Intention, beliefs and mood assessed using electronic diaries predicts attendance at cardiac rehabilitation:An observational study

Background: Cardiac rehabilitation is effective in promoting physical/psychological recovery following acute coronary syndrome. Yet, rates of attendance at outpatient cardiac rehabilitation by eligible patients are low. Objectives: This study examined the determinants of attendance at outpatient cardiac rehabilitation in acute coronary syndrome patients following discharge until cardiac rehabilitation commencement. Design: A weekly electronic diary measured cardiac-related cognitions and mood and examined their relation to attendance at outpatient cardiac rehabilitation. Settings: Three United Kingdom National Health Service secondary care settings in two Health Board areas in Scotland. Participants: Acute coronary syndrome patients were recruited from March 2012 to June 2013 prior to hospital discharge. Of 488 eligible patients referred for cardiac rehabilitation, 214 consented. Results: 166 participants provided, on average, 5 weeks of diary entries before cardiac rehabilitation commenced. High intention (i.e. low “do not intend”) to attend CR and its rate of increase over time predicted attendance. Low negative emotional representation, high perceived necessity, high confidence in maintaining function, low negative affect, and high positive affect following discharge predicted attendance at cardiac rehabilitation. The rate of change in cardiac-related mood and these cognitions was not predictive. Baseline and rate of change in “do not intend” entirely mediated relationships between a) perceived necessity, b) negative affect and attendance at cardiac rehabilitation. Conclusions: Negative affect in the first weeks following discharge represents the key challenge to a patient maintaining their intention to attend cardiac rehabilitation. Intervention to improve attendance should focus on improving intention to attend following discharge and during recovery by improving patient understanding of cardiac rehabilitation and reducing negative affect

Solve a Complex Issue with The BRIDGE

Complex issues in work, school, community or life can significantly impact productivity, performance, and goal attainment. Collective brainpower can many times be the best way to creatively solve the issues. The BRIDGE is a tool that communities, businesses, educators, staff, volunteers, and youth can use to structure the collection of those creative ideas and streamline the process for developing an implementation plan. The BRIDGE fluidly incorporates adaptations of several organization analysis tools designed by business scholars arranged in a logical flow: Covey's Circle of Control/Influence, Lewin's Force Field Analysis, SWOT, and Kotter's Change Model. The BRIDGE model supports the research of Welsh scholar David Snowden and his Cynefin Decision Making Framework. Snowden contends that different situations require different responses to successfully navigate them. His framework interprets complexity theory with four domains of decision making: obvious, complicated, complex and chaotic. Decisions in the complex domain require experimentation and creativity to come up with a new approach. The BRIDGE model lends itself well to solving those complex decisions. The BRIDGE has been used to solve complex issues with a variety of groups: 1) a nonprofit start-up created structure, policies and procedures to run their new organization; 2) a 4-H group identified a new training program; 3) a focus group of leaders in the long-term services and supports industry identified talent development as a critical concern, which led to the creation of two new non-credit curricula to improve workforce skills; 4) a training department for a for-profit company developed a plan for management approval to implement a new initiative; 5) an FFA chapter developed several service learning projects for their school and community and at the same time learned valuable critical-thinking skills; and 6) a trucking company created a strategic plan to lead the company into a new phase of services. The BRIDGE model actively engages groups of diverse people. The structure of the process allows for dynamic exchange of ideas that are captured on idea cards and ultimately churn and meld into synthesized solutions supported by the entire group.AUTHOR AFFILIATION: Myra Wilson, program director, Ohio State Alber Enterprise Center, [email protected] (Corresponding Author); Cynthia Bond, assistant professor and OSU Extension educator, community development; David Marrison, associate professor and OSU Extension educator, agriculture and natural resources; Emily Marrison, OSU Extension educator, family and consumer sciences; Amanda Woods, Healthy Finances program specialist, OSU Extension family and consumer sciences; Kyle White, OSU Extension area leader and educator, community developmentComplex issues in work, school, community, or life can significantly impact productivity, performance, and goal attainment. Collective brainpower can many times be the best way to creatively solve issues. The BRIDGE is a tool that communities, businesses, educators, staff, volunteers, and youth can use to structure the collection of those creative ideas and streamline the process for developing an implementation plan. The BRIDGE model actively engages groups of diverse people. The structure of the process allows for dynamic exchange of ideas that are captured on idea cards and ultimately churn and meld into synthesized solutions supported by the entire group. Learn how you can become a certified facilitator of The BRIDGE

Differential expression of the BCAT isoforms between breast cancer subtypes

© 2020, The Author(s). Background: Biological characterisation of breast cancer subtypes is essential as it informs treatment regimens especially as different subtypes have distinct locoregional patterns. This is related to metabolic phenotype, where altered cellular metabolism is a fundamental adaptation of cancer cells during rapid proliferation. In this context, the metabolism of the essential branched-chain amino acids (BCAAs), catalysed by the human branched-chain aminotransferase proteins (hBCAT), offers multiple benefits for tumour growth. Upregulation of the cytosolic isoform of hBCAT (hBCATc), regulated by c-Myc, has been demonstrated to increase cell migration, tumour aggressiveness and proliferation in gliomas, ovarian and colorectal cancer but the importance of the mitochondrial isoform, hBCATm has not been fully investigated. Methods: Using immunohistochemistry, the expression profile of metabolic proteins (hBCAT, IDH) was assessed between breast cancer subtypes, HER2 + , luminal A, luminal B and TNBC. Correlations between the percentage and the intensity of protein expression/co-expression with clinical parameters, such as hormone receptor status, tumour stage, lymph-node metastasis and survival, were determined. Results: We show that hBCATc expression was found to be significantly associated with the more aggressive HER2 + and luminal B subtypes, whilst hBCATm and IDH1 associated with luminal A subtype. This was concomitant with better prognosis indicating a differential metabolic reliance between these two subtypes, in which enhanced expression of IDH1 may replenish the α-ketoglutarate pool in cells with increased hBCATm expression. Conclusion: The cytosolic isoform of BCAT is associated with tumours that express HER2 receptors, whereas the mitochondrial isoform is highly expressed in tumours that are ER + , indicating that the BCAT proteins are regulated through different signalling pathways, which may lead to the identification of novel targets for therapeutic applications targeting dysregulated cancer metabolism

Decreased expression of the mitochondrial bcat protein correlates with improved patient survival in idh-wt gliomas

Background and research question: Gliomas represent 43% of all solid intracranial tumours, of which glioblastomas have the poorest prognosis. Recently, the human cytosolic branched-chain aminotransferase protein (hBCATc), which metabolises the branched-chain amino acids (BCAA), was identified as a biomarker and therapeutic target for glioblastomas carrying wild-type isocitrate dehydrogenase (IDH-WT) genes. However, the clinical utility of the mitochondrial isoform, hBCATm, which also metabolises BCAAs, was not determined nor its potential role in predicting patient survival.Methods: Glioblastomas, of grades II-IV, from 53 patients were graded by a neuropathologist, where the IDH and MGMT status were assessed. Tumours positive for hBCATm, hBCATc and BCKDC were characterised using immunohistochemistry and Western blot analysis using antibodies specific to these proteins.Results: Here, we report that in IDH-WT tumours, the expression of hBCATm is significantly increased (p=0.034) relative to IDH mutation gliomas, and significantly correlates with patient survival, on Kaplan-Meier analysis, where low hBCATm expression is a positive prognostic factor (p=0.003). Moreover, increased hBCATm expression in these glioblastomas correlated with tumour grade indicating their role as a predictive biomarker of glioma progression. Multiple banding was observed for the branched-chain α-keto acid dehydrogenase complex, which catalyses the committed step in BCAA metabolism, but a significant change in expression was absent (p=0.690). Conclusion: Until now, IDH-WT glioblastomas have a uniformly poor prognosis, however we demonstrate for the first time that relatively low hBCATm may select for a better performing subset within this group and may represent a therapeutic target in these hard to treat patients

Vitamin K supplementation to improve vascular stiffness in CKD:The K4Kidneys randomized controlled trial

BACKGROUND:Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS:To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 μg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS:We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS:Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com)

Study protocol of a multicentre randomised controlled trial of self-help cognitive behaviour therapy for working women with menopausal symptoms (MENOS@Work)

Background Hot flushes and night sweats (HFNS) – the main symptoms of the menopause transition – can reduce quality of life and are particularly difficult to manage at work. A cognitive behaviour therapy (CBT) intervention has been developed specifically for HFNS that is theoretically based and shown to reduce significantly the impact of HFNS in several randomised controlled trials (RCTs). Self-help CBT has been found to be as effective as group CBT for these symptoms, but these interventions are not widely available in the workplace. This paper describes the protocol of an RCT aiming to assess the efficacy of CBT for menopausal symptoms implemented in the workplace, with a nested qualitative study to examine acceptability and feasibility. Methods/Design One hundred menopausal working women, aged 45–60 years, experiencing bothersome HFNS for two months will be recruited from several (2–10) large organisations into a multicentre randomised controlled trial. Women will be randomly assigned to either treatment (a self-help CBT intervention lasting 4 weeks) or to a no treatment-wait control condition (NTWC), following a screening interview, consent, and completion of a baseline questionnaire. All participants will complete follow-up questionnaires at 6 weeks and 20 weeks post-randomisation. The primary outcome is the rating of HFNS; secondary measures include HFNS frequency, mood, quality of life, attitudes to menopause, HFNS beliefs and behaviours, work absence and presenteeism, job satisfaction, job stress, job performance, disclosure to managers and turnover intention. Adherence, acceptability and feasibility will be assessed at 20 weeks post-randomisation in questionnaires and qualitative interviews. Upon trial completion, the control group will also be offered the intervention. Discussion This is the first randomised controlled trial of a self-management intervention tailored for working women who have troublesome menopausal symptoms

Exome Sequencing Reveals Common and Rare Variants in F5 Associated With ACE Inhibitor and Angiotensin Receptor Blocker–Induced Angioedema

Angioedema occurring in the head and neck region is a rare and sometimes life‐threatening adverse reaction to angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Few studies have investigated the association of common variants with this extreme reaction, but none have explored the combined influence of rare variants yet. Adjudicated cases of ACEI‐induced angioedema (ACEI‐AE) or ARB‐induced angioedema (ARB‐AE) and controls were recruited at five different centers. Sequencing of 1,066 samples (408 ACEI‐AE, ARB‐AE, and 658 controls) was performed using exome‐enriched sequence data. A common variant of the F5 gene that causes an increase in blood clotting (rs6025, p.Arg506Gln, also called factor V Leiden), was significantly associated with both ACEI‐AE and ARB‐AE (odds ratio: 2.85, 95% confidence interval (CI), 1.89–4.25). A burden test analysis of five rare missense variants in F5 was also found to be associated with ACEI‐AE or ARB‐AE, P = 2.09 × 10−3. A combined gene risk score of these variants, and the common variants rs6025 and rs6020, showed that individuals carrying at least one variant had 2.21 (95% CI, 1.49–3.27, P = 6.30 × 10−9) times the odds of having ACEI‐AE or ARB‐AE. The increased risk due to the common Leiden allele was confirmed in a genome‐wide association study from the United States. A high risk of angioedema was also observed for the rs6020 variant that is the main coagulation defect‐causing variant in black African and Asian populations. We found that deleterious missense variants in F5 are associated with an increased risk of ACEI‐AE or ARB‐AE

Identifying the neutrino mass spectrum from a supernova neutrino burst

We study the role that the future detection of the neutrino burst from a galactic supernova can play in the reconstruction of the neutrino mass spectrum. We consider all possible 3$\nu$ mass and flavor spectra which describe the solar and atmospheric neutrino data. For each of these spectra we find the observable effects of the supernova neutrino conversions both in the matter of the star and the earth. We show that studies of the electron neutrino and anineutrino spectra as well as observations of the neutral current effects from supernova will allow us (i) to identify the solar neutrino solution, (ii) to determine the type of mass hierarchy (normal or inverted) and (iii) to probe the mixing $|U_{e3}|^2$ to values as low as $10^{-4} - 10^{-3}$.Comment: 53 pages, 13eps figures. Substantial changes made, new results, figures and tables adde