How the EU’s Geographical Indications scheme helps foster economic development in rural areas

Products associated with specific locations in Europe, such as Roquefort and Parma ham, are protected under the EU’s ‘Geographical Indications’ scheme. This ensures these products can only be legally sold if they are produced in specified areas. As Riccardo Crescenzi, Fabrizio De Filippis, Mara Giua and Cristina Vaquero-Piñeiro write, Geographical Indications play a vital role for local development in rural areas with limited public expenditure. They provide protection against reproduction elsewhere, facilitate an upward effect on pricing and quality reputation, and improve demographic trends and sectoral re-composition

Geographical Indications and local development: the strength of territorial embeddedness

Can Geographical Indications (GIs) promote local economic development in rural areas? This paper explores the impact of GIs that identify and endorse agri-food products which are strictly embedded within the territory from which they originate. Examining Italian wine protected by GIs through an innovative dataset and by means of propensity score matching and difference-in-differences models make it possible to compare the local economic development trajectories of rural municipalities afforded GIs with the correspondent dynamics of a counterfactual group of similar municipalities without GI status since 1951. Rural municipalities with GIs experience population growth and economic reorganization towards non-farming sectors, which frequently involve higher value-added activities

A distinct epigenetic program underlies the 1;7 translocation in myelodysplastic syndromes

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Feasibility, Adherence and Efficacy of Liraglutide Treatment in a Sample of Individuals With Mood Disorders and Obesity

Background: Liraglutide is a once-daily injectable medication approved for the treatment of obesity. Hereby we report the feasibility, adherence and efficacy of liraglutide treatment in a sample of individuals with mood disorders and obesity.Methods and Sample: Twenty-nine patients with Bipolar or Major Depressive Disorder received liraglutide once daily subcutaneously at a dose gradually titrated from 0.6 to 3 mg. All patients were obese and had previously failed multiple healthy lifestyle interventions, including exercise and diet programs. Patients' weight was recorded before liraglutide treatment (T0) and then 1 (T1), 3 (T3), and 6 months (T6) following T0.Results: Mean baseline (T0) weight was 110.54 Kg (±24.95). Compared to baseline, the percentage of weight loss was 3.37% at T1, 7.85% at T3, and 10.20% at T6. Thirty-one percent (n = 9) of patients had no side effects, 34.48% (n = 10) had one, 24.14% (n = 7) had two, and 10.34% (n = 3) had three side effects. All 29 subjects were still on liraglutide at T1; 79.31 and 48.28% were on liraglutide at T3 and T6. No significant relationship was found between liraglutide dose and likelihood to continue the medication. No patient showed a worsening of the psychiatric condition due to liraglutide treatment. Acceptability and satisfaction with treatment were good for the 48% that completed the study.Conclusions: Liraglutide treatment was efficacious, accepted and tolerated by ~50% of our sample, followed up for a period of 180 days. Larger, longer, controlled, prospective studies are warranted

NPM1 Deletion Is Associated with Gross Chromosomal Rearrangements in Leukemia

BACKGROUND: NPM1 gene at chromosome 5q35 is involved in recurrent translocations in leukemia and lymphoma. It also undergoes mutations in 60% of adult acute myeloid leukemia (AML) cases with normal karyotype. The incidence and significance of NPM1 deletion in human leukemia have not been elucidated. METHODOLOGY AND PRINCIPAL FINDINGS: Bone marrow samples from 145 patients with myelodysplastic syndromes (MDS) and AML were included in this study. Cytogenetically 43 cases had isolated 5q-, 84 cases had 5q- plus other changes and 18 cases had complex karyotype without 5q deletion. FISH and direct sequencing investigated the NPM1 gene. NPM1 deletion was an uncommon event in the "5q- syndrome" but occurred in over 40% of cases with high risk MDS/AML with complex karyotypes and 5q loss. It originated from large 5q chromosome deletions. Simultaneous exon 12 mutations were never found. NPM1 gene status was related to the pattern of complex cytogenetic aberrations. NPM1 haploinsufficiency was significantly associated with monosomies (p<0.001) and gross chromosomal rearrangements, i.e., markers, rings, and double minutes (p<0.001), while NPM1 disomy was associated with structural changes (p=0.013). Interestingly, in complex karyotypes with 5q- TP53 deletion and/or mutations are not specifically associated with NPM1 deletion. CONCLUSIONS AND SIGNIFICANCE: NPM1/5q35 deletion is a consistent event in MDS/AML with a 5q-/-5 in complex karyotypes. NPM1 deletion and NPM1 exon 12 mutations appear to be mutually exclusive and are associated with two distinct cytogenetic subsets of MDS and AML

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic-phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

Background: Imatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features. Methods: A total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI. Results: Second-generation TKIs were chosen for most patients aged &lt;45 years (69.2%), whereas imatinib was used in 76.7% of patients aged &gt;65 years (p&nbsp;&lt;&nbsp;.001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with &gt;3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p&nbsp;=&nbsp;.002). In multivariable analysis, factors correlated with imatinib use were age &gt; 65 years, spleen size, the presence of comorbidities, and ≥3 concomitant medications. Conclusions: This observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use

Analysis of Early Events during the First Year of Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Phase - Chronic Myeloid Leukemia: A "Campus CML" Study

Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML). However, the rst months of therapy are crucial, as optimal response is dened as the achievement of molecular milestones at 3, 6 and 12 months (mo.) and as many toxicities, also causing a TKI switch, are more frequent in the 1st yea

p21WAF1/CIP1 Upregulation through the Stress Granule-Associated Protein CUGBP1 Confers Resistance to Bortezomib-Mediated Apoptosis

p21(WAF1/CIP1) is a well known cyclin-dependent kinase inhibitor induced by various stress stimuli. Depending on the stress applied, p21 upregulation can either promote apoptosis or prevent against apoptotic injury. The stress-mediated induction of p21 involves not only its transcriptional activation but also its posttranscriptional regulation, mainly through stabilization of p21 mRNA levels. We have previously reported that the proteasome inhibitor MG132 induces the stabilization of p21 mRNA, which correlates with the formation of cytoplasmic RNA stress granules. The mechanism underlying p21 mRNA stabilization, however, remains unknown.We identified the stress granules component CUGBP1 as a factor required for p21 mRNA stabilization following treatment with bortezomib ( =  PS-341/Velcade). This peptide boronate inhibitor of the 26S proteasome is very efficient for the treatment of myelomas and other hematological tumors. However, solid tumors are sometimes refractory to bortezomib treatment. We found that depleting CUGBP1 in cancer cells prevents bortezomib-mediated p21 upregulation. FISH experiments combined to mRNA stability assays show that this effect is largely due to a mistargeting of p21 mRNA in stress granules leading to its degradation. Altering the expression of p21 itself, either by depleting CUGBP1 or p21, promotes bortezomib-mediated apoptosis.We propose that one key mechanism by which apoptosis is inhibited upon treatment with chemotherapeutic drugs might involve upregulation of the p21 protein through CUGBP1