Psychological risk and protective factors for disability in chronic low back pain - a longitudinal analysis in primary care

Background: Utilizing psychological resources when dealing with chronic low back pain might aid the prevention of disability. The observational study at hand examined the longitudinal impact of resilience and coping resources on disability in addition to established risk factors. Methods: Four hundred eighty four patients with chronic low back pain (>3 months) were recruited in primary care practices and followed up for one year. Resilience, coping, depression, somatization, pain and demographic variables were measured at baseline. At follow-up (participation rate 89%), data on disability was collected. We first calculated bivariate correlations of all the predictors with each other and with follow-up disability. We then used a multiple regression to evaluate the impact of all the predictors on disability together. Results: More than half of the followed up sample showed a high degree of disability at baseline (53.7%) and had suffered for more than 10 years from pain (50.4%). Besides gender all of the predictors were bivariately associated with follow-up disability. However in the main analysis (multiple regression), disability at follow up was only predicted by baseline disability, age and somatization. There was no relationship between resilience and disability, nor between coping resources and disability. Conclusions: Although it is known that there are cross-sectional relationships between resilience/coping resources and disability we were not able to replicate it in the multiple regression. This can have several reasons: a) the majority of patients in our sample were much more disabled and suffered for a longer time than in other studies. Therefore our results might be limited to this specific population and resilience and coping resources might still have a protective influence in acute or subacute populations. b) We used a rather broad operationalization of resilience. There is emerging evidence that focusing on more concrete sub facets like (pain) self-efficacy and acceptance might be more beneficial

The permanently chaperone-active small heat shock protein Hsp17 from Caenorhabditis elegans exhibits topological separation of its N-terminal regions

Small Heat shock proteins (sHsps) are a family of molecular chaperones that bind nonnative proteins in an ATP-independent manner. Caenorhabditis elegans encodes 16 different sHsps, among them Hsp17, which is evolutionarily distinct from other sHsps in the nematode. The structure and mechanism of Hsp17 and how these may differ from other sHsps remain unclear. Here, we find that Hsp17 has a distinct expression pattern, structural organization, and chaperone function. Consistent with its presence under nonstress conditions, and in contrast to many other sHsps, we determined that Hsp17 is a mono-disperse, permanently active chaperone in vitro, which interacts with hundreds of different C. elegans proteins under physiological conditions. Additionally, our cryo-EM structure of Hsp17 reveals that in the 24-mer complex, 12 N-terminal regions are involved in its chaperone function. These flexible regions are located on the outside of the spherical oligomer, whereas the other 12 N-terminal regions are engaged in stabilizing interactions in its interior. This allows the same region in Hsp17 to perform different functions depending on the topological context. Taken together, our results reveal structural and functional features that further define the structural basis of permanently active sHsps

Monitoring of Gene Expression in Bacteria during Infections Using an Adaptable Set of Bioluminescent, Fluorescent and Colorigenic Fusion Vectors

A family of versatile promoter-probe plasmids for gene expression analysis was developed based on a modular expression plasmid system (pZ). The vectors contain different replicons with exchangeable antibiotic cassettes to allow compatibility and expression analysis on a low-, midi- and high-copy number basis. Suicide vector variants also permit chromosomal integration of the reporter fusion and stable vector derivatives can be used for in vivo or in situ expression studies under non-selective conditions. Transcriptional and translational fusions to the reporter genes gfpmut3.1, amCyan, dsRed2, luxCDABE, phoA or lacZ can be constructed, and presence of identical multiple cloning sites in the vector system facilitates the interchange of promoters or reporter genes between the plasmids of the series. The promoter of the constitutively expressed gapA gene of Escherichia coli was included to obtain fluorescent and bioluminescent expression constructs. A combination of the plasmids allows simultaneous detection and gene expression analysis in individual bacteria, e.g. in bacterial communities or during mouse infections. To test our vector system, we analyzed and quantified expression of Yersinia pseudotuberculosis virulence genes under laboratory conditions, in association with cells and during the infection process

Transitkunst. Studien zur Literatur 1890-2010

Die Chiffre „Transit“ vereinigt mit Aspekten wie Mobilität, Flüchtigkeit und Vorläufigkeit zentrale Begriffe des Zeiterlebens zwischen 1890 und 2010. Vor dem Hintergrund mehrerer Krisen und Katastrophen sowie tiefgreifender Umwandlungsprozesse erscheint das Leben als Durchgangsstadium, in dem sich nur noch ein temporäres, fragmentarisches Netz von Orientierungspunkten entwerfen lässt. Das Transitäre durchdringt nahezu alle Facetten des Individuums und seiner Lebensbereiche: vom Wahrnehmen der Inkohärenz in der Folge gesellschaftlicher Umwälzungen, über den Verlust ‚sicherer‘ Orte bis zum Erfahren der eigenen Identität als provisorisch. Die Reaktion auf solche Übergangszustände ist oft eine Intensivierung der Suchbewegungen nach Sicherheit, Nähe und Glück, die jedoch selbst zunehmend transitive Zwischenstellungen markieren. Die Literatur zeichnet sich unter dieser Perspektive durch die Adaptation transittypischer Themen und Inhalte aus, desgleichen durch die autoreflexive Übertragung von Konzepten wie Momenthaftigkeit, Unvollständigkeit und Flexibilität in das eigene narrative Programm. Die Beiträge des Bandes nähern sich verschiedenen Formen eines solchen inhaltlichen und/oder formalen ‚Dazwischen‘ an. Die Idee des Transits erweist sich dabei für diese vielfältigen literatur- und kulturwissenschaftlichen Untersuchungen als ebenso funktionale wie inspirierende Klammer, der es gelingt, im bewussten Einlassen auf das im Durchgang Begriffene die heterogenen Facetten des 20. Jahrhunderts zu verbinden: zu einer Art Zeitbild und Ästhetik des Transits

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Study protocol: Transition from localized low back pain to chronic widespread pain in general practice: identification of risk factors, preventive factors and key elements for treatment--a cohort study

Background Chronic localized pain syndromes, especially chronic low back pain (CLBP), are common reasons for consultation in general practice. In some cases chronic localized pain syndromes can appear in combination with chronic widespread pain (CWP). Numerous studies have shown a strong association between CWP and several physical and psychological factors. These studies are population-based cross-sectional and do not allow for assessing chronology. There are very few prospective studies that explore the predictors for the onset of CWP, where the main focus is identifying risk factors for the CWP incidence. Until now there have been no studies focusing on preventive factors keeping patients from developing CWP. Our aim is to perform a cross sectional study on the epidemiology of CLBP and CWP in general practice and to look for distinctive features regarding resources like resilience, self-efficacy and coping strategies. A subsequent cohort study is designed to identify the risk and protective factors of pain generalization (development of CWP) in primary care for CLBP patients. Methods/Design Fifty-nine general practitioners recruit consecutively, during a 5 month period, all patients who are consulting their family doctor because of chronic low back pain (where the pain is lasted for 3 months). Patients are asked to fill out a questionnaire on pain anamnesis, pain-perception, co-morbidities, therapy course, medication, socio demographic data and psychosomatic symptoms. We assess resilience, coping resources, stress management and self-efficacy as potential protective factors for pain generalization. Furthermore, we raise risk factors for pain generalization like anxiety, depression, trauma and critical life events. During a twelve months follow up period a cohort of CLBP patients without CWP will be screened on a regular basis (3 monthly) for pain generalization (outcome: incident CWP). Discussion This cohort study will be the largest study which prospectively analyzes predictors for transition from CLBP to CWP in primary care setting. In contrast to the typically researched risk factors, which increase the probability of pain generalization, this study also focus intensively on protective factors, which decrease the probability of pain generalization

Proteinaceous Transformers: Structural and Functional Variability of Human sHsps

The proteostasis network allows organisms to support and regulate the life cycle of proteins. Especially regarding stress, molecular chaperones represent the main players within this network. Small heat shock proteins (sHsps) are a diverse family of ATP-independent molecular chaperones acting as the first line of defense in many stress situations. Thereby, the promiscuous interaction of sHsps with substrate proteins results in complexes from which the substrates can be refolded by ATP-dependent chaperones. Particularly in vertebrates, sHsps are linked to a broad variety of diseases and are needed to maintain the refractive index of the eye lens. A striking key characteristic of sHsps is their existence in ensembles of oligomers with varying numbers of subunits. The respective dynamics of these molecules allow the exchange of subunits and the formation of hetero-oligomers. Additionally, these dynamics are closely linked to the chaperone activity of sHsps. In current models a shift in the equilibrium of the sHsp ensemble allows regulation of the chaperone activity, whereby smaller oligomers are commonly the more active species. Different triggers reversibly change the oligomer equilibrium and regulate the activity of sHsps. However, a finite availability of high-resolution structures of sHsps still limits a detailed mechanistic understanding of their dynamics and the correlating recognition of substrate proteins. Here we summarize recent advances in understanding the structural and functional relationships of human sHsps with a focus on the eye-lens &alpha;A- and &alpha;B-crystallins

Even worse — risk factors and protective factors for transition from chronic localized low back pain to chronic widespread pain in general practice

STUDY DESIGN: Prospective cohort study with patients with chronic low back pain (CLBP) at primary care setting. OBJECTIVE: The aim of our study was to identify predictors for transition from localized CLBP to chronic widespread pain in general practice. In contrast to the typically investigated risk factors, this study also focuses intensively on protective factors, which decrease the probability of chronic widespread pain. For this, we investigated the resources resilience and coping strategies, which are suspected as potential protective factors for incident chronic pain syndromes. SUMMARY OF BACKGROUND DATA: In primary care, about a quarter of patients with CLBP experience chronic widespread pain (CWP). METHODS: Patients experiencing localized CLBP were included and evaluated after a 6- and 12-month follow-up period regarding the development of CWP. Potential risk factors (sociodemographic data, pain characteristics, depression, anxiety, somatization), protective factors (resilience, coping strategies), and sample characteristics were assessed at baseline. Predictor identification was done by multivariate logistic regression analysis. RESULTS: The 1-year incidence for the onset of CWP among patients with CLBP was 23.8%. We identified the 3 risk factors, female sex, long duration of back pain, and a high rate of psychosomatic symptoms, for the onset of CWP among patients with CLBP. Coping resources and resilience had no impact on the transition from CLBP to CWP. CONCLUSION: The results suggest that CWP is no independent entity but rather a particularly negative occurrence on a continuum of chronic pain. Processes of somatization play a major role in the development of this extreme. LEVEL OF EVIDENCE: 2