Towards an objective theory of subjective liking: A first step in understanding the sense of beauty.

The study of the electroencephalogram signals recorded from subjects during an experience is a way to understand the brain processes that underlie their physical and emotional involvement. Such signals have the form of time series, and their analysis could benefit from applying techniques that are specific to this kind of data. Neuroaesthetics, as defined by Zeki in 1999, is the scientific approach to the study of aesthetic perceptions of art, music, or any other experience that can give rise to aesthetic judgments, such as liking or disliking a painting. Starting from a proprietary dataset of 248 trials from 16 subjects exposed to art paintings, using a real ecological context, this paper analyses the application of a novel symbolic machine learning technique, specifically designed to extract information from unstructured data and to express it in form of logical rules. Our purpose is to extract qualitative and quantitative logical rules, to relate the voltage at specific frequencies and in specific electrodes, and that, within the limits of the experiment, may help to understand the brain process that drives liking or disliking experiences in human subjects.

SARS-CoV-2 RNA contamination on surfaces of a COVID-19 ward in a hospital of Northern Italy: what risk of transmission?

OBJECTIVE: SARS-CoV-2 can reportedly exist on inanimate surfaces for a long duration, but there is limited data available from Italian COVID-19 hospital wards, especially for non-intensive care units hosting patients that do not require mechanical ventilation. Identification of the extent of environmental contamination can help in understanding possible virus transmission routes, limit hospital infections and protect healthcare workers. Thus, we investigated virus contamination on surfaces of the acute COVID-19 ward of an Italian hospital. MATERIALS AND METHODS: Ward surfaces, including four points inside and six points outside the patients' rooms were sampled by swabs, seven hours after routine sanitation. To minimize the risk of underestimation of virus detection, two different sensitive molecular methods were used comparatively, and specific internal controls were added to enhance the efficiency of all the analysis steps. RESULTS: SARS-CoV-2 contamination was detected in only three out of all the collected samples, i.e., on two floors and one-bathroom sink, likely reflecting aerosol and saliva contamination, respectively. The overall level of contamination was low, and the floors exhibited a very low level of SARS-CoV-2 presence, evidenced by only one of the two methods used. CONCLUSIONS: The existence of SARS-CoV-2 on hospital surfaces may be limited, although it was reported to persist for a longer duration on surfaces under controlled laboratory conditions. Thus, effective transmission of SARS-CoV-2 by surfaces/fomites within the hospital ward may be a rare event. However, the results highlight the importance of assessing method sensitivity and including controls when investigating low-level virus contamination so as to avoid the risk of underestimation of virus presence.

Morning vs. evening administration of antiviral therapy in COVID-19 patients. A preliminary retrospective study in Ferrara, Italy.

OBJECTIVE: At the end of 2019, the Novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), spread rapidly from China to the whole world. Circadian rhythms can play crucial role in the complex interplay between viruses and organisms, and temporized schedules (chronotherapy) have been positively tested in several medical diseases. We aimed to compare the possible effects of a morning vs. evening antiviral administration in COVID patients. PATIENTS AND METHODS: We retrospectively evaluated all patients admitted to COVID internal medicine units with confirmed SARS-CoV-2 infection, and treated with darunavir-ritonavir (single daily dose, for seven days). Age, sex, length of stay (LOS), pharmacological treatment, and timing of antiviral administration (morning or evening), were recorded. Outcome indicators were death or LOS, and laboratory parameters, e.g., variations in C-reactive protein (CRP) levels, ratio of arterial oxygen partial pressure (PaO2, mmHg) to fractional inspired oxygen (FiO2) (PaO2/FiO2), and leucocyte count. RESULTS: The total sample consisted of 151 patients, 33 (21.8%) of whom were selected for antiviral treatment. The mean age was 61.8±18.3 years, 17 (51.5%) were male, and the mean LOS was 13.4±8.6 days. Nine patients (27.3%) had their antiviral administration in the morning, and 24 (72.7%) had antiviral administration in the evening. No fatalities occurred. Despite the extremely limited sample size, morning group subjects showed a significant difference in CRP variation, compared to that in evening group subjects (-65.82±33.26 vs. 83.32±304.89, respectively, p<0.032). No significant differences were found for other parameters. CONCLUSIONS: This report is the first study evaluating temporized morning vs. evening antiviral administration in SARS-CoV-2 patients. The morning regimen was associated with a significant reduction in CRP values. Further confirmations with larger and multicenter samples of patients could reveal novel potentially useful insights.

A challenging case of pigmented Bowen's disease and differential diagnosis of pagetoid pigmented skin lesions.

We report a singular case of pigmented pagetoid Bowen's disease showing transitional features between extramammary Paget's disease and in situ squamous cell carcinoma.^ieng

Differentiation of pagetoid cutaneous neoplasms can be very challenging on hematoxylin and eosin-stained sections.

Thermo- radio- and optically stimulated luminescence of Ce-doped KYF4 single crystals.

The goals of this work are to determine the luminescence properties of KYF4 single crystals doped with different concentrations of Ce3+ ions and to evaluate their possible application as a detector of beta radiation. In particular, thermoluminiscence, radioluminiscence and optically stimulated luminescence properties of KYF4: Ce3+ exposed to beta radiation have been studied and very good dosimetric properties have been obtained within the dose range 0.02-20 Gy.

Short implants (6mm) vs. vertical bone augmentation and standard-length implants (≥9mm) in atrophic posterior mandibles: a 5-year retrospective study.

This retrospective study compared the 5-year clinical and radiographic outcomes of short implants (6 mm) (short group), and standard-length implants (≥9mm) placed after a vertical augmentation with autologous bone blocks (augmentation group), supporting partial fixed prostheses in the posterior mandible. Forty-five partially edentulous patients were enrolled in the study and evaluated after 5 years: 22 (51 implants) in the augmentation group and 23 (46 implants) in the short group. Eight surgical complications occurred in the augmentation group versus none in the short group (P=0.003). One short implant failed before loading and one standard-length implant failed after 4 years because of peri-implantitis (P=1.0). Eight biological and two prosthetic complications occurred in the augmentation group vs. three biological and three prosthetic complications in the short group (P=0.09 and P=1.0, respectively). A mean marginal bone loss of 1.61±1.12mm in the augmentation group and 0.68±0.68mm in the short group was found (P=0.002). Within the limitations of this study, both techniques resulted in successful clinical results after 5 years, but short implants exhibited less surgical complications and marginal bone loss than standard-length implants placed in augmented bone.

New algorithm for analyzing phosphorescence curves: Its application to the K2YF5:Pr compound.

Analysis of phosphorescence curves is an alternative procedure to glow curve analysis in order to find the parameters characterizing trap and recombination centers of thermoluminescence materials. In this article a new algorithm to analyze phosphorescence curves is reported, which is derived from the set of coupled differential equation describing the carrier traffic without resorting to approximations. The new algorithm has been employed to analyze the phosphorescence curves of the K2YF5:Pr compound.

Detection of HHV-6-specific mRNA and antigens in PBMCs of individuals with chromosomally integrated HHV-6 (ciHHV-6).

After inheritance of chromosomally integrated HHV-6 (ciHHV-6), viral DNA is found in every nucleated cell. The prevalence of ciHHV-6 is estimated to be 0.2-5% of humans. There are conflicting data on the potential for replication, possibly leading to clinical implications. We analysed peripheral blood mononuclear cells (PBMCs) from individuals with ciHHV-6 proven by fluorescence in situ hybridization (FISH) for HHV-6-specific mRNA (U94, U42, U22) and antigens by means of reverse transcription PCR and an indirect immunoperoxidase staining. U94 transcripts indicative of latent infection were detected in six (54.5%) out of 11 individuals at least once. Transcripts indicative of lytic infection (i.e. U42 and U22) were detected in four (36.4%) out of 11 individuals at least once. HHV-6 antigen was detected in seven (70%) out of 10 individuals at least once. The presence of viral mRNA and proteins supports virus gene expression from ciHHV-6, which may lead to virus replication. Considering the properties of active HHV-6 infection together with obvious replicative activity in individuals with ciHHV-6, pathophysiological effects leading to clinical consequences of chromosomally integrated viral DNA might be considered.

Analysis of the main dosimetric peak of Al2O3:C compounds with a model of interacting traps.

The glow curve of Al2O3:C compounds has been analyzed by employing a model consisting of two active traps, thermally disconnected traps and one recombination centre. The analysis takes into account interaction among traps and the thermal quenching of the thermoluminescent emission.

Radioluminescence of red-emitting Eu-doped phosphors for fiberoptic dosimetry.

Fiberoptic dosimetry (FOD) technique has become an attractive method for real-time dosimetry. Al(2)O(3):Cis one of the most used radioluminescence materials for FOD due to its high efficiency but it presents the drawback of emitting in the spectral region, where spurious luminescence is also important. Optical filtering is the simplest technique to remove spurious luminescence, but is useful when red-emitting scintillators are employed. In this work, the feasibility of using red-emitting Eu-doped phosphors as FOD scintillators has been investigated.

Panbacterial real-time PCR to evaluate bacterial burden in chronic wounds treated with Cutimed™ Sorbact™.

The impact of polymicrobial bacterial infection on chronic wounds has been studied extensively, but standard bacteriological analysis is not always sensitive enough. Molecular approaches represent a promising alternative to the standard bacteriological analysis. This work aimed to assess the usefulness of a panbacterial quantitative real-time PCR reaction to quantitate the total bacterial load in chronic wounds treated with Cutimed™ Sorbact™, a novel therapeutic approach based on hydrophobic binding of bacteria to a membrane. The results obtained by panbacterial real-time PCR on conserved sequences of the bacterial 16S gene show that the bacterial burden significantly decreased in 10 out of 15 healing chronic wounds, and did not change in 5 out of 5 non-healing chronic wounds. On the contrary, classical culture for S. aureus and P. aeruginosa, and real-time PCR for Bacteroides and Fusobacterium did not show any correlation with the clinical outcome. Our study also shows that quantification of chronic wounds by panbacterial real-time PCR is to be performed on biopsies and not on swabs. These results show that panbacterial real-time PCR is a promising and quick method of determining the total bacterial load in chronic wounds, and suggest that it might be an important biomarker for the prognosis of chronic wounds under treatment.

Kinetic study of the thermoluminescence of KMgF3:LaF3 compounds employing the general one trap model.

The parameters characterising the trap centres involved in the thermoluminescence of KMgF3:LaF3 compounds have been found by deconvolving the glow curve with the General One Trap model (GOT). For the fitting procedure the Levenberg-Marquardt method has been employed. Tm-T(stop) measurements along with initial rise measurements were performed in order to estimate the number of peaks the glow curve is made up of, and the corresponding activation energies. Instead of the Runge-Kutta method, a novel algorithm has been employed to integrate the differential equation of the GOT model, which reduces the computational time nearly 30 times with respect to the former when the glow curve is recorded with a lineal heating rate profile. The strong computational time reduction makes feasible a large number of runs with different guess values. An interesting result is that the concentration of disconnected deep traps is much less than the concentration of trap centres.

A combined bovine herpesvirus 1 gB-gD DNA vaccine induces immune response in mice.

Although DNA vaccines have several advantages over conventional vaccines, antibody production and protection are often not adequate, particularly in single plasmid vaccine formulations. Here we assessed the potential for a combined vaccine based on plasmids encoding the membrane-anchored or secreted forms of bovine herpesvirus type 1 (BHV-1) glycoprotein B and D (gB and gD) to induce neutralizing and cell mediated immune responses in mice. Animals were injected by intramuscular, subcutaneous and intranasal routes. Mice immunized with the combined vaccine containing the secreted forms of BHV-1 glycoproteins developed higher titers of anti-BHV-1 neutralizing antibodies, compared to wild type gB/gD combined plasmids and to single plasmid injected groups. Cellular immunity was also developed in mice immunized with combined vaccines, whereas low or no response were observed in single plasmid injected animals. The data suggest the potential use of this combined vaccine in in vivo trials of calves, in order to evaluate its protective efficacy.

Human herpesvirus 6 infects the central nervous system of multiple sclerosis patients in the early stages of the disease.

The presence and the replicative state of human herpesvirus 6 (HHV-6) were evaluated in clinical samples from multiple sclerosis (MS) patients at the first time of MS diagnosis. HHV-6 variant B was present in peripheral blood mononuclear cells of 5/32 (15%) patients, but persisted with a latent infection. Viral sequences were present also in cerebrospinal fluid (CSF), both free in the liquid (7/32, 22%) and latent in the cellular fraction (3/32, 9%), as shown by analysis of viral transcription. In these cases, variant A was detected. HHV-6 DNA sequences present in the CSF were associated to mature viral particles. In fact, in vitro infectious assays of CSF showed the presence of replication-competent virions. These results show that about 20% of MS patients have active foci of HHV-6 variant A infection in the early stages of the disease and suggest that viral replication takes place within the central nervous system.

Structures of ceftazidime and its transition-state analogue in complex with AmpC beta-lactamase: implications for resistance mutations and inhibitor design.

Third-generation cephalosporins are widely used beta-lactam antibiotics that resist hydrolysis by beta-lactamases. Recently, mutant beta-lactamases that rapidly inactivate these drugs have emerged. To investigate why third-generation cephalosporins are relatively stable to wild-type class C beta-lactamases and how mutant enzymes might overcome this, the structures of the class C beta-lactamase AmpC in complex with the third-generation cephalosporin ceftazidime and with a transition-state analogue of ceftazidime were determined by X-ray crystallography to 2.0 and 2.3 A resolution, respectively. Comparison of the acyl-enzyme structures of ceftazidime and loracarbef, a beta-lactam substrate, reveals that the conformation of ceftazidime in the active site differs from that of substrates. Comparison of the structures of the acyl-enzyme intermediate and the transition-state analogue suggests that ceftazidime blocks formation of the tetrahedral transition state, explaining why it is an inhibitor of AmpC. Ceftazidime cannot adopt a conformation competent for catalysis due to steric clashes that would occur with conserved residues Val211 and Tyr221. The X-ray crystal structure of the mutant beta-lactamase GC1, which has improved activity against third-generation cephalosporins, suggests that a tandem tripeptide insertion in the Omega loop, which contains Val211, has caused a shift of this residue and also of Tyr221 that would allow ceftazidime and other third-generation cephalosporins to adopt a more catalytically competent conformation. These structural differences may explain the extended spectrum activity of GC1 against this class of cephalosporins. In addition, the complexed structure of the transition-state analogue inhibitor (K(i) 20 nM) with AmpC reveals potential opportunities for further inhibitor design.

Structure-based design and in-parallel synthesis of inhibitors of AmpC beta-lactamase.

BACKGROUND: Group I beta-lactamases are a major cause of antibiotic resistance to beta-lactams such as penicillins and cephalosporins. These enzymes are only modestly affected by classic beta-lactam-based inhibitors, such as clavulanic acid. Conversely, small arylboronic acids inhibit these enzymes at sub-micromolar concentrations. Structural studies suggest these inhibitors bind to a well-defined cleft in the group I beta-lactamase AmpC; this cleft binds the ubiquitous R1 side chain of beta-lactams. Intriguingly, much of this cleft is left unoccupied by the small arylboronic acids. RESULTS: To investigate if larger boronic acids might take advantage of this cleft, structure-guided in-parallel synthesis was used to explore new inhibitors of AmpC. Twenty-eight derivatives of the lead compound, 3-aminophenylboronic acid, led to an inhibitor with 80-fold better binding (2; K(i) 83 nM). Molecular docking suggested orientations for this compound in the R1 cleft. Based on the docking results, 12 derivatives of 2 were synthesized, leading to inhibitors with K(i) values of 60 nM and with improved solubility. Several of these inhibitors reversed the resistance of nosocomial Gram-positive bacteria, though they showed little activity against Gram-negative bacteria. The X-ray crystal structure of compound 2 in complex with AmpC was subsequently determined to 2.1 A resolution. The placement of the proximal two-thirds of the inhibitor in the experimental structure corresponds with the docked structure, but a bond rotation leads to a distinctly different placement of the distal part of the inhibitor. In the experimental structure, the inhibitor interacts with conserved residues in the R1 cleft whose role in recognition has not been previously explored. CONCLUSIONS: Combining structure-based design with in-parallel synthesis allowed for the rapid exploration of inhibitor functionality in the R1 cleft of AmpC. The resulting inhibitors differ considerably from beta-lactams but nevertheless inhibit the enzyme well. The crystal structure of 2 (K(i) 83 nM) in complex with AmpC may guide exploration of a highly conserved, largely unexplored cleft, providing a template for further design against AmpC beta-lactamase.

Energetic, structural, and antimicrobial analyses of beta-lactam side chain recognition by beta-lactamases.

BACKGROUND: Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these beta-lactams, most often through bacterial expression of beta-lactamases, threatens public health. To understand how beta-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because beta-lactams form covalent adducts with beta-lactamases. This has complicated functional analyses and inhibitor design. RESULTS: To investigate the contribution to interaction energy of the key amide (R1) side chain of beta-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well as four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine beta-lactamases. Therefore, binding energies can be calculated directly from K(i) values. The K(i) values measured span four orders of magnitude against the Group I beta-lactamase AmpC and three orders of magnitude against the Group II beta-lactamase TEM-1. The acylglycineboronic acids have K(i) values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of beta-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of beta-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to beta-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 A and 1.75 A resolution; these structures suggest interactions that are important to the affinity of the inhibitors. CONCLUSIONS: Acylglycineboronic acids allow us to begin to dissect interaction energies between beta-lactam side chains and beta-lactamases. Surprisingly, there is little correlation between the affinity contributed by R1 side chains and their occurrence in beta-lactam inhibitors or beta-lactam substrates of serine beta-lactamases. Nevertheless, presented in acylglycineboronic acids, these side chains can lead to inhibitors with high affinities and specificities. The structures of their complexes with AmpC give a molecular context to their affinities and may guide the design of anti-resistance compounds in this series.

Mice genetic immunization with plasmid DNA encoding a secreted form of HSV-1 gB induces a protective immune response against herpes simplex virus type 1 infection.

Intramuscularly (i.m.) delivered plasmid DNA encoding a secreted form of glycoprotein B of herpes simplex virus type 1 (HSV-1 gB1s) was evaluated for the ability to elicit a protective immune response in Balb/c mice. Animals received three i.m. injections of a gB1s expression plasmid (pRP-RSV-gB1s) or of a wild-type transmembrane gB1 coding plasmid (pRP-RSV-gB1), while control mice were injected with the vector alone (pRP-RSV). A specific antibody response was observed in almost all immunized animals, and in most cases antibodies were also detected after 1 month in the absence of further vaccine boosts. Serum antibodies mostly displayed neutralizing activity against HSV-1. Glycoprotein B1s DNA immunization was also effective in protecting animals against the primary infection induced by a subsequent HSV-1 challenge and limited HSV-1 infection of sensitive ganglia.