Decellularized aortic conduits: could their cryopreservation affect post-implantation outcomes? A morpho-functional study on porcine homografts

Decellularized porcine aortic valve conduits (AVCs) implanted in a Vietnamese Pig (VP) experimental animal model were matched against decellularized and then cryopreserved AVCs to assess the effect of cryopreservation on graft hemodynamic performance and propensity to in vivo repopulation by host\u2019s cells. VPs (n = 12) underwent right ventricular outflow tract substitution using AVC allografts and were studied for 15-month follow-up. VPs were randomized into two groups, receiving AVCs treated with decellularization alone (D; n = 6) or decellularization/cryopreservation (DC; n = 6), respectively. Serial echocardiography was carried out to follow up hemodynamic function. All explanted AVCs were processed for light and electron microscopy. No signs of dilatation, progressive stenosis, regurgitation, and macroscopic calcification were echocardiographically observed in both D and DC groups. Explanted D grafts exhibited near-normal features, whereas the presence of calcification, inflammatory infiltrates, and disarray of elastic lamellae occurred in some DC grafts. In the unaltered regions of AVCs from both groups, almost complete re-endothelialization was observed for both valve cusps and aorta walls. In addition, side-by-side repopulation by recipient\u2019s fibroblasts, myofibroblasts, and smooth muscle cells was paralleled by ongoing tissue remodeling, as revealed by the ultrastructural identification of typical canals of collagen fibrillogenesis and elastogenesis-related features. Incipient neo-vascularization and re-innervation of medial and adventitial tunicae of grafted aortic walls were also detected for both D and DC groups. Cryopreservation did not affect post-implantation AVC hemodynamic behavior and was topically propensive to cell repopulation and tissue renewal, although graft deterioration including calcification was present in several areas. Thus, these preliminary data provide essential information on feasibility of decellularization and cryopreservation coupling in the perspective of treatment optimization and subsequent clinical trials using similarly treated human allografts as innovative heart valve substitutes

Role of coronary microvascular dysfunction in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is one of the greatest unmet needs in modern medicine. The lack of an appropriate therapy may reflect the lack of an accurate comprehension of its pathophysiology. Coronary microvascular rarefaction in HFpEF was first hypothesized in an autopsy study that showed how HFpEF patients had lower microvascular density and more myocardial fibrosis than control subjects. This was later confirmed in vivo when it was noted that HFpEF is associated with reduced myocardial flow reserve (MFR) at single photon emission computed tomography (SPECT) and that coronary microvascular dysfunction may play a role in HFpEF disease processes. HFpEF patients were found to have lower coronary flow reserve (CFR) and a higher index of microvascular resistance (IMR). What is the cause of microvascular dysfunction? In 2013, a new paradigm for the pathogenesis of HFpEF has been proposed. It has been postulated that the presence of a proinflammatory state leads to coronary microvascular endothelial inflammation and reduced nitric oxide bioavailability, which ultimately results in heart failure. Recently, it has also been noted that inflammation is the main driver of HFpEF, but via an increase in inducible nitric oxide synthase (iNOS) resulting in a decrease in unfolded protein response. This review summarizes the current evidence on the etiology of coronary microvascular dysfunction in HFpEF, focusing on the role of inflammation and its possible prevention and therapy

Hybrid membranes for blood-contacting surfaces: preliminary characterization

The hemocompatibility of any mechanical circulatory support device is mostly conditioned by the nature of the blood-contacting surface. Hybrid membranes as the inner surfaces of the artificial ventricle were produced by coupling a polymeric material (polycarbonate urethane) with decellularized biological tissues (animal pericardia). Physicochemical and mechanical characteristics of the hybrid membranes were carefully evaluated confirming satisfactory features in terms of composition and mechanical resistance

An exploratory study into the role and interplay of intrinsic and extrinsic cues in Australian consumers’ evaluations of fish.

This study explores the role and interplay of intrinsic and extrinsic cues when evaluating fish quality and in shaping consumers' attitudes toward fish consumption. A sensory analysis of nine different fish including five variants of barramundi was conducted to determine how consumers evaluated the fish on intrinsic cues. Focus groups were then conducted to explore the impact of extrinsic cues on attitudes and purchase intentions. While the sensory analysis revealed distinct differences between barramundi variants on intrinsic cues (notably taste), the focus groups revealed that, as a brand, barramundi is perceived much more favourably and consistently. Consumers used extrinsic cues, particularly country of origin, as surrogate indicators of quality. Aquaculture producers need to ensure intrinsic product quality and consistency, as while consumers use the extrinsic cue of "Australian grown" as a surrogate indicator of quality, as their familiarity and confidence with seafood grows, this overreliance on extrinsic cues may diminish

Impact of a magnetic field on the thermodynamics of magnetized quark matter

We investigate the effect of a magnetic field on the thermodynamics of magnetized quark matter at finite temperature. By using the Nambu Jona-Lasino (NJL) model, we show that the lattice results for the quark consensate can be reproduced when the coupling constant G of the model decreases with the magnetic field and the temperature. Our results show that thermodynamic quantities and quark condensates are very sensitive to the dependence of G with the temperature, even in the absence of a magnetic field.We investigate the effect of a magnetic field on the thermodynamics of magnetized quark matter at finite temperature. By using the Nambu Jona-Lasino (NJL) model, we show that the lattice results for the quark consensate can be reproduced when the coupling706FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESC - FUNDAÇÃO DE AMPARO À PESQUISA E INOVAÇÃO DO ESTADO DE SANTA CATARINACNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçãosem informação13th International Workshop on Hadron PhysicsWe thank G. Endrodi for helpful discussions and for providing the lattice data for u and d quark condensates. We also thank FAEPEX, FAPESP, FAPESC and CNPq for financial support

Uracil/ftorafur/leucovorin combined with irinotecan (TEGAFIRI) or oxaliplatin (TEGAFOX) as first-line treatment for metastatic colorectal cancer patients: results of randomised phase II study

This randomised phase II study evaluates the safety and efficacy profile of uracil/tegafur/leucovorin combined with irinotecan (TEGAFIRI) or with oxaliplatin (TEGAFOX). One hundred and forty-three patients with measurable, non-resectable metastatic colorectal cancer were randomised in a multicentre study to receive TEGAFIRI (UFT 250 mg m−2 day days 1–14, LV 90 mg day days 1–14, irinotecan 240 mg m−2 day 1; q21) or TEGAFOX (UFT 250 mg m−2 day days 1–14, LV 90 mg day days 1–14, oxaliplatin 120 mg m−2 day 1; q21). Among 143 randomised patients, 141 were analysed (68 received TEGAFIRI and 73 TEGAFOX). The main characteristics of the two arms were well balanced. The most common grade 3–4 treatment-related adverse events were neutropenia (13% of cases with TEGAFIRI; 1% in the TEGAFOX group). Diarrhoea was prevalent in the TEGAFIRI arm (16%) vs TEGAFOX (4%). Six complete remission (CR) and 19 partial remission (PR) were recorded in the TEGAFIRI arm (odds ratio (OR): 41.7; 95% confidence limit (CL), 29.1–55.1%), and six CR and 22 PR were recorded in the TEGAFOX group, (OR: 38.9; 95% CL, 27.6–51.1). At a median time follow-up of 17 months (intequartile (IQ) range 12–23), a median survival probability of 20 and 19 months was obtained in the TEGAFIRI and TEGAFOX groups, respectively. Median time to progression was 8 months for both groups. TEGAFIRI and TEGAFOX are both effective and tolerable first-line therapies in MCRC patients. The employment of UFT/LV given in doublet combination is interesting and the presented data appear comparable to equivalent infusion regimens described in the literature. The safety profile of the two combinations also allows an evaluation with other biological agents such as monoclonal antibodies

Prognostic analysis and outcomes of metastatic pancreatic cancer patients receiving nab-paclitaxel plus gemcitabine as second or later-line treatment

Background: Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. Methods: The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. Results: AG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS. Conclusions: This study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy

Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC)

This study was performed to determine the activity of adding continuous infusion (CI) of 5-fluorouracil (5-FU) to gemcitabine (GEM) vs GEM alone in advanced pancreatic cancer (APC). In all, 94 chemo-naïve patients with APC were randomised to receive GEM alone (arm A: 1000 mg m−2 per week for 7 weeks followed by a 2 week rest period, then weekly for 3 consecutive weeks out of every 4 weeks) or in combination with CI 5-FU (arm B: CI 5-FU 200 mg m−2 day−1 for 6 weeks followed by a 2 week rest period, then for 3 weeks every 4 weeks). Overall response rate (RR) was the primary end point and criteria for decision were planned according to the Simon's optimal two-stage design. The overall RR was 8% (arm A) and 11% (arm B) (95% confidence interval: 0.5–16% and 2–22%), respectively, and stable disease was 29 and 28%. The median duration of RR was 34 weeks (range 25–101 weeks) for GEM and 26 weeks (range 16–46 weeks) for the combination. The median progression-free survival (PFS) was 14 weeks (range 2–65 weeks) and 18 weeks (range 4–51 weeks), respectively. The median overall survival (OS) was 31 weeks (range 1–101 weeks) and 30 weeks (1–101 weeks). Toxicity was mild in both arms. This study does not show promising activity in terms of RR, PFS and OS for the double combination arm in APC

A Massive Open Online Course on Particle Accelerators

International audienceThe TIARA (Test Infrastructure and Accelerator Research Area) project funded by the European Union 7th framework programme made a survey of provision of education and training in accelerator science in Europe. This survey highlighted the need for more training opportunities targeting undergraduate-level students. This need is now being addressed by the European Union H2020 project ARIES (Accelerator Research and Innovation for European Science and Society) via the preparation of a Massive Online Open Course (MOOC) on particle accelerator science and engineering. We present here the current status of this project, the main elements of the syllabus, how it will be delivered, and the schedule for providing the course