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Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156–0.366]) vs non-diabetic subjects 0.352% [0.269–0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46–30.10] vs non-diabetic subjects 76.24 MPa [26.81–132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p

This article aims to frame Participatory Guarantee Systems (PGSs) in the evolution of relations between (urban) consumers and (rural) producers in Italy in the light of the food sovereignty aspirations of Alternative Food Networks, and to what extent PGSs are actually capable of responding to these expectations. The evidence gathered shows how PGSs support the spread of agroecology, food sovereignty and the democratisation of food supply chains.

The presence and coexistence of deagrarianization and reagrarianization movements within Italian Inner Areas implies the adoption of keys to understanding their evolution that take into account both processes that generate the so-called "voids" (e.g. demographic decline, erosion of territorial capital, etc.) and processes of territorial resistance and renaissance. Accordingly, the paper explores the nature and peculiarities of both movements in Central Sardinia, specifically in the territories of Barbagia, Mandrolisai and Ogliastra. Empirically, it focuses on the mechanisms that characterize a young farmers’ back-to-the-land process by individuating the motivational aspects that determine the choices for starting an agricultural business for the first time or taking over an existing farm, and identifying the elements that place the action of the farm beyond its perimeter, in an articulated system in which the new agrarization is a pivotal element of a broad process of territorial regeneration and reconnection with urban areas.

Qual è il valore sociale dell’alternanza scuola lavoro? Può un progetto di alternanza scuola lavoro promuovere i valori del movimento cooperativo? Questo articolo propone una parziale risposta a queste domande partendo da un progetto di alternanza sviluppato in provincia di Trento. La proposta formativa ha offerto una introduzione sulla cooperazione e sulla realizzazione di video dall’altra; successivamente è stata proposta la realizzazione di video-interviste ad anziani cooperatori del territorio; infine, i giovani hanno effettuato il montaggio di una decina di video. Al termine del progetto, durato un anno scolastico, sono stati intervistati tre in-segnanti e dodici ragazzi e ragazze andando ad indagare la loro percezione dell’esperienza di alternanza, il cambiamento di prospettiva rispetto al movimento cooperativo, i valori che hanno identificato attraverso l’esperienza e come questa abbia influito sul loro essere attivi nella società. Dai risultati emerge come l’alternanza scuola lavoro possa essere una modalità per trasmettere valori condivisi.

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N-terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome.A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits.A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk.Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger prospective studies, it would identify a new class of skeletal-related irAEs.

Despite perpetuate dynamics of marginalization-peripheralization which have characterized the nuanced profile of the Italian inner areas, currently, it is possible to intercept in these territories marked by significant processes of deagrarianization and depeasantization, a parallel trend of return to the land. This (re)discovered attraction for the “art of farming” in the “difficult countryside” reflects the emergence of a new demand for stability addressed to these territorial contexts by new generations of farmers who aspire to start with a newly emerging entrepreneurial idea or in some cases, to continue a previous family tradition. The article focuses on the role that young farmers have in triggering a process of territorial regeneration and eco-social transformation in inner areas. In doing so, the analysis develops through the identification of the sub-processes of innovation and social construction of the quality of the products and services provided by the new generations of farmers in different Alpine valleys in Trentino Alto-Adige and Liguria. The activity of new farmers contributes to make emerge inner areas not as passive perceivers of macro-economic dynamics, rather as active and dynamic social spaces within which territorial uniqueness regains value in new business strategies, also influencing social representation of quality. Furthermore, with the activation of specific innovation strategies, farms diversify their functions thus contributing to reshape the profile of the territory and significantly determine its capacity to connect with the “outside”.

Oxidative stress, a key mediator of cardiovascular disease, metabolic alterations, and cancer, is independently associated with menopause and obesity. Yet, among postmenopausal women, the correlation between obesity and oxidative stress is poorly examined. Thus, in this study, we compared oxidative stress states in postmenopausal women with or without obesity. Body composition was assessed via DXA, while lipid peroxidation and total hydroperoxides were measured in patient’s serum samples via thiobarbituric-acid-reactive substances (TBARS) and derivate-reactive oxygen metabolites (d-ROMs) assays, respectively. Accordingly, 31 postmenopausal women were enrolled: 12 with obesity and 19 of normal weight (mean (SD) age 71.0 (5.7) years). Doubled levels of serum markers of oxidative stress were observed in women with obesity in women with obesity compared to those of normal weight (H2O2: 32.35 (7.3) vs. 18.80 (3.4) mg H2O2/dL; malondialdehyde (MDA): 429.6 (138.1) vs. 155.9 (82.4) mM in women with or without obesity, respectively; p < 0.0001 for both). Correlation analysis showed that both markers of oxidative stress increased with an increasing body mass index (BMI), visceral fat mass, and trunk fat percentage, but not with fasting glucose levels. In conclusion, obesity and visceral fat are associated with a greater increase in oxidative stress in postmenopausal women, possibly increasing cardiometabolic and cancer risks.

In this study, a novel approach was developed to quantify endocannabinoids (eCBs), and was based on the liquid biosensor BIONOTE. This device is composed of a probe that can be immersed in a solution, and an electronic interface that can record a current related to the oxy-reductive reactions occurring in the sample. The two most representative members of eCBs have been analysed in vitro by BIONOTE: anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG). Bovine serum albumin was used to functionalize the probe and improve the sensibility of the whole analytical system. We show that BIONOTE is able to detect both AEA and 2-AG at concentrations in the low nanomolar range, and to discriminate between these eCBs and their moieties arachidonic acid, ethanolamine and glycerol. Notably, BIONOTE distinguished these five different molecules, and it was also able to quantify AEA in human plasma. Although this is just a proof-of-concept study, we suggest BIONOTE as a cheap and user-friendly prototype sensor for high throughput quantitation of eCB content in biological matrices, with an apparent diagnostic potential for tomorrow’s medicine.

Bisphenol A (BPA) is an endocrine disruptor that negatively affects spermatogenesis, a process where Sertoli cells play a central role. Thus, in the present study we sought to ascertain whether BPA could modulate the endocannabinoid (eCB) system in exposed mouse primary Sertoli cells. Under our experimental conditions, BPA turned out to be cytotoxic to Sertoli cells with an half-maximal inhibitory concentration (IC50) of ~6.0 µM. Exposure to a non-cytotoxic dose of BPA (i.e., 0.5 μM for 48 h) increased the expression levels of specific components of the eCB system, namely: type-1 cannabinoid (CB1) receptor and diacylglycerol lipase-α (DAGL-α), at mRNA level, type-2 cannabinoid (CB2) receptor, transient receptor potential vanilloid 1 (TRPV1) receptors, and DAGL-β, at protein level. Interestingly, BPA also increased the production of inhibin B, but not that of transferrin, and blockade of either CB2 receptor or TRPV1 receptor further enhanced the BPA effect. Altogether, our study provides unprecedented evidence that BPA deranges the eCB system of Sertoli cells towards CB2- and TRPV1-dependent signal transduction, both receptors being engaged in modulating BPA effects on inhibin B production. These findings add CB2 and TRPV1 receptors, and hence the eCB signaling, to the other molecular targets of BPA already known in mammalian cells.

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