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Abstract Thousands of disease cases and hundreds of deaths occur globally each year due to invasive meningococcal disease. Neisseria meningitidis serogroup B (MenB) is the leading cause of such disease in developed countries. Two vaccines, 4CMenB and MenB‐fHbp, that protect against MenB are available and include one or two forms respectively of factor H binding protein (fHbp), a key protective antigen. Studies of circulating meningococci have identified over 1380 different fHbp amino acid sequences, which form three immunologically distinct clusters, termed variants 1, 2, and 3. Neither of the current vaccines contains a variant 2 antigen, which is less well characterized than fHbp variants 1 and 3. We characterized the interaction of fHbp variant 2 with humAb 1B1 using biochemical methods and live meningococcal assays. Further, we determined the crystal structure of the complex at 2.4 Å resolution, clearly revealing the epitope and providing the first detailed report of an antibody with distinct specificity for fHbp variant 2. Extensive mutagenesis and binding studies elucidated key hotspots in the interface. This combination of structural and functional studies provides a molecular explanation for the bactericidal potency and specificity of humAb 1B1 for fHbp variant 2. Our studies, focused on fHbp variant 2, expand the understanding of this previously under characterized group of the vast family of variants of fHbp, a virulence factor present on all meningococci. Moreover, the definition of a protective conformational epitope on fHbp variant 2 may support the design and development of novel variant 2‐containing MenB vaccines affording greater breadth of protection.

Abstract Aims To assess the extent of Coronavirus-related disruption to health and social care treatment and social interactions among people with lived or living experience of substance use in Scotland, and explore potential reasons for variations in disruption. Design Cross sectional mixed methods interview, incorporating a social network ‘egonet interview’ approach asking about whether participants had interactions with a range of substance use, health, social care or third sector organisations, or informal social interactions. Setting Five Alcohol and Drug Partnership Areas in Scotland. Participants 57 (42% women) participants were involved in the study, on average 42 years old. Measurements Five-point Likert scale reporting whether interactions with a range of services and people had gotten much better, better, no different (or no change), worse, or much worse since COVID19 and lockdown. Ratings were nested within participants (Individuals provided multiple ratings) and some ratings were also nested within treatment service (services received multiple ratings). The nested structure was accounted for using cross classified ordinal logistic multilevel models. Findings While the overall average suggested only a slight negative change in interactions (mean rating 2.93), there were substantial variations according to type of interaction, and between individuals. Reported change was more often negative for mental health services (Adjusted OR = 0.93 95% CI 0.17,0.90), and positive for pharmacies (3.03 95% CI 1.36, 5.93). The models found between-participant variation of around 10%, and negligible between-service variation of around 1% in ratings. Ratings didn’t vary by individual age or gender but there was variation between areas. Conclusions Substance use treatment service adaptations due to COVID19 lockdown led to both positive and negative service user experiences. Social network methods provide an effective way to describe complex system-wide interaction patterns, and to measure variations at the individual, service, and area level.

Metal sub-microparticles (SMPs) and nanoparticles (NPs) presence in food is attributable to increasing pollution from the environment in raw materials and finished products. In the present study, a multifaceted analytical strategy based on Environmental Scanning Electron Microscopy and High-Angle Annular Dark-Field—Scanning Transmission Electron Microscopy coupled with Energy-Dispersive X-ray Spectroscopy (ESEM-EDX, HAADF-STEM-EDX) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was proposed for the detection and characterization of metal and metal-containing SMPs and NPs in durum wheat samples, covering a size measurement range from 1 nm to multiple µm. ESEM-EDX and ICP-MS techniques were applied for the assessment of SMP and NP contamination on the surface of wheat grains collected from seven geographical areas characterized by different natural and anthropic conditions, namely Italy, the USA, Australia, Slovakia, Mexico, Austria, and Russia. ICP-MS showed significant differences among the mean concentration levels of metals, with the USA and Italy having the highest level. ESEM-EDX analysis confirmed ICP-MS concentration measurements and measured the highest presence of particles < 0.8 µm in size in samples from Italy, followed by the USA. Less marked differences were observed when particles < 0.15 µm were considered. HAADF-STEM-EDX was applied to a selected number of samples for a preliminary assessment of internal contamination by metal SMPs and NPs, and to expand the measurable particle size range. The multifaceted approach provided similar results for Fe-containing SMPs and NPs. ICP-MS and ESEM-EDX also highlighted the presence of a significant abundance of Ti- and Al-containing particles, while for STEM-EDX, sample preparation artifacts complicated the interpretation. Finally, HAADF-STEM-EDX results provided relevant information about particles in the low nm range, since, by applying this technique, no particles smaller than 50 nm were observed in accordance with ESEM-EDX.

Solid-phase microextraction (SPME) has been widely proposed for the extraction, clean-up, and preconcentration of analytes of environmental concern. Enrichment capabilities, preconcentration efficiency, sample throughput, and selectivity in extracting target compounds greatly depend on the materials used as SPME coatings. Supramolecular materials have emerged as promising porous coatings to be used for the extraction of target compounds due to their unique selectivity, three-dimensional framework, flexible design, and possibility to promote the interaction between the analytes and the coating by means of multiple oriented functional groups. The present review will cover the state of the art of the last 5 years related to SPME coatings based on metal organic frameworks (MOFs), covalent organic frameworks (COFs), and supramolecular macrocycles used for environmental applications.

Abstract Dental calculus is a valuable resource for the reconstruction of dietary habits and oral microbiome of past populations. In 2020 the remains of Duke Alessandro Farnese and his wife Maria D’Aviz were exhumed to get novel insights into the causes of death. This study aimed to investigate the dental calculus metabolome of the noble couple by untargeted metabolomics. The pulverized samples were decalcified in a water-formic acid mixture, extracted using methanol/acetonitrile and analyzed by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) using a reversed-phase separation followed by electrospray ionization and full scan in positive and negative ion mode. Waters Synapt-G2-Si High-Definition hybrid quadrupole time-of-flight mass spectrometer was used. Significant features were then identified using MSE acquisition mode, recording information on exact mass precursor and fragment ions within the same run. This approach, together with data pre-treatment and multivariate statistical analysis allowed for the identification of compounds able to differentiate between the investigated samples. More than 200 metabolites were identified, being fatty acids, alcohols, aldehydes, phosphatidylcholines, phosphatidylglycerols, ceramides and phosphatidylserines the most abundant classes. Metabolites deriving from food, bacteria and fungi were also determined, providing information on the habits and oral health status of the couple.

[This corrects the article DOI: 10.1371/journal.pone.0290792.].

The COVID-19 pandemic has profoundly impacted on cancer patients' psychological well-being and clinical status. We assessed the levels of anxiety, depression, and distress and the attitude towards COVID-19 vaccination in cancer patients, accepting vaccination at the Verona University Hospital and Camposampiero Hospital in the Veneto region. Self-reported questionnaires were administered to patients undergoing COVID-19 vaccination between March and May 2021 (first and second dose). Twenty-seven items were investigated: i) demographics/clinical characteristics; ii) anxiety, depression, and distress (Hospital Anxiety and Depression Scale-HADS-and Distress Thermometer-DT); iii) four specific items regarding awareness about infection risks, interference with anticancer treatments, and vaccine side effects. Sixty-two and 57% of the patients who accepted to be vaccinated responded to the survey in the two participating Hospitals, respectively. Mean age was 63 years (SD: 12 years; range 19-94 years), women were slightly more prevalent (57.6%), most participants were married (70%), and either worker or retired (60%). Borderline and clinical levels of anxiety were recorded in 14% and 10% of respondents; borderline and clinical levels of depression in 14% and 8%; and moderate and severe distress levels in 33% and 9%. Overall, there was high confidence that vaccination would reduce the risk of contracting COVID-19 (70%), which would make patients feel less worried about contracting the infection (60%). Fear that vaccine-related side effects would interfere with anticancer treatment and/or global health status was low (10% and 9% for items 3 and 4, respectively) and significantly associated with baseline levels of anxiety, depression, and distress at multivariate analysis. Results did not differ between the Verona and Camposampiero cohorts. During the COVID-19 vaccination campaign, adult cancer patients demonstrated high levels of confidence towards vaccination; baseline levels of anxiety, depression, and distress were the only significant predictors of reduced confidence.

Phthalate esters (PAEs) are the most widely used plasticizers worldwide and are considered as ubiquitous environmental contaminants. Due to both their ubiquity and potential health and environmental risks, their determination is a matter of worldwide concern. In the present study, an efficient method based on ultrasonic-assisted solvent extraction followed by gas chromatography-mass spectrometry is proposed for the simultaneous determination of PAEs and di(2-ethylhexyl) adipate in estuarine sediments and shells. Method optimization was successfully carried out according to Quality by Design principles. Shaking time, ultrasonic time, extractant volume, and solvent type were selected as Critical Method Parameters. Validation proved method reliability for the determination of the investigated analytes, achieving detection limits in the 0.1–0.7 ng g–1 and 0.1–0.5 ng g–1 range for sediments and shells, respectively. A good precision was obtained with RSD < 20% and trueness (recovery) in the 73(±7)–120(±10)% and 70(±10)–111(±3)% range, for sediments and shells, respectively. Finally, the method was applied to analyze sediment samples and mollusc shells, collected from the Curonian Lagoon (Southeast Baltic Sea). Di(2-ethylhexyl) phthalate was present in all the analyzed samples, thus pointing out its ubiquity in estuarine environment. PAEs were also found in shell debris or living mussels, highlighting them as a hotspot of organic contaminants, especially in transitional environments, where accumulation of organic rich deposits is limited.

The impact of the anthropic activities in Antarctica is a concerning issue. According to the Scientific Committee on Antarctic Research, attention has to be paid to the next-generation contaminants deriving from both long-range atmospheric transport and local sources. In this study, the capabilities of transmission electron microscopy with energy-dispersive X-ray spectroscopy and Raman micro-spectroscopy were exploited to evaluate the size, morphology, and chemical composition of small micro- and nanoparticles, as well as their aggregates, in surface snow samples collected during the 2020–2021 austral summer in the coastal area of Victoria Land near the Mario Zucchelli research station. The presence of biological particles, mineral dust, sea salts, and small carbonaceous and plastic micro- and nanoparticles was assessed. Sulfate, carbonate, and nitrate minerals were detected in all the samples, whereas polyethylene, poly(ethylene-co-vinyl-acetate), and different kinds of carbonaceous materials were predominantly identified in the samples closest to the research base. The presence of small micro- and nanoparticles containing heavy metals and plastic polymers in samples collected in the areas surrounding the Italian research base highlights the impact of anthropogenic activities on the polar environment, suggesting the need for continuous monitoring to evaluate possible threats to the delicate Antarctic ecosystem.

BackgroundIn an observational study in Geneva (Switzerland), we found that administering a standardized THC/CBD oil was feasible, safe, and beneficial in an elderly polymedicated population with severe dementia, behavioral troubles, and pain. Those findings need to be confirmed in a randomized clinical trial.ObjectivesThe MedCanDem trial is a randomized, double-blind cross-over placebo-controlled trial to study the efficacy of cannabinoids in improving painful symptoms during severe dementia disorders in patients living in long-term care facilities in Geneva. This manuscript describes the MedCanDem trial protocol.Materials and methodsParticipants will be patients suffering from severe dementia associated with pain and behavioral troubles and living in long-term care facilities. We selected five facilities specialized in caring for severely demented patients in Geneva (Switzerland). A total of 24 subjects will be randomized 1:1 to the sequence study intervention/placebo or the sequence placebo/study intervention. Patients will receive study intervention treatment or placebo for eight weeks, and then after a one-week wash-out, treatments will be inversed for another eight weeks. The intervention will be a standardized THC/CBD 1:2 oil extract, and the placebo will be a hemp seed oil. The primary outcome is the reduction from the baseline of the Cohen-Mansfield score; secondary outcomes include the reduction in the Doloplus scale, the reduction of rigidity, the monitoring of concomitant drugs prescription and de-prescription, the safety assessment, and a pharmacokinetic evaluation. The primary and secondary outcomes will be assessed at the baseline, after 28 days, and at the end of both study periods. In addition, safety laboratory analysis, pharmacokinetic evaluation, and therapeutic drug monitoring for the cannabinoids will be evaluated through a blood sample analysis conducted at the beginning and the end of both study periods.Discussion and conclusionThis study will allow us to confirm the clinical results observed during the observational study. It represents one of the few studies aiming to prove natural medical cannabis efficacy in a population of non-communicating patients with severe dementia, experimenting with behavioral troubles, pain, and rigidity.Trial registrationThe trial has Swissethics authorization (BASEC 2022-00999), and it is registered on clinicaltrials.gov (NCT05432206) and the SNCTP (000005168).

The citation network of patents citing prior art arises from the legal obligation of patent applicants to properly disclose their invention. One way to study the relationship between current patents and their antecedents is by analyzing the similarity between the textual elements of patents. Many patent similarity indicators have shown a constant decrease since the mid-70s. Although several explanations have been proposed, more comprehensive analyses of this phenomenon have been rare. In this paper, we use a computationally efficient measure of patent similarity scores that leverages state-of-the-art Natural Language Processing tools, to investigate potential drivers of this apparent similarity decrease. This is achieved by modeling patent similarity scores by means of generalized additive models. We found that non-linear modeling specifications are able to distinguish between distinct, temporally varying drivers of the patent similarity levels that explain more variation in the data (R2 ∼ 18%) compared to previous methods. Moreover, the model reveals an underlying trend in similarity scores that is fundamentally different from the one presented previously.

ContextThe management of behavioral symptoms and rigidity in patients with dementia constitutes a significant challenge. Short-term studies suggest an interest in the use of medical cannabis, but long-term data are lacking.ObjectivesThe objective of this study was to investigate the feasibility and long-term safety of administering tetrahydrocannabinol/cannabidiol (THC/CBD) treatment as an additional drug to a poly medicated population with severe dementia, evaluate clinical improvements, and collect information on the pharmacokinetics of cannabinoids and possible drug–drug interactions.MethodsA prospective observational study of patients with severe dementia living in a long-term care home to whom the physicians had prescribed a medical cannabis treatment. Data were collected over 2 years. We assessed the changes in medical cannabis dosages, safety parameters, variations in neuropsychiatric problems, agitation, rigidity, the most invalidating daily activity, and disabling behavior trouble scores. We evaluated the pharmacokinetics of cannabinoids by measuring plasma levels and analyzing the enzymatic activity.ResultsWe assessed 19 patients (81.4 years—17 women and two men) receiving an average of 12.4 mg THC/24.8 mg CBD per day for up to 13 months, with no reported problems related to the treatment and limited adverse drug reactions. Clinical scores showed a marked improvement that was stable over time, deprescription of other medications, and care facilitated. The pharmacokinetic evaluation showed an expected slight reduction in the enzymatic activity of CYP1A2 and CYP2C19.ConclusionA long-term THC/CBD (1:2) medication can be administered safely and with overall positive clinical improvement to poly medicated older adults with severe dementia and associated problems. The results must be confirmed in a randomized trial.

Starting from considerations on the high seismic vulnerability of nonstructural elements, and at the same time the scarce consideration of their performance at the different stages of the design and assessment process, this paper proposes a very simple and ready-to-use seismic classification scheme for nonstructural elements. The proposed approach is based on a limited set of information, which may take advantage of the availability of a numerical model of the building and its results, although it may also rely on code formulations and evaluations of seismic performance from the literature. The different seismic classes are assigned to nonstructural elements by quantifying their expected seismic performance by means of fragility curves. This classification may be applied to newly designed nonstructural elements to help identify the best typology for the site and building of interest, and also for existing nonstructural elements that are already installed in existing buildings. In the latter case, the classification may help in defining a prioritization scheme for interventions required to make nonstructural elements safer for the building of concern. The feasibility of the proposed procedure is demonstrated by its application to two case studies, referring to existing buildings located at different seismicity sites.

The safety of food contact materials is a hot topic since chemicals can migrate from packaging into food, thus raising health concerns about and/or producing changes in the organoleptic properties of foodstuffs. Migration tests are required to demonstrate the compliance with current regulations and to investigate the transferred compounds. In this context, mass spectrometry is the analytical technique of choice for the detection and quantitation of both intentionally added substances, such as antioxidants, stabilizers, processing aids, and non-intentionally added substances (NIAS). Untargeted strategies represent a major analytical challenge, providing a comprehensive fingerprinting of the packaging material and migrating components, allowing for NIAS identification. Hyphenated mass spectrometry-based techniques have been devised for screening the presence of migrating contaminants and for quantitation purposes. Both low-resolution (LRMS) and high-resolution (HRMS) methods were screened, with a special emphasis on the latter because of its capability to directly characterize food contact materials with minimal/no sample preparation, avoiding chromatographic separation, and reducing sample handling, analysis costs, and time. Examples related to the migration of contaminants from existing or newly developed bioplastic materials will be discussed, providing an overview of the most used MS-based methods, covering the state-of-the-art approaches from 2012 up to 2022.

Omental infarction and epiploic appendagitis are rare causes of acute abdominal pain in the pediatric population. Radiological evaluation is necessary to establish a specific diagnosis and to differentiate appendicitis from these conditions as they can be often managed conservatively without surgical intervention.

Epstein–Barr virus (EBV) is estimated to infect more than 98% of adults worldwide and is one of the most common human viruses. Acute acalculous cholecystitis (AAC) of the gallbladder is an atypical complication of infectious mononucleosis caused by EBV. Conservative management has been described in the context of AAC caused by EBV. A surgical approach must be considered in the case of acute complications such as perforation or gallbladder gangrene. We present the case of a 10-year-old female patient with AAC due to infectious mononucleosis syndrome caused by primary EBV infection.

Relational event models shift the analytical focus away from network ties defined in terms of transitions between mutually exclusive states of connectivity, to bonding processes emerging from observable flows linking senders and receivers of action. In this framework, the possibility to connect social mechanisms of theoretical interest to sequences of observed relational events depends on the relative speed at which these mechanisms operate. Building on established non-parametric methods in survival analysis, in this paper we introduce a new approach to the analysis of the internal time distribution of relational mechanisms of broad theoretical interest in research on the evolutionary dynamics of social and other kinds of networks. We propose general algorithms that may be adopted to study the time structure of theoretically relevant network mechanisms. We illustrate the practical value of our proposal in an analysis of a large sample of high-frequency financial transactions observed over a period of 11 years. We show how the internal time structure of the social mechanisms that control flows of market transactions is sensitive to institutional change in transaction regimes induced by successive financial crises. The results we report invite reflection on a new notion of network “structure” incorporating change as one of its constitutive elements. The study suggests a number of conjectures that provide broad conceptual bases for the development of testable hypotheses about the forces that shape the evolutionary dynamics of network structure.

Turbidite successions can behave either as aquitards or aquifers depending on their lithological and hydraulic features. In particular, post-depositional processes can increase rock permeability due to fracture development in the competent layers. Thus, at a local scale, turbidite systems warrant further detailed investigations, aimed at reconstructing reliable hydrogeological models. The objective of this work was to investigate from the hydrogeological perspective a turbiditic aquifer located in southern Italy, where several perennial and seasonal springs were detected. Considering the complex hydrodynamics of these systems at the catchment scale, to reach an optimal characterization, a multidisciplinary approach was adopted. The conceptual framework employed microbial communities as groundwater tracers, together with the physicochemical features and isotopic signature of springs and streams from water samples. Meanwhile, geophysical investigations coupled with the geological survey provided the contextualization of the hydrogeological data into the detailed geological reconstruction of the study area. This modus operandi allowed us to typify several differences among the samples, allowing identification of sources and paths of surface water and groundwater, along with diffuse groundwater outflow along streams. As a final result, a hydrogeological conceptual model was reconstructed, underlining how at a very local scale the lithologic, hydraulic, and geomorphological heterogeneity of the studied relief can lead to an improved hydrogeological conceptual model compared to that of other turbidite systems. These results open new questions about the hydrogeological behavior of turbiditic aquifers, which could be pivotal in future research. In fact, these systems could support relevant ecosystems and anthropic activities, especially where climate change will force the research of new (and probably less hydrogeologically efficient) water sources.

Methyl farnesoate (MF), a juvenile hormone, can influence phenotypic traits and stimulates male production in daphnids. MF is produced endogenously in response to stressful conditions, but it is not known whether this hormone can also be released into the environment to mediate stress signaling. In the present study, for the first time, a reliable solid-phase microextraction–gas chromatography–mass spectrometry (SPME-GC-MS) method was developed and validated for the ultra-trace analysis of MF released in growth medium by Daphnia pulex maintained in presence of crowding w/o MK801, a putative upstream inhibitor of MF endogenous production. Two different clonal lineages, I and S clones, which differ in the sensitivity to the stimuli leading to male production, were also compared. A detection limit of 1.3 ng/L was achieved, along with good precision and trueness, thus enabling the quantitation of MF at ultra-trace level. The achieved results demonstrated the release of MF by both clones at the 20 ng/L level in control conditions, whereas a significant decrease in the presence of crowding was assessed. As expected, a further reduction was obtained in the presence of MK801. These findings strengthen the link between environmental stimuli and the MF signaling pathway. Daphnia pulex, by releasing the juvenile hormone MF in the medium, could regulate population dynamics by means of an autoregulatory feedback loop that controls the intra- and extra-individual-level release of MF produced by endogenous biosynthesis.

The Better hEAring Rehabilitation (BEAR) project aims to provide a new clinical profiling tool—a test battery—for hearing loss characterization. Although the loss of sensitivity can be efficiently measured using pure-tone audiometry, the assessment of supra-threshold hearing deficits remains a challenge. In contrast to the classical “attenuation-distortion” model, the proposed BEAR approach is based on the hypothesis that the hearing abilities of a given listener can be characterized along two dimensions, reflecting independent types of perceptual deficits (distortions). A data-driven approach provided evidence for the existence of different auditory profiles with different degrees of distortions. Ten tests were included in a test battery, based on their clinical feasibility, time efficiency, and related evidence from the literature. The tests were divided into six categories: audibility, speech perception, binaural processing abilities, loudness perception, spectro-temporal modulation sensitivity, and spectro-temporal resolution. Seventy-five listeners with symmetric, mild-to-severe sensorineural hearing loss were selected from a clinical population. The analysis of the results showed interrelations among outcomes related to high-frequency processing and outcome measures related to low-frequency processing abilities. The results showed the ability of the tests to reveal differences among individuals and their potential use in clinical settings.

Neisseria meningitidis serogroup B (MenB) is the leading cause of meningococcal meningitis and sepsis in industrialized countries, with the highest incidence in infants and adolescents. Two recombinant protein vaccines that protect against MenB are now available (i.e. 4CMenB and MenB-fHbp). Both vaccines contain the Factor H Binding Protein (fHbp) antigen, which can bind the Human Factor H (fH), the main negative regulator of the alternative complement pathway, thus enabling bacterial survival in the blood. fHbp is present in meningococcal strains as three main variants which are immunologically distinct. Here we sought to obtain detailed information about the epitopes targeted by anti-fHbp antibodies induced by immunization with the 4CMenB multicomponent vaccine. Thirteen anti-fHbp human monoclonal antibodies (mAbs) were identified in a library of over 100 antibody fragments (Fabs) obtained from three healthy adult volunteers immunized with 4CMenB. Herein, the key cross-reactive mAbs were further characterized for antigen binding affinity, complement-mediated serum bactericidal activity (SBA) and the ability to inhibit binding of fH to live bacteria. For the first time, we identified a subset of anti-fHbp mAbs able to elicit human SBA against strains with all three variants and able to compete with human fH for fHbp binding. We present the crystal structure of fHbp v1.1 complexed with human antibody 4B3. The structure, combined with mutagenesis and binding studies, revealed the critical cross-reactive epitope. The structure also provided the molecular basis of competition for fH binding. These data suggest that the fH binding site on fHbp v1.1 can be accessible to the human immune system upon immunization, enabling elicitation of human mAbs broadly protective against MenB. The novel structural, biochemical and functional data are of great significance because the human vaccine-elicited mAbs are the first reported to inhibit the binding of fH to fHbp, and are bactericidal with human complement. Our studies provide molecular insights into the human immune response to the 4CMenB meningococcal vaccine and fuel the rationale for combined structural, immunological and functional studies when seeking deeper understanding of the mechanisms of action of human vaccines.

Factor H binding protein (fHbp) is a meningococcal virulence factor and a component of vaccines against serogroup B Neisseria meningitidis. Here, the authors characterize the vaccine-elicited human antibody Fab 1A12 and present both the free and the fHbp-bound Fab 1A12 crystal structures.

The bacterium Pseudomonas aeruginosa (PA) and the yeast Candida albicans (CA) are pathogens that cohabit the mucosa of the respiratory tracts of animals and humans. Their virulence is largely determined by chemical communication driven by quorum sensing systems (QS), and the cross perception of their quorum sensing molecules (QSM) can modulate the prevalence of one microorganism over the other. Aiming to investigate whether some of the protein components dissolved in the mucus layering the respiratory mucosa might interfere with virulence and cross-communication of these, and eventually other microorganisms, ligand binding assays were carried out to test the scavenging potential of the bovine and porcine forms of the Lipocalin odorant binding protein (OBP) for several QSMs (farnesol, and acylhomoserine lactones), and for pyocyanin, a toxin produced by PA. In addition, the direct antimicrobial activity of the OBPs was tested by time kill assay (TKA) against CA, PA and other bacteria and yeasts. The positivity of all the ligand binding assays and the antimicrobial activity determined for CA, and for some of the other microorganisms tested, let hypothesize that vertebrate OBPs might behave as humoral components of innate immunity, active against pathogenic bacteria and fungi. In addition, TKAs with mutants of bovine OBP with structural properties different from those of the native form, and with OBP forms tagged with histidines at the amino terminal, provided information about the mechanisms responsible of their antimicrobial activity and suggested possible applications of the OBPs as alternative or co-adjuvants to antibiotic therapeutic treatments.

In vivo solid-phase microextraction (SPME) has been recently proposed for the extraction, clean-up and preconcentration of analytes of biological and clinical concern. Bioanalysis can be performed by sampling exo- or endogenous compounds directly in living organisms with minimum invasiveness. In this context, innovative and miniaturized devices characterized by both commercial and lab-made coatings for in vivo SPME tissue sampling have been proposed, thus assessing the feasibility of this technique for biomarker discovery, metabolomics studies or for evaluating the environmental conditions to which organisms can be exposed. Finally, the possibility of directly interfacing SPME to mass spectrometers represents a valuable tool for the rapid quali- and quantitative analysis of complex matrices. This review article provides a survey of in vivo SPME applications focusing on the extraction of tissues, cells and simple organisms. This survey will attempt to cover the state-of- the-art from 2014 up to 2019.

Pure-tone audiometry still represents the main measure to characterize individual hearing loss and the basis for hearing-aid fitting. However, the perceptual consequences of hearing loss are typically associated not only with a loss of sensitivity but also with a loss of clarity that is not captured by the audiogram. A detailed characterization of a hearing loss may be complex and needs to be simplified to efficiently explore the specific compensation needs of the individual listener. Here, it is hypothesized that any listener's hearing profile can be characterized along two dimensions of distortion: Type I and Type II. While Type I can be linked to factors affecting audibility, Type II reflects non-audibility-related distortions. To test this hypothesis, the individual performance data from two previous studies were reanalyzed using an unsupervised-learning technique to identify extreme patterns in the data, thus forming the basis for different auditory profiles. Next, a decision tree was determined to classify the listeners into one of the profiles. The analysis provides evidence for the existence of four profiles in the data. The most significant predictors for profile identification were related to binaural processing, auditory nonlinearity, and speech-in-noise perception. This approach could be valuable for analyzing other data sets to select the most relevant tests for auditory profiling and propose more efficient hearing-deficit compensation strategies.

Mass spectrometry is the most powerful technique for the detection and identification of organic compounds. It can provide molecular weight information and a wealth of structural details that give a unique fingerprint for each analyte. Due to these characteristics, mass spectrometry-based analytical methods are showing an increasing interest in the scientific community, especially in food safety, environmental, and forensic investigation areas where the simultaneous detection of targeted and nontargeted compounds represents a key factor. In addition, safety risks can be identified at the early stage through online and real-time analytical methodologies. In this context, several efforts have been made to achieve analytical instrumentation able to perform real-time analysis in the native environment of samples and to generate highly informative spectra. This review article provides a survey of some instrumental innovations and their applications with particular attention to spray-based MS methods and food analysis issues. The survey will attempt to cover the state of the art from 2012 up to 2017.

A new methodology for the real time monitoring of hydraulic oil aging based on the vapor analysis using metal oxide semiconductor (MOX) gas sensors has been successfully developed. A dedicated hydraulic test bench was designed and realized to age the oil under controlled condition. Gas chromatographic analyses were performed to detect oil volatile compounds (VOCs) and their concentrations at increasing oil working time. Moreover, a laboratory sensor system have been realized to test the headspace of the same samples. Both measurements highlighted a decrease of the VOCs concentrations.

Physiological studies have shown that noise-induced sensorineural hearing loss (SNHL) enhances the amplitude of envelope coding in auditory-nerve fibers. As pitch coding of unresolved complex tones is assumed to rely on temporal envelope coding mechanisms, this study investigated pitch-discrimination performance in listeners with SNHL. Pitch-discrimination thresholds were obtained for 14 normal-hearing (NH) and 10 hearing-impaired (HI) listeners for sine-phase (SP) and random-phase (RP) complex tones. When all harmonics were unresolved, the HI listeners performed, on average, worse than NH listeners in the RP condition but similarly to NH listeners in the SP condition. The increase in pitch-discrimination performance for the SP relative to the RP condition ( F 0 DL ratio) was significantly larger in the HI as compared with the NH listeners. Cochlear compression and auditory-filter bandwidths were estimated in the same listeners. The estimated reduction of cochlear compression was significantly correlated with the increase in the F 0 DL ratio, while no correlation was found with filter bandwidth. The effects of degraded frequency selectivity and loss of compression were considered in a simplified peripheral model as potential factors in envelope enhancement. The model revealed that reducing cochlear compression significantly enhanced the envelope of an unresolved SP complex tone, while not affecting the envelope of a RP complex tone. This envelope enhancement in the SP condition was significantly correlated with the increased pitch-discrimination performance for the SP relative to the RP condition in the HI listeners.

The study investigated the effects of choline combined with Bangerter filter in the treatment of amblyopia. All amblyopic subjects used a Bangerter filter on the corrective spectacle lens (1d over the left eye, 1d over the right eye). Choline was then administered orally to 39 patients once daily, five days per week for the entire study period. Subjects treated with the Bangerter filter showed a mean visual acuity of 0.27 logMAR; at 12mo of treatment, the mean visual acuity reached 0.09 logMAR. Patients treated with the Bangerter filter and citicoline showed a mean visual acuity of 0.35 logMAR; at 12mo of treatment, the mean visual acuity reached 0.01 logMAR. No significant changes in the angle of deviation were observed in both groups. Subjects in both forms of amblyopia therapies demonstrated an increase in visual acuity. However, these effects were markedly enhanced when coupled with the administration of choline. Findings suggest that the effects are particularly relevant in the more severe amblyopic cases.