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

Bright Field Microscopy as an Alternative to Whole Cell Fluorescence in Automated Analysis of Macrophage Images

Fluorescence microscopy is the standard tool for detection and analysis of cellular phenomena. This technique, however, has a number of drawbacks such as the limited number of available fluorescent channels in microscopes, overlapping excitation and emission spectra of the stains, and phototoxicity.We here present and validate a method to automatically detect cell population outlines directly from bright field images. By imaging samples with several focus levels forming a bright field -stack, and by measuring the intensity variations of this stack over the -dimension, we construct a new two dimensional projection image of increased contrast. With additional information for locations of each cell, such as stained nuclei, this bright field projection image can be used instead of whole cell fluorescence to locate borders of individual cells, separating touching cells, and enabling single cell analysis. Using the popular CellProfiler freeware cell image analysis software mainly targeted for fluorescence microscopy, we validate our method by automatically segmenting low contrast and rather complex shaped murine macrophage cells.The proposed approach frees up a fluorescence channel, which can be used for subcellular studies. It also facilitates cell shape measurement in experiments where whole cell fluorescent staining is either not available, or is dependent on a particular experimental condition. We show that whole cell area detection results using our projected bright field images match closely to the standard approach where cell areas are localized using fluorescence, and conclude that the high contrast bright field projection image can directly replace one fluorescent channel in whole cell quantification. Matlab code for calculating the projections can be downloaded from the supplementary site: http://sites.google.com/site/brightfieldorstaining

Evaluation of methods for detection of fluorescence labeled subcellular objects in microscope images

<p>Abstract</p> <p>Background</p> <p>Several algorithms have been proposed for detecting fluorescently labeled subcellular objects in microscope images. Many of these algorithms have been designed for specific tasks and validated with limited image data. But despite the potential of using extensive comparisons between algorithms to provide useful information to guide method selection and thus more accurate results, relatively few studies have been performed.</p> <p>Results</p> <p>To better understand algorithm performance under different conditions, we have carried out a comparative study including eleven spot detection or segmentation algorithms from various application fields. We used microscope images from well plate experiments with a human osteosarcoma cell line and frames from image stacks of yeast cells in different focal planes. These experimentally derived images permit a comparison of method performance in realistic situations where the number of objects varies within image set. We also used simulated microscope images in order to compare the methods and validate them against a ground truth reference result. Our study finds major differences in the performance of different algorithms, in terms of both object counts and segmentation accuracies.</p> <p>Conclusions</p> <p>These results suggest that the selection of detection algorithms for image based screens should be done carefully and take into account different conditions, such as the possibility of acquiring empty images or images with very few spots. Our inclusion of methods that have not been used before in this context broadens the set of available detection methods and compares them against the current state-of-the-art methods for subcellular particle detection.</p

The clinical course of low back pain: a meta-analysis comparing outcomes in randomised clinical trials (RCTs) and observational studies.

BACKGROUND: Evidence suggests that the course of low back pain (LBP) symptoms in randomised clinical trials (RCTs) follows a pattern of large improvement regardless of the type of treatment. A similar pattern was independently observed in observational studies. However, there is an assumption that the clinical course of symptoms is particularly influenced in RCTs by mere participation in the trials. To test this assumption, the aim of our study was to compare the course of LBP in RCTs and observational studies. METHODS: Source of studies CENTRAL database for RCTs and MEDLINE, CINAHL, EMBASE and hand search of systematic reviews for cohort studies. Studies include individuals aged 18 or over, and concern non-specific LBP. Trials had to concern primary care treatments. Data were extracted on pain intensity. Meta-regression analysis was used to compare the pooled within-group change in pain in RCTs with that in cohort studies calculated as the standardised mean change (SMC). RESULTS: 70 RCTs and 19 cohort studies were included, out of 1134 and 653 identified respectively. LBP symptoms followed a similar course in RCTs and cohort studies: a rapid improvement in the first 6 weeks followed by a smaller further improvement until 52 weeks. There was no statistically significant difference in pooled SMC between RCTs and cohort studies at any time point:- 6 weeks: RCTs: SMC 1.0 (95% CI 0.9 to 1.0) and cohorts 1.2 (0.7to 1.7); 13 weeks: RCTs 1.2 (1.1 to 1.3) and cohorts 1.0 (0.8 to 1.3); 27 weeks: RCTs 1.1 (1.0 to 1.2) and cohorts 1.2 (0.8 to 1.7); 52 weeks: RCTs 0.9 (0.8 to 1.0) and cohorts 1.1 (0.8 to 1.6). CONCLUSIONS: The clinical course of LBP symptoms followed a pattern that was similar in RCTs and cohort observational studies. In addition to a shared 'natural history', enrolment of LBP patients in clinical studies is likely to provoke responses that reflect the nonspecific effects of seeking and receiving care, independent of the study design

Chick Embryo Partial Ischemia Model: A New Approach to Study Ischemia Ex Vivo

Background: Ischemia is a pathophysiological condition due to blockade in blood supply to a specific tissue thus damaging the physiological activity of the tissue. Different in vivo models are presently available to study ischemia in heart and other tissues. However, no ex vivo ischemia model has been available to date for routine ischemia research and for faster screening of anti-ischemia drugs. In the present study, we took the opportunity to develop an ex vivo model of partial ischemia using the vascular bed of 4th day incubated chick embryo. Methodology/Principal Findings: Ischemia was created in chick embryo by ligating the right vitelline artery using sterile surgical suture. Hypoxia inducible factor- 1 alpha (HIF-1a), creatine phospho kinase-MB and reactive oxygen species in animal tissues and cells were measured to confirm ischemia in chick embryo. Additionally, ranolazine, N-acetyl cysteine and trimetazidine were administered as an anti-ischemic drug to validate the present model. Results from the present study depicted that blocking blood flow elevates HIF-1a, lipid peroxidation, peroxynitrite level in ischemic vessels while ranolazine administration partially attenuates ischemia driven HIF-1a expression. Endothelial cell incubated on ischemic blood vessels elucidated a higher level of HIF-1a expression with time while ranolazine treatment reduced HIF-1a in ischemic cells. Incubation of caprine heart strip on chick embryo ischemia model depicted an elevated creatine phospho kinase-MB activity under ischemic condition while histology of the treated heart sections evoked edema and disruption of myofibril structures. Conclusions/Significance: The present study concluded that chick embryo partial ischemia model can be used as a novel ex vivo model of ischemia. Therefore, the present model can be used parallel with the known in vivo ischemia models in understanding the mechanistic insight of ischemia development and in evaluating the activity of anti-ischemic drug.status: publishe

Genome-Wide Analysis of Effectors of Peroxisome Biogenesis

Peroxisomes are intracellular organelles that house a number of diverse metabolic processes, notably those required for β-oxidation of fatty acids. Peroxisomes biogenesis can be induced by the presence of peroxisome proliferators, including fatty acids, which activate complex cellular programs that underlie the induction process. Here, we used multi-parameter quantitative phenotype analyses of an arrayed mutant collection of yeast cells induced to proliferate peroxisomes, to establish a comprehensive inventory of genes required for peroxisome induction and function. The assays employed include growth in the presence of fatty acids, and confocal imaging and flow cytometry through the induction process. In addition to the classical phenotypes associated with loss of peroxisomal functions, these studies identified 169 genes required for robust signaling, transcription, normal peroxisomal development and morphologies, and transmission of peroxisomes to daughter cells. These gene products are localized throughout the cell, and many have indirect connections to peroxisome function. By integration with extant data sets, we present a total of 211 genes linked to peroxisome biogenesis and highlight the complex networks through which information flows during peroxisome biogenesis and function

Sodium reduction in cooked meat products by using commercial potassium phosphate mixtures

In addition to salt (NaCl), sodium phosphate also increases the sodium content of meat products. Thus, the effects of replacing sodium phosphate with potassium phosphate on sodium content and properties of low-salt cooked bologna-type sausage and cooked ham were studied. Four sausage formulations were prepared. In formulations 1 and 2, the target sodium content was 0.55 g Na/100 g, and in recipes 3 and 4, 0.63 g Na/100 g. The salt content in formulation 2 was the same as in formulation 3, namely 1.2% NaCl, but the sodium content in the former was lower. In the cooked hams of recipes 1 and 2, the salt content was 1.4%, and in recipes 3 and 4, 1.8%. Sodium phosphate was used in recipes 1 and 3, and potassium phosphate in recipes 2 and 4. Very low-salt (i.e. 1.0-1.4% NaCl) meat products can be prepared providing that phosphates are added. Further reduction of sodium content in low-salt meat products is possible by replacing sodium phosphate with potassium phosphate. The extent of sodium reduction depends on the phosphates used and their sodium content, being equivalent to a sodium content of 0.2% NaCl or more. The replacement resulted in no adverse effects. Alkaline phosphates are also recommended in very low-salt products to minimize risk of purge.Suolan lisäksi natriumfosfaatti suurentaa lihavalmisteiden natriumpitoisuutta. Useat natriumfosfaatit sisältävät 30 % natriumia. Tämän vuoksi tutkimuksessa selvitettiin, miten natriumfosfaatin korvaaminen kaliumfosfaatilla vaikuttaa leikkelemakkaran ja kinkkuleikkeen ominaisuuksiin. Tutkimuksessa valmistettiin neljä erilaista leikkelemakkaramassaa normaalia pienemmällä suolapitoisuudella. Massoissa 1 ja 2 tavoitenatriumpitoisuus oli 0,55 g Na/100 g sekä massoissa 3 ja 4 0,63 g Na/100 g. Muista valmistusaineista kuin suolasta ja natriumfosfaatista tuleva natriumin määrä oli kaikissa resepteissä sama. Massoissa 1 ja 3 suolalisäykset olivat 1 ja 1,2 %, ja fosfaattina käytettiin natriumfosfaattia. Massoissa 2 ja 4 suolalisäykset olivat 1,2 ja 1,4 % NaCl, ja fosfaattina käytettiin kaliumfosfaattia, jonka pH oli korkeampi kuin käytetyn natriumfosfaatin.Tutkimuksessa valmistettiin myös neljä erilaista kinkkuleikettä. Kinkkuleikkeissä 1 ja 2 suolaa lisättiin 1,4 % ja kinkkuleikkeissä 3 ja 4 1,8 %. Kinkkuleikkeissä 1 ja 3 käytettiin natriumfosfaattia ja kinkkuleikkeissä 2 ja 4 kaliumfosfaattia, jonka pH arvo oli korkeampi kuin käytetyn natriumfosfaatin. Tutkimuksessa todettiin, että fosfaattia on käytettävä, jos lihavalmisteet valmistetaan hyvin pienillä suolapitoisuuksilla (1,0-1,4 % NaCl). Lihavalmisteiden natriumpitoisuutta voidaan pienentää korvaamalla natriumfosfaatti kaliumfosfaatilla. Tällä tavoin aikaansaatu natriumpitoisuuden pieneneminen vastaa samaa natriumin määrää, jonka 0,2 % NaCl sisältää. Kaliumfosfaatin ei todettu aiheuttavan haittavaikutuksia makkaraan eikä keittokinkkuun. Hyvin pienen natriumpitoisuuden tuotteissa suositellaan käytettäväksi emäksistä kaliumfosfaattia, joka parantaa tuotteen vedensidontakykyä ja siten varmistaa hyvän rakenteen

Sodium reduction in cooked meat products by using commercial potassium phosphate mixtures

In addition to salt (NaCl), sodium phosphate also increases the sodium content of meat products. Thus, the effects of replacing sodium phosphate with potassium phosphate on sodium content and properties of low-salt cooked bologna-type sausage and cooked ham were studied. Four sausage formulations were prepared. In formulations 1 and 2, the target sodium content was 0.55 g Na/100 g, and in recipes 3 and 4, 0.63 g Na/100 g. The salt content in formulation 2 was the same as in formulation 3, namely 1.2% NaCl, but the sodium content in the former was lower. In the cooked hams of recipes 1 and 2, the salt content was 1.4%, and in recipes 3 and 4, 1.8%. Sodium phosphate was used in recipes 1 and 3, and potassium phosphate in recipes 2 and 4. Very low-salt (i.e. 1.0-1.4% NaCl) meat products can be prepared providing that phosphates are added. Further reduction of sodium content in low-salt meat products is possible by replacing sodium phosphate with potassium phosphate. The extent of sodium reduction depends on the phosphates used and their sodium content, being equivalent to a sodium content of 0.2% NaCl or more. The replacement resulted in no adverse effects. Alkaline phosphates are also recommended in very low-salt products to minimize risk of purge