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Background Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate the inflammatory microenvironment through PD1/PD-L1 pathway. Methods Inflammatory microenvironment was created in vitro by the activation of T cells isolated from healthy donors and rheumatoid arthritis (RA) patients with anti-CD3 and anti-CD28 antibodies. Direct and indirect co-cultures between DPSCs and PBMCs were carried out to evaluate the activation of immunomodulatory checkpoints in DPSCs and the inflammatory pattern in PBMCs. Results Our data suggest that the inflammatory stimuli trigger DPSCs immunoregulatory functions that can be exerted by both direct and indirect contact. As demonstrated by using a selective PD-L1 inhibitor, DPSCs were able to activate compensatory pathways targeting to orchestrate the inflammatory process by modulating pro-inflammatory cytokines in pre-activated T lymphocytes. The involvement of PD-L1 mechanism was also observed in autologous inflammatory status (pulpitis) and after direct exposure to pre-activated T cells from RA patients suggesting that immunomodulatory/anti-inflammatory properties are strictly related to their stemness status. Conclusions Our findings point out that the communication with the inflammatory microenvironment is essential in licensing their immunomodulatory properties. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02664-4.

"L'area di studio comprende l'area urbana e suburbana di Roma con 52 siti censiti. I rilievi sono stati effettuati con il metodo fitosociologhico di Braun- Blanquet distinguendo 4 tipi di vegetazione: vegetazione ruderale, vegetazione soggetta a calpèestio, vegetazione erbacea dei muri, vegetazione arbustiva e arborea. Tutta la vegetazione è descritta con tabelle fitosociologiche di 25 tipi di mvegetazione e 248 rilievi."

The organic food market grew steadily during the past decade (Hamm and Gronefeld 2004, Spiller 2006). This increase is accompanied by challenges in market structures, distribution channels as well as differentiation of expectations and buying motives of organic food consumers. On this regard, the “hedonistic” motives for purchasing of organic food, that also include sensory features like taste or appearance, gained importance in comparison to other motivations. Therefore, some scientists pointed out that sensory attributes are important elements that should be taken into account in the marketing strategies by organic food distributors (Brennan and Kuri 2002, Padel and Midmore 2005) than even before. The objective of this paper is to explore sensory experiences, expectations and perceptions of Italian and German organic consumers underlining differences between the two countries when purchasing and eating organic food. Ten focus group interviews composed by 6-10 consumers were performed during 2009 in different locations in Italy and Germany. The focus groups content was transcribed and then analyzed using qualitative content analysis. Results indicated that, although sensory attributes are not the main purchase driver, taste and, especially for Italy, odour are the most important sensory features taken into account by organic consumers especially for the first purchase. However, it seems that the ability to differentiate between various categories of sensory perception is characterized by a low level of development which may limit the set of possibilities when trying to reach consumers by affecting their senses. Furthermore, consumers were able to mention several aspects such as intensity, naturalness and authenticity that they consider to be important when it comes to the sensory properties of organic products. Other findings suggests that sensory perception is a learnable ability which offers an opportunity for the actors of the organic food market to bring their customers closer to their products by a corresponding training of consumers’ sensory abilities. Regarding the concept of standardisation consumers pointed out that sensory properties should not be standardized, especially for heavy users. In both countries, one part of the organic consumers seem to appreciate sensory marketing activities whereas another part apparently does not. For Italian consumers who appreciate sensory marketing, non-subjective as well as subjective marketing information is considered to be suitable, whereas in Germany non-subjective aspects seem to be predominant. Further research may be useful in order to detect the right marketing tools that are able to support a sensory-based strategy of product presentation and positioning., Proceedings in Food System Dynamics, Proceedings in System Dynamics and Innovation in Food Networks 2012

INTRODUCTION: Defects of prokineticin pathway affect the neuroendocrine control of reproduction, but their role in the pathogenesis of central hypogonadism remains undefined, and the functional impact of the missense PROKR2 variants has been incompletely characterized. MATERIAL AND METHODS: In a series of 246 idiopathic central hypogonadism patients, we found three novel (p.V158I, p.V334M, and p.N15TfsX30) and six already known (p.L173R, p.T260M, p.R268C, p.V274D, p.V331M, and p.H20MfsX23) germline variants in the PROKR2 gene. We evaluated the effects of seven missense alterations on two different prokineticin receptor 2 (PROKR2)-dependent pathways: inositol phosphate-Ca(2+) (Gq coupling) and cAMP (Gs coupling). RESULTS: PROKR2 variants were found in 16 patients (6.5%). Expression levels of variants p.V158I and p.V331M were moderately reduced, whereas they were markedly impaired in the remaining cases, except p.V334M, which was significantly overexpressed. The variants p.T260M, p.R268C, and p.V331M showed no remarkable changes in cAMP response (EC50) whereas the IP signaling appeared more profoundly affected. In contrast, cAMP accumulation cannot be stimulated through the p.L173R and p.V274D, but IP EC50 was similar to wt inp.L173R and increased by 10-fold in p.V274D. The variant p.V334M led to a 3-fold increase of EC50 for both cAMP and IP. CONCLUSION: Our study shows that single PROKR2 missense allelic variants can either affect both signaling pathways differently or selectively. Thus, the integrity of both PROKR2-dependent cAMP and IP signals should be evaluated for a complete functional testing of novel identified allelic variants.

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary–gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.

Age-related bone loss in men is a poorly understood phenomenon, although increasing data on the pathophysiology of bone in men is becoming available. Most of what we know on bone pathophysiology derives from studies on women. The well-known association between menopause and osteoporosis is far from been disproven. However, male osteoporosis is a relatively new phenomenon. Its novelty is in part compensated for by the number of studies on female osteoporosis and bone pathophysiology. On the other hand, the deeper understanding of female osteoporosis could lead to an underestimation of this condition in the male counterpart. The longer life-span exposes a number of men to the risk of mild-to-severe hypogonadism which in turn we know to be one of the pathogenetic steps toward the loss of bone mineral content in men and in women. Hypogonadism might therefore be one among many corrigible risk factors such as cigarette smoking and alcohol abuse against which clinicians should act in order to prevent osteoporosis and its complications. Treatments with calcium plus vitamin D and bisphophonates are widely used in men, when osteoporosis is documented and hypogonadism has been excluded. The poor knowledge on male osteoporosis accounts for the lack of well shared protocols for the clinical management of the disease. This review focuses on the clinical approach and treatment strategy for osteoporosis in men with particular attention to its relationship with male hypogonadism.

The article explores sensory experiences and expectations of organic producers regarding the consumer relevant-information for sensory properties of organic products. Individual interviews to ten prominent Italian organic producers were administered and analysed using both qualitative and quantitative content analysis and conceptual mapping. Findings show that organic producers carry out sensory analysis generally in a non-systematic and non-standardized way. However, despite high costs and lack of expertise, they state the need to improve reliability and to increase sensory tests on their products in order to better meet consumer wants. The negative influence of variability in sensory features of organic products during the shelf-life was highlighted and the need of training initiatives to improve consumer's sensory knowledge and skills was expressed. From these findings, suggestions for further research are provided.

Micro-RNA, a new class of small, non-coding RNAs, have been shown to be deregulated in several human carcinomas. In particular, SNP rs2910164 in pre-miR146a appears to be correlated with papillary thyroid carcinoma and may be involved in its genetic predisposition. Since data on follicular thyroid carcinomas (FTC) are lacking, we evaluated the involvement of SNP rs2910164 in FTC.Thirty-nine cases of FTC and 20 follicular adenomas, defined according to WHO criteria, were selected. DNA and RNA were extracted from formalin-fixed paraffin-embedded blocks of both neoplastic and non-neoplastic areas. The DNA region of pre-miR146a, containing SNP rs2910164, was sequenced. Total RNA including miRNAs was used for stem-loop RT reactions, and applying a standard TaqMan PCR kit protocol for real-time PCR. Wilcoxon signed-rank test and Friedman test were used for statistical analyses.In 31% of FTC, the G allele was observed in neoplastic tissues, compared with the non-neoplastic areas (p0.05), whereas the CC phenotype was completely absent in tumours. Moreover, the expression of pre-miR146a was found to be significantly down-regulated in neoplastic tissues from FTC cases (p = 0.043), although no significant differences were seen in follicular thyroid adenomas.The expression profile of pre-miR146a can be correlated with FTC tumourigenesis. The G allele in SNP rs2910164 appears to be correlated with the transition from normal to neoplastic tissue. The GG and GC alleles appear to be associated with an increased risk for FTC, while the CC allele seems to play a protective role.

Objective Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Design Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Methods We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). Results 90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann’s syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH. Conclusions Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.

Der vorliegende Beitrag untersucht Erwartungen und Wahrnehmungen deutscher Verbraucher im Hinblick auf die französische Klub-Birnensorte Angelys. Dazu wurden leitfadengestützte Fo- kusgruppeninterviews mit jeweils acht bis zehn Teilnehmern an fünf Standorten in Deutschland von April bis Mai 2012 durchgeführt. Die Aufzeichnungen der Interviews wurden verbatim transkribiert und mittels qualitativer Inhaltsanalyse analysiert. Die Ergebnisse zeigen, dass Qualitätswahrnehmung bei Verbrauchern eine entscheidende Rolle spielt. Die Teilnehmer der Studie reagierten unterschiedlich auf Angelys. Die Reaktionen reichten von Ablehnung bis hin zur Würdigung von sensorischen Eigenschaften der Birne und ihrer kommerziellen Merkmale. So erwies sich beispielsweise das Aussehen als wichtiger Indikator für die Qualität und führte sowohl zu Bestätigung, als auch zu Überraschung unter den Teilnehmern. Die braun-berostete Birne wurde als kompakt, barock, klassisch und interessant, aber auch als alt, unförmig und überlagert beschrieben. Diese Assoziationen sind zum einen auf das sensorische Gedächtnis der Konsumenten als auch auf geringe Sortenkenntnisse zurückzuführen. Auch das Markenkonzept der Birne wurde intensiv diskutiert. Aus den gewonnen Ergebnissen werden Handlungsempfehlungen für die Vermarktung abgeleitet und zukünftiger Forschungsbedarf identifiziert.

Hemochromatosis is a progressive iron overload disorder that is prevalent among individuals of European descent. It is usually inherited in an autosomal-recessive pattern and associated with missense mutations in HFE, an atypical major histocompatibility class I gene. Recently, we described a large family with autosomal-dominant hemochromatosis not linked to HFE and distinguished by early iron accumulation in reticuloendothelial cells. Through analysis of a large pedigree, we have determined that this disease maps to 2q32. The gene encoding ferroportin (SLC11A3), a transmembrane iron export protein, lies within a candidate interval defined by highly significant lod scores. We show that the iron-loading phenotype in autosomal-dominant hemochromatosis is associated with a nonconservative missense mutation in the ferroportin gene. This missense mutation, converting alanine to aspartic acid at residue 77 (A77D), was not seen in samples from 100 unaffected control individuals. We propose that partial loss of ferroportin function leads to an imbalance in iron distribution and a consequent increase in tissue iron accumulation.

We explore sensory experiences and expectations of Italian and German organic consumers when purchasing and eating organic food. Ten focus group interviews were performed and the results were analyzed using qualitative content analysis. Outcomes indicated that although sensory attributes are not the main purchase drivers, flavor and odor are the most important in driving consumers' choice. Findings also suggested that training consumers' sensory abilities offers new market opportunities to organic marketers. From a marketing perspective, Italian consumers seem to equally appreciate nonsubjective as well as subjective marketing information about organic products, whereas in Germany non subjective aspects appear to be predominant.

none 4 In this review, we identify the key drivers that affect the intention to adopt Precision Agriculture technologies. We collected research articles about the adoption of precision agriculture and we split them in two groups: (1) ex-post assessment that make use of utility-based models, and (2) ex-ante assessments that make use of predictive models, and especially the Technology Acceptance Model. We identified the main classes of constructs that were used to interpret what led the farmer to use technology. Dealing with both ex-ante and ex-post drivers, we offer an accurate representation of all the drivers that influence PA adoption. We depict three classes: financial, sociodemographic, and competitive-contingent factors. Furthermore, this review shows that the design of a proper adoption process needs to contemplate all the three classes of drivers and that farmers can be more easily attracted by disruptive innovation, rather than by sustaining innovation. open Pierpaoli E.; Carli G.; Pignatti E.; Canavari M. Pierpaoli E.; Carli G.; Pignatti E.; Canavari M.