Patients' views on responsibility for the management of musculoskeletal disorders – A qualitative study

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal disorders are very common and almost inevitable in an individual's lifetime. Enabling self-management and allowing the individual to take responsibility for care is stated as desired in the management of these disorders, but this may be asking more than people can generally manage. A willingness among people to take responsibility for musculoskeletal disorders and not place responsibility out of their hands or on employers but to be shared with medical professionals has been shown. The aim of the present study was to describe how people with musculoskeletal disorders think and reason regarding responsibility for prevention, treatment and management of the disorder.</p> <p>Methods</p> <p>Individual interviews with a strategic sample of 20 individuals with musculoskeletal disorders were performed. The interviews were tape-recorded, transcribed verbatim and analysed according to qualitative content analysis.</p> <p>Results</p> <p>From the interviews an overarching theme was identified: own responsibility needs to be met. The analysis revealed six interrelated categories: Taking on responsibility, Ambiguity about responsibility, Collaborating responsibility, Complying with recommendations, Disclaiming responsibility, and Responsibility irrelevant. These categories described different thoughts and reasoning regarding the responsibility for managing musculoskeletal disorders. Generally the responsibility for prevention of musculoskeletal disorders was described to lie primarily on society/authorities as they have knowledge of what to prevent and how to prevent it. When musculoskeletal disorders have occurred, health care should provide fast accessibility, diagnosis, prognosis and support for recovery. For long-term management, the individuals themselves are responsible for making the most out of life despite disorders.</p> <p>Conclusion</p> <p>No matter what the expressions of responsibility for musculoskeletal disorders are, own responsibility needs to be met by society, health care, employers and family in an appropriate way, with as much or as little of the "right type" of support needed, based on the individual's expectations.</p

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe

Normal Hematopoietic Stem Cell Function in Mice with Enforced Expression of the Hippo Signaling Effector YAP1

The Hippo pathway has recently been implicated in the regulation of organ size and stem cells in multiple tissues. The transcriptional cofactor yes-associated protein 1 (Yap1) is the most downstream effector of Hippo signaling and is functionally repressed by the upstream components of the pathway. Overexpression of YAP1 stimulates proliferation of stem and progenitor cells in many tissues, consistent with inhibition of Hippo signaling. To study the role of Hippo signaling in hematopoietic stem cells (HSCs), we created a transgenic model with inducible YAP1 expression exclusively within the hematopoietic system. Following 3 months induction, examination of blood and bone marrow in the induced mice revealed no changes in the distribution of the hematopoietic lineages compared to control mice. Moreover, the progenitor cell compartment was unaltered as determined by colony forming assays and immunophenotyping. To address whether YAP1 affects the quantity and function of HSCs we performed competitive transplantation experiments. We show that ectopic YAP1 expression does not influence HSC function neither during steady state nor in situations of hematopoietic stress. This is in sharp contrast to effects seen on stem- and progenitor cells in other organs and suggests highly tissue specific functions of the Hippo pathway in regulation of stem cells

Adipocyte mitochondrial genes and the forkhead factor FOXC2 are decreased in type 2 diabetes patients and normalized in response to rosiglitazone

<p>Abstract</p> <p>Background</p> <p>FOXC2 has lately been implicated in diabetes and obesity as well as mitochondrial function and biogenesis and also as a regulator of mtTFA/Tfam. In this study, the expression of FOXC2 and selected genes involved in mitochondrial function and biogenesis in healthy subjects and in a matched cohort with type 2 diabetes patients before and after treatment with rosiglitazone was determined. Quantitative real time PCR was used to analyze both RNA and DNA from biopsies from subcutaneous adipose tissue.</p> <p>Methods</p> <p>Blood samples and subcutaneous abdominal fat biopsies were collected from 12 T2D patients, of which 11 concluded the study, pre-treatment and 90 days after initiation of rosiglitazone treatment, and from 19 healthy control subjects on the first and only visit from healthy subjects. Clinical parameters were measured on the blood samples. RNA and DNA were prepared from the fat biopsies and gene expression was measured with real time PCR.</p> <p>Results</p> <p>The expression level of genes in the mitochondrial respiratory complexes I - IV were significantly downregulated in the diabetic patients and restored in response to rosiglitazone treatment. Rosiglitazone treatment also increased the relative number of mitochondria in diabetic patients compared with controls. Furthermore, the transcription factors FOXC2 and mtTFA/Tfam displayed a response pattern identical to the mitochondrial genes.</p> <p>Conclusions</p> <p>FOXC2, mtTFA/Tfam and subunits of the respiratory complexes I - IV show equivalent regulation in gene expression levels in response to TZD treatment. This, together with the knowledge that FOXC2 has a regulatory function of mtTFA/Tfam and mitochondrial biogenesis, suggests that FOXC2 has a possible functional role in the TZD activated mitochondrial response.</p

Responsibility for managing musculoskeletal disorders – A cross-sectional postal survey of attitudes

Background: Musculoskeletal disorders are a major burden on individuals, health systems and social care systems and rehabilitation efforts in these disorders are considerable. Self-care is often considered a cost effective treatment alternative owing to limited health care resources. But what are the expectations and attitudes in this question in the general population? The purpose of this study was to describe general attitudes to responsibility for the management of musculoskeletal disorders and to explore associations between attitudes and background variables. Methods: A cross-sectional, postal questionnaire survey was carried out with a random sample of a general adult Swedish population of 1770 persons. Sixty-one percent (n = 1082) responded to the questionnaire and was included for the description of general attitudes towards responsibility for the management of musculoskeletal disorders. For the further analyses of associations to background variables 683–693 individuals could be included. Attitudes were measured by the &quot;Attitudes regarding Responsibility for Musculoskeletal disorders&quot; (ARM) instrument, where responsibility is attributed on four dimensions; to myself, as being out of my hands, to employers or to (medical) professionals. Multiple logistic regression was used to explore associations between attitudes to musculoskeletal disorders and the background variables age, sex, education, physical activity, presence of musculoskeletal disorders, sick leave and whether the person had visited a care provider. Results: A majority of participants had internal views, i.e. showed an attitude of taking personal responsibility for musculoskeletal disorders, and did not place responsibility for the management out of their own hands or to employers. However, attributing shared responsibility between self and medical professionals was also found.The main associations found between attitude towards responsibility for musculoskeletal disorders and investigated background variables were that physical inactivity (OR 2.92–9.20), musculoskeletal disorder related sick leave (OR 2.31–3.07) and no education beyond the compulsory level (OR 3.12–4.76) increased the odds of attributing responsibility externally, i.e placing responsibility on someone or something else.Conclusion: Respondents in this study mainly saw themselves as responsible for managing musculoskeletal disorders. The associated background variables refined this finding and one conclusion is that, to optimise outcome when planning the prevention, treatment and management of these disorders, people&apos;s attitudes should be taken into account

Programmable in situ amplification for multiplexed imaging of mRNA expression

In situ hybridization methods enable the mapping of mRNA expression within intact biological samples. With current approaches, it is challenging to simultaneously map multiple target mRNAs within whole-mount vertebrate embryos, representing a significant limitation in attempting to study interacting regulatory elements in systems most relevant to human development and disease. Here, we report a multiplexed fluorescent in situ hybridization method based on orthogonal amplification with hybridization chain reactions (HCR). With this approach, RNA probes complementary to mRNA targets trigger chain reactions in which fluorophore-labeled RNA hairpins self-assemble into tethered fluorescent amplification polymers. The programmability and sequence specificity of these amplification cascades enable multiple HCR amplifiers to operate orthogonally at the same time in the same sample. Robust performance is achieved when imaging five target mRNAs simultaneously in fixed whole-mount and sectioned zebrafish embryos. HCR amplifiers exhibit deep sample penetration, high signal-to-background ratios and sharp signal localization

Cell fusions in mammals

Cell fusions are important to fertilization, placentation, development of skeletal muscle and bone, calcium homeostasis and the immune defense system. Additionally, cell fusions participate in tissue repair and may be important to cancer development and progression. A large number of factors appear to regulate cell fusions, including receptors and ligands, membrane domain organizing proteins, proteases, signaling molecules and fusogenic proteins forming alpha-helical bundles that bring membranes close together. The syncytin family of proteins represent true fusogens and the founding member, syncytin-1, has been documented to be involved in fusions between placental trophoblasts, between cancer cells and between cancer cells and host cells. We review the literature with emphasis on the syncytin family and propose that syncytins may represent universal fusogens in primates and rodents, which work together with a number of other proteins to regulate the cell fusion machinery

Genetically predicted circulating B vitamins in relation to digestive system cancers

Funder: United Kingdom Research and Innovation Future Leaders Fellowship (MR/T043202/1)Funder: EC‐Innovative Medicines Initiative (BigData@Heart)Funder: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z)Abstract: Background: Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations. Methods: Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants. Results: Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer. Conclusions: These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer

Critical Role of CD2 Co-stimulation in Adaptive Natural Killer Cell Responses Revealed in NKG2C-Deficient Humans

Infection by human cytomegalovirus (HCMV) leads to NKG2C-driven expansion of adaptive natural killer (NK) cells, contributing to host defense. However, approximately 4% of all humans carry a homozygous deletion of the gene that encodes NKG2C ($\textit{NKG2C}^{-/-}$). Assessment of NK cell repertoires in 60 $\textit{NKG2C}^{-/-}$ donors revealed a broad range of NK cell populations displaying characteristic footprints of adaptive NK cells, including a terminally differentiated phenotype, functional reprogramming, and epigenetic remodeling of the interferon (IFN)-$\gamma$ promoter. We found that both NKG2C$^{-}$ and NKG2C$^{+}$ adaptive NK cells expressed high levels of CD2, which synergistically enhanced ERK and S6RP phosphorylation following CD16 ligation. Notably, CD2 co-stimulation was critical for the ability of adaptive NK cells to respond to antibody-coated target cells. These results reveal an unexpected redundancy in the human NK cell response to HCMV and suggest that CD2 provides "signal 2" in antibody-driven adaptive NK cell responses.This work was supported by grants from the Swedish Research Council, the Swedish Children’s Cancer Society, the Swedish Cancer Society, the Tobias Foundation, the Swedish Foundation for Strategic Research, the Karolinska Institutet, the Wenner-Gren Foundation, the Norwegian Cancer Society, the Norwegian Research Council, the South-Eastern Norway Regional Health Authority, and the KG Jebsen Center for Cancer Immunotherapy. J.T. and J.A.T. are supported by the MRC and the Welcome Trust with partial funding from the National Institute for Health Research Cambridge Biomedical Research Centre. V.B. is supported by the French National Research Agency (ANR) (grant no. NKIR-ANR-13-PDOC- 0025-01)