The Egyptian Cardiothoracic Surgeon (ECTS - E-Journal)
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MicroRNAs in cardiovascular disease: an introduction for clinicians.
No full textMicroRNAs (miRNAs) are small, non-coding, RNA molecules approximately 22 nucleotides in length which act as post-transcriptional regulators of gene expression. Individual miRNAs have been shown to regulate the expression of multiple genes. Conversely, the expression of individual genes can be regulated by multiple miRNAs. Consequently, since their discovery just over 20 years ago, miRNAs have been identified as key regulators of complex biological processes linked to multiple cardiovascular pathologies, including left ventricular hypertrophy, ischaemic heart disease, heart failure, hypertension and arrhythmias. Furthermore, since the finding that miRNAs are present in the circulation, they have been investigated as novel biomarkers, especially in the context of acute myocardial infarction (AMI) and heart failure. While there is little convincing evidence that miRNAs can outperform traditional biomarkers, such as cardiac troponins, in the diagnosis of AMI, there is potential for miRNAs to complement existing risk prediction models and act as valuable markers of post-AMI prognosis. Encouragingly, the concept of miRNA-based therapeutics is developing, with synthetic antagonists of miRNAs (antagomiRs) currently in phase II trials for the treatment of chronic hepatitis C virus infection. In the cardiovascular field, promising preclinical studies suggest that they could be useful in treating disorders ranging from heart failure to dyslipidaemia, although several challenges related to specificity and targeted delivery remain to be overcome. Through this review, we provide clinicians with a brief overview of the ever-expanding world of miRNAs
Core outcome sets for use in effectiveness trials involving people with bipolar and schizophrenia in a community-based setting (PARTNERS2): study protocol for the development of two core outcome sets.
No full textBACKGROUND: In the general population the prevalence of bipolar and schizophrenia is 0.24% and 1.4% respectively. People with schizophrenia and bipolar disorder have a significantly reduced life expectancy, increased rates of unemployment and a fear of stigma leading to reduced self-confidence. A core outcome set is a standardised collection of items that should be reported in all controlled trials within a research area. There are currently no core outcome sets available for use in effectiveness trials involving bipolar or schizophrenia service users managed in a community setting. METHODS: A three-step approach is to be used to concurrently develop two core outcome sets, one for bipolar and one for schizophrenia. First, a comprehensive list of outcomes will be compiled through qualitative research and systematic searching of trial databases. Focus groups and one-to-one interviews will be completed with service users, carers and healthcare professionals. Second, a Delphi study will be used to reduce the lists to a core set. The three-round Delphi study will ask service users to score the outcome list for relevance. In round two stakeholders will only see the results of their group, while in round three stakeholders will see the results of all stakeholder group by stakeholder group. Third, a consensus meeting with stakeholders will be used to confirm outcomes to be included in the core set. Following the development of the core set a systematic literature review of existing measures will allow recommendations for how the core outcomes should be measured and a stated preference survey will explore the strength of people's preferences and estimate weights for the outcomes that comprise the core set. DISCUSSION: A core outcome set represents the minimum measurement requirement for a research area. We aim to develop core outcome sets for use in research involving service users with schizophrenia or bipolar managed in a community setting. This will inform the wider PARTNERS2 study aims and objectives of developing an innovative primary care-based model of collaborative care for people with a diagnosis of bipolar or schizophrenia
The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity.
No full textChordin-mediated regulation of bone morphogenetic protein (BMP) family growth factors is essential in early embryogenesis and adult homoeostasis. Chordin binds to BMPs through cysteine-rich von Willebrand factor type C (vWC) homology domains and blocks them from interacting with their cell surface receptors. These domains also self-associate and enable chordin to target related proteins to fine-tune BMP regulation. The chordin-BMP inhibitory complex is strengthened by the secreted glycoprotein twisted gastrulation (Tsg); however, inhibition is relieved by cleavage of chordin at two specific sites by tolloid family metalloproteases. As Tsg enhances this cleavage process, it serves a dual role as both promoter and inhibitor of BMP signalling. Recent developments in chordin research suggest that rather than simply being by-products, the cleavage fragments of chordin continue to play a role in BMP regulation. In particular, chordin cleavage at the C-terminus potentiates its anti-BMP activity in a type-specific manner
Negative pressure wound therapy for treating leg ulcers.
No full textBACKGROUND: Leg ulcers are open skin wounds that occur between the ankle and the knee that can last weeks, months or even years and are a consequence of arterial or venous valvular insufficiency. Negative pressure wound therapy (NPWT) is a technology that is currently used widely in wound care and is promoted for use on wounds. NPWT involves the application of a wound dressing to the wound, to which a machine is attached. The machine applies a carefully controlled negative pressure (or vacuum), which sucks any wound and tissue fluid away from the treated area into a canister. OBJECTIVES: To assess the effects of negative pressure wound therapy (NPWT) for treating leg ulcers in any care setting. SEARCH METHODS: For this review, in May 2015 we searched the following databases: the Cochrane Wounds Group Specialised Register (searched 21 May 2015); the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2015, Issue 4); Ovid MEDLINE (1946 to 20 May 2015); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 20 May 2015); Ovid EMBASE (1974 to 20 May 2015); EBSCO CINAHL (1982 to 21 May 2015). There were no restrictions based on language or date of publication. SELECTION CRITERIA: Published or unpublished randomized controlled trials (RCTs) comparing the effects of NPWT with alternative treatments or different types of NPWT in the treatment of leg ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment and data extraction. MAIN RESULTS: We included one study, with 60 randomized participants, in the review. The study population had a range of ulcer types that were venous arteriolosclerotic and venous/arterial in origin. Study participants had recalcitrant ulcers that had not healed after treatment over a six-month period. Participants allocated to NPWT received continuous negative pressure until they achieved 100% granulation (wound preparation stage). A punch skin-graft transplantation was conducted and the wound then exposed to further NPWT for four days followed by standard care. Participants allocated to the control arm received standard care with dressings and compression until 100% granulation was achieved. These participants also received a punch skin-graft transplant and then further treatment with standard care. All participants were treated as in-patients until healing occurred.There was low quality evidence of a difference in time to healing that favoured the NPWT group: the study reported an adjusted hazard ratio of 3.2, with 95% confidence intervals (CI) 1.7 to 6.2. The follow-up period of the study was a minimum of 12 months. There was no evidence of a difference in the total number of ulcers healed (29/30 in each group) over the follow-up period; this finding was also low quality evidence.There was low quality evidence of a difference in time to wound preparation for surgery that favoured NPWT (hazard ratio 2.4, 95% CI 1.2 to 4.7).Limited data on adverse events were collected: these provided low quality evidence of no difference in pain scores and Euroqol (EQ-5D) scores at eight weeks after surgery. AUTHORS' CONCLUSIONS: There is limited rigorous RCT evidence available concerning the clinical effectiveness of NPWT in the treatment of leg ulcers. There is some evidence that the treatment may reduce time to healing as part of a treatment that includes a punch skin graft transplant, however, the applicability of this finding may be limited by the very specific context in which NPWT was evaluated. There is no RCT evidence on the effectiveness of NPWT as a primary treatment for leg ulcers
Vitamin D supplementation to prevent depression and poor physical function in older adults: Study protocol of the D-Vitaal study, a randomized placebo-controlled clinical trial
No full textApiculture in the Anthropocene:Between Posthumanism and Critical Animal Studies
No full textThis chapter identifies a paradox in the concept of the Anthropocene; a tension between its powerful rejection of notions of human transcendence of the natural world and its implicit but unmistakable call for human responsibility on a scale that presupposes such transcendence. Diagnosing this as a tension between contrasting conceptions of human agency, the one as ultimately sovereign and determinative, the other as at best partial, contingent and entangled with various nonhuman agencies, the chapter traces the same paradox through the tension between critical and posthumanist currents in human-animal studies, by working the discussion through the recent and rapid worldwide decline in honeybee populations known as Colony Collapse Disorder, stressing that this is precisely the sort of socio-ecological crisis we should expect to see more frequently in the Anthropocene. A critical animal studies approach to Colony Collapse Disorder is evaluated, with honeybees viewed as a kind of ‘livestock’ and commercial beekeeping or apiculture understood as part of an ‘animal-industrial complex’. The chapter then articulates a more posthumanist approach, which it suggests is better equipped to acknowledge the specificities of honeybees and the nuances of human-apian relations, before finally reckoning the implications of these alternative accounts of Colony Collapse Disorder back into the paradoxical notions of human agency and responsibility at the heart of the Anthropocene
Societal preferences for rheumatoid arthritis treatments: evidence from a discrete choice experiment.
No full textOBJECTIVE: There is a concern that cost-effectiveness analysis using quality-adjusted life years does not capture all valuable benefits of treatments. The objective of this study was to determine the value society places on aspects of RA treatment to inform policymaking. METHODS: A discrete choice experiment was administered to a representative sample of the Canadian general population. The discrete choice experiment, developed using focus groups, had seven attributes (route and frequency of administration, chance of benefit, chance of serious and minor side effects, confidence in evidence and life expectancy). A conditional logit regression model was used to estimate the significance and relative importance of attributes in influencing preferences on the quality-adjusted life years scale. RESULTS: Responses from 733 respondents who provided rational responses were analysed. Six attribute levels within four attributes significantly influenced preferences for treatments: a willingness to trade a year of life expectancy over a 10-year period to increase the probability of benefiting from treatment, or two-thirds of a year to reduce minor or serious side effects to the lowest level or improve the confidence in benefit/side-effect estimates. There was also some evidence of a preference for oral drug delivery, though a subgroup analysis suggested this preference was restricted to injection-naive respondents. CONCLUSION: Our results suggest society values the degree of confidence in the estimates of risks and benefits of RA treatments and the route of administration, as well as benefits and side effects. This study provides important evidence to policymakers determining the cost-effectiveness of treatments in arthritis
No Association between Daily Walking and Knee Structural Changes in People at Risk of or with Mild Knee Osteoarthritis. Prospective Data from the Multicenter Osteoarthritis Study.
No full textOBJECTIVE: We investigated the association between objectively measured daily walking and knee structural change, defined either as radiographic worsening or as cartilage loss, in people at risk of or with knee osteoarthritis (OA). METHODS: Participants from the Multicenter Osteoarthritis Study (MOST) with Kellgren-Lawrence grades 0-2 and daily walking (measured with the StepWatch) at the 60-month visit were included. Participants had fixed-flexion, weight-bearing radiographs and knee magnetic resonance images (MRI) at 60 and 84 months. Radiographic worsening was read in both knees using the Osteoarthritis Research Society International grading, and MRI were read for 1 knee using the Whole-Organ MRI Score semiquantitative scoring. OR and 95% CI were calculated comparing those in the middle tertile against the lowest and highest tertiles of daily walking using logistic regression models and generalized estimating equations. Data on walking with moderate to vigorous intensity (min with > 100 steps/min/day) were associated to structural change using multivariate and logistic regression models. RESULTS: The 1179 study participants (59% women) were 67.0 years old (± 7.6), with a mean (± SD) body mass index of 29.8 kg/m(2) (± 5.3) who walked 6981 (± 2630) steps/day. After adjusting for confounders, we found no significant associations between daily walking and radiographic worsening or cartilage loss. More time spent walking at a moderate to vigorous intensity was not associated with either radiographic worsening or cartilage loss. CONCLUSION: Results from the MOST study indicated no association between daily walking and structural changes over 2 years in the knees of people at risk of or with mild knee OA