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Background: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation. Objectives: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM. Methods: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. Results: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007). Conclusions: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.

Cardiovascular disease remains an integral field on which new research in both the biomedical and technological fields is based, as it remains the leading cause of mortality and morbidity worldwide. However, despite the progress of cardiac imaging techniques, the heart remains a challenging organ to study. Artificial intelligence (AI) has emerged as one of the major innovations in the field of diagnostic imaging, with a dramatic impact on cardiovascular magnetic resonance imaging (CMR). AI will be increasingly present in the medical world, with strong potential for greater diagnostic efficiency and accuracy. Regarding the use of AI in image acquisition and reconstruction, the main role was to reduce the time of image acquisition and analysis, one of the biggest challenges concerning magnetic resonance; moreover, it has been seen to play a role in the automatic correction of artifacts. The use of these techniques in image segmentation has allowed automatic and accurate quantification of the volumes and masses of the left and right ventricles, with occasional need for manual correction. Furthermore, AI can be a useful tool to directly help the clinician in the diagnosis and derivation of prognostic information of cardiovascular diseases. This review addresses the applications and future prospects of AI in CMR imaging, from image acquisition and reconstruction to image segmentation, tissue characterization, diagnostic evaluation, and prognostication.

Recently, crowdsourcing has been proposed as a tool for fighting misinformation online. Will internet users listen to crowdsourced fact-checking, and how? In this experiment we test how participants follow others’ opinions to evaluate the validity of a science-themed Facebook post and examine which factors mediate the use of this information. Participants observed a post presenting either scientific information or misinformation, along with a graphical summary of previous participants’ judgements. Even though most participants reported not having used information from previous raters, their responses were influenced by previous assessments. This happened regardless of whether prior judgements were accurate or misleading. Presenting crowdsourced fact-checking however did not translate into the blind copying of the majority response. Rather, participants tended to use this social information as a cue to guide their response, while also relying on individual evaluation and research for extra information. These results highlight the role of individual reasoning when evaluating online information, while pointing to the potential benefit of crowd-sourcing-based solutions in making online users more resilient to misinformation.

Introduction. This study aimed to estimate the incidence of SARS-CoV-2 infection among pregnant women during the first pandemic wave in Italy, and to describe CO-VID-19 disease characteristics and maternal and perinatal outcomes. Materials and methods. National population-based prospective cohort study collecting information on women with SARS-CoV-2 diagnosis, confirmed within 7 days from hospital admission. Results. The national SARS-CoV-2 rate was 6.04 per 1,000 births (95% CI 5.62-6.49) among pregnant women and 7.54 (95% CI 7.47-7.61) among women in reproductive age. 72.1% of the cohort developed mild COVID-19 disease without pneumonia nor need for ventilatory support. Severe disease was significantly associated with women’s previous comorbidities (OR 2.55; 95% CI 0.98-6.90), obesity (OR 4.76; 95% CI 1.79-12.66) and citizenship from High Migration Pressure Countries (OR 3.43; 95% CI 1.27-9.25). Conclusions. During the first pandemic wave in Italy, the SARS-CoV-2 rate among pregnant women was lower compared to that detected among women of reproductive age, and risks of severe COVID-19 disease and adverse maternal and perinatal outcomes were rare.

The new coronavirus emergency spread to Italy when little was known about the infection’s impact on mothers and newborns. This study aims to describe the extent to which clinical practice has protected childbirth physiology and preserved the mother–child bond during the first wave of the pandemic in Italy. A national population-based prospective cohort study was performed enrolling women with confirmed SARS-CoV-2 infection admitted for childbirth to any Italian hospital from 25 February to 31 July 2020. All cases were prospectively notified, and information on peripartum care (mother–newborn separation, skin-to-skin contact, breastfeeding, and rooming-in) and maternal and perinatal outcomes were collected in a structured form and entered in a web-based secure system. The paper describes a cohort of 525 SARS-CoV-2 positive women who gave birth. At hospital admission, 44.8% of the cohort was asymptomatic. At delivery, 51.9% of the mothers had a birth support person in the delivery room; the average caesarean section rate of 33.7% remained stable compared to the national figure. On average, 39.0% of mothers were separated from their newborns at birth, 26.6% practised skin-to-skin, 72.1% roomed in with their babies, and 79.6% of the infants received their mother’s milk. The infants separated and not separated from their SARS-CoV-2 positive mothers both had good outcomes. At the beginning of the pandemic, childbirth raised awareness and concern due to limited available evidence and led to “better safe than sorry” care choices. An improvement of the peripartum care indicators was observed over time.

Background: Despite the low spatial resolution of 2D-multisegment late gadolinium enhancement (2D-MSLGE) sequences, it may be useful in uncooperative patients instead of standard 2D single segmented inversion recovery gradient echo late gadolinium enhancement sequences (2D-SSLGE). The aim of the study is to assess the feasibility and comparison of 2D-MSLGE reconstructed with artificial intelligence reconstruction deep learning noise reduction (NR) algorithm compared to standard 2D-SSLGE in consecutive patients with ischemic cardiomyopathy (ICM). Methods: Fifty-seven patients with known ICM referred for a clinically indicated CMR were enrolled in this study. 2D-MSLGE were reconstructed using a growing level of NR (0%,25%,50%,75%and 100%). Subjective image quality, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were evaluated in each dataset and compared to standard 2D-SSLGE. Moreover, diagnostic accuracy, LGE mass and scan time were compared between 2D-MSLGE with NR and 2D-SSLGE. Results: The application of NR reconstruction ≥50% to 2D-MSLGE provided better subjective image quality, CNR and SNR compared to 2D-SSLGE (p < 0.01). The best compromise in terms of subjective and objective image quality was observed for values of 2D-MSLGE 75%, while no differences were found in terms of LGE quantification between 2D-MSLGE versus 2D-SSLGE, regardless the NR applied. The sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 2D-MSLGE NR 75% were 87.77%,96.27%,96.13%,88.16% and 94.22%, respectively. Time of acquisition of 2D-MSLGE was significantly shorter compared to 2D-SSLGE (p < 0.01). Conclusion: When compared to standard 2D-SSLGE, the application of NR reconstruction to 2D-MSLGE provides superior image quality with similar diagnostic accuracy.

Aims: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients. Methods and results: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction [removed]3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort. Conclusion: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation.

Introduction. The study was implemented to provide guidance to decision-makers and clinicians by describing hospital care offered to women who gave birth with confirmed SARS-CoV-2 infection. Materials and methods. National population‐based prospective cohort study involving all women with confirmed SARS-CoV-2 infection who gave birth between February 25 and April 22, 2020 in any Italian hospital. Results. The incidence rate of confirmed SARS-CoV-2 infection in women who gave birth was 2.1 per 1000 maternities at a national level and 6.9/1000 in the Lombardy Region. Overall one third of the women developed a pneumonia and 49.7% assumed at least one drug against SARS-CoV-2 infection. Caesarean rate was 32.9%, no mothers nor newborns died. Six percent of the infants tested positive for SARS-CoV-2 at birth. Conclusions. Clinical features and outcomes of COVID-19 in women who gave birth are similar to those described for the general population, most women developing mild to moderate illness.

Stress computed tomography perfusion (Stress-CTP) and computed tomography-derived fractional flow reserve (FFRCT) are functional techniques that can be added to coronary computed tomography angiography (cCTA) to improve the management of patients with suspected coronary artery disease (CAD). This retrospective analysis from the PERFECTION study aims to assess the impact of their availability on the management of patients with suspected CAD scheduled for invasive coronary angiography (ICA) and invasive FFR. The management plan was defined as optimal medical therapy (OMT) or revascularization and was recorded for the following strategies: cCTA alone, cCTA+FFRCT, cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP. In 291 prospectively enrolled patients, cCTA+FFRCT, cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP showed a similar rate of reclassification of cCTA findings when FFRCT and Stress-CTP were added to cCTA. cCTA, cCTA+FFRCT, cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP showed a rate of agreement versus the final therapeutic decision of 63%, 71%, 89%, 84% (cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP vs cCTA and cCTA+FFRCT: p < 0.01), respectively, and a rate of agreement in terms of the vessels to be revascularized of 57%, 64%, 74%, 71% (cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP vs cCTA and cCTA+FFRCT: p < 0.01), respectively, with an effective radiation dose (ED) of 2.9 ± 1.3 mSv, 2.9 ± 1.3 mSv, 5.9 ± 2.7 mSv, and 3.1 ± 2.1 mSv. The addition of FFRCT and Stress-CTP improved therapeutic decision-making compared to cCTA alone, and a sequential strategy with cCTA+FFRCT+Stress-CTP represents the best compromise in terms of clinical impact and radiation exposure.

Staphylococcus lugdunensis is a coagulase-negative Staphylococcus that emerges as an important opportunistic pathogen. However, little is known about the regulation underlying the transition from commensal to virulent state. Based on knowledge of S. aureus virulence, we suspected that the agr quorum sensing system may be an important determinant for the pathogenicity of S. lugdunensis. We investigated the functions of the transcriptional regulator AgrA using the agrA deletion mutant. AgrA played a role in cell pigmentation: DargA mutant colonies were white while the parental strains were slightly yellow. Compared with the wild-type strain, the DargA mutant was affected in its ability to form biofilm and was less able to survive in mice macrophages. Moreover, the growth of DagrA was significantly reduced by the addition of 10% NaCl or 0.4 mM H2O2 and its survival after 2 h in the presence of 1 mM H2O2 was more than 10-fold reduced. To explore the mechanisms involved beyond these phenotypes, the DagrA proteome and transcriptome were characterized by mass spectrometry and RNA-Seq. We found that AgrA controlled several virulence factors as well as stress-response factors, which are well correlated with the reduced resistance of the DagrA mutant to osmotic and oxidative stresses. These results were not the consequence of the deregulation of RNAIII of the agr system, since no phenotype or alteration of the proteomic profile has been observed for the DRNAIII mutant. Altogether, our results highlighted that the AgrA regulator of S. lugdunensis played a key role in its ability to become pathogenic.

Disinformation about science can impose enormous economic and public health burdens. A recently proposed strategy to help online users recognise false content is to follow the techniques of professional fact checkers, such as looking for information on other websites (lateral reading) and looking beyond the first results suggested by search engines (click restraint). In two preregistered online experiments (N = 5387), we simulated a social media environment and tested two interventions, one in the form of a pop-up meant to advise participants to follow such techniques, the other based on monetary incentives. We measured participants’ ability to identify whether information was scientifically valid or invalid. Analysis of participants’ search style reveals that both monetary incentives and pop-up increased the use of fact-checking strategies. Monetary incentives were overall effective in increasing accuracy, whereas the pop-up worked when the source of information was unknown. Pop-up and incentives, when used together, produced a cumulative effect on accuracy. We suggest that monetary incentives enhance content relevance, and could be combined with fact-checking techniques to counteract disinformation.

Staphylococcus lugdunensis is a coagulase-negative Staphylococcus that emerges as an important opportunistic pathogen. However, little is known about the regulation underlying the transition from commensal to virulent state. Based on knowledge of S. aureus virulence, we suspected that the agr quorum sensing system may be an important determinant for the pathogenicity of S. lugdunensis. We investigated the functions of the transcriptional regulator AgrA using the agrA deletion mutant. AgrA played a role in cell pigmentation: DargA mutant colonies were white while the parental strains were slightly yellow. Compared with the wild-type strain, the DargA mutant was affected in its ability to form biofilm and was less able to survive in mice macrophages. Moreover, the growth of DagrA was significantly reduced by the addition of 10% NaCl or 0.4 mM H2O2 and its survival after 2 h in the presence of 1 mM H2O2 was more than 10-fold reduced. To explore the mechanisms involved beyond these phenotypes, the DagrA proteome and transcriptome were characterized by mass spectrometry and RNA-Seq. We found that AgrA controlled several virulence factors as well as stress-response factors, which are well correlated with the reduced resistance of the DagrA mutant to osmotic and oxidative stresses. These results were not the consequence of the deregulation of RNAIII of the agr system, since no phenotype or alteration of the proteomic profile has been observed for the DRNAIII mutant. Altogether, our results highlighted that the AgrA regulator of S. lugdunensis played a key role in its ability to become pathogenic.

Objective: The aim of this paper is to investigate the use of fully convolutional neural networks (FCNNs) to segment scar tissue in the left ventricle from cardiac magnetic resonance with late gadolinium enhancement (CMR-LGE) images. Methods: A successful FCNN in the literature (the ENet) was modified and trained to provide scar-tissue segmentation. Two segmentation protocols (Protocol 1 and Protocol 2) were investigated, the latter limiting the scar-segmentation search area to the left ventricular myocardial tissue region. CMR-LGE from 30 patients with ischemic-heart disease were retrospectively analyzed, for a total of 250 images, presenting high variability in terms of scar dimension and location. Segmentation results were assessed against manual scar-tissue tracing using one-patient-out cross validation. Results: Protocol 2 outperformed Protocol 1 significantly (p value < 0.05), with median sensitivity and Dice similarity coefficient equal to 88.07% [inter-quartile range (IQR) 18.84%] and 71.25% (IQR 31.82%), respectively. Discussion: Both segmentation protocols were able to detect scar tissues in the CMR-LGE images but higher performance was achieved when limiting the search area to the myocardial region. The findings of this paper represent an encouraging starting point for the use of FCNNs for the segmentation of nonviable scar tissue from CMR-LGE images.

Ce rapport présente les fiches descriptives des 32 unités d’habitats de niveau 3 (biocénose) et 119 unités de niveau 4 (faciès et associations) de la typologie des biocénoses benthiques de Méditerranée version 2, pour servir d’outil d’aide à l’identification et la conservation des habitats. Les habitats ont été décrits sur la base des descriptions existantes dans d’autres typologies complétées par les connaissances disponibles. Ce travail a également permis de mettre à jour la typologie pour suivre les évolutions taxonomiques des espèces caractéristiques, clarifier des libellés d’unité et supprimer un faciès. Toutes les fiches descriptives sont également disponibles en ligne sur les pages habitats de l’INPN.

Ce rapport présente les fiches descriptives des 32 unités d’habitats de niveau 3 (biocénose) et 119 unités de niveau 4 (faciès et associations) de la typologie des biocénoses benthiques de Méditerranée version 2, pour servir d’outil d’aide à l’identification et la conservation des habitats. Les habitats ont été décrits sur la base des descriptions existantes dans d’autres typologies complétées par les connaissances disponibles. Ce travail a également permis de mettre à jour la typologie pour suivre les évolutions taxonomiques des espèces caractéristiques, clarifier des libellés d’unité et supprimer un faciès. Toutes les fiches descriptives sont également disponibles en ligne sur les pages habitats de l’INPN.

The aim of this systematic review is to collect clinical trials conducted using essential oils (EOs) in obstetric symptoms by evaluating if and in which context the aromatherapy practice is effective in obstetrics. The research was conducted by using the databases of EMBASE, Medline, Biosis and Toxcenter, PubMed, and Google Scholar search engine, selecting articles from January 2004 to July 2020. This study was performed according to the MOOSE and PRISMA guidelines. Only the randomized clinical trials were considered, and in cases of multiple publications, it was considered the most up to date information. Biases were highlighted. In the presence of homogeneous data, pooling statistics and meta-analysis were applied. The research led to 71 articles, 17 of which were eligible. Among the trials selected, eight investigated the effectiveness of EOs on anxiety, depression, and stress. Two concerned the treatment of nausea and vomiting, six evaluated the application of EOs on labor for pain treatment, and two showed the effectiveness in the treatment of episiotomy. The heterogeneity of works carried out so far has made it possible to develop a meta-analysis only in the field of pain treatment during childbirth, identifying the effectiveness of the EOs Lavandula spp. and Rosa damascena.

Along most Mediterranean coasts, the endemic seagrass species Posidonia oceanica builds extensive meadows and complex peat-like bioconstruction known as ‘mattes’. These belowground deposits are recognized as a valuable long-term archive allowing the reconstruction and the study of palaeo-climatic and palaeo-ecological changes in the coastal environment over the Holocene period. One of the P. oceanica matte cores sampled during a coring survey along the eastern continental shelf of Corsica Island (France, NW Mediterranean) revealed the unprecedented finding of a dead bank of the scleractinian coral Cladocora caespitosa embedded in the matte. Measurement of the morphological and biometrical features of corallite fragments coupled to biogeosedimentological analysis and radiocarbon dating contributed to provide a basis for the reconstruction of the stratigraphic sequence since the mid-Holocene (last 4750 years). The study of the sediment core enabled identification of three major phases: (i) the settlement of the C. caespitosa colonies (~4750-3930 cal yr BP), (ii) the coexistence of the C. caespitosa bank and the P. oceanica meadow (~3930-1410 cal yr BP), followed by (iii) the death of the coral bank and the development of only the P. oceanica meadow (~1410 cal yr BP-present). The sclerochronological analysis completed on the well-preserved corallite fragments revealed that the mean annual growth rate of the coral ranged between 1.9 and 3.1 mm yr− 1 with a mean value estimated at 2.3 ± 0.8 mm yr− 1 . Trend analysis showed semi-millennial to millennial oscillations in annual growth rates which are probably related to environmental climatic changes since the Cold Phase of the Subatlantic period (2925-2200 cal yr BP). During the Roman Warm Period (2200-1500 cal yr BP), the decline and the death of the bank (~1410 cal yr BP) was probably due to the combined effect of a prolonged increase in summer temperatures and an increase in the competition with the P. oceanica meadow.

Rationale and objectives: A new postprocessing algorithm named adaptive statistical iterative reconstruction (ASIR)-V has been recently introduced. The aim of this article was to analyze the impact of ASIR-V algorithm on signal, noise, and image quality of coronary computed tomography angiography. Materials and Methods: Fifty consecutive patients underwent clinically indicated coronary computed tomography angiography (Revolution CT; GE Healthcare, Milwaukee, WI). Images were reconstructed using filtered back projection and ASIR-V 0%, and a combination of filtered back projection and ASIR-V 20%–80% and ASIR-V 100%. Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated for left main coronary artery (LM), left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) and were compared between the different postprocessing algorithms used. Similarly a four-point Likert image quality score of coronary segments was graded for each dataset and compared. A cutoff value of P <.05 was considered statistically significant. Results: Compared to ASIR-V 0%, ASIR-V 100% demonstrated a significant reduction of image noise in all coronaries (P <.01). Compared to ASIR-V 0%, SNR was significantly higher with ASIR-V 60% in LM (P <.01), LAD (P <.05), LCX (P <.05), and RCA (P <.01). Compared to ASIR-V 0%, CNR for ASIR-V ≥60% was significantly improved in LM (P <.01), LAD (P <.05), and RCA (P <.01), whereas LCX demonstrated a significant improvement with ASIR-V ≥80%. ASIR-V 60% had significantly better Likert image quality scores compared to ASIR-V 0% in segment-, vessel-, and patient-based analyses (P <.01). Conclusions: Reconstruction with ASIR-V 60% provides the optimal balance between image noise, SNR, CNR, and image quality.

Tumour vasculature supports the growth and progression of solid cancers with both angiogenesis (endothelial cell proliferation) and vasculogenic mimicry (VM, the formation of vascular structures by cancer cells themselves) predictors of poor patient outcomes. Increased circulating platelet counts also predict poor outcome for cancer patients but the influence of platelets on tumour vasculature is incompletely understood. Herein, we show with in vitro assays that platelets did not influence angiogenesis but did actively inhibit VM formation by cancer cell lines. Both platelet sized beads and the releasates from platelets were partially effective at inhibiting VM formation suggesting that direct contact maximises the effect. Platelets also promoted cancer cell invasion in vitro. B16F10 melanomas in Bcl-xPlt20/Plt20 thrombocytopenic mice showed a higher content of VM than their wildtype counterparts while angiogenesis did not differ. In a xenograft mouse model of breast cancer with low-dose aspirin to inactivate the platelets, the burden of MDA-MB-231-LM2 breast cancer cells was reduced and the gene expression profile of the cancer cells was altered; but no effect on tumour vasculature was observed. Taken together, this study provides new insights into the action of platelets on VM formation and their involvement in cancer progression.

Salmonella spp. represent a public health concern for humans and animals due to the increase of antibiotic resistances. In this scenario, the use of essential oils (EOs) could be a valid tool against Salmonella contamination of meat. This work compares the in vitro effectiveness of an Italian mixture of feed additives based on EOs (GR-OLI) with EO of Origanum vulgare L., recently admitted by European Food Safety Authority (EFSA) for animal use. Twenty-nine Salmonella serotypes isolated from poultry and pig farms were used to assess GR-OLI and O. vulgare EO antimicrobial propeties. O. vulgare EO was active on the disaggregation of mature biofilm, while GR-OLI was capable of inhibiting biofilm formation and disaggregating preformed biofilm. Furthermore, GR-OLI inhibited bacterial adhesion to Caco-2 cells in a dose-dependent manner. Both products showed inhibition of bacterial growth at all time points tested. Finally, the synergistic action of GR-OLI with commonly used antibiotics against resistant strains was investigated. In conclusion, the mixture could be used both to reduce the meat contamination of Salmonella spp. before slaughter, and in synergy with low doses of ciprofloxacin against resistant strains. Although EOs as feed additives are already used in animal husbandry, no scientific study has ever highlighted their real antimicrobial potential.

High-resolution seismic reflection data have been used over the last decades to estimate the thickness of the long-term Blue Carbon sink associated to the below-ground sediment deposit (matte) of the Posidonia oceanica meadows. Time-to-depth conversion of these geophysical datasets was usually performed assuming a sound velocity in this structure, but appropriate seismic interval velocity measurements is necessary to achieve accurate calibration. This study describes the first methodology to estimate the seismic interval velocity in the matte. This approach performed on the eastern continental shelf of Corsica island (France, NW Mediterranean) is based on measurements of the vertical matte profile from high-resolution seismic reflection profiles (s TWTT) and from seafloor morpho-bathymetric DTM (multibeam echosounders - MBES and Light Detection and Ranging - LiDAR surveys) calibrated with ground-truthing data. A biogeosedimentological analysis of horizontal cores sampled in vertical matte escarpments has been undertaken to identify the potential relationship of sediment and environmental parameters with sound velocity. The cross-comparison and the data intercalibration show significant correlation of MBES (R2 = 0.872) and LiDAR datasets (R2 = 0.883) with direct underwater measurements. Seismic interval velocities (n = 367) have been found to range between 1631.9 and 1696.8 m s−1 (95% confidence interval) and are estimated on average at 1664.4 m s−1, which is similar to the literature for unconsolidated marine sediments. The prediction map provided by the ordinary kriging method emphasized, however, a high variability of sound velocity within the study area. The results showed that changes in sound velocity in the matte are positively and strongly correlated with sand and gravel content and environmental factors such as distance to coastal river mouths and coastline. However, it was found that a negative relationship linked sound velocity with total and coarse organi

Infections caused by Enterococcus spp. are a major concern in the clinical setting. In Enterococcus faecalis, the capsular polysaccharide diheteroglycan (DHG), composed of ß-d-galactofuranose-(1 → 3)-ß-d-glucopyranose repeats, has been described as an important virulence factor and as a potential vaccine candidate against encapsulated strains. Synthetic structures emulating immunogenic polysaccharides present many advantages over native polysaccharides for vaccine development. In this work, we described the synthesis of a library of DHG oligomers, differing in length and order of the monosaccharide constituents. Using suitably protected thioglycoside building blocks, oligosaccharides up to 8-mer in length built up from either Galf-Glcp or Glcp-Galf dimers were generated, and we evaluated their immunoreactivity with antibodies raised against DHG. After the screening, we selected two octasaccharides, having either a galactofuranose or glucopyranose terminus, which were conjugated to a carrier protein for the production of polyclonal antibodies. The resulting antibodies were specific toward the synthetic structures and mediated in vitro opsonophagocytic killing of different encapsulated E. feacalis strains. The evaluated oligosaccharides are the first synthetic structures described to elicit antibodies that target encapsulated E. faecalis strains and are, therefore, promising candidates for the development of a well-defined enterococcal glycoconjugate vaccine.

The most prevalent cause of nosocomial bloodstream infection (BSI) among non-C. albicans Candida species, Candida parapsilosis, may not only be resistant to azole antifungal agents but also disseminate to vulnerable patients. In this survey of BSIs occurring at a large Italian hospital between May 2014 and May 2019, C. parapsilosis accounted for 28.5% (241/844) of all Candida isolates causing BSI episodes. The majority of episodes (151/844) occurred in medical wards. Across the 5 yearly periods, the rates of azole non-susceptibility were 11.8% (4/34), 17.8% (8/45), 28.6% (12/42), 32.8% (19/58), and 17.7% (11/62), respectively, using the Sensititre YeastOne® method. Among azole non-susceptible isolates (54/241; 22.4%), 49 were available for further investigation. Using the CLSI reference method, all 49 isolates were resistant to fluconazole and, except one (susceptible dose-dependent), to voriconazole. Forty (81.6%) isolates harbored the Erg11p Y132F substitution and nine (18.4%) isolates the Y132F in combination with the Erg11p R398I substitution. According to their genotypes, as defined using a microsatellite analysis based on six short tandem repeat markers, 87.7% of isolates (43/49) grouped in two major clusters (II and III), whereas 4.1% of isolates (2/49) belonged to a separate cluster (I). Interestingly, all the isolates from cluster II harbored the Y132F substitution, and those from cluster III harbored both Y132F and R398I substitutions. Of 56 non-Italian isolates included as controls, two Indian isolates with the Y132F substitution had a genotype clearly differing from that of the isolates from clusters II and I. In conclusion, these findings show the dominance of clonal Y132F isolates in our hospital and suggest detection of the Y132F substitution as helpful tool to prevent transmission among hospitalized patients at risk of BSI.

The aim of this study was to evaluate the antibacterial properties of graphene oxide (GO) against Enterococcus faecalis in vitro conditions and when used to coat dentin surface to prevent E. faecalis adhesion. The ATCC strain of E. faecalis 29212 has been used to perform a viability test. The pellet was suspended in ultrapure water, NaCl, PBS buffer, CaCl2 and MgCl2, Luria−Bertani broth solutions. The viability was evaluated by the colony forming unit counting method. Atomic force microscopy images and the measure of surface zeta potential variation were analyzed. Dentin discs were covered with a film of GO (n = 15) or were not treated (n = 15). Bacterial suspension was added to each sample of dentine discs and microbial counts were calculated. Statistically significant differences between two groups were assessed by a two‐tailed unpaired t‐test. Bacteria cell morphology was investigated with scanning electron microscopy. The highest growth inhibition was obtained in ddH2O and CaCl2 solution while, in PBS and NaCl, GO had poor antibacterial efficacy with a growth enhancing effect in the latter. GO on dentin discs demonstrated high antibacterial activity. GO film has demonstrated acceptable adhesion properties to root dentin and a role in the inhibition of bacterial film proliferation and biofilm formation.

Background: In many cases of pancreatic adenocarcinoma (PDAC), the diagnosis comes as a surprise to the patient, who often faces a disease that is already at an advanced stage, with poor prognosis. The clinical visit during which the diagnosis is communicated together with the first information regarding the planned treatments is of paramount importance. We hypothesize that the clarity of such information can influence patients’ engagement and thus their level of compliance. Aims: This study aims to collect (a) quantitative data on the level of PDAC patient engagement, (b) data on the rate of understanding of the information received from the doctor, and (c) data on level of compliance; the possible associations between these variables will be analyzed. Methods: This is a single-center, observational, cross-sectional cohort study on patients diagnosed with PDAC, approved by the Ethics Committee of the San Raffaele Hospital. As no preliminary data are available on the association between PDAC patients’ understanding rate and their level of engagement and of compliance, no power calculation is possible. This is a pilot study, aimed at enrolling at least 45 PDAC patients during a period of 3 months. Conclusion: COMMUNIcation and Patient Engagement at Diagnosis of PAncreatic CAncer (COMMUNI. CARE) will be the first study specifically investigating whether there is a relation between PDAC patients’ engagement, rate of understanding at the time of diagnosis, and compliance.

This work focuses on the comparison of microstructure and tribological behaviour (dry sliding vs. 100Cr6 steel) of anodic layers produced on wrought AA6082-T5 by hard anodizing (HA), plasma electrolytic oxidation (PEO, sometimes also termed MAO, Micro-Arc Oxidation) and novel electro-chemical oxidation (ECO), derived from PEO minimising its disruptive plasma discharge. The results showed that PEO and HA do not decrease the coefficient of friction of AA6082, whilst ECO does (particularly after sealing with a phosphate-based solution), thanks to its smooth surface and decreased stability of Fe–O based transfer layers. All the anodizing treatments improve wear resistance of AA6082: ECO showed the highest wear resistance, due to the beneficial combination of compact microstructure, high and uniform thickness, high microhardness and adhesion.

Contains fulltext : 203309.pdf (publisher's version ) (Closed access)

Contains fulltext : 203309.pdf (publisher's version ) (Closed access)

Contains fulltext : 203309.pdf (publisher's version ) (Closed access)

Anthropogenic climate change, and global warming in particular, has strong and increasing impacts on marine ecosystems (Poloczanska et al., 2013; Halpern et al., 2015; Smale et al., 2019). The Mediterranean Sea is considered a marine biodiversity hot-spot contributing to more than 7% of world's marine biodiversity including a high percentage of endemic species (Coll et al., 2010). The Mediterranean region is a climate change hotspot, where the respective impacts of warming are very pronounced and relatively well documented (Cramer et al., 2018). One of the major impacts of sea surface temperature rise in the marine coastal ecosystems is the occurrence of mass mortality events (MMEs). The first evidences of this phenomenon dated from the first half of'80 years affecting the Western Mediterranean and the Aegean Sea (Harmelin, 1984; Bavestrello and Boero, 1986; Gaino and Pronzato, 1989; Voultsiadou et al., 2011). The most impressive phenomenon happened in 1999 when an unprecedented large scale MME impacted populations of more than 30 species from different phyla along the French and Italian coasts (Cerrano et al., 2000; Perez et al., 2000). Following this event, several other large scale MMEs have been reported, along with numerous other minor ones, which are usually more restricted in geographic extend and/or number of affected species (Garrabou et al., 2009; Rivetti et al., 2014; Marbà et al., 2015; Rubio-Portillo et al., 2016, authors' personal observations). These events have generally been associated with strong and recurrent marine heat waves (Crisci et al., 2011; Kersting et al., 2013; Turicchia et al., 2018; Bensoussan et al., 2019) which are becoming more frequent globally (Smale et al., 2019). Both field observations and future projections using Regional Coupled Models (Adloff et al., 2015; Darmaraki et al., 2019) show the increase in Mediterranean sea surface temperature, with more frequent occurrence of extreme ocean warming events. As a result, new MMEs ar

The microbial infection of the endodontic space occurs in a necrotic tooth as a result of dental caries, trauma, periodontal disease, or previous root canal therapy. The disruption of the biofilms and the reduction of the bacterial load inside root canals are crucial for the success of root canal therapy. The aim of this study was to compare, in vitro, the antibiofilm efficacy of a novel passive sonic irrigation (PSI) device with passive ultrasonic irrigation (PUI) and conventional needle irrigation (CNI). Forty-four single-rooted human teeth were inoculated with a culture of E. faecalis for 28 days. The specimens were randomly divided into three groups: PUI, CNI, and PSI (n = 12). The activation protocols were performed using both 17% EDTA and 5.25% NaOCl. Residual bacterial biofilm was taken by means of a canal brush and colony-forming unit (CFU) were counted. The data were analyzed using one-way ANOVA and Games-Howell's post hoc tests. A major reduction in CFU was observed in the PSI and PUI groups, in comparison with the CNI group. No difference was found (p > 0.05) in terms of CFU reduction between PSI and PUI. PSI could be as effective as PUI in the removal of bacterial biofilms from straight root canals.

Enterococci have emerged as important nosocomial pathogens due to their resistance against the most commonly used antibiotics. Alternative treatments or prevention options are aimed at polysaccharides and surface-related proteins that play important roles in pathogenesis. Previously, we have shown that two Enterococcus faecium proteins, the secreted antigen A and the peptidyl-prolyl cis-trans isomerase, as well as the Enterococcus faecalis polysaccharide diheteroglycan are able to induce opsonic and cross-protective antibodies. Here, we evaluate the use of glycoconjugates consisting of these proteins and an enterococcal polysaccharide to develop a vaccine with broader strain coverage. Diheteroglycan was conjugated to these two enterococcal proteins. Rabbit sera raised against these glycoconjugates showed IgG titers towards the corresponding conjugate, as well as to the respective protein and carbohydrate antigens. Effective opsonophagocytic killing for the two sera was observed against different E. faecalis and E. faecium strains. ELISA against whole bacterial cells showed immune recognition of the sera towards 22 enterococcal strains. Moreover, sera conferred protection in a mouse infection model against E. faecalis and E. faecium strains. Our results suggest that these glycoconjugates are promising candidates for vaccine formulations with a broader coverage against these nosocomial pathogens and that the evaluated proteins are potential carrier proteins.

We designed new 3-arylthio- and 3-aroyl-1H-indole derivatives 3–22 bearing a heterocyclic ring at position 5, 6 or 7 of the indole nucleus. The 6- and 7-heterocyclyl-1H-indoles showed potent inhibition of tubulin polymerization, binding of colchicine to tubulin and growth of MCF-7 cancer cells. Compounds 13 and 19 inhibited a panel of cancer cells and the NCI/ADR-RES multidrug resistant cell line at low nanomolar concentrations. Compound 13 at 50 nM induced 77% G2/M in HeLa cells, and at 20 nM caused 50% stable arrest of mitosis. As an inhibitor of HepG2 cells (IC50 = 20 nM), 13 was 4-fold superior to 19. Compound 13 was a potent inhibitor of the human U87MG glioblastoma cells at nanomolar concentrations, being nearly one order of magnitude superior to previously reported arylthioindoles. The present results highlight 13 as a robust scaffold for the design of new anticancer agents.

Today, liposomes are an advanced technology of drug carriers with a dozen drugs in clinical practice and many more in clinical trials. A bottleneck associated with the clinical translation of liposomes has long been 'opsonization', i.e. the adsorption of plasma proteins at the liposome surface resulting in their rapid clearance from circulation. For decades, the most popular way to avoid opsonization has been grafting polyethylene glycol (PEG) onto the liposome surface. Recent studies have clarified that grafting PEG onto the liposome surface reduces, but does not completely prevent protein binding. In this work, we employed dynamic light scattering, zeta-potential analysis, one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE), semi-quantitative densitometry and cell imaging to explore the bio-nano-interactions between human plasma (HP) and Onivyde, a PEGylated liposomal drug that has recently been approved by the Food and Drug Administration (FDA) for the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). To properly evaluate the role of PEGylation, an unPEGylated variant of Onivyde was used as a reference. Collectively, our findings suggest that: (i) although PEGylated, Onivyde is not "stealth" in HP; (ii) surface chemistry is more important than PEGylation in controlling the bio-nano-interactions between Onivyde and plasma components. Of note is that the PC was found to boost the cellular uptake of Onivyde in the pancreas ductal adenocarcinoma cell line (PANC-1) thus suggesting its prominent role in its indication for PDAC treatment. Relevant implications for drug delivery and drug design are discussed.

A specific split liver transplantation (SLT) program has been pursued in the North Italian Transplant program (NITp) since November 1997. After 5 yr, 1,449 liver transplants were performed in 7 transplant centers, using 1,304 cadaveric donors. Whole liver transplantation (WLT) and SLT were performed in 1, 126 and 323 cases, respectively. SLTs were performed in situ as 147 left lateral segments (LLS), 154 right trisegment liver (RTL) grafts, and 22 modified split livers (MSL), used for couples of adult recipients. After a median posttransplant follow-up of 22 months, SLTs achieved a 3-yr patient and graft survival not significantly different from the entire series of transplants (79.4 and 72.2% vs. 80.6 and 74.9%, respectively). Recipients receiving a WLT or a LLS showed significantly better outcomes than patients receiving RTL and MSL (P < 0.03 for patients and P < 0.04 for graft survival). At the multivariate analysis, donor age of > 60 yr, RTL transplant, < 50 annual transplants volume, urgent transplantation (United Network for Organ Sharing (UNOS) status I and IIA), ischemia time of > 7 hours, and retransplantation were factors independently related to graft failure and to significantly worst patient survival. Right grafts procured from RTL and either split procured as MSL had a similar outcome of marginal whole livers. In conclusion, in 5 yr, the increased number of pediatric transplants due to split liver donation reduced to 3% the in-list children mortality, and a decrease in the adult patient dropout rate from 27.2 to 16.2% was observed. Such results justify a more widespread adoption of SLT protocols, organizational difficulties not being a limit for the application of such technique.

© 2015 Elsevier Masson SAS. Aggressive behavior and diffuse infiltrative growth are the main features of Glioblastoma multiforme (GBM), together with the high degree of resistance and recurrence. Evidence indicate that GBM-derived stem cells (GSCs), endowed with unlimited proliferative potential, play a critical role in tumor development and maintenance. Among the many signaling pathways involved in maintaining GSC stemness, tumorigenic potential, and anti-apoptotic properties, the PDK1/Akt pathway is a challenging target to develop new potential agents able to affect GBM resistance to chemotherapy. In an effort to find new PDK1/Akt inhibitors, we rationally designed and synthesized a small family of 2-oxindole derivatives. Among them, compound 3 inhibited PDK1 kinase and downstream effectors such as CHK1, GS3Ka and GS3Kß, which contribute to GCS survival. Compound 3 appeared to be a good tool for studying the role of the PDK1/Akt pathway in GCS self-renewal and tumorigenicity, and might represent the starting point for the development of more potent and focused multi-target therapies for GBM.

Bioconstructions such as coralligenous outcrops and maerl beds are typical Mediterranean underwater seascapes. Fine-scale knowledge on the distribution of these sensitive habitats is crucial for their effective management and conservation. In the present study, a thorough review of existing spatial datasets showing the distribution of coralligenous and maerl habitats across the Mediterranean Sea was undertaken, highlighting current gaps in knowledge. Predictive modelling was then carried out, based on environmental predictors, to produce the first continuous maps of these two habitats across the entire basin. These predicted occurrence maps for coralligenous outcrops and maerl beds provide critical information about where the two habitats are most likely to occur. The collated occurrence data and derived distribution model outputs can help addressing the challenge of developing basin-wide spatial plans and to guide cost-effective future surveys and monitoring efforts towards areas that are presently poorly-sampled.

This synopsis focuses on the effects of climate change on Mediterranean seagrasses, and associated communities, and on the contribution of the main species, Posidonia oceanica, to the mitigation of climate change effects through sequestering carbon dioxide. Whilst the regression of seagrass meadows is well documented, generally linked to anthropogenic pressures, global warming could be a cause of new significant regression, notably linked to the introduction of exotic species, the rise of Sea-Surface Temperature (SST), and relative sea level. Seagrass communities could also be affected by climate change through the replacement of high structural complexity seagrass species by species of lower complexity and even by opportunistic introduced species. Although it is currently very difficult to predict the consequences of these alterations and their cascade effects, two main potential conflicting trends in the functioning of seagrass ecosystems are acceleration of the herbivore pathway or the detritivore pathway. The mean net primary production of the dominant species, Posidonia oceanica, is relatively high and can be estimated to range between 92.5 to 144.7 g C m-2 a-1. Around 27% of the total carbon fixed by this species enters the sedimentary pathway leading to formation, over millennia, of highly organic deposits, rich in refractory carbon. At the Mediterranean scale, the sequestration rate might reach 1.09 Tg C a-1. The amount of this stored carbon is estimated to range from 71 to 273 kg C m-2, which when considered at the Mediterranean scale would represent 11 to 42% of the CO2 emissions produced by Mediterranean countries since the beginning of the Industrial Revolution. The greatest value of the P. oceanica ecosystem, in the context of mitigation of global climate change, is linked to this vast long-term carbon stock accumulated over millennia, and therefore, efforts should be focused on preserving the meadows to keep this reservoir intact.

Objectives To compare Magnetic Resonance (MR) and Computed Tomography (CT) for the assessment of left (LV) and right (RV) ventricular functional parameters. Methods Seventy nine patients underwent both Cardiac CT and Cardiac MR. Images were acquired using short axis (SAX) reconstructions for CT and 2D cine b-SSFP (balanced- steady state free precession) SAX sequence for MR, and evaluated using dedicated software. Results CT and MR images showed good agreement: LV EF (Ejection Fraction) (52±14% for CT vs. 52±14% for MR; r0 0.73; p>0.05); RV EF (47±12% for CT vs. 47±12% for MR; r00.74; p>0.05); LV EDV (End Diastolic Volume) (74± 21 ml/m 2 for CT vs. 76±25 ml/m 2 for MR; r00.59; p>0.05); RV EDV (84±25 ml/m 2 for CT vs. 80±23 ml/m 2 for MR; r0 0.58; p>0.05); LV ESV (End Systolic Volume)(37±19 ml/m 2 for CT vs. 38±23 ml/m 2 for MR; r00.76; p>0.05); RV ESV (46±21 ml/m 2 for CT vs. 43±18 ml/m 2 for MR; r00.70; p>0.05). Intra- and inter-observer variability were good, and the performance of CT was maintained for different EF subgroups. Conclusions Cardiac CT provides accurate and reproducible LVand RV volume parameters compared with MR, and can be considered as a reliable alternative for patients who are not suitable to undergo MR. Key Points • Cardiac-CT is able to provide Left and Right Ventricular function. • Cardiac-CT is accurate as MR for LV and RV volume assessment. • Cardiac-CT can provide accurate evaluation of coronary arteries and LV and RV function.

Rhabdomyosarcoma (RMS) is a paediatric soft-tissue sarcoma arising from skeletal muscle precursors coexpressing markers of proliferation and differentiation. Inducers of myogenic differentiation suppress RMS tumourigenic phenotype. The Notch target gene HES1 is upregulated in RMS and prevents tumour cell differentiation in a Notch-dependent manner. However, Notch receptors regulating this phenomenon are unknown. In agreement with data in RMS primary tumours, we show here that the Notch3 receptor is overexpressed in RMS cell lines versus normal myoblasts. Notch3-targeted downregulation in RMS cells induces hyper-phosphorylation of p38 and Akt essential for myogenesis, resulting in the differentiation of tumour cells into multinucleated myotubes expressing Myosin Heavy Chain. These phenomena are associated to a marked decrease in HES1 expression, an increase in p21(Cip1) level and the accumulation of RMS cells in the G1 phase. HES1-forced overexpression in RMS cells reverses, at least in part, the pro-differentiative effects of Notch3 downregulation. Notch3 depletion also reduces the tumourigenic potential of RMS cells both in vitro and in vivo. These results indicate that downregulation of Notch3 is sufficient to force RMS cells into completing a correct full myogenic program providing evidence that it contributes, partially through HES1 sustained expression, to their malignant phenotype. Moreover, they suggest Notch3 as a novel potential target in human RMS. Cell Death and Differentiation (2012) 19, 871-881; doi:10.1038/cdd.2011.171; published online 25 November 2011

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (>= 50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model facto Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.