Observational assessment and maternal reports of motivation in children and adolescents with Down Syndrome

Despite a lack of consistent empirical evidence, there has been an ongoing assumption that intellectual disability is associated with reduced levels of motivation. The participants in this study were 33 children with Down syndrome ages 10–15 years and 33 typically developing 3–8-year-old children. Motivation was measured through observational assessments of curiosity, preference for challenge, and persistence, as well as maternal reports. There were no significant group differences on motivation tasks, but mothers of children with Down syndrome rated their children significantly lower on motivation than did parents of typically developing children. There were some intriguing group differences in the pattern of correlations among observations and parent reports. The findings challenge long-held views that individuals with intellectual disability are invariably deficient in motivation.

High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men

Background-Although dyslipoproteinemia is associated with arterial atherothrombosis, little is known about plasma lipoproteins in venous thrombosis patients. Methods and Results-We determined plasma lipoprotein subclass concentrations using nuclear magnetic resonance spectroscopy and antigenic levels of apolipoproteins AI and B in blood samples from 49 male venous thrombosis patients and matched controls aged <55 years. Venous thrombosis patients had significantly lower levels of HDL particles, large HDL particles, HDL cholesterol, and apolipoprotein AI and significantly higher levels of LDL particles and small LDL particles. The quartile-based odds ratios for decreased HDL particle and apolipoprotein AI levels in patients compared with controls were 6.5 and 6.0 (95% CI, 2.3 to 19 and 2.1 to 17), respectively. Odds ratios for apolipoprotein B/apolipoprotein AI ratio and LDL cholesterol/HDL cholesterol ratio were 6.3 and 2.7 (95% CI, 1.9 to 21 and 1.1 to 6.5), respectively. When polymorphisms in genes for hepatic lipase, endothelial lipase, and cholesteryl ester transfer protein were analyzed, patients differed significantly from controls in the allelic frequency for the TaqI B1/B2 polymorphism in cholesteryl ester transfer protein, consistent with the observed pattern of lower HDL and higher LDL. Conclusions-Venous thrombosis in men aged <55 years old is associated with dyslipoproteinemia involving lower levels of HDL particles, elevated levels of small LDL particles, and an elevated ratio of apolipoprotein B/apolipoprotein AI. This dyslipoproteinemia seems associated with a related cholesteryl ester transfer protein genotype difference. © 2005 American Heart Association, Inc.

Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome)

Abstract Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9.

Genetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovaries

Several studies have demonstrated an association between polycystic ovary syndrome (PCOS) and the dinucleotide repeat microsatellite marker D19S884, which is located in intron 55 of the fibrillin-3 (FBN3) gene. Fibrillins, including FBN1 and 2, interact with latent transforming growth factor (TGF)-β-binding proteins (LTBP) and thereby control the bioactivity of TGFβs. TGFβs stimulate fibroblast replication and collagen production. The PCOS ovarian phenotype includes increased stromal collagen and expansion of the ovarian cortex, features feasibly influenced by abnormal fibrillin expression. To examine a possible role of fibrillins in PCOS, particularly FBN3, we undertook tagging and functional single nucleotide polymorphism (SNP) analysis (32 SNPs including 10 that generate non-synonymous amino acid changes) using DNA from 173 PCOS patients and 194 controls. No SNP showed a significant association with PCOS and alleles of most SNPs showed almost identical population frequencies between PCOS and control subjects. No significant differences were observed for microsatellite D19S884. In human PCO stroma/cortex (n = 4) and non-PCO ovarian stroma (n = 9), follicles (n = 3) and corpora lutea (n = 3) and in human ovarian cancer cell lines (KGN, SKOV-3, OVCAR-3, OVCAR-5), FBN1 mRNA levels were approximately 100 times greater than FBN2 and 200–1000-fold greater than FBN3. Expression of LTBP-1 mRNA was 3-fold greater than LTBP-2. We conclude that FBN3 appears to have little involvement in PCOS but cannot rule out that other markers in the region of chromosome 19p13.2 are associated with PCOS or that FBN3 expression occurs in other organs and that this may be influencing the PCOS phenotype.

Quality of life and genetics in men with prostate cancer

As family history has been established as a risk factor for prostate cancer, attempts have been made to isolate predisposing genetic variants that are related to hereditary prostate cancer. With many genetic variants still to be identified and investigated, it is not yet possible to fully understand the impact of genetic variants on prostate cancer development. The high survival rates among men with prostate cancer have meant that other issues, such as quality of life (QoL), have also become important. Through their effect on a person’s health, a range of inherited genetic variants may potentially influence QoL in men with prostate cancer, even prior to treatment. Until now, limited research has been conducted on the relationship between genetics and QoL. Thus, this study contributes to an emerging field by aiming to identify certain genetic variants related to the QoL found in men with prostate cancer. It is hoped that this study may lead to future research that will identify men who have an increased risk of a poor QoL following prostate cancer treatment, which will aid in developing treatments that are individually tailored to support them. Previous studies have established that genetic variants of Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor 1 (IGF-1) may play a role in prostate cancer development. VEGF and IGF-1 have also been reported to be associated with QoL in people with ovarian cancer and colorectal cancer, respectively. This study completed a series of secondary analyses using two major data-sets (from 850 men newly diagnosed with prostate cancer, and approximately 550 men from the general Queensland population), in which genetic variants of VEGF and IGF-1 were investigated for associations with prostate cancer susceptibility and QoL. The first aim of this research was to investigate genetic variants in the VEGF and IGF-I gene for an association with the risk of prostate cancer. It was found that one IGF-1 genetic variant (rs35765) had a statistically significant association with prostate cancer (p = 0.04), and one VEGF genetic variant (rs2146323) had a statistically significant association with advanced prostate cancer (p = 0.02). The estimates suggest that carriers of the CA and AA genotype for rs35765 may have a reduced risk of developing prostate cancer (Odds Ratio (OR) = 0.72, 95% Confidence Interval (CI) = 0.55, 0.95, OR = 0.60, 95% CI = 0.26, 1.39, respectively). Meanwhile, carriers of the CA and AA genotype for rs2146323 may be at increased risk of advanced prostate cancer, which was determined by a Gleason score of above 7 (OR = 1.72, 95% CI = 1.12, 2.63, OR = 1.90, 95% CI = 1.08, 3.34, respectively). Utilising the widely used short-form health survey, the SF-36v2, the second aim of this study was to investigate the relationship between prostate cancer and QoL prior to treatment. Assessing QoL at this time-point was important as little research has been conducted to evaluate if prostate cancer affects QoL regardless of treatment. The analyses found that mean SF-36v2 scale scores related to physical health were higher by at least 0.3 Standard Deviations (SD) among men with prostate cancer than the general population comparison group. This difference was considered clinically significant (defined by group differences in mean SF-36v2 scores by at least 0.3 SD). These differences were also statistically significant (p<0.05). Mean QoL scale scores related to mental health were similar between men with prostate cancer and those from the general population comparison group. The third aim of this study was to investigate genetic variants in the VEGF and IGF-1 gene for an association with QoL in prostate cancer patients prior to their treatment. It was essential to evaluate these relationships prior to treatment, before the involvement of these genes was potentially interrupted by treatment. The analyses found that some genetic variants had a small clinically significant association (0.3 SD) to some QoL domains experienced by these men. However, most relationships were not statistically significant (p>0.05). Most of the associations found identified that a small sub-group of men with prostate cancer (approximately 2%) reported, on average, a slightly better QoL than the majority of the prostate cancer patients. The fourth aim of this research was to investigate whether associations between genetic variants in VEGF and IGF-1 and QoL were specific to men with prostate cancer, or were also applicable to the general male population. It was found that twenty out of one-hundred relationships between the genetic variants of VEGF and IGF-1 and QoL health-measures and scales examined differed between these groups. In the majority of the relationships involving VEGF SNPs that differed, a clinically significant difference (0.3 or more SD) between mean scores among the genotype groups in prostate cancer patients was found, while mean scores among men from the general-population comparison group were similar. For example, prostate cancer participants who carried at least one T allele (CT or TT genotype) for rs3024994 had a clinically significant higher (0.3 SD) mean QoL score in terms of the role-physical scale, than participants who carried the CC genotype. This was not seen among men from the general population sample, as the mean score was similar between genotype groups. The opposite was seen in regards to the IGF-1 SNPs examined. Overall, these relationships were not considered to directly impact on the clinical options for men with prostate cancer. As this study utilised secondary data from two separate studies, there are a number of important limitations that should be acknowledged including issues of multiple comparisons, power, and missing or unavailable data. It is recommended that this study be replicated as a better-designed study that takes greater consideration of the many factors involved in prostate cancer and QoL. Investigation into other genetic variants of VEGF or IGF-1 is also warranted, as is consideration of other genes and their relationship with QoL. Through identifying certain genetic variants that have a modest association to prostate cancer, this project adds to the knowledge surrounding VEGF and IGF-1 and their role in prostate cancer susceptibility. Importantly, this project has also introduced the potential role genetics plays in QoL, through investigating the relationships between genetic variants of VEGF and IGF-1 and QoL.

Determinants of skin self-examination (SSE) in men aged 50 years or older

Background: Queensland men aged 50 years and older are at high risk for melanoma. Early detection via skin self examination (SSE) (particularly whole-body SSE) followed by presentation to a doctor with suspicious lesions, may decrease morbidity and mortality from melanoma. Prevalence of whole-body SSE (wbSSE) is lower in Queensland older men compared to other population subgroups. With the exception of the present study no previous research has investigated the determinants of wbSSE in older men, or interventions to increase the behaviour in this population. Furthermore, although past SSE intervention studies for other populations have cited health behaviour models in the development of interventions, no study has tested these models in full. The Skin Awareness Study: A recent randomised trial, called the Skin Awareness Study, tested the impact of a video-delivered intervention compared to written materials alone on wbSSE in men aged 50 years or older (n=930). Men were recruited from the general population and interviewed over the telephone at baseline and 13 months. The proportion of men who reported wbSSE rose from 10% to 31% in the control group, and from 11% to 36% in the intervention group. Current research: The current research was a secondary analysis of data collected for the Skin Awareness Study. The objectives were as follows: • To describe how men who did not take up any SSE during the study period differed from those who did take up examining their skin. • To determine whether the intervention program was successful in affecting the constructs of the Health Belief Model it was aimed at (self-efficacy, perceived threat, and outcome expectations); and whether this in turn influenced wbSSE. • To determine whether the Health Action Process Approach (HAPA) was a better predictor of wbSSE behaviour compared to the Health Belief Model (HBM). Methods: For objective 1, men who did not report any past SSE at baseline (n=308) were categorised as having ‘taken up SSE’ (reported SSE at study end) or ‘resisted SSE’ (reported no SSE at study end). Bivariate logistic regression, followed by multivariable regression, investigated the association between participant characteristics measured at baseline and resisting SSE. For objective 2 proxy measures of self-efficacy, perceived threat, and outcome expectations were selected. To determine whether these mediated the effect of the intervention on the outcome, a mediator analysis was performed with all participants who completed interviews at both time points (n=830) following the Baron and Kenny approach, modified for use with structural equation modelling (SEM). For objective 3, control group participants only were included (n=410). Proxy measures of all HBM and HAPA constructs were selected and SEM was used to build up models and test the significance of each hypothesised pathway. A likelihood ratio test compared the HAPA to the HBM. Results: Amongst men who did not report any SSE at baseline, 27% did not take up any SSE by the end of the study. In multivariable analyses, resisting SSE was associated with having more freckly skin (p=0.027); being unsure about the statement ‘if I saw something suspicious on my skin, I’d go to the doctor straight away’ (p=0.028); not intending to perform SSE (p=0.015), having lower SSE self-efficacy (p<0.001), and having no recommendation for SSE from a doctor (p=0.002). In the mediator analysis none of the tested variables mediated the relationship between the intervention and wbSSE. In regards to health behaviour models, the HBM did not predict wbSSE well overall. Only the construct of self-efficacy was a significant predictor of future wbSSE (p=0.001), while neither perceived threat (p=0.584) nor outcome expectations (p=0.220) were. By contrast, when the HAPA constructs were added, all three HBM variables predicted intention to perform SSE, which in turn predicted future behaviour (p=0.015). The HAPA construct of volitional self-efficacy was also associated with wbSSE (p=0.046). The HAPA was a significantly better model compared to the HBM (p<0.001). Limitations: Items selected to measure HBM and HAPA model constructs for objectives 2 and 3 may not have accurately reflected each construct. Conclusions: This research added to the evidence base on how best to target interventions to older men; and on the appropriateness of particular health behaviour models to guide interventions. Findings indicate that to overcome resistance those men with more negative pre-existing attitudes to SSE (not intending to do it, lower initial self-efficacy) may need to be targeted with more intensive interventions in the future. Involving general practitioners in recommending SSE to their patients in this population, alongside disseminating an intervention, may increase its success. Comparison of the HBM and HAPA showed that while two of the three HBM variables examined did not directly predict future wbSSE, all three were associated with intention to self-examine skin. This suggests that in this population, intervening on these variables may increase intention to examine skin, but not necessarily the behaviour itself. Future interventions could potentially focus on increasing both the motivational variables of perceived threat and outcome expectations as well as a combination of both action and volitional self-efficacy; with the aim of increasing intention as well as its translation to taking up and maintaining regular wbSSE.

Substance-related expectancies among men who have sex with men : development of psychometric tools to predict unprotected sexual activity

Significant research has demonstrated direct and indirect associations between substance use and sexual behaviour. Substance use is related to sexual risk-taking and HIV seroconversion among some substance-using MSM. It remains unclear what factors mediate or underlie this relationship, and which substances are associated with greater harm. Substance-related expectancies are hypothesised as potential mechanisms. A conceptual model based on social-cognitive theory was tested, which explores the role of demographic factors, substance use, substance-related expectancies and novelty-seeking personality characteristics in predicting unprotected anal intercourse (UAI) while under the influence, across four commonly used substance types. Phase 1, a qualitative study (N = 20), explored how MSM perceive the effects of substance use on their thoughts, feelings and behaviours, including sexual behaviours. Information was attained through discussion and interviews, resulting in the establishment of key themes. Results indicated MSM experience a wide range of reinforcing aspects associated with substance use. General and specific effects were evident across substance types, and were associated with sexual behaviour and sexual risk-taking. Phase 2 consisted of developing a comprehensive profile of substance-related expectancies for MSM (SEP-MSM) regarding alcohol, cannabis, amyl nitrite and stimulants that possessed sound psychometric properties and was appropriate for use among this group. A cross-sectional questionnaire with 249 participants recruited through gay community networks was used to validate these measures, and involved online data collection, participants rating expectancy items and subsequent factor analysis. Results indicated expectancies can be reliably assessed, and predicted substance use patterns. Phase 3 examined demographic factors, substance use, substance-related expectancies, and novelty-seeking traits among another community sample of MSM (N = 277) throughout Australia, in predicting UAI while under the influence. Using a cross-sectional design, participants were recruited through gay community networks and completed online questionnaires. The SEP-MSM, and associated substance use, predicted UAI. This research extends social-cognitive theory regarding sexual behaviour, and advances understanding of the role of expectancies associated with substance use and sexual risk-taking. Future applications of the SEP-MSM in health promotion, prevention, clinical interventions and research are likely to contribute to reducing harm associated with substance-using MSM (e.g., HIV transmission).

Gay men, intimate partner violence, and help-seeking : the incomprehensibility of being a victim

A recurring finding within the research on same-sex intimate partner violence (IPV) is that victims rarely seek assistance from police or other service providers. A study by William Leonard et al (2008: 47) in Victoria, Australia, found that around two thirds of gay, lesbian, bisexual and transgender victims did not report such violence. It also appears that men are less likely than women to seek help for IPV (Turell and Cornell-Swanson 2005:79–80), and for those that do, informal support networks are approached more often than formal services (Merrill and Wolfe 2000: 16; Farrell and Cerise 2006: 4).

An exploration of Online Shopping Cart Abandonment Syndrome – a matter of risk and reputation

ABSRACT. Despite the surge in online retail sales in recent years there still remains reluctance by consumers to complete the online shopping process. A number of authors have attributed consumers’ reluctance to purchase online to apparent barriers. However, such barriers as yet have not been fully examined within a theoretical context. This research explores the application of the perceived risk theoretical framework. Specifically, performance risk and the influence of perceived performance risk has on the phenomenon of Internet Abandoned Cart Syndrome (ACS) is evaluated. To explore this phenomenon, a number of extrinsic cues are identified as playing a major role in the performance evaluation process of online purchases. The results of this study suggest the extrinsic cues of brand, reputation, design and price have an overall impact on the performance evaluation process just prior to an online purchase. Varying these cues either positively or negatively had a strong impact on performance evaluation. Further, it was found that positive or negative reputation was heavily associated with shopping cart abandonment.

The role of insulin and IGF2 signalling on metabolic pathways in prostate cancer progression

Prostate cancer (CaP) is the most commonly diagnosed cancer in males in Australia, North America, and Europe. If found early and locally confined, CaP can be treated with radical prostatectomy or radiation therapy; however, 25-40% patients will relapse and go on to advanced disease. The most common therapy in these cases is androgen deprivation therapy (ADT), which suppresses androgen production from the testis. Lack of the testicular androgen supply causes cells of the prostate to undergo apoptosis. However, in some cases the regression initially seen with ADT eventually gives way to a growth of a population of cancerous cells that no longer require testicular androgens. This phenotype is essentially fatal and is termed castrate resistant prostate cancer (CRPC). In addition to eventual regression, there are many undesirable side effects which accompany ADT, including development of a metabolic syndrome, which is defined by the U.S. National Library of Medicine as “a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes.” This project will focus on the effect of ADT induced hyperinsulinemia, as mimicked by treating androgen receptor positive CaP cells with insulin in a serum (hormone) deprived environment. While this side effect is not widely explored, in this thesis it is demonstrated for the first time that insulin upregulates pathways important to CaP progression. Our group has previously shown that during CaP progression, the enzymes necessary for de novo steroidogenesis are upregulated in the LNCaP xenograft model, total steroid levels are increased in tumours compared to pre castrate levels, and de novo steroidogenesis from radio-labelled acetate has been demonstrated. Because of the CaP dependence on AR for survival, we and other groups believe that CaP cells carry out de novo steroidogenesis to survive in androgen deprived conditions. Because (a) men on ADT often develop metabolic syndrome, and (b) men with lifestyle-induced obesity and hyperinsulinemia have worse prognosis and faster disease progression, and because (c) insulin causes steroidogenesis in other cell lines, the hypothesis that insulin may contribute to CaP progression through upregulation of steroidogenesis was explored. Insulin upregulates steroidogenesis enzymes at the mRNA level in three AR positive cell lines, as well as upregulating these enzymes at the protein level in two cell lines. It has also been demonstrated that insulin increases mitochondrial (functional) levels of steroid acute regulatory protein (StAR). Furthermore, insulin causes increased levels of total steroids in and induction of de novo steroid synthesis by insulin has been demonstrated at levels induced sufficient to activate AR. The effect of insulin analogs on CaP steroidogenesis in LNCaP and VCaP cells has also been investigated because epidemiological studies suggest that some of the analogs developed may have more cancer stimulatory effects than normal insulin. In this project, despite the signalling differences between glargine, X10, and insulin, these analogs did not appear to induce steroidogenesis any more potently that normal insulin. The effect of insulin of MCF7breast cancer cells was also investigated with results suggesting that breast cancer cells may be capable of de novo steroidogenesis, and that increase in estradiol production may be exacerbated by insulin. Insulin has also been long known to stimulate lipogenesis in the liver and adipocytes, and has been demonstrated to increase lipogenesis in breast cancer cells; therefore, investigation of the effect of insulin on lipogenesis, which is a hallmark of aggressive cancers, was investigated. In CaP progression sterol regulatory element binding protein (SREBP) is dysregulated and upregulates fatty acid synthase (FASN), acetyl CoA-carboxylase, and other lipogenesis genes. SREBP is important for steroidogenesis and in this project has been shown to be upregulated by insulin in CaP cells. Fatty acid synthesis provides building blocks of membrane growth, provides substrates for acid oxidation, the main energy source for CaP cells, provides building blocks for anti-apoptotic and proinflammatory molecules, and provides molecules that stimulate steroidogenesis. In this project it has been shown that insulin upregulates FASN and ACC, which synthesize fatty acids, as well as upregulating hormone sensitive lipase (HSL), diazepam-binding inhibitor (DBI), and long-chain acyl-CoA synthetase 3 (ACSL3), which contribute to lipid activation of steroidogenesis. Insulin also upregulates total lipid levels and de novo lipogenesis, which can be suppressed by inhibition of the insulin receptor (INSR). The fatty acids synthesized after insulin treatment are those that have been associated with CaP; furthermore, microarray data suggests insulin may upregulate fatty acid biosynthesis, metabolism and arachidonic acid metabolism pathways, which have been implicated in CaP growth and survival. Pharmacological agents used to treat patients with hyperinsulinemia/ hyperlipidemia have gained much interest in regards to CaP risk and treatment; however, the scientific rationale behind these clinical applications has not been examined. This thesis explores whether the use of metformin or simvastatin would decrease either lipogenesis or steroidogenesis or both in CaP cells. Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitor, which blocks synthesis of cholesterol, the building block of steroids/ androgens. It has also been postulated to down regulate SREBP in other metabolic disorders. It has been shown in this thesis, in LNCaP cells, that simvastatin inhibited and decreased insulin induced steroidogenesis and lipogenesis, respectively, but increased these pathways in the absence of insulin. Conversely, metformin, which activates AMP-activated protein kinase (AMPK) to shut down lipogenesis, cholesterol synthesis, and protein synthesis, highly suppresses both steroidogenesis and lipogenesis in the presence and absence of insulin. Lastly, because it has been demonstrated to increase steroidogenesis in other cell lines, and because the elucidation of any factors affecting steroidogenesis is important to understanding CaP, the effect of IGF2 on steroidogenesis in CaP cells was investigated. In patient samples, as men progress to CRPC, IGF2 mRNA and the protein levels of the receptors it may signal through are upregulated. It has also been demonstrated that IGF2 upregulates steroidogenic enzymes at both the mRNA and protein levels in LNCaP cells, increases intracellular and secreted steroid/androgen levels in LNCaPs to levels sufficient to stimulate the AR, and upregulated de novo steroidogenesis in LNCaPs and VCaPs. As well, inhibition of INSR and insulin-like growth factor 1 receptor (IGF1R), which IGF2 signals through, suggests that induction of steroidogenesis may be occurring predominantly through IGF1R. In summary, this project has illuminated for the first time that insulin is likely to play a large role in cancer progression, through upregulation of the steroidogenesis and lipogenesis pathways at the mRNA and protein levels, and production levels, and demonstrates a novel role for IGF-II in CaP progression through stimulation of steroidogenesis. It has also been demonstrated that metformin and simvastatin drugs may be useful in suppressing the insulin induction of these pathways. This project affirms the pathways by which ADT- induced metabolic syndrome may exacerbate CaP progression and strongly suggests that the monitoring and modulation of the metabolic state of CaP patients could have a strong impact on their therapeutic outcomes.

The effect of exercise intensity on fat oxidation and non-exercise activity thermogenesis in overweight/obese men

It is frequently reported that the actual weight loss achieved through exercise interventions is less than theoretically expected. Amongst other compensatory adjustments that accompany exercise training (e.g., increases in resting metabolic rate and energy intake), a possible cause of the less than expected weight loss is a failure to produce a marked increase in total daily energy expenditure due to a compensatory reduction in non-exercise activity thermogenesis (NEAT). Therefore, there is a need to understand how behaviour is modified in response to exercise interventions. The proposed benefits of exercise training are numerous, including changes to fat oxidation. Given that a diminished capacity to oxidise fat could be a factor in the aetiology of obesity, an exercise training intensity that optimises fat oxidation in overweight/obese individuals would improve impaired fat oxidation, and potentially reduce health risks that are associated with obesity. To improve our understanding of the effectiveness of exercise for weight management, it is important to ensure exercise intensity is appropriately prescribed, and to identify and monitor potential compensatory behavioural changes consequent to exercise training. In line with the gaps in the literature, three studies were performed. The aim of Study 1 was to determine the effect of acute bouts of moderate- and high-intensity walking exercise on NEAT in overweight and obese men. Sixteen participants performed a single bout of either moderate-intensity walking exercise (MIE) or high-intensity walking exercise (HIE) on two separate occasions. The MIE consisted of walking for 60-min on a motorised treadmill at 6 km.h-1. The 60-min HIE session consisted of walking in 5-min intervals at 6 km.h-1 and 10% grade followed by 5-min at 0% grade. NEAT was assessed by accelerometer three days before, on the day of, and three days after the exercise sessions. There was no significant difference in NEAT vector magnitude (counts.min-1) between the pre-exercise period (days 1-3) and the exercise day (day 4) for either protocol. In addition, there was no change in NEAT during the three days following the MIE session, however NEAT increased by 16% on day 7 (post-exercise) compared with the exercise day (P = 0.32). During the post-exercise period following the HIE session, NEAT was increased by 25% on day 7 compared with the exercise day (P = 0.08), and by 30-33% compared with the pre-exercise period (day 1, day 2 and day 3); P = 0.03, 0.03, 0.02, respectively. To conclude, a single bout of either MIE or HIE did not alter NEAT on the exercise day or on the first two days following the exercise session. However, extending the monitoring of NEAT allowed the detection of a 48 hour delay in increased NEAT after performing HIE. A longer-term intervention is needed to determine the effect of accumulated exercise sessions over a week on NEAT. In Study 2, there were two primary aims. The first aim was to test the reliability of a discontinuous incremental exercise protocol (DISCON-FATmax) to identify the workload at which fat oxidation is maximised (FATmax). Ten overweight and obese sedentary male men (mean BMI of 29.5 ¡Ó 4.5 kg/m2 and mean age of 28.0 ¡Ó 5.3 y) participated in this study and performed two identical DISCON-FATmax tests one week apart. Each test consisted of alternate 4-min exercise and 2-min rest intervals on a cycle ergometer. The starting work load of 28 W was increased every 4-min using 14 W increments followed by 2-min rest intervals. When the respiratory exchange ratio was consistently >1.0, the workload was increased by 14 W every 2-min until volitional exhaustion. Fat oxidation was measured by indirect calorimetry. The mean FATmax, ƒtV O2peak, %ƒtV O2peak and %Wmax at which FATmax occurred during the two tests were 0.23 ¡Ó 0.09 and 0.18 ¡Ó 0.08 (g.min-1); 29.7 ¡Ó 7.8 and 28.3 ¡Ó 7.5 (ml.kg-1.min-1); 42.3 ¡Ó 7.2 and 42.6 ¡Ó 10.2 (%ƒtV O2max) and 36.4 ¡Ó 8.5 and 35.4 ¡Ó 10.9 (%), respectively. A paired-samples T-test revealed a significant difference in FATmax (g.min-1) between the tests (t = 2.65, P = 0.03). The mean difference in FATmax was 0.05 (g.min-1) with the 95% confidence interval ranging from 0.01 to 0.18. Paired-samples T-test, however, revealed no significant difference in the workloads (i.e. W) between the tests, t (9) = 0.70, P = 0.4. The intra-class correlation coefficient for FATmax (g.min-1) between the tests was 0.84 (95% confidence interval: 0.36-0.96, P < 0.01). However, Bland-Altman analysis revealed a large disagreement in FATmax (g.min-1) related to W between the two tests; 11 ¡Ó 14 (W) (4.1 ¡Ó 5.3 ƒtV O2peak (%)).These data demonstrate two important phenomena associated with exercise-induced substrate oxidation; firstly, that maximal fat oxidation derived from a discontinuous FATmax protocol differed statistically between repeated tests, and secondly, there was large variability in the workload corresponding with FATmax. The second aim of Study 2 was to test the validity of a DISCON-FATmax protocol by comparing maximal fat oxidation (g.min-1) determined by DISCON-FATmax with fat oxidation (g.min-1) during a continuous exercise protocol using a constant load (CONEX). Ten overweight and obese sedentary males (BMI = 29.5 ¡Ó 4.5 kg/m2; age = 28.0 ¡Ó 4.5 y) with a ƒtV O2max of 29.1 ¡Ó 7.5 ml.kg-1.min-1 performed a DISCON-FATmax test consisting of alternate 4-min exercise and 2-min rest intervals on a cycle ergometer. The 1-h CONEX protocol used the workload from the DISCON-FATmax to determine FATmax. The mean FATmax, ƒtV O2max, %ƒtV O2max and workload at which FATmax occurred during the DISCON-FATmax were 0.23 ¡Ó 0.09 (g.min-1); 29.1 ¡Ó 7.5 (ml.kg-1.min-1); 43.8 ¡Ó 7.3 (%ƒtV O2max) and 58.8 ¡Ó 19.6 (W), respectively. The mean fat oxidation during the 1-h CONEX protocol was 0.19 ¡Ó 0.07 (g.min-1). A paired-samples T-test revealed no significant difference in fat oxidation (g.min-1) between DISCON-FATmax and CONEX, t (9) = 1.85, P = 0.097 (two-tailed). There was also no significant correlation in fat oxidation between the DISCON-FATmax and CONEX (R=0.51, P = 0.14). Bland- Altman analysis revealed a large disagreement in fat oxidation between the DISCONFATmax and CONEX; the upper limit of agreement was 0.13 (g.min-1) and the lower limit of agreement was ¡V0.03 (g.min-1). These data suggest that the CONEX and DISCONFATmax protocols did not elicit different rates of fat oxidation (g.min-1). However, the individual variability in fat oxidation was large, particularly in the DISCON-FATmax test. Further research is needed to ascertain the validity of graded exercise tests for predicting fat oxidation during constant load exercise sessions. The aim of Study 3 was to compare the impact of two different intensities of four weeks of exercise training on fat oxidation, NEAT, and appetite in overweight and obese men. Using a cross-over design 11 participants (BMI = 29 ¡Ó 4 kg/m2; age = 27 ¡Ó 4 y) participated in a training study and were randomly assigned initially to: [1] a lowintensity (45%ƒtV O2max) exercise (LIT) or [2] a high-intensity interval (alternate 30 s at 90%ƒtV O2max followed by 30 s rest) exercise (HIIT) 40-min duration, three times a week. Participants completed four weeks of supervised training and between cross-over had a two week washout period. At baseline and the end of each exercise intervention,ƒtV O2max, fat oxidation, and NEAT were measured. Fat oxidation was determined during a standard 30-min continuous exercise bout at 45%ƒtV O2max. During the steady state exercise expired gases were measured intermittently for 5-min periods and HR was monitored continuously. In each training period, NEAT was measured for seven consecutive days using an accelerometer (RT3) the week before, at week 3 and the week after training. Subjective appetite sensations and food preferences were measured immediately before and after the first exercise session every week for four weeks during both LIT and HIIT. The mean fat oxidation rate during the standard continuous exercise bout at baseline for both LIT and HIIT was 0.14 ¡Ó 0.08 (g.min-1). After four weeks of exercise training, the mean fat oxidation was 0.178 ¡Ó 0.04 and 0.183 ¡Ó 0.04 g.min-1 for LIT and HIIT, respectively. The mean NEAT (counts.min-1) was 45 ¡Ó 18 at baseline, 55 ¡Ó 22 and 44 ¡Ó 16 during training, and 51 ¡Ó 14 and 50 ¡Ó 21 after training for LIT and HIIT, respectively. There was no significant difference in fat oxidation between LIT and HIIT. Moreover, although not statistically significant, there was some evidence to suggest that LIT and HIIT tend to increase fat oxidation during exercise at 45% ƒtV O2max (P = 0.14 and 0.08, respectively). The order of training treatment did not significantly influence changes in fat oxidation, NEAT, and appetite. NEAT (counts.min-1) was not significantly different in the week following training for either LIT or HIIT. Although not statistically significant (P = 0.08), NEAT was 20% lower during week 3 of exercise training in HIIT compared with LIT. Examination of appetite sensations revealed differences in the intensity of hunger, with higher ratings after LIT compared with HIIT. No differences were found in preferences for high-fat sweet foods between LIT and HIIT. In conclusion, the results of this thesis suggest that while fat oxidation during steady state exercise was not affected by the level of exercise intensity, there is strong evidence to suggest that intense exercise could have a debilitative effect on NEAT.