Echocardiographic follow-up in patients with mild to moderate mitral stenosis: is a yearly examination justified?

The result of this study showed that echocardiographic and Doppler parameters in patients with mild to moderate mitral stenosis did not undergo any major changes over a relatively long observation period, reflecting the substantial stability of the valve disease process. Thus, unless such patients experience clinical deterioration, a yearly echocardiographic examination appears to be unjustified.     

Dye‐Doped Polyhedral Oligomeric Silsesquioxane (POSS)‐Modified Polymeric Matrices for Highly Efficient and Photostable Solid‐State Lasers

Here, the design, synthesis, and characterization of laser nanomaterials based on dye‐doped methyl methacrylate (MMA) crosslinked with octa(propyl‐methacrylate) polyhedral oligomeric silsesquioxane (8MMAPOSS) is reported in relation to their composition and structure. The influence of the silicon content on the laser action of the dye pyrromethene 567 (PM567) is analyzed in a systematic way by increasing the weight proportion of POSS from 1 to 50%. The influence of the inorganic network structure is studied by replacing the 8MMAPOSS comonomer by both the monofunctionalized heptaisobutyl‐methacryl‐POSS (1MMAPOSS), which defines the nanostructured linear network with the POSS cages appearing as pendant groups of the polymeric chains, and also by a new 8‐hydrogenated POSS incorporated as additive to the polymeric matrices. The new materials exhibit enhanced thermal, optical, and mechanical properties with respect to the pure organic polymers. The organization of the molecular units in these nanomaterials is studied through a structural analysis by solid‐state NMR. The domain size of the dispersed phase assures a homogeneous distribution of POSS into the polymer, thus, a continuous phase corresponding to the organic matrix incorporates these nanometer‐sized POSS crosslinkers at a molecular level, in agreement with the transparency of the samples. The silicon–oxygen core framework has to be covalently bonded into the polymer backbone instead of being a simple additive and both the silica content and crosslinked degree exhibit a critical influence on the laser action.     

Lactic acid bacteria biodiversity in Italian marinated seafood salad and their interactions on the growth of Listeria monocytogenes

The aim of this research was to study the biodiversity of lactic acid bacteria (LAB) in marinated seafood salad (pH 5.0) and their interaction on the growth of Listeria monocytogenes. LAB were highly present in the samples considered in this study, reaching values of 8.0 log cfu/g at the end of product’s shelf-life. A high biodiversity in terms of LAB species and strains was detected by means of RAPD–PCR within the 171 bacterial isolates collected. Among them Lactobacillus curvatus, Lactobacillus sanfranciscensis and Enterococcus were present in all the salad batches considered. Three challenge tests against L. monocytogenes were carried out in order to assess the growth of this pathogen in the presence of dominant populations of LAB. L. monocytogenes tended to decrease in time, suggesting that a stable concentration of LAB inhibits the development of this pathogenic micro-organism.     

In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP

1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm.     

Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions

With the progress of sequencing technologies, an ever-increasing number of variants of unknown functional and clinical significance (VUS) have been identified in both coding and non-coding regions of the main Breast Cancer (BC) predisposition genes. The aim of this study is to identify a mutational profile of coding and intron-exon junction regions of 12 moderate penetrance genes (ATM, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53) in a cohort of 450 Italian patients with Hereditary Breast/Ovarian Cancer Syndrome, wild type for germline mutation in BRCA1/2 genes. The analysis was extended to 5′UTR and 3′UTR of all the genes listed above and to the BRCA1 and BRCA2 known regulatory regions in a subset of 120 patients. The screening was performed through NGS target resequencing on the Illumina platform MiSeq. 8.7% of the patients analyzed is carriers of class 5/4 coding variants in the ATM (3.6%), BRIP1 (1.6%), CHEK2 (1.8%), PALB2 (0.7%), RAD51C (0.4%), RAD51D (0.4%), and TP53 (0.2%) genes, while variants of uncertain pathological significance (VUSs)/class 3 were identified in 9.1% of the samples. In intron-exon junctions and in regulatory regions, variants were detected respectively in 5.1% and in 32.5% of the cases analyzed. The average age of disease onset of 44.4 in non-coding variant carriers is absolutely similar to the average age of disease onset in coding variant carriers for each proband’s group with the same cancer type. Furthermore, there is not a statistically significant difference in the proportion of cases with a tumor onset under age of 40 between the two groups, but the presence of multiple non-coding variants in the same patient may affect the aggressiveness of the tumor and it is worth underlining that 25% of patients with an aggressive tumor are carriers of a PTEN 3′UTR-variant. This data provides initial information on how important it might be to extend mutational screening to the regulatory regions in clinical practice.     

Extension of Collagen Deposition in COVID-19 Post Mortem Lung Samples and Computed Tomography Analysis Findings

Lung fibrosis has specific computed tomography (CT) findings and represents a common finding in advanced COVID-19 pneumonia whose reversibility has been poorly investigated. The aim of this study was to quantify the extension of collagen deposition and aeration in postmortem cryobiopsies of critically ill COVID-19 patients and to describe the correlations with qualitative and quantitative analyses of lung CT. Postmortem transbronchial cryobiopsy samples were obtained, formalin fixed, paraffin embedded and stained with Sirius red to quantify collagen deposition, defining fibrotic samples as those with collagen deposition above 10%. Lung CT images were analyzed qualitatively with a radiographic score and quantitatively with computer-based analysis at the lobe level. Thirty samples from 10 patients with COVID-19 pneumonia deceased during invasive mechanical ventilation were included in this study. The median [interquartile range] percent collagen extension was 6.8% (4.6–16.2%). In fibrotic compared to nonfibrotic samples, the qualitative score was higher (260 (250–290) vs. 190 (120–270), p = 0.036) while the gas fraction was lower (0.46 (0.32–0.47) vs. 0.59 (0.37–0.68), p = 0.047). A radiographic score above 230 had 100% sensitivity (95% confidence interval, CI: 66.4% to 100%) and 66.7% specificity (95% CI: 41.0% to 92.3%) to detect fibrotic samples, while a gas fraction below 0.57 had 100% sensitivity (95% CI: 66.4% to 100%) and 57.1% specificity (95% CI: 26.3% to 88.0%). In COVID-19 pneumonia, qualitative and quantitative analyses of lung CT images have high sensitivity but moderate to low specificity to detect histopathological fibrosis. Pseudofibrotic CT findings do not always correspond to increased collagen deposition.     

Trace elements bioaccumulation in Porcellionides pruinosus (Brandt, 1833) and related biomarkers of exposure

In the last years, the increase of anthropogenic activities has led to a progressive pollution of ecosystems. Oniscidean isopods are a group of terrestrial animals known as excellent bio‐indicators and bio‐accumulators, because of their capacity to accumulate contaminants and to implement appropriate strategies of detoxification. For this study, we collected Porcellionides pruinosus from two different sites in the Corinth region (Greece), a polluted site and a control site, to assess the heavy metal pollution status. We conducted an inductively coupled plasma mass spectrometry (ICP‐MS) analysis for the detection of trace elements in animals' hepatopancreas and soil; we performed also immunohistochemistry for detection of metallothioneins 1 (MT1) and heat shock protein 70 (HSP70s). The results suggest a great capacity of the species in trace elements bioaccumulation and the high degree of pollution of the area near Agioi Theodoroi where the metal pollution index (MPI) is threefolds higher than the control site, due to the presence of significantly higher concentration of arsenic, cadmium, cobalt, chromium, manganese, molybdenum, and lead found in hepatopancreas and soil. The environmental stress is confirmed by the expression of the relative biomarkers of exposure MT1 and HSP70. Our study, with a multimarker approach, consents getting a complete analysis of environmental quality and the effect of pollution on organisms and shows for the first time the heavy metals contamination status in certain Greece area. Furthermore, P. pruinosus proved to be an appropriate indicator of pollution in terrestrial ecosystems.