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Gaetano Caramori,1 Paolo Ruggeri,1 Fabio Arpinelli,2 Laura Salvi,2 Giuseppe Girbino11Unità Operativa Complessa di Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università degli Studi di Messina, Messina, Italy; 2Direzione Medica, GSK, Verona, ItalyAbstract: Patients with chronic obstructive pulmonary disease (COPD) demonstrate a greater osteoporosis prevalence than the general population. This osteoporosis risk may be enhanced by treatment with inhaled corticosteroids (ICSs), which are recommended for COPD management when combined with long-acting bronchodilators, but may also be associated with reduced bone mineral density (BMD). We conducted a narrative literature review reporting results of randomized controlled trials (RCTs) of an ICS versus placebo over a treatment period of at least 12 months, with the aim of providing further insight into the link between bone fractures and ICS therapy. As of 16 October 2017, we identified 17 RCTs for inclusion. The ICSs studied were budesonide (six studies), fluticasone propionate (five studies), mometasone furoate (three studies), beclomethasone dipropionate, triamcinolone acetonide, and fluticasone furoate (one each). We found no difference in the number of bone fractures among patients receiving ICSs versus placebo across the six identified RCTs reporting fracture data. BMD data were available for subsets of patients in few studies, and baseline BMD data were rare; where these data were given, they were reported for treatment groups without stratification for factors known to affect BMD. Risk factors for reduced BMD and fractures, such as smoking and physical activity, were also often not reported. Furthermore, a standardized definition of the term “fracture” was not employed across these studies. The exact relationship between long-term ICS use and bone fracture incidence in patients with stable COPD remains unclear in light of our review. We have, however, identified several limiting factors in existing studies that may form the basis of future RCTs designed specifically to explore this relationship.Keywords: COPD, inhaled corticosteroids, osteoporosis, fracture risk

Purpose: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. Methods: We studied 2573 men and women aged 50–75 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. Results: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. Conclusions: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes. © 2016 Springer-Verlag Berlin Heidelberg

Excess fatty acid oxidation and generation of reactive carbonyls with formation of advanced lipoxidation endproducts (ALEs) is involved in nonalcoholic steatohepatitis (NASH) by triggering inflammation, hepatocyte injury, and fibrosis. This study aimed at verifying the hypothesis that ablation of the ALE-receptor galectin-3 prevents experimental NASH by reducing receptor-mediated ALE clearance and downstream events.Galectin-3-deficient (Lgals3(-/-)) and wild type (Lgals3(+/+)) mice received an atherogenic diet or standard chow for 8 months. Liver tissue was analyzed for morphology, inflammation, cell and matrix turnover, lipid metabolism, ALEs, and ALE-receptors.Steatosis was significantly less pronounced in Lgals3(-/-) than Lgals3(+/+) animals on atherogenic diet. NASH, invariably detected in Lgals3(+/+) mice, was observed, to a lower extent, only in 3/8 Lgals3(-/-) mice, showing less inflammatory, degenerative, and fibrotic phenomena than Lgals3(+/+) mice. This was associated with higher circulating ALE levels and lower tissue ALE accumulation and expression of other ALE-receptors. Up-regulation of hepatic fatty acid synthesis and oxidation, inflammatory cell infiltration, pro-inflammatory cytokines, endoplasmic reticulum stress, hepatocyte apoptosis, myofibroblast transdifferentiation, and impaired Akt phosphorylation were also significantly attenuated in Lgals3(-/-) animals. Galectin-3 silencing in liver endothelial cells resulted in reduced N(ε)-carboxymethyllysine-modified albumin uptake and ALE-receptor expression.Galectin-3 ablation protects from diet-induced NASH by decreasing hepatic ALE accumulation, with attenuation of inflammation, hepatocyte injury, and fibrosis. It also reduced up-regulation of lipid synthesis and oxidation causing less fat deposition, oxidative stress, and possibly insulin resistance. These data suggest that galectin-3 is a major receptor involved in ALE uptake by the liver.

See Appendix A for the complete list of the IDES_2 Investigators; Appendix B for the SPIRIT 2013 Checklist; Appendix C for Forms and Questionnaires; and Appendix D for World Health Organization Trial Registration Data Set. (DOC 252 kb)

Apart from late motor nerve dysfunction, factors affecting muscle strength in diabetes are largely unknown. This study was aimed at assessing muscle strength correlates in diabetic subjects encompassing a wide range of peripheral nerve function and various degrees of micro and macrovascular complications.Four-hundred consecutive patients with type 1 and 2 diabetes (aged 46.4 ± 13.9 and 65.8 ± 10.3 years, respectively) from the Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes (SAMBA) were examined for upper and lower body muscle isometric maximal voluntary contraction by dynamometry. Univariate and multivariate regression analyses were applied to identify strength correlates. Isometric force at both the upper and lower limbs was significantly lower in subjects with than in those without any complication. At univariate analysis, it was strongly associated with age, diabetes duration, physical activity (PA) level, cardio-respiratory fitness, anthropometric parameters, surrogate measures of complications, and parameters of sensory and autonomic, but not motor (except amplitude) neuropathy. Multivariate analysis revealed that upper and lower body strength correlated independently with male gender and, inversely, with age, autonomic neuropathy score (or individual autonomic function abnormalities), and vibration perception threshold, but not sensory-motor neuropathy score. Diabetes duration and PA level were excluded from the model.Both upper and lower body muscle strength correlate with measures of diabetic complications and particularly with parameters of sensory and especially autonomic nerve function, independently of diabetes duration and PA level, thus suggesting the involvement of mechanisms other than manifest motor nerve impairment.

Scientific and technological advances which took place during the twentieth century have totally changed the relationship between science and society and, as a consequence, the relationship between science and law, that are nowadays more and more involved in several fields of the governmental action. Public authorities working at a local, a supranational and a global level, are often in charge of regulating the risks which arise also from new technologies; therefore, today, many policy and decision-making processes enshrine a scientific or technological dimension that often lead policymakers to seek scientific advice, in order to provide public policies and decisions related to risks with a solid foundation and legitimation. Science-based decision-making processes are particularly relevant in the European Union context, where “the best available science” becomes a key input in many decisions adopted by EU institutions, in particular in the food safety domain, that is somewhat paradigmatic with regard to the issue of risk regulation in the EU. The outbreak of the 1996 BSE crisis, and other food scandals, have shown the inadequacy of the former EU approach to food safety regulation, as applied until then, and called for a reform of the system, that lead to the enactment of regulation (EC) n. 178/2002 and the establishment of the European Food Safety Authority (EFSA). The cornerstone of the new global and science-based EU food policy is the risk analysis scheme, structured upon three different components: risk assessment, risk management and risk communication. In the dichotomy between risk assessment and risk management, respectively entrusted to EFSA and to the European Commission, we can find one of the key features of this legislation, with the aim to ensure the excellence and, first and foremost, the independence of the scientific outputs from political influences, on the one hand, and providing political authorities with sound scientific basis for their regulatory choices, on the other. In practice, a clear-cut distinction between risk assessment and risk management is nevertheless problematic, and this has been demonstrated by the concrete way in which one of the most important, and also contested, regulatory fields (like GMOs’ regulation) has worked until today. In the context of the GM food and feed authorization procedure established at the EU level there is a close interaction between risk assessment and risk management spheres, resulting in a relevant influence by EFSA on the Commission risk management decisions. In several cases, the European Commission showed a great reliance on scientific information and advice deriving from risk assessment conducted by EFSA. The role of EFSA in this framework is however strongly contested. EFSA is often blamed of not being really and totally independent from political and economic interests, with consequential problems with regard to the recognition of the Authority as the legitimacy provider of the measures adopted by the European Commission in the health and in the food safety domain. Risk management measures mostly consist in a balance between opposite interests and values; this balance involved a certain discretion by the political authorities, which is particularly wide in cases where scientific uncertainty requires to behave on a precautionary basis, so granting a sort of “advanced” protection. However, the exercise of this discretion have to be balanced with the results of the scientific risk assessment, able to granting the (technical and scientific) legitimation needed for the risk management activity. The complex balance between the technical and scientific moment, and the political one, is the heart of our matter, namely of the risk regulation process; behind it, there is a tension between the functional necessity for science-based decision-making and the wider demand for some kind of public participation; this tension is epitomized in the dichotomy “input-output legitimacy”. The EU risk regulation in the food domain is therefore paradigmatic in studying and in understanding the wide and complex questions related to the legitimation of the EU decisionmaking processes (and of the European Union itself), still often perceived (although less and less) as being affected by a legitimacy and democratic deficit.