"It Looks Good on Paper, But It Was Never Meant to Be Real": Mixed-Gender Events in the Paralympic Movement.

Although the Paralympic Games have been around for over 60 years, women remain underrepresented in almost all aspects of the Paralympic Movement. It has been suggested that a way to increase women's involvement is through the implementation of mixed-gender events. On paper, this approach makes sense. However, when it comes to the implementation of mixed-gender opportunities for women, it is less clear how effective these events are in increasing participation by women in Para sport. Through document analysis and interviews with athletes and organizers of mixed-gender Paralympic sport, we explore the various strategies that four mixed-gender sports have used to address the issue of gender parity. Using critical feminist theories, we illustrate how larger social, political, and cultural ideas about gender influence women's experiences within these events and discuss the potential of using mixed-gender initiatives to address gender parity within the Paralympic Movement.

Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Progressive microvascular dysfunction in type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to brain regions during local metabolic demand, thereby increasing risks of dementia. Having previously demonstrated that resveratrol can enhance vasodilator function in the systemic circulation, we hypothesised that resveratrol could similarly benefit the cerebral circulation. We aimed to determine the most efficacious dose of resveratrol to improve cerebral vasodilator responsiveness (CVR) in T2DM. METHODS AND RESULTS: In a double-blind, placebo-controlled, balanced crossover intervention, 36 dementia-free, non-insulin dependent T2DM older adults (49-78 years old) consumed single doses of synthetic trans-resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to assess CVR to a hypercapnic stimulus, both before and 45 min after treatment. CVR, measured bilaterally in the middle cerebral arteries (MCA) and posterior cerebral arteries (PCA), was expressed as the percentage change in mean blood flow velocity from baseline to the peak velocity attained during hypercapnia. Resveratrol consumption increased CVR in the MCA; mean within-individual changes for each dose from placebo were 13.8 ± 3.5% for 75 mg (P = 0.001), 8.9 ± 3.5% for 150 mg (P = 0.016), and 13.7 ± 3.3% for 300 mg (P < 0.001); only the 75 mg dose was efficacious in the PCA (13.2 ± 4.5%, P = 0.016). CONCLUSIONS: Our results provide the first clinical evidence of an acute enhancement of vasodilator responsiveness in cerebral vessels following consumption of resveratrol in this population who are known to have endothelial dysfunction and sub-clinical cognitive impairment. Importantly, maximum improvement was observed with the lowest dose used. CLINICAL TRIAL REGISTRATION: ACTRN12614000891628 (www.anzctr.org.au).

Combined use of filtered and edited 1 H NMR spectroscopy to detect 13 C-enriched compounds in complex mixtures.

In conventional metabolism and pharmacokinetic studies, radioactive isotopes are used to identify and quantify the breakdown products of xenobiotics. However, the stable isotope (13) C provides a cheaper and less hazardous alternative. Metabolites of (13) C-enriched xenobiotics can be detected, quantified and identified by (13) C-filtered NMR spectroscopy. However, one obstacle to using (13) C is its 1.1% natural abundance that produces a background signal in (13) C-filtered NMR spectra of crude biological extracts. The signal makes it difficult to distinguish between (13) C-enriched xenobiotics resonances from endogenous metabolites unrelated to the xenobiotic. This study proposes that the (13) C background signal can be distinguished from resonances of (13) C-enriched xenobiotics by the absence of a (12) C component in the xenobiotic. This is detected by combined analysis of (13) C-filtered and -edited NMR spectra. The theory underlying the approach is described and the method is demonstrated by the detection of sub-microgram amounts of (13) C-enriched phenacetin in crude extracts of hepatocyte microsomes.

Difference, adapted physical activity and human development: potential contribution of capabilities approach.

This paper is a call to Adapted Physical Activity (APA) professionals to increase the reflexive nature of their practice. Drawing upon Foucault's concept of governmentality (1977) APA action may work against its own publicized goals of empowerment and self-determination. To highlight these inconsistencies, we will draw upon historical and social factors that explain the implicit dangers of practice not following policy. We propose that APA practitioners work according to ethical guidelines, based upon a capabilities approach (Nussbaum, 2006, 2011; Sen, 2009) to counteract possible adverse effects of APA practitioner action. A capabilities approach is conducive to the development of each individual's human potential, by holistically considering the consequences of physical activity (i.e., biological, cultural, social, and psychological dimensions). To conclude, this paper will offer suggestions that may lead to an ethical reflection aligned with the best interest of APA's users.

Cultural influences on physical activity and exercise beliefs in patients with chronic kidney disease: 'The Culture-CKD Study'-a qualitative study.

OBJECTIVES: This study used a mixed-method approach to explore cultural and ethnic influences on the perception of, and decision to engage with or not to engage with, physical activity and exercise therapy in patients with chronic kidney disease (CKD). DESIGN: Qualitative research was conducted through the use of semistructured interviews and focus groups. Self-reported physical activity levels were measured using the General Practice Physical Activity Questionnaire (GPPAQ), and self-efficacy for exercise with Bandura's Self-Efficacy for Exercise Scale. SETTING: This study was conducted in a non-clinical setting of a single National Health Service Hospital Trust between April 2018 and July 2019. PARTICIPANTS: Participants >18 years of age with a diagnosis of CKD, from black African, black Caribbean, South Asian or white ethnicity were eligible for the study. 84 patients with a diagnosis of CKD (stages 2-5), aged 25-79 (mean age 57) were recruited. Semistructured interviews (n=20) and six single-sex, ethnic-specific focus group discussions were undertaken (n=36). OUTCOMES: Primary outcome was to explore the perceptions, attitudes and values about exercise and physical activity in different ethnic groups through qualitative interviews, analysed using an inductive thematic analysis approach. Questionnaires were analysed using Pearson correlation to determine if there was a significant relationship between the self-efficacy and GPPAQ levels. RESULTS: Qualitative analysis provided four primary themes: I am who I am, Change of identity, Influences to physical activity and exercise and Support and education. Quantitative analysis using Pearson correlation revealed a significant correlation between GPPAQ levels of activity and self-efficacy to regulate exercise behaviour (r=-0.40, p=0.001). CONCLUSION: Understanding the cultural, attitudes and beliefs of individuals with CKD from a variety of ethnic backgrounds is complex. Understanding of patients' experiences, thoughts and beliefs may be of relevance to clinicians when designing CKD exercise services. TRIAL REGISTRATION NUMBER: NCT03709212; Pre-results.

Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure.

BACKGROUND AND AIMS: Flow-mediated dilatation of the brachial artery (FMD) is a biomarker of endothelial function and cardiovascular health. Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity. Various food ingredients such as polyphenols have been shown to improve FMD. We investigated whether consuming resveratrol, a polyphenol found in red wine, can enhance FMD acutely and whether there is a dose-response relationship for this effect. METHODS AND RESULTS: 19 overweight/obese (BMI 25-35 kg m(-2)) men or post-menopausal women with untreated borderline hypertension (systolic BP: 130-160 mmHg or diastolic BP: 85-100 mmHg) consumed three doses of resveratrol (resVida™ 30, 90 and 270 mg) and a placebo at weekly intervals in a double-blind, randomized crossover comparison. One hour after consumption of the supplement, plasma resveratrol and FMD were measured. Data were analyzed by linear regression versus log(10) dose of resveratrol. 14 men and 5 women (age 55 ± 2 years, BMI 28.7 ± 0.5 kg m(-2), BP 141 ± 2/89 ± 1 mmHg) completed this study. There was a significant dose effect of resveratrol on plasma resveratrol concentration (P < 0.001) and on FMD (P < 0.01), which increased from 4.1 ± 0.8% (placebo) to 7.7 ± 1.5% after 270 mg resveratrol. FMD was also linearly related to log(10) plasma resveratrol concentration (P < 0.01). CONCLUSION: Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner. This effect may contribute to the purported cardiovascular health benefits of grapes and red wine.

A multi-criteria weight of evidence approach for deriving ecological benchmarks for radioactive substances.

Dose rate benchmarks are required in the tiered approaches used to screen out benign exposure scenarios in radiological ecological risk assessment. Such screening benchmarks, namely the predicted no-effect dose rates (PNEDR), have been derived by applying, as far as possible, the European guidance developed for chemicals. To derive the ecosystem level (or generic) PNEDR, radiotoxicity EDR(10) data (dose rates giving a 10% effect in comparison with the control) were used to fit a species sensitivity distribution (SSD) and estimate the HDR(5) (the hazardous dose rate affecting 5% of species with a 10% effect). Then, a multi-criteria approach was developed to justify using an assessment factor (AF) to apply to the HDR(5) for estimating a PNEDR value. Several different statistical data treatments were considered which all gave reasonably similar results. The suggested generic screening value of 10 microGy h(-1) (incremental dose rate) was derived using the lowest available EDR(10) value per species, an unweighted SSD, and an AF of 2 applied to the estimated HDR(5). Consideration was also given to deriving screening benchmark values for organism groups but this was not thought to be currently appropriate due to few relevant data being currently available.

Protection of the environment from ionising radiation in a regulatory context--an overview of the PROTECT coordinated action project.

The outcome of the PROTECT project (Protection of the Environment from Ionising Radiation in a Regulatory Context) is summarised, focusing on the protection goal and derivation of dose rates which may detrimentally affect wildlife populations. To carry out an impact assessment for radioactive substances, the estimated dose rates produced by assessment tools need to be compared with some form of criteria to judge the level of risk. To do this, appropriate protection goals need to be defined and associated predefined dose rate values, or benchmarks, derived and agreed upon. Previous approaches used to estimate dose rates at which there may be observable changes in populations or individuals are described and discussed, as are more recent derivations of screening benchmarks for use in regulatory frameworks. We have adopted guidance and procedures used for assessment and regulation of other chemical stressors to derive benchmarks. On the basis of consultation with many relevant experts, PROTECT has derived a benchmark screening dose rate, using data on largely reproductive effects to derive species sensitivity distributions, of 10 microGy h(-1) which can be used to identify situations which are below regulatory concern with a high degree of confidence.

Health-related quality of life in obese children and adolescents.

OBJECTIVE: This review addresses the effect of overweight and obese weight status on pediatric health-related quality of life (HRQOL). METHOD: Web of Science, Medline, CINAHL, Cochrane Library, EMBASE, AMED and PubMed were searched for peer-reviewed studies in English reporting HRQOL and weight status in youth (<21 years), published before March 2008. RESULTS: Twenty-eight articles were identified. Regression of HRQOL against body mass index (BMI) using pooled data from 13 studies utilizing the Pediatric Quality of Life Inventory identified an inverse relationship between BMI and pediatric HRQOL (r=-0.7, P=0.008), with impairments in physical and social functioning consistently reported. HRQOL seemed to improve with weight loss, but randomized controlled trials were few and lacked long-term follow-up. CONCLUSIONS: Little is known about the factors associated with reduced HRQOL among overweight or obese youth, although gender, age and obesity-related co-morbidities may play a role. Few studies have examined the differences in HRQOL between community and treatment-seeking samples. Pooled regressions suggest pediatric self-reported HRQOL can be predicted from parent proxy reports, although parents of obese youths tend to perceive worse HRQOL than children do about themselves. Thus, future research should include both pediatric and parent proxy perspectives.

Effect of dietary omega-3 polyunsaturated fatty acids on experimental periodontitis in the mouse.

BACKGROUND AND OBJECTIVE: Periodontitis is an infective disease caused predominantly by gram-negative anerobes. The host inflammatory response to these bacteria causes alveolar bone loss, which characterizes periodontitis. Omega-3 polyunsaturated fatty acids have recognized anti-inflammatory effects; their oxygenated derivatives are key mediators in reducing inflammation. In this study we tested the hypothesis that dietary supplementation with tuna fish oil rich in the n-3 polyunsaturated fatty acid, docosahexaenoic acid, would reduce alveolar bone loss in mice inoculated with periodontopathic bacteria. MATERIAL AND METHODS: Adult mice were fed experimental diets containing either 10% tuna oil or Sunola oil for 57 d. After 14 d, 35 mice on each diet were inoculated orally with Porphyromonas gingivalis, with a mixture of P. gingivalis and Fusobacterium nucleatum, with carboxymethylcellulose or remained untreated. The mice were killed, and soft tissue biopsies from the oral cavity of treated mice were used to determine the polyunsaturated fatty acid concentrations. The maxilla was removed, stained and digitally imaged to assess bone loss around the upper molars. RESULTS: n-3 polyunsaturated fatty acid levels were significantly higher in oral soft tissues of mice fed tuna oil compared with the control group. Mice fed tuna oil and inoculated with P. gingivalis or with the combination of F. nucleatum and P. gingivalis exhibited 72% and 54% less alveolar bone loss respectively, compared with the treatment control group. CONCLUSION: Alveolar bone loss was inversely related to n-3 polyunsaturated fatty acid tissue levels. In conclusion, fish oil dietary supplementation may have potential benefits as a host modulatory agent in the prevention and/or adjunctive management of periodontitis.

Do estuaries pose a toxic contamination risk for wading birds?

The impact of potentially toxic chemicals on wildlife is commonly assessed by comparing the intake of the contaminant with the "no observable effects level" (NOAEL) of intake. It is known, however, that there are considerable uncertainties inherent in this method. This study presents a Monte-Carlo based model to assess the degree of risk posed to birds (dunlin, Calidris alpina) from important estuarine habitats, and to show the limitations of such risk assessments, particularly with regard to data availability. The model was applied to predict the uptake of metals (Hg, Pb) in this shorebird species in Poole Harbour and the Severn Estuary/Bristol Channel, UK, two internationally important shorebird habitats. The results show that in both areas, Pb and Hg concentrations may pose an ecologically relevant toxic risk to wading birds. For Pb, uncertainty in NOAEL values dominates the overall uncertainty. Use of lethal toxicity data (LD50/100) was investigated as a method for assessing sub-lethal impacts from Hg. It was found that this method led to a significant under-estimate of the potential impact of Hg contamination, compared with direct estimation of NOAEL.

Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects.

OBJECTIVE: Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals. DESIGN: Overweight and obese adults were randomly assigned to high-flavanol cocoa (HF, 902 mg flavanols), HF and exercise, low-flavanol cocoa (LF, 36 mg flavanols), or LF and exercise for 12 weeks (exercise duration was 3 x 45 min per week at 75% of age-predicted maximum heart rate). Body composition was assessed by dual-energy X-ray absorptiometry at 0 and 12 weeks. Brachial artery flow-mediated dilatation (FMD), supine blood pressure (BP) and fasting plasma insulin, and glucose levels were assessed at 0, 6 and 12 weeks, respectively. Insulin sensitivity/resistance was determined using the modified homeostasis model assessment of insulin resistance (HOMA2). RESULTS: A total of 49 subjects (M=18; F=31) completed the intervention. Baseline averages were as follows: body mass index=33.5 kg/m(2); BP=123/76 mm Hg; HOMA2=2.4; FMD=4.3%; rate of fat oxidation during exercise=0.34 g min(-1); abdominal fat=45.7% of total abdominal mass. Compared to LF, HF increased FMD acutely (2 h post-dose) by 2.4% (P<0.01) and chronically (over 12 weeks; P<0.01) by 1.6% and reduced insulin resistance by 0.31% (P<0.05), diastolic BP by 1.6 mm Hg and mean arterial BP by 1.2 mm Hg (P<0.05), independent of exercise. Regular exercise increased fat oxidation during exercise by 0.10 g min(-1) (P<0.01) and reduced abdominal fat by 0.92% (P<0.05). CONCLUSION: Although HF consumption was shown to improve endothelial function, it did not enhance the effects of exercise on body fat and fat metabolism in obese subjects. However, it may be useful for reducing cardiometabolic risk factors in this population.

The Social Empowerment of Difference: The Potential Influence of Para sport.

This article explores the significance of parasport culture in highlighting an emancipatory understanding of difference and enhancing social empowerment. Disability studies are used to illuminate the influence of ableist ideology on people with impairments. Rather than being suppressed, difference should be recognized and valued in parasport practices and ideologies, leading to a pluralist culture, in which farther and wider social emancipation can be grounded. Acceptance of difference is an absolute and essential precondition for parasport cultures to promote positive social change for people with disabilities.

Effect of alpha-tocopherol on restenosis after angioplasty in a model of experimental atherosclerosis.

The ability of alpha-tocopherol to reduce restenosis after angioplasty was tested in a rabbit model in which angioplasty was performed on established atherosclerotic lesions. Lesions induced by 4 wk of cholesterol feeding after focal desiccation of femoral arteries were balloon dilated. 3 wk after angioplasty, angiographically determined minimum luminal diameters were less in the untreated group (0.80 +/- 0.51 mm) than in the group treated with oral alpha-tocopherol beginning 19 d before angioplasty (1.38 +/- 0.29 mm; P < 0.01). The cross-sectional area of the intima-media was greater in the untreated group (1.18 +/- 0.48 mm2) than in the alpha-tocopherol group (0.62 +/- 0.25 mm2, P < 0.0001). These differences were not due to vasoconstriction or altered plasma cholesterol. Alpha-tocopherol thus reduced restenosis after angioplasty in this model. In rabbit vascular smooth muscle cells, oxidized low density lipoprotein stimulated DNA synthesis. Alpha-tocopherol treatment inhibited DNA synthesis stimulated by oxidized low density lipoprotein, but not by serum. The findings are consistent with the hypothesis that oxidized lipids can stimulate hyperplasia and that antioxidants may limit hyperplasia by inhibiting either the oxidation or the proliferative effects of oxidants on cells.

Transforming growth factor beta 1 inhibition of p34cdc2 phosphorylation and histone H1 kinase activity is associated with G1/S-phase growth arrest.

Transforming growth factor beta 1 (TGF beta 1) is a potent inhibitor of epithelial cell proliferation. We present data which indicate that epithelial cell proliferation is inhibited when TGF beta 1 is added throughout the prereplicative G1 phase. Cultures become reversibly blocked in late G1 at the G1/S-phase boundary. The inhibitory effects of TGF beta 1 on cell growth occur in the presence of the RNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. Associated with this inhibitory effect is a decrease in the phosphorylation and histone H1 kinase activity of the p34cdc2 protein kinase. These data suggest that TGF beta 1 growth inhibition in epithelial cells involves the regulation of p34cdc2 activity at the G1/S transition.

Repression of caspase-3 and RNA-binding protein HuR cleavage by cyclooxygenase-2 promotes drug resistance in oral squamous cell carcinoma.

A well-studied RNA-binding protein Hu Antigen-R (HuR), controls post-transcriptional gene regulation and undergoes stress-activated caspase-3 dependent cleavage in cancer cells. The cleavage products of HuR are known to promote cell death; however, the underlying molecular mechanisms facilitating caspase-3 activation and HuR cleavage remains unknown. Here, we show that HuR cleavage associated with active caspase-3 in oral cancer cells treated with ionizing radiation and chemotherapeutic drug, paclitaxel. We determined that oral cancer cells overexpressing cyclooxygenase-2 (COX-2) limited the cleavage of caspase-3 and HuR, which reduced the rate of cell death in paclitaxel resistant oral cancer cells. Specific inhibition of COX-2 by celecoxib, promoted apoptosis through activation of caspase-3 and cleavage of HuR in paclitaxel-resistant oral cancer cells, both in vitro and in vivo. In addition, oral cancer cells overexpressing cellular HuR increased the half-life of COX-2 mRNA, promoted COX-2 protein expression and exhibited enhanced tumor growth in vivo in comparison with cells expressing a cleavable form of HuR. Finally, our ribonucleoprotein immunoprecipitation and sequencing (RIP-seq) analyses of HuR in oral cancer cells treated with ionizing radiation (IR), determined that HuR cleavage product-1 (HuR-CP1) bound and promoted the expression of mRNAs encoding proteins involved in apoptosis. Our results indicated that, cellular non-cleavable HuR controls COX-2 mRNA expression and enzymatic activity. In addition, overexpressed COX-2 protein repressed the cleavage of caspase-3 and HuR to promote drug resistance and tumor growth. Altogether, our observations support the use of the COX-2 inhibitor celecoxib, in combination with paclitaxel, for the management of paclitaxel resistant oral cancer cells.

Regulation of transforming growth factor beta 1 action by multiple transducing pathways: evidence for both G protein-dependent and -independent signaling.

The effects of cholera toxin (CT) on transforming growth factor beta 1-stimulated protooncogene expression, [gamma-35S]GTP binding, GTPase activity and growth under anchorage-independent and -dependent conditions were studied in AKR-2B fibroblast cells. CT was shown to inhibit TGF beta 1-stimulated c-sis and c-myc mRNA expression. Actinomycin D decay and nuclear runon experiments demonstrated that this inhibition was not due to an increased decay of protooncogene message, but to a decreased transcriptional activation. These inhibitory effects were not secondary to changes in the ability of TGF beta 1 to bind to its receptor(s) since radioreceptor assays and affinity labeling studies demonstrated that CT had no effect on TGF beta 1 binding. ADP ribosylation of AKR-2B plasma membranes with [alpha-32P]NAD+ revealed a Mr 45,000 protein as the major CT substrate. The labeling of this Mr 45,000 protein in membranes could be inhibited by prior pretreatment of the cells with increasing concentrations of CT. Treatment of membranes with nanogram concentrations of CT abolished the increase in [gamma-35S]GTP binding following addition of TGF beta 1 as well as decreased basal binding. Similarly, CT pretreatment of membranes inhibited TGF beta 1-stimulated GTPase activity. Unexpectedly however, the stimulatory effects of TGF beta 1 on anchorage-independent growth in soft agar were unaffected by CT. Only pertussis toxin was able to inhibit TGF beta 1-induced colony formation in soft agar in a dose-dependent manner. Furthermore, differential effects of both CT and pertussis toxin were observed on TGF beta 1-stimulated monolayer growth; CT was inhibitory, whereas pertussis toxin was without effect. These results suggest that the diverse biological effects of TGF beta 1 are mediated through multiple intracellular pathways distinguishable by their toxin sensitivities.

Translational regulation of inhibin ßA by TGFß via the RNA-binding protein hnRNP E1 enhances the invasiveness of epithelial-to-mesenchymal transitioned cells.

The epithelial-to-mesenchymal transition (EMT) is a cellular process that functions during embryonic development and tissue regeneration, thought to be aberrantly activated in epithelial-derived cancer and has an important role in the process of metastasis. The transforming growth factor (TGF)-ß signaling pathway is a key inducer of EMT and we have elucidated a posttranscriptional mechanism by which TGFß modulates expression of select transcripts via the RNA-binding protein hnRNP E1 during EMT. One such transcript inhibin ßA is a member of the TGFß superfamily. Here, we show by polysome profiling that inhibin ßA is translationally regulated by TGFß via hnRNP E1. TGFß treatment or knockdown of hnRNP E1 relieves silencing of the inhibin ßA transcript, resulting in increased protein expression and secreted levels of the inhibin ßA homodimer, activin A. Our data indicate that the translational upregulation of inhibin ßA enhances the migration and invasion of cells that have undergone an EMT and promotes cancer progression in vivo.

Adiposity is related to decrements in cardiorespiratory fitness in obese and normal-weight children.

BACKGROUND: Obese children are typically less physically active than their normal-weight peers and are often assumed to be 'unfit'. OBJECTIVE: Investigate the relationships between adiposity, physical activity levels and cardiorespiratory fitness (CRF) in obese and normal-weight children. A secondary aim was to examine obese/normal-weight differences in CRF. METHODS: Obese (N = 107) and normal-weight (N = 132) 10-13-year-olds participated. Fat-free mass (FFM), percent fat, physical activity and peak oxygen uptake (VO2peak ) were assessed. Analyses were adjusted for socioeconomic status (SES). RESULTS: Higher percent fat was inversely associated with VO2peak normalized for mass (r = -0.780, P < 0.001) even after controlling for physical activity (r = -0.673, P < 0.001). While higher percent fat was also inversely associated with VO2peak normalized for FFM, this was only significant in males (r = -0.247, P = 0.004) and did not persist after controlling for physical activity (r = -0.059 P = 0.526). Compared with normal-weight children, obese children had higher absolute VO2peak , lower VO2peak corrected for mass (P ≤ 0.009) and lower VO2peak corrected for FFM (P = 0.041) that did not persist after controlling for SES (P = 0.086). CONCLUSION: Obesity-related inefficiencies in CRF were evident. Higher adiposity was associated with poorer CRF relative to mass, irrespective of physical activity levels. However, low physical activity levels may be responsible for associations between adiposity and CRF relative to FFM seen in boys, indicating the importance of encouraging physical activity.

Loss of transforming growth factor beta 1 (TGF-beta 1)-induced growth arrest and p34cdc2 regulation in ras-transfected epithelial cells.

Transforming growth factor beta 1 (TGF-beta 1) is a potent inhibitor of mink lung epithelial (CCL64) cell growth in culture. The fact that many transformed epithelial cells have escaped from negative growth control by TGF-beta 1 suggests that transfected epithelial cells may be an appropriate model for investigating the growth-inhibitory mechanism of TGF-beta 1. We transfected CCL64 cells with a mouse c-myc oncogene (pSVc-myc1), a mutated Harvey-ras (Ha-ras) oncogene, or a combination of both. The results indicate that cells transfected with c-myc alone exhibit normal morphology and maintain sensitivity to TGF-beta 1 growth arrest, but are unable to form colonies in soft agar in the presence or absence of TGF-beta 1. Cells transfected with Ha-ras, or co-transfected with c-myc, display a transformed morphology, grow spontaneously under anchorage-independent conditions and acquire a complete resistance to growth inhibition by TGF-beta 1. Affinity cross-linking of [125I]TGF-beta 1 to cell-surface receptors from these transfectants revealed that all three TGF-beta receptor types were present and no significant differences in [125I]TGF-beta 1 labeling of these receptors was observed. Since we have previously demonstrated that modulation of p34cdc2 kinase is a marker for TGF-beta 1 growth inhibition, we investigated p34cdc2 activity in the CCL64 transfected clones. The results show that in the control CCL64 cells and in the myc-transfected clones TGF-beta 1 regulation of p34cdc2 activity is maintained. In the ras- and ras + myc-transfected cells p34cdc2 phosphorylation and histone H1 kinase activity is significantly increased and regulation by TGF-beta 1 is lost.