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Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.

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Microgels are interesting as potential delivery systems for antimicrobial peptides. In order to elucidate membrane interactions of such systems, we here investigate effects of microgel charge density on antimicrobial peptide loading and release, as well as consequences of this for membrane interactions and antimicrobial effects, using ellipsometry, circular dichroism spectroscopy, nanoparticle tracking analysis, dynamic light scattering and z-potential measurements. Anionic poly(ethyl acrylate-co-methacrylic acid) microgels were found to incorporate considerable amounts of the cationic antimicrobial peptides LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW) and to protect incorporated peptides from degradation by infection-related proteases at high microgel charge density. As a result of their net negative z-potential also at high peptide loading, neither empty nor peptide-loaded microgels adsorb at supported bacteria-mimicking membranes. Instead, membrane disruption is mediated almost exclusively by peptide release. Mirroring this, antimicrobial effects against several clinically relevant bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa) were found to be promoted by factors facilitating peptide release, such as decreasing peptide length and decreasing microgel charge density. Microgels were further demonstrated to display low toxicity towards erythrocytes. Taken together, the results demonstrate some interesting opportunities for the use of microgels as delivery systems for antimicrobial peptides, but also highlight several key factors which need to be controlled for their successful use., QC 20180327

Background: The aims of this study were to estimate the risk for diabetic retinopathy (DR) and to identify risk factors. We investigated a nationwide population-based cohort with diabetes diagnosed at age 15-34 years. Patients and methods: Of 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) 444 (56%) patients with retinal photos available for classification of retinopathy participated in a follow-up study 15-19 (median 17) years after diagnosis. Mean age was 42.3 +/- 5.7 years, BMI 26.1 +/- 4.1 kg/m(2), 62% were male and 91% had type 1 diabetes. A sub-study was performed in 367 patients with retinal photos from both the 9 and 17 year follow up and the risk for development of retinopathy between 9 and 17 years of follow up was calculated. Results: After median 17 years 324/444 (73%, 67% of T1D and 71% of T2D), had developed any DR but only 5.4% proliferative DR. Male sex increased the risk of developing retinopathy (OR 1.9, 95% CI 1.2-2.9). In the sub-study obesity (OR 1.2, 95% CI 1.04-1.4), hyperglycemia (OR 2.5, 95% CI 1.6-3.8) and tobacco use (OR 2.9, 95% CI 1.1-7.3) predicted onset of retinopathy between 9 and 17 years after diagnosis of diabetes. Conclusion: The number of patients with severe retinopathy after 17 years of diabetes disease was small. The risk of developing retinopathy with onset between 9 and 17 years after diagnosis of diabetes was strongly associated to modifiable risk factors such as glycemic control, obesity and tobacco use. (C) 2017 Elsevier B.V. All rights reserved., Funding Agencies|Gorthon Foundation Helsingborg; Committee for the blind in Malmohus County; Swedish Diabetes Association; Lundstrom Foundation; Novo-Nordisk Foundation; Research Funds of Malmo University Hospital; Swedish Research Council [14531, 14287]; Juvenile Diabetes Research Foundation-Wallenberg Diabetes Research Program [K98-99JD-128B]; Swedish Life Insurance Foundation; Trygg-Hansa Foundation; Faculty of Medicine at Umea University; Swedish Association for Patients with Kidney Disease; Swedish Society of Medicine and Heart and Lung foundation

Membrane interactions are critical for the successful use of inorganic nanoparticles as antimicrobial agents and as carriers of, or co-actives with, antimicrobial peptides (AMPs). In order to contribute to an increased understanding of these, we here investigate effects of particle size (42-208 nm) on layered double hydroxide (LDH) interactions with both bacteria-mimicking and mammalian-mimicking lipid membranes. LDH binding to bacteria-mimicking membranes, extraction of anionic lipids, as well as resulting membrane destabilization, was found to increase with decreasing particle size, also translating into size-dependent synergistic effects with the antimicrobial peptide LL-37. Due to strong interactions with anionic lipopolysaccharide and peptidoglycan layers, direct membrane disruption of both Gram-negative and Gram-positive bacteria is suppressed. However, LDH nanoparticles cause size-dependent charge reversal and resulting flocculation of both liposomes and bacteria, which may provide a mechanism for bacterial confinement or clearance. Taken together, these findings demonstrate a set of previously unknown behaviors, including synergistic membrane destabilization and dual confinement/killing of bacteria through combined LDH/AMP exposure, of potential therapeutic interest.

AIMS: The main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34 years). METHODS: All 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19 years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. RESULTS: After median 17 years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1 kg/m(2) ), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p = 0.041), BMI (p = 0.012) and HbA1c (p < 0.001) were significant predictors of developing diabetic nephropathy between 9 and 17 years of diabetes. At 17 years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1 mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.05 1.12 per 1 mmHg increase) were associated with DN. CONCLUSIONS: Patients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9 years of follow-up was a risk marker for later development of diabetic nephropathy. Copyright © 2014 John Wiley & Sons, Ltd.

OBJECTIVE: Simple methods for the evaluation of dynamic b-cell function in epidemiological and clinical studies of patients with type 2 diabetes (T2D) are needed. The aim of this study was to evaluate the dynamic beta-cell function in young patients with T2D with different disease durations and treatments. METHODS: Overall, 54 subjects with T2D from the Diabetes Incidence Study in Sweden (DISS) and 23 healthy control participants were included in this cross-sectional study. Beta-cell function was assessed by intravenous (i.v.) administration of arginine followed by i.v. glucose. The acute insulin and C-peptide responses to arginine (AIRarg and Ac-pepRarg, respectively) and to glucose (AIRglu and Ac-pepRglu, respectively)were estimated.Homeostasis model assessment of b-cell function(HOMA-b) andCpeptide assessments were also used for comparisons between patients with T2D and control participants. RESULTS: AIRarg and Ac-pepRarg, but not AIRglu and Ac-pepRglu, could differentiate between patients with different disease durations. AIRglu values were 89% (P < 0.001) lower and AIRarg values were 29% (P < 0.01) lower in patients with T2D compared with control participants. HOMA-b and fasting plasma C-peptide levels did not differ between the T2D and control groups. CONCLUSION: In young patients with T2D, the insulin secretory response to i.v. glucose is markedly attenuated, whereas i.v. arginine-stimulated insulin release is better preserved and can distinguish between patients with different disease duration and antidiabetic therapies. This suggests that the i.v. arginine stimulation test may provide an estimate of functional beta-cell reserve.

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Analysing trends in population breast cancer mortality statistics appears a simple method of estimating the effectiveness of mammographic screening programmes. We reviewed such studies of population-based screening in Europe to assess their value.

Aims: After initiation of treatment in Type 1 diabetes, a period with lower insulin requirement often follows, reflecting increased insulin sensitivity and improved insulin secretion. We explored if efficiency of proinsulin processing is associated with the remission phenomenon. Methods Seventy-eight patients with new-onset Type 1 diabetes were followed prospectively for 3 years. Daily insulin dosage, HbA(1c), plasma glucose, proinsulin, C-peptide, glucagon concentrations and islet antibodies were determined at diagnosis and after 3, 6, 9, 12, 18, 24, 30 and 36 months. We studied remission, defined as an insulin dose < 0.3 U kg-1 24 h-1 and HbA(1c) within the normal range, in relation to the above-mentioned variables. Results A rise and subsequent decline in plasma proinsulin and C-peptide concentrations was observed. Forty-five per cent of the patients experienced remission at one or more times, characterized by higher proinsulin and C-peptide levels, and lower proinsulin/C-peptide ratios, indicating more efficient proinsulin processing, compared with those not in remission. Non-remission also tended to be associated with higher glucagon values. Patients entering remission were more often men, had higher BMI at diagnosis, but did not differ at baseline with respect to islet antibody titres compared with patients with no remission. Conclusions Remissions after diagnosis of Type 1 diabetes were associated with lower proinsulin/C-peptide ratios, suggesting more efficient proinsulin processing, and tended to have lower glucagon release than non-remissions. This indicates that, in remission, the residual islets maintain a secretion of insulin and glucagon of benefit for control of hepatic glucose production.