), which implied that the paths from paid work and housework on self-reported health via stress (mediator) was very weak because their indirect effects were close to zero. Conclusions Our findings suggest that although stress in terms of time pressure has a direct negative effect on health, it does not indirectly influence the positive effects of work-related time use activities on self-reported health among elderly men and women. The results support the time availability hypothesis that the elderly may not have the same time pressure as younger adults after retirement

Uniform Selection as a Primary Force Reducing Population Genetic Differentiation of Cavitation Resistance across a Species Range

Background: Cavitation resistance to water stress-induced embolism determines plant survival during drought. This adaptive trait has been described as highly variable in a wide range of tree species, but little is known about the extent of genetic and phenotypic variability within species. This information is essential to our understanding of the evolutionary forces that have shaped this trait, and for evaluation of its inclusion in breeding programs. Methodology: We assessed cavitation resistance (P 50), growth and carbon isotope composition in six Pinus pinaster populations in a provenance and progeny trial. We estimated the heritability of cavitation resistance and compared the distribution of neutral markers (FST) and quantitative genetic differentiation (QST), for retrospective identification of the evolutionary forces acting on these traits. Results/Discussion: In contrast to growth and carbon isotope composition, no population differentiation was found for cavitation resistance. Heritability was higher than for the other traits, with a low additive genetic variance (h 2 ns = 0.4360.18, CVA = 4.4%). QST was significantly lower than FST, indicating uniform selection for P50, rather than genetic drift. Putativ