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Increased circulating sclerostin levels and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Recent data from our group have shown that T2D affects the expression of genes controlling bone formation (SOST and RUNX2) and that accumulation of AGEs is associated with impaired bone microarchitecture. Whether the expression of the Wnt beta-catenin target genes is altered in T2D, and whether AGEs accumulation it is associated with type 1 Collagen (COL1A1) alteration is still unknown. We hypothesized that increased SOST gene expression leads to downregulation of Wnt β- catenin target genes (TCF/LEF1) and AGEs accumulation is related to a downregulation of COL1A1 in bones from subjects with T2D. We analyzed bone tissue from femoral heads of 14 T2D postmenopausal women (mean HbA1c 6.5%) and 21 age- and BMI-comparable nondiabetic women undergoing hip replacement surgery. We found that TCF-LEF1 was significantly lower in T2D compared to non- diabetic subjects (p=0.0092). Dickkopf -1 (DKK-1), the other inhibitor of beta-catenin-dependent Wnt signalling besides sclerostin, was not different between groups (p=0.1083). However, analysis of correlation showed that DKK-1 increases with age (r2=0.038; p=0.043) and HbA1c (r2=0.503; p=0.048) in T2D subjects. COL1A1 gene expression was lower in T2D compared to controls although significance was not fully reached (p=0.0564). Importantly, AGEs bone content was significantly higher in T2D compared to nondiabetics (1.5 fold increase; p In conclusion, our data show that even in patients with relatively good glycemic control, T2D affects the expression of collagen and Wnt beta-catenin target genes. We also found that accumulation of AGEs is possibly associated with alteration in collagen gene expression. We provide novel insights that may help understand the mechanisms underlying bone fragility in T2D. Disclosure G. Leanza: None. F. Tramontana: None. F. Cannata: None. A. Piccoli: None. M. Faraj: None. V. Viola: None. R. Strollo: None. N. Napoli: None. P. Pozzilli: None. Funding Campus Bio-Medico University

Endogenous bioactive lipids are part of a complex network that modulates a plethora of cellular and mo-lecular processes involved in health and disease, of which inflammation represents one of the mostprominent examples. Inflammation serves as a well-conserved defence mechanism, triggered in theevent of chemical, mechanical or microbial damage, that is meant to eradicate the source of damageand restore tissue function. However, excessive inflammatory signals, or impairment of pro-resolving/anti-inflammatory pathways leads to chronic inflammation, which is a hallmark of chronic pathologies.Allmainclassesofendogenousbioactivelipids–namely eicosanoids, specialized pro-resolving lipid me-diators, lysoglycerophopsholipids and endocannabinoids–have been consistently involved in thechronic inflammation that characterises pathologies such ascancer, diabetes, atherosclerosis, asthma,as well as autoimmune and neurodegenerative disorders and inflammatory bowel diseases. This reviewgathers the current knowledge concerning the involvement of endogenous bioactive lipids in the patho-genic processes of chronic inflammatory pathologies.

Increased circulating sclerostin and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Whether the expression of the sclerostin-encoding SOST gene is altered in T2D, and whether it is associated with AGEs accumulation or regulation of other bone formation-related genes is unknown. We hypothesized that AGEs accumulate and SOST gene expression is upregulated in bones from subjects with T2D, leading to downregulation of bone forming genes (RUNX2 and osteocalcin) and impaired bone microarchitecture and strength. We obtained bone tissue from femoral heads of 19 T2D postmenopausal women (mean glycated hemoglobin [HbA1c] 6.5%) and 73 age- and BMI-comparable nondiabetic women undergoing hip replacement surgery. Despite similar bone mineral density (BMD) and biomechanical properties, we found a significantly higher SOST (p = .006) and a parallel lower RUNX2 (p = .025) expression in T2D compared with non-diabetic subjects. Osteocalcin gene expression did not differ between T2D and non-diabetic subjects, as well as circulating osteocalcin and sclerostin levels. We found a 1.5-fold increase in total bone AGEs content in T2D compared with non-diabetic women (364.8 ± 78.2 versus 209.9 ± 34.4 μg quinine/g collagen, respectively; p < .001). AGEs bone content correlated with worse bone microarchitecture, including lower volumetric BMD (r = -0.633; p = .02), BV/TV (r = -0.59; p = .033) and increased trabecular separation/spacing (r = 0.624; p = .023). In conclusion, our data show that even in patients with good glycemic control, T2D affects the expression of genes controlling bone formation (SOST and RUNX2). We also found that accumulation of AGEs is associated with impaired bone microarchitecture. We provide novel insights that may help understand the mechanisms underlying bone fragility in T2D. © 2020 American Society for Bone and Mineral Research (ASBMR).

AIM To compare a Mediterranean diet (MED) with a high-fibre vegetarian diet (HFV) in terms of hunger-satiety perception through post-prandial assessment of appetite-related hormones glucagon-like peptide 1 (GLP-1) and oxyntomodulin, as well as self-rated visual analogue scale (VAS) quantification, in overweight/obese subjects with type 2 diabetes (T2D). MATERIALS AND METHODS Twelve T2D subjects (Male to female ratio = 7:5), mean age 63 ± 8.5 years, were enrolled in a randomized, controlled, crossover study. Participants consumed an MED meal as well as an isocaloric meal rich in complex carbohydrate as well as an isocaloric MED meal in two different visits with a 1-week washout period between the two visits. Appetite ratings, glucose/insulin, and gastrointestinal hormone concentrations were measured at fasting and every 30' until 210' following meal consumption. RESULTS GLP-1 and oxyntomodulin levels were significantly higher following MED meal compared with HFV meals (210' area under the curve, p < 0.022 and p < 0.023, respectively). Both MED and HFV meal resulted in a biphasic pattern of GLP-1 and oxyntomodulin, although MED meal was related to a delayed, significantly higher second GLP-1 peak at 150' compared with that of HFV meal (p < 0.05). MED meal was related to lower glucose profile compared with HFV meal (p < 0.039), whereas we did not observe significant changes in terms of self-reported VAS scores and insulin trend. CONCLUSIONS In T2D overweight/obese subjects, an MED meal is more effective than a HFV meal in terms of post-prandial plasma glucose homoeostasis and GLP-1 and oxyntomodulin release. These changes were not confirmed by VAS appetite self-assessment over a 210' period.

Several grassroots initiatives in the last two decades have shown the need for different food practices that should be locally based and founded on ethical goals of social and environmental justice. Among the many “alternative food networks”, the Community Supported Agriculture model is particularly significant and interesting. By redefining meanings and social norms around food practices, this model actualizes significant processes of food re-socialization and re-territorialization. Focusing on Italy, this study aims to contribute to the understanding of the potential of this model. It does so through two investigations carried out in 2019 and 2020, aimed at analyzing, respectively, structural and organizational aspects of CSAs and the features of resilience shown by these initiatives during the first COVID-19 pandemic lockdown. On the whole, the two surveys give us the image of a radically innovative experience, potentially capable of deeply redefining production and consumption practices, being rooted in socially-shared knowledge, motivations, willingness, commitment and sense of community. In addition to being characterized by a determination to pursue sustainability and equity goals, the model shows a remarkable character of resilience thanks to the original arrangements that the common value basis and the strong sense of interdependence and solidarity of its members can provide.

Fragility fractures are major complications in type 2 diabetes (T2D), but mechanisms underlying bone fragility are still poorly clarified. Bone mineral density (BMD) underestimates T2D fracture incidence, since a normal or even higher BMD is associated with a greater fracture risk than healthy population. We hypothesized that bone fragility in T2D results from poor bone microarchitecture and bone quality caused by WNT signaling impairment and lower bone formation. We aimed to evaluate the association between bone gene expression of WNT pathway and features of bone microarchitecture and strength. We enrolled T2D (n=13) and nondiabetic (controls, n=75) postmenopausal women undergoing standard hip arthroplasty. Serum and proximal femur samples from recruited subjects were collected at the moment of surgical procedure. Gene expression of sclerostin (SOST), WNT5a, WNT10b, SFRP5, GSK3β, osteocalcin and RUNX2 was analyzed by real-time PCR. Total-body, lumbar and femoral BMD were assessed by bone densitometry. A trabecular core from bone samples was analyzed by Micro X-ray computed tomography and by compression tests. Age (75.23 ± 8.47 vs. 73.24 ± 5.77) and BMI (29.92 ± 5.38 vs. 27.68 ± 5.62 Kg/m2) did not differ between T2D and controls respectively. Glycated hemoglobin was 6.48 ± 1.7 mmol/mol. We found that T2D subjects had no differences in BMD and in bone microarchitecture parameters compared to controls. Neither bone turnover nor WNT serum markers differed among groups. SOST gene expression was increased (p=0.003) whereas RUNX2 expression was decreased in T2D vs. controls (p=0.017), independently by BMI and age. Osteocalcin and other WNT related genes expression did not differ among groups. Compression tests did not show impairment in bone strength in T2D vs. controls. In conclusion, although a good glycemic control and no alterations in bone density, microarchitecture and strength, we found an increase in SOST and a decrease in RUNX2 gene expression, implying a lower bone formation in T2D. Disclosure A. Piccoli: None. F. Cannata: None. F. Russo: None. V.L. Greto: None. C. Isgrò: None. G. Leanza: None. R. Strollo: None. C. Massaroni: None. C. Pedone: None. S. Silvestri: None. G. Vadalà: None. V. Denaro: None. T. Bisogno: None. R. Papalia: None. P. Pozzilli: None. M. Maccarrone: None. N. Napoli: None. Funding Campus Bio-Medico University

Objective. Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and its pathogenesis has not yet been completely clarified. Patients with SLE show a deranged lipid metabolism, which can contribute to the immunopathogenesis of the disease and to the accelerated atherosclerosis. Resolvin D1 (RvD1), a product of the metabolism of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), acts as a specialized proresolving mediator which can contribute in restoring the homeostasis in inflamed tissues. The aim of the present pilot study is to evaluate plasma levels of RvD1 in patients with SLE and healthy subjects, investigating its potential role as a biomarker of SLE and assessing its relationship with disease activity and laboratory parameters. Methods. Thirty patients with SLE and thirty age- and sex-matched healthy subjects (HSs) have been consecutively recruited at Campus Bio-Medico University Hospital. RvD1 plasma levels were measured by ELISA according to the manufacturer’s protocol (Cayman Chemical Co.). RvD1 levels were compared using Mann–Whitney test. Discriminatory ability for SLE has been evaluated by the area under the ROC curve. Results. Lower levels of RvD1, 45.6 (35.5–57.4) pg/ml, in patients with SLE have been found compared to HSs, 65.1 (39.43–87.95) pg/ml (p=0.0043). The area under the ROC curve (AUC) for RvD1 was 0.71 (95% CI: 0.578–0.82) and the threshold value of RvD1 for the classification of SLE was Conclusions. The present preliminary study allows hypothesizing a dysregulation of RvD1 in patients with SLE, confirming the emerging role of bioactive lipids in this disease.

Phrenic nerve paralysis is a condition typically occurring after invasive procedures in the chest and neck. Here we describe a case of transient unilateral diaphragmatic paralysis in a child with status asthmaticus complicated by complete right lung atelectasis. Common causes of this disorder and possible implications for our case are discussed.