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Introduction: The panorama of drug-induced ototoxicity has widened in the last decades; moreover, post-marketing data are necessary to gain a better insight on ototoxic adverse drug reactions (ADRs). The aim of this study was to perform an analysis of ADR reports describing drug-induced ototoxicity from the Italian spontaneous reporting system (SRS).Methods: As a measure of disproportionality, we calculated the reporting odds ratios (RORs) and 95% confidence intervals (CIs) with a case/non-case methodology. Cases were all suspected ADR reports regarding drug-induced ototoxicity collected into the Italian SRS from 2001 to 2017. Non-cases included all other ADRs reported in the same period.Results: Of 325,980 reports, 652 included at least one ototoxic ADR, compared with 325,328 non-cases. Statistically significant adjusted RORs were found for drugs for cardiovascular disorders, urologicals, teriparatide, amikacin, prulifloxacin, rifampicin and isoniazid, cisplatin, hormone antagonists, tacrolimus, pomalidomide, tramadol, and antidepressants. Significant adjusted RORs in relation to tinnitus were also observed for doxazosin (ROR 5.55, 95% CI 2.06–14.93), bisoprolol (4.28, 1.59–11.53), nebivolol (8.06, 3.32–19.56), ramipril (3.96, 2.17–7.23), irbesartan (19.60, 9.19–41.80), betamethasone (4.01, 1.28–12.52), moxifloxacin (4.56, 1.71–12.34), ethambutol (12.25, 3.89–38.57), efavirenz (16.82, 5.34–52.96), sofosbuvir/ledipasvir (5.95, 1.90–18.61), etoposide (7.09, 2.63–19.12), abatacept (6.51, 2.42–17.53), indometacin (6.30, 2.02–19.72), etoricoxib (5.00, 2.23–11.23), tapentadol (4.37, 1.09–17.62), and timolol combinations (23.29, 9.53–56.95). Moreover, significant adjusted RORs for hypoacusis regarded clarithromycin (3.95, 1.86–8.40), azithromycin (10.23, 5.03–20.79), vancomycin (6.72, 2.14–21.11), methotrexate (3.13, 1.00–9.81), pemetrexed (4.38, 1.40–13.76), vincristine (5.93, 1.88–18.70), vinorelbine (21.60, 8.83–52.82), paclitaxel (2.34, 1.03–5.30), rituximab (3.20, 1.19–8.63), interferon alfa-2b (17.44, 8.56–35.53), thalidomide (16.92, 6.92–41.38), and deferasirox (41.06, 20.07–84.01).Conclusions: This study is largely consistent with results from literature. Nevertheless, propafenone, antituberculars, hormone antagonists, teriparatide, tramadol, and pomalidomide are unknown for being ototoxic. Hypoacusis after the use of vinorelbine, methotrexate, and pemetrexed is unexpected, such as tinnitus related with etoposide, nebivolol, betamethasone, abatacept, sofosbuvir/ledipasvir, and tapentadol, but these considerations require further investigation to better define the risk due to the paucity of data. Moreover, physicians should be aware of the clinical significance of ototoxicity and be conscious about the importance of their contribution to spontaneous reporting.

Fever is a hallmark of infections and inflammatory diseases, represented by an increase of 1–4°C in core body temperature. Fever-range hyperthermia (FRH) has been shown to increase neutrophil recruitment to local sites of infection. Here, we evaluated the impact of a short period (1 h) of FRH (STFRH) on pro-inflammatory and bactericidal human neutrophil functions. STFRH did not affect neutrophil spontaneous apoptosis but reverted the lipopolysaccharide (LPS)-induced anti-apoptotic effect compared with that under normothermic conditions. Furthermore, STFRH accelerated phorbol myristate acetate (PMA)-induced NETosis evaluated either by the nuclear DNA decondensation at 2 h post-stimulation or by the increase in extracellular DNA that colocalized with myeloperoxidase (MPO) at 4 h post-stimulation. Increased NETosis upon STFRH was associated with an increase in reactive oxygen species (ROS) production but not in autophagy levels. STFRH also increased NETosis in response to Pseudomonas aeruginosa challenge but moderately reduced its phagocytosis. However, these STFRH-induced effects did not influence the ability of neutrophils to kill bacteria after 4 h of co-culture. STFRH also significantly reduced neutrophil capacity to release the pro-inflammatory cytokines chemokine (C-X-C motif) ligand 8/interleukin 8 (CXCL8/IL-8) and IL-1β in response to LPS and P. aeruginosa challenge. Altogether, these results indicate that a short and mild hyperthermal period is enough to modulate neutrophil responses to bacterial encounter. They also suggest that fever spikes during bacterial infections might lead neutrophils to trigger an emergency response promoting neutrophil extracellular trap (NET) formation to ensnare bacteria in order to wall off the infection and to reduce their release of pro-inflammatory cytokines in order to limit the inflammatory response.

ABSTRACT Group B Streptococcus (GBS) infections constitute a major cause of invasive disease during the first three months of life and an unmet medical need that could be addressed by maternal vaccination. The GBS capsular polysaccharides (CPSs) have shown promise as vaccine targets in clinical studies. A highly specific serological assay to quantify maternal and neonatal anti-CPS antibody levels will be instrumental for GBS vaccine licensure. Here, we describe the development and comparison of two novel multiplex immunoassays (MIAs) based on the Luminex technology for the quantification of IgG antibodies recognizing the five most frequent GBS capsular variants (Ia, Ib, II, III, and V) out of the ten types identified. The first assay is based on the use of biotinylated CPSs coupled to streptavidin-derivatized magnetic microspheres (Biotin-CPS MIA), while the second is a sandwich assay with plain CPSs coupled to magnetic microspheres coated with polysaccharide-specific mouse monoclonal antibodies (Sandwich MIA). Both assays showed good specificity, linearity, and precision, although the Biotin-CPS MIA presented higher sensitivity and lower complexity than the Sandwich MIA. A panel of human sera representing a wide range of anti-CPS IgG concentrations was tested in parallel by the two assays, which resulted in comparable titers. Our data support the preservation of antigenic epitopes in the biotinylated polysaccharides and the suitability of the Biotin-CPS MIA for the precise determination of GBS anti-CPS IgG concentrations in human sera. IMPORTANCE Group B streptococcal infections can cause death in neonates up to 3 months of age. Intrapartum antibiotic prophylaxis in GBS-colonized mothers has limited early infections but has no impact after the first week of life. The development of a maternal vaccine to address this unmet medical need has been identified as a priority by the World Health Organization, and the GBS CPSs are considered the best antigen targets. However, to date there are no accepted standardized assays to measure immune responses to the investigational vaccines and for establishment of serocorrelates of protection. Here, we describe the performance of two microsphere-based pentaplex immunoassays for the determination of antibodies recognizing the five most frequent GBS serotypes. Our data confirm that an assay based on biotinylated polysaccharides coupled to streptavidin microspheres would be suitable for the intended purpose.

On Saturday the16th March 2019, AIRP participated at the 1st European ADPKD Patient Summit – a unique event designed to promote patient-centred care by providing an interactive forum for patients and experts to discuss ADPKD care, research and advocacy. Forty patient representatives from 15 countries, including Italy, Belgium, Finland, Denmark, France, Germany, Ireland, Lithuania, Netherlands, Spain, Sweden, Switzerland, Turkey, UK and USA joined the ADPKD experts and spokespersons from the European Kidney Health Alliance and EURORDIS. The Summit was co-hosted by PKD International, a global network of patient organizations created to fight all forms of polycystic kidney disease (PKD), and the European ADPKD Forum (EAF), a multidisciplinary, international faculty of experts dedicated to improving the health and quality of life of people with ADPKD. The event aimed to help, inform and empower patients and families to: • be fully involved in the management of their own health and talk about ADPKD with their healthcare team and participate in making decisions about their care • make the best use of the services available • learn about ADPKD research and boost ADPKD advocacy. The programme was designed and delivered together by patients and EAF experts from across Europe, based on the ADPKD Patient Route Map launched in 2018 (available at www.pkdinternational.org) and the EAF Multidisciplinary Position Statement on ADPKD Care (free online here at the Nephrology, Dialysis and Transplantation journal). During the first plenary session of the day, Prof. Albert Ong, Prof. Djalila Mekahli and David Baron (PKD Foundation) updated the participants on some of the latest international developments in ADPKD research, namely the Polycystic Kidney Disease Outcomes Consortium (PKDOC), ADPKD paediatric registries and the Standardised Outcomes in Nephrology – Polycystic Kidney Disease (SONG-PKD) study. Flavia Galletti (AIRP Italy) then moderated a session on the important steps that patients and caregivers can take, together with their healthcare team, to help protect their kidneys and reduce the risk of cardiovascular disease (including heart attacks and stroke). Prof. Tevfik Ecder discussed current recommendations on smoking cessation and managing high blood pressure, together with salt restriction and coffee intake. According to Prof. Ecder, these measures will become even more vital as obesity and diabetes, which also increase the risk of cardiovascular diseases, become more common. In addition, Prof. Mekahli explained how these aspects apply to children with ADPKD. Other sessions, led jointly by patient representatives and experts from across Europe, focused on predicting the progress of ADPKD, treating liver cysts and pain, genetics and genetic testing, renal replacement therapy (i.e. dialysis and transplantation) and how patients can better understand and get involved in research. There were also plenary sessions on current research and patient advocacy in ADPKD, and on the perspective of industry. Videos and slides from this very successful Summit will soon be available on the PKD International website. In addition, each breakout group resulted in a series of aspirations and priorities for ADPKD care and research in the future. These will be soon developed into a Summit ‘Manifesto’.

This work is aimed at investigating the mixing process of highly viscous paints, used to colour leathers in the tanning industry, through Computational Fluid Dynamics (CFD). In particular, a mixing tank is fed with a master liquid and different liquid pigments and then stirred by Cowles impellers in order to obtain a paint of a uniform colour. The typical dynamic viscosity of the liquids in this process is µ ~ O(0.1-10) Pa·s, while the Cowles rotational speed is usually very high, i.e. 3000-5000 rpm. The numerical model is based on the solution of the unsteady Reynolds-Averaged Navier–Stokes (RANS) equations for continuity, momentum and species mass fractions, the latter being used to describe the different components. The impeller motion is modelled through the Sliding Deforming Mesh (SDM) approach, using rotating (unstructured) meshes in the impeller region and a static (structured) mesh in the remainder of the tank. The master liquid and coloured pigments are assumed to stratify within the tank at initial time and the steady rotational speed is then imposed abruptly to the impellers. The level of homogeneity in the stirred tank is evaluated through the analysis of component concentration fields over time. In particular, such local concentrations can be used to determine the mixture colour in different regions of the tank, and hence predict the degree of homogeneity at different times; this is accomplished by defining a proper homogeneity indicator based on the spatial variance of the estimated colour. The proposed numerical model provides an efficient method to investigate the colour of the mixture and to evaluate an appropriate mixing time. The methodology gives also important indications for the tank design, especially useful in the case of non-conventional impellers, high rotation rates and viscous fluids.

Microfluidics is gaining increasing interest in the field of chemical engineering, as miniaturization may lead to a significant intensification of chemical processes. Since the flow is laminar, achieving a good mixing of reactants is one of the main challenges. The simplest geometry is constituted by a T-shaped mixer in which the two inlets join perpendicularly the mixing channel. The inlet cross section is usually square while the mixing channel cross-section is a rectangle as straight walls facilitate experimental and modelling analysis. The present work, on the contrary, is aimed at investigating through Computational Fluid Dynamics the effect of a cross-section with lateral inclined walls, to emulate a microfabrication technology based on laser machining. The presence of inclined walls is found to hamper mixing at high Reynolds numbers as the flow is unable to break the mirror symmetry and thus to undergo the engulfment regime. However, at low Reynold numbers the mixing is improved because the vortex regime presents a lower degree of symmetry with respect to that of T-mixers with straight walls.

In recent years, the replacement of fossil resources with renewable ones has received great interest, especially as regards the production of new valuable bio-products and bio-fuels, in order to replace the traditional petroleum-based ones. In this context, the exploitation of waste biomasses into added-value bio-chemicals is strongly encouraged. Among these ones, the algae ones are attracting considerable attention, in particular macroalgae which cause eutrophication problems in estuaries and lagoons, due to the drastic reduction of dissolved oxygen during their decomposition. This is true for Orbetello lagoon (Italy), where a large amount of algal biomasses is removed every year through an expensive practice, with consequent environmentally serious disposal problems. In this work, for the first time, the acid-catalyzed conversion of two different macroalgae harvested in Orbetello lagoon, Chaetomorpha linum (Muller) Kutzing and Valonia aegagropila C. Agardh, into levulinic acid was studied and optimized, adopting a one-pot hydrothermal treatment, under microwave heating and in the presence of aqueous diluted mineral acids, H2SO4 and HCl. Levulinic acid is a versatile platform chemical, classified by the United States Department of Energy as one of the top-12 promising bio-based building blocks. The effect of the main reaction parameters to give levulinic acid was investigated and discussed, in particular the type and concentration of the acid catalyst, the temperature and the reaction time. The highest levulinic acid yields of 19 wt% for Chaetomorpha linum and 16 wt% for Valonia aegagropila, calculated respect to the weight of the starting dried biomass, were reached. The achieved results are very promising and confirm the significant potential of these green algae as renewable starting feedstocks for levulinic acid production.

The salivary glands (SG) of ixodid ticks play a pivotal role in blood feeding, producing both the cement and the saliva. The cement is an adhesive substance that helps the attachment of the tick to the host skin, while the saliva contains a rich mixture of antihemostatic, anti-inflammatory, and immunomodulatory substances that allow ticks to properly acquire the blood meal. The tick saliva is also a vehicle used by several pathogens to be transmitted to the vertebrate host, including various bacterial species from the genus Rickettsia. Rickettsia rickettsii is a tick-borne obligate intracellular bacterium that causes the severe Rocky Mountain spotted fever. In Brazil, the dog yellow tick Amblyomma aureolatum is a vector of R. rickettsii. In the current study, the effects of an experimental infection with R. rickettsii on the global gene expression profile of A. aureolatum SG was determined by next-generation RNA sequencing. A total of 260 coding sequences (CDSs) were modulated by infection, among which 161 were upregulated and 99 were downregulated. Regarding CDSs in the immunity category, we highlight one sequence encoding one microplusin-like antimicrobial peptide (AMP) (Ambaur-69859). AMPs are important effectors of the arthropod immune system, which lack the adaptive response of the immune system of vertebrates. The expression of microplusin was confirmed to be significantly upregulated in the SG as well as in the midgut (MG) of infected A. aureolatum by a quantitative polymerase chain reaction preceded by reverse transcription. The knockdown of the microplusin expression by RNA interference caused a significant increase in the prevalence of infected ticks in relation to the control. In addition, a higher rickettsial load of one order of magnitude was recorded in both the MG and SG of ticks that received microplusin-specific dsRNA. No effect of microplusin knockdown was observed on the R. rickettsii transmission to rabbits. Moreover, no significant differences in tick engorgement and oviposition were recorded in ticks that received dsMicroplusin, demonstrating that microplusin knockdown has no effect on tick fitness. Further studies must be performed to determine the mechanism of action of this AMP against R. rickettsii.

The embryonic cuticle is necessary for normal seed development and seedling establishment in Arabidopsis. Although mutants with defective embryonic cuticles have been identified, neither the deposition of cuticle material, nor its regulation, has been described during embryogenesis. Here we use electron microscopy, cuticle staining and permeability assays to show that cuticle deposition initiates de novo in patches on globular embryos. By combining these techniques with genetics and gene expression analysis, we show that successful patch coalescence to form a continuous cuticle requires a signalling involving the endosperm-specific subtilisin protease ALE1 and the receptor kinases GSO1 and GSO2, which are expressed in the developing embryonic epidermis. Transcriptome analysis shows that this pathway regulates stress-related gene expression in seeds. Consistent with these findings we show genetically, and through activity analysis, that the stress-associated MPK6 protein acts downstream of GSO1 and GSO2 in the developing embryo. We propose that a stress-related signalling pathway has been hijacked in some angiosperm seeds through the recruitment of endosperm-specific components. Our work reveals the presence of an inter-compartmental dialogue between the endosperm and embryo that ensures the formation of an intact and functional cuticle around the developing embryo through an "auto-immune" type interaction.

Hydrocephalus is one of the lesser known causes of central olfactory loss. The pathogenesis of hydrocephalus involves the olfactory bulbs or tracts, and more rarely, other frontotemporal cortical regions. We describe a case of olfactory dysfunction in a macrocephalic 63-year-old female patient with arrested hydrocephalus. Her olfactory function was assessed by using the Sniffin’ Sticks test, olfactory event-related potentials (OERPs), and 3-Tesla magnetic resonance imaging (MRI). An OERP examination suggested partial impairment of the central olfactory pathways and central parietal regions where OERP amplitude is maximal. Indeed, we found an evident olfactory potential trace with an increased latency only on Pz derivation. However, structural MRI showed important cortical brain thinning and large expansion of the third ventricle, with evident damage of the olfactory frontotemporal areas. The Sniffin’ Sticks test and MRI supported the diagnosis of anosmia, while OERP findings indicated partial preservation of olfactory function, likely due to an adaptation of the central olfactory system. These findings highlight the importance of a multi-integrated approach to detect olfactory impairment.

The aim of this study is to explore risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies of 205 laboratory-confirmed cases infected with SARS-CoV-2 during the Lombardy outbreak. All patients received the best supportive care and specific interventions that included the main drugs being tested for repurposing to treat COVID-19, such as hydroxychloroquine, anticoagulation and antiviral drugs, steroids, and interleukin-6 pathway inhibitors. Clinical, laboratory, and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality. Univariate analyses showed prognostic significance for age greater than 70 years, the presence of two or more relevant comorbidities, a P/F ratio less than 200 at presentation, elevated LDH (lactate dehydrogenase) and CRP (C-reactive protein) values, intermediate- or therapeutic-dose anticoagulation, hydroxychloroquine, early antiviral therapy with lopinavir/ritonavir, short courses of steroids, and tocilizumab therapy. Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (OR 3.26) and a reduction in mortality for patients treated with anticoagulant (−0.37), antiviral lopinavir/ritonavir (−1.22), or steroid (−0.59) therapy. In contrast, hydroxychloroquine and tocilizumab have not been confirmed to have a significant effect in the treatment of SARS-CoV-2 pneumonia. Results from this real-life single-center experience are in agreement and confirm actual literature data on SARS-CoV-2 pneumonia in terms of both clinical risk factors for in-hospital mortality and the effectiveness of the different therapies proposed for the management of COVID19 disease.

Next-generation plasma-based accelerators can push electron beams to GeV energies within centimeter distances. The plasma, excited by a driver pulse, is indeed able to sustain huge electric fields that can efficiently accelerate a trailing witness bunch, which was experimentally demonstrated on multiple occasions. Thus, the main focus of the current research is being shifted towards achieving a high quality of the beam after the plasma acceleration. In this paper we present a beam-driven plasma wakefield acceleration experiment, where initially preformed high-quality witness beam was accelerated inside the plasma and characterized. In this experiment the witness beam quality after the acceleration was maintained on high level, with 0.2% final energy spread and 3.8 μm resulting normalized transverse emittance after the acceleration. In this article, for the first time to our knowledge, the emittance of the plasma wakefield accelerated beam was directly measured.

Background: developmental dysplasia of the hip has an incidence of 3–5 out of 1000 children. Currently, only postnatal screening is available. Objective: to test the feasibility of a method based on Graf technique application at antenatal ultrasound in assessing the normal development of the hip in unselected term fetuses. Methods: a prospective cohort study in a single university tertiary hospital from January 2017 to January 2020. Single uncomplicated term pregnancies (37–40 weeks) attending our center for routine ultrasound were consecutively recruited for the purpose of the study. A 3D volume acquisition was launched on the coxofemoral joint of the fetus by a single expert operator, and offline analysis was then performed in the multiplanar mode by two operators (blinded to each other analysis) in order to measure the alpha and beta angles according to our modified Graf technique. Intra- and inter-observer variations were calculated. Reference charts for normal values of both angles were produced. Postnatal ultrasound was then performed to measure the Graf angles in newborns, confirming a normal development of the hip. Results: in the study period, 433 uncomplicated term pregnancies underwent 3D ultrasound for the assessment of the fetal hip. One case was subsequently excluded because of confirmed postnatal diagnosis of developmental dysplasia of the hip. The measurement of our modified Graf angles was feasible at prenatal ultrasound with a good reproducibility. The inter-rater and intra-rater reliability of both angles was substantial. Reference charts for normal values of both angles were produced. Conclusions: the evaluation of the coxofemoral joint in fetuses at term of gestation has never been attempted before. The Graf technique application, currently employed at postnatal ultrasound, may also be adapted to prenatal ultrasound with a substantial reproducibility. However, there was no evidence of a linear relationship between prenatal and postnatal alpha angles and beta angles. Further research is needed to establish if developmental dysplasia of the hip could be diagnosed antenatally.

Despite the very simple geometry and the laminar flow, T-shaped microreactors have been found to be characterized by different and complex steady and unsteady flow regimes, depending on the Reynolds number. In particular, flow unsteadiness modifies strongly the mixing process; however, little is known on how this change may affect the yield of a chemical reaction. In the present work, experiments and 3-dimensional numerical simulations are carried out jointly to analyze mixing and reaction in a T-shaped microreactor with the ultimate goal to investigate how flow unsteadiness affects the reaction yield. The onset of the unsteady asymmetric regime enhances the reaction yield by more than 30%; however, a strong decrease of the yield back to values typical of the vortex regime is observed when the flow undergoes a transition to the unsteady symmetric regime.

Recent high-intensity laser experiments (Cole et al 2018 Phys. Rev. X 8 011020; Poder et al 2018 Phys. Rev. X 8 031004) have shown evidence of strong radiation reaction in the quantum regime. Experimental evidence of quantum effects on radiation reaction and electron–positron pair cascades has, however, proven challenging to obtain and crucially depends on maximising the quantum parameter of the electron (defined as the ratio of the electric field it feels in its rest frame to the Schwinger field). The quantum parameter can be suppressed as the electrons lose energy by radiation reaction as they traverse the initial rise in the laser intensity. As a result the shape of the intensity temporal envelope becomes important in enhancing quantum radiation reaction effects and pair cascades. Here we show that a realistic laser pulse with a faster rise time on the leading edge, achieved by skewing the temporal envelope, results in curtailing of pair yields as the peak power is reduced. We find a reduction in pair yields by orders of magnitude in contrast to only small reductions reported previously in large-scale particle-in-cell code simulations (Hojbota et al 2018 Plasma Phys. Control. Fusion 60 064004). Maximum pairs per electron are found in colliding 1.5 GeV electrons with a laser wakefield produced envelope 7.90 × 10 ^−2 followed by a short 50 fs Gaussian envelope, 1.90 × 10 ^−2 , while it is reduced to 8.90 × 10 ^−5 , a factor of 100, for an asymmetric envelope.

The injection of hydrogen into the natural gas network can contribute to the large-scale integration of renewables, as hydrogen can be easily produced through electrolysis from wind or solar energy. However, the addition of hydrogen to natural gas influences fuel properties, asking for the assessment of the safe and efficient operation of existing end-user equipment, such as domestic burners and boilers. In this work, 3-dimensional resolved numerical simulations based on Computational Fluid Dynamics are carried out to shed light on the effect of H2 addition on the combustion process occurring in condensing boilers equipped with perforated cylindrical burners. To this purpose, multi-hole geometries emulating a portion of a perforated burner are analyzed. Since the burner holes are positioned very close to each other, the interaction of the adjacent laminar premixed flames is observed to occur with influence on the flow and thermo-chemical fields which differ from those of a single premixed flame. The addition of hydrogen was found to lead to an anticipation of the reaction zone, although the general features observed with the G222 gas (23% H2, 77% CH4 ) were alike those of the G20 gas (100% CH4).

Recent legislation concerning air pollutant emissions from ships (Tier III) has considerably decreased NOx emission limits for recreational ships with less than 500 gross tonnages and greater than 24 m load line length (LLL), the so-called “large yachts”. For these yachts, which adopt multiple Diesel engines with maximum power ranging from 800 to 2000 kW, the new NOx limit is less than 2 g/kWh. To satisfy that limit, engine makers suggest the adoption of a classic SCR system with urea injection but this methodology, in addition to requiring a large space for installation, does not seem so appropriate for diesel engines of large yachts that normally operate at low power with exhaust temperatures often well below 300 °C, therefore not sufficient to allow the correct functioning of the SCR. The aforementioned circumstances have prompted Sanlorenzo Spa (La Spezia – Italy), one of the world’s leading companies in the production of pleasure boats, to collaborate with the University of Pisa in the study of alternative solutions to SCR systems. Recently there is a great interest in innovative NOx abatement systems, based on the possibility of absorbing NOx molecules into seawater through the utilization of appropriate aqueous solutions containing targeted saline oxidizing agents. The present study describes the first results of a research program aimed to identify, from one side, the best saline oxidizing agent for an aqueous NOx abatement and, from the other, the best washing methodology compatible with the propulsion layouts usually adopted on yachts. In the engine testing laboratories of the Department of Energy, Systems, Territory and Construction Engineering (DESTeC) of the University of Pisa, an experimental apparatus has been created to reproduce the real conditions of underwater engine exhausting. This device was combined with a small 1.2 L direct injection diesel engine. The first results showed a reduction of the NOx emissions of about 27% by using a gas washing with wet scrubber, followed by bubbling in water, using 0.2 molar NaClO saline solutions.

The biogas production through the anaerobic digestion (AD) of giant reed (Arundo donax L.) biomass has received increasing attention. However, due to the presence of lignin, a low CH4 yield can be obtained. Aiming to improve the CH4 yield from giant reed biomass, the effectiveness of a thermo-chemical pre-treatment based on KOH was evaluated in this paper. The usefulness of a washing step before the AD was also assessed. The pre-treatment led to a specific CH4 yield up to 232 mL CH4 g−1 VS which was 21% higher than that from untreated biomass; the maximum daily rate of production was improved by 42%, AD duration was reduced by 10%, and CH4 concentration in the biogas was increased by 23%. On the contrary, the washing step did not improve the AD process. Besides, washing away the liquid fraction led to biomass losses, reducing the overall CH4 production. The use of a KOH-based pre-treatment appears as a good option for enhancing the AD of giant reed, also presenting potential environmental and agronomical benefits, like the avoidance of salty wastewater production and the likely improvement of the digestate quality, due to its enriched K content.

ABSTRACT Objective To evaluate solubility and sealing ability of Mineral Trioxide Aggregate (MTA) and root-end filling materials. Material and Methods The materials evaluated were: MTA, Calcium Silicate Cement with zirconium oxide (CSC/ZrO2), and zinc oxide/eugenol (ZOE). Solubility test was performed according to ANSI/ADA. The difference between initial and final mass of the materials was analyzed after immersion in distilled water for 7 and 30 days. Retrograde cavities in human teeth with single straight root canal were performed by using ultrasonic tip CVD 9.5107-8. The cavities were filled with the evaluated materials to evaluate sealing ability using the bacterial leakage test with Enterococcus faecalis. Bacterial leakage was evaluated every 24 hours for six weeks observing the turbidity of Brain Heart infusion (BHI) medium in contact with root apex. Data were submitted to ANOVA followed by Tukey tests (solubility), and Kruskal-Wallis and Dunn tests (sealing ability) at a 5% significance level. Results For the 7-day period, ZOE presented highest solubility when compared with the other groups (p

(1) Background: Influenza vaccination uptake in nursing home (NH) workers is uncommon. The aim of this study was to understand the choice architecture of influenza vaccination acceptance or refusal among them and to promote vaccination acceptance using the nudge approach. (2) Methods: In autumn 2019, a nudge intervention with a contextual qualitative analysis of choice architecture of vaccination was performed among the staff of eight Tuscan NHs. In summer 2020, a cross-sectional study including the staff of 111 NHs (8 in the nudge, 103 in the comparison group) was conducted to assess the impact of the nudge intervention in promoting vaccination uptake. (3) Results: Macro-categories of motivations for vaccination uptake that emerged from the qualitative analysis were risk perception, value dimension, and trust, while those regarding refusal were risk perception, distrust, value dimension, and reasons related to one’s health. Considering the cross-sectional study, influenza vaccination uptake in the 2018–2019 season was similar in the two groups (23.6% vs. 22.2% respectively, in the nudge and comparison group), but significantly different in the 2019–2020 season: 28% in the nudge vs. 20% in the comparison group. Also, the intention to get the vaccine in the 2020–2021 season was significantly different in the two groups: 37.9% in the nudge and 30.8% in the comparison group. (4) Conclusions: Nudge interventions-simple, fast, low cost-could be effective in promoting vaccination acceptance among NH workers and the analysis of choice architecture could be useful in improving tailored, new nudge interventions aimed at modifying irrational biased and cognitive errors.

Natural biomacromolecules such as structural proteins and polysaccharides are composed of the basic building blocks of life: amino acids and carbohydrates. Understanding their molecular structure, self-assembly and interaction in solvents such as ionic liquids (ILs) is critical for unleashing a flora of new materials, revolutionizing the way we fabricate multi-structural and multi-functional systems with tunable physicochemical properties. Ionic liquids are superior to organic solvents because they do not produce unwanted by-products and are considered green substitutes because of their reusability. In addition, they will significantly improve the miscibility of biopolymers with other materials while maintaining the mechanical properties of the biopolymer in the final product. Understanding and controlling the physicochemical properties of biopolymers in ionic liquids matrices will be crucial for progress leading to the ability to fabricate robust multi-level structural 1D fiber materials. It will also help to predict the relationship between fiber conformation and protein secondary structures or carbohydrate crystallinity, thus creating potential applications for cell growth signaling, ionic conductivity, liquid diffusion and thermal conductivity, and several applications in biomedicine and environmental science. This will also enable the regeneration of biopolymer composite fiber materials with useful functionalities and customizable options critical for additive manufacturing. The specific capabilities of these fiber materials have been shown to vary based on their fabrication methods including electrospinning and post-treatments. This review serves to provide basic knowledge of these commonly utilized protein and polysaccharide biopolymers and their fiber fabrication methods from various ionic liquids, as well as the effect of post-treatments on these fiber materials and their applications in biomedical and pharmaceutical research, wound healing, environmental filters and sustainable and green chemistry research.

A “cradle-to-grave” life cycle assessment is performed to identify the environmental issues of polyhydroxyalkanoates (PHAs) produced through a hybrid thermochemical-biological process using anaerobically digested sewage sludge (ADSS) as feedstock. The assessment includes a measure of the energy performance of the process. The system boundary includes: (i) Sludge pyrolysis followed by volatile fatty acids (VFAs) production; (ii) PHAs-enriched biomass production using a mixed microbial culture (MMC); (iii) PHAs extraction with dimethyl carbonate; and iv) PHAs end-of-life. Three scenarios differing in the use of the syngas produced by both pyrolysis and biochar gasification, and two more scenarios differing only in the external energy sources were evaluated. Results show a trade-off between environmental impacts at global scale, such as climate change and resources depletion, and those having an effect at the local/regional scale, such as acidification, eutrophication, and toxicity. Process configurations based only on the sludge-to-PHAs route require an external energy supply, which determines the highest impacts with respect to climate change, resources depletion, and water depletion. On the contrary, process configurations also integrating the sludge-to-energy route for self-sustainment imply more onsite sludge processing and combustion; this results in the highest values of eutrophication, ecotoxicity, and human toxicity. There is not a categorical winner among the investigated configurations; however, the use of a selected mix of external renewable sources while using sludge to produce PHAs only seems the best compromise. The results are comparable to those of both other PHAs production processes found in the literature and various fossil-based and bio-based polymers, in terms of both non-biogenic GHG emissions and energy demand. Further process advancements and technology improvement in high impact stages are required to make this PHAs production process a competitive candidate for the production of biopolymers on a wide scale.

Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC50 values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G2/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.

The aim of this cross-sectional study is to address whether health literacy (HL) and vaccine confidence are related with influenza vaccination uptake among staff of nursing homes (NHs). It was conducted in Tuscany (Italy) in autumn 2018, including the staff of 28 NHs. A questionnaire was used to collect individual data regarding influenza vaccination in 2016–2017 and 2017–2018 seasons; the intention to be vaccinated in 2018–2019; as well as demographic, educational, and health information. It included also the Italian Medical Term Recognition (IMETER) test to measure HL and eight Likert-type statements to calculate a Vaccine Confidence Index (VCI). The number of employees that fulfilled the questionnaire was 710. The percentage of influenza vaccination uptake was low: only 9.6% got vaccinated in 2016–2017 and 2017–2018 and intended to vaccinate in 2018–2019. The VCI score and the IMETER-adjusted scores were weakly correlated (Rho = 0.156). At the multinomial logistic regression analysis, the VCI was a positive predictor of vaccination uptake. In conclusion, vaccine confidence is the strongest predictor of influenza vaccination uptake among the staff of NHs. The development of an adequate vaccine literacy measurement tool could be useful to understand whether skills could be related to vaccine confidence.

Thin films promise new opportunities for the manipulation of surface states of topological semimetals with the potential to realize new states that cannot be obtained in bulk materials. Here, we report transport studies of gated Hall bar structures fabricated from approximately 50-nm-thick, (001)-oriented epitaxial films of cadmium arsenide, a prototype three-dimensional Dirac semimetal, in magnetic fields up to 45 T. The films exhibit a quantized Hall effect with pronounced odd-integer plateaus that is strikingly different from that of the more widely studied (112)-oriented films. We show that the unusual quantum Hall effect is a consequence of the inverted bulk band structure of cadmium arsenide that creates topological-insulator-like states at the bottom and top interfaces, each exhibiting a half-integer quantum Hall effect. A small potential offset between the two surfaces results in the crossing of the Landau levels and gives rise to the filling factor sequences observed in the experiments. Moreover, at large negative values of gate bias, the filling factor ν=1 is abruptly preempted by an insulating state that is accompanied by the collapse of the well-developed quantum Hall effect. We suggest that this new phase cannot be explained within a single-particle picture and discuss the role of Coulomb interactions between spatially separated surface states.

In the recent years the progressive decrease in fossil petroleum resources and gradual deprivation of the environment have attracted increasing interest towards the use of biomass as renewable carbon source for the production of chemicals and transportation fuels. In particular, lignocellulosic biomass represents an abundant and inexpensive renewable resource with high carbon sequestration ability and non-polluting. In this paper, the valorisation of mixtures made of n-butanol (n-BuOH), butyl levulinate (BL) and dibutyl ether (DBE), in different percentages, as additive fuel for compression ignition (CI) internal combustion engine (ICE) was studied. These mixtures can be directly obtained from the catalytic alcoholysis reaction of the cellulosic fraction of raw and pre-treated lignocellulosic biomasses. Moreover, the possibility to recycle and reutilize the excess alcohol (n-Butanol), during the catalytic alcoholysis reaction, has been considered since it represents an opportunity to reduce the overall costs of the process. Therefore, a blend constituted only by BL and DBE has been also tested. The model mixtures were prepared by using commercial reactants, characterized by compositions analogous to those of the reaction mixtures. These model mixtures were tested as blend with Diesel fuel in a CI-ICE with the measurement of pollutant emission and performance. Results have been compared with those obtained fuelling the engine with a commercial Diesel fuel. As a whole, tests results have evidenced the potentiality of these novel blending mixtures to reduce the emissions of particulate without any significant increase in the other pollutants and negligible changes in engine power and efficiency.

In the present study, a Computational Fluid Dynamics (CFD) model was set up to analyse the dynamic behaviour of LNG (Liquefied Natural Gas) tanks adopted in heavy trucks refuelling stations in normal operating conditions or during process upsets. The CFD model was based on the Volume-Of-Fluid (VOF) method to simulate the transient behaviour of a multi-phase flow in a 100 m3 vertical cylindrical tank. The model first considered a fully insulated vessel, and subsequently it was modified to take into account possible damages of the insulation layer, this being a critical upset scenario. The CFD model allowed predicting the dynamic pressure build up in the damaged tank, thus obtaining key indications for the evaluation of the vessel mechanical resistance and set up of safety measures. The model also provided the prediction of vapor temperature with respect to time and external heat source, that is a key issue to assess the effectiveness of the thermal insulation.