Under pressure to exercise: a cross-sectional study of characteristics and predictors of compulsive exercise in early adolescents.

BACKGROUND: To investigate the frequency of compulsive exercise among early adolescents, and determine the associated impact of sex, physical activity level, exercise habits, motivational regulation, dieting behaviour and health-related quality of life (HRQoL) on compulsive exercise. METHODS: Cross-sectional design with 8th grade adolescents (n = 572, mean ± SD age 13.9 ± 0.3 yrs). Outcome assessment was compulsive exercise (Compulsive Exercise Test, CET). Total CET score ≥ 15 was defined as clinical CET score. Further assessment included exercise motivation (Behavioural Regulation of Exercise Questionnaire-2), HRQoL (KIDSCREEN 27), accelerometer-assessed physical activity and Andersen test for cardiorespiratory fitness. Exercise obsession was defined as clinical CET score and < 60 min/day with moderate-to-vigorous objectively assessed physical activity. RESULTS: Small sex differences were found for CET total score. Seven percent of the adolescents were classified with clinical CET score, and four percent with exercise obsession. Adolescents with clinical CET score had higher body mass index, more weight loss attempts, and lower physical fitness compared to adolescents with non-clinical CET score. Being a boy, higher scores on introjected motivational regulation and HRQOL subscale parent relation and autonomy, use of exercise monitoring tool, and number of weight loss attempt the past 12 months explained 39% of the total CET score variance. Physical activity level did not predict compulsive exercise. CONCLUSIONS: Compulsive exercise in early adolescents was predicted by exercise motivation, exercise habit, and dieting, but not physical activity level. This implicates a distinction of obsessive cognitions about physical activity from performed physical activity in adolescents, and that such cognitions must be addressed in future initiatives that aim to improve adolescents' general physical activity level, health, and wellbeing. Trial registration ClinicalTrials.gov: NCT03906851. Although there is a huge concern about adolescents being insufficiently physically active, there are also adolescents who struggle with issues of compulsive exercise. The issues of compulsive exercise have been rarely studied in adolescents. We therefore aimed to describe compulsive exercise and factors that were associated with and could explain presence of compulsive exercise. A total of 572 8th graders (age 13.9 ± 0.3 yrs) responded to this study. We found that the score on compulsive exercise was higher in boys than in girls, and that adolescents with high score on compulsive exercise had higher body mass index, more weight loss attempts, and lower physical fitness compared to adolescents with low score on compulsive exercise. Also, we found that exercise obsessions, i.e., thinking of exercise without actually exercising, was present in four percent of the respondents. Being a boy, attempting weight loss, exercising to avoid shame/guilt, and exercising for the perceived value of exercise predicted compulsive exercise. Awareness of the compulsive exercise and exercise obsessions is important in public health initiatives that aim to increase adolescents' physical activity level.

Assessing physical activity in people with mental illness: 23-country reliability and validity of the simple physical activity questionnaire (SIMPAQ).

BACKGROUND: Physical inactivity is a key contributor to the global burden of disease and disproportionately impacts the wellbeing of people experiencing mental illness. Increases in physical activity are associated with improvements in symptoms of mental illness and reduction in cardiometabolic risk. Reliable and valid clinical tools that assess physical activity would improve evaluation of intervention studies that aim to increase physical activity and reduce sedentary behaviour in people living with mental illness. METHODS: The five-item Simple Physical Activity Questionnaire (SIMPAQ) was developed by a multidisciplinary, international working group as a clinical tool to assess physical activity and sedentary behaviour in people living with mental illness. Patients with a DSM or ICD mental illness diagnoses were recruited and completed the SIMPAQ on two occasions, one week apart. Participants wore an Actigraph accelerometer and completed brief cognitive and clinical assessments. RESULTS: Evidence of SIMPAQ validity was assessed against accelerometer-derived measures of physical activity. Data were obtained from 1010 participants. The SIMPAQ had good test-retest reliability. Correlations for moderate-vigorous physical activity was comparable to studies conducted in general population samples. Evidence of validity for the sedentary behaviour item was poor. An alternative method to calculate sedentary behaviour had stronger evidence of validity. This alternative method is recommended for use in future studies employing the SIMPAQ. CONCLUSIONS: The SIMPAQ is a brief measure of physical activity and sedentary behaviour that can be reliably and validly administered by health professionals.

An investigation of the process of change in psychopathology and exercise during inpatient treatment for adults with longstanding eating disorders.

BACKGROUND: Excessive exercise is recognized as a predictor of poor outcome in eating disorders. However, little is known about how excessive exercise might affect the treatment process. The aim of this study was to describe process of weekly changes in eating disorder psychopathology, general psychopathology and exercise, and the possible interactive effects of excessive exercise on these changes during inpatient treatment of longstanding eating disorders. METHODS: Eighty-four patients meeting the DSM-IV criteria for Anorexia Nervosa, Bulimia Nervosa, or Eating Disorders Not Otherwise Specified received inpatient cognitive-behavioural therapy including, physical activity and nutritional counselling treatment over 12 weeks. Excessive exercise was defined as having ≥6 episodes of driven exercise during week 1 of treatment. Excessive exercisers received one additional session of individual counseling with the clinical exercise physiologist. The study used repeated measurements during treatment and collected measures of eating disorders: psychopathology (EDE-Q), general psychopathology (SCL-5), and frequencies of exercise and body mass index (BMI). Statistical analysis was performed using repeated measures ANOVA. RESULTS: Both eating disorders and general psychopathology were reduced from admission to discharge in excessive exercisers and non-exercisers. There was an overall interaction effect between time (week) and excessive exercise for the process of exercise and eating disorders psychopathology reduction. This interaction effect was also found in week 10 vs 11 regarding general psychopathology. The excessive exercisers showed steep reduction at first, followed by a smaller increase towards the end of treatment in both eating disorder and general psychopathology; this pattern was not found among the non-exercisers. CONCLUSION: The process of change in exercise and psychopathology during inpatient treatment of longstanding eating disorders differs across excessive and non-excessive exercisers. Although excessive exercisers were given special attention for their exercise cognition and behavior during treatment, it is apparent that this part of treatment must be further developed.

Evaluation of in vivo T cell kinetics: use of heavy isotope labelling in type 1 diabetes.

CD4(+) memory cell development is dependent upon T cell receptor (TCR) signal strength, antigen dose and the cytokine milieu, all of which are altered in type 1 diabetes (T1D). We hypothesized that CD4(+) T cell turnover would be greater in type 1 diabetes subjects compared to controls. In vitro studies of T cell function are unable to evaluate dynamic aspects of immune cell homoeostasis. Therefore, we used deuterium oxide ((2) H(2)O) to assess in vivo turnover of CD4(+) T cell subsets in T1D (n = 10) and control subjects (n = 10). Serial samples of naive, memory and regulatory (T(reg)) CD4(+) T cell subsets were collected and enrichment of deoxyribose was determined by gas chromatography-mass spectrometry (GC-MS). Quantification of T cell turnover was performed using mathematical models to estimate fractional enrichment (f, n = 20), turnover rate (k, n = 20), proliferation (p, n = 10) and disappearance (d*, n = 10). Although turnover of T(regs) was greater than memory and naive cells in both controls and T1D subjects, no differences were seen between T1D and controls in T(reg) or naive kinetics. However, turnover of CD4(+) memory T cells was faster in those with T1D compared to control subjects. Measurement and modelling of incorporated deuterium is useful for evaluating the in vivo kinetics of immune cells in T1D and could be incorporated into studies of the natural history of disease or clinical trials designed to alter the disease course. The enhanced CD4(+) memory T cell turnover in T1D may be important in understanding the pathophysiology and potential treatments of autoimmune diabetes.

Physical fitness, bone mineral density and associations with physical activity in females with longstanding eating disorders and non-clinical controls.

AIM: To examine (i) aerobic fitness, muscular strength, and bone mineral density (BMD) in female inpatients with longstanding eating disorders and non-clinical controls, and (ii) associated and explanatory factors for BMD among the inpatients. METHODS: Adult females with DSM-IV anorexia nervosa (AN), bulimia nervosa (BN) or eating disorders not otherwise specified (EDNOS) (n=59, mean(SD) age 30.1(8.5) yrs and ED duration 14.3 yrs) and non-clinical age-matched controls (n=53, mean(SD) age 31.3(8.3) yrs) accepted participation in this cross-sectional study. Measurements included accelerometer assessed and self reported amount of different types of physical activities, VO2max on treadmill, 1RM in leg and chest press, and BMD in lumbar spine (L2-L4), femur neck and total body analyzed by DXA. RESULTS: Muscular strength and BMD were lower in patients with AN, not in patients with BN or EDNOS, compared to controls. Aerobic fitness did not differ between patients and controls. BMD in the patients was positively associated with body weight, muscular strength and self reported high impact PA (min.w-1), not self reported general weight-bearing PA (min.w-1) or accelerometer assessed PA (counts.min). History of AN (28%) and muscular strength (9%) contributed significantly to explain the variance in total body BMD. CONCLUSION: Muscular strength and only high impact PA are associated with BMD in patients with longstanding ED. An implication of this is the need for more specific guidelines regarding types of PA recommended for this patient population. Special considerations should be made for severely malnourished patients, and for patients with osteoporosis.

Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin.

Immune responses to autoantigens are in part controlled by deletion of autoreactive cells through genetically regulated selection mechanisms. We have directly analyzed peripheral CD4+ proinsulin (PI) 76-90 (SLQPLALEGSLQKRG)-specific T cells using soluble fluorescent major histocompatibility complex class II tetramers. Subjects with type I diabetes and healthy controls with high levels of peripheral proinsulin-specific T cells were characterized by the presence of a disease-susceptible polymorphism in the insulin variable number of tandem repeats (INS-VNTR) gene. Conversely, subjects with a 'protective' polymorphism in the INS-VNTR gene had nearly undetectable levels of proinsulin tetramer-positive T cells. These results strongly imply a direct relationship between genetic control of autoantigen expression and peripheral autoreactivity, in which proinsulin genotype restricts the quantity and quality of the potential T-cell response. Using a modified tetramer to isolate low-avidity proinsulin-specific T cells from subjects with the susceptible genotype, transcript arrays identified several induced pro-apoptotic genes in the control, but not diabetic subjects, likely representing a second peripheral mechanism for maintenance of tolerance to self antigens.

Dieting to win or to be thin? A study of dieting and disordered eating among adolescent elite athletes and non-athlete controls.

OBJECTIVE: To examine the prevalence of dieting, reasons for dieting and prevalence of disordered eating among adolescent elite athletes and age-matched controls, and to examine the differences between athletes competing in leanness and non-leanness sports. METHODS: First-year students of 16 different Norwegian Elite Sport High Schools (athlete group, n = 682) and two randomly selected ordinary high schools from a county representative of the general Norwegian population (control group, n = 423) were invited to participate in this cross-sectional study. A total of 606 athletes and 355 controls completed the questionnaire, giving a response rate of 89% and 84%, respectively. The questionnaire contained questions regarding training patterns, menstrual status and history, dieting, use of pathogenic weight control methods and the drive for thinness (DT) and body dissatisfaction (BD) subscales from the Eating Disorders Inventory. MAIN OUTCOME MEASURE: Disordered eating, defined as meeting one or more of the following criteria: DT score > or =15 (girls) and > or =10 (boys), BD score > or =14 (girls) and > or =10 (boys), body mass index <17.9 kg/m(2) (girls) and <17.5 kg/m(2) (boys), current and/or > or =3 previous efforts to lose weight, use of pathogenic weight control methods and self-reported menstrual dysfunction. RESULTS: A higher prevalence of control subjects were dieting and classified with disordered eating compared with the athletes. An improvement of appearance was a more common reason for dieting among controls compared with athletes. No differences in dieting or disordered eating were found between leanness and non-leanness sports athletes. CONCLUSIONS: Self-reported disordered eating is more prevalent among controls than adolescent elite athletes, and losing weight to enhance performance is an important reason for dieting among adolescent elite athletes.

Physical activity in treatment units for eating disorders: clinical practice and attitudes.

OBJECTIVE: Physical activity (PA) in eating disorders (ED) may be harmful, but in a therapeutic setting also beneficial. The purpose of this survey was to examine these contradictory aspects of PA in ED specialist treatment settings. We examined whether 1) PA is assessed by the unit, 2) the units have guidelines for managing excessive PA, 3) the units have staff with higher education and special competence in PA and exercise science, 4) how units regard PA in ED, 5) whether regular PA is integrated in the treatment programs, and 6) how the units rate the role of PA in the treatment of ED compared with other mental disorders. METHODS: Of the 49 units located in Scandinavia and the United Kingdom, 41 (84%) responded to a questionnaire. RESULTS: In 28 units (68%) PA was assessed regularly. Excessive PA was considered a harmful symptom in ED, and most units reported guidelines to manage excessive PA. Thirty-two units included PA in their treatment programmes. Clinicians found PA most relevant in the treatment of obesity and, except for binge eating, less for ED. CONCLUSION: PA was more commonly integrated in treatment compared to previous studies. Future research should address how to manage excessive PA, and the potential beneficial role of PA in the treatment of ED.

Characterization of cytochrome P450-mediated drug metabolism in cats.

In this study we examined activities of cytochrome P450 (CYP)1A, 2C, 2D and 3A using hepatic microsomes from five male and five female cats. CYP1A, 2C, 2D and 3A activities were referred by ethoxyresorufin O-deethylation (EROD), tolbutamide hydroxylation (TBH), bufuralol 1'-hydroxylation (BLH) and midazolam 1'- and 4-hydroxylation respectively. The anti-rat CYP1A2 and CYP3A2 serum significantly inhibited EROD and midazolam 1'- and 4-hydroxylation, suggesting that EROD and midazolam 1'- and 4-hydroxylation were catalysed by CYP1A and 3A in cats respectively. Quinidine inhibited BLH in cats microsomes at quite low concentrations, suggesting that BLH was catalysed by CYP2D in cats. Tolbutamide hydroxylation activities were negligible in hepatic microsomes from both male and female cats, suggesting CYP2C activities of cats are extremely low. This suggests that CYP2C substrates should be carefully administered to cats. Although there is no sexual difference in CYP1A activities, there are differences in CYP2D and 3A activities of cats. CYP2D activities were higher (3-fold), but CYP3A activities were lower (one-fifth) in female cats. These results might suggest that CYP2D and 3A substrates should be prescribed for male and female cats using different dosage regimen.

The heart failure revascularisation trial (HEART): rationale, design and methodology.

BACKGROUND: Most patients with heart failure due to left ventricular systolic dysfunction (LVSD) secondary to coronary artery disease (CAD) have evidence of myocardium in jeopardy (reversible ischaemia and/or stunning hibernation). It is not known whether revascularisation in such cases is safe or beneficial. AIMS: To determine whether revascularisation will improve the survival of patients with LVSD and heart failure secondary to CAD and myocardium in jeopardy. METHODS: This is a randomised controlled trial comparing revascularisation or not, in addition to optimal medical therapy with ACE inhibitors, beta-blockers, aldosterone antagonists and an anti-thrombotic agent. Patients must have heart failure requiring treatment with diuretics, a left ventricular ejection fraction <35% and evidence of coronary disease. Myocardial viability and ischaemia are assessed by a broad range of techniques including stress echocardiography and nuclear imaging. All imaging tests are reviewed in core laboratories to ensure uniform reporting. Any conventional revascularisation technique is permitted. The primary outcome measure is all cause mortality. Symptoms, quality of life and health economic issues will also be explored. Assuming an annual mortality of 10% in the control group and allowing for substantial cross-over rates, a study of 800 patients followed for 5 years has 80% power with an alpha of 0.05 (two-sided) to show a 25% reduction in mortality with revascularisation. RESULTS: At the time of writing 180 patients have been screened for inclusion, 111 have consented to participate and 70 have been randomised. The results of viability testing are awaited in 22 patients. Twenty-six patients had been investigated for myocardial viability and/or by angiography prior to consent, as part of the routine practice in that cardiology department. Of 68 patients who have completed assessment only after consent, 47 (69%) were included. The principal reason for drop-out between consent and randomisation was lack of evidence of myocardial ischaemia or hibernation. CONCLUSION: The HEART trial will help to determine whether investigation of myocardial ischaemia and/or viability with a view to revascularisation should become part of the routine care of patients with heart failure due to LVSD and CAD.

Recombinant Arabidopsis SQD1 converts udp-glucose and sulfite to the sulfolipid head group precursor UDP-sulfoquinovose in vitro.

The sulfolipid sulfoquinovosyldiacylglycerol is a component of plant photosynthetic membranes and represents one of the few naturally occurring sulfonic acids with detergent properties. Sulfolipid biosynthesis involves the transfer of sulfoquinovose, a 6-deoxy-6-sulfoglucose, from UDP-sulfoquinovose to diacylglycerol. The formation of the sulfonic acid precursor, UDP-sulfoquinovose, from UDP-glucose and a sulfur donor is proposed to be catalyzed by the bacterial SQDB proteins or the orthologous plant SQD1 proteins. To investigate the underlying enzymatic mechanism and to elucidate the de novo synthesis of sulfonic acids in biological systems, we developed an in vitro assay for the recombinant SQD1 protein from Arabidopsis thaliana. Among different possible sulfur donors tested, sulfite led to the formation of UDP-sulfoquinovose in the presence of UDP-glucose and SQD1. An SQD1 T145A mutant showed greatly reduced activity. The UDP-sulfoquinovose formed in this assay was identified by co-chromatography with standards and served as substrate for the sulfolipid synthase associated with spinach chloroplast membranes. Approximate K(m) values of 150 microm for UDP-glucose and 10 microm for sulfite were established for SQD1. Based on our results, we propose that SQD1 catalyzes the formation of UDP-sulfoquinovose from UDP-glucose and sulfite, derived from the sulfate reduction pathway in the chloroplast.

Analysis of flowering time in ecotypes of Arabidopsis thaliana.

There exists variation in the timing of the initiation of flowering among different ecotypes of Arabidopsis thaliana. We have examined the basis of this variation between the early flowering Columbia (Col) ecotype and the late flowering ecotypes. Coimbra (Co-4), Geneva (Ge-2), and Zu-rich (Zu-0). In crosses of Col to Co-4, Ge-2, and Zu-0, the late flowering trait behaved as a single dominant gene the F1 plants were late flowering and in segregating F, populations a 3:1 ratio of late to early flowering plants was observed. This dominant gene resides in a region of chromosome 4 that contains a gene (FRIGIDA) conferring late flowering in certain other Arabidopsis ecotypes. Allelism tests indicate that the same genesis responsible for late flowering in Co-4, Ge-2. Zu-0, and the San Feliu (Sf-2) ecotype. These and previous results indicate that FRIGIDA accounts for much of the later flowering observed in various ecotypes of Arabidopsis.

Ecotype-Specific Expression of a Flowering Mutant Phenotype in Arabidopsis thaliana.

The majority of mutations that delay flowering in Arabidopsis thaliana have been identified in studies of the Landsberg erecta (Ler) ecotype. In this report we describe a gene (referred to as FLD) that, when mutated, delays flowering in the Columbia ecotype but has a minimal phenotype in the Ler genetic background. The late-flowering phenotype of fld mutants requires a non-Ler allele of another gene involved in the control of flowering time, Flowering Locus C. fld mutants retain a photoperiod response, and the flowering time of fld mutants can be reduced by cold treatment and low red/far-red light ratios.

Interaction of FLC and late-flowering mutations in Arabidopsis thaliana.

The phenotype caused by mutations that affect the timing of flowering in Arabidopsis thaliana has been most extensively analyzed in the Landsberg erecta (Ler) genetic background. In Ler, the late-flowering phenotype of FRIGIDA and mutations in LUMINIDEPENDENS is suppressed by the Ler allele of FLC. In this study, the interactions of nine mutations conferring late flowering with the FLC allele of the Columbia ecotype (FLC-Col), which does not suppress late flowering, were examined. The effect on flowering time of combining six of the mutations with FLC-Col was additive; plants containing FLC-Col with fd, gi, fwa, fha, ft, and fe flowered slightly later than plants containing these mutations with the Ler allele of FLC. In contrast, a synergistic effect was observed between FLC-Col and three mutations; fca, fpa, and fve plants became extremely late flowering when combined with FLC-Col. Maximum delay in flowering for the majority of the mutant strains required FLC-Col in a homozygous state, although for fpa and fe a single copy of FLC-Col allowed maximum lateness. In addition, the fd and fe mutations became more dominant in the presence of FLC-Col.