Ugi multicomponent reaction to prepare peptide–peptoid hybrid structures with diverse chemical functionalities

Monodisperse sequenced peptides and peptoids present unique nano-structures based on their self-assembled secondary and tertiary structures. However, the generation of peptide and peptoid hybrid oligomers in a sequence-defined manner via Ugi multicomponent reaction has not yet been studied. Herein, we report a synthetic strategy that enables both the modification of peptides as well as the generation of sequence-defined peptide–peptoid hybrid structures. Our synthetic methodology rests on the fusion of solid phase peptide synthesis with Ugi multicomponent reactions. We evidence that a diversity of chemical functionalities can be inserted into peptides or used in the design of peptide–peptoid hybrids exploiting a wide functional array including amines, carboxylic acids, hydrocarbons, carbohydrates as well as polymers, introducing a sequence-defined synthetic platform technology for precision peptoid hybrids

Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials

BACKGROUND: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. METHODS: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. RESULTS: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: - 0.10, (95% CI - 0.17, - 0.03); p = 0.007], VLDL (ES: - 0.26 (- 0.51, - 0.01); p = 0.044], triglycerides (ES: - 0.39 (- 0.55, - 0.24; p ≤ 0.001] and HbA1c (ES: - 0.27 (- 0.48, - 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: - 0.59 (- 1.17, - 0.01); p = 0.045] and IL-6 (ES: - 1.67 (- 3.14, - 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). CONCLUSIONS: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802

Omega-3 polyunsaturated fatty acid supplementation versus placebo on vascular health, glycaemic control, and metabolic parameters in people with type 1 diabetes: a randomised controlled preliminary trial

Background: The role of omega-3 polyunsaturated fatty acids (n-3PUFA), and the potential impact of n-3PUFA supplementation, in the treatment and management of type 1 diabetes (T1D) remains unclear and controversial. Therefore, this study aimed to examine the efficacy of daily high-dose-bolus n-3PUFA supplementation on vascular health, glycaemic control, and metabolic parameters in subjects with T1D. Methods: Twenty-seven adults with T1D were recruited to a 6-month randomised, double-blind, placebo-controlled trial. Subjects received either 3.3 g/day of encapsulated n-3PUFA or encapsulated 3.0 g/day corn oil placebo (PLA) for 6-months, with follow-up at 9-months after 3-month washout. Erythrocyte fatty acid composition was determined via gas chromatography. Endpoints included inflammation-associated endothelial biomarkers (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], E-selectin, P-selectin, pentraxin-3, vascular endothelial growth factor [VEGF]), and their mediator tumor necrosis factor alpha [TNFα] analysed via immunoassay, vascular structure (carotid intima-media thickness [CIMT]) and function (brachial artery flow mediated dilation [FMD]) determined via ultrasound technique, blood pressure, glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial metabolism. Results: Twenty subjects completed the trial in full. In the n-3PUFA group, the mean ± SD baseline n-3PUFA index of 4.93 ± 0.94% increased to 7.67 ± 1.86% (P  0.05). Conclusions: This study indicates that daily high-dose-bolus of n-3PUFA supplementation for 6-months does not improve vascular health, glucose homeostasis, or metabolic parameters in subjects with T1D. The findings from this preliminary RCT do not support the use of therapeutic n-3PUFA supplementation in the treatment and management of T1D and its associated complications. Trial Registration ISRCTN, ISRCTN40811115. Registered 27 June 2017, http://www.isrctn.com/ISRCTN40811115

Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss

<p>Abstract</p> <p>Background</p> <p>Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine.</p> <p>Methods</p> <p>A prospective study was carried out in 31 obese subjects (22 male and 19 female) with the inclusion criteria whose body mass index and age was 36.46 ± 2.22 and 38.48 ± 2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD) due to the incorporation of virgin olive oil as the principal source of fat (≥30 ml/day), moderate red wine intake (200–400 ml/day), green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12) were analyzed by paired Student's <it>t </it>test.</p> <p>Results</p> <p>There was an extremely significant (p < 0.0001) reduction in body weight (108.62 kg→ 94.48 kg), body mass index (36.46 kg/m²→31.76 kg/m²), systolic blood pressure (125.71 mmHg→109.05 mmHg), diastolic blood pressure (84.52 mmHg→ 75.24 mmHg), total cholesterol (208.24 mg/dl→186.62 mg/dl), triacylglicerols (218.67 mg/dl→113.90 mg/dl) and glucose (109.81 mg/dl→ 93.33 mg/dl). There was a significant (p = 0.0167) reduction in LDLc (114.52 mg/dl→105.95 mg/dl) and an extremely significant increase in HDLc (50.10 mg/dl→54.57 mg/dl). The most affected parameter was the triacylglicerols (47.91% of reduction).</p> <p>Conclusion</p> <p>The SKMD is safe, an effective way of losing weight, promoting non-atherogenic lipid profiles, lowering blood pressure and improving fasting blood glucose levels. Future research should include a larger sample size, a longer term use and a comparison with other ketogenic diets.</p

A situation analysis of hospitalised physically abused pre-school children in South Africa: Contributing social factors

Lettere En WysbegeerteMaatskaplike WerkPlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

A situation analysis of hospitalised physically abused pre-school children in South Africa: Contributing social factors

The experience of physical abuse is a traumatic event, which is so intense and frightening that it overwhelms the child's ability to cope with his/her normal developmental tasks. The goal of the study was to expand social worker's knowledge of the social circumstances of physically abused preschool children who are hospitalised, and to offer guidelines for professionals from a variety of disciplines to identify and assess physical abuse. To obtain the goals, the objectives were threefold: first to present demographic data on children with intentional physical injuries and their families; second, to describe the experiences of the perpetrators and circumstances under which the abuse took place; and third, to determine how social workers assess children who are suspected of having been physically abused. The study was conducted at the Red Cross Children's Hospital in Cape Town, South Africa. Both qualitative and quantitative methods were applied. The diagnoses reported were drawn from a sample of preschool aged children presenting with intentional physical injuries at the hospital over a four month period, interviews with four perpetrators using set guidelines, and conducting a survey with four of the social workers employed at the hospital using a self-completion questionnaire. The findings offered demographic details of the abused children and confirmed that children under the age of six were the most vulnerable age group to be subjected to physical abuse. Head injuries and gunshot wounds were the most frequent occurring physical injuries in this sample, indicating gang activities, effects of poverty and substance misuse. Four case studies are presented following the interviews with the perpetrators/parents, which give a situation analysis of these social circumstances under which the abuse took place. The social circumstances under which the physical abuse took place, and criteria used for assessment can be used as a framework for professionals rendering services to children.Articl

Bibliographie Africaniste

Jean S., de Beauchesne G., Hartweg R. Bibliographie Africaniste. In: Journal de la Société des Africanistes, 1957, tome 27, fascicule 2. pp. 221-278

Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus.

BACKGROUND: People with type 2 diabetes mellitus are at increased risk from cardiovascular disease. Dietary omega-3 polyunsaturated fatty acids (PUFAs) are known to reduce triglyceride levels, but their impact on cholesterol levels, glycemic control and vascular outcomes are not well known. OBJECTIVES: To determine the effects of omega-3 PUFA supplementation on cardiovascular outcomes, cholesterol levels and glycemic control in people with type 2 diabetes mellitus. SEARCH STRATEGY: We carried out a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, bibliographies of relevant papers and contacted experts for identifying additional trials. SELECTION CRITERIA: All randomised controlled trials were included where omega-3 PUFA supplementation or dietary intake was randomly allocated and unconfounded in people with type 2 diabetes. Authors of large trials were contacted for missing information. DATA COLLECTION AND ANALYSIS: Trials were assessed for inclusion. Authors were contacted for missing information. Data was extracted and quality assessed independently in duplicate. Fixed-effect meta-analysis was carried out. MAIN RESULTS: Twenty three randomised controlled trials (1075 participants) were included with a mean treatment duration of 8.9 weeks. The mean dose of omega-3 PUFA used in the trials was 3.5 g/d. No trials with vascular events or mortality endpoints were identified. Among those taking omega-3 PUFA triglyceride levels were significantly lowered by 0.45 mmol/L (95% confidence interval (CI) -0.58 to -0.32, P &lt; 0.00001) and VLDL cholesterol lowered by -0.07 mmol/L (95% CI -0.13 to 0.00, P = 0.04). LDL cholesterol levels were raised by 0.11 mmol/L (95% CI 0.00 to 0.22, P = 0.05). No significant change in or total or HDL cholesterol, HbA1c, fasting glucose, fasting insulin or body weight was observed. The increase in VLDL remained significant only in trials of longer duration and in hypertriglyceridemic patients. The elevation in LDL cholesterol was non-significant in subgroup analyses. No adverse effects of the intervention were reported. AUTHORS' CONCLUSIONS: Omega-3 PUFA supplementation in type 2 diabetes lowers triglycerides and VLDL cholesterol, but may raise LDL cholesterol (although results were non-significant in subgroups) and has no statistically significant effect on glycemic control or fasting insulin. Trials with vascular events or mortality defined endpoints are needed