The Exploration Ethic: Its Historical-Intellectual Basis. Outlook for Space (1980 - 2000)

Principle components of the exploration ethic are discussed. Attempts were made to justify both the historical and intellectual aspects of the concept. It was noted that intellectual justification is strongly grounded on: (1) the complementarity of objective and normative inquiry as to method, and (2) interdisciplinary alliance of ethics of adaptive systems with contemporary decision sciences, as a theoretical basis. Historical exploration justification was associated with: (1) periods of civilization transition, (2) changes in the process of exploration which cause change in types of rationals used, sponsors involved, and explorers interest, and (3) the incorrectness of proven prior cost/benefit calculations

Tips for Designing Publications for Underrepresented Audiences

The article presents a number of practical tips on designing publications for underrepresented and non-traditional audiences. The process of designing an effective publication requires the incorporation of cultural preferences of the target audience. Incorporating design principles that consider culture in the areas of formatting written content and selecting images, graphics, and pictures that are representative of the target audience are important. Other tips, such as using local resources to ensure the product is a quality publication that incorporates language and images reflective of the intended audience, are also useful

Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome

OBJECTIVE: This study tested the hypothesis that phosphodiesterase 5 inhibition alone or in combination with ACE inhibition improves glucose homeostasis and fibrinolysis in individuals with metabolic syndrome. RESEARCH DESIGN AND METHODS: Insulin sensitivity, beta-cell function, and fibrinolytic parameters were measured in 18 adults with metabolic syndrome on 4 separate days after a randomized, crossover, double-blind, 3-week treatment with placebo, ramipril (10 mg/day), tadalafil (10 mg o.d.), and ramipril plus tadalafil. RESULTS: Ramipril decreased systolic and diastolic blood pressure, ACE activity, and angiotensin II and increased plasma renin activity. Ramipril did not affect insulin sensitivity or beta-cell function. In contrast, tadalafil improved beta-cell function (P = 0.01). This effect was observed in women (331.9 +/- 209.3 vs. 154.4 +/- 48.0 32 micro x mmol(-1) x l(-1), respectively, for tadalafil treatment vs. placebo; P = 0.01) but not in men. There was no effect of any treatment on fibrinolysis. CONCLUSIONS Phosphodiesterase 5 inhibition may represent a novel strategy for improving beta-cell function in metabolic syndrome

AS PROTEÍNAS DE FOLHA DE MANDIOCA: ASPECTOS FISIOLÓGICOS, NUTRICIONAIS E IMPORTÂNCIA TECNOLÓGICA

Some aspects of leaf proteins, specially from cassava (Manihot esculenta Crantz), as physiologic origin, amino acid composition, biochemical properties, nutritional role and technological process are reviewed. Cassava leaves present high protein content (20-30% w/w dry basis), of satisfactory quality when compared to FAO recommended pattern, and also high content of vitamins A and C and minerals. Some potential applications for human nutrition, animal feed or biotechnology industries are discussed. Alguns aspectos ligados à tecnologia de proteínas de folhas, com ênfase para as folhas de mandioca (Manihot esculenta Crantz), são revisados. A composição em aminoácidos, as propriedades bioquímicas, a importância nutricional e os princípios dos métodos de extração são apresentados. As folhas de mandioca apresentam elevado teor de proteínas (20-30% base seca), de valor nutricional adequado às recomendações da FAO, além de altos teores de vitaminas A e C e de minerais. Algumas aplicações potenciais em nutrição humana ou animal ou como substrato para a indústria de biotecnologia são discutidas

Dietary adaptation for weight loss maintenance at Yale (DAWLY): Protocol and predictions for a randomized controlled trial

BackgroundCurrent therapies for obesity treatment are effective at producing short-term weight loss, but weight loss maintenance remains a significant challenge. Here we investigate the impact of pre-intervention dietary fat intake on the efficacy of a dietary supplement to support weight loss maintenance. Preclinical work demonstrates that a vagal afferent pathway critical for sensing dietary lipids is blunted by a high-fat diet (HFD), resulting in a reduced preference for a low-fat emulsion and severe blunting of the dopamine (DA) response to the gastric infusion of lipids. Infusion of the gut lipid messenger oleoylethanolamide (OEA), which is also depleted by HFD, immediately reverses this DA blunting and restores preference for the low-fat emulsion. Studies of OEA supplementation for weight loss in humans have had limited success. Given the strong effect of HFD on this pathway, we designed a study to test whether the efficacy of OEA as a weight loss treatment is related to pre-intervention habitual intake of dietary fat.Methods/DesignWe employed a randomized, double-blind, placebo-controlled trial in which 100 adults with overweight/obesity (OW/OB) were randomized to receive either OEA or placebo daily for 16 months. Following a baseline evaluation of diet, metabolic health, adiposity, and brain response to a palatable an energy dense food, participants in both groups underwent a 4-month behavioral weight loss intervention (LEARN®) followed by a 1-year maintenance period. The study aims are to (1) determine if pre-intervention dietary fat intake moderates the ability of OEA to improve weight loss and weight loss maintenance after a gold standard behavioral weight loss treatment; (2) identify biomarkers that predict outcome and optimize a stratification strategy; and (3) test a model underlying OEA’s effectiveness.DiscussionFocusing on interventions that target the gut-brain axis is supported by mounting evidence for the role of gut-brain signaling in food choice and the modulation of this circuit by diet. If successful, this work will provide support for targeting the gut-brain pathway for weight loss maintenance using a precision medicine approach that is easy and inexpensive to implement.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT04614233]

Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes.

BACKGROUND: Evidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols with shorter (14-16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined offer unique opportunities to address this challenge. METHODS: We compared metabolite profiles in patients with congenital lipodystrophy or loss-of-function insulin resistance (INSR gene) mutations with healthy controls. RESULTS: The absence of significant differences in triacylglycerol species in the INSR group suggest that changes previously observed in epidemiological studies are not purely a consequence of insulin resistance. The presence of triacylglycerols with lower carbon numbers and high saturation in patients with lipodystrophy suggests that these metabolite changes may be associated with primary adipose tissue dysfunction. The observed pattern of triacylglycerol species is indicative of increased de novo lipogenesis in the liver. To test this we investigated the distribution of these triacylglycerols in lipoprotein fractions using size exclusion chromatography prior to mass spectrometry. This associated these triacylglycerols with very low-density lipoprotein particles, and hence release of triacylglycerols into the blood from the liver. To test further the hepatic origin of these triacylglycerols we induced de novo lipogenesis in the mouse, comparing ob/ob and wild-type mice on a chow or high fat diet, confirming that de novo lipogenesis induced an increase in relatively shorter, more saturated fatty acids. CONCLUSIONS: Overall, these studies highlight hepatic de novo lipogenesis in the pathogenesis of metabolic dyslipidaemia in states where energy intake exceeds the capacity of adipose tissue

Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption

Background: Diet is a major contributor to metabolic disease risk, but there is controversy as to whether increased incidences of diseases such as non-alcoholic fatty liver disease arise from consumption of saturated fats or free sugars. Here, we investigate whether a sub-set of triacylglycerols (TAGs) were associated with hepatic steatosis and whether they arise from de novo lipogenesis (DNL) from the consumption of carbohydrates. Results: We conduct direct infusion mass spectrometry of lipids in plasma to study the association between specific TAGs and hepatic steatosis assessed by ultrasound and fatty liver index in volunteers from the UK-based Fenland Study and evaluate clustering of TAGs in the National Survey of Health and Development UK cohort. We find that TAGs containing saturated and monounsaturated fatty acids with 16-18 carbons are specifically associated with hepatic steatosis. These TAGs are additionally associated with higher consumption of carbohydrate and saturated fat, hepatic steatosis, and variations in the gene for protein phosphatase 1, regulatory subunit 3b (PPP1R3B), which in part regulates glycogen synthesis. DNL is measured in hyperphagic ob/ob mice, mice on a western diet (high in fat and free sugar) and in healthy humans using stable isotope techniques following high carbohydrate meals, demonstrating the rate of DNL correlates with increased synthesis of this cluster of TAGs. Furthermore, these TAGs are increased in plasma from patients with biopsy-confirmed steatosis. Conclusion: A subset of TAGs is associated with hepatic steatosis, even when correcting for common confounding factors. We suggest that hepatic steatosis risk in western populations is in part driven by increased DNL following carbohydrate rich meals in addition to the consumption of saturated fat

Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.

BACKGROUND: Diet is a major contributor to metabolic disease risk, but there is controversy as to whether increased incidences of diseases such as non-alcoholic fatty liver disease arise from consumption of saturated fats or free sugars. Here, we investigate whether a sub-set of triacylglycerols (TAGs) were associated with hepatic steatosis and whether they arise from de novo lipogenesis (DNL) from the consumption of carbohydrates. RESULTS: We conduct direct infusion mass spectrometry of lipids in plasma to study the association between specific TAGs and hepatic steatosis assessed by ultrasound and fatty liver index in volunteers from the UK-based Fenland Study and evaluate clustering of TAGs in the National Survey of Health and Development UK cohort. We find that TAGs containing saturated and monounsaturated fatty acids with 16-18 carbons are specifically associated with hepatic steatosis. These TAGs are additionally associated with higher consumption of carbohydrate and saturated fat, hepatic steatosis, and variations in the gene for protein phosphatase 1, regulatory subunit 3b (PPP1R3B), which in part regulates glycogen synthesis. DNL is measured in hyperphagic ob/ob mice, mice on a western diet (high in fat and free sugar) and in healthy humans using stable isotope techniques following high carbohydrate meals, demonstrating the rate of DNL correlates with increased synthesis of this cluster of TAGs. Furthermore, these TAGs are increased in plasma from patients with biopsy-confirmed steatosis. CONCLUSION: A subset of TAGs is associated with hepatic steatosis, even when correcting for common confounding factors. We suggest that hepatic steatosis risk in western populations is in part driven by increased DNL following carbohydrate rich meals in addition to the consumption of saturated fat

Development and characterisation of novel electrospun polylactic acid/tubular clay nanocomposites

A novel material formulation method of polylactic acid /tubular clay nanocomposites via electrospinning was introduced and the important processing parameters such as solution concentration, clay loading, material feed rate were particularly investigated. The hybrid fibre diameter, the clay dispersability and the thermal properties of such nanocomposites were then characterised by using the scanning electron microscopy, wide-angle X-ray diffraction and differential scanning calorimetry, respectively, to establish a fundamental structure–property relationship for the future application

OPtimising Treatment for MIld Systolic hypertension in the Elderly (OPTiMISE): protocol for a randomised controlled non-inferiority trial

Introduction: Recent evidence suggests that larger blood pressure reductions and multiple antihypertensive drugs may be harmful in older people, particularly frail individuals with polypharmacy and multi-morbidity. However, there is a lack of evidence to support de-prescribing of antihypertensives, which limits the practice of medication reduction in routine clinical care. The aim of this trial is to examine whether antihypertensive medication reduction is possible in older patients without significant changes in blood pressure control at follow-up. Methods and analysis: This trial will use a Primary Care based, open label, randomised controlled trial design. A total of 540 participants will be recruited, aged ≥80 years, with systolic blood pressure <150 mmHg and receiving ≥2 antihypertensive medications. Participants will have no compelling indication for medication continuation and will be considered to potentially benefit from medication reduction due to existing polypharmacy, co-morbidity and frailty. Following a baseline appointment, individuals will be randomised to a strategy of medication reduction (intervention) with optional self-monitoring or usual care (control). Those in the intervention group will have one antihypertensive medication stopped. The primary outcome will be to determine if a reduction in medication can achieve a proportion of participants with clinically safe blood pressure levels at 12 week follow-up (defined as a systolic blood pressure <150mmHg) which is non-inferior (within 10%) to that achieved by the usual care group. Qualitative interviews will be used to understand the barriers and facilitators to medication reduction. The study will use economic modelling to predict the long term effects of any observed changes in blood pressure and quality-of-life. Ethics and dissemination: The protocol and written information has been approved by a Research Ethics Committee, medicines regulatory authority (MHRA), and national and local health research authorities. All research outputs will be published in peer-reviewed journals and presented at national and international conferences