Assessment of biochemical liver markers, physical activity, fitness and body mass index for a cardiometabolic risk model in childhood.

AIM: The aim of this study was to investigate clustered cardiometabolic risk scores in healthy 10- to 12-year-olds using anthropometric characteristics, measurements of cardiorespiratory fitness (CRF) and physical activity and blood markers of metabolic disease. We also evaluated how including markers of liver cell injury would affect the clustered cardiometabolic risk assessment model. METHODS: This cross-sectional study focused on 99 children aged 10-12 years. The main outcome included assessing participants with increased and low cardiometabolic risk factors using a clustered risk score model that incorporated markers implicated in metabolic syndrome pathogenesis. Two clustered risk scores were calculated, one incorporating markers of liver cell injury. RESULTS: Children classified as 'increased risk' exhibited significantly lower CRF and higher body mass index Z-scores than their 'low-risk' peers. No significant differences in physical activity were observed. This trend remained unchanged when markers of liver injury were included in the clustered risk assessment model. CONCLUSION: The clustered risk score model is a scientifically robust method of cardiometabolic risk assessment, which reiterates the importance of weight reduction and CRF promotion in childhood. Our study did not show a significant contribution of liver injury markers, and further research is needed to evaluate their effect on cardiometabolic risk stratification in childhood.

The biochemical, physiological and psychological consequences of a "1,000 miles in 1,000 hours" walking challenge.

The combined effects of 42 days of chronic sleep disruption and repeated hourly bouts of physical exertion have not been described. This case study reports the physiological and psychological demands placed on one individual who walked 1 mile in each consecutive hour for a period of 1,000 h (42 days), covering a total distance of 1,000 miles. The participant walked at a mean speed of 1.75 m/s completing each mile in approximately 15 min. Over the course of the challenge, the individual lost 1.6 kg in body weight. Markers of skeletal muscle damage, increased gradually whilst free testosterone levels decreased over the course of the challenge. Stress hormones increased whilst inflammatory markers (CRP) initially rose but then returned towards baseline over the course of the study. Cognitive motor performance measured via reaction time was maintained throughout the 42 days. The participant also displayed mood states typical of an elite athlete at baseline and throughout the challenge. Participation in this novel '1,000 mile 1,000 h' walking challenge evoked considerable physiological stress in a fit, healthy middle-aged participant but did not markedly alter cognitive performance or mood over the 42-day period.

Physical activity, walking and leanness: an analysis of the Northern Ireland Sport and Physical Activity Survey (SAPAS).

OBJECTIVE: To report on the contribution walking makes to total weekly physical activity and the relationship between the volume and intensity of walking and leanness in a representative sample of the Northern Ireland population. METHOD: 4563 adults participated in this cross-sectional survey of physical activity behaviour. Self-reported height and weight was used to determine inverse body mass index (iBMI) as a measure of leanness. Data across all domains of physical activity including self-reported volume and intensity of walking (in bouts of 10 min or more) were analysed to determine their contribution to leanness using ANCOVA, having controlled for age, gender, socio-economic and smoking status. RESULTS: Over 68% of the participants reported walking >10 minutes during the previous week but only 24% report walking at a brisk or fast pace. Time walking at a brisk or fast pace for personal transport was identified as having the strongest positive association with being lean (F(1,4256)=10.45, ß=0.051 cm(2) kg(-1) min(-1) (SE=0.016),P=0.001). CONCLUSIONS: In addition to increasing the amount of walking and the percentage of people walking regularly, public health messages encouraging an increase in walking pace may be valuable to increase the proportion of the population meeting physical activity guidelines and gaining associated health benefits.

Training effects of short bouts of stair climbing on cardiorespiratory fitness, blood lipids, and homocysteine in sedentary young women.

OBJECTIVES: To study the training effects of eight weeks of stair climbing on Vo2max, blood lipids, and homocysteine in sedentary, but otherwise healthy young women. METHODS: Fifteen women (mean (SD) age 18.8 (0.7) years) were randomly assigned to control (n = 7) or stair climbing (n = 8) groups. Stair climbing was progressively increased from one ascent a day in week 1 to five ascents a day in weeks 7 and 8. Training took place five days a week on a public access staircase (199 steps), at a stepping rate of 90 steps a minute. Each ascent took about two minutes to complete. Subjects agreed not to change their diet or lifestyle over the experimental period. RESULTS: Relative to controls, the stair climbing group displayed a 17.1% increase in Vo2max and a 7.7% reduction in low density lipoprotein cholesterol (p < 0.05) over the training period. No change occurred in total cholesterol, high density lipoprotein cholesterol, triglycerides, or homocysteine. CONCLUSIONS: The study confirms that accumulating short bouts of stair climbing activity throughout the day can favourably alter important cardiovascular risk factors in previously sedentary young women. Such exercise may be easily incorporated into the working day and therefore should be promoted by public health guidelines.

Different patterns of brisk walking are equally effective in decreasing postprandial lipaemia.

OBJECTIVE: To compare the effects of different patterns of brisk walking on day-long plasma triacylglycerol concentrations in sedentary adults. DESIGN: A three-trial, repeated measures design in which subjects were studied in the fasted state and throughout a day during which they consumed three standardized, mixed meals. On different occasions, subjects undertook no exercise (control), walked briskly for 10 min before each meal (short walks) or walked briskly for 30min before breakfast (long walk). SUBJECTS: Seven postmenopausal sedentary women and three sedentary men aged between 34 and 66y, with body mass index between 24 and 35 kg/m2. MEASUREMENTS: Plasma concentrations of triacylglycerol, non-esterified fatty acids, glucose and insulin, metabolic rate and whole-body substrate oxidation in the fasted state and at hourly intervals for 3 h after each meal. RESULTS: Postprandial plasma triacylglycerol concentrations were lower (P= 0.009) during the walking trials than during the control trial (average values: control 2.08 +/- 0.28 mmol/l; short walks 1.83 +/- 0.22mmol/l; long walk 1.84 +/- 0.22mmol/l (mean+/-s.e.) but did not differ between the two patterns of walking. The difference between control and walking trials increased as successive meals were consumed (interaction of trial x meal P= 0.03). Plasma triacylglycerol concentration increased during the 3 h after breakfast, changed little after lunch and decreased after the evening meal (interaction of meal x time P=0.001). When both walking trials were treated as one condition, walking increased postprandial fat oxidation (average values: control, 0.066 +/- 0.009 g/min;walking 0.074 +/- 0.008 g/min; P < 0.01). CONCLUSIONS: Thirty minutes of brisk walking, undertaken in one session or accumulated throughout a day, reduces postprandial plasma triacylglycerol concentrations and increases fat oxidation.

Postprandial lipemia in young men and women of contrasting training status.

This study compared the postprandial triacylglycerol (TAG) response to a high-fat meal in trained and untrained normolipidemic young adults after 2 days' abstinence from exercise. Fifty-three subjects (11 endurance-trained men, 9 endurance-trained women, 10 sprint/strength-trained men, 11 untrained men, 11 untrained women) consumed a meal (1.2 g fat, 1.1 g carbohydrate, 66 kJ per kg body mass) after a 12-h fast. Venous blood samples were obtained in the fasted state and at intervals until 6 h. Postprandial responses were the areas under the plasma or serum concentration-vs.-time curves. Neither fasting TAG concentrations nor the postprandial TAG response differed between trained and untrained subjects. The insulinemic response was 29% lower in endurance-trained men than in untrained men [mean difference -37.4 (95% confidence interval -62.9 to -22.9) microIU/ml x h, P = 0.01]. Responses of plasma glucose, serum insulin, and plasma nonesterified fatty acids were all lower for endurance-trained men than for untrained men. These findings suggest that, in young adults, no effect of training on postprandial lipemia can be detected after 60 h without exercise. The effect on postprandial insulinemia may persist for longer.

Postprandial lipemia: effects of intermittent versus continuous exercise.

PURPOSE: The purpose of this study was to assess whether exercise performed in continuous and discontinuous formats reduced postprandial lipemia to a similar degree. METHODS: Fifteen normolipidemic and three borderline hyperlipidemic healthy males (ages 30.6 +/- 9.0 (mean +/- SD) yr, BMI 23.1 +/- 1.4 kg.m-2) participated in three trials, each conducted over 2 d. Subjects refrained from exercise for the 2 d preceding each trial. On day one, subjects rested (control trial), or ran at 60% of maximal oxygen uptake in either one 90-min session (continuous exercise trial), or three 30-min sessions (intermittent exercise trial). On day two, subjects ingested a high-fat test breakfast (1.2 g fat, 1.2 g carbohydrate, 70 kJ energy per kilogram body mass). Blood samples were obtained in the fasted state and at intervals for 6 h postprandially. RESULTS: Fasting plasma triacylglycerol (TAG) concentrations did not differ between trials. Areas under the TAG versus time curves were 18.1 +/- 6.7% (mean +/- SEM) and 17.7 +/- 7.6% (both P < 0.05) lower than control in the continuous exercise and intermittent exercise trials, respectively. Plasma glucose responses to the test meal did not differ between trials, but the serum insulin response was lower in the intermittent exercise trial compared with that in the control. CONCLUSION: The results suggest that both intermittent and continuous exercise can reduce postprandial lipemia.

Training effects of short and long bouts of brisk walking in sedentary women.

This study compared the effects of short and long bouts of brisk walking in sedentary women. Forty seven women aged 44.4 +/- 6.2 yr (mean +/- SD) were randomly assigned to either three 10-min walks per day (short bouts), one 30-min walk per day (long bouts) or no training (control). Brisk walking was done on 5 d x wk(-1), at 70 to 80% of maximal heart rate, typically at speeds between 1.6 and 1.8 m x s(-1) (3.5 and 4.0 mph), for 10 wk. Subjects agreed not to make changes to their diet. Twelve short-bout walkers, 12 long-bout walkers, and 10 controls completed the study. Relative to controls, VO2max (short-bout, +2.3 +/- 0.1 mL x kg(-1) x min(-1); long-bout, +2.4 +/- 0.1 mL x kg(-1) x min(-1); controls, -0.5 +/- 0.1 mL x kg(-1) x min[-1]) and the VO2 at a blood lactate concentration of 2 mmol x L(-1) increased in walkers (both P < 0.05), with no difference in response between walking groups. Neither heart rate during standard, submaximal exercise nor resting systolic blood pressure changed in a different way in walkers and controls. The sum of four skinfold thicknesses decreased in both walking groups (P < 0.05) but body mass (short-bout, -1.7 +/- 1.7 kg; long-bout, -0.9 +/- 2.0 kg; controls, +0.6 +/- 0.7 kg) and waist circumference decreased significantly only in short-bout walkers. Changes in anthropometric variables did not differ between short- and long-bout walkers. Thus short bouts of brisk walking resulted in similar improvements in fitness and were at least as effective in decreasing body fatness as long bouts of the same total duration.

Impact of the nutritional regimen on protein catabolism and nitrogen balance in patients with acute renal failure.

BACKGROUND: Patients with acute renal failure are in substantial negative nitrogen balance as a result of their extremely high protein catabolic rates. We prospectively evaluated a series of patients with acute renal failure managed with continuous venovenous hemofiltration to determine which nutritional and nonnutritional variables might influence protein catabolism and nitrogen balance. METHODS: Forty consecutive patients (aged 52 +/- 20 years; mean +/- SD) were monitored for 357 treatment days (average treatment duration 8.9 +/- 8.6 days). All data (including nutritional regimen, laboratory values, APACHE II score, administered blood products, hemofiltration parameters, and medications) were collected daily. RESULTS: For all patients, the mean normalized protein catabolic rate was 1.4 +/- 0.5 g/kg per day. The rate did not differ between those who received nutrition support and those who did not. The net nitrogen deficit was less in those patients receiving nutrition support (-6.0 +/- 5.2 vs -14.0 +/- 5.6 g N/d; p = .02). Using regression techniques (adjusted for the within-person correlation and the previous day's normalized protein catabolic rate), the level of protein and energy provision and the interaction between protein and energy provision were predictive of the normalized protein catabolic rate. Predicted values, using this equation, suggest that at low protein administration rates (< 1 g/kg per day), increasing energy provision may reduce the protein catabolism. However, at this level of protein provision, patients remain in negative nitrogen balance. At protein administration rates necessary to achieve nitrogen balance (approximately 1.5 to 1.8 g/kg per day), protein catabolism may increase. Providing relatively low levels of energy may diminish the magnitude of this increase. CONCLUSION: These results suggest that the optimal nutritional regimen for patients with acute renal failure may require a high-protein (approximately 1.5 to 1.8 g/kg per day) and a relatively low-energy (approximately 25 to 35 kcal/kg per day) content.

Urea kinetics during continuous hemofiltration.

Urea kinetic analysis allows for the calculation of the urea distribution volume and urea generation rate. This method was employed in patients with acute renal failure managed by continuous venovenous hemofiltration (CVVH). Based on serial serum urea nitrogen concentration measurements, each patient's treatment course consisted of both steady state and non-steady state periods. Thirteen data sets were obtained from 11 critically ill patients treated with CVVH. The duration of therapy was 9.5 +/- 7.5 days (mean +/- SD). Serum urea nitrogen concentration fell from 114 +/- 32 mg/dl to a steady state value of 79 +/- 17 mg/dl (p < 0.0005). The urea distribution volume was 0.55 +/- 0.11 L/kg (range 0.29-0.73), and the urea generation rate 11.7 +/- 3.1 mg urea N/min (range 7.1-17.3). The steady state serum urea nitrogen concentration had a linear relationship to the rate of urea generation (r = 0.92). Urea kinetic analysis permitted the simultaneous determination of the urea generation rate and distribution volume, on an individualized basis, in patients with acute renal failure treated with CVVH.

Revlens: a new, soft acrylic rubber extended-wear contact lens.

Revlens is a new, soft acrylic rubber extended-wear contact lens. We fitted 21 eyes in 15 patients. The indications included 15 eyes in 10 patients with aphakia due to congenital cataracts. The developmental cataracts were associated with persistent hyperplastic primary vitreous, Down's syndrome, microphthalmos and Peter's anomaly. The remaining five patients included one Tyrosinase negative oculocutaneous albino and four anisometropic amblyopes. Three of the aphakic patients were unable to wear this lens. One preferred her previous rigid lens, another refused any contact lens and went back to glasses, and a third did not adapt to the lens because of social circumstances. Thus 12 of the 15 patients (80%) who were monitored for at least 6 months (average: 9 months) readily accepted this new lens.

Construction and functional analysis of a series of synthetic RNA polymerase III promoters.

RNA polymerase III promoters were constructed by cloning chemically synthesized double stranded analogues of the box A and box B consensus sequences into suitable vectors. In contrast to approaches adopted previously for the analysis of RNA polymerase III promoters, this method has no limitation on the structure and number of variants generated, and allows critical sequences in various permutations to be studied. Furthermore, the series of synthetic polymerase III promoters created constitute a collection of point mutation variants and hence provide a powerful tool for the analysis of nucleotides essential for promoter function. The results demonstrate that these two boxes, when separated by approximately 50 base pairs, are sufficient to direct efficient transcription, and that substitution of certain nucleotides causes reduced template activity.

Construction and functional analysis of a series of synthetic RNA polymerase III promoters.

RNA polymerase III promoters were constructed by cloning chemically synthesized double-stranded analogues of the box A and box B consensus sequences into suitable vectors. In contrast to approaches adopted previously for the analysis of RNA polymerase III promoters, this method has no limitation on the structure and number of variants generated and allows critical sequences in various permutations to be studied. Furthermore, the series of synthetic polymerase III promoters created constitute a collection of point mutation variants and hence provide a powerful tool for the analysis of nucleotides essential for promoter function. The results demonstrate that these two boxes, when separated by 51 base pairs, are sufficient to direct efficient transcription and that substitution of certain nucleotides causes reduced template activity.

Directed semisynthetic point mutational analysis of an RNA polymerase III promoter.

The transcription of tRNA and Alu repeat genes in vitro by RNA polymerase III has been shown to be dependent on the presence of two intragenic regions, which contain the consensus sequences RGYNNRRYGG (box A) and GA/TTCRANNC (box B), located 30-60 nucleotides apart. The role of box B and some of its variants was analyzed by a novel method involving the chemical synthesis of double stranded analogues of box B which were subsequently cloned into recombinant vectors carrying box A alone. This method creates a series of semi-synthetic RNA polymerase III promoters and has no limitation on the structure and number of variants which can be generated. The results showed the "wild type" sequence GTTCGAGAC and the sequence GTTCGTGAC (an A to T transversion of the 6th position) were active in promoting RNA polIII transcription. However, the box B sequences CTTCGAGAC and GTACGAGA, where the only departures from the consensus are a G to C and an A to T transversion in the 1st and 3rd positions respectively, were unable to restore promoter function.

The Alu family repeat promoter has a tRNA-like bipartite structure.

The essential sequences needed for Alu repeat transcription by RNA polymerase III were mapped. Experimental evidence is presented showing that the Alu repeat promoters are organised in a bipartite structure similar to the split tRNA promoters as suggested by DNA sequence homology. Furthermore, by combining fragments from efficiently and inefficiently transcribed natural Alu repeats in several recombinant clones, it was possible to investigate the regions responsible for their differences. It is clear that, apart from the short stretches of homology with the tRNA consensus sequence, there is very little constraint in the promoter sequences. However, our studies indicate that some influence on the efficiency of transcription may be exerted by regions outside the accepted promoter components.