Increasing skeletal muscle carnitine availability does not alter the adaptations to high-intensity interval training

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Accepted manuscript online: 27 March 2017Increasing skeletal muscle carnitine availability alters muscle metabolism during steady-state exercise in healthy humans. We investigated whether elevating muscle carnitine, and thereby the acetyl-group buffering capacity, altered the metabolic and physiological adaptations to 24 weeks of high-intensity interval training (HIIT) at 100% maximal exercise capacity (Wattmax ). Twenty-one healthy male volunteers (age 23±2 years; BMI 24.2±1.1 kg/m(2) ) performed 2x3 minute bouts of cycling exercise at 100% Wattmax , separated by five minutes rest. Fourteen volunteers repeated this protocol following 24 weeks of HIIT and twice-daily consumption of 80g carbohydrate (CON) or 3g L-carnitine+carbohydrate (CARN). Before HIIT, muscle phosphocreatine (PCr) degradation (P<0.0001), glycogenolysis (P<0.0005), PDC activation (P<0.05), and acetylcarnitine (P<0.005) were 2.3, 2.1, 1.5 and 1.5-fold greater, respectively, in exercise bout two compared to bout one, whilst lactate accumulation tended (P<0.07) to be 1.5-fold greater. Following HIIT, muscle free carnitine was 30% greater in CARN vs CON at rest and remained 40% elevated prior to the start of bout two (P<0.05). Following bout two, free carnitine content, PCr degradation, glycogenolysis, lactate accumulation, and PDC activation were all similar between CON and CARN, albeit markedly lower than before HIIT. VO2max , Wattmax and work-output were similarly increased in CON and CARN, by 9, 15 and 23% (P<0.001). In summary, increased reliance on non-mitochondrial ATP resynthesis during a second bout of intense exercise is accompanied by increased carnitine acetylation. Augmenting muscle carnitine during 24 weeks of HIIT did not alter this, nor enhance muscle metabolic adaptations or performance gains beyond those with HIIT alone. This article is protected by copyright. All rights reserved.This research was supported by a BBSRC PhD studentship award for CS

Fisheries in the Development of Indian Economy

Fisheries sector plays a vital role in Indian economy through substantial forex earnings, employment generation and ensuring nutritional and food security. Contribution of fisheries to total Gross Domestic Product (GDP) at current prices is about 1.3 percent. The fisheries economy of our country has undergone rapid structural changes during the last few decades. The vast technological options available to fishers led them for a fast shift from traditional to mechanised and motorised fishing methods in marine fisheries and from traditional to improved seed production and culture practices in inland fisheries

Art therapy-based interventions to address burnout and psychosocial distress in healthcare workers-a systematic review

Background Burnout and psychosocial distress are serious and growing issues for healthcare workers (HCWs) and healthcare systems across the globe. Exacerbated by changes in healthcare delivery during and following the Covid-19 pandemic, these issues negatively affect HCW wellbeing, clinical outcomes and patient safety. Art Therapy has demonstrated promise as a suitable but under researched intervention, warranting further investigation. This systematic review aims to ascertain what art therapy-based interventions used to address burnout and / or psychosocial distress in HCWs have been reported in the health and social care literature and how these have been evaluated. Methods Six databases (PubMed, PsycINFO, MEDLINE, EMBASE, CINAHL, ProQuest Central), Google Scholar and three clinical trial registries (CENTRAL, ICTRP and ClinicalTrials.gov) were searched for studies using art therapy-based methods to engage with burnout risk or psychosocial distress in HCWs. Following screening for eligibility study characteristics and outcomes were extracted by two reviewers independently. Studies were evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Tools. Outcomes were grouped for analysis. Quantitative and qualitative results were synthesised and integrated using narrative synthesis. Results Twenty-seven studies, drawn from thirteen countries, spanning five continents were selected for inclusion. Fifty percent were published in the last five years, indicating growing global research in the field. Fourteen studies used quantitative research methods and thirteen used qualitative methods. A total of 1580 participants took part in the studies, with nurses most broadly represented (59%). Interventions were mostly delivered in groups (95%) and by an art therapist (70%). Heterogeneity and insufficient randomised controlled trials precluded the possibility of meta-analysis. However, a review of available data showed evidence of medium to large effects for emotional exhaustion (burnout), work-related stress and common mental health issues. A content analysis of qualitative data of perceived effect complemented quantitative findings. Conclusion Global research into the use of art therapy-based methods to address burnout and psychosocial distress in HCWs is growing. Whilst further high-quality evidence such as randomised controlled trials would be beneficial, findings suggest that art therapy-based methods should be strongly considered as an acceptable and effective treatment for symptoms of emotional exhaustion (burnout) and psychosocial distress in HCWs

Fish oil omega-3 fatty acids partially prevent lipid-induced insulin resistance in human skeletal muscle without limiting acylcarnitine accumulation

This is the author accepted manuscript. The final version is available from Portland Press via the DOI in this record Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic-hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater following n6PUFA compared with Control and n3PUFA, suggesting that mitochondrial lipid overload was responsible for the lower insulin action observed. Despite these favourable metabolic effects of n3PUFA, accumulation of total muscle acylcarnitine was not attenuated when compared with n6PUFA. These findings demonstrate that n3PUFA exert beneficial effects on insulin-stimulated skeletal muscle glucose storage and oxidation independently of total acylcarnitine accumulation, which does not always reflect mitochondrial lipid overload.This research study was funded by The Royal Society [Grant RG100575]

Emergency ambulance service involvement with residential care homes in the support of older people with dementia : an observational study

© 2014 Amador et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Older people resident in care homes have a limited life expectancy and approximately two-thirds have limited mental capacity. Despite initiatives to reduce unplanned hospital admissions for this population, little is known about the involvement of emergency services in supporting residents in these settings.METHODS: This paper reports on a longitudinal study that tracked the involvement of emergency ambulance personnel in the support of older people with dementia, resident in care homes with no on-site nursing providing personal care only. 133 residents with dementia across 6 care homes in the East of England were tracked for a year. The paper examines the frequency and reasons for emergency ambulance call-outs, outcomes and factors associated with emergency ambulance service use. RESULTS: 56% of residents used ambulance services. Less than half (43%) of all call-outs resulted in an unscheduled admission to hospital. In addition to trauma following a following a fall in the home, results suggest that at least a reasonable proportion of ambulance contacts are for ambulatory care sensitive conditions. An emergency ambulance is not likely to be called for older rather than younger residents or for women more than men. Length of residence does not influence use of emergency ambulance services among older people with dementia. Contact with primary care services and admission route into the care home were both significantly associated with emergency ambulance service use. The odds of using emergency ambulance services for residents admitted from a relative's home were 90% lower than the odds of using emergency ambulance services for residents admitted from their own home. CONCLUSIONS: Emergency service involvement with this vulnerable population merits further examination. Future research on emergency ambulance service use by older people with dementia in care homes, should account for important contextual factors, namely, presence or absence of on-site nursing, GP involvement, and access to residents' family, alongside resident health characteristics.Peer reviewedFinal Published versio

Increasing skeletal muscle carnitine content in older individuals increases whole-body fat oxidation during moderate-intensity exercise

This is the final version. Available on open access from Wiley via the DOI in this recordData availability: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.Intramyocellular lipid (IMCL) utilization is impaired in older individuals, and IMCL accumulation is associated with insulin resistance. We hypothesized that increasing muscle total carnitine content in older men would increase fat oxidation and IMCL utilization during exercise, and improve insulin sensitivity. Fourteen healthy older men (69 ± 1 year, BMI 26.5 ± 0.8 kg/m2 ) performed 1 h of cycling at 50% VO2 max and, on a separate occasion, underwent a 60 mU/m2 /min euglycaemic hyperinsulinaemic clamp before and after 25 weeks of daily ingestion of a 220 ml insulinogenic beverage (44.4 g carbohydrate, 13.8 g protein) containing 4.5 g placebo (n = 7) or L-carnitine L-tartrate (n = 7). During supplementation, participants performed twice-weekly cycling for 1 h at 50% VO2 max. Placebo ingestion had no effect on muscle carnitine content or total fat oxidation during exercise at 50% VO2 max. L-carnitine supplementation resulted in a 20% increase in muscle total carnitine content (20.1 ± 1.2 to 23.9 ± 1.7 mmol/kg/dm; p < 0.01) and a 20% increase in total fat oxidation (181.1 ± 15.0 to 220.4 ± 19.6 J/kg lbm/min; p < 0.01), predominantly due to increased IMCL utilization. These changes were associated with increased expression of genes involved in fat metabolism (ACAT1, DGKD & PLIN2; p < 0.05). There was no change in resting insulin-stimulated whole-body or skeletal muscle glucose disposal after supplementation. This is the first study to demonstrate that a carnitine-mediated increase in fat oxidation is achievable in older individuals. This warrants further investigation given reduced lipid turnover is associated with poor metabolic health in older adults.Dunhill Medical Trus

Estimates of linkage disequilibrium and effective population size in rainbow trout

<p>Abstract</p> <p>Background</p> <p>The use of molecular genetic technologies for broodstock management and selective breeding of aquaculture species is becoming increasingly more common with the continued development of genome tools and reagents. Several laboratories have produced genetic maps for rainbow trout to aid in the identification of loci affecting phenotypes of interest. These maps have resulted in the identification of many quantitative/qualitative trait loci affecting phenotypic variation in traits associated with albinism, disease resistance, temperature tolerance, sex determination, embryonic development rate, spawning date, condition factor and growth. Unfortunately, the elucidation of the precise allelic variation and/or genes underlying phenotypic diversity has yet to be achieved in this species having low marker densities and lacking a whole genome reference sequence. Experimental designs which integrate segregation analyses with linkage disequilibrium (LD) approaches facilitate the discovery of genes affecting important traits. To date the extent of LD has been characterized for humans and several agriculturally important livestock species but not for rainbow trout.</p> <p>Results</p> <p>We observed that the level of LD between syntenic loci decayed rapidly at distances greater than 2 cM which is similar to observations of LD in other agriculturally important species including cattle, sheep, pigs and chickens. However, in some cases significant LD was also observed up to 50 cM. Our estimate of effective population size based on genome wide estimates of LD for the NCCCWA broodstock population was 145, indicating that this population will respond well to high selection intensity. However, the range of effective population size based on individual chromosomes was 75.51 - 203.35, possibly indicating that suites of genes on each chromosome are disproportionately under selection pressures.</p> <p>Conclusions</p> <p>Our results indicate that large numbers of markers, more than are currently available for this species, will be required to enable the use of genome-wide integrated mapping approaches aimed at identifying genes of interest in rainbow trout.</p

Personalized versus standardized dosing strategies for the treatment of childhood amblyopia: study protocol for a randomized controlled trial

Background: Amblyopia is the commonest visual disorder of childhood in Western societies, affecting, predominantly, spatial visual function. Treatment typically requires a period of refractive correction (‘optical treatment’) followed by occlusion: covering the nonamblyopic eye with a fabric patch for varying daily durations. Recent studies have provided insight into the optimal amount of patching (‘dose’), leading to the adoption of standardized dosing strategies, which, though an advance on previous ad-hoc regimens, take little account of individual patient characteristics. This trial compares the effectiveness of a standardized dosing strategy (that is, a fixed daily occlusion dose based on disease severity) with a personalized dosing strategy (derived from known treatment dose-response functions), in which an initially prescribed occlusion dose is modulated, in a systematic manner, dependent on treatment compliance. Methods/design: A total of 120 children aged between 3 and 8 years of age diagnosed with amblyopia in association with either anisometropia or strabismus, or both, will be randomized to receive either a standardized or a personalized occlusion dose regimen. To avoid confounding by the known benefits of refractive correction, participants will not be randomized until they have completed an optical treatment phase. The primary study objective is to determine whether, at trial endpoint, participants receiving a personalized dosing strategy require fewer hours of occlusion than those in receipt of a standardized dosing strategy. Secondary objectives are to quantify the relationship between observed changes in visual acuity (logMAR, logarithm of the Minimum Angle of Resolution) with age, amblyopia type, and severity of amblyopic visual acuity deficit. Discussion: This is the first randomized controlled trial of occlusion therapy for amblyopia to compare a treatment arm representative of current best practice with an arm representative of an entirely novel treatment regimen based on statistical modelling of previous trial outcome data. Should the personalized dosing strategy demonstrate superiority over the standardized dosing strategy, then its adoption into routine practice could bring practical benefits in reducing the duration of treatment needed to achieve an optimal outcome

Association analysis of PRNP gene region with chronic wasting disease in Rocky Mountain elk

<p>Abstract</p> <p>Background</p> <p>Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids including white-tailed (<it>Odocoileus virginianus</it>) and mule deer (<it>Odocoileus hemionus</it>), Rocky Mountain elk (<it>Cervus elaphus nelsoni</it>), and moose (<it>Alces alces</it>). A leucine variant at position 132 (132L) in prion protein of Rocky Mountain elk confers a long incubation time with CWD, but not complete resistance. However, variants in regulatory regions outside the open reading frame of <it>PRNP </it>have been associated with varying degrees of susceptibility to prion disease in other species, and some variants have been observed in similar regions of Rocky Mountain elk <it>PRNP</it>. Thus, additional genetic variants might provide increased protection, either alone or in combination with 132L.</p> <p>Findings</p> <p>This study provided genomic sequence of all exons for <it>PRNP </it>of Rocky Mountain elk. Many functional sites in and around the <it>PRNP </it>gene region were sequenced, and this report approximately doubled (to 75) the number of known variants in this region. A haplotype-tagging approach was used to reduce the number of genetic variants required to survey this variation in the <it>PRNP </it>gene region of 559 Rocky Mountain elk. Eight haplotypes were observed with frequencies over 1.0%, and one haplotype was present at 71.2% frequency, reflecting limited genetic diversity in the <it>PRNP </it>gene region.</p> <p>Conclusions</p> <p>The presence of 132L cut odds of CWD by more than half (Odds Ratio = 0.43; P = 0.0031), which was similar to a previous report. However after accounting for 132L, no association with CWD was found for any additional variants in the <it>PRNP </it>region (P > 0.05).</p

Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity