Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Opisthorchiasis and cholangiocarcinoma in South East Asia: an unresolved problem

The prevalence of cholangiocarcinoma (CCA) in Southeast Asia is much higher than other areas of the world. Eating raw, fermented or undercooked cyprinid fish, infected with the liver fluke, Opisthorchis viverrini sensu lato, results in chronic biliary inflammation, periductal fibrosis, and increased cancer risk. There may be associated glomerulonephritis. The process of infection is difficult to disrupt because eating practices have proven extremely difficult to change, and the life cycle of the fluke cannot be broken due to high prevalence in canine and feline reservoir hosts. Fecal analysis and ELISA tests can be used to diagnose opisthorchiasis. Diagnosis of CCA is complex, partly due to the lack of definitive imaging characteristics and also due to the difficulty of obtaining samples for cytology or histology. This cancer has proven to be resistant to common chemotherapy treatments and so the two avenues of treatment available are surgical resection and liver transplantation, both requiring early detection of the tumor for the best chances of success. Late presentation of symptoms reduces the chances of successful surgical intervention. While liver fluke infections can be treated with praziquantel, individuals will often become re-infected, and multiple reinfections can be more harmful than a singular, long term infection. A key research need is for the detection and characterization of novel biomarkers in all parts of the carcinogenic pathway for early diagnosis

The failure of suicide prevention in primary care: family and GP perspectives - a qualitative study

Background Although Primary care is crucial for suicide prevention, clinicians tend to report completed suicides in their care as non-preventable. We aimed to examine systemic inadequacies in suicide prevention from the perspectives of bereaved family members and GPs.Methods Qualitative study of 72 relatives or close friends bereaved by suicide and 19 General Practitioners who have experienced the suicide of patients.Results Relatives highlight failures in detecting symptoms and behavioral changes and the inability of GPs to understand the needs of patients and their social contexts. A perceived overreliance on anti-depressant treatment is a major source of criticism by family members. GPs tend to lack confidence in the recognition and management of suicidal patients, and report structural inadequacies in service provision.Conclusions Mental health and primary care services must find innovative and ethical ways to involve families in the decision-making process for patients at risk of suicide

Evidence-based care of older people with suspected cognitive impairment in general practice: protocol for the IRIS cluster randomised trial

Background: Dementia is a common and complex condition. Evidence-based guidelines for the management of people with dementia in general practice exist; however, detection, diagnosis and disclosure of dementia have been identified as potential evidence-practice gaps. Interventions to implement guidelines into practice have had varying success. The use of theory in designing implementation interventions has been limited, but is advocated because of its potential to yield more effective interventions and aid understanding of factors modifying the magnitude of intervention effects across trials. This protocol describes methods of a randomised trial that tests a theory-informed implementation intervention that, if effective, may provide benefits for patients with dementia and their carers. Aims: This trial aims to estimate the effectiveness of a theory-informed intervention to increase GPs’ (in Victoria, Australia) adherence to a clinical guideline for the detection, diagnosis, and management of dementia in general practice, compared with providing GPs with a printed copy of the guideline. Primary objectives include testing if the intervention is effective in increasing the percentage of patients with suspected cognitive impairment who receive care consistent with two key guideline recommendations: receipt of a i) formal cognitive assessment, and ii) depression assessment using a validated scale (primary outcomes for the trial). Methods: The design is a parallel cluster randomised trial, with clusters being general practices. We aim to recruit 60 practices per group. Practices will be randomised to the intervention and control groups using restricted randomisation. Patients meeting the inclusion criteria, and GPs’ detection and diagnosis behaviours directed toward these patients, will be identified and measured via an electronic search of the medical records nine months after the start of the intervention. Practitioners in the control group will receive a printed copy of the guideline. In addition to receipt of the printed guideline, practitioners in the intervention group will be invited to participate in an interactive, opinion leader-led, educational face-to-face workshop. The theory-informed intervention aims to address identified barriers to and enablers of implementation of recommendations. Researchers responsible for identifying the cohort of patients with suspected cognitive impairment, and their detection and diagnosis outcomes, will be blind to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12611001032943 (date registered 28 September, 2011)

A case study of bovine tuberculosis in an area of County Donegal, Ireland

A descriptive analysis, to investigate the potential risk factors that might have contributed to the increased incidence of bovine tuberculosis (BTB) herd-breakdowns in the reference area of Co. Donegal during the fifth year of the four-area project (FAP), was performed. Seventy two different herds were restricted for BTB during the FAP; 10 of these herds were restricted twice, resulting in a total of 82 BTB breakdowns. During the first four years of the FAP, the number of BTB herd breakdowns in the area varied from a lowest of nine to a maximum of 18 per year, and were geographically dispersed. In the fifth year of the study a considerable increase in the number of BTB breakdowns (n = 32) was observed, and there was a spatial 'cluster' of infected herds in the eastern part of the study area. The increased number of BTB breakdowns during the fifth year most likely occurred because of the recrudescence of infection, herd-to-herd transmission and, to a lesser extent, purchase of infected cattle. Infected badgers remain as a possible but less likely source of infection, especially as an explanation for the cluster of infected herds. The analysis supports the hypothesis that BTB in herds is a problem that cannot be addressed successfully by dedicating our efforts to the elimination of single risk factors. Neither is it a problem that needs to be investigated only at the herd level, but rather at the area level, including groups of contiguous herds

High-efficiency Rosa26 knock-in vector construction for Cre-regulated overexpression and RNAi

Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. The Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF; Clinical Trials.gov NCT 003 58215) was designed to evaluate the effect of the long-acting erythropoietin-stimulating agent darbepoetin alfa on mortality and morbidity (and quality of life) in patients with HF and anaemia. Approximately 2600 patients with New York Heart Association class II-IV, an ejection fraction = 9.0 g/dL will be enrolled. Patients are randomized 1:1 to double-blind subcutaneous administration of darbepoetin alfa or placebo. Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL (but not exceeding 14.5 g/dL) with sham adjustments of the dose of placebo. The primary endpoint is the time to death from any cause or first hospital admission for worsening HF, whichever occurs first. The study will complete when similar to 1150 subjects experience a primary endpoint

Susceptibility to Predation Affects Trait-Mediated Indirect Interactions by Reversing Interspecific Competition

Numerous studies indicate that the behavioral responses of prey to the presence of predators can have an important role in structuring assemblages through trait-mediated indirect interactions. Few studies, however, have addressed how relative susceptibility to predation influences such interactions. Here we examine the effect of chemical cues from the common shore crab Carcinus maenas on the foraging behavior of two common intertidal gastropod molluscs. Of the two model consumers studied, Littorina littorea is morphologically more vulnerable to crab predation than Gibbula umbilicalis, and it exhibited greater competitive ability in the absence of predation threat. However, Littorina demonstrated a greater anti-predator response when experimentally exposed to predation cues, resulting in a lower level of foraging. This reversed the competitive interaction, allowing Gibbula substantially increased access to shared resources. Our results demonstrate that the susceptibility of consumers to predation can influence species interactions, and suggest that inter-specific differences in trait-mediated indirect interactions are another mechanism through which non-consumptive predator effects may influence trophic interactions

Patient advocacy: barriers and facilitators

BACKGROUND: During the two recent decades, advocacy has been a topic of much debate in the nursing profession. Although advocacy has embraced a crucial role for nurses, its extent is often limited in practice. While a variety of studies have been generated all over the world, barriers and facilitators in the patient advocacy have not been completely identified. This article presents the findings of a study exploring the barriers and facilitators influencing the role of advocacy among Iranian nurses. METHOD: This study was conducted by grounded theory method. Participants were 24 Iranian registered nurses working in a large university hospital in Tehran, Iran. Semi-structured interviews were used for data collection. All interviews were transcribed verbatim and simultaneously Constant comparative analysis was used according to the Strauss and Corbin method. RESULTS: Through data analysis, several main themes emerged to describe the factors that hindered or facilitated patient advocacy. Nurses in this study identified powerlessness, lack of support, law, code of ethics and motivation, limited communication, physicians leading, risk of advocacy, royalty to peers, and insufficient time to interact with patients and families as barriers to advocacy. As for factors that facilitated nurses to act as a patient advocate, it was found that the nature of nurse-patient relationship, recognizing patients' needs, nurses' responsibility, physician as a colleague, and nurses' knowledge and skills could be influential in adopting the advocacy role. CONCLUSION: Participants believed that in this context taking an advocacy role is difficult for nurses due to the barriers mentioned. Therefore, they make decisions and act as a patient's advocate in any situation concerning patient needs and status of barriers and facilitators. In most cases, they can not act at an optimal level; instead they accept only what they can do, which we called 'limited advocacy' in this study. It is concluded that advocacy is contextually complex, and is a controversial and risky component of the nursing practice. Further research is needed to determine the possibility of a correlation between identified barriers/ facilitators and the use of advocacy

Research priorities for the COVID-19 pandemic and beyond: A call to action for psychological science

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has caused the coronavirus disease 2019 (COVID-19) pandemic represents the greatest international biopsychosocial emergency the world has faced for a century, and psychological science has an integral role to offer in helping societies recover. The aim of this paper is to set out the shorter- and longer-term priorities for research in psychological science that will (a) frame the breadth and scope of potential contributions from across the discipline; (b) enable researchers to focus their resources on gaps in knowledge; and (c) help funders and policymakers make informed decisions about future research priorities in order to best meet the needs of societies as they emerge from the acute phase of the pandemic. The research priorities were informed by an expert panel convened by the British Psychological Society that reflects the breadth of the discipline; a wider advisory panel with international input; and a survey of 539 psychological scientists conducted early in May 2020. The most pressing need is to research the negative biopsychosocial impacts of the COVID-19 pandemic to facilitate immediate and longer-term recovery, not only in relation to mental health, but also in relation to behaviour change and adherence, work, education, children and families, physical health and the brain, and social cohesion and connectedness. We call on psychological scientists to work collaboratively with other scientists and stakeholders, establish consortia, and develop innovative research methods while maintaining high-quality, open, and rigorous research standards

Research priorities for the COVID-19 pandemic and beyond: A call to action for psychological science

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has caused the coronavirus disease 2019 (COVID-19) pandemic represents the greatest international biopsychosocial emergency the world has faced for a century, and psychological science has an integral role to offer in helping societies recover. The aim of this paper is to set out the shorter- and longer-term priorities for research in psychological science that will (a) frame the breadth and scope of potential contributions from across the discipline; (b) enable researchers to focus their resources on gaps in knowledge; and (c) help funders and policymakers make informed decisions about future research priorities in order to best meet the needs of societies as they emerge from the acute phase of the pandemic. The research priorities were informed by an expert panel convened by the British Psychological Society that reflects the breadth of the discipline; a wider advisory panel with international input; and a survey of 539 psychological scientists conducted early in May 2020. The most pressing need is to research the negative biopsychosocial impacts of the COVID-19 pandemic to facilitate immediate and longer-term recovery, not only in relation to mental health, but also in relation to behaviour change and adherence, work, education, children and families, physical health and the brain, and social cohesion and connectedness. We call on psychological scientists to work collaboratively with other scientists and stakeholders, establish consortia, and develop innovative research methods while maintaining high-quality, open, and rigorous research standards