A qualitative study on the role of cultural background in patients perspectives on rehabilitation

Background Low back pain (LBP) is one of the major concerns in health care. In Switzerland, musculoskeletal problems represent the third largest illness group with 9.4 million consultations per year. The return to work rate is increased by an active treatment program and saves societal costs. However, results after rehabilitation are generally poorer in patients with a Southeast European cultural background than in other patients. This qualitative research about the rehabilitation of patients with LBP and a Southeast European cultural background, therefore, explores possible barriers to successful rehabilitation. Methods We used a triangulation of methods combining three qualitative methods of data collection: 13 semi-structured in-depth interviews with patients who have a Southeast European cultural background and live in Switzerland, five semi-structured in-depth interviews and two focus groups with health professionals, and a literature review. Between June and December 2008, we recruited participants at a Rehabilitation Centre in the German-speaking part of Switzerland. Results To cope with pain, patients prefer passive strategies, which are not in line with recommended coping strategies. Moreover, the families of patients tend to support passive behaviour and reduce the autonomy of patients. Health professionals and researchers propagate active strategies including activity in the presence of pain, yet patients do not consider psychological factors contributing to LBP. The views of physicians and health professionals are in line with research evidence demonstrating the importance of psychosocial factors for LBP. Treatment goals focusing on increasing daily activities and return to work are not well understood by patients partly due to communication problems, which is something that patients and health professionals are aware of. Additional barriers to returning to work are caused by poor job satisfaction and other work-related factors. Conclusions LBP rehabilitation can be improved by addressing the following points. Early management of LBP should be activity-centred instead of pain-centred. It is mandatory to implement return to work management early, including return to adapted work, to improve rehabilitation for patients. Rehabilitation has to start when patients have been off work for three months. Using interpreters more frequently would improve communication between health professionals and patients, and reduce misunderstandings about treatment procedures. Special emphasis must be put on the process of goal-formulation by spending more time with patients in order to identify barriers to goal attainment. Information on the return to work process should also include the financial aspects of unemployment and disability.

Steroid hormone related male biased parasitism in chamois, Rupicapra rupicapra rupicapra

Parasites are linked with their host in a trophic interaction with implications for both hosts and parasites. Interaction stretches from the host's immune response to the structuring of communities and the evolution of biodiversity. As in many species sex determines life history strategy, response to parasites may be sex-specific. Males of vertebrate species tend to exhibit higher rates of parasites than females. Sex-associated hormones may influence immunocompetence and are hypothesised to lead to this bias. In a field study, we tested the prediction of male biased parasitism (MBP) in free ranging chamois (Rupicapra rupicapra rupicapra), which are infested intensely by gastrointestinal and lung helminths. We further investigated sex differences in faecal androgen (testosterone and epiandrosterone), cortisol and oestrogen metabolites using enzyme immunoassays (EIA) to evaluate the impact of these hormones on sex dependent parasite susceptibility. Non-invasive methods were used and the study was conducted throughout a year to detect seasonal patterns. Hormone levels and parasite counts varied significantly throughout the year. Male chamois had a higher output of gastrointestinal eggs and lungworm larvae when compared to females. The hypothesis of MBP originating in sex related hormone levels was confirmed for the elevated output of lungworm larvae, but not for the gastrointestinal nematodes. The faecal output of lungworm larvae was significantly correlated with androgen and cortisol metabolite levels. Our study shows that sex differences in steroid levels play an important role to explain MBP, although they alone cannot fully explain the phenomenon.

Role of proton MR for the study of muscle lipid metabolism

1H-MR spectroscopy (MRS) of intramyocellular lipids (IMCL) became particularly important when it was recognized that IMCL levels are related to insulin sensitivity. While this relation is rather complex and depends on the training status of the subjects, various other influences such as exercise and diet also influence IMCL concentrations. This may open insight into many metabolic interactions; however, it also requires careful planning of studies in order to control all these confounding influences. This review summarizes various historical, methodological, and practical aspects of 1H-MR spectroscopy (MRS) of muscular lipids. That includes a differentiation of bulk magnetic susceptibility effects and residual dipolar coupling that can both be observed in MRS of skeletal muscle, yet affecting different metabolites in a specific way. Fitting of the intra- (IMCL) and extramyocellular (EMCL) signals with complex line shapes and the transformation into absolute concentrations is discussed. Since the determination of IMCL in muscle groups with oblique fiber orientation or in obese subjects is still difficult, potential improvement with high-resolution spectroscopic imaging or at higher field strength is considered. Fat selective imaging is presented as a possible alternative to MRS and the potential of multinuclear MRS is discussed. 1H-MRS of muscle lipids allows non-invasive and repeated studies of muscle metabolism that lead to highly relevant findings in clinics and patho-physiology.

Role of endogenous Fas (CD95/Apo-1) ligand in balloon-induced apoptosis, inflammation, and neointima formation

BACKGROUND: Fas (CD95/Apo-1) ligand (FasL)-induced apoptosis in Fas-bearing cells is critically involved in modulating immune reactions and tissue repair. Apoptosis has also been described after mechanical vascular injury such as percutaneous coronary intervention. However, the relevance of cell death in this context of vascular repair remains unknown. METHODS AND RESULTS: To determine whether FasL-induced apoptosis is causally related to neointimal lesion formation, we subjected FasL-deficient (generalized lymphoproliferative disorder [gld], C57BL/6J) and corresponding wild-type (WT) mice to carotid balloon distension injury, which induces marked endothelial denudation and medial cell death. FasL expression in WT mice was induced in injured vessels compared with untreated arteries (P<0.05; n=5). Conversely, absence of functional FasL in gld mice decreased medial and intimal apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling [TUNEL] index) at 1 hour and 7 days after balloon injury (P<0.05; n=6). In addition, peritoneal macrophages isolated from gld mice showed no apoptosis and enhanced migration (P<0.05; n=4). In parallel, we observed increased balloon-induced macrophage infiltrations (anti-CD68) in injured arteries of FasL-deficient animals (P<0.05; n=6). Together with enhanced proliferation (bromodeoxyuridine index; P<0.05), these events resulted in a further increase in medial and neointimal cells (P<0.01; n=8) with thickened neointima in gld mice (intima/media ratio, x3.8 of WT; P<0.01). CONCLUSIONS: Our data identify proapoptotic and antiinflammatory effects of endogenous FasL as important factors in the process of neointimal lesion formation after balloon injury. Moreover, they suggest that activation of FasL may decrease neointimal thickening after percutaneous coronary intervention.

Congenital syndactyly in cattle: four novel mutations in the low density lipoprotein receptor-related protein 4 gene (LRP4)

BACKGROUND: Isolated syndactyly in cattle, also known as mulefoot, is inherited as an autosomal recessive trait with variable penetrance in different cattle breeds. Recently, two independent mutations in the bovine LRP4 gene have been reported as the primary cause of syndactyly in the Holstein and Angus cattle breeds. RESULTS: We confirmed the previously described LRP4 exon 33 two nucleotide substitution in most of the affected Holstein calves and revealed additional evidence for allelic heterogeneity by the identification of four new LRP4 non-synonymous point mutations co-segregating in Holstein, German Simmental and Simmental-Charolais families. CONCLUSION: We confirmed a significant role of LRP4 mutations in the pathogenesis of congenital syndactyly in cattle. The newly detected missense mutations in the LRP4 gene represent independent mutations affecting different conserved protein domains. However, the four newly described LRP4 mutations do still not explain all analyzed cases of syndactyly.

Quantitation of Guggenheimella bovis and treponemes in bovine tissues related to digital dermatitis

Digital dermatitis is an inflammation of uncertain aetiology in the skin of the foot of cattle. In 2005, a novel microorganism, Guggenheimella bovis, was isolated from the advancing front of digital dermatitis lesions, suggesting a possible role in pathogenesis. In the present study, tissue samples of 20 affected cows were examined by quantitative PCR for G. bovis, treponemes and the total eubacterial load. High numbers of eubacteria and treponemes were found in most lesions, whereas only a few lesions contained Guggenheimella, and only at low concentrations. The results argue against the relevance of G. bovis in the aetiology of digital dermatitis in cattle, but are consistent with a role for treponemes.

Insulin resistance in mice lacking neuronal nitric oxide synthase is related to an alpha-adrenergic mechanism

BACKGROUND: nitric oxide (NO) plays an important role in the regulation of cardiovascular and glucose homeostasis. Mice lacking the gene encoding the neuronal isoform of nitric oxide synthase (nNOS) are insulin-resistant, but the underlying mechanism is unknown. nNOS is expressed in skeletal muscle tissue where it may regulate glucose uptake. Alternatively, nNOS driven NO synthesis may facilitate skeletal muscle perfusion and substrate delivery. Finally, nNOS dependent NO in the central nervous system may facilitate glucose disposal by decreasing sympathetic nerve activity. METHODS: in nNOS null and control mice, we studied whole body glucose uptake and skeletal muscle blood flow during hyperinsulinaemic clamp studies in vivo and glucose uptake in skeletal muscle preparations in vitro. We also examined the effects of alpha-adrenergic blockade (phentolamine) on glucose uptake during the clamp studies. RESULTS: as expected, the glucose infusion rate during clamping was roughly 15 percent lower in nNOS null than in control mice (89 (17) vs 101 (12) [-22 to -2]). Insulin stimulation of muscle blood flow in vivo, and intrinsic muscle glucose uptake in vitro, were comparable in the two groups. Phentolamine, which had no effect in the wild-type mice, normalised the insulin sensitivity in the mice lacking the nNOS gene. CONCLUSIONS: insulin resistance in nNOS null mice was not related to defective insulin stimulation of skeletal muscle perfusion and substrate delivery or insulin signaling in the skeletal muscle cell, but to a sympathetic alpha-adrenergic mechanism.

Different migration of vascular smooth muscle cells from human coronary artery bypass vessels. Role of Rho/ROCK pathway

BACKGROUND: We examined whether vascular smooth muscle (VSMC) or endothelial cell (EC) migration from internal mammary artery (MA) differed from VSMC or EC migration from saphenous vein (SV). METHODS AND RESULTS: Migration to PDGF-BB (1-10 ng/ml) was lower in VSMC from MA than SV; however, attachment, movement without chemokine, and chemokinesis were identical. Unlike VSMC, migration of EC was similar in response to several mediators. Expression of PDGF receptor-beta was lower in VSMC from MA than SV, while alpha-receptor expression was higher. PDGF-BB-induced RhoA activity was lower in MA than SV, while basal activity was identical. Rosuvastatin and hydroxyfasudil impaired PDGF-BB-induced migration of VSMC from MA and SV. Mevalonate and geranylgeranylpyrophosphate rescued inhibition by rosuvastatin. PDGF-BB induced less stress fiber formation in VSMC from MA than SV. A dominant negative RhoA mutant inhibited stress fiber formation to PDGF-BB, while a constitutively active mutant resulted in maximal stress fiber formation in MA and SV. Rosuvastatin and hydroxyfasudil impaired PDGF-BB-induced stress fiber formation in MA and SV. CONCLUSIONS: VSMC migration to PDGF-BB is lower in MA than SV, which is at least in part related to lower activity of the Rho/ROCK pathway.

Moving from sustainable management to sustainable governance of natural resources: The role of social learning processes in rural India, Bolivia and Mali

The present paper discusses a conceptual, methodological and practical framework within which the limitations of the conventional notion of natural resource management (NRM) can be overcome. NRM is understood as the application of scientific ecological knowledge to resource management. By including a consideration of the normative imperatives that arise from scientific ecological knowledge and submitting them to public scrutiny, ‘sustainable management of natural resources’ can be recontextualised as ‘sustainable governance of natural resources’. This in turn makes it possible to place the politically neutralising discourse of ‘management’ in a space for wider societal debate, in which the different actors involved can deliberate and negotiate the norms, rules and power relations related to natural resource use and sustainable development. The transformation of sustainable management into sustainable governance of natural resources can be conceptualised as a social learning process involving scientists, experts, politicians and local actors, and their corresponding scientific and non-scientific knowledges. The social learning process is the result of what Habermas has described as ‘communicative action’, in contrast to ‘strategic action’. Sustainable governance of natural resources thus requires a new space for communicative action aiming at shared, intersubjectively validated definitions of actual situations and the goals and means required for transforming current norms, rules and power relations in order to achieve sustainable development. Case studies from rural India, Bolivia and Mali explore the potentials and limitations for broadening communicative action through an intensification of social learning processes at the interface of local and external knowledge. Key factors that enable or hinder the transformation of sustainable management into sustainable governance of natural resources through social learning processes and communicative action are discussed.

Plasma leptin levels in men are not related to the development of lipoatrophy during antiretroviral therapy

OBJECTIVES: To assess the correlations between the hormone leptin and lipoatrophy in HIV-positive, treatment-naive patients on combination antiretroviral therapy (cART). DESIGN: Case-control study nested in a multicentre cohort of HIV-infected adults. Cases were patients that developed lipoatrophy and controls those who did not. PATIENTS AND METHODS: Clinical parameters and plasma leptin determinations were studied in 97 HIV-1-infected, treatment-naive Caucasian men (10 cases and 87 controls) on an unchanged and virologically successful drug regimen with a zidovudine/lamivudine backbone at baseline and after 2 years of cART. The association of plasma leptin levels and the development of lipoatrophy was investigated. RESULTS: Two years of cART was not associated with a change in plasma leptin levels. Plasma leptin levels remained sensible to changes in body mass index. There was no difference in leptin levels between patients who developed lipoatrophy and controls, neither before nor after cART. The only predictor of development of lipoatrophy was a higher age (P = 0.02). CONCLUSIONS: Leptin as measured in plasma is unlikely to play a major role in the genesis of lipoatrophy.

[Integration process and organ-related fantasies in patients undergoing organ transplantation]

This review deals with an important aspect of organ transplantation, namely the process of psychic organ integration and organ-related fantasies. The body schema and body self are two important concepts in the integration of a transplanted organ. Different models and theories on organ integration are presented and will be discussed. There is evidence that beside the emotional impact and the influence on well-being, organ integration depends closely on psychic processes involving in the incorporation of the transplanted organ and the respective organ-related fantasies. Therefore, these organ fantasies - whether unconscious or conscious - may play an important role in the future development of the instinctive and highly individual relation the patients elaborate with the new organ. Beside the concern with the new organ, a bereavement to the lost old and sick organ may also influence the patients thoughts. Moreover, the good resolving of all these issues evokes the "good practice" patients develop towards the new situation. This will bring up issues as compliance, infections, rejection episodes and - most important - also organ survival.

Clinical significance of cell cycle- and apoptosis-related markers in biliary tract cancer: a tissue microarray-based approach revealing a distinctive immunophenotype for intrahepatic and extrahepatic cholangiocarcinomas

Cholangiocarcinoma is the second most common malignant tumor of the liver. We analyzed, immunohistochemically, the significance of cell cycle- and apoptosis-related markers in 128 cholangiocarcinomas (42 intrahepatic, 70 extrahepatic, and 16 gallbladder carcinomas) combined in a tissue microarray. Follow-up was available for 57 patients (44.5%). In comparison with normal tissue (29 specimens), cholangiocarcinomas expressed significantly more frequently p53, bcl-2, bax, and COX-2 (P.05 <). Intrahepatic tumors were significantly more frequently bcl-2+ and p16+, whereas extrahepatic tumors were more often p53+ (P < .05). Loss of p16 expression was associated with reduced survival of patients. Our data show that p53, bcl-2, bax, and COX-2 have an important role in the pathogenesis of cholangiocarcinomas. The differential expression of p16, bcl-2, and p53 between intrahepatic and extrahepatic tumors demonstrates that there are location-related differences in the phenotype and the genetic profiles of these tumors. Moreover, p16 was identified as an important prognostic marker in cholangiocarcinomas.

Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper

Nonallergic rhinitis (NAR) can be defined as a chronic nasal inflammation which is not caused by systemic IgE-dependent mechanisms. It is common and probably affects far more than 200 million people worldwide. Both children and adults are affected. However, its exact prevalence is unknown and its phenotypes need to be evaluated using appropriate methods to better understand its pathophysiology, diagnosis and management. It is important to differentiate between infectious rhinitis, allergic/NAR and chronic rhinosinusitis, as management differs for each of these cases. Characterization of the phenotype, mechanisms and management of NAR represents one of the major unmet needs in allergic and nonallergic diseases. Studies on children and adults are required in order to appreciate the prevalence, phenotype, severity and co-morbidities of NAR. These studies should compare allergic and NAR and consider different age group populations including elderly subjects. Mechanistic studies should be carried out to better understand the disease(s) and risk factors and to guide towards an improved diagnosis and therapy. These studies need to take the heterogeneity of NAR into account. It is likely that neuronal mechanisms, T cells, innate immunity and possibly auto-immune responses all play a role in NAR and may also contribute to the symptoms of allergic rhinitis.

Exploration of the role of serum factors in maintaining bone mass during hibernation in black bears

Disuse osteoporosis is a condition in which reduced mechanical loading (e.g. bed-rest, immobilization, or paralysis) results in unbalanced bone turnover. The American black bear is a unique, naturally occurring model for the prevention of disuse osteoporosis. Bears remain mostly inactive for up to half a year of hibernation annually, yet they do not lose bone mechanical strength or structural properties throughout hibernation. The long-term goal of this study is to determine the biological mechanism through which bears maintain bone during hibernation. This mechanism could pinpoint new signaling pathway targets for the development of drugs for osteoporosis prevention. In this study, bone specific alkaline phosphatase (BSALP), a marker of osteoblast activity, and tartrate resistant acid phosphatase (TRACP), a marker of osteoclast number, were quantified in the serum of hibernating and active black bears. BSALP and TRACP decreased during hibernation, suggesting a balanced reduction in bone turnover. This decrease in BSALP and TRACP were correlated positively to serum adiponectin and inversely to serum neuropeptide Y, suggesting a possible role of these hormones in suppressing bone turnover during hibernation. Osteocalcin (OCN) and undercarboxylated OCN increased dramatically in the serum of hibernating bears. These increases were inversely correlated with adiponectin, glucose, and serotonin, suggesting that OCN may have a unique role in energy homeostasis during hibernation. Finally, MC3T3-E1 osteoblasts were cultured in the serum from active and hibernating bears, and seasonal cell responses were quantified. Cells cultured in serum from hibernating bears had a reduced caspase-3/7 response, and more living cells, after apoptotic threat. The caspase-3/7 response was positively correlated to serum adiponectin and to gene expression of OCN and Runx2, suggesting that reduced caspase-3/7 activity may be related to the reduced differentiation potential of osteoblasts in hibernation serum, and that adiponectin is a potential effector hormone. In summary, the activities of osteoblasts and osteoclasts are reduced during hibernation in bears. This reduced turnover is due, in part, to hormonal control. Further study of potential effectors adiponectin and neuropeptide Y may provide insight into the biological mechanism through which bears maintain bone throughout hibernation.

Regulation of mitochondrial function by hypoxia and inflammation in sepsis: A putative role for hypoxia inducible factor

Sepsis-related organ failure is the leading cause of mortality in European intensive care units (ICU). Although the inflammatory cascade of mediators in response to infection is well known, the relationships between regional inflammation, microvascular heterogeneity, hypoxia and hypoxia-inducible gene expression, and finally, organ dysfunction, are unknown. Growing evidence suggests that not only low oxygen supply to the tissues secondary to macrovascular and microvascular alterations, but also altered cellular oxygen utilization is involved in the development of multiorgan dysfunction [1]–[3]. Microbial products and innate and adaptive dysregulated immune response to infection directly affect parenchymal cells of organs and may contribute to multiorgan dysfunction.