The Pharmacological Activities of the Metabolites of N-[(Trimethylamineboryl)-Carbonyl]-L-Phenylalanine Methyl Ester

The metabolites of N-[(trimethylamineboryl)-carbonyl]-L-phenylalanine methyl ester 1 proved to be active in a number of pharmacological screens where the parent had previously demonstrated potent activity. The proposed metabolites demonstrated significant activity as cytotoxic, hypolipidemic, and anti-inflammatory agents. In cytotoxicity screens several of the proposed metabolites afforded better activity than the parent compound against the growth of suspended and solid tumor cell lines. Evaluation of in vivo hypolipidemic activity demonstrated that the proposed metabolites of 1 were only moderately active and were generally less effective than the parent compound. Interestingly, L-phenylalanine methyl ester hydrochloride 3, which contains no boron atom, demonstrated equivalent hypolipidemic activity as the parent at 8 mg/kg/day in CF1 male mice. As anti-inflammatory agents the proposed metabolites demonstrated variable capacities to reduce foot pad inflammation. These compounds were similarly effective as the parent 1 at blocking local pain and were generally better than the parent at protecting CF1 male mice from LPS induced sepsis

Making management (more) relevant: breaking down disciplinary walls and pursuing neglected independent variables

The Walls Project encourages educators to broaden management teaching beyond individual and organizational variables and outcomes to systemic variables and outcomes. Its focus is on discovering independent variables that have social and environmental impacts and are currently neglected. Founded by six individuals who met at a RMLE UnConference in 2017,the Project decided to share pedagogical materials, examine them for commonalities, and present their findings at the MOBTC conference in 2019. This article summarizes these materials with an eye to revealing several variables of consequence, such as socioeconomic status and belief in economic growth, which are studied and taught infrequently in business schools. We suggest that researchers examine business curricula for similar neglected variables, study their impact across systems levels, and then develop them pedagogically to enhance management education that has a social and environmental impact

Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss

Glucagon analogues show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analogue, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a prerequisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics

Area-level deprivation and adiposity in children: is the relationship linear?

OBJECTIVE: It has been suggested that childhood obesity is inversely associated with deprivation, such that the prevalence is higher in more deprived groups. However, comparatively few studies actually use an area-level measure of deprivation, limiting the scope to assess trends in the association with obesity for this indicator. Furthermore, most assume a linear relationship. Therefore, the aim of this study was to investigate associations between area-level deprivation and three measures of adiposity in children: body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). DESIGN: This is a cross-sectional study in which data were collected on three occasions a year apart (2005-2007). SUBJECTS: Data were available for 13,333 children, typically aged 11-12 years, from 37 schools and 542 lower super-output areas (LSOAs). MEASURES: Stature, mass and WC. Obesity was defined as a BMI and WC exceeding the 95th centile according to British reference data. WHtR exceeding 0.5 defined obesity. The Index of Multiple Deprivation affecting children (IDACI) was used to determine area-level deprivation. RESULTS: Considerable differences in the prevalence of obesity exist between the three different measures. However, for all measures of adiposity the highest probability of being classified as obese is in the middle of the IDACI range. This relationship is more marked in girls, such that the probability of being obese for girls living in areas at the two extremes of deprivation is around half that at the peak, occurring in the middle. CONCLUSION: These data confirm the high prevalence of obesity in children and suggest that the relationship between obesity and residential area-level deprivation is not linear. This is contrary to the 'deprivation theory' and questions the current understanding and interpretation of the relationship between obesity and deprivation in children. These results could help make informed decisions at the local level

Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss

Glucagon analogs show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular, its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analog, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a pre-requisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics

Academic performance of undergraduate dental students with learning disabilities

© 2017 British Dental Association. All rights reserved.Aims To compare the academic performance of undergraduate dental students with known learning disabilities (LDs) to their peers.Methods This study analysed the results of students in applied dental knowledge (ADK) progress tests across four cohorts of dental students. A mixed model analysis of variance (ANOVA) was conducted to compare the performance of students with known disability to their peers. ADK test sitting was treated as a repeated measures variable, and the outcome variable of interest was percentage score on the ADK.Results Students' performance data on five ADK test sittings (ADK15, ADK16, ADK17, ADK18, and ADK19) by disability showed a significant main effect of test but no significant effect of disability or any interaction between disability and test.Conclusions This is the first study that explores the academic performance of dental students with a diagnosis of disability. The findings give reassurance to all stakeholders that, within the study population, students with LDs are not disadvantaged in knowledge-based assessments, demonstrating compliance with the legal obligations. Further research is required to explore how generalisable these findings are, as well as assess academic, clinical, and behavioural attributes of students with learning disabilities

Habitat structure: a fundamental concept and framework for urban soil ecology

Habitat structure is defined as the composition and arrangement of physical matter at a location. Although habitat structure is the physical template underlying ecological patterns and processes, the concept is relatively unappreciated and underdeveloped in ecology. However, it provides a fundamental concept for urban ecology because human activities in urban ecosystems are often targeted toward management of habitat structure. In addition, the concept emphasizes the fine-scale, on-the-ground perspective needed in the study of urban soil ecology. To illustrate this, urban soil ecology research is summarized from the perspective of habitat structure effects. Among the key conclusions emerging from the literature review are: (1) habitat structure provides a unifying theme for multivariate research about urban soil ecology; (2) heterogeneous urban habitat structures influence soil ecological variables in different ways; (3) more research is needed to understand relationships among sociological variables, habitat structure patterns and urban soil ecology. To stimulate urban soil ecology research, a conceptual framework is presented to show the direct and indirect relationships among habitat structure and ecological variables. Because habitat structure serves as a physical link between sociocultural and ecological systems, it can be used as a focus for interdisciplinary and applied research (e.g., pest management) about the multiple, interactive effects of urbanization on the ecology of soils

Attraction of the Invasive Halyomorpha halys (Hemiptera: Pentatomidae) to Traps Baited with Semiochemical Stimuli Across the United States

A recent identification of the two-component aggregation pheromone of the invasive stink bug species, Halyomorpha halys (Stål), in association with a synergist, has greatly improved the ability to accurately monitor the seasonal abundance and distribution of this destructive pest. We evaluated the attraction of H. halys to black pyramid traps baited with lures containing the pheromone alone, the synergist methyl (2E,4E,6Z)-decatrienoate (MDT) alone, and the two lures in combination. Traps were deployed around areas of agricultural production including fruit orchards, vegetables, ornamentals, or row crops in Delaware, Maryland, North Carolina, New Jersey, New York, Ohio, Oregon, Pennsylvania, Virginia, and West Virginia from mid-April to mid-October, 2012 and 2013. We confirmed that H. halys adults and nymphs are attracted to the aggregation pheromone season long, but that attraction is significantly increased with the addition of the synergist MDT. H. halys adults were detected in April with peak captures of overwintering adults in mid- to late May. The largest adult captures were late in the summer, typically in early September. Nymphal captures began in late May and continued season long. Total captures declined rapidly in autumn and ceased by mid-October. Captures were greatest at locations in the Eastern Inland region, followed by those in the Eastern Coastal Plain and Pacific Northwest. Importantly, regardless of location in the United States, all mobile life stages of H. halys consistently responded to the combination of H. halys aggregation pheromone and the synergist throughout the entire season, suggesting that these stimuli will be useful tools to monitor for H. halys in managed system

From trial to population: A study of a family-based community intervention for childhood overweight implemented at scale

To assess how outcomes associated with participation in a family-based weight management intervention (MEND 7–13, Mind, Exercise, Nutrition..Do it!) for childhood overweight or obesity implemented at scale in the community vary by child, family, neighbourhood and MEND programme characteristics

Differences in school environment, school policy and actions regarding overweight prevention between Dutch schools. A nationwide survey

<p>Abstract</p> <p>Background</p> <p>Schools are regarded as an important setting for the prevention of overweight. This study presents a nationally representative picture of the obesogenity of the school environment, the awareness of schools regarding overweight, and actions taken by the schools aiming at overweight prevention. In addition, differences between school levels were studied.</p> <p>Methods</p> <p>In 2006-2007, questionnaires were sent to all Dutch secondary schools (age group 12-18 years). Prevalences of the outcome variables were calculated for the schools in total and by school level. The association between school level and outcome variables were analysed by a log linear regression.</p> <p>Results</p> <p>Unhealthy foods and drinks are widely available at secondary schools. One third of the schools indicated that overweight has increased among students and half of the schools agreed that schools were (co)responsible for the prevention of overweight. Only 3% of the schools have a policy on overweight prevention. Small differences were observed between vocational education schools and higher education schools. The presence of vending machines did not differ by school level, but at vocational education schools, the content of the vending machines was less healthy.</p> <p>Conclusion</p> <p>This study describes the current situation at schools which is essential for the development and evaluation of future overweight prevention policies and interventions. In general, secondary schools are not actively involved in overweight prevention and the nutritional environment at most schools could be improved. The small differences between school levels do not give reason for a differential approach for a certain school level for overweight prevention.</p