MicroRNAs in a hypertrophic heart: from foetal life to adulthood

The heart is the first organ to form and undergoes adaptive remodelling with age. Ventricular hypertrophy is one such adaptation, which allows the heart to cope with an increase in cardiac demand. This adaptation is necessary as part of natural growth from foetal life to adulthood. It may also occur in response to resistance in blood flow due to various insults on the heart and vessels that accumulate with age. The heart can only compensate to this increase in workload to a certain extent without losing its functional architecture, ultimately resulting in heart failure. Many genes have been implicated in cardiac hypertrophy, however none have been shown conclusively to be responsible for pathological cardiac hypertrophy. MicroRNAs offer an alternative mechanism for cellular regulation by altering gene expression. Since 1993 when the function of a non-coding DNA sequence was first discovered in the model organism Caenorhabditis elegans, many microRNAs have been implicated in having a central role in numerous physiological and pathological cellular processes. The level of control these antisense oligonucleotides offer can often be exploited to manipulate the expression of target genes. Moreover, altered levels of microRNAs can serve as diagnostic biomarkers, with the prospect of diagnosing a disease process as early as during foetal life. Therefore, it is vital to ascertain and investigate the function of microRNAs that are involved in heart development and subsequent ventricular remodelling. Here we present an overview of the complicated network of microRNAs and their target genes that have previously been implicated in cardiogenesis and hypertrophy. It is interesting to note that microRNAs in both of these growth processes can be of possible remedial value to counter a similar disease pathophysiology.

A 'slow pace of life' in Australian old-endemic passerine birds is not accompanied by low basal metabolic rates

Life history theory suggests that species experiencing high extrinsic mortality rates allocate more resources toward reproduction relative to self-maintenance and reach maturity earlier ('fast pace of life') than those having greater life expectancy and reproducing at a lower rate ('slow pace of life'). Among birds, many studies have shown that tropical species have a slower pace of life than temperate-breeding species. The pace of life has been hypothesized to affect metabolism and, as predicted, tropical birds have lower basal metabolic rates (BMR) than temperate-breeding birds. However, many temperate-breeding Australian passerines belong to lineages that evolved in Australia and share 'slow' life-history traits that are typical of tropical birds. We obtained BMR from 30 of these 'old-endemics' and ten sympatric species of more recently arrived passerine lineages (derived from Afro-Asian origins or introduced by Europeans) with 'faster' life histories. The BMR of 'slow' temperate-breeding old-endemics was indistinguishable from that of new-arrivals and was not lower than the BMR of 'fast' temperate-breeding non-Australian passerines. Old-endemics had substantially smaller clutches and longer maximal life spans in the wild than new arrivals, but neither clutch size nor maximum life span was correlated with BMR. Our results suggest that low BMR in tropical birds is not functionally linked to their 'slow pace of life' and instead may be a consequence of differences in annual thermal conditions experienced by tropical versus temperate species.

Qualitative observation in a clinical setting: challenges at end of life

This paper explores the methodological challenges associated with undertaking qualitative observation in the clinical setting at end of life. The authors reflect on their experiences of using non-participant observation to explore the nursing care delivered to dying patients in acute hospital wards. The challenges of observation as a method, clearly defining the participant group and involving vulnerable populations, such as the dying patients and their families, will be discussed. Consideration is also given to defining and working within the observational field, the researchers' dual roles, cost versus benefit, impact of culture, religion and ethnicity, and the determination of research limits/boundaries, with reflections from the authors' own experiences used to exemplify the issues.

Quality of life in outpatients with depression in China

BACKGROUND: Quality of life (QOL) is an important outcome measure for patients with depression, but QOL research involving large samples of patients has been uncommon. The purpose of this study was to evaluate the QOL of Chinese outpatients with depression and its determinants. METHODS: Using a cross-sectional survey design, data were collected continuously from 19,984 outpatients; 19,950 usable questionnaires were obtained. Along with the QOL index (WHOQOL-BREF), the questionnaire also included participants' sociodemographic characteristics, outpatient visits, and medication use information. RESULTS: Less than 5% of depressed patients reported "good" or "very good" QOL, while less than 3% were satisfied with their general health. The overall score was low (54.12); four QOL domain (physical health, psychological, social relationships, and environment) scores (range, 35.03-40.10) were significantly lower than in other community population surveys. QOL scores were significantly lower among first-visit than non-first-visit patients. Medication users reported significantly higher QOL scores than non-users, with NaSSA more effective than SSRIs, followed by other types, SNRIs, and no medication, in that order. LIMITATIONS: Since this was an observational, cross-sectional survey with continuous outpatient data collection method instead of random sampling, generalization of the results is limited, and causality cannot be determined. However, the "natural" observational design, large sample size, and similarity in findings with other studies reveal the "real world" QOL of depressed outpatients in mainland China. CONCLUSIONS: Depressed patients had a low QOL, and the scores of first-visit patients with severe symptoms were significantly lower than non-first-visit patients. Though medication can improve patients' QOL, different types of medications have different impacts.

Neighbourhood environment, physical activity, quality of life and depressive symptoms in Hong Kong older adults: a protocol for an observational study

INTRODUCTION: The neighbourhood environment can assist the adoption and maintenance of an active lifestyle and affect the physical and mental well-being of older adults. The psychosocial and behavioural mechanisms through which the environment may affect physical and mental well-being are currently poorly understood. AIM: This observational study aims to examine associations between the physical and social neighbourhood environments, physical activity, quality of life and depressive symptoms in Chinese Hong Kong older adults.

METHODS AND ANALYSES: An observational study of the associations of measures of the physical and social neighbourhood environment, and psychosocial factors, with physical activity, quality of life and depressive symptoms in 900 Hong Kong older adults aged 65+ years is being conducted in 2012-2016. The study involves two assessments taken 6 months apart. Neighbourhood walkability and access to destinations are objectively measured using Geographic Information Systems and environmental audits. Demographics, socioeconomic status, walking for different purposes, perceived neighbourhood and home environments, psychosocial factors, health status, social networks, depressive symptoms and quality of life are being assessed using validated interviewer-administered self-report measures and medical records. Physical functionality is being assessed using the Short Physical Performance Battery. Physical activity and sedentary behaviours are also being objectively measured in approximately 45% of participants using accelerometers over a week. Physical activity, sedentary behaviours, quality of life and depressive symptoms are being assessed twice (6 months apart) to examine seasonality effects on behaviours and their associations with quality of life and depressive symptoms.

ETHICS AND DISSEMINATION: The study received ethical approval from the University of Hong Kong Human Research Ethics Committee for Non-Clinical Faculties (EA270211) and the Department of Health (Hong Kong SAR). Data are stored in a password-protected secure database for 10 years, accessible only to the named researchers. Findings will be submitted for publication in peer-reviewed journals.

Comparison of fracture rates between indigenous and non-indigenous populations: a systematic review protocol

INTRODUCTION: Over recent years, there has been concerted effort to 'close the gap' in the disproportionately reduced life expectancy and increased morbidity experienced by indigenous compared to non-indigenous persons. Specific to musculoskeletal health, some data suggest that indigenous peoples have a higher risk of sustaining a fracture compared to non-indigenous peoples. This creates an imperative to identify factors that could explain differences in fracture rates. This protocol presents our aim to conduct a systematic review, first, to determine whether differences in fracture rates exist for indigenous versus non-indigenous persons and, second, to identify any risk factors that might explain these differences.

METHODS AND ANALYSIS: We will conduct a systematic search of PubMed, OVID, MEDLINE, CINAHL and EMBASE to identify articles that compare all-cause fracture rates at any skeletal site between indigenous and non-indigenous persons of any age. Eligibility of studies will be determined by 2 independent reviewers. Studies will be assessed for methodological quality using a previously published process. We will conduct a meta-analysis and use established statistical methods to identify and control for heterogeneity where appropriate. Should heterogeneity prevents numerical syntheses, we will undertake a best-evidence analysis to determine the level of evidence for differences in fracture between indigenous and non-indigenous persons.

ETHICS AND DISSEMINATION: This systematic review will use published data; thus, ethical permissions are not required. In addition to peer-reviewed publication, findings will be presented at (inter)national conferences, disseminated electronically and in print, and will be made available to key country-specific decision-makers with authority for indigenous health.

Personality and innate immune defenses in a wild bird: evidence for the pace-of-life hypothesis

We tested the two main evolutionary hypotheses for an association between immunity and personality. The risk-of-parasitism hypothesis predicts that more proactive (bold, exploratory, risk-taking) individuals have more vigorous immune defenses because of increased risk of parasite exposure. In contrast, the pace-of-life hypothesis argues that proactive behavioral styles are associated with shorter lifespans and reduced investment in immune function. Mechanistically, associations between immunity and personality can arise because personality differences are often associated with differences in condition and stress responsiveness, both of which are intricately linked with immunity. Here we investigate the association between personality (measured as proactive exploration of a novel environment) and three indices of innate immune function (the non-specific first line of defense against parasites) in wild superb fairy-wrens Malurus cyaneus. We also quantified body condition, hemoparasites (none detected), chronic stress (heterophil:lymphocyte ratio) and circulating corticosterone levels at the end of the behavioral test (CORT, in a subset of birds). We found that fast explorers had lower titers of natural antibodies. This result is consistent with the pace-of-life hypothesis, and with the previously documented higher mortality of fast explorers in this species. There was no interactive effect of exploration score and duration in captivity on immune indices. This suggests that personality-related differences in stress responsiveness did not underlie differences in immunity, even though behavioral style did modulate the effect of captivity on CORT. Taken together these results suggest reduced constitutive investment in innate immune function in more proactive individuals.

Monitoring and accountability for the Pacific response to the non-communicable diseases crisis

BACKGROUND: Non-communicable diseases (NCD) are the leading cause of premature death and disability in the Pacific. In 2011, Pacific Forum Leaders declared "a human, social and economic crisis" due to the significant and growing burden of NCDs in the region. In 2013, Pacific Health Ministers' commitment to 'whole of government' strategy prompted calls for the development of a robust, sustainable, collaborative NCD monitoring and accountability system to track, review and propose remedial action to ensure progress towards the NCD goals and targets. The purpose of this paper is to describe a regional, collaborative framework for coordination, innovation and application of NCD monitoring activities at scale, and to show how they can strengthen accountability for action on NCDs in the Pacific. A key component is the Dashboard for NCD Action which aims to strengthen mutual accountability by demonstrating national and regional progress towards agreed NCD policies and actions.

DISCUSSION: The framework for the Pacific Monitoring Alliance for NCD Action (MANA) draws together core country-level components of NCD monitoring data (mortality, morbidity, risk factors, health system responses, environments, and policies) and identifies key cross-cutting issues for strengthening national and regional monitoring systems. These include: capacity building; a regional knowledge exchange hub; innovations (monitoring childhood obesity and food environments); and a robust regional accountability system. The MANA framework is governed by the Heads of Health and operationalised by a multi-agency technical Coordination Team. Alliance membership is voluntary and non-conditional, and aims to support the 22 Pacific Island countries and territories to improve the quality of NCD monitoring data across the region. In establishing a common vision for NCD monitoring, the framework combines data collected under the WHO Global Framework for NCDs with a set of action-orientated indicators captured in a NCD Dashboard for Action.

SUMMARY : Viewing NCD monitoring as a multi-component system and providing a robust, transparent mutual accountability mechanism helps align agendas, roles and responsibilities of countries and support organisations. The dashboard provides a succinct communication tool for reporting progress on implementation of agreed policies and actions and its flexible methodology can be easily expanded, or adapted for other regions.