Identification and characterization of a lymphocytic Rho-GTPase effector: rhotekin-2

Rhotekin belongs to the group of proteins containing a Rho-binding domain that are target peptides (effectors) for the Rho-GTPases. We previously identified a novel cDNA with homology to human rhotekin and in this study we cloned and characterized the coding region of this novel 12-exon gene. The ORF encodes a 609 amino-acid protein comprising a Class I Rho-binding domain and pleckstrin homology (PH) domain. Cellular cDNA expression of this new protein, designated Rhotekin-2 (RTKN2), was shown in the cytosol and nucleus of CHO cells. Using bioinformatics and RTPCR we identified three major splice variants, which vary in both the Rho-binding and PH domains. Real-time PCR studies showed exclusive RTKN2 expression in pooled lymphocytes and further purification indicated sole expression in CD4^_pos T-cells and bone marrow-derived B-cells. Gene expression was increased in quiescent T-cells but negligible in activated proliferating cells. In malignant samples expression was absent in myeloid leukaemias, low in most B-cell malignancies and CD8^pos T-cell malignancies, but very high in CD4^pos/CD8^pos T-lymphoblastic lymphoma. As the Rho family is critical in lymphocyte development and function, RTKN2 may play an important role in lymphopoiesis.

Coronary artery stenoses: detection with calcium scoring, CT angiography, and both methods combined

PURPOSE: To investigate prospectively the relative accuracy of computed tomographic (CT) angiography, calcium scoring (CS), and both methods combined in demonstrating coronary artery stenoses by using conventional angiography as the reference standard. MATERIALS AND METHODS: The study was approved by the institutional review board Human Research Ethics Committee, and all patients completed written informed consent. Fifty patients (40 men, 10 women) aged 62 years ± 11 (± standard deviation) who were suspected of having coronary artery disease underwent both conventional coronary angiography and multisection coronary CT angiography with CS. Sensitivity and specificity of CS, CT angiography, and both methods combined in demonstrating luminal stenosis greater than or equal to 50% were determined for each arterial segment, coronary vessel, and patient. Receiver operating characteristic (ROC) curves were generated for CS prediction of significant stenosis, and the Mann-Whitney U test was used for comparison of CS between groups. RESULTS: When used with segment-specific electrocardiographic phase reconstructions, CT angiography demonstrated stenosed segments with 79% sensitivity and 95% specificity. Mean calcium score was greater in segments, vessels, and patients with stenoses than in segments, vessels, and patients without stenoses (P < .001 for all); nine (16%) of 56 stenosed segments, however, had a calcium score of 0. The patient calcium score correlated strongly with the number of stenosed arteries (Spearman {rho} = 0.75, P < .001). CS was more accurate in demonstrating stenosis in patients than in segments (areas under ROC curve were 0.88 and 0.74, respectively). CT angiography, however, was more accurate than CS in demonstrating stenosis in patients, vessels, and segments. The sensitivity and specificity of CS varied according to the threshold used, but when the calcium score cutoff (ie, >150) matched the specificity of CT angiography (95%), the sensitivity of CS in demonstrating stenosed segments was 29% (compared with 79% for CT angiography). Combining CT angiography with CS (at threshold of 400) improved the sensitivity of CT angiography (from 93% to 100%) in demonstrating significant coronary disease in patients, without a loss of specificity (85%); this finding, however, was not statistically significant. CONCLUSION: CT angiography is more accurate than CS in demonstrating coronary stenoses. A patient calcium score of greater than or equal to 400, however, can be used to potentially identify patients with significant coronary stenoses not detected at CT angiography.

The reliability of performance of healthy adults on three visual perception tests

Problems with visual perceptual skills have been shown to have a negative impact on the daily living skills of individuals and are, therefore, commonly assessed by occupational therapists. The purpose of this study was to examine two types of reliability (internal consistency and test-retest reliability) of three newly revised or developed adult visual perception tests. The participants were 50 healthy adults, aged 18 to 55 years, from Melbourne, Victoria, Australia. The participants completed the Developmental Test of Visual Perception - Adolescent and Adult (DTVP-A), the Motor-Free Visual Perception Test - Third Edition (MVPT-3) and the Test of Visual Perceptual Skills (non-motor) - Third Edition (TVPS-3). Internal consistency was examined using Cronbach's alpha calculations and test-retest reliability was analysed using Spearman rho non-parametric correlation coefficients.

The results indicated that the DTVP-A, the MVPT-3 and the TVPS-3 had total scale internal consistency correlation scores of 0.60 or higher (0.60, 0.69 and 0.63 respectively). The majority of the subscales of each test had lower correlation coefficients than the overall scores (ranging from 0.22 to 0.49). For the DTVP-A, MVPT-3 and TVPS-3 total scale scores, the test-retest reliability correlation coefficients were statistically significant (rho = 0.46, p<0.05; rho = 0.62, p<0.01; and rho = 0.59, p<0.01, respectively). Overall, the three visual perceptual tests exhibited low to moderate levels of internal consistency and test-retest reliability.

Using simulated patients to develop doctors' skills in facilitating bahaviour change : addressing childhood obesity

Objectives : This study aimed to describe the application, feasibility and outcomes of using simulated patients (SPs) to increase the skills of general practitioners (GPs) delivering a behavioural intervention to reduce childhood overweight and mild obesity.

Methods : Five female actors were trained as SPs. A total of 67 GPs from 46 general practices in Melbourne, Victoria, Australia, conducted two simulated consultation visits regarding healthy lifestyle family behaviour change, during which they practised their skills and received formative feedback. The GPs and SPs rated GP performance immediately after each consultation. Subsequently, 139 parents of overweight or obese 5–9-year-old children rated GP performance during real-life consultations. Other measures included child body mass index (BMI) Z-scores (at baseline and at a 9-month follow-up) and GP-reported levels of comfort and competence and the perceived value of SP visits.

Results : Simulated patient ratings, but not GP self-ratings, of GP performance predicted both parent ratings of real-life consultations (Spearman's rho 0.39 for correlation with SP rating at Visit 1) and subsequent reductions in BMI Z-scores between baseline and follow-up (Visit 1, rho − 0.45; Visit 2, rho − 0.46). GP levels of comfort and competence were maintained during and after the SP visits. A total of 95% of GPs rated simulated consultations as useful, although only 18% said they would pay for them.

Conclusions : Simulated patient assessment may predict real patient feedback and clinical outcomes, helping to identify doctors who require further training in behaviour change techniques. Randomised controlled trials may establish whether SPs actually raise skills or improve outcomes.

The reliability of two visual motor integration tests used with health adults

Occupational therapists often assess the visual motor integration (VMI) skills of children, adults, and the elderly, which are parts of the Body Functions and Structures of the International Classification of Functioning, Disability and Health. Objective. As it is imperative that therapists use tests and measures with strong psychometric properties, this study aims to examine the reliability of two VMI tests used with adults. Method. Sixty-one healthy adults, 18 males and 43 females, with an average age of 31.82 years, completed the Developmental Test of Visual Motor Integration (DTVMI) and the Full Range Test of Visual Motor Integration (FRTVMI). The Cronbach's alpha coefficient was used to examine the tests’ internal consistency, while the Spearman's rho correlation was used to evaluate the test–retest reliability, intrarater reliability, and interrater reliability of the two VMI tests. Results. The Cronbach's alpha coefficient for the DTVMI and FRTVMI was 0.66 and 0.80, respectively. The test–retest reliability coefficient was 0.77 (p < .001) for the DTVMI and 0.61 (p < .001) for the FRTVMI. The interrater reliability correlation was significant for both DTVMI at 0.79 (p < .001) and FRTVMI at 0.80 (p < .001). The DTVMI intrarater reliability correlation result was 0.95 (p < .001) and the FRTVMI at 0.87 (p < .001). Conclusion. Overall, the DTVMI and the FRTVMI exhibited moderate to high levels of reliability when used with a sample of healthy adults. Both VMI tests appear to exhibit reasonable levels of reliability and are recommended for use with adults and the elderly.

Striated muscle activator of Rho signalling (STARS) is a PGC-1α/oestrogen-related receptor-α target gene and is upregulated in human skeletal muscle after endurance exercise

Exercise improves the ability of skeletal muscle to metabolise fats and sugars. For these improvements to occur the muscle detects a signal caused by exercise, resulting in changes in genes and proteins that control metabolism. We show that endurance exercise increases the amount of a protein called striated muscle activator of Rho signalling (STARS) as well as several other proteins influenced by STARS.We also show that the amount of STARS can be increased by signals directed from proteins called peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC-1α) and oestrogen-related receptor-α (ERRα). We also observed that when we reduce the amount of STARS in muscle cells, we block the ability of PGC-1α/ERRα to increase a gene called carnitine palmitoyltransferase-1β (CPT-1β), which is important for fat metabolism. Our study has shown that the STARS pathway is regulated by endurance exercise. STARS may also play a role in fat metabolism in muscle.

Convergent validity of two visual motor integration tests

Background: Occupational therapists often assess visual motor integration (VMI) skills. It is, therefore, imperative that therapists use VMI tests with robust measurement properties.

Objective: This study examined the convergent validity of two VMI tests used to assess children, adolescents and adults.

Method: Three groups of healthy participants (n = 153) completed the Beery-Buktenica Developmental Test of Visual-Motor Integration (DTVMI) and the Full Range Test of Visual Motor Integration (FRTVMI). Seventy-three children aged 5-10 years (37 males and 36 females; mean age 7.5 years, SD = 2.20), 19 adolescents aged 11-17 years (8 males and 11 females; 13.1 years, SD = 2.16), and 61 adults (18 males and 43 females; mean age 31.82 years, SD = 11.20) completed the DTVMI and the FRTVMI. Spearman rho correlation coefficients were used to investigate whether each pair of the VMI test scores for each of the three participant age groups were associated.

Results: The Spearman rho correlation coefficients between all three versions of the DTVMI and FRTVMI were statistically significant. For the child group, the correlation coefficient was rho = 0.70 (p<0.000), while the correlation between the VMI scores obtained by the adolescent group on the two tests was rho = 0.77 (p<0.000). For the adult participant group, the correlation coefficient between the DTVMI and the FRTVMI was rho = 0.70 (p<0.000).

Conclusion: The VMI scores obtained by the three participant age groups on the DTVMI and the FRTVMI were all significantly correlated with each other. Overall, the DTVMI and the FRTVMI exhibited large levels of convergent validity with each other, indicating that the two tests appear to measure similar visual-motor integration constructs.

The reliability of two visual motor integration tests used with children

Occupational therapists often assess the visual motor integration (VMI) skills of children and young people. It is important that therapists use tools with strong psychometric properties. This study aims to examine the reliability of 2 VMI tests. Ninety-two children between the ages of 5 and 17 years (response rate of 31%) completed 2 VMI tests: the Developmental Test of Visual Motor Integration (DTVMI) and the Full Range Test of Visual Motor Integration (FRTVMI). Cronbach's alpha coefficient was used to examine the internal consistency of the 2 VMI tests whereas Spearman's rho correlation was used to evaluate the test–retest reliability, intrarater reliability, and interrater reliability of the 2 VMI tests. The Cronbach's alpha coefficient for the DTVMI was .82 and .72 for the FRTVMI. The test–retest reliability coefficient was .73 (p = .000) for the DTVMI and .49 (p = .05) for the FRTVMI. The interrater correlation was significant for both the DTVMI at .94 (p = .000) and FRTVMI at .68 (p = .001). The DTVMI intrarater reliability correlation result was .90 (p = .000) and the FRTVMI at .85 (p = .000). Overall, the DTVMI exhibited a higher level of reliability than the FRTVMI. Both VMI tests appear to exhibit reasonable levels of reliability and are recommended for use with children and young people.

Associations between fruit and vegetable intake, leisure-time physical activity, sitting time and self-rated health among older adults : cross-sectional data from the WELL study

Background
Lifestyle behaviours, such as healthy diet, physical activity and sedentary behaviour, are key elements of healthy ageing and important modifiable risk factors in the prevention of chronic diseases. Little is known about the relationship between these behaviours in older adults. The purpose of this study was to explore the relationship between fruit and vegetable (F&V) intake, leisure-time physical activity (LTPA) and sitting time (ST), and their association with self-rated health in older adults.

Methods
This cross-sectional study comprised 3,644 older adults (48% men) aged 55-65 years, who participated in the Wellbeing, Eating and Exercise for a Long Life ("WELL") study. Respondents completed a postal survey about their health and their eating and physical activity behaviours in 2010 (38% response rate). Spearman's coefficient (rho) was used to evaluate the relationship between F&V intake, LTPA and ST. Their individual and shared associations with self-rated health were examined using ordinal logistic regression models, stratified by sex and adjusted for confounders (BMI, smoking, long-term illness and socio-demographic characteristics).

Results
The correlations between F&V intake, LTPA and ST were low. F&V intake and LTPA were positively associated with self-rated health. Each additional serving of F&V or MET-hour of LTPA were associated with approximately 10% higher likelihood of reporting health as good or better among women and men. The association between ST and self-rated health was not significant in the multivariate analysis. A significant interaction was found (ST*F&V intake). The effect of F&V intake on self-rated health increased with increasing ST in women, whereas the effect decreased with increasing ST in men.

Conclusion
This study contributes to the scarce literature related to lifestyle behaviours and their association with health indicators among older adults. The findings suggest that a modest increase in F&V intake, or LTPA could have a marked effect on the health of older adults. Further research is needed to fully understand the correlates and determinants of lifestyle behaviours, particularly sitting time, in this age group.

Procedural memory predicts social skills in persons with schizophrenia

Despite a growing number of studies that have investigated the relationship between neurocognition and psychosocial outcome in schizophrenia, no studies have looked at the relationship between procedural memory and social skills measures in schizophrenia. The goal of this study was to investigate whether procedural memory, often preserved in schizophrenia, could predict nonverbal social skills in chronic patients with schizophrenia. Fourteen outpatients with schizophrenia participated in our study. Procedural memory was evaluated using the Mirror Reading Test, and nonverbal and verbal social skills were evaluated using a structured role play test. As predicted, there was a significant positive correlation between the learning index of the Mirror Reading Test and nonverbal skills (Spearman &rho;=0.559, p = 0.038), but not for verbal communication skills or processing skills. Although preliminary, these results provide the first evidence of an association between procedural memory and nonverbal social skills in patients with schizophrenia.

The regulation and function of the striated muscle activator of rho signaling (STARS) protein

Healthy living throughout the lifespan requires continual growth and repair of cardiac, smooth, and skeletal muscle. To effectively maintain these processes muscle cells detect extracellular stress signals and efficiently transmit them to activate appropriate intracellular transcriptional programs. The striated muscle activator of Rho signaling (STARS) protein, also known as Myocyte Stress-1 (MS1) protein and Actin-binding Rho-activating protein (ABRA) is highly enriched in cardiac, skeletal, and smooth muscle. STARS binds actin, co-localizes to the sarcomere and is able to stabilize the actin cytoskeleton. By regulating actin polymerization, STARS also controls an intracellular signaling cascade that stimulates the serum response factor (SRF) transcriptional pathway; a pathway controlling genes involved in muscle cell proliferation, differentiation, and growth. Understanding the activation, transcriptional control and biological roles of STARS in cardiac, smooth, and skeletal muscle, will improve our understanding of physiological and pathophysiological muscle development and function.

Recruitment into diabetes prevention programs : what is the impact of errors in self-reported measures of obesity?

Background
Error in self-reported measures of obesity has been frequently described, but the effect of self-reported error on recruitment into diabetes prevention programs is not well established. The aim of this study was to examine the effect of using self-reported obesity data from the Finnish diabetes risk score (FINDRISC) on recruitment into the Greater Green Triangle Diabetes Prevention Project (GGT DPP).

Methods
The GGT DPP was a structured group-based lifestyle modification program delivered in primary health care settings in South-Eastern Australia. Between 2004–05, 850 FINDRISC forms were collected during recruitment for the GGT DPP. Eligible individuals, at moderate to high risk of developing diabetes, were invited to undertake baseline tests, including anthropometric measurements performed by specially trained nurses. In addition to errors in calculating total risk scores, accuracy of self-reported data (height, weight, waist circumference (WC) and Body Mass Index (BMI)) from FINDRISCs was compared with baseline data, with impact on participation eligibility presented.

Results
Overall, calculation errors impacted on eligibility in 18 cases (2.1%). Of n = 279 GGT DPP participants with measured data, errors (total score calculation, BMI or WC) in self-report were found in n = 90 (32.3%). These errors were equally likely to result in under- or over-reported risk. Under-reporting was more common in those reporting lower risk scores (Spearman-rho = −0.226, p-value < 0.001). However, underestimation resulted in only 6% of individuals at high risk of diabetes being incorrectly categorised as moderate or low risk of diabetes.

Conclusions
Overall FINDRISC was found to be an effective tool to screen and recruit participants at moderate to high risk of diabetes, accurately categorising levels of overweight and obesity using self-report data. The results could be generalisable to other diabetes prevention programs using screening tools which include self-reported levels of obesity.

Validating the multimedia activity recall for children and adolescents in a large New Zealand sample

The aim of the study was to validate the self-report Multimedia Activity Recall for Children and Adolescents (MARCA) against accelerometry for the assessment of physical activity in New Zealand children. Participants (n = 716, 10-18 years) recalled 3-4 days of activity using the MARCA and underwent a partially overlapping 7-day accelerometry protocol during a national survey. Spearman correlation coefficients (&rho;) assessed the association between accelerometer-derived counts per minute and MARCA-derived physical activity level and time in locomotion. Both data sources estimated time spent in light and moderate-vigorous physical activity. Association and agreement between methods for light physical activity and moderate-vigorous physical activity was assessed using correlations and Bland-Altman plots respectively, and paired t-tests conducted. Accelerometer-derived activity counts were moderately correlated with both MARCA-derived physical activity level and locomotion (&rho; = 0.38, P < 0.0001). The correlation between methods was -0.14 for light physical activity and 0.28 for moderate-vigorous physical activity (P < 0.0001). The MARCA overestimated moderate-vigorous physical activity compared with accelerometry (120 min, P < 0.0001), which increased as moderate-vigorous physical activity time increased. Some sex and ethnicity (Māori [indigenous] versus non-Māori) differences were observed. Overall, the MARCA indicated moderate validity for assessment of physical activity level, locomotion and moderate-vigorous physical activity and poor validity for assessment of light physical activity. This was comparable to other self-report tools. The MARCA has utility for future large-scale research.

Doubly labeled water validation of a computerized use-of-time recall in active young people

OBJECTIVE: Low levels of daily energy expenditure (insufficient physical activity and increased sedentary time) have been associated with adverse health outcomes in young people. The Multimedia Activity Recall for Children and Adolescents (MARCA) is a computerized, self-report, use-of-time tool that can assess daily energy expenditure. The study aim was to validate the MARCA for the estimation of energy expenditure in young people, using the criterion standard doubly labeled water. MATERIALS/METHODS: Over a 15 day assessment period, 32 participants (10-18 years) completed the MARCA and underwent a doubly labeled water protocol. Indirect calorimetry was used to assess resting metabolic rate. Total daily energy expenditure (TEE) and activity-related energy expenditure (AEE) were estimated from both the MARCA and doubly labeled water. Association and agreement between methods for TEE and AEE were assessed using Spearman correlations and Bland-Altman plots, respectively. RESULTS: Compared to doubly labeled water, the MARCA over-estimated TEE by an average of 50 kcal/day (limits of agreement -1 589 to 1 490 kcal/day) and under-estimated AEE 105 kcal/day (limits of agreement -1 404 to 1 614 kcal/day). The MARCA showed strong correlation with doubly labeled water for TEE (rho=0.70, p<0.0001) and moderate correlation for AEE (rho=0.56, p=0.0009). CONCLUSIONS: Overall, the MARCA indicated moderate validity for the assessment of daily TEE and AEE. The wide limits of agreement indicate the MARCA has greater utility for group-level rather than individual-level estimates.