(-)-Epicatechin and its colonic metabolite hippuric acid protect against dexamethasone-induced atrophy in skeletal muscle cells

Cocoa flavanols have been shown to improve muscle function and may offer a novel approach to protect against muscle atrophy. Hippuric acid (HA) is a colonic metabolite of (-)-epicatechin (EPI), the primary bioactive compound of cocoa, and may be responsible for the associations between cocoa supplementation and muscle metabolic alterations. Accordingly, we investigated the effects of EPI and HA upon skeletal muscle morphology and metabolism within an in vitro model of muscle atrophy. Under atrophy-like conditions (24h 100μM dexamethasone (DEX)), C2C12 myotube diameter was significantly greater following co-incubation with either 25μM HA (11.19±0.39μm) or 25μM EPI (11.01±0.21μm) compared to the vehicle control (VC; 7.61±0.16μm, both P < .001). In basal and leucine-stimulated states, there was a significant reduction in myotube protein synthesis (MPS) rates following DEX treatment in VC (P = .024). Interestingly, co-incubation with EPI or HA abrogated the DEX-induced reductions in MPS rates, whereas no significant differences versus control treated myotubes (CTL) were noted. Furthermore, co-incubation with EPI or HA partially attenuated the increase in proteolysis seen in DEX-treated cells, preserving LC3 α/β II:I and caspase-3 protein expression in atrophy-like conditions. The protein content of PGC1α, ACC, and TFAM (regulators of mitochondrial function) were significantly lower in DEX-treated versus. CTL cells (all P < .050). However, co-incubation with EPI or HA was unable to prevent these DEX-induced alterations. For the first time we demonstrate that EPI and HA exert anti-atrophic effects on C2C12 myotubes, providing novel insight into the association between flavanol supplementation and favourable effects on muscle health

High-affinity anion binding by steroidal squaramide receptors

Exceptionally powerful anion receptors have been constructed by placing squaramide groups in axial positions on a steroidal framework. The steroid preorganizes the squaramide NH groups such that they can act cooperatively on a bound anion, while maintaining solubility in nonpolar media. The acidic NH groups confer higher affinities than previously-used ureas or thioureas. Binding constants exceeding 1014?M?1 have been measured for tetraethylammonium salts in chloroform by employing a variation of Cram’s extraction procedure. The receptors have also been studied as transmembrane anion carriers in unilamellar vesicles. Unusually their activities do not correlate with anion affinities, thus suggesting an upper limit for binding strength in the design of anion carrier

Using computer algorithms to elucidate zebra finch reproductive behaviour

Birds that experience variation in climatic conditions must maintain a stable nest temperature during incubation for successful hatching of offspring. Varying nest structure and incubation behaviour may be the methods birds use to regulate nest temperature. We used a modeling approach to investigate how birds adjust incubation behaviour to ambient temperature. Hidden Markov Models (HMM) have been used previously to predict the spatial distribution of animals based on the models’ ability to classify movement behaviour. We used a HMM to predict zebra finch (Taeniopygia guttata) incubation behaviour and nest structure from a nest temperature data set. The full data set consisted of data logger nest temperature records and video recordings of incubation behaviour in two different temperature conditions. Nest temperature from data loggers was used to obtain predictions about the timing, duration and frequency of incubation which could then be compared to video recordings of incubation behaviour and the structure of nests. Predicted results would be that zebra finches in a colder temperature would incubate for longer periods of time than warmer temperatures, and that experience at those temperatures would play a role in how successful their breeding attempt will be. This research explores new uses of computational techniques in animal behaviour, animal cognition, and behavioural ecology, provides new information about behavioural regulation of nest temperature during incubation, and develops practical techniques for inferring behaviour from data loggers in the field and in the lab

Absolute risk representation in cardiovascular disease prevention: comprehension and preferences of health care consumers and general practitioners involved in a focus group study

Background Communicating risk is part of primary prevention of coronary heart disease and stroke, collectively referred to as cardiovascular disease (CVD). In Australia, health organisations have promoted an absolute risk approach, thereby raising the question of suitable standardised formats for risk communication. Methods Sixteen formats of risk representation were prepared including statements, icons, graphical formats, alone or in combination, and with variable use of colours. All presented the same risk, i.e., the absolute risk for a 55 year old woman, 16% risk of CVD in five years. Preferences for a five or ten-year timeframe were explored. Australian GPs and consumers were recruited for participation in focus groups, with the data analysed thematically and preferred formats tallied. Results Three focus groups with health consumers and three with GPs were held, involving 19 consumers and 18 GPs. Consumers and GPs had similar views on which formats were more easily comprehended and which conveyed 16% risk as a high risk. A simple summation of preferences resulted in three graphical formats (thermometers, vertical bar chart) and one statement format as the top choices. The use of colour to distinguish risk (red, yellow, green) and comparative information (age, sex, smoking status) were important ingredients. Consumers found formats which combined information helpful, such as colour, effect of changing behaviour on risk, or comparison with a healthy older person. GPs preferred formats that helped them relate the information about risk of CVD to their patients, and could be used to motivate patients to change behaviour. Several formats were reported as confusing, such as a percentage risk with no contextual information, line graphs, and icons, particularly those with larger numbers. Whilst consumers and GPs shared preferences, the use of one format for all situations was not recommended. Overall, people across groups felt that risk expressed over five years was preferable to a ten-year risk, the latter being too remote. Conclusions Consumers and GPs shared preferences for risk representation formats. Both groups liked the option to combine formats and tailor the risk information to reflect a specific individual's risk, to maximise understanding and provide a good basis for discussion

RNA interference in the cat flea, Ctenocephalides felis : Approaches for sustained gene knockdown and evidence of involvement of Dicer-2 and Argonaute2

This work was supported by a Knowledge Transfer Network BBSRC Industrial Case (# BB/L502467/1) studentship in association with Zoetis Inc. We acknowledge the expert help provided by Nikki Kernell (Zoetis Inc., Kalamazoo) during the feeding trials. Declarations of interest: none.Peer reviewedPublisher PD

Anticholinergic burden (prognostic factor) for prediction of dementia or cognitive decline in older adults with no known cognitive syndrome (Review)

Funding Information: National Institute on Aging, NIH Grants, and the Branta Foundation Funding Information: We followed best practice in design, conduct, and reporting of our prognosis review as detailed in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019). The review was supported by the Cochrane Prognostic Methods Group, partners within the Cochrane Mental Health and Neuroscience Network, and the UK National Institute for Health Research Complex Reviews Support Unit (NIHR CRSU). Funding Information: American Philosophical Society, the National Institute on Aging grants, and by the Illinois Department of Public Health to DAB Funding Information: This protocol was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Dementia and Cognitive Improvement group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service or the Department of Health Publisher Copyright: Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.Peer reviewedPublisher PD

Riparian reserves protect butterfly communities in selectively logged tropical forest

Selective logging is the most widespread habitat disturbance in tropical forests. Primary forest set-asides along riparian zones are mandated in many countries and a key question is whether these riparian reserves provide biodiversity conservation benefits. We characterise butterfly communities in fixed-width riparian reserves of 30 m on each bank along narrow streams (<10 m) paired with interior logged forest transects, and in primary forests within a selective logging concession in the south-western Brazilian Amazon. We found that primary forest species richness was more similar to riparian reserves than to paired interior logged forest points, whereas abundance remained higher in both riparian reserves and interior logged points, likely due to the intrusion of canopy-dwelling species in disturbed habitats, as previously reported in the literature. Butterfly assemblages within riparian reserves were more similar to unlogged primary forests than interior logged points, and canopy height in riparian reserves was associated with increased assemblage similarity to primary forest points. Changes in abundance relative to primary forest were of a larger magnitude in interior logged points than in riparian reserves within logged forests, highlighting the role of riparian reserves in maintaining primary forest-like communities. We found no particular primary forest butterfly clades to be more sensitive to changes in abundance than other clades. Synthesis and applications. Mandatory conservation set-asides around streams or rivers (riparian buffers) have an important role in protecting the abundance and composition of primary forest butterfly assemblages within selective logging concessions in tropical rainforests. This study highlights the need to assess the conservation value of protecting unlogged riparian forest strips in other taxa to inform policy

Addressing transport safety and accessibility for people with a disability in developing countries: a formative evaluation of the Journey Access Tool in Cambodia

Background: The intersection between health, disability and transport has significant practical challenges for people with a disability living in low- and middle-income countries (LMICs), where road infrastructure is poor and travel unsafe. Lack of transport access to health, education, employment and other services impedes achievement of the Sustainable Development Goals and affects quality of life. The Journey Access Tool (JAT) combines access audit and road safety audit approaches to identify barriers to transport on journeys taken by people with a disability. To be useful and effective, it must fit the expectations of people with a disability (be acceptable) and be feasible for use in different settings (adoptable). Accordingly, a formative evaluation process was undertaken in Phnom Penh, Cambodia. Objectives: To undertake a formative evaluation of the JAT using an iterative process to tailor the tool, pilot its use by people with a disability, and develop a template for its implementation in other LMICs. Methods: An iterative process of consultation and three pilots was undertaken. Participants were people with a disability who undertook journeys with a public transport component accompanied by assistants. Focus groups were held after each pilot, and results were integrated into JAT revisions. Results: Issues of terminology were resolved early, as were process issues related to the length of time taken to complete the JAT. Interpersonal issues were more difficult to address, with assistants tending to exceed their role and record their own comments. Use of the tool provided rich information on barriers. Conclusions: The JAT was both acceptable and adoptable for people with a disability and other stakeholders, and the experience gained will facilitate adaptation of the tool to new settings. The tool has significant potential to shape and support advocacy for change and engagement with transport services and also health, education, employment and other services

PAX-D:study protocol for a randomised placebo-controlled trial evaluating the efficacy and mechanism of pramipexole as add-on treatment for people with treatment resistant depression

Introduction: Clinical depression is usually treated in primary care with psychological therapies and antidepressant medication. However, when patients do not respond to at least two or more antidepressants within a depressive episode, they are considered to have treatment resistant depression (TRD). Previous small randomised controlled trials suggested that pramipexole, a dopamine D2/3 receptor agonist, may be effective for treating patients with unipolar and bipolar depression as it is known to influence motivational drive and reward processing. PAX-D will compare the effects of pramipexole versus placebo when added to current antidepressant medication for people with TRD. Additionally, PAX-D will investigate the mechanistic effect of pramipexole on reward sensitivity using a probabilistic decision-making task. Methods and analysis: PAX-D will assess effectiveness in the short- term (during the first 12 weeks) and in the longer-term (48 weeks) in patients with TRD from the UK. The primary outcome will be change in self-reported depressive symptoms from baseline to Week 12 post-randomisation measured using the QIDS-SR. Performance on the decision-making task will be measured at Week 0, Week 2, and Week 12. Secondary outcomes include anhedonia, anxiety, and health economic measures including quality of life, capability, wellbeing, and costs. PAX-D will also assess the adverse effects of pramipexole including impulse control difficulties. Discussion: Pramipexole is a promising augmentation agent for treatment resistant depression and may be a useful addition to existing treatment regimes. PAX-D will assess its effectiveness and test for a potential mechanism of action in patients with treatment resistant depression

Can Healthcare Assistant Training (CHAT) improve the relational care of older people? Study protocol for a pilot cluster-randomised controlled trial

Background People aged 75 years and over account for one in four of all hospital admissions. There has been increasing recognition of problems in the care of older people, particularly in hospitals. Evidence suggests that older people judge the care they receive in terms of kindness, empathy, compassion, respectful communication and being seen as a person not just a patient. These are aspects of care to which we refer when we use the term 'relational care'. Healthcare assistants deliver an increasing proportion of direct care to older people, yet their training needs are often overlooked. Methods/design This study will determine the acceptability and feasibility of a cluster randomised controlled trial of 'Older People's Shoes' a two-day training intervention for healthcare assistants caring for older people in hospital. Within this pilot, two-arm, parallel, cluster randomised controlled trial, healthcare assistants within acute hospital wards are randomised to either the two-day training intervention or training as usual. Registered nurses deliver 'Older People's Shoes' over two days, approximately one week apart. It contains three components: experiential learning about ageing, exploration of older people's stories, and customer care. Outcomes will be measured at the level of patient (experience of emotional care and quality of life during their hospital stay), healthcare assistant (empathy and attitudes towards older people), and ward (quality of staff/patient interaction). Semi-structured interviews of a purposive sample of healthcare assistants receiving the intervention, and all trainers delivering the intervention, will be undertaken to gain insights into the experiences of both the intervention and the trial, and its perceived impact on practice. Trial registration The study was registered as an International Standard Randomised Contolled Trial (ISRCTN10385799) on 29 December 2014