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BACKGROUND Rural intention and experience during medical school have been related to subsequent rural work. However, their relative contributions and the timing of their effects are not known. These data are critical to effective educational interventions able to improve rural medical workforce numbers, an international priority. METHODS Participants were graduates of an Australian MBBS degree between 2006 and 2016, who completed both entry and exit surveys approved by the Medical Deans of Australia, including workplace intention data. Rural/urban workplace intention changes from entry to exit were analysed using multinomial logistic regression. Binary logistic regression was used to assess actual rural versus urban work, obtained from a public practitioner registration website. RESULTS Of 547 eligible undergraduates, 169 completed a year-long rural clinical school (RCS). A subset of 93 of the 547 graduates practiced rurally, of whom 42 had completed RCS. Both rural background and RCS predicted rural practice intention; both were also significantly related to actual rural work. Enduring rural intention was associated with nearly sevenfold odds of actually practicing rurally, compared with an enduring urban intention. Those who changed practice intention from entry to exit were more likely to practice in the region of their exit intention. Of special note: Rural Clinical School of Western Australia (RCSWA) exposure particularly affects urban origin students such that the odds of changing from an urban to a rural orientation immediately after their rural experience were more than fourfold higher than those not so participating. DISCUSSION Both intention and RCSWA experience are associated with subsequent rural work. The impacts of RCSWA were able to be localised after the rural educational experience. Amongst those with mutable intention, exit intention was that most strongly related to actual work, suggesting this as the most reliable point to select for further rural training.

Background Non-resolving inflammation associates with obesity and insulin resistance, and may be dependent on the balance of inflammatory substances and specialised pro-resolving mediators of inflammation (SPM) that act to halt the inflammatory response. This controlled trial examined the effect of weight loss on neutrophil synthesis of SPM in volunteers with the metabolic syndrome (MetS). Methods Volunteers with MetS (n = 42) were matched for age and gender and randomly assigned to a 12-wk weight loss program followed by 4-wk weight stabilization or a 16-wk weight maintenance program. At baseline and 16 weeks, isolated neutrophils were stimulated with calcium ionophore and the released SPM were measured by LC-MS/MS. Results At baseline the SPM resolvin (Rv) E1, 18R-RvE3, RvD2 and Maresin-1 (MaR-1) were detected from stimulated neutrophils. The concentration of released RvE1 was at least 6-fold that of other detected SPM. Weight loss of 4.7 ± 0.8 kg, led to a 2-fold increase in RvE1, P = 0.013, relative to the weight maintenance group. The increase in RvE1 after weight loss was related to, but independent of leukotriene B4. Conclusion Following weight loss, human neutrophils from individuals with the metabolic syndrome are capable of releasing larger amounts of RvE1 upon stimulation.

Objective(s) Cardiovascular disease (CVD) remains a leading cause of mortality in chronic kidney disease (CKD) patients. Interventions targeting traditional risk factors have largely proven ineffective in CKD patients in part because of the increased role of nontraditional risk factors such as chronic inflammation. Omega-3 fatty acids (ω3FA) are inexpensive and safe natural agents, which target inflammation and have potential cardioprotective benefits. The aim of the study was to determine the effects of ω3FA supplementation upon serum interleukin (IL)-12, IL-18, and highly sensitive C-reactive protein (hsCRP) in patients with Stage 3-4 CKD. Methods We performed a post-hoc analysis of a randomized placebo-controlled trial in 73 nondiabetic CKD patients to determine the effects of ω3FA supplementation (4 g daily for 8 weeks) upon serum levels of IL-12, IL-18, and hsCRP. Results There were no preintervention differences in IL-12, IL-18, or hsCRP between treatment groups. Postintervention levels of IL-12, IL-18, and hsCRP were similar between the treatment groups. However, IL-12 and IL-18 increased in both treatment groups over the intervention period, whereas hsCRP remained unchanged. The magnitude of increase in serum IL-18 (ΔIL-18) was significantly less in participants in the ω3FA treatment group compared to placebo (P = .047). Conclusion(s) This study has shown that 4 g daily ω3FA supplementation may lower serum IL-18 levels in patients with moderate CKD. Although there were no apparent effects on several other markers of inflammation, this study provides evidence for a specific effect of ω3FA on inflammatory pathways.

Background: The contribution of rural clinical school (RCS) and rural origin to developing a long-term rural medical workforce was examined.Methods: Longitudinal cohort study, after undergraduate l...

Background: Workforce decisions of medical students with prior tertiary education, relative to those without, are not known.Methods: Rural workforce outcomes for three separate streams of medical s...

BACKGROUND Diastolic dysfunction (DD) is an important cause of cardiovascular disease (CVD) mortality in chronic kidney disease (CKD) patients. Non-traditional risk factors, such as arterial stiffness and inflammation, are implicated in the pathogenesis of DD in CKD patients. AIM To determine the association between inflammatory markers (interleukin (IL)-12, IL-18, highly sensitive C-reactive protein (hsCRP)) and non-invasive markers of arterial stiffness (24-h pulse pressure (PP)) with DD in stages 3-4 CKD patients. METHODS We performed a sub-analysis of 78 non-diabetic stages 3-4 CKD subjects to determine the relationship between 24-h PP, IL-12, IL-18 and hsCRP with DD. RESULTS DD was present in 38 subjects (49%). Subjects with DD were significantly older (61.0 ± 1.9 vs 50.2 ± 2.0 years; P < 0.001) and had higher 24-h PP (48(95% confidence interval 45, 52) vs 43(95% confidence interval 41, 45) mmHg; P < 0.005); 24-h PP was associated with DD (P = 0.02), but this was no longer significant after adjustment for age (P = 0.31). Serum IL-12, IL-18 and hsCRP levels were not significantly different between subjects with or without DD. CONCLUSION Asymptomatic subclinical DD was present in 50% of a cohort of stages 3-4 CKD patients but was not associated with IL-12, IL-18 or hsCRP. The association between 24-h PP and DD was no longer apparent following adjustment for age, but given the small sample size, our findings will need to be explored in larger-sized cohorts of individuals with moderate-stage CKD.

In the original publication of this article [1], an error occurred during the publication of this article in Table 2.

Background: Type 2 diabetes mellitus is a metabolic disorder characterized by high glucose and insulin resistance. It is strongly linked to lifestyle, including poor diet and physical inactivity. Lupin is a novel food ingredient, rich in protein and fibre with negligible sugar and starch, which can be incorporated into various foods to reduce glycaemic load. Regular consumption of lupin-enriched foods may be a novel and easily achievable means of reducing overall glycaemic load and improving glycaemic control in diabetes. Objective: To determine whether regular consumption of lupin-enriched foods can improve glycaemic control and lower blood pressure in people with type 2 diabetes mellitus. Design: Fourteen men and 8 women (mean age 58.0 ± 6.6 years and BMI 29.0 ± 3.5 kg m−2) with type 2 diabetes mellitus were recruited from the general population to take part in a double-blind, randomised, controlled cross-over study. Participants consumed lupin or control foods for breakfast and lunch every day, and for dinner at least 3 days per week during the 8-week treatment periods. Lupin-enriched foods consisted of bread, pasta, Weetbix™ cereal and crumbs, with energy-matched control products. Treatments were completed in random order with an 8-week washout period. All participants monitored their blood glucose levels pre- and post-breakfast and lunch, and their blood pressure in the morning and evening, 3 days per week for the duration of each treatment period. Results: Seventeen participants completed both treatment arms, with all 22 participants (14 males, 8 females) analysed on an intention-to-treat basis. Eight weeks consumption of lupin-enriched food had no significant effect on mean blood glucose levels (mean difference: −0.08 ± 0.06 mmol L−1, p = 0.214) or post-prandial blood glucose levels (−0.13 ± 0.10 mmol L−1, p = 0.196). There was no effect on home systolic (−0.4 ± 0.4 mmHg, p = 0.33) or diastolic (0.3 ± 0.3 mmHg, p = 0.321) blood pressure and heart rate (0.5 ± 0.3 bpm, p = 0.152), and no effect on body weight throughout the treatment periods. Conclusion: Regular consumption of lupin-enriched foods had no significant effect on glycaemic control or blood pressure in people with type 2 diabetes mellitus.

Background Type 2 diabetes mellitus is characterized by peripheral insulin resistance and low-grade systemic inflammation. Inflammation resolution is recognised as an important process driven by specialised pro-resolving mediators of inflammation (SPMs) and has the potential to moderate chronic inflammation. Alcohol has the potential to affect synthesis of SPMs by altering key enzymes involved in SPM synthesis and may influence ongoing inflammation associated with Type 2 diabetes mellitus. Aims (i) To examine the effects of alcohol consumed as red wine on plasma SPM in men and women with Type 2 diabetes in a randomised controlled trial and (ii) compare baseline plasma SPM levels in the same patients with those of healthy volunteers. Methods Twenty-four patients with Type 2 diabetes mellitus were randomized to a three-period crossover study with men drinking red wine 300 ml/day (∼31 g alcohol/day) and women drinking red wine 230 ml/day (∼24 g alcohol/day), or equivalent volumes of dealcoholized red wine (DRW) or water, each for 4 weeks. The SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins (Rv) (RvE1-RvE3), 17-hydroxydocosahexaenoic acid (17-HDHA), and D-series resolvins (RvD1, 17R-RvD1, RvD2, RvD5), 14-hydroxydocosahexaenoic acid (14-HDHA) and Maresin 1 were measured at the end of each period. A baseline comparison of plasma SPM, hs CRP, lipids and glucose was made with healthy volunteers. Results Red wine did not differentially affect any of the SPM measured when compared with DRW or water. Baseline levels of the hs-CRP and the SPM 18-HEPE, 17-HDHA, RvD1 and 17R-RvD1 in patients with Type 2 diabetes mellitus were all significantly elevated compared with healthy controls and remained so after adjusting for age and gender. Conclusion Moderate alcohol consumption as red wine does not alter plasma SPM in patients with Type 2 diabetes mellitus. The elevation of SPM levels compared with healthy volunteers may be a homeostatic response to counter ongoing inflammation.

Background Emerging evidence suggests that increasing intakes of nitrate-rich vegetables may be an effective approach to reduce blood pressure. Objective Our primary aim was to determine whether daily consumption of nitrate-rich vegetables over 4 wk would result in lower blood pressure. Design Thirty participants with prehypertension or untreated grade 1 hypertension were recruited to a randomized controlled crossover trial with 4-wk treatment periods separated by 4-wk washout periods. Participants completed 3 treatments in random order: 1) increased intake (∼200 g/d) of nitrate-rich vegetables [high-nitrate (HN); ∼150 mg nitrate/d], 2) increased intake (∼200 g/d) of nitrate-poor vegetables [low-nitrate (LN); ∼22 mg nitrate/d], and 3) no increase in vegetables (control; ∼6 mg nitrate/d). Compliance was assessed with the use of food diaries and by measuring plasma nitrate and carotenoids. Nitrate metabolism was assessed with the use of plasma, salivary, and urinary nitrate and nitrite concentrations. The primary outcome was blood pressure assessed by using 24-h ambulatory, home, and clinic measurements. Secondary outcomes included measures of arterial stiffness. Results Plasma nitrate and nitrite concentrations increased with the HN treatment in comparison to the LN and control treatments (P 0.05) after adjustment for pretreatment values, treatment period, and treatment order. Similarly, no differences were observed between treatments for arterial stiffness measures (P > 0.05). Conclusion Increased intake of nitrate-rich vegetables did not lower blood pressure in prehypertensive or untreated grade 1 hypertensive individuals when compared with increased intake of nitrate-poor vegetables and no increase in vegetables. This trial was registered at www.anzctr.org.au as ACTRN12615000194561.

Context: Monash University and the University of Western Australia admit both school-leavers and graduates into their Bachelor of Medicine and Bachelor of Surgery (MBBS) courses. The Undergraduate Medicine and Health Sciences Admission Test (UMAT) and the Graduate Medical Schools Admissions Test (GAMSAT) are used for selection, along with an academic score and an interview score. The aim of this study was to compare the relative predictive validity of the selected components in the two entry streams, particularly UMAT versus GAMSAT. Methods: Aggregated scores for course outcomes were calculated in the categories of knowledge, clinical and total scores, at four-time points. A path analysis was conducted based on multivariate regressions with model constraint parameters defined across the outcome variables to investigate change over time. Results: Academic scores were the strongest predictors of knowledge scores and end of course results. Interview scores had a small positive increasing effect, being stronger for clinical than knowledge outcomes. The effect size for GAMSAT was greater than for UMAT. Conclusions: Aptitude tests and interview scores added small but significant incremental predictive value to previous academic achievement. GAMSAT showed larger predictive value on outcomes than UMAT, for which one section (UMAT 3) had a negative effect.

The possibility that the validity of assessment is compromised by repeated sittings of highly competitive and high profile selection tests has been documented and is of concern to stake-holders. An illustrative example is the Undergraduate Medicine and Health Sciences Admission Test (UMAT) used by some medical and dental courses in Australia and New Zealand. The proficiencies of all applicants who sat the UMAT from one to four sittings between 2006 and 2012 were estimated on the same metric using the probabilistic Rasch model. A fit index characterising each profile's degree of conformity to the model was also calculated. Confirming expectations, mean proficiencies increased with repeated sittings on all three UMAT scales with the greatest difference (which was nevertheless relatively small) between the first two sittings. The fit index showed that the increases in proficiency estimates arose from additional easier items being answered correctly on repeated sittings rather than additional more difficult ones, suggesting that improvements are not on the substantive construct of the variable of assessment but in skills in answering the questions. Although strategies for dealing with the increase in proficiency estimates on repeated sittings could be canvassed, these results suggest that the validity of results on repeated sittings was not compromised. Accordingly, it might be concluded that although particular individuals might improve substantially between sittings, any validity is not likely to be compromised with the possibility that for some applicants, the second sitting might be the most valid.

Background Deficits in the rural medical workforce is an international issue. In Australia, The Rural Clinical School intervention is effective for initial recruitment of rural doctors. However, the extent of survival is not yet established. This paper summarises rural survival over a 10-year period. Methods Rural Clinical School graduates of Western Australia were surveyed annually, 2006–2015, and post Graduate Years (PGY) 3–12 included. Survival was described as “tours of service”, where a tour was either a period of ≥1 year, or a period of ≥2 weeks, working rurally. A tour ended with a rural work gap of ≥52 weeks. Considering each exit from urban as an event, semi-parametric repeated measures survival models were fitted. Results Of 468 graduates, using the ≥2 weeks definition, 239 PGY3–12 graduates spent at least one tour rurally (average 61.1, CI 52.5–69.7 weeks), and a total length of 14,607 weeks. Based on the tour definition of ≥1 year, 120 graduates completed at least one tour (average 1.89, 1.69–2.10 years), and a total of 227 years’ rural work. For both definitions, the number of tours increased from one to four by PGY10/11, giving 17,786 total weeks (342 years) across all PGYs for the ≥2 weeks tour definition, and 256 years total for ≥1 year. Significantly more graduates exited from urban work for the 2007–09 middle cohort compared with 2010–11 (HR 1.876, p = 0.022), but no significant difference between 2002 and 06 and 2010–11. Rural origin, age and gender were not statistically significant. Conclusions PGY3–12 RCS graduates contributed substantially to the rural workforce: 51% did so by short rotations, while 26% contributed whole years of service. There was an apparent peak in entry and survival for the middle cohort and decline thereafter, likely attributable to lack of advanced/specialist vocational training. These data indicate a real commitment to rural practice by RCS graduates, and the need for rural vocational training as a key element of a successful rural survival strategy.

To examine outstanding issues in the relationship of alcohol to hypertension. These include whether the increase in BP with alcohol is causally related, the nature of the relationship in women, the contribution of alcohol-related increases in BP to cardiovascular disease and the aetiology of alcohol-related hypertension. Intervention studies and Mendelian randomisation analyses confirm the alcohol–BP relationship is causal. The concept that low-level alcohol intake reduces BP in women is increasingly unsustainable. Alcohol-related hypertension is in the causal pathway between alcohol use and increased risk for several cardiovascular outcomes. The aetiology of alcohol-related hypertension is multifactorial with recent data highlighting the effects of alcohol on the vasoconstrictor 20-HETE and oxidative stress. The high prevalence of both alcohol use and hypertension mandates a careful alcohol history in every patient with elevated BP. Early intervention for excessive alcohol use offers the promise of lower levels of BP and reduced risk of adverse cardiovascular outcomes.

Background Whether graduate entrants to medical school perform better academically than undergraduate entrants remains controversial. Differences in the discipline backgrounds of graduates may, at least in part, have accounted for differences in the results of comparative studies reported to date. This study aimed to address the dual issues of whether academic performance and progression rates were different between GE and UG students and the extent to which the discipline background of GE students may underpin any differences observed. Methods Relative academic performance as well as indicators of student progression (supplementary examinations, repeat years, leave of absence, withdrawal from the programme) were compared between graduate entrants (GE) (N = 410) and both school leaver entrants (SLE) (N = 865) and non-standard entrants (some prior tertiary education) (NSE) (N = 148) who combined for the final 4 yr. of a 6 yr. MBBS undergraduate programme in 8 consecutive cohorts from 2006 to 2013 in Western Australia. Results Examination scores were generally at or very close to a distinction grade or higher across all groups. Higher mean examination scores were seen for GE versus both SLE and NSE in the first 2 years with no significant differences in the final 2 years. GE from biological science / science backgrounds (N = 241) or physical science backgrounds (N = 26) performed the same as SLE and NSE throughout the programme. GE with a health / allied health background (N = 91), however, performed better throughout. They also performed better when compared to their GE counterparts from a humanities (N = 32) or a biological science / science background. GE had increased odds of withdrawing when compared to SLE (OR 2.50, 95% CI 1.30, 4.79, P = 0.006), but not compared to NSE. NSE had increased odds of repeating at least one level when compared to either GE (OR 2.74, 95% CI 1.21, 6.21, P = 0.016) or SLE (OR 4.10, 95% CI 1.93, 8.70, P

OBJECTIVE Rural exposure during medical school is associated with increased rural work after graduation. How much of the increase in rural workforce by these graduates is due to pre-existing interest and plans to work rurally and how much is related to the extended clinical placement is not known. DESIGN This cohort study compared the employment location of medical graduates who professed no rural interest as undergraduates (negative control), with those who applied but did not participate in Rural Clinical School of Western Australia (RCSWA) (positive control), and those who applied and participated in RCSWA (participants). PARTICIPANTS All 1026 University of Western Australia students who had an opportunity to apply for a year-long rotation in RCSWA from 2004 to 2010, and who had subsequently graduated by the end of 2011, were included. MAIN OUTCOME MEASURE Graduates' principal workplace location (AHPRA, Feb 2014). RESULT The three groups differed significantly in their graduate work locations (χ2 = 39.2, P < 0.001). In multivariate analysis, only being of older age at graduation (OR 2.28 (95% CI 1.40, 3.72), P = 0.001), being from a rural background (OR 2.99 (95% CI 1.85, 4.85), P < 0.001), being a recipient of a Medical Rural Bonded Scholarship (OR 3.36 (95% CI 1.68, 6.73, P = 0.001) and actually participating in the RCSWA remained significantly related to rural work (OR 3.10 (95% CI 1.95, 4.93), P < 0.001). CONCLUSION After accounting for other factors relating to rural work, RCSWA graduates were three times more likely to work rurally than either control group. These data suggest that RCSWA has a significant independent effect on rural workforce.

summary Background and objective: The high incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) is related partially to chronic inflammation. n-3 Fatty acids have been shown to have antiinflammatory effects and to reduce the risk of CVD. Specialized Proresolving Lipid Mediators (SPMs) derived from the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) actively promote the resolution of inflammation. This study evaluates the effects of n-3 fatty acid supplementation on plasma SPMs in patients with CKD. Methods: In a double-blind, placebo-controlled intervention of factorial design, 85 patients were randomized to either n-3 fatty acids (4 g), Coenzyme Q10 (CoQ) (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. The SPMs 18-HEPE, 17-HDHA, RvD1, 17R-RvD1, and RvD2, were measured in plasma by liquid chromatographyetandem mass spectrometry before and after intervention. Results: Seventy four patients completed the 8 weeks intervention. n-3 Fatty acids but not CoQ significantly increased (P < 0.0001) plasma levels of 18-HEPE and 17-HDHA, the upstream precursors to the Eand D-series resolvins, respectively. RvD1 was significantly increased (P ¼ 0.036) after n-3 fatty acids, but no change was seen in other SPMs. In regression analysis the increase in 18-HEPE and 17-HDHA after n-3 fatty acids was significantly predicted by the change in platelet EPA and DHA, respectively. Conclusion: SPMs are increased after 8 weeks n-3 fatty acid supplementation in patients with CKD. This may have important implications for limiting ongoing low grade inflammation in CKD.

Open Access Article. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence., Coffee is a rich source of polyphenols, primarily chlorogenic acids (CGA). Certain polyphenols and polyphenol-rich foods and beverages have been shown to improve endothelial function and lower blood pressure (BP). The aim of the present study was to investigate the acute effect of two doses of CGA (5-CGA) on endothelial function and BP. In a cross-over study, 16 healthy men and women received: (i) 0 mg purified 5-CGA (control group); (ii) 450 mg purified 5-CGA; (iii) 900 mg purified 5-CGA; and (iv) 200 mg purified (−)-epicatechin (positive control) in random order one week apart. Peak and continuous mean (60 to 240 s post ischaemia) flow-mediated dilation (FMD) was measured at baseline, 1 h and 4 h. BP was measured at baseline and every 30 min to 4 h. Plasma CGA and epicatechin levels were significantly increased at both 1 h and 4 h post their respective treatments. Peak FMD was not significantly altered by either dose of 5-CGA or the epicatechin, relative to control (p > 0.05). Relative to control, effects on continuous mean FMD response following 450 mg 5-CGA and 900 mg of 5-CGA (0.47 ± 0.16%, p = 0.016 and 0.65 ± 0.16%, p < 0.001, respectively) at 1 h and (0.18 ± 0.17%, p = 0.99 and 0.44 ± 0.16%, p < 0.05, respectively) at 4 h. There was no significant effect of any of the treatments on BP. In conclusion, the present study has found no significant effect of 5-CGA, at 450 and 900 mg, on peak FMD response. However, there were significant improvements in mean post-ischaemic FMD response, particularly at the 1 h time point in this group of healthy individuals.

Predicting workplace performance of junior doctors from before entry or during medical school is difficult and has limited available evidence. This study explored the association between selected predictor variables and workplace based performance in junior doctors during their first postgraduate year.Two cohorts of medical students (n = 200) from one university in Western Australia participated in the longitudinal study. Pearson correlation coefficients and multivariate analyses utilizing linear regression were used to assess the relationships between performance on the Junior Doctor Assessment Tool (JDAT) and its sub-components with demographic characteristics, selection scores for medical school entry, emotional intelligence, and undergraduate academic performance.Grade Point Average (GPA) at the completion of undergraduate studies had the most significant association with better performance on the overall JDAT and each subscale. Increased age was a negative predictor for junior doctor performance on the Clinical management subscale and understanding emotion was a predictor for the JDAT Communication subscale. Secondary school performance measured by Tertiary Entry Rank on entry to medical school score predicted GPA but not junior doctor performance.The GPA as a composite measure of ability and performance in medical school is associated with junior doctor assessment scores. Using this variable to identify students at risk of difficulty could assist planning for appropriate supervision, support, and training for medical graduates transitioning to the workplace.

Metabolism of arachidonic acid by cytochrome P450 ω-hydroxylase leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) that regulates vascular function, sodium homeostasis and blood pressure (BP). Supplementation with n-3 fatty acids is known to alter arachidonic acid metabolism and reduce the formation of the lipid peroxidation products F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied.We previously reported a significant effect of n-3 fatty acids but not coenzyme Q10 (CoQ) to reduce BP in a double-blind, placebo-controlled intervention, wherein patients with chronic kidney disease (CKD) were randomized to n-3 fatty acids (4 g), CoQ (200 mg), both supplements or control (4 g olive oil), daily for 8 weeks. This study examined the effect of n-3 fatty acids on plasma and urinary 20-HETE in the same study, as well as plasma and urinary F2-isoprostanes, and relate these to changes in BP.Seventy-four patients completed the 8-week intervention. n-3 fatty acids but not CoQ significantly reduced plasma 20-HETE (P = 0.001) and F2-isoprostanes (P 0.001). In regression models adjusted for BP at baseline, postintervention plasma 20-HETE was a significant predictor of the fall in SBP (P 0.0001) and DBP (P 0.0001) after n-3 fatty acids.This is the first report that n-3 fatty acid supplementation reduces plasma 20-HETE in humans and that this associates with reduced BP. These results provide a plausible mechanism for the reduction in BP observed in patients with CKD following n-3 fatty acid supplementation.

Background Neutrophils release leukotriene (LT)B4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB4. Objective This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. Design In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. Results Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB5 (P Conclusion n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation.

Background Cardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress, and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesized by cytochrome P450 (CYP450) enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F2-isoprostanes), markers of inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs), and specialized pro-resolving mediators of inflammation (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Methods Normotensive men (n = 22) were randomly allocated to drink RW (375 ml/d) or the equivalent volume of dealcoholized red wine (DRW) or water for 4 weeks in a 12-week, 3-period crossover trial. BP, heart rate, 20-HETE, F2-isoprostanes, and SPM were measured at baseline, 4, 8, and 12 weeks. Results Drinking RW increased BP (p

Evidence for a beneficial effect of dietary nitrate, through the nitrate-nitrite-NO pathway, on measures of cardiovascular function in healthy individuals is accumulating. It is less clear whether increased dietary nitrate intake from green leafy vegetables would have similar beneficial vascular effects in those at increased risk of developing hypertension. Our aim was to assess the effects of short-term regular consumption of increased nitrate from green leafy vegetables on blood pressure and arterial stiffness in individuals with high-normal blood pressure. Thirty-eight men and women ages 30-70 years with systolic blood pressure 120 to 139 mm Hg were recruited to a randomized controlled crossover trial. The effects of a 7-day high-nitrate diet intervention (increased nitrate intake by at least 300 mg/day from green leafy vegetables) were compared to a 7-day low-nitrate diet intervention. Outcome measures included pre- and postintervention salivary and plasma nitrate and nitrite concentrations; ambulatory, home, and office blood pressure; augmentation index; and carotid-femoral pulse wave velocity. The high-nitrate diet intervention resulted in at least a fourfold increase in salivary and plasma nitrate and nitrite (P

Endothelial nitric oxide (NO) is fundamental to cardiovascular health. Dietary nitrate and nitrate from endothelial derived NO metabolism provides a significant contribution to the circulating NO pool through the nitrate-nitrite-NO pathway. A critical step in this pathway is the reduction of nitrate to nitrite by the oral microbiota. We aimed to assess the effects of antibacterial mouthwash use on markers of nitrate-nitrite-NO metabolism and blood pressure in treated hypertensive men and women.Fifteen treated hypertensive men and women (mean age 65 years) were recruited to a randomized controlled cross-over trial. The effects of 3-day use of antibacterial mouthwash on oral nitrate to nitrite reduction, salivary and plasma nitrate and nitrite, plasma cyclic guanosine monophosphate (cGMP) and systolic and diastolic blood pressure were compared to control (water).Relative to control, 3-day antibacterial mouthwash use resulted in decreased oral nitrate to nitrite reduction (P = 0.02), decreased salivary nitrite (P = 0.01) and increased salivary nitrate (P0.001), and there was a trend toward a decrease in plasma nitrite concentration (P = 0.09). Use of antibacterial mouthwash over 3 days also resulted in higher systolic blood pressure (2.3mm Hg; 95% CI: 0.5, 4.0; P = 0.01), but not diastolic blood pressure (P = 0.4) or plasma cGMP (P = 0.7), relative to control.Interruption of the nitrate-nitrite-NO pathway through the use of antibacterial mouthwash was paralleled by a small elevation of systolic blood pressure in treated hypertensive men and women.

Genetic background partly determines the efficacy of interventions to lower blood pressure (BP). The CYP4F2 and CYP4A11 enzymes are renal 20-hydroxyeicosatetraenoic acid (20-HETE) synthases that regulate BP. Gene variants of CYP4F2 and CYP4A11 associate with hypertension and stroke. We showed that a gene variant of CYP4F2 but not CYP4A11 was associated with increased 20-HETE excretion and BP.To compare BP and 20-HETE responses in carriers of the CYP4F2 1347G/A polymorphism and controls CYP4F2-GG (wildtype), during weight loss.Volunteers genotyped as CYP4F2GA/AA (n = 26) and controls genotyped as CYP4F2 GG (n = 27) were counselled to reduce weight for 12 weeks, followed by 4 weeks of weight stabilization. Weight, 24-h BP, pulse pressure and urinary 20-HETE were measured at baseline, 12 and 16 weeks.At baseline, SBP was (+1.7 mmHg, P = 0.047) in the CYP4F2 GA/AA genotype. Compared with baseline, weight fell by 3.9 kg, P = 0.0001, in both genotypes, and was maintained to 16 weeks. SBP fell by (-7.6 mmHg, P = 0.004) in both genotypes after 12 weeks. However, after weight stabilization, SBP was +3.6 mmHg, P = 0.004 in CYP4F2 GA/AA genotype. DBP and heart rate changed similarly over time. Pulse pressure fell with weight loss (P0.001), but was elevated in the CYP4F2 GA/AA genotype at all time-points (+3.1 mmHg, P0.001). Urinary 20-HETE was similar at baseline and 12 weeks but elevated in the CYP4F2 GA/AA genotype (P = 0.017) after weight stabilization.Maintenance of lower BP after weight loss is more difficult for carriers of the CYP4F2 G1347A polymorphism and may be related to increased arterial stiffness and increased 20-HETE synthesis.

Background Characteristics of short-term blood pressure (BP) variation may influence cardiovascular disease risk via effects on vascular function. Objective In a cross-sectional study of a group of treated hypertensive and untreated largely normotensive subjects we investigated the relationships of measures of short-term BP variation with brachial artery vasodilator function. Methods A total of 163 treated hypertensive ( n = 91) and untreated largely normotensive ( n = 72) men and women were recruited from the general population. Measures of systolic and diastolic BP variation were calculated from 24 h ambulatory BP assessments and included: (i) rate of measurement-to-measurement BP variation (SBP-var and DBP-var); and (ii) day-to-night BP dip (SBP-dip and DBP dip). Endothelium-dependent vasodilation was assessed as flow-mediated dilation (FMD) and endothelium-independent vasodilation was assessed in response to glyceryl trinitrate (GTN). Relationships were explored using univariate and multivariate linear regression. Results The relationships of brachial artery vasodilator function with BP variation were not significantly different between treated hypertensive and untreated subjects, therefore these groups were combined for analysis. In univariate analysis, higher SBP-var ( P P = 0.004) were associated with lower FMD; and higher SBP-var ( P = 0.002) and lower SBP-dip ( P = 0.003) and DBP-dip ( P = 0.001) were associated with lower GTN-mediated dilation. In multivariate analysis, lower SBP-dip ( P = 0.007) and DBP-dip ( P = 0.03) were independently associated with lower GTN response. Conclusions Our results indicate that a lower day-to-night BP dip is independently associated with impaired smooth muscle cell function. Although rate of BP variation was associated with measures of endothelial and smooth muscle cell function, relationships were attenuated after accounting for age and BP.

Flavonoids and nitrate in a fruit and vegetable diet may be protective against cardiovascular disease and cognitive decline through effects on nitric oxide (NO) status. The circulating NO pool is increased via distinct pathways by dietary flavonoids and nitrate. Our aim was to investigate the acute effects of apples, rich in flavonoids, and spinach, rich in nitrate, independently and in combination on NO status, cognitive function and mood in a randomised, controlled, cross-over trial with healthy men and women (n = 30). The acute effects of four energy-matched treatments (control, apple, spinach and apple + spinach) were compared. Endpoints included plasma nitric oxide status (determined by measuring S-nitrosothiols + other nitroso species (RXNO)), plasma nitrate and nitrite, salivary nitrate and nitrite, urinary nitrate and nitrite as well as cognitive function (determined using the Cognitive Drug Research (CDR) computerized cognitive assessment battery) and mood. Relative to control, all treatments resulted in higher plasma RXNO. A significant increase in plasma nitrate and nitrite, salivary nitrate and nitrite as well as urinary nitrate and nitrite was observed with spinach and apple + spinach compared to control. No significant effect was observed on cognitive function or mood. In conclusion, flavonoid-rich apples and nitrate-rich spinach augmented NO status acutely with no concomitant improvements or deterioration in cognitive function and mood.

Several lines of evidence indicate that quercetin, a polyphenol derived in the diet from fruit and vegetables, contributes to cardiovascular health. We aimed to investigate the effects of dietary quercetin on endothelial function and atherosclerosis in mice fed a high-fat diet. Wild-type C57BL/6 (WT) and apolipoprotein E gene knockout (ApoE(-/-)) mice were fed: (i) a high-fat diet (HFD) or (ii) a HFD supplemented with 0.05% w/w quercetin (HFD+Q), for 14 weeks. Compared with animals fed HFD, HFD+Q attenuated atherosclerosis in ApoE(-/-) mice. Treatment with the HFD+Q significantly improved endothelium-dependent relaxation of aortic rings isolated from WT but not ApoE(-/-) mice and attenuated hypochlorous acid-induced endothelial dysfunction in aortic rings of both WT and ApoE(-/-) mice. Mechanistic studies revealed that HFD+Q significantly improved plasma F2-isoprostanes, 24h urinary nitrite, and endothelial nitric oxide synthase activity, and increased heme oxygenase-1 (HO-1) protein expression in the aortas of both WT and ApoE(-/-) mice (P

The vasodilation accompanying acute alcohol ingestion is hard to reconcile with the strong evidence linking chronic alcohol consumption with hypertension. Cytochrome P450 (CYP450) eicosanoids derived from arachidonic acid include vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20-hydroxyeicosatrienoic acid (20-HETE). This study aimed to examine the relationship between CYP450 eicosanoids and blood pressure (BP), and compared the effect of single session of drinking red wine with de-alcoholized red wine (DRW) or water over 24 h.Twenty-five normotensive men were randomly assigned to drink either 375 ml of red wine (41 g of alcohol) or the equivalent volume of DRW or water, with a light meal on 3 separate days. Ambulatory BP and heart rate were measured over 24 h. Blood samples were obtained before and 2, 4 and 24 h after beverage consumption.Blood pressure fell in the first 4 h after red wine consumption (P = 0.001), but was significantly higher after 20 h (P = 0.037). Plasma 20-HETE fell in the 2 h after consumption of all beverages, but over the 24-h period was relatively higher after red wine consumption (P = 0.025). The largest difference in 20-HETE was 2 h after consuming red wine and coincided with the highest blood alcohol level. There were no significant effects of red wine on plasma EETs.Acute consumption of alcohol as red wine results in a relative increase in plasma levels of the vasoconstrictor 20-HETE over 24 h without affecting EETs, and may contribute to the BP elevation that associates with a binge drinking pattern or be a homeostatic response to the acute fall in BP induced by alcohol.

Cholesterol oxidation products have been demonstrated to possess a wide variety of biological properties and have been implicated in playing an important role in the development of atherosclerosis. We have developed an analytical method using capillary gas chromatography-mass spectrometry (GC-MS) for the analysis of cholesterol oxidation products in low-density lipoprotein (LDL). The method uses programmed multiple selected ion monitoring (SIM), providing enhanced sensitivity and accuracy of peak detection over full-scan mass spectra. The major oxidation products of cholesterol in oxidized LDL were identified as 7β-hydroxy-cholesterol and 7-keto-cholesterol. Minor products included 4β-hydroxy-cholesterol, 6β-hydroxy-cholesterol and cholesterol-5α,6α-epoxide. Native LDL contains 7-lathosterol, which is a biosynthetic precursor of cholesterol, as well as low levels of 7β-hydroxy-cholesterol and 7-keto-cholesterol. 7-Lathosterol was not detected in oxidized LDL. A time course oxidation of native LDL with 8 μM CuCl2 demonstrated a rapid increase in 7β-hydroxy-cholesterol and 7-keto-cholesterol over the first 4 h. Cholesterol-5α,6α-epoxide, and β4-hydroxy- and 6β-hydroxy-cholesterol levels increased gradually, while 7-lathosterol decreased over the same period. This method was used to measure the levels of 7-lathosterol and cholesterol oxides in the LDL of 20 healthy subjects in order to establish the mean concentration and a reference range. This method can be used for the characterization and quantitation of oxysterols in native and oxidized LDL and may afford an additional index of oxidative modification of plasma lipoproteins.

Introduction Medical schools are in general over-represented by students from high socio-economic status backgrounds. The University of Western Australia Medical School has been progressively widening the participation of students from a broader spectrum of the community both through expanded selection criteria and quota-based approaches for students of rural, indigenous and other socio-educationally disadvantaged backgrounds. We proposed that medical students entering medical school from such backgrounds would ultimately be more likely to practice in areas of increased socio-economic disadvantage. Methods The current practice address of 2829 medical students who commenced practice from 1980 to 2011 was ascertained from the Australian Health Practitioner Regulation Agency (AHPRA) Database. Logistic regression was utilised to determine the predictors of the likelihood of the current practice address being in the lower 8 socio-economic deciles versus the top 2 socio-economic deciles. Results Those who were categorised in the lower 8 socio-economic deciles at entry to medical school had increased odds of a current practice address in the lower 8 socio-economic deciles 5 or more years after graduation (OR 2.05, 95% CI 1.72, 2.45, P

DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC) at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F2-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids (p = 0.015). Post-intervention plasma F2-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count (p = 0.025).The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients.

Cross-sectional and longitudinal population studies have provided a considerable corpus of evidence for an inverse association between light to moderate alcohol intake and both coronary artery disease and stroke. The formulation of balanced public health advice on the basis of such studies, however, needs to take into account the full spectrum of the effects of alcohol on the cardiovascular system, particularly its equally well documented effect to increase level of blood pressure and prevalence of hypertension. In this review, the broader implications of the association of alcohol with hypertension are discussed, principally in the context of the effect of higher levels of alcohol consumption to increase ischaemic and haemorrhagic stroke, left ventricular hypertrophy, congestive cardiomyopathy, cardiac arrhythmia and sudden cardiac death.

Although prospective studies suggest light-to-moderate chronic alcohol intake protects against coronary artery disease in type 2 diabetic patients, the balance of effects on individual cardiovascular risk factors needs further assessment. We examined the effects of alcohol consumption on 24-h ambulatory blood pressure (BP) and heart rate (HR), high-density lipoprotein cholesterol, fibrinogen, C-reactive protein, homocysteine, and glycaemic control in well controlled type 2 diabetes.Twenty-four participants aged 49-66 year were randomized to a three-period crossover study with women drinking red wine 230 ml/day (∼24 g alcohol/day) and men drinking red wine 300 ml/day (∼31 g alcohol/day), or equivalent volumes of dealcoholized red wine (DRW) or water, each for 4 weeks. Ambulatory BP and HR were monitored every 30 min for 24 h at the end of each period. Home blood glucose monitoring was carried out twice weekly throughout.Red wine increased awake SBP and DBP relative to water by 2.5 ± 1.2 /1.9 ± 0.7 mmHg (P = 0.033, P = 0.008, respectively), with a similar nonsignificant trend relative to DRW. Asleep DBP fell with red wine relative to DRW (2.0 ± 0.8 mmHg, P = 0.016) with a similar nonsignificant trend relative to water. Red wine increased 24-h, awake and asleep HR relative to water and DRW. Relative to DRW, red wine did not affect glycaemic control or any other cardiovascular risk factor.In well controlled type 2 diabetic individuals 24-31 g alcohol/day (∼2-3 standard drinks) raises awake BP and 24-h HR and lowers asleep BP but does not otherwise favourably or adversely modify cardiovascular risk factors.

Overall there is good evidence that alcohol consumption induces oxidative stress, and leads to lipid peroxidation, effects which have been linked to alcohol-related toxicity and disease and may be relevant to alcoholatherosclerosis interrelationships. On the other hand, a protective effect of light to moderate alcohol consumption against cardiovascular disease is well recognized, with the further hypothesis that red wine offers extra cardiovascular protection due to its rich content of antioxidant phenolic compounds. Although this hypothesis is given some credence from in vitro data, controlled studies in humans have produced conflicting results. Clearly, the equally well described pro-oxidant effects of alcohol and its metabolism have been insufficiently considered in the pursuit of what to many is an intuitively attractive hypothesis. Further studies are required to determine if red wine phenolics are actually absorbed from the gut and whether they offer any overall antioxidant protection in vivo. The hypothesis that red wine offers extra cardiovascular protection compared to other alcoholic beverages is not proven and must await the outcome of studies in which the full spectrum of the pro-oxidant and antioxidant effects of alcoholic beverages are duly considered. In the absence of such studies, there are no grounds at present for the promotion of the consumption of alcoholic beverages on the basis of their putative "antioxidant" properties.

In 1998, in addition to previous academic achievement, an aptitude test (UMAT) and a structured interview were introduced into selection for the Bachelor of Dental Science (BDSc), the undergraduate dental course at the University of Western Australia. The aim of this study was to determine the relationship between the combination of school-leaver dental students' entry scores, some demographic characteristics and subsequent student performance in the undergraduate course. Three hundred and ninety-eight school-leavers who enrolled in the BDSc from 1999 through 2011 were studied. Regression models were constructed comprising entry scores, gender and age as predictors in relation to subsequent academic performance. The main outcome measure was the weighted average mark (WAM) for each of five academic year levels as well as results in specific units, defined as either 'knowledge' based or 'clinically' based. Of the variables studied, previous academic performance and female gender had the strongest relationship with yearly WAM for Years 1 through 4 and for both 'knowledge' based and 'clinically' based units. The interview score showed a strong relationship in the major clinical years and in a range of 'clinically' based units. UMAT scores were less consistent in relationship to WAM. These results support assessment through a highly structured interview together with prior academic achievement as an evidence-based approach to selection of students for this undergraduate dental course.

Flavonoids and nitrates in fruits and vegetables may protect against cardiovascular disease. Dietary flavonoids and nitrates can augment nitric oxide status via distinct pathways, which may improve endothelial function and lower blood pressure. Recent studies suggest that the combination of flavonoids and nitrates can enhance nitric oxide production in the stomach. Their combined effect in the circulation is unclear. Here, our objective was to investigate the independent and additive effects of flavonoid-rich apples and nitrate-rich spinach on nitric oxide status, endothelial function, and blood pressure. A randomized, controlled, crossover trial with healthy men and women (n=30) was conducted. The acute effects of four energy-matched treatments (control, apple, spinach, and apple+spinach), administered in random order, were compared. Measurements included plasma nitric oxide status, assessed by measuring S-nitrosothiols+other nitrosylated species (RXNO) and nitrite, blood pressure, and endothelial function, measured as flow-mediated dilatation of the brachial artery. Results are means and 95% CI. Relative to control, all treatments resulted in higher RXNO (control, 33 nmol/L, 26, 42; apple, 51 nmol/L, 40, 65; spinach, 86 nmol/L, 68, 110; apple+spinach, 69 nmol/L, 54, 88; P

Background Cholesterol and blood pressure lowering therapies are effective in the secondary prevention of ischemic stroke. Aim To determine whether 30 days of treatment with atorvastatin, or irbesartan, initiated within 96 h of symptom onset improves recovery from acute ischemic stroke. Methods Eighty-one patients with acute ischemic stroke participated in this double-blind, placebo-controlled, randomized trial of atorvastatin (80 mg) vs. placebo, and/or irbesartan (150 mg) vs. placebo. Fifty-two patients (randomized 53 ± 22 h after onset of symptoms) completed the 30-day primary outcome follow-up. Results The primary outcome, maximal brain infarct size at days 3 and 30 measured by perfusion computed tomography, was not significantly altered by random assignment to irbesartan (1088 (IQR 216, 2594) mm2 at day 3, compared with 398 (144, 2053) mm2 among the placebo group, P=0·79 controlling for baseline values; and 822 (159, 1717) mm2 at day 30, cf 280 (76, 1330) mm2; P=0·63); or atorvastatin (454 (107, 1765) mm2 cf 825 (265, 2509) mm2 at day 3; P=0·33; and 462 (43, 1399) mm2 cf 280 (128, 1559) mm2 at day 30, P=0·79). There were no other significant differences among the treatment groups with the exception of: • high sensitivity C-reactive protein concentrations, which were lower in the irbesartan treatment group at day 30 (mean difference 12·6 mg/L; 95% CI: −25·1, −0·1; P=0·048); and • the mean cerebral blood flow in the affected cerebral hemisphere at 30 days after stroke, which was significantly reduced by random assignment to irbesartan compared with placebo in both the affected cerebral hemisphere (−7·5 mL/100 mL/min (95% CI: −1·7 to −13·4, P=0·01)) and in the unaffected hemisphere (−7·3 mL/100 mL/min (95% CI: −1·3, −13·4; P=0·02)). Atorvastatin therapy was well tolerated, but irbesartan therapy was associated with an increased rate of withdrawal from therapy ( n=10 (29%), compared with n=3 (9%) who withdrew from placebo, P=0·04). Conclusions Treatment with atorvastatin and irbesartan, initiated on day 3 after acute ischemic stroke, did not appear to substantially modify infarct growth.

Background: In 1998, a new selection process which utilised an aptitude test and an interview in addition to previous academic achievement was introduced into an Australian undergraduate medical course. Aims: To test the outcomes of the selection criteria over an 11-year period. Methods: 1174 students who entered the course from secondary school and who enrolled in the MBBS from 1999 through 2009 were studied in relation to specific course outcomes. Regression analyses using entry scores, sex and age as independent variables were tested for their relative value in predicting subsequent academic performance in the 6-year course. The main outcome measures were assessed by weighted average mark for each academic year level; together with results in specific units, defined as either ‘knowledge’-based or ‘clinically’ based. Results: Previous academic performance and female sex were the major independent positive predictors of performance in the course. The interview score showed positive predictive power during the latter years of the course and in a range of ‘clinically’ based units. This relationship was mediated predominantly by the score for communication skills. Conclusions: Results support combining prior academic achievement with the assessment of communication skills in a structured interview as selection criteria into this undergraduate medical course.

Addition of fibre or protein to carbohydrate-rich foods can reduce the glycaemic response to those foods. This may assist with glycaemic management in individuals with type 2 diabetes. Lupin is a legume rich in fibre and protein. We assessed the acute effects of lupin- and soya-based beverages on glucose and insulin responses in type 2 diabetic individuals. We hypothesised that the lupin and soya beverages would lower the acute glycaemic response compared with a control beverage containing no protein or fibre, and that lupin would reduce the postprandial glucose more than soya. In a randomised, controlled, cross-over trial, twenty-four diabetic adults (nineteen men and five women) attended three testing sessions, each 1 week apart. At each session, participants consumed a beverage containing 50 g glucose (control), 50 g glucose plus lupin kernel flour with 12·5 g fibre and 22 g protein (lupin), or 50 g glucose plus 12·5 g fibre and 22 g protein from soya isolates (soya). Serum glucose, insulin and C-peptide were measured periodically for 4 h following beverage consumption. Compared with the control beverage, the 4 h post-beverage glucose response was lower (P P P = 0·25) and C-peptide (P = 0·07) responses did not differ significantly between lupin and soya, but lupin resulted in a lower insulin response compared with soya (P = 0·013). Adding lupin or soya to a carbohydrate-rich beverage reduces glycaemia acutely in type 2 diabetic individuals. This may have a beneficial role in glycaemic management.

The cytochrome P-450 arachidonic acid metabolite 20-HETE is central to the regulation of vascular tone, renal function, and blood pressure and is synthesized in the rat kidney in response to angiotensin II (ANG II) and endothelin-1 (ET-1). There are very few studies examining the cellular synthesis of 20-HETE in humans. We aimed to measure human neutrophil and platelet 20-HETE levels under basal conditions and after ANG II, ET-1, and calcium ionophore (CaI). 20-HETE was measured in human platelets and neutrophils after saline (control), CaI (2.5 μg/ml), and ANG II or ET-1 (10 nmol/l-1 μmol/l) incubations. The effect of cells, which were preincubated with the ω-hydroxylase inhibitor N-hydroxy- N′-(4- butyl-2-methylphenyl) (HET0016, 10 nM), ANG II types 1 or 2 (AT1or AT2) receptor inhibition with irbesartan (1 μmol/l) or PD-123319 (1 μmol/l), or endothelin receptor subtypes A or B (ETAor ETB) receptor inhibition with BQ-123 or BQ-778 (100 nmol/l), was studied. Neutrophil and platelet content and release of 20-HETE was significantly increased by CaI and blocked by the ω-hydroxylase inhibitor HET0016. ANG II and ET-1 significantly increased neutrophil and platelet content and release of 20-HETE. ANG II increased 20-HETE via the AT2receptor. ET-1 increased 20-HETE through the ETBreceptor in platelets and both the ETAand ETBreceptors in neutrophils. These studies show that human platelets and neutrophils synthesize 20-HETE in response to ANG II and ET-1. 20-HETE synthesis in both cell types was predominantly mediated via the AT2and ETBreceptors. Stimulation via these receptor pathways has generally been thought to be cardioprotective and requires further studies in clinical situations associated with low-grade inflammation or where ANG II and ET-1 are elevated to clarify the role of 20-HETE.

Regular consumption of diets with increased protein or fibre intakes may benefit body weight and composition and cardiovascular disease risk factors. Lupin flour is a novel food ingredient high in protein and fibre.To investigate the effects of a lupin-enriched diet, during and following energy restriction, on body weight and composition and cardiovascular disease risk factors in overweight individuals.Participants (n = 131) were recruited to a 12-month parallel-design trial. They were randomly assigned to consume lupin-enriched foods or matching high-carbohydrate control foods. All participants underwent 3 months of weight loss, 1 month of weight stabilization and 8 months of weight maintenance. Body weight and composition and cardiovascular disease risk factors were assessed at baseline, 4 and 12 months.Lupin, relative to control, did not significantly influence (mean difference (95% CI)) weight loss at 4 months (0.1 kg (-1.2, 1.4)) and 12 months (-0.6 kg (-2.0, 0.8)), maintenance of weight loss from 4 to 12 months (-0.7 kg (-1.83, 0.48)) or measures of body fat and fat-free mass. Relative to control, 24-h ambulatory systolic (-1.3 mm Hg (-2.4, -0.3), P = 0.016) and diastolic (-1.0 mm Hg (-1.9, -0.2), P = 0.021) blood pressures were lower at 12 months but not at 4 months; fasting insulin concentrations and homeostasis model assessment (HOMA) scores were significantly lower at 4 months (-1.2 mU l(-1) (-1.3, -1.1), P = 0.004 and -0.6 units (-1.0, -0.19), P = 0.004) and 12 months (-1.3 mU l(-1) (-1.4, -1.1), P0.001 and -0.7 units (-1.1, -0.24), P = 0.002).A diet higher in protein and fibre derived from lupin-enriched foods does not enhance weight loss or improve the maintenance of weight loss. However, such a diet may provide cardiovascular health benefits in terms of insulin sensitivity and blood pressure.

Sesamin, the major lignan found in sesame, has been shown to increase vitamin E levels by inhibiting its metabolism via the cytochrome P 450 isozyme CYP4F2. CYP4F2 and CYP4A11 are the predominant human isoforms that synthesize 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid. Considerable evidence suggests that 20-HETE may play a role in the pathogenesis of hypertension. We hypothesized that sesamin could be an inhibitor of 20-HETE synthesis. This study investigated the effects of sesamin on 20-HETE synthesis in vitro and the effect of sesame supplementation on plasma and urinary 20-HETE concentrations in humans. Human microsomes were used to investigate the potency and selectivity of sesamin inhibition of 20-HETE synthesis. Sesamin inhibited human renal and liver microsome 20-HETE synthesis with IC 50 50 : 1.9 μmol/L) and had reduced activity toward CYP4A11 (IC 50 : >150 μmol/L), as well as cytochrome P epoxygenation of arachidonic acid (IC 50 : >50 μmol/L). In a randomized, controlled crossover trial, overweight men and women (n=33) consumed 25 g/d of sesame (≈50 mg/d of sesame lignan) or an isocaloric matched control for 5 weeks each. Relative to control, sesame supplementation resulted in a 28% decrease in plasma and a 32% decrease in urinary 20-HETE ( P

Chronic kidney disease (CKD) associates with increased cardiovascular disease (CVD) risk. Hypertension is a major determinant of progression of CKD. Omega-3 fatty acids (omger3FA) protect against CVD via improvements in blood pressure, heart rate, vascular reactivity and serum lipids. Coenzyme Q(10) (CoQ) may improve blood pressure and vascular function. This study determined whether omega3FA and CoQ have independent or additive effects in improving the cardiovascular profile, particularly blood pressure and heart rate, in nondiabetic patients with CKD stages 3-4.In a double-blind, placebo-controlled intervention, patients were randomized to either omega3FA (4 g), CoQ (200 mg), both supplements or control (4 g), daily for 8 weeks.Eighty-five patients aged 56.5 +/- 1.4 years; BMI 27.3 +/- 0.5 kg/m(2); supine blood pressure 125.0/72.3mmHg; and glomerular filtration rate 35.8 +/- 1.2 ml/min/1.73m(2), were randomized. Seventy-four completed the study. omega3FA, but not CoQ, reduced 24-h ambulatory heart rate (P0.0001) and blood pressure (P0.0001). Main effects for omega3FA on 24-h measurements were -3.3 +/- 0.7/ -2.9 +/- 0.5mmHg and -4.0 +/- 0.5 bpm. Postintervention blood pressure showed significant interactions between treatments. omega3FA reduced triglycerides 24% (P0.001). There were no changes in glomerular filtration rate, urinary albumin or total protein excretion, cholesterol, HDL-cholesterol (C), LDL-C, glucose, insulin, or high-sensitivity C-reactive protein.This study has shown that omega3FA reduce blood pressure, heart rate and triglycerides in patients with CKD. CoQ had no independent effect on blood pressure but increased heart rate. These results show that omega3FA lower blood pressure and may reduce cardiovascular risk in nondiabetic patients with moderate-to-severe CKD.

Background: Several studies show that proteins, including whey and casein, are more satiating than carbohydrates. It follows that skim milk would be more satiating than sugar-rich beverages. However, this has yet to be shown. Objective: The objective was to investigate the effects of drinking skim milk in comparison with a fruit drink at breakfast on selfreported postmeal satiety and energy intake at lunch. Design: In a randomized crossover trial, 34 overweight women (n = 21) and men (n = 13) attended 2 sessions 1 wk apart. At each session, participants consumed a fixed-energy breakfast together with either 600 mL skim milk (25 g protein, 36 g lactose, , 1g fat; 1062 kJ) or 600 mL fruit drink (,1 g protein, 63 g sugar, , 1g fat; ’1062 kJ). Participants provided satiety ratings throughout the morning. Four hours after breakfast they consumed an ad libitum lunch, and energy intake was assessed. Results: Participants consumed significantly less energy at lunch after consuming skim milk (mean: 2432 kJ; 95% CI: 2160, 2704 kJ) than after consuming the fruit drink (mean: 2658 kJ; 95% CI: 2386, 2930 kJ), with a mean difference of ’8.5% (P , 0.05). In addition, self-reports of satiety were higher throughout the morning after consumption of skim milk than after consumption of the fruit drink (P , 0.05) with the differences becoming larger over the 4h( P , 0.05). Conclusion: Consumption of skim milk, in comparison with a fruit drink, leads to increased perceptions of satiety and to decreased energy intake at a subsequent meal. This trial was registered with the Australian New Zealand Clinical Trials Registry at www.anzctr.org. au as ACTRN12608000510347. Am J Clin Nutr 2009;90:70‐5.

Enhanced oxidative stress is implicated in the development of atherosclerosis in humans and animal models. F(2)-isoprostanes are formed in vivo via free radical peroxidation of arachidonic acid, and their quantification has allowed assessment of oxidative stress in vivo. F(2)-isoprostanes associate with lipids, although their distribution in human plasma lipoproteins is unknown. Our aim was to determine the distribution and levels of F(2)-isoprostanes in lipoproteins isolated from human plasma by ultracentrifugation and fast protein liquid chromatography (FPLC). F(2)-isoprostanes were significantly higher in HDL compared with LDL or VLDL after isolation by ultracentrifugation or FPLC. Furthermore, HDL3 particles contained elevated levels of F(2)-isoprostanes compared with HDL2. Platelet activating factor acetylhydrolase (PAF-AH), which hydrolyses esterified F(2)-isoprostanes from phospholipids, was predominantly associated with LDL. Reduced F(2)-isoprostanes in LDL may be related to higher PAF-AH activity in LDL. Paraoxonase 1 (PON-1) activity was associated with HDL2 and may be a contributing factor to the lower F(2)-isoprostanes in HDL2 compared with HDL3. Further studies are required to establish the implications of these findings on HDL function.