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2020 De Gruyter. All rights reserved. Objectives: Heart rate variability (HRV) is often measured during clinical and experimental cardiovascular reflex tests (CRT), as a reflection of cardiac autonomic modulation, despite limited characterization of the rapid responses that occur. Therefore, we evaluated the responsiveness of HRV indices in 20 healthy young adults (age, 27 ± 6 y; mass, 76.9 ± 16.8 kg; height, 1.79 ± 0.12 m) during four separate established CRT. Methods: These included the [I] orthostatic challenge, [II] isometric handgrip, [III] cold pressor and [IV] cold diving reflex tests. Electrocardiogram was recorded throughout, with HRV derived from RR intervals at rest and from each CRT. On a separate day, a subgroup of participants (n=9) completed the same protocol for a second time. Results: The maximal slope of heart rate change (dTdt) was significantly different between all CRT, with the orthostatic challenge producing the fastest increase (2.56 ± 0.48) and the cold pressor the fastest reduction (−1.93 ± 0.68) in heart rate. Overall HRV, reflected by Poincaré plot ratio (SD1:SD2), was significantly reduced during all CRT ([I], −0.41 ± 0.12; [II], −0.19 ± 0.05; [III], −0.36 ± 0.12; [IV], −0.44 ± 0.11; p<0.05) relative to baseline and this was reproducible in time-series. However, when HRV indices were correlated to mean-RR an exponential growth-like relationship was evident (R2 ranging from: 0.52-0.62). Conclusions: These unique outcomes demonstrate that short-term alterations in HRV are evident during CRT, while indicating the importance of adjusting for, or at least reporting, underlying heart rate when interpreting such measures.

Background Dietary fish oil provides polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and is associated with modified oxygen consumption, contractile fatigue and physiological responses to ischaemia or hypoxia in striated muscle. This study systematically investigated the membrane incorporation of fatty acids, with a focus on DHA, into skeletal muscle in relation to functional/metabolic differences and their responsiveness to fish oil doses. Methods Male Sprague-Dawley rats were randomised to isoenergetic diets (10% fat by weight). Human Western-style diets were simulated with 5.5% tallow, 2.5% n-6 PUFA sunflower seed oil and 2% olive oil (Control). High-DHA tuna oil exchanged for olive oil provided a Low (0.32%) or moderate (Mod) (1.25%) fish oil diet. Membrane phospholipid fatty acid composition was analysed in samples of five skeletal muscles selected for maximum variation in muscle fibre-type. Results Concentrations of DHA varied according to muscle fibre type, very strongly associated with fast oxidative glycolytic fibre population (r2 = 0.93; P < 0.01). No relationship was evident between DHA and fast glycolytic or slow oxidative fibre populations. Fish oil diets increased membrane incorporation of DHA in all muscles, mainly at the expense of n-6 PUFA linoleic and arachidonic acid. Conclusion The exquisite responsiveness of all skeletal muscles to as little fish oil as the equivalent of 1-2 fish meals per week in a human diet and the selective relationship to fatigable muscle fibre-types supports an integral role for DHA in muscle physiology, and particularly in fatigue resistance of fast-twitch muscles.

Background and Purpose- We hypothesized that total marine n-3 polyunsaturated fatty acids (PUFA), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the diet and in adipose tissue (biomarkers of long-term intake and endogenous exposure) were inversely associated with the risk of ischemic stroke and its subtypes. Methods- The Diet, Cancer and Health cohort consisted of 57 053 participants aged 50 to 65 years at enrolment. All participants filled in a food frequency questionnaire and had an adipose tissue biopsy taken at baseline. Information on ischemic stroke during follow-up was obtained from The Danish National Patient Register, and all cases were validated. Cases and a random sample of 3203 subjects from the whole cohort had their fatty acid composition of adipose tissue determined by gas chromatography. Results- During 13.5 years of follow-up 1879 participants developed an ischemic stroke. Adipose tissue content of EPA was inversely associated with total ischemic stroke (hazard ratio [HR], 0.74; 95% CI, 0.62-0.88) when comparing the highest with the lowest quartile. Also, lower rates of large artery atherosclerosis were seen with higher intakes of total marine n-3 PUFA (HR, 0.69; 95% CI, 0.50-0.95), EPA (HR, 0.66; 95% CI, 0.48-0.91) and DHA (HR, 0.72; 95% CI, 0.53-0.99), and higher adipose tissue content of EPA (HR, 0.52; 95% CI, 0.36-0.76). Higher rates of cardioembolism were seen with higher intakes of total marine n-3 PUFA (HR, 2.50; 95% CI, 1.38-4.53) and DHA (HR, 2.12; 95% CI, 1.21-3.69) as well as with higher adipose tissue content of total marine n-3 PUFA (HR, 2.63; 95% CI, 1.33-5.19) and DHA (HR, 2.00; 95% CI, 1.04-3.84). The EPA content in adipose tissue was inversely associated with small-vessel occlusion (HR, 0.69; 95% CI, 0.55-0.88). Conclusions- EPA was associated with lower risks of most types of ischemic stroke, apart from cardioembolism, while inconsistent findings were observed for total marine n-3 PUFA and DHA.

While 'public health medicine' is a specialised field, most medical practitioners practice 'public health' to some extent, e.g., undertaking preventative screening tests or advising individuals about lifestyle interventions. While requirements to demonstrate capability in public health are common to medical education around the world, medical programs face a challenge to integrate public health education and promote health advocacy in an environment where the doctor: patient relationship is at the core of learning. Students who spend part of their medical education working within general practice or community settings have an opportunity to observe and identify issues of public health importance, and to see how they impact at both a personal and a population level. This paper aims to illustrate how a year-long research project can provide an opportunity for medical students to learn about public health issues and methods to investigate them. Analysis was undertaken of the research topics chosen by eight successive cohorts of medical students, representing 519 students, who successfully completed a research project. Over half of the student research projects (51.8%) directly related to Australian national health priority areas of dementia, obesity, arthritis and musculoskeletal conditions, asthma, diabetes, mental health, injury prevention and control, cardiovascular health and cancer control, and a further 28.5% of projects had a specific public health focus, within domains that include lifestyles and health, communicable disease, and healthy growth and development. Researching public health topics in the community setting represents a practical way to engage medical students in learning about public health, and can help to develop their potential to become 'clinician researchers', investigating and understanding issues relevant to their communities.

We investigated the risk of ischemic stroke and its subtypes when red meat or poultry was substituted with fish. A total of 57,053 participants aged 50-65 years at baseline were included in the Danish Diet, Cancer and Health study. All participants filled in a food-frequency questionnaire at recruitment. Potential ischemic stroke cases were identified by linkage to the Danish National Patient Register, and all cases were validated and subclassified. Substitutions were investigated as 150 g/week of fish for 150 g/week of red meat or of poultry using multivariable Cox proportional hazard regression models. During 13.5 years of follow-up, 1879 participants developed an ischemic stroke. Replacing red meat or poultry with fish was not associated with the rate of total ischemic stroke, but there was a statistically significant lower rate of large artery atherosclerosis when fish replaced processed (hazard ratio (HR): 0.78; 95% confidence interval (CI): 0.67; 0.90) and unprocessed (HR: 0.87; 95% CI: 0.75; 0.99) red meat. A statistically significant higher rate of cardioembolism was found when poultry was replaced by total fish (HR: 1.42; 95% CI: 1.04; 1.93). When fatty fish replaced unprocessed red meat, a statistically significant lower rate of small-vessel occlusion was found (HR: 0.88; 95% CI: 0.77; 0.99). In conclusion, replacing red meat with fish was not associated with risk of total ischemic stroke but was associated with a lower risk of subtypes of ischemic stroke.

Evidence-based medical practice is best achieved by developing research understanding in medical practitioners. To this end, medical councils worldwide increasingly recognise the importance of medical schools graduating students with well-developed research skills and research capacity. To meet this need, the principles of programmatic assessment were implemented in designing a research and critical analysis curriculum and assessment program that aimed to enhance the research and critical analysis skills of medical students. The program was developed by mapping assessment tasks to a research capabilities framework that was in turn scaffolded to different levels of Miler's pyramid. The curriculum and assessments were integrated with the science, clinical, and professional aspects of the medical course. The progressive longitudinal development of research skills, with feedback and academic mentoring, culminated in the students' capacity to undertake an independent research project. Designing an assessment program for learning encouraged students to develop their research capacity by involving them in their learning.

Regular fish or fish oil intake is associated with a low incidence of heart failure clinically, and fish oil-induced reduction in cardiac remodelling seen in hypertrophy models may contribute. We investigated whether improved cardiac energy efficiency in non-hypertrophied hearts translates into attenuation of cardiac dysfunction in hypertrophied hearts. Male Wistar rats (n 33) at 8 weeks of age were sham-operated or subjected to abdominal aortic stenosis to produce pressure-overload cardiac hypertrophy. Starting 3 weeks post-operatively to follow initiation of hypertrophy, rats were fed a diet containing 10% olive oil (control) or 5% fish oil (ROPUFA® 30 (17% EPA, 10% DHA))+5% olive oil (FO diet). At 15 weeks post-operatively, ventricular haemodynamics and oxygen consumption were evaluated in the blood-perfused, isolated working heart. Resting and maximally stimulated cardiac output and external work were >60% depressed in hypertrophied control hearts but this was prevented by FO feeding, without attenuating hypertrophy. Cardiac energy efficiency was lower in hypertrophy, but greater in FO hearts for any given cardiac mass. Coronary blood flow, restricted in hypertrophied control hearts, increased with increasing work in hypertrophied FO hearts, revealing a significant coronary vasodilator reserve. Pronounced cardiac dysfunction in hypertrophied hearts across low and high workloads, indicative of heart failure, was attenuated by FO feeding in association with membrane incorporation of n-3 PUFA, principally DHA. Dietary fish oil may offer a new approach to balancing the high oxygen demand and haemodynamic requirements of the failing hypertrophied heart independently of attenuating hypertrophy

Research skills are fundamental to the building of the evidence basis of professional practice, are at the core of lifelong professional learning and are the keys to discovery, innovation and knowledge transfer. Research competency is thus increasingly recognised as an important educational goal for graduates in many professions. This paper describes a flexible program, adaptable to any professional course of study that allows students to engage in meaningful, scholarly and authentic research. Students are supported to undertake a research activity that spans the research continuum from development of a research question through to dissemination of findings, and strategic points in-between.

Background: Epidemiological studies and randomised clinical trials (RCTs) report disparate findings in relation to omega-3 polyunsaturated fatty acids (n-3 PUFA) benefit for cardiac patients. With RCTs interpretation is potentially confounded by background n-3 PUFA intake. The goal of this pilot, small cohort, pre-surgical supplementation study was to evaluate post-operative atrial fibrillation (AF) and cardiac molecular expression profiles employing two data analysis approaches - by treatment randomisation and by stratification using measured n-3 PUFA. Methods: Patients (n=20) received 3g/day of fish or placebo oil (FO vs PO) in a double blind randomised protocol prior to elective coronary artery graft and valve surgery. Groups were matched for age, gender, and mean treatment duration (~20 days). Resected atrial myocardium was sampled for assay of viability metabolic markers, and blood obtained for erythrocyte membrane lipid measurement. Results: There was substantial overlap of cell membrane n-3 PUFA content across PO and FO groups, and no group treatment effects on AF incidence or myocardial molecular marker levels were detected. In contrast, data stratification using membrane n-3 PUFA content (at 8% total membrane lipid) achieved significant separation of patients (by n-6:n-3 PUFA ratio), a significant differential cardiac expression of the marker peroxisomal proliferator-activated receptor, but no difference in AF incidence. Conclusions: This small n-3 PUFA case study demonstrates that the same cohort may yield differing findings when evaluated using randomisation or stratification approaches based on direct molecular measures in cell membranes.

Oxygen efficiency influences skeletal muscle contractile function during physiological hypoxia. Dietary fish oil, providing docosahexaenoic acid (DHA), reduces the oxygen cost of muscle contraction. This study used autologous perfused rat hindlimb model to examine the effects of a fish oil diet on skeletal muscle fatigue during an acute hypoxic challenge. Male Wistar rats were fed a diet rich in saturated fat (SF), long chain (LC) n-6 polyunsaturated fatty acids (n-6 PUFA), or LC n-3 PUFA DHA from fish oil (FO) (8weeks). During anaesthetised and ventilated conditions (normoxia 21% O2 [SaO2-98%] and hypoxia 14% O2 [SaO2-89%]) the hindlimb was perfused at a constant flow and the gastrocnemius-plantaris-soleus muscle bundle was stimulated via sciatic nerve (2Hz, 6-12V, 0.05ms) to established fatigue. Caffeine (2.5, 5, 10mM) was supplied to the contracting muscle bundle via the arterial cannula to assess force recovery. Hypoxia, independent of diet, attenuated maximal twitch tension (normoxia: 82±8; hypoxia 41±2g.g-1 tissue w.w.). However, rats fed fish oil sustained higher peak twitch tension compared to the SF and n-6 PUFA groups (P<0.05) and the time to decline to 50% of maximum twitch tension was extended (SF; 546±58, n-6PUFA; 522±58, FO; 792±96 s; P<0.05). In addition, caffeine stimulated skeletal muscle contractile recovery was enhanced in the fish oil fed animals (SF; 41±3, n-6PUFA; 40±4, FO; 52±7% recovery; P<0.05). These results support a physiological role of DHA in skeletal muscle membranes when exposed to low-oxygen stress that is consistent with the attenuation of muscle fatigue under physiologically normoxic conditions.

Background: This study aimed to assess and compare health literacy levels in a range of university-based health students. Methods: A survey containing the Health Literacy Questionnaire (HLQ) was administered to students enrolled in university-based medical, allied health or nursing degree programs. The HLQ scores and scale scores were compared across student groups. Results: In total, 374 students (24% response rate) with a median age of 25 years (range: 17-61 years), returned completed surveys. Three students who did not identify their degree programs were excluded from the final analysis which included 371 respondents; 242 graduate-entry medical students (65%), 67 allied health students (18%) and 62 nursing students (17%). Overall, the medical students had the highest score for seven of the nine HLQ scales; while the nursing students had the lowest score for all of the nine HLQ scales. Conclusion: These results show that health literacy profiles are different across student groups. In order to provide excellent patient-centred care, and to successfully look after their own health, a high level of health literacy is required by future health professionals. Health literacy training modules, tailored according to the different needs of the student groups, should therefore be included in university-based health professional degree programs.

Nutrition is central to optimizing training adaptation and performance. Dietary fish oil provides long chain omega-3 polyunsaturated fatty acids (LC n–3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that are essential for biological function beyond providing metabolic energy. Emerging evidence demonstrates fish oil, without compromising carbohydrate or protein, can support the physiological stress of exhaustive exercise via direct modulation of systems physiology. Intake of DHA-rich fish oil elevates the erythrocyte omega-3 index, reflective of heart and skeletal muscle incorporation, and modulates oxygen usage during exercise without compromise to maximal aerobic power. Alternatively, the emerging role of circulating EPA has primarily focused upon immune and inflammatory support, including muscle damage, where preliminary evidence suggests attenuation of inflammatory response in less trained individuals. Future studies will need to further consider the biological difference that DHA can offer in these fields. Despite physiological benefits, provision of dietary fish oil has not yet been demonstrated to have performance enhancing effects in well-trained or elite athletes. Nonetheless, there are specific exercise conditions that are discussed in this chapter that warrant further investigations. Notwithstanding, these studies must occur with the highest standards of biological plausibility including monitoring of tissue incorporation and implementing study design in agreement with the most recent recommendations for demonstrating interaction of nutrition and performance.

of a poster presentation at the 2016 National Medicines Symposium, 19-20 May, Canberra, Australia.

High intakes of dietary fish oil increase myocardial membrane incorporation of the long chain omega-3 polyunsaturated fatty acid (n-3 PUFA) docosahexaenoic acid (DHA; 22:6n-3) and of physiological consequence, heart rate is slowed and cardiac arrhythmia's are reduced.(1,2,3) Myocardial muscle membrane composition is also responsive to very small dietary fish oil intakes,(1) equivalent to what could be achieved in the human dietary intake range through regular consumption of fish.

A definitive understanding of the role of dietary lipids in determining cardioprotection (or cardiodetriment) has been elusive. Randomized trial findings have been variable and sex specificity of dietary interventions has not been determined. In this investigation the sex-selective cardiac functional effects of three diets enriched by omega-3 or omega-6 polyunsaturated fatty acids (PUFA) or enriched to an equivalent extent in saturated fatty acid components were examined in rats after an 8-wk treatment period. In females the myocardial membrane omega-6:omega-3 PUFA ratio was twofold higher than males in the omega-6 diet replacement group. In diets specified to be high in omega-3 PUFA or in saturated fat, this sex difference was not apparent. Isolated cardiomyocyte and heart Langendorff perfusion experiments were performed, and molecular measures of cell viability were assessed. Under basal conditions the contractile performance of omega-6 fed female cardiomyocytes and hearts was reduced compared with males. Omega-6 fed females exhibited impaired systolic resilience after ischemic insult. This response was associated with increased postischemia necrotic cell damage evaluated by coronary lactate dehydrogenase during reperfusion in omega-6 fed females. Cardiac and myocyte functional parameters were not different between omega-3 and saturated fat dietary groups and within these groups there were no discernible sex differences. Our data provide evidence at both the cardiac and cardiomyocyte levels that dietary saturated fatty acid intake replacement with an omega-6 (but not omega-3) enriched diet has selective adverse cardiac effect in females. This finding has potential relevance in relation to women, cardiac risk, and dietary management.

Reactive oxygen species paradoxically underpin both ischaemia/reperfusion (I/R) damage and ischaemic preconditioning (IPC) cardioprotection. Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) are highly susceptible to peroxidation, but are paradoxically cardioprotective. This study tested the hypothesis that LCn-3 PUFA cardioprotection is underpinned by peroxidation, upregulating antioxidant activity to reduce I/R-induced lipid oxidation, and the mechanisms of this nutritional preconditioning contrast to mechanisms of IPC. Rats were fed: fish oil (LCn-3 PUFA); sunflower seed oil (n-6 PUFA); or beef tallow (saturated fat, SF) enriched diets for six weeks. Isolated hearts were subject to: 180 min normoxic perfusion; a 30 min coronary occlusion ischaemia protocol then 120 min normoxic reperfusion; or a 3 x 5 min global IPC protocol, 30 min ischaemia, then reperfusion. Dietary LCn-3 PUFA raised basal: membrane docosahexaenoic acid (22:6n-3 DHA); fatty acid peroxidisability index; concentrations of lipid oxidation products; and superoxide dismutase (MnSOD) activity (but not CuZnSOD or glutathione peroxidase). Infarct size correlated inversely with basal MnSOD activity (r2 = 0.85) in the ischaemia protocol and positively with I/R-induced lipid oxidation (lipid hydroperoxides (LPO), r2 = 0.475; malondialdehyde (MDA), r2 = 0.583) across ischaemia and IPC protocols. While both dietary fish oil and IPC infarct-reduction were associated with reduced I/R-induced lipid oxidation, fish oil produced nutritional preconditioning by prior LCn-3 PUFA incorporation and increased peroxidisability leading to up-regulated mitochondrial SOD antioxidant activity.

of a presentation.

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of a presentation at the AMEE 2015 conference, 4-9 September, Glasgow, United Kingdom.

Research is increasingly recognised as a key component of medical curricula, offering a range of benefits including development of skills in evidence-based medicine. The literature indicates that experienced academic supervision or mentoring is important in any research activity and positively influences research output. The aim of this project was to investigate the human research ethics experiences and knowledge of three groups: medical students, and university academic staff and clinicians eligible to supervise medical student research projects; at two Australian universities. Training in research ethics was low amongst academic staff and clinicians eligible to supervise medical student research. Only two-thirds of academic staff (67.9 %) and students (65.7 %) and less than half of clinicians surveyed (47.1 %; p = 0.014) indicated that specific patient consent was required for a doctor to include patient medical records within a research publication. There was limited awareness of requirements for participant information and consent forms amongst all groups. In the case of clinical trials, fewer clinicians (88.4 %) and students (83.3 %) than academics (100 %) indicated there was a requirement to obtain consent (p = 0.009). Awareness of the ethics committee focus on respect was low across all groups. This project has identified significant gaps in human research ethics understanding among medical students, and university academic staff and clinicians. The incorporation of research within medical curricula provides the impetus for medical schools and their institutions to ensure that academic staff and clinicians who are eligible and qualified to supervise students' research projects are appropriately trained in human research ethics.

[Editorial] Your patients seek sage health and therapeutic advice. However, focussing on strong evidence-based advice is challenging while wading through disparate clinical studies and dispelling the confusing, sometimes apparently contradictory, out-of-context or incorrect messages trafficking to the public via news and internet media, fuelled by the noisy plethora of commercial 'nutriceutical' and 'food pharmacy' products. The cardiovascular benefits of dietary omega-3 long chain polyunsaturated fatty acids (LC PUFA) have been of increasing public and health professional attention and interest for the past several decades. It is therefore timely and important that such benefits are reviewed by Nestel et al., in this issue of Heart Lung and Circulation [1]. In this update of the 2008 National Heart Foundation of Australia (NHF) recommendations on clinical evidence for omega-3 PUFA in prevention and treatment of cardiovascular disease, Nestel et al. conclude that whilst there are clear benefits of eating fish, there is no additional support to recommend the use of refined fish oil supplements.

of a presentation at the AMEE 2015 conference, 4-9 September, Glasgow, United Kingdom.

of a presentation at the HERDSA 2015 Conference, 6-9 July, Melbourne, Australia.

Dietary fish oil (FO) modulates muscle O2 consumption and contractile function, predictive of effects on muscle fatigue. High doses unattainable through human diet and muscle stimulation parameters used engender uncertainty in their physiological relevance. We tested the hypothesis that nutritionally relevant FO doses can modulate membrane fatty acid composition and muscle fatigue. Male Sprague-Dawley rats were randomised to control (10 % olive oil (OO) by weight) or low or moderate FO diet (LowFO and ModFO) (HiDHA tuna fish oil) for 15 weeks (LowFO: 0·3 % FO, 9·7 % OO, 0·25 % energy as EPA + DHA; ModFO: 1·25 % FO, 8·75 % OO, 1·0 % energy as EPA + DHA). Hindlimb muscle function was assessed under anaesthesia in vivo using repetitive 5 s burst sciatic nerve stimulation (0·05 ms, 7-12 V, 5 Hz, 10 s duty cycle, 300 s). There were no dietary differences in maximum developed muscle force. Repetitive peak developed force fell to 50 % within 62 (SEM 10) s in controls and took longer to decline in FO-fed rats (LowFO 110 (SEM 15) s; ModFO 117 (SEM 14) s) (P<0·05). Force within bursts was better sustained with FO and maximum rates of force development and relaxation declined more slowly. The FO-fed rats incorporated higher muscle phospholipid DHA-relative percentages than controls (P<0·001). Incorporation of DHA was greater in the fast-twitch gastrocnemius (Control 9·3 (SEM 0·8) %, LowFO 19·9 (SEM 0·4), ModFO 24·3 (SEM 1·0)) than in the slow-twitch soleus muscle (Control 5·1 (SEM 0·2), LowFO 14·3 (SEM 0·7), ModFO 18·0 (SEM 1·4)) (P <0·001), which was comparable with the myocardium, in line with muscle fibre characteristics. The LowFO and ModFO diets, emulating human dietary and therapeutic supplement intake, respectively, both elicited muscle membrane DHA enrichment and fatigue resistance, providing a foundation for translating these physiological effects to humans.