Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.     

Assessing the health research’s social impact: a systematic review

Scientometrics - In recent year, a growing attention is dedicated to the assessment of research’s social impact. While prior research has often dealt with results of research, the last decade...     

Sensitivity Analysis and Model Validation of a 2-DoF Mini Spherical Robot

This paper is focused on the development and validation of an error kinematic model of a mini spherical robot, aimed at its kinematic calibration. The robot is actually a spatial five-bar linkage, provided with two rotational degrees of freedom. A non-overconstrained kinematics is assumed for the robot in order to provide a simple mathematical model and allow a sensitivity analysis of all the involved geometric parameters. A simplified version of the model is proposed. It differs only for the degree of approximation. A comparison between full and reduced models is presented by means of numerical simulations, analyzing their behavior in a significant region of the robot workspace. In order to validate both of them a robot calibration is carried out on a physical prototype of the robot using a vision system, namely a fixed camera in a eye-to-hand configuration. An iterative algorithm aimed at the experimental identification of the geometric data of the robot is used. Some experimental results show the effectiveness of the study.     

H mesh prosthesis in the treatment of ventral hernia

The Authors report their experience in the treatment of ventral hernias using a Marlex mesh moulded in an original way with a technique partially derived from plastic surgery. The complete mobilization of the umbilicus through a circular incision allows to fit this prosthesis symmetrically below the rectus abdominis muscles for the entire extension of the hernia.     

Modeling and biological investigations of an unusual behavior of novel synthesized acridine-based polyamine ligands in the binding of double helix and G-quadruplex DNA

Three novel 2,7-substituted acridine derivatives were designed and synthesized to investigate the effect of this functionalization on their interaction with double-stranded and G-quadruplex DNA. Detailed investigations of their ability to bind both forms of DNA were carried out by using spectrophotometric, electrophoretic, and computational approaches. The ligands in this study are characterized by an open-chain (L1) or a macrocyclic (L2, L3) framework. The aliphatic amine groups in the macrocycles are joined by ethylene (L2) or propylene chains (L3). L1 behaved similarly to the lead compound m-AMSA, efficiently intercalating into dsDNA, but stabilizing G-quadruplex structures poorly, probably due to the modest stabilization effect exerted by its protonated polyamine chains. L2 and L3, containing small polyamine macrocyclic frameworks, are known to adopt a rather bent and rigid conformation; thus they are generally expected to be sterically impeded from recognizing dsDNA according to an intercalative binding mode. This was confirmed to be true for L3. Nevertheless, we show that L2 can give rise to efficient π-π and H-bonding interactions with dsDNA. Additionally, stacking interactions allowed L2 to stabilize the G-quadruplex structure: using the human telomeric sequence, we observed the preferential induction of tetrameric G-quadruplex forms. Thus, the presence of short ethylene spacers seems to be essential for obtaining a correct match between the binding sites of L2 and the nucleobases on both DNA forms investigated. Furthermore, current modeling methodologies, including docking and MD simulations and free energy calculations, provide structural evidence of an interaction mode for L2 that is different from that of L3; this could explain the unusual stabilizing ability of the ligands (L2>L3>L1) toward G-quadruplex that was observed in this study.     

Solid Acid‐Catalysed Michael‐Type Conjugate Addition of Indoles to Electron‐Poor CC Bonds: Towards High Atom Economical Semicontinuous Processes

In this paper a novel application of solid acid catalysts in the chemoselective Friedel–Crafts (FC) alkylation of indoles is reported. The optimal protocol allows highly functionalised indolyl compounds to be synthesised in excellent yields through conjugate addition of indoles with α,β‐unsaturated ketones and nitro compounds. Finally, the use of commercial Amberlyst‐15 as the heterogeneous catalyst for highly atom efficient continuous and semicontinuous Friedel–Crafts processes is described.     

Premixed metal fibre burners based on a Pd catalyst

As an alternative to previously developed catalytic FeCrAlloy fibre mat burners based on perovskite catalysts, new catalytic burners have been developed based on Pd catalyst on lantana-stabilised Al₂O₃ and different fibre structures (NIT100A, NIT100S and NIT200S by ACOTECH NV). All development steps are considered, shifting from catalyst preparation (based on combustion synthesis of γ-Al₂O₃) to the optimisation of lantana and Pd loadings, from the definitions of the best catalyst-deposition conditions (washcoating) to the catalytic burners performances, determined in an ad hoc developed combustion chamber. The results show almost half pollutants emissions and better performance compared to various non-catalytic counterparts, especially as far as CO and NO_x emissions are concerned. Some flame instability problems were though registered, especially for one of the catalytic burner mattresses employed, at low specific power inputs and excesses of air (<375 kW/m² and <12%, respectively). Further, PdO/Pd transition is shown to influence the dynamic behaviour of the catalytic burners.     

Imaging of KCa3.1 Channels in Tumor Cells with PET and Small-Molecule Fluorescent Probes

The Ca²⁺ activated K⁺ channel K_Ca3.1 is overexpressed in several human tumor cell lines, e. g. clear cell renal carcinoma, prostate cancer, non-small cell lung cancer. Highly aggressive cancer cells use this ion channel for key processes of the metastatic cascade such as migration, extravasation and invasion. Therefore, small molecules, which are able to image this K_Ca3.1 channel in vitro and in vivo represent valuable diagnostic and prognostic tool compounds. The [¹⁸F]fluoroethyltriazolyl substituted senicapoc was used as positron emission tomography (PET) tracer and showed promising properties for imaging of K_Ca3.1 channels in lung adenocarcinoma cells in mice. The novel senicapoc BODIPY conjugates with two F-atoms ( 9 a ) and with a F-atom and a methoxy moiety ( 9 b ) at the B-atom led to the characteristic punctate staining pattern resulting from labeling of single K_Ca3.1 channels in A549-3R cells. This punctate pattern was completely removed by preincubation with an excess of senicapoc confirming the high specificity of K_Ca3.1 labeling. Due to the methoxy moiety at the B-atom and the additional oxyethylene unit in the spacer, 9 b exhibits higher polarity, which improves solubility and handling without reduction of fluorescence quantum yield. Docking studies using a cryo-electron microscopy (EM) structure of the K_Ca3.1 channel confirmed the interaction of 9 a and 9 b with a binding pocket in the channel pore.     

The influence of drying air temperature on the physical properties of dried and rehydrated eggplant

Drying processes generally cause volume and surface change of foodstuffs. Information on the porous structure and the mechanical properties of dried food products is needed for determining food quality, process design and estimating properties such as density and moisture diffusivity.In this work we investigated the structural changes induced in eggplant by convective air drying at four different temperatures (40, 50, 60 and 70 °C) and their effect on the subsequent rehydration process. Drying and rehydration kinetic curves were also measured.The changes in physical properties, such as porosity, pore-size distribution and bulk density were determined by Hg porosimetry, scanning electron microscopy and optical microscopy while their effect on the textural characteristics by dynamometric measurements.As expected, the increase of the drying air temperature causes shorter drying times. The drying temperature influences strongly the microstructure of dried samples: the porosity increases with the air temperature, but the structure is better preserved at intermediate temperature (60 °C) as confirmed by the lower firmness values with respect to the other dehydrated samples (40, 50 and 70 °C). In these latter, the longer drying time and the higher temperature, respectively, causes the development of a wrinkled structure. In particular, at 70 °C the structure of dehydrated samples appears totally broken with a consequent faster water uptake during rehydration.