The effect of high-fat meals and exercise on endothelial function and triacylglycerol concentrations in adolescent boys

The thesis investigated the effect of exercise on endothelial function (measured as flow-mediated dilation (FMD)) and triacylglycerol concentrations following the ingestion of a high-fat breakfast and lunch in adolescent boys. The validity of measuring lipid and lipoprotein concentrations from a capillary blood sample, and the reproducibility of the postprandial FMD and triacylglycerol concentration responses to the high-fat meals, was established. The effects of prior continuous moderate-intensity exercise (60 min walking at 60% V ̇O2peak), repeated very short duration sprints (40 x 6 s maximal effort cycle sprints) and accumulated moderate-intensity exercise (6 x 10 min running at 70% V ̇O2peak) on endothelial function and triacylglycerol concentrations in adolescent boys were then established across three studies, each consisting of two, 2-day main trials (control and exercise). On day 1, participants were either inactive or completed the prescribed exercise. On day 2, FMD and triacylglycerol concentrations were measured prior to, and following, ingestion of a high-fat breakfast and lunch. In each control trial FMD was reduced (signifying endothelial dysfunction), compared to fasting, by 20-32% and 24-33% following the high-fat breakfast and lunch. Following continuous moderate-intensity exercise, repeated very-short duration sprints and accumulated moderate-intensity exercise these reductions were only 8% and 10% (main effect trial, P = 0.002; main effect time, P = 0.023; interaction effect trial x time, P = 0.088), 2% and 5% (main effect trial, P = 0.012; main effect time, P = 0.004; interaction effect trial x time, P = 0.003) and 1% and 3% (main effect trial, P = 0.020; main effect time, P < 0.001; interaction effect trial x time, P = 0.014) respectively. The continuous moderate-intensity exercise and repeated very short duration sprints also significantly reduced the total area under the triacylglycerol concentration versus time curve by 22% (Control vs. Exercise; 12.68 (sem 1.37) vs. 9.84 (sem 0.75) mmol L-1 6.5h, P = 0.018) and 13% (Exercise vs. Control: 8.65 (sem 0.97) vs. 9.92 (sem 1.16) mmol L-1 6.5h, P = 0.023). The accumulated moderate-intensity exercise also reduced the total area under the triacylglycerol concentration versus time curve by 11%, but this reduction was not significant (Control vs. Exercise: 10.71 (sem 0.94) vs. 9.56 (sem 0.67) mmol L-1 6.5h, respectively, P = 0.183). The experimental evidence from these studies emphasise that exercise might offer an acceptable, non-pharmacological means of influencing CHD risk when individuals are young. The results of these studies can help shape future physical activity guidelines

The accumulation of exercise and postprandial endothelial function in boys

The purpose of this study was to investigate the effect of accumulating 60min of exercise on endothelial function and triacylglycerol concentrations following the ingestion of a high-fat breakfast and lunch in 14 adolescent boys (aged 12 to 14 years). Two, 2-day main trials (control and exercise) were completed in a counter-balanced, cross-over design. Participants were inactive on day 1 of the control trial but on day 1 of the exercise trial completed 6×10min runs at 70% of peak oxygen uptake, spread over the day. On day 2, triacylglycerol concentrations and flow-mediated dilation (FMD) were measured prior to, and following, ingestion of the high-fat meals. In the control trial, FMD was reduced by 30% and 33% (P0.05). These results support the concept of accumulating physical activity for health in adolescents as the accumulated exercise attenuated the decline in FMD seen following the consumption of high-fat meals. © 2013 John Wiley & Sons A/S

Acute high-intensity interval rowing increases thrombin generation in healthy men

PURPOSE: High-intensity exercise induces several health benefits, but may acutely and transiently increase the risk of cardiovascular events due to thrombotic changes promoting blood coagulation and thrombin formation. This study examined the effects of high-intensity exercise on plasma thrombin generation and triacylglycerol concentrations. METHODS: Sixteen healthy men completed two, 2-day conditions separated by 1 week. On day 1, participants rested (control) or completed four, 3-min high-intensity rowing intervals at an average rating of perceived exertion of 17 (exercise). Venous blood samples were collected pre- and post-intervention to determine plasma thrombin generation. On day 2, participants rested and consumed a glucose load (0 h) and high-fat meal (2 h). Fifteen venous blood samples were collected between 0 and 8 h to measure plasma thrombin generation and triacylglycerol concentrations. RESULTS: On day 1, lag time was shorter and peak thrombin and endogenous thrombin potential were greater in the exercise than control condition (ES ≥ 0.37, main effect condition P ≤ 0.03), and post-intervention compared with pre-intervention (ES ≥ 0.49, main effect time P ≤ 0.003). The magnitude of the post-intervention change was greater in the exercise than control condition for all thrombin generation parameters (condition by time interaction P ≤ 0.05). On day 2, no differences in postprandial thrombin generation parameters were seen between conditions (P ≥ 0.21). The total area under the curve for triacylglycerol was lower in the exercise than control condition (ES = 0.34, P = 0.02). CONCLUSION: An acute bout of high-intensity interval rowing increased plasma thrombin generation immediately after exercise, but these differences were eliminated 16–24 h after exercise

Effect of exercise on postprandial endothelial function in adolescent boys

The ingestion of high-fat meals induces a state of endothelial dysfunction in adults. This dysfunction is attenuated by prior exercise. The response of young people to these nutritional and physiological stressors has not been established. Thus, the purpose of the present study was to investigate if a bout of moderate-intensity exercise influenced endothelial function (as indicated by flow-mediated dilation (FMD)) following the ingestion of a high-fat breakfast and lunch in adolescent boys (aged 12·6–14·3 years). Two, 2 d main trials (control and exercise) were completed by thirteen adolescent boys in a counter-balanced, cross-over design. Participants were inactive on day 1 of the control trial, but completed 60 min of walking at 60% peak oxygen uptake in the exercise trial. On day 2, endothelial function was assessed via FMD prior to, and following, ingestion of a high-fat breakfast and lunch. There was no difference in fasting FMD between the control and exercise trial (P¼0·449). In the control trial, FMD was reduced by 32% following consumption of the high-fat breakfast and by 24% following lunch. In the exercise trial, the corresponding reductions were 6 and 10 %, respectively (main effect trial, P¼0·002). These results demonstrate that moderate-intensity exercise can attenuate the decline in FMD seen following the consumption of high-fat meals in adolescent boys

Effect of repeated sprints on postprandial endothelial function and triacylglycerol concentrations in adolescent boys

This study investigated if repeated, very short duration sprints influenced endothelial function (indicated by flow-mediated dilation) and triacylglycerol concentrations following the ingestion of high-fat meals in adolescent boys. Nine adolescent boys completed two, 2-day main trials (control and exercise), in a counter-balanced, cross-over design. Participants were inactive on day 1 of the control trial but completed 40 x 6 s maximal cycle sprints on day 1 of the exercise trial. On day 2 capillary blood samples were collected and flow-mediated dilation measured prior to, and following, ingestion of a high-fat breakfast and lunch. Fasting flow-mediated dilation and plasma triacylglycerol concentration were similar in the control and exercise trial (P>0.05). In the control trial flow-mediated dilation was reduced by 20% and 27% following the high-fat breakfast and lunch; following exercise these reductions were negated (main effect trial, P<0.05; interaction effect trial x time, P<0.05). The total area under the plasma triacylglycerol concentration versus time curve was 13% lower on day 2 in the exercise trial, compared to the control trial (8.65 (0.97) vs. 9.92 (1.16) mmol·L-1·6.5h, P<0.05). These results demonstrate that repeated 6 s maximal cycle sprints can have beneficial effects on postprandial endothelial function and triacylglycerol concentrations in adolescent boys

The Decreasing Significance of Stigma in the Lives of Bisexual Men: Keynote Address, Bisexual Research Convention, London

This article is constructed around a keynote address given at the Bisexual Research Convention, held in London 2010. The keynote was delivered by sociologist Eric Anderson, on behalf of himself and the other authors of this article. The keynote reflected upon a body of ongoing research, funded by the American Institute of Bisexuality and collected by this team of researchers, into the changing relationship between men and homophobia. It first contextualizes 20th-century attitudes toward homo/bisexuality before showing a declining significance of biphobia and homophobia in men's lives today. In accordance with the keynote, this article draws from preliminary findings of multiple ongoing studies of bisexual men in the United States and the United Kingdom

The effect of prior walking on coronary heart disease risk markers in South Asian and European men.

Purpose: Heart disease risk is elevated in South Asians possibly due to impaired postprandial metabolism. Running has been shown to induce greater reductions in postprandial lipaemia in South Asian than European men but the effect of walking in South Asians is unknown. Methods: Fifteen South Asian and 14 White European men aged 19-30 years completed two, 2-d trials in a randomised crossover design. On day 1, participants rested (control) or walked for 60 min at approximately 50% maximum oxygen uptake (exercise). On day 2, participants rested and consumed two high fat meals over a 9h period during which 14 venous blood samples were collected. Results: South Asians exhibited higher postprandial triacylglycerol (geometric mean (95% confidence interval) 2.29(1.82 to 2.89) vs. 1.54(1.21 to 1.96) mmol·L-1·hr-1), glucose (5.49(5.21 to 5.79) vs. 5.05(4.78 to 5.33) mmol·L-1·hr-1), insulin (32.9(25.7 to 42.1) vs. 18.3(14.2 to 23.7) µU·mL-1·hr-1) and interleukin-6 (2.44(1.61 to 3.67) vs. 1.04(0.68 to 1.59) pg·mL-1·hr-1) than Europeans (all ES ≥ 0.72, P≤0.03). Between-group differences in triacylglycerol, glucose and insulin were not significant after controlling for age and percentage body fat. Walking reduced postprandial triacylglycerol (1.79(1.52 to 2.12) vs. 1.97(1.67 to 2.33) mmol·L-1·hr-1) and insulin (21.0(17.0 to 26.0) vs. 28.7(23.2 to 35.4) µU·mL-1·hr-1) (all ES ≥ 0.23. P≤0.01), but group differences were not significant. Conclusions: Healthy South Asians exhibited impaired postprandial metabolism compared with White Europeans, but these differences were diminished after controlling for potential confounders. The small-moderate reduction in postprandial triacylglycerol and insulin after brisk walking was not different between the ethnicities

The community-based prevention of diabetes (ComPoD) study: A randomised, waiting list controlled trial of a voluntary sector-led diabetes prevention programme

© 2019 The Author(s). Objective: This two-site randomised trial compared the effectiveness of a voluntary sector-led, community-based diabetes prevention programme to a waiting-list control group at 6 months, and included an observational follow-up of the intervention arm to 12 months. Methods: Adults aged 18-75 years at increased risk of developing type 2 diabetes due to elevated blood glucose and being overweight were recruited from primary care practices at two UK sites, with data collected in participants' homes or community venues. Participants were randomised using an online central allocation service. The intervention, comprising the prototype "Living Well, Taking Control" (LWTC) programme, involved four weekly two-hour group sessions held in local community venues to promote changes in diet and physical activity, plus planned follow-up contacts at two, three, six, nine and 12 months alongside 5 hours of additional activities/classes. Waiting list controls received usual care for 6 months before accessing the programme. The primary outcome was weight loss at 6 months. Secondary outcomes included glycated haemoglobin (HbA1c), blood pressure, physical activity, diet, health status and well-being. Only researchers conducting analyses were blinded. Results: The target sample of 314 participants (157 each arm) was largely representative of local populations, including 44% men, 26% from ethnic minorities and 33% living in deprived areas. Primary outcome data were available for 285 (91%) participants (141 intervention, 144 control). Between baseline and 6 months, intervention participants on average lost more weight than controls (- 1.7 kg, 95% CI - 2.59 to - 0.85). Higher attendance was associated with greater weight loss (- 3.0 kg, 95% CI - 4.5 to - 1.5). The prototype LWTC programme more than doubled the proportion of participants losing > 5% of their body weight (21% intervention vs. 8% control, OR 2.83, 95% CI 1.36 to 5.90) and improved self-reported dietary behaviour and health status. There were no impacts on HbA1c, blood pressure, physical activity and well-being at 6 months and, amongst intervention participants, few further changes from six to 12-months (e.g. average weight re-gain 0.36 kg, 95% CI - 0.20 to 0.91). There were no serious adverse events but four exercise-related injuries were reported in the intervention arm. Conclusions: This voluntary sector-led diabetes prevention programme reached a broad spectrum of the population and had modest effects on weight-related outcomes, but limited impacts on other diabetes risk factors. Trial registration: Trial registration number: ISRCTN70221670, 5 September 2014 Funder (National Institute for Health Research School for Public Health Research) project reference number: SPHR-EXE-PES-COM

Novel Structural Components of the Ventral Disc and Lateral Crest in Giardia intestinalis

Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis, one of the most common protozoan diarrheal diseases in the world. Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure, the ventral disc. Surrounding the ventral disc is a less characterized putatively contractile structure, the lateral crest, which forms a continuous perimeter seal with the substrate. A better understanding of ventral disc and lateral crest structure, conformational dynamics, and biogenesis is critical for understanding the mechanism of giardial attachment to the host. To determine the components comprising the ventral disc and lateral crest, we used shotgun proteomics to identify proteins in a preparation of isolated ventral discs. Candidate disc-associated proteins, or DAPs, were GFP-tagged using a ligation-independent high-throughput cloning method. Based on disc localization, we identified eighteen novel DAPs, which more than doubles the number of known disc-associated proteins. Ten of the novel DAPs are associated with the lateral crest or outer edge of the disc, and are the first confirmed components of this structure. Using Fluorescence Recovery After Photobleaching (FRAP) with representative novel DAP::GFP strains we found that the newly identified DAPs tested did not recover after photobleaching and are therefore structural components of the ventral disc or lateral crest. Functional analyses of the novel DAPs will be central toward understanding the mechanism of ventral disc-mediated attachment and the mechanism of disc biogenesis during cell division. Since attachment of Giardia to the intestine via the ventral disc is essential for pathogenesis, it is possible that some proteins comprising the disc could be potential drug targets if their loss or disruption interfered with disc biogenesis or function, preventing attachment

An Active Site Aromatic Triad in Escherichia coli DNA Pol IV Coordinates Cell Survival and Mutagenesis in Different DNA Damaging Agents

DinB (DNA Pol IV) is a translesion (TLS) DNA polymerase, which inserts a nucleotide opposite an otherwise replication-stalling N2-dG lesion in vitro, and confers resistance to nitrofurazone (NFZ), a compound that forms these lesions in vivo. DinB is also known to be part of the cellular response to alkylation DNA damage. Yet it is not known if DinB active site residues, in addition to aminoacids involved in DNA synthesis, are critical in alkylation lesion bypass. It is also unclear which active site aminoacids, if any, might modulate DinB's bypass fidelity of distinct lesions. Here we report that along with the classical catalytic residues, an active site “aromatic triad”, namely residues F12, F13, and Y79, is critical for cell survival in the presence of the alkylating agent methyl methanesulfonate (MMS). Strains expressing dinB alleles with single point mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in addition to its role in TLS, modulates DinB's accuracy in bypassing distinct lesions. The high bypass fidelity of prevalent alkylation lesions is evident even when the DinB active site performs error-prone NFZ-induced lesion bypass. The analyses carried out with the active site aromatic triad suggest that the DinB active site residues are poised to proficiently bypass distinctive DNA lesions, yet they are also malleable so that the accuracy of the bypass is lesion-dependent