Development and management of winemaking sustainability: an explorative survey in Sicily

Sustainability is reshaping the global wine industry. This paper provides a fact-finding contribution to the knowledge on how the Sicilian winegrowing sector is facing the challenge of the new scenario of sustainable productions. To reach this goal we carried out an explorative analysis of those Sicilian wineries involved in 2 important sustainability programs in the Italian wine sector, Magis and SOStain, aimed at improve the implementation of sustainable viticulture and wine production. The results of our research concerning 5 wineries in Sicily reveal that adopting sustainable productive methods has lead in general to good technical and financial results by improving their business efficiencies and management systems, with positive socio-economic implications at a local level

Sustainability initiatives and experiences in the Sicilian wine industry

The Italian wine sector shows an increasing interest towards sustainability issues. As a result, a wide number of programs and initiatives concerning environmental, social and economic sustainability has been developed in recent years. The aim of this manuscript is to describe the adaptation of the Sicilian wine sector to the new scenario of sustainable productions. To this purpose a direct survey of 5 Sicilian wineries involved in two different sustainability programs, SOStain and Magis, was carried out. The findings of the study reveal that the sustainability path undertaken by the wineries analyzed has led to management awareness that company activities can ensure social and human benefits, as well as fulfill environmental and economic objectives in the long term

β-arrestin1-mediated acetylation of Gli1 regulates Hedgehog/Gli signaling and modulates self-renewal of SHH medulloblastoma cancer stem cells

Background Aberrant Sonic Hedgehog/Gli (Hh/Gli) signaling pathway is a critical regulator of Sonic hedgehog medulloblastoma (SHH-MB). Cancer stem cells (CSCs), thought to be largely responsible for tumor initiation, maintenance, dissemination and relapse, have been identified in SHH-MB. Since we previously demonstrated that Hh/Gli signaling controls CSCs features in SHH-MB and that in these tumors miR-326 is down regulated, here we investigated whether there is a functional link between Hh/Gli signaling and miR-326. Methods We evaluated β-arrestin1 (Arrb1) and its intragenic miR-326 levels in CSCs derived from SHH-MB. Subsequently, we modulated the expression of Arrb1 and miR-326 in CSCs in order to gain insight into their biological role. We also analyzed the mechanism by which Arrb1 and miR-326 control Hh/Gli signaling and self-renewal, using luciferase and protein immunoprecipitation assays. Results Low levels of Arrb1 and miR-326 represent a feature of CSCs derived from SHH-MB. We observed that re-expression of Arrb1 and miR-326 inhibits Hh/Gli signaling pathway at multiple levels, which cause impaired proliferation and self-renewal, accompanied by down regulation of Nanog levels. In detail, miR-326 negatively regulates two components of the Hh/Gli pathway the receptor Smoothened (Smo) and the transcription factor Gli2, whereas Arrb1 suppresses the transcriptional activity of Gli1, by potentiating its p300-mediated acetylation. Conclusions Our results identify a new molecular mechanism involving miR-326 and Arrb1 as regulators of SHH-MB CSCs. Specifically, low levels of Arrb1 and miR-326 trigger and maintain Hh/Gli signaling and self-renewal

Subclinical Atrial Fibrillation on Prolonged ECG Holter Monitoring: Results from the Multicenter Real-World SAFARI (Silent Atrial Fibrillation ANCE-Sicily Research Initiative) Study

Background: The detection of subclinical/silent atrial fibrillation (SAF) in the general population is of the utmost importance, given its potential adverse consequences. Incident AF has been observed in 30% to 70% of patients with implanted devices, but its prevalence may indeed be lower in the general population. The prospective, multicentric, observational Silent Atrial Fibrillation ANCE Research Initiative (SAFARI) study aimed at assessing the SAF prevalence in a real-world outpatient setting by the means of a small, wearable, prolonged ECG Holter monitoring (>5 days) device (CGM HI 3-Lead ECG; CGM TELEMEDICINE, Piacenza, Italy). Methods: Patients = 55 years of age at risk for AF were screened according to the inclusion criteria to undergo prolonged 3-lead ECG Holter monitoring. SAF episodes were classified as follows: Class A, <30 s; Class B, 30 to 299 s; and Class C, =300 s. Results: In total, 119 patients were enrolled (64 men; median age 71 (IQR 55-85) years). At a median of 13.5 (IQR 5-21) days of monitoring, SAF episodes were found in 19 patients (16%). A total of 10,552 arrhythmic episodes were registered, 6901 in Class A (n = 7 patients), 2927 in Class B (n = 3), and 724 in Class C (n = 9), (Class A vs. B and C, p < 0.001). This latter group had multiple (all-class) episodes, and two patients had >1000 episodes. There were no clinical, echocardiographic, or laboratory findings able to discriminate patients with SAF from those in sinus rhythm in univariate and multivariable analyses; of note is that the Class C patients showed a higher diastolic blood pressure, resting heart rate, and indexed LA volume. Conclusions. Over a median of 13 days of Holter monitoring, the SAFARI study confirmed the usefulness of small wearable devices in detecting SAF episodes in real-world outpatients at risk for, but with no prior history of, AF

Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. \ua9 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved

Tuberculosis outcomes among international migrants living in Europe compared with the nonmigrant population: A systematic review and meta-analysis

Objectives: Migration status refers to socioeconomic factors that challenge access to the health care system and increase the risk of developing tuberculosis (TB) with worse outcomes. This systematic review and meta-analysis aimed to investigate the outcomes of TB among international migrants arriving in Europe compared with the nonmigrant population. Methods: A systematic review and meta-analysis were conducted to identify studies investigating TB-related outcomes among migrants and nonmigrants in Europe. Six investigators searched PubMed, Scopus, and Web of Science from inception to March 2024 and screened the abstracts of potentially eligible articles. Studies reporting TB-related outcomes in both migrants and nonmigrants were also included. Studies with migrant definitions other than the one from the inclusion criteria, with no control group, and with no discernible data, including nonhuman samples or written in a non-English language, were excluded. Data were reported as relative risks (RRs) or odds ratios with their 95% confidence intervals (CIs). The risk of bias was assessed using the Newcastle–Ottawa Scale (PROSPERO Registration number: CRD42024529629). Results: Of the 1,109 papers screened, 34 were included, consisting of 601,293 participants (459,670 nonmigrants and 141,623 migrants). The meta-analysis, adjusted for potential confounders, showed that migrants presented a lower mortality risk (RR = 0.391, 95% CI: 0.276-0.554; P <0.0001; I2 = 71.6%), a lower rate of treatment completion (RR = 0.313; 95% CI: 0.163-0.600; P <0.0001), and a higher rate of loss to follow-up (RR = 4.331, 95% CI: 1.542-12.163, P = 0.005; I2 = 55.8%). Treatment success, cure, not evaluated, and sustained treatment success showed no significant differences between migrants and nonmigrants. No adjusted analyses could be performed for cure, not evaluated, and sustained treatment success. Only three studies had a high risk of bias. Conclusions: Migrants living in Europe have lower mortality rates; however, TB management is affected by a higher risk of loss to follow-up and discontinuation. Therefore, migrant-targeted TB care is necessary to improve the fight against TB in Europe

Point-of-care fresh CAR T cells for pediatric or young adult BCP-ALL that is relapsed/refractory or in very-high-risk first relapse

: The point-of-care, automated manufacturing of CAR T cells can reduce the waiting window and increase the therapy accessibility to patients with relapsed/refractory (r/r) BCP-ALL as compared to commercially available drug products (DP). We conducted a phase I/II trial (NCT04787263) on the use of 2nd generation (4.1BB), CD19-CAR T cells, for the treatment of BCP-ALL patients with either 1st relapse and very high-risk (VHR) characteristics or >2nd relapse and rapidly progressing disease preventing access to the commercial DP. CAR-T cells were manufactured with a 12-day process using CliniMACS Prodigy®, from a fresh apheresis and infused fresh. Three dose levels were tested in the phase I, namely 1.0, 2.0 and 3.0×106 CAR+T cells/kg. Nineteen pts were enrolled, 13/19 (68%) in first VHR relapse. The designed dose was always successfully produced. No dose-limiting toxicities were observed in the phase I. Grade 1-2 cytokine release syndrome was observed in 13/19 (68%) patients. Grade 1-2 immune effector cell-associated neurotoxicity syndrome occurred in 2 patients and resolved spontaneously. All patients achieved bone marrow complete remission with negative minimal residual disease. Eight pts (42%) received hematopoietic stem cell transplantation (HSCT) consolidation. Overall, CR was maintained in 13/19 patients (68%), 7 of them having received HSCT. Importantly, all patients but one treated with 3.0x106 CAR+T cells/kg maintain CR. The 3y-EFS and OS of the whole cohort are 68% and 83%, respectively. Our data suggest that the point-of-care, manufacturing of autologous, anti-CD19 CAR T cells can successfully treat patients with BCP-ALL including those with 1st relapse and VHR characteristics. (NCT04787263)

Novel Medicinal Mushroom Blend as a Promising Supplement in Integrative Oncology: A Multi-Tiered Study using 4T1 Triple-Negative Mouse Breast Cancer Model

Abstract: Although medicinal mushroomextracts have been proposed as promising anti-cancer agents, their precise impacts on metastatic breast cancer are still to be clarified. For this purpose, the present study exploited the eect of a novel medicinal mushroom blend, namely Micotherapy U-care, in a 4T1 triple-negative mouse breast cancer model. Mice were orally administered with Micotherapy U-care, consisting of a mixture of Agaricus blazei, Ophiocordyceps sinensis, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes. The syngeneic tumor-bearing mice were generated by injecting 4T1 cells in both supplemented and non-supplemented mice. After sacrifice 35 days later, specific endpoints and pathological outcomes of the murine pulmonary tissue were evaluated. (i) Histopathological and ultrastructural analysis and (ii) immunohistochemical assessment of TGF-ß1, IL-6 and NOS2, COX2, SOD1 as markers of inflammation and oxidative stress were performed. The QoL was comparatively evaluated. Micotherapy U-care supplementation, starting before 4T1 injection and lasting until the end of the experiment, dramatically reduced the pulmonary metastases density, also triggering a decrease of fibrotic response, and reducing IL-6, NOS, and COX2 expression. SOD1 and TGF-ß1 results were also discussed. These findings support the valuable potential of Micotherapy U-care as adjuvant therapy in the critical management of triple-negative breast cancer

Donor-derived GD2-specific CAR T cells in relapsed or refractory neuroblastoma

Allogeneic chimeric antigen receptor (CAR) T cells targeting disialoganglioside-GD2 (ALLO_GD2-CART01) could be a therapeutic option for patients with relapsed or refractory, high-risk neuroblastoma (r/r HR-NB) whose tumors did not respond to autologous GD2-CART01 or who have profound lymphopenia. We present a case series of five children with HR-NB refractory to more than three different lines of therapy who received ALLO_GD2-CART01 in a hospital exemption setting. Four of them had previously received allogeneic hematopoietic stem cell transplantation. All patients experienced grade 2 or 3 cytokine release syndrome and one grade 2 neurotoxicity. Moderate acute graft-versus-host-disease occurred in four patients. ALLO_GD2-CART01 persisted for >6 weeks. Post-treatment, two complete responses were achieved and one maintained; in addition, one partial response and one stable disease were observed. Comparing the transcriptomic profiles obtained by RNA sequencing analyses of drug products with patient-matched, peripheral blood ALLO_GD2-CART01 collected at expansion, we found upregulation of genes associated with T cell activation and migration. In addition, after infusion, transcriptomic signaling analysis showed enrichment of genes involved in response to decreased oxygen levels, humoral immune response, cell polarization and immune-synapse formation. In comparison to autologous CAR T cells, ALLO_GD2-CAR T cells were characterized by pathways associated with T cell proliferation, immune-synapse formation and cell chemotaxis. The safety and efficacy of ALLO_GD2-CART01 in children with r/r HR-NB deserve further investigation in a prospective trial