Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo^®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo^® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo^®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo^® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.     

UK food and nutrition security during and after the COVID‐19 pandemic

The COVID‐19 pandemic is a major shock to society in terms of health and economy that is affecting both UK and global food and nutrition security. It is adding to the ‘perfect storm’ of threats to society from climate change, biodiversity loss and ecosystem degradation, at a time of considerable change, rising nationalism and breakdown in international collaboration. In the UK, the situation is further complicated due to Brexit. The UK COVID‐19 Food and Nutrition Security project, lasting one year, is funded by the Economic and Social Research Council and is assessing the ongoing impact of COVID‐19 on the four pillars of food and nutrition security: access, availability, utilisation and stability. It examines the food system, how it is responding, and potential knock on effects on the UK’s food and nutrition security, both in terms of the cascading risks from the pandemic and other threats. The study provides an opportunity to place the initial lessons being learnt from the on‐going responses to the pandemic in respect of food and nutrition security in the context of other long‐term challenges such as climate change and biodiversity loss.     

Intracranial capillary hemangiomas: literature review in pediatric and adult population

Neurosurgical Review - Capillary hemangiomas (CHs) of the central nervous system represent a rare diagnosed pathology. CHs are benign vascular tumors whose most common manifestations are dermal and...     

The role of multiparametric MRI in active surveillance for low-risk prostate cancer: The ROMAS randomized controlled trial

BackgroundWe aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial.Materials and methodsBetween 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading.ResultsA total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001).ConclusionsThe early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy.     

Esophageal adenocarcinoma after sleeve gastrectomy: actual or potential threat? Italian series and literature review

BackgroundSleeve gastrectomy (SG) leads to esophageal mucosal damage in an elevated percentage of cases, configuring a clinical condition of Barrett’s esophagus (BE) in a proportion as high as 15–18.8%. BE may rarely evolve into esophageal adenocarcinoma (EAC).ObjectivesTo raise awareness of BE as a precancerous lesion which may progress toward malignancy after this popular bariatric procedure.SettingBariatric referral centers, Italy.MethodsAll patients referred to our bariatric center who developed an EAC after SG between 2012 and 2019 were reviewed and consecutively included in this study. The available scientific literature regarding this complication is additionally reviewed.ResultsThe 3 male patients comprised in this case series underwent laparoscopic SG between 2012 and 2015 in different bariatric referral centers. Age and body mass index at baseline ranged from 21–54 years and 43.1–75.6 kg/m², respectively. All patients were lost to follow-up early after surgery (3.7 ± 1.4 months), and were diagnosed with EAC at a mean of 27.3 ± 7.6 months after SG. The 4 reported cases in the scientific literature developed an EAC at a mean of 32.5 ± 23 months from SG. Overall, a diagnosis of EAC was made approximately 30.3 ± 17.1 months postoperatively, which seems relatively and worryingly early after surgery.ConclusionAlthough the rate and probability of progression from BE to EAC is still not well defined, assuming that the rising popularity and execution of SG leads to a growth in the BE incidence, then the preoperative identification and stratification of cancer risk factors in this subset of patients is strongly encouraged. Clinical and endoscopic follow-ups are essential to allow for prevention and early diagnosis and for epidemiologic data collection purposes.     

Reimbursement models to tackle market failures for antimicrobials: Approaches taken in France,Germany, Sweden,the United Kingdom,and the United States

IntroductionThe pipeline of new antibacterials remains limited. Reasons include low research investments, limited commercial prospects, and scientific challenges. To complement existing initiatives such as research grants, governments are exploring policy options for providing new market incentives to drug developers.Materials and methodsReimbursement interventions for antibacterials in France, Germany, Sweden, US, and UK were reviewed and analysed by the authors.ResultsIn France, Germany, and the US, implemented interventions centre on providing exceptions in cost-containment mechanisms to allow higher prices for certain antibacterials. In the US, also, certain antibacterials are granted additional years of protection from generic competition (exclusivity) and faster regulatory review. The UK is piloting a model that will negotiate contracts with manufacturers to pay a fixed annual fee for ongoing supply of as many units as needed. Sweden is piloting a model that will offer manufacturers of selected antibacterials contracts that would guarantee a minimum annual revenue. A similar model of guaranteed minimal annual revenues is under consideration in the US (PASTEUR Act).ConclusionsThe UK and Sweden are piloting entirely novel procurement and reimbursement models. Existing interventions in the US, France, and Germany represent important, but relatively minor interventions. More countries should explore the use of novel models and international coordination will be important for ‘pull’ incentives to be effective. If adopted, the PASTEUR legislation in the US would constitute a significant ‘pull’ incentive.     

SMC1 involvement in fragile site expression

Common fragile sites have been involved in neoplastic transformation, although their molecular basis is still poorly understood. Here, we demonstrate that inhibition of the SMC1 by RNAi is sufficient to induce fragile site expression. By investigating normal, ATM- and ATR-deficient cell lines, we provide evidence that the contribution of SMC1 in preventing the collapse of stalled replication fork is an Atr-dependent pathway. Using a fluorescent antibody specific for gamma-H2AX, we show that very rare discrete nuclear foci appear 1 and 2 h after exposure to aphidicolin and/or RNAi-SMC1, but became more numerous and distinct after longer treatment times. In this context, fragile sites might be viewed as an in vitro phenomenon originating from double-strand breaks formed because of a stalled DNA replication that lasted too long to be managed by physiological rescue acting through the Atr/Smc1 axis. We propose that in vivo, following an extreme replication block, rare cells could escape checkpoint mechanisms and enter mitosis with a defect in genome assembly, eventually leading to neoplastic transformation.     

An image-based modeling framework for patient-specific computational hemodynamics

We present a modeling framework designed for patient-specific computational hemodynamics to be performed in the context of large-scale studies. The framework takes advantage of the integration of image processing, geometric analysis and mesh generation techniques, with an accent on full automation and high-level interaction. Image segmentation is performed using implicit deformable models taking advantage of a novel approach for selective initialization of vascular branches, as well as of a strategy for the segmentation of small vessels. A robust definition of centerlines provides objective geometric criteria for the automation of surface editing and mesh generation. The framework is available as part of an open-source effort, the Vascular Modeling Toolkit, a first step towards the sharing of tools and data which will be necessary for computational hemodynamics to play a role in evidence-based medicine.     

Malignant thymoma in children: a 20-year review

Malignant thymomas are extremely rare in children, with only 27 cases reported thus far in the pediatric surgical literature. We report four additional cases diagnosed at this institution over the past 20 years (ages 3 to 14 years). Clinical presentations included superior vena cava syndrome, cough, dyspnea, cyanosis, enlarging mediastinal mass, spontaneous pneumothorax, and pleuropericardial effusion. Three patients underwent incomplete resection of the mass or biopsy because of "unresectability" and were treated with radiotherapy and adjunctive chemotherapy. One patient underwent near complete macroscopic resection as well as radiotherapy and chemotherapy. All patients died at intervals ranging from 6 months to 2 1/2 years after diagnosis. Three patients were found to have metastatic disease prior to death or at autopsy. In one case, the initial pathological diagnosis was lymphocytic thymoma. After ultrastructural studies were performed, the diagnosis was changed to thymic T-cell lymphoma. This patient subsequently developed acute lymphoblastic leukemia 3 months after surgical resection followed by radiotherapy. Malignant thymomas are highly aggressive tumors in children. A radical surgical approach with complete excision of the tumor and contiguous structures in continuity, with adjunctive radiotherapy and chemotherapy remains the only hope for survival in children with these rare lesions.