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Background Eosinophilic dermatosis of hematologic malignancy (EDHM) is a rare dermatosis associated with blood tumors. Objective To characterize the expression of T-cell and B-cell markers and pruritogenic mediators in EDHM skin. Methods Immunohistochemical and immunofluorescence analysis were performed in 12 skin samples of EDHM, 11 samples of bullous pemphigoid (BP), and 5 samples from healthy controls (HC). Serum levels of interleukin (IL) 4 were analyzed in 11 patients with EDHM, 11 BP patients, and 5 HC by enzyme-linked immunosorbent assay. Results T-cell markers, including clusters of differentiation (CD) 3, CD4, CD8, and CD5 were significantly overexpressed in EDHM and BP skin compared to HC. A predominance of CD4+ over CD8+ cells and GATA3+ (helper T cell type 2 [Th2] marker) over T-bet+ (Th1 marker) cells were observed. FOXP3 expression was increased but the FOXP3/CD4 ratio was low. B-cell markers were under-represented, without significant differences between the 3 groups. IL-4 and IL-31 were significantly overexpressed in EDHM and BP compared to HC and colocalized with the Th2-associated marker GATA3. Eotaxin-1 was significantly overexpressed in EDHM compared to BP and HC. IL-4 serum concentration was significantly increased in EDHM and BP compared to HC. Limitations Small sample size; retrospective design. Conclusions Targeting Th2-related molecules, in particular IL-4, holds promise for EDHM management.

Rationale and Objectives To evaluate an MRI radiomics-powered machine learning (ML) model's performance for the identification of deep myometrial invasion (DMI) in endometrial cancer (EC) patients and explore its clinical applicability. Materials and Methods Preoperative MRI scans of EC patients were retrospectively selected. Three radiologists performed whole-lesion segmentation on T2-weighted images for feature extraction. Feature robustness was tested before randomly splitting the population in training and test sets (80/20% proportion). A multistep feature selection was applied to the first, excluding noninformative, low variance features and redundant, highly-intercorrelated ones. A Random Forest wrapper was used to identify the most informative among the remaining. An ensemble of J48 decision trees was tuned and finalized in the training set using 10-fold cross-validation, and then assessed on the test set. A radiologist evaluated all MRI scans without and with the aid of ML to detect the presence of DMI. McNemars's test was employed to compare the two readings. Results Of the 54 patients included, 17 had DMI. In all, 1132 features were extracted. After feature selection, the Random Forest wrapper identified the three most informative which were used for ML training. The classifier reached an accuracy of 86% and 91% and areas under the Receiver Operating Characteristic curve of 0.92 and 0.94 in the cross-validation and final testing, respectively. The radiologist performance increased from 82% to 100% when using ML (p = 0.48). Conclusion We proved the feasibility of a radiomics-powered ML model for DMI detection on MR T2-w images that might help radiologists to increase their performance.

Purpose An ongoing pandemic of COVID-19 that started in Hubei, China has resulted in massive strain on the healthcare infrastructure in Lombardy, Italy. The management of these patients is still evolving. Materials and methods This is a single-center observational cohort study of critically ill patients infected with COVID-19. Bedside clinicians abstracted daily patient data on history, treatment, and short-term course. We describe management and a proposed severity scale for treatment used in this hospital. Results 44 patients were enrolled; with incomplete information on 11. Of the 33 studied patients, 91% were male, median age 64; 88% were overweight or obese. 45% were hypertensive, 12% had been taking an ACE-inhibitor. Noninvasive ventilation was performed on 39% of patients for part or all or their ICU stay with no provider infection. Most patients received antibiotics for pneumonia. Patients also received lopinivir/ritonavir (82%), hydroxychloroquine (79%), and tocilizumab (12%) according to this treatment algorithm. Nine of 10 patients survived their ICU course and were transferred to the floor, with one dying in the ICU. Conclusions ICU patients with COVID-19 frequently have hypertension. Many could be managed with noninvasive ventilation, despite the risk of aerosolization. The use of a severity scale augmented clinician management., Highlights • COVID-19 is a global pandemic that has recently devastated Italy • Hospitals in Italy have experience strain on resources and used non-intensivists to manage critically ill patients. • Investigators created a severity scale for communicating with non-intensivist for triage and management • Hospitals should consider adapting or revising a severity scale when utilizing non-intensivist physicians.

L-Glutamate (L-Glu) is a well-known flavour enhancer that is present in several foodstuffs. Although L-Glu is generally recognized as safe, the use in foodstuffs remains controversial and then its fast and accurate monitoring represents an important issue. In this work a sensitive and interference-free disposable amperometric biosensor for glutamate monitoring in foodstuffs was developed. The biosensor was prepared by immobilizing glutamate oxidase through co-crosslinking with bovine serum albumin and glutaraldehyde onto a screen printed disposable platinum electrode modified with a permselective overoxidized polypyrrole film. The enzyme immobilization was optimized by using different experimental procedures. The optimized glutamate biosensor was integrated in a flow injection system and characterized in terms of linearity (0.005–1.0 mM, r2 = 0.992), limits of detection (1.8 μM) and quantitation (5.4 μM), repeatability (RSD

To evaluate, in a multi-institutional context, the role of Dose Volume Histogram (DVH) sharing in order to achieve higher plan quality, to harmonize prostate Stereotactic Body Radiation Therapy (SBRT) plans and to assess if the planner's experience in SBRT could lead to lower dose at organs at risk (OARs).During the first phase five patients enrolled for prostate SBRT were planned by multiple physicists according to common protocol. The prescription dose was 35 Gy in 5 fractions. Dosimetric parameters, modulation index (MIt), plan parameters, and planner experience level (EL) were statistically analyzed. During the second phase median DVHs from all centers were shared and physicists replanned one patient of the five, aiming at inter-planner harmonization and further OARs sparing. Data were summarized by Spearman-correlogram (p 0.05) and boxplots. The Kruskal-Wallis test was used to compare the re-plans to the original plans.Seventy-eight SBRT plans from 13 centers were evaluated. EL correlated with modulation of plan parameters and reduction of OARs doses, such as volume receiving 28 Gy of rectum (rectum-V28Gy), rectum-V32Gy, and bladder-V30Gy. The re-plans showed significant reduced variability in rectum-V28Gy and increased PTV dose homogeneity. No significant difference in plan complexity metrics and plan parameters between plans and re-plans were obtained.Planner's experience in prostate SBRT was correlated with dosimetric parameters. Sharing median DVHs reduced variability among centers whilst keeping the same level of plan complexity. SBRT planning skills can benefit from a replanning phase after sharing DVHs from multiple centers, improving plan quality and concordance among centers.

Resumen Recientemente han surgido numerosas publicaciones sobre la aplicacion del bloqueo del plano del musculo erector de la columna espinal en poblacion adulta. Existen escasos reportes del uso de este bloqueo en cirugia pediatrica. Nuestro objetivo es reportar 2 casos de adolescentes, uno con diagnostico de pectus excavatum y otro de pectus carinatum, sometidos a cirugia reconstructiva esternal a los que se realizo bloqueo del plano del musculo erector de la columna espinal bilateral en inyeccion unica como tecnica analgesica. El bloqueo se realizo antes de la cirugia con los pacientes sometidos a anestesia general en posicion de decubito lateral, guiado por ecografia utilizando 20 ml de bupivacaina al 0,25% por lado. Luego de la cirugia fueron extubados y trasladados a la Unidad de Cuidados Intensivos. Durante su hospitalizacion los valores de la escala visual analoga fueron menores de 4 y no fue requerido el uso de opioides de larga duracion durante el intraoperatorio ni el postoperatorio de los pacientes. El bloqueo del plano del musculo erector de la columna espinal bilateral en inyeccion unica fue efectivo como tecnica analgesica para el intra y el postoperatorio en cirugia de pectus excavatum y pectus carinatum en poblacion adolescente.

Numerous publications have emerged on the application of erector spinae plane block in adult population. There are few reports of the use of this block in pediatric patients. The objective is to report 2 cases of adolescents, one diagnosed with pectus excavatum and the other one with pectus carinatum undergoing reconstructive surgery in which a bilateral single-shot erector spinae plane block was performed as an analgesic technique. The block was performed before surgery under general anesthesia in lateral decubitus position, guided by ultrasound using 20ml of 0.25% bupivacaine per side. After the surgery they were extubated and transferred to the Intensive Care Unit. During their postoperative period they had visual analogic scale values less than 4 and no long term narcotics were used during the intraoperative and postoperative period. Bilateral single shot erector spinae plane block was effective as an analgesic technique for the intraoperative and postoperative period in pectus excavatum and pectus carinatum surgery in adolescents.

Andrographolide is a major diterpenoid of Andrographis paniculata and possesses several biological activities, including protection against oxidative stress mediated neurotoxicity, inflammation-mediated neurodegeneration, and cerebral ischemia. However, this molecule shows low bioavailability, poor water solubility, and high chemical and metabolic instability. The present study reports preparation of solid lipid nanoparticles (SLN) to deliver andrographolide (AG) into the brain. SLN were prepared using Compritol 888 ATO as solid lipid and Brij 78 as surfactant and applying emulsion/evaporation/solidifying method as preparative procedure. Nanoparticles have a spherical shape, small dimensions, and narrow size distribution. Encapsulation efficiency of AG-loaded SLN was found to be 92%. Nanoparticles showed excellent physical and chemical stability during storage at 4°C for one month. The lyophilized product was also stable at 25°C during the same period. SLN remained unchanged also in the presence of human serum albumin and plasma. In vitro release at pH 7.4 was also studied. The release of AG was prolonged and sustained when the compound was entrapped in SLN. The ability of SLN to cross the blood-brain barrier (BBB) was evaluated first in vitro by applying a permeation test with artificial membrane (parallel artificial membrane permeability assay, PAMPA) to predict passive and transcellular permeability through the BBB, and then by using hCMEC/D3 cells, a well-established in vitro BBB model. In vitro results proved that nanoparticles improved permeability of AG compared to free AG. Fluorescent nanoparticles were then prepared for in vivo tests in healthy rats. After intravenous administration, fluorescent SLN were detected in brain parenchyma outside the vascular bed, confirming their ability to overcome the BBB.

Benzene derivatives (BDs) constitute a class of environmental pollutants whose exposure poses a grave risk to human health. These compounds rapidly diffuse from the atmosphere to the marine ecosystem: for this reason, their monitoring in seawater is every day more compelling. In this work, nanoconfined liquid phase nanoextraction (NLPNE), a versatile extraction technique recently described, has been for the first time applied to the gas chromatographic mass spectrometry (GC/MS) analysis of BDs in seawater. Ex-situ and in-situ NLPNE procedures have been developed and optimized in terms of extraction capabilities, analysis time, precision, and accuracy. Compared to the traditional extraction procedures, based on solid-phase microextraction (SPME) and liquid-liquid extraction (LLE), the proposed NLPNE methods allowed a rapid on-site analysis of benzene compounds with low solvent consumption, higher enrichment factors, and improved automation grade. Determination coefficients ranging from 0.9929 to 0.9997 were obtained for all BDs in the range 0.10–500 ng mL−1 and 5.00–500 ng mL−1, for ex-situ and in-situ NLPNE, respectively. Ex-situ and in-situ limits of detection ranged from 0.2 to 7.6 ng mL−1 and 0.04–1.00 ng mL−1. Our results suggest that NLPNE coupled to GC-MS can be considered a powerful technique for high-throughput analyses of trace compounds in environmental, food and biological samples.

A fundamental issue in proteomics is the peptide identification by database searching and the assessment of the goodness of fit between experimental and theoretical data. Despite the different number of ways to measure the quality of search results, the definition of a scoring criterion is still highly desirable in ion-trap based proteomics. Indeed, in order to fully take advantage of a low resolution MS/MS dataset, it is essential to strike a balance between greater information capture and reduced number of incorrect peptide assignments. In addition, the development of user-specified rules is a crucial aspect when very similar proteins of the same family are analyzed in order to infer the origin species. In this study, a post-processing validation scheme is provided for the evaluation of proteomic data in shot-gun ion-trap proteomics, when a flexible database searching based on the error tolerant mode is adopted in combination with a low-specificity enzyme to maximize sequence coverage. To validate peptide assignments, we used standard β-casein digested with trypsin/chymotrypsin or trypsin alone and the popular search engine MASCOT to identify the relevant (known) peptide sequences. A linear combination between peptide ion score and normalized delta score (i.e. the difference between the best and the second best ion score, divided by the best score) is proposed to increase the accuracy in sequence assignments from low-resolution tandem mass spectra. Finally, the optimized post-processing database validation was successfully applied to the direct analysis of milk tryptic/chymotryptic digests of different origin, without resorting to two-dimensional electrophoresis that is usually performed for protein separation in ion-trap proteomics. The identification of species-specific amino acidic sequences among the validated peptide spectrum matches has allowed to fully discriminate between the animal species, so evaluating accurately the milk authenticity.

A dedicated proteomic approach based on nano-Liquid Chromatography coupled with tandem mass spectrometry in ion trap is proposed for the analysis of proteins trapped in sorbent resin cartridges used to remove inflammatory mediators from blood by coupled plasma filtration adsorption (CPFA). The final purpose of the proposed proteomic approach was to obtain a reference map of plasma proteins trapped in CPFA sorbents used for the extracorporeal blood purification of healthy pigs, with the potential impact to design new bio-filters able to control the inflammatory imbalance under pathological conditions, such as severe sepsis. The five main steps of the proteomics analysis, (i) protein extraction from resin cartridges, (ii) two-dimensional gel electrophoresis (2D-PAGE) for protein separation and profiling, (iii) in-gel proteolytic digestion, (iv) tandem mass analysis of peptides resulting from enzymatic cleavage and (v) bioinformatics, for protein identification and post-processing validation of MS/MS data sets, have been carefully evaluated. Prior to electrophoresis, the efficiency of different extraction solutions and procedures to recovery plasma proteins trapped into the sorbents were tested. Then, a rapid one-step procedure for protein extraction was optimized. Protein bands corresponding to the main plasma proteins, namely porcine serum albumin, serotransferrin and immunoglobulins, were identified. In addition, the presence of haptoglobin, hemopexin, α-1 acid glycoprotein and fetuin-A, that are known as acute-phase reaction proteins, was observed, suggesting that CPFA resins led to a non-specifically protein depletion from plasma, rather than targeting specific molecules.

Purpose A large-scale multi-institutional planning comparison on lung cancer SABR is presented with the aim of investigating possible criticism in carrying out retrospective multicentre data analysis from a dosimetric perspective. Methods Five CT series were sent to the participants. The dose prescription to PTV was 54 Gy in 3 fractions of 18 Gy. The plans were compared in terms of PTV-gEUD 2 (generalized Equivalent Uniform Dose equivalent to 2 Gy), mean dose to PTV, Homogeneity Index (PTV-HI), Conformity Index (PTV-CI) and Gradient Index (PTV-GI). We calculated the maximum dose for each OAR (organ at risk) considered as well as the MLD 2 (mean lung dose equivalent to 2 Gy). The data were stratified according to expertise and technology. Results Twenty-six centers equipped with Linacs, 3DCRT (4% – 1 center), static IMRT (8% – 2 centers), VMAT (76% – 20 centers), CyberKnife (4% – 1 center), and Tomotherapy (8% – 2 centers) collaborated. Significant PTV-gEUD 2 differences were observed (range: 105–161 Gy); mean-PTV dose, PTV-HI, PTV-CI, and PTV-GI were, respectively, 56.8 ± 3.4 Gy, 14.2 ± 10.1%, 0.70 ± 0.15, and 4.9 ± 1.9. Significant correlations for PTV-gEUD 2 versus PTV-HI, and MLD 2 versus PTV-GI, were observed. Conclusions The differences in terms of PTV-gEUD 2 may suggest the inclusion of PTV-gEUD 2 calculation for retrospective data inter-comparison.

A controllable composition and morphology AuAg/ZnO catalyst, prepared by an easily scalable method, was, for the first time, explored for the electrocatalytic reduction of CO2. It was found that the composition of the bimetallic alloy contributes to the overall CO2 reduction performance. In particular, as also demonstrated by density functional theory calculations, CO production increases, decreasing the Au content in the catalyst alloy. The experimental investigation reveals that the products are H2 and CO, which production rate increases in the presence of ZnO, up to a Faradic efficiency of 94.7 % at 0.4 V. On the other hand, controlling the oleic acid covering it is possible to modulate the surface properties allowing to obtain, at 0.6 V, H2/CO ratios equal to 1.1 and 1.9 for nanocatalysts thermally treated for 2 and 5 h, respectively.