• Associations between breakfast frequency and adiposity indicators in children from 12 countries

      Zakrzewski-Fruer, Julia K.; Gillison, F.B.; Cumming, S.; Church, T.S.; Katzmarzyk, P.T.; Broyles, Stephanie T.; Champagne, C.M.; Chaput, J-P.; Denstel, K.D.; Fogelholm, M.; et al. (Nature Publishing Group, 2015-12-08)
      OBJECTIVES: Reports of inverse associations between breakfast frequency and indices of obesity are predominantly based on samples of children from high-income countries with limited socioeconomic diversity. Using data from the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE), the present study examined associations between breakfast frequency and adiposity in a sample of 9–11-year-old children from 12 countries representing a wide range of geographic and socio-cultural variability. METHODS: Multilevel statistical models were used to examine associations between breakfast frequency (independent variable) and adiposity indicators (dependent variables: body mass index (BMI) z-score and body fat percentage (BF%)), adjusting for age, sex, and parental education in 6941 children from 12 ISCOLE study sites. Associations were also adjusted for moderate-to-vigorous physical activity, healthy and unhealthy dietary patterns and sleep time in a sub-sample (n=5710). Where interactions with site were significant, results were stratified by site. RESULTS: Adjusted mean BMI z-score and BF% for frequent breakfast consumers were 0.45 and 20.5%, respectively. Frequent breakfast consumption was associated with lower BMI z-scores compared with occasional (P<0.0001, 95% confidence intervals (CI): 0.10–0.29) and rare (P<0.0001, 95% CI: 0.18–0.46) consumption, as well as lower BF% compared with occasional (P<0.0001, 95% CI: 0.86–1.99) and rare (P<0.0001, 95% CI: 1.07–2.76). Associations with BMI z-score varied by site (breakfast by site interaction; P=0.033): associations were non-significant in three sites (Australia, Finland and Kenya), and occasional (not rare) consumption was associated with higher BMI z-scores compared with frequent consumption in three sites (Canada, Portugal and South Africa). Sub-sample analyses adjusting for additional covariates showed similar associations between breakfast and adiposity indicators, but lacked site interactions. CONCLUSIONS: In a multinational sample of children, more frequent breakfast consumption was associated with lower BMI z-scores and BF% compared with occasional and rare consumption. Associations were not consistent across all 12 countries. Further research is required to understand global differences in the observed associations.
    • Effective behaviour change techniques in the prevention and management of childhood obesity

      Martin, J.; Chater, Angel M.; Lorencatto, F. (Nature Publishing Group, 2013-10-31)
      Rates of childhood obesity are increasing, and it is essential to identify the active components of interventions aiming to prevent and manage obesity in children. A systematic review of behaviour change interventions was conducted to find evidence of behaviour change techniques (BCTs) that are most effective in changing physical activity and/or eating behaviour for the prevention or management of childhood obesity. An electronic search was conducted for randomised controlled trials published between January 1990 and December 2009. Of 4309 titles and abstracts screened, full texts of 135 articles were assessed, of which 17 published articles were included in this review. Intervention descriptions were coded according to the behaviour-specific CALO-RE taxonomy of BCTs. BCTs were identified and compared across obesity management (n=9) vs prevention (n=8) trials. To assess the effectiveness of individual BCTs, trials were further divided into those that were effective (defined as either a group reduction of at least 0.13 body mass index (BMI) units or a significant difference in BMI between intervention and control groups at follow-up) vs non-effective (reported no significant differences between groups). We reliably identified BCTs utilised in effective and non-effective prevention and management trials. To illustrate the relative effectiveness of each BCT, effectiveness ratios were calculated as the ratio of the number of times each BCT was a component of an intervention in an effective trial divided by the number of times they were a component of all trials. Results indicated six BCTs that may be effective components of future management interventions (provide information on the consequences of behaviour to the individual, environmental restructuring, prompt practice, prompt identification as role model/position advocate, stress management/emotional control training and general communication skills training), and one that may be effective in prevention interventions (prompting generalisation of a target behaviour). We identified that for management trials, providing information on the consequences of behaviour in general was a feature of non-effective interventions and for prevention trials, providing information on the consequences of behaviour in general, providing rewards contingent on successful behaviour and facilitating social comparison were non-effective. To design effective behaviour change programmes for the prevention and management of childhood obesity, we would recommend utilising the BCTs identified as effective in this review. The impact on intervention effectiveness of combining BCTs should be the topic of further research.
    • Effects of stimulation of mu opioid and nociceptin/orphanin FQ peptide (NOP) receptors on alcohol drinking in rhesus monkeys

      Flynn, Shawn M.; Epperly, Phillip M.; Davenport, April T.; Cami-Kobeci, Gerta; Husbands, Stephen M.; Ko, Mei-Chuan; Czoty, Paul W. (Nature Publishing Group, 2019-04-10)
      Alcohol use disorder (AUD) persists as a devastating public health problem; widely effective pharmacological treatments are needed. Evidence from rodent models suggests that stimulating brain receptors for the neuropeptide nociceptin/orphanin FQ (NOP) can decrease ethanol drinking. We characterized the effects of the mu opioid peptide (MOP) receptor agonist buprenorphine and the buprenorphine analog (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6 methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028), which stimulates MOP and NOP receptors, in a translational nonhuman primate model of AUD. Rhesus monkeys drank a 4% ethanol solution 6 h per day, 5 days per week via an operant behavioral panel in their home cages. To assess behavioral selectivity, monkeys responded via a photo-optic switch to earn food pellets. After characterizing the acute effects of BU08028 (0.001–0.01 mg/kg, i.m.) and buprenorphine (0.003–0.056 mg/kg, i.m.), the drugs were administered chronically using a model of pharmacotherapy assessment that incorporates clinical aspects of AUD and treatment. Acutely, both drugs decreased ethanol drinking at doses that did not affect food-maintained responding. During chronic treatment, effects of BU08028 and buprenorphine were maintained for several weeks without development of tolerance or emergence of adverse effects. BU08028 was ~0.5 and 1.0 log units more potent in acute and chronic studies, respectively. The selective NOP receptor agonist SCH 221510 also selectively decreased ethanol intakes when given acutely (0.03–1.0 mg/kg, i.m.), whereas the MOP antagonist naltrexone (1.7–5.6 mg/kg, i.m.) decreased both ethanol intake and food pellets delivered. These data demonstrate that bifunctional MOP/NOP agonists, which may have therapeutic advantages to MOP-selective drugs, can decrease alcohol drinking in nonhuman primates.
    • Fbp17 and cip4 recruit ship2 and lamellipodin to prime the plasma membrane for fast endophilin-mediated endocytosis

      Hak, Laura Chan Wah; Khan, Shaheen; Meglio, Ilaria Di; Law, Ah-Lai; Häsler, Safa Lucken-Ardjomande; Quintaneiro, Leonor M.; Ferreira, Antonio P.A.; Krause, Matthias; McMahon, Harvey T.; Boucrot, Emmanuel; et al. (Nature Publishing Group, 2018-07-30)
      Endocytosis mediates the cellular uptake of micronutrients and the turnover of plasma membrane proteins. Clathrin-mediated endocytosis is the major uptake pathway in resting cells 1 , but several clathrin-independent endocytic routes exist in parallel 2,3 . One such pathway, fast endophilin-mediated endocytosis (FEME), is not constitutive but triggered upon activation of certain receptors, including the β 1 adrenergic receptor 4 . FEME activates promptly following stimulation as endophilin is pre-enriched by the phosphatidylinositol-3,4-bisphosphate-binding protein lamellipodin 4,5 . However, in the absence of stimulation, endophilin foci abort and disassemble after a few seconds. Looking for additional proteins involved in FEME, we found that 20 out of 65 BAR domain-containing proteins tested colocalized with endophilin spots. Among them, FBP17 and CIP4 prime the membrane of resting cells for FEME by recruiting the 5′-lipid phosphatase SHIP2 and lamellipodin to mediate the local production of phosphati-dylinositol-3,4-bisphosphate and endophilin pre-enrichment. Membrane-bound GTP-loaded Cdc42 recruits FBP17 and CIP4, before being locally deactivated by RICH1 and SH3BP1 GTPase-activating proteins. This generates the transient assembly and disassembly of endophilin spots, which lasts 5–10 seconds. This mechanism periodically primes patches of the membrane for prompt responses upon FEME activation.
    • Goat and buffalo milk fat globule membranes exhibit better effects at inducing apoptosis and reduction the viability of HT-29 cells

      Ji, Xiaoxi; Xu, Weili; Cui, Jie; Ma, Ying; Zhou, Shaobo (Nature Publishing Group, 2019-02-22)
      Bovine milk fat globule membrane (MFGM) has shown many health benefits, however, there has not been much study on non-cattle MFGMs. The purpose of this study was to compare the anti-proliferation effects and investigate the mechanisms of MFGMs from bovine, goat, buffalo, yak and camel milk in HT-29 cells. Results showed that protein content in MFGM of yak milk is the highest among five MFGM. All MFGMs inhibited cellular proliferation which was in agreement with cell morphology and apoptosis. However, the number of cells in S-phase from 24 h to 72 h was increased significantly by treatment with goat, buffalo and bovine MFGMs (100 μg/mL), but not yak and camel. All MFGMs treatment significantly reduced the mitochondrial membrane potential (with an order of goat>buffalo>bovine>camel>yak) and Bcl-2 expression, but increased the expression of both Bax and Caspase-3. Taken together, the results indicate that all MFGMs, especially goat and buffalo MFGMs, showed better effects at inducing apoptosis and inhibition of the proliferation of HT-29 cells. The mechanism might be arresting the cell cycle at S phase, depolarization of mitochondrial membrane potential, down-regulation of Bcl-2 expression and increase of Bax and Caspase-3 expression.
    • Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE

      Carmona, G.; Perera, U.; Gillett, C.; Naba, A.; Law, Ah-Lai; Sharma, V.P.; Wang, J.; Wyckoff, J.; Balsamo, M.; Mosis, F.; et al. (Nature Publishing Group, 2016-03-21)
      Cancer invasion is a hallmark of metastasis. The mesenchymal mode of cancer cell invasion is mediated by elongated membrane protrusions driven by the assembly of branched F-actin networks. How deregulation of actin regulators promotes cancer cell invasion is still enigmatic. We report that increased expression and membrane localization of the actin regulator Lamellipodin correlate with reduced metastasis-free survival and poor prognosis in breast cancer patients. In agreement, we find that Lamellipodin depletion reduced lung metastasis in an orthotopic mouse breast cancer model. Invasive 3D cancer cell migration as well as invadopodia formation and matrix degradation was impaired upon Lamellipodin depletion. Mechanistically, we show that Lamellipodin promotes invasive 3D cancer cell migration via both actin-elongating Ena/VASP proteins and the Scar/WAVE complex, which stimulates actin branching. In contrast, Lamellipodin interaction with Scar/WAVE but not with Ena/VASP is required for random 2D cell migration. We identified a phosphorylation-dependent mechanism that regulates selective recruitment of these effectors to Lamellipodin: Abl-mediated Lamellipodin phosphorylation promotes its association with both Scar/WAVE and Ena/VASP, whereas Src-dependent phosphorylation enhances binding to Scar/WAVE but not to Ena/VASP. Through these selective, regulated interactions Lamellipodin mediates directional sensing of epidermal growth factor (EGF) gradients and invasive 3D migration of breast cancer cells. Our findings imply that increased Lamellipodin levels enhance Ena/VASP and Scar/WAVE activities at the plasma membrane to promote 3D invasion and metastasis.
    • Perception of studying dental law and ethics among postgraduate dental students in the UK

      Wassif, Hoda; ; University of Bedfordshire (Nature Publishing Group, 2015-08-14)
      Law and ethics is an integral part of medical and dental professional practice. The subject is touched upon in the undergraduate curriculum. Historically, dentists interested in postgraduate study in this subject have accessed courses on medical law and ethics. While there are areas of shared interest (for example, consent, confidentiality) there are differences in emphasis and content (for example, end of life care, organ transplants, etc) which are not relevant to dentistry. A new postgraduate certificate (PgCert) course was approved by the University of Bedfordshire designed specifically for dental practitioners, making it the only university accredited course in the UK that is specific to dental staff. Students' perception of the subject of dental law and ethics at a postgraduate level was not known. The first PgCert student cohort was assessed at the start and the end of the course using two questionnaires. Sixteen students, all qualified dental practitioners working in the UK, took part. The perception toward the subject of dental law and ethics was in-line with the current guideline and regulations governing the dental profession. Perception of dental law was clearer at the end of the course compared to the beginning while dental ethics remained a challenging subject.