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Objective. To study the correlations between corneal distortion and morphological features in different kinds of eyes such as healthy ones (HE), ones previously undergone myopic PRK (PRKE), ones affected by keratoconus (KCE) and keratoconus eyes previously undergone corneal collagen crosslinking (CCCE). Materials and Methods. In this retrospective comparative study, a total of 106 HE of 106 patients, 58 PRKE of 58 patients, 33 KCE of 33 patients, 28 CCCE of 28 patients were included. A complete examination of all eyes was followed by tomographic (Pentacam, Oculus, Wetzlar, Germany) and biomechanical (Corvis ST, Oculus, Wetzlar, Germany) evaluation. Differences among Corvis ST (CST) parameters in the different groups have been analyzed. Linear regressions between central corneal thickness (CCT), intraocular pressure (IOP) and anterior corneal curvature measured with Simulated Keratometry (SK), versus corneal deformation parameters measured with Corvis ST in the different groups, have been run using SPSS software version 18.0. Results, HE showed a significant correlation between main curvature power of the cornea within the central 3 mm expressed in Diopters (KM) and 6 CST parameters; between CCT and 4 CST parameters and between IOP and 5 CST parameters. PRKE showed a significant correlation between KM and 3 CST parameters; between IOP and 4 CST parameters and none between CCT and CST parameters. KCE showed a significant correlation between SK and 3 CST parameters; between IOP and 3 CST parameters and none between CCT and CST parameters. CCCE showed a significant correlation between KM and 5 CST parameters; between CCT and 1 CST parameters and between IOP and 5 CST parameters. Discussion. Data of this study suggest that both corneal curvature and IOP could have a greater influence on the corneal deformation, compared to central corneal thickness (CCT). These results should be taken into account by further studies aiming to assess biomechanical corneal characteristics.

Anna Annunziata,1 Antonietta Coppola,1 Paolo Andreozzi,2 Maurizia Lanza,1 Francesca Simioli,1 Novella Carannante,3 Camilla Di Somma,1 Pierpaolo Di Micco,4 Giuseppe Fiorentino1 1Department of Critic Area, I Unit COVID, Monaldi-Cotugno Hospital, Naples, Italy; 2Endoscopy and Gastroenterology Unit, Marcianise Hospital, Asl Caserta, Caserta, Italy; 3First Division Infectious Disease, Cotugno Hospital, Naples, Italy; 4UOC Internal Medicine, Fatebenefratelli Hospital, Naples, ItalyCorrespondence: Antonietta Coppola Email antonietta.coppola84@gmail.comAbstract: Gastrointestinal involvement in SARS-CoV-2 disease (COVID-19) can occur and evolve fatally. Reports are emerging that SARS-CoV-2 virus attacks the pancreatic cells, causing the boost of amylase and lipase serum activity and rarely frank pancreatitis. We retrospectively assessed all the patients admitted to the respiratory sub-intensive care and evaluated pancreatitis cases and their course. In our study, we included all patients admitted to our respiratory sub-intensive care unit from 1st to 30th November. All patients had a confirmed diagnosis of COVID-19 and a CT finding of interstitial pneumonia associated with signs of respiratory failure. We observed the course and evaluated who developed acute pancreatitis according to standard definitions. In this study, etiology of acute pancreatitis was defined on the basis of risk factors (ie, biliary pancreatitis was defined in presence of common bile duct stone or sludge at CT or MR). According to the Revised Atlanta Classification, we diagnosed and classified the patients and evaluated the radiological severity according to the Balthazar index and a computed tomography severity index. We found that 19% (15 of 78 patients) met the criteria for acute pancreatitis. The mortality rate among patients with pancreatitis was 20%. Interestingly, in our population, cholelithiasis’ imaging findings were found in only 7% of the patients, whereas no patient-reported alcohol consumption. Considering that alcohol and biliary stones represent the two major causes of AP in the general population, it is reasonable to hypothesize that SARS-CoV-2 could play a role in the etiology of acute pancreatitis in a subgroup of these patients.Keywords: COVID-19, gastrointestinal involvement, ARDS

Vincenzo Scorcia,1 Mauro Soda,1 Andrea Lucisano,1 Michele Lanza,2 Giuseppe Giannaccare1 1Department of Ophthalmology, University Magna Græcia, Catanzaro, Italy; 2Multidisciplinary Department of Medical, Surgical and Dental Specialities, Università della Campania “Luigi Vanvitelli”, Naples, ItalyCorrespondence: Vincenzo ScorciaDepartment of Ophthalmology, University Magna Græcia, Viale Europa, Germaneto, Catanzaro 88100, ItalyTel +39 3334800929Fax +39 09613647094Email vscorcia@libero.itPurpose: To compare visual outcomes of two newly developed monofocal intraocular lenses (IOLs) (I-Stream H and CT Lucia 211P) implanted in patients undergoing surgery for senile cataract.Methods: This prospective, comparative, single-center, randomized study included 94 eyes of 94 patients undergoing cataract surgery. Patients were randomized to receive the implantation of I-Stream H IOL (Group 1) or CT Lucia 211P IOL (Group 2). Each patient underwent a complete ocular examination before (V0), 1 month (V1), 3 months (V2) and 6 months (V3) after surgery, including visual acuity testing, objective refraction, slit-lamp biomicroscopy, contrast sensitivity testing and visual function index questionnaire (VF-14).Results: After surgery, a significant increase of best-corrected visual acuity (BCVA), CS and VF-14 and a significant decrease of SE were detected in both groups at each time point compared to baseline (always p< 0.01). No significant differences in the postoperative increase of BCVA (p=0.12), CS (p=0.21) and VF-14 (p=0.31) and decrease of SE (p=0.08) were detected comparing patients from Group 1 and Group 2 at V3. Mean and median prediction error, as well as absolute prediction error values, did not significantly differ between the two groups (p> 0.05). Eyes with an actual refraction within 0.25, 0.50 and 1 D were 53.1%, 85.1% and 100% for Group 1 and 55.3%, 87.2% and 100% for Group 2 (p> 0.05).Conclusion: I-Stream H and CT Lucia 211P allowed a satisfied recovery of visual function after senile cataract surgery; both IOLs were shown to have similar outcomes of visual performance.Keywords: intraocular lens, IOL, I-Stream H, CT Lucia 211P, cataract surgery

Inappropriate wound healing (WH) management can cause significant comorbidities, especially in patients affected by chronic and metabolic diseases, such as diabetes. WH involves several different, partially overlapping processes, including hemostasis, inflammation, cell proliferation, and remodeling. Oxidative stress in WH contributes to WH impairment because of the overexpression of radical oxygen species (ROS) and nitrogen species (RNS). This study aimed to evaluate the in vitro antioxidative action of a gel containing a Propionibacterium extract (Emorsan® Gel) and assess its skin re-epithelialization properties in a mouse model of WH. The scavenging effects of the bacterial extract were assessed in vitro through the ABTS and DPPH assays and in L-929 murine fibroblasts. The effects of the Emorsan® Gel were studied in vivo in a murine model of WH. After WH induction, mice were treated daily with vehicle or Emorsan® Gel for 6 or 12 days. According to the in vitro tests, the Propionibacterium extract exerted an inhibitory effect on ROS and RNS, consequently leading to the reduction in malondialdehyde (MDA) and nitrite levels. Before proceeding with the in vivo study, the Emorsan® Gel was verified to be unabsorbed. Therefore, the observed effects could be ascribed to a local action. The results obtained in vivo showed that through local reduction of oxidative stress and inflammation (IL-1β, TNF-α), the Emorsan® Gel significantly reduced the infiltration of mast cells into the injured wound, leading to the amelioration of symptoms such as itch and skin irritation. Therefore, the Emorsan® Gel improved the speed and percentage of wound area closure by improving the tissue remodeling process, prompting vascular–endothelial growth factor (VEGF) and transforming growth factor (TGF)- β production and reducing the expression of adhesion molecules. Emorsan® Gel, by its ability to inhibit free radicals, could reduce local inflammation and oxidative stress, thus enhancing the speed of wound healing.

Eleonora Comi,1,2 Marco Lanza,1 Flora Ferrari,1 Valeria Mauri,1,3 Gianfranco Caselli,1 Lucio Claudio Rovati1 1Department of Pharmacology and Toxicology, Rottapharm Biotech, 2PhD Program in Neuroscience, University of Milan-Bicocca, 3Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, Italy Purpose: CR4056, (2-phenyl-6-(1H-imidazol-1yl) quinazoline), an imidazoline-2 (I2) receptor ligand, is a promising analgesic drug that has been reported to be effective in several animal models of pain. The aim of this study was to evaluate the effects of CR4056 in two well-established rat models of osteoarthritis (OA), mimicking the painful and structural components of human OA.Methods: Knee OA was induced either by single intra-articular injection of monoiodoacetate (MIA) or by medial meniscal tear (MMT) in the right knee of male rats. In the MIA model, allodynia and hyperalgesia were measured as paw withdrawal threshold to mechanical stimulation. In the MMT model, pain behavior was analyzed as weight-bearing asymmetry (i.e. difference in hind paw weight distribution, HPWD) between the injured and the contralateral limbs.Results: Acute oral administration of CR4056, 14 days after MIA injection, significantly and dose-dependently reduced allodynia and hyperalgesia 90 minutes after treatment, whereas acute naproxen administration significantly reduced allodynia but not hyperalgesia. After 7 days of repeated treatment, both CR4056 and naproxen showed significant anti-allodynic and anti-hyperalgesic effects in the MIA model. Rats undergoing MMT surgery developed a significant and progressive asymmetry in HPWD compared with sham-operated animals. Repeated treatment with CR4056 significantly reduced the progression of the pain behavior, whereas naproxen had no effects.Conclusion: The data presented here show that the I2 ligand CR4056 could be a new effective treatment for OA pain. The compound is currently under Phase II clinical evaluation for this indication. Keywords: osteoarthritis, pain, CR4056, imidazoline-2 receptors, MIA, MMT

Tukezban Huseynova,1 Farah Abdulaliyeva,2 Michele Lanza3 1Briz-L Eye Clinic, 2National Ophthalmology Center, Baku, Azerbaijan; 3Second University of Naples, Caserta, Campania, Italy Purpose: To compare the keratometric and pachymetric parameters of healthy eyes with those affected by steep cornea and keratoconus (KC) using Scheimpflug camera.Setting: Briz-L Eye Clinic, Baku, Azerbaijan.Design: A cross-sectional study.Methods: In this study, 49 KC (Amsler–Krumeich stage 1) eyes and 36 healthy eyes were enrolled. A complete ophthalmic evaluation and a Scheimpflug camera scan were performed in every eye included in the study. Tomographic parameters such as parameters from the front and back cornea, maximum keratometry reading (Kmax), corneal volume (CV), anterior chamber volume (ChV), anterior chamber depth (ACD), anterior chamber angle (AC angle), keratometric power deviation (KPD), maximum front elevation (Max FE), and maximum back elevation (Max BE), as well as pachymetric progression indices (PPI), Ambrosio relational thickness (ART), index of surface variance (ISV), index of vertical asymmetry (IVA), center keratoconus index (CKI), index of height asymmetry (IHA), index of height decentration (IHD), and radius minimum (RM) were collected and statistically compared between the two groups.Results: PPI, ART, ISV, IVA, CKI, IHA, IHD, and RM parameter values were significantly different (P

Cristina Meregalli,1 Cecilia Ceresa,1 Annalisa Canta,1 Valentina Alda Carozzi,1 Alessia Chiorazzi,1 Barbara Sala,1 Norberto Oggioni,1 Marco Lanza,2 Ornella Letar,i2 Flora Ferrari,2 Federica Avezza,1 Paola Marmiroli,1 GianFranco Caselli,2 Guido Cavaletti11Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, 2Pharmacology and Toxicology Department, Rottapharm | Madaus Research Center, Monza, ItalyAbstract: Although bortezomib (BTZ) is the frontline treatment for multiple myeloma, its clinical use is limited by the occurrence of painful peripheral neuropathy, whose treatment is still an unmet clinical need. Previous studies have shown chronic BTZ administration (0.20 mg/kg intravenously three times a week for 8 weeks) to female Wistar rats induced a peripheral neuropathy similar to that observed in humans. In this animal model of BTZ-induced neurotoxicity, the present authors evaluated the efficacy of CR4056, a novel I2 ligand endowed with a remarkable efficacy in several animal pain models. CR4056 was administered in a wide range of doses (0.6–60 mg/kg by gavage every day for 2–3 weeks) in comparison with buprenorphine (Bupre) (28.8 µg/kg subcutaneously every day for 2 weeks) and gabapentin (Gaba) (100 mg/kg by gavage every day for 3 weeks). Chronic administration of BTZ reduced nerve conduction velocity and induced allodynia. CR4056, Bupre, or Gaba did not affect the impaired nerve conduction velocity. Conversely, CR4056 dose-dependently reversed BTZ-induced allodynia (minimum effective dose 0.6 mg/kg). The optimal dose found, 6 mg/kg, provided a constant pain relief throughout the treatment period and without rebound after suspension, being effective when coadministered with BTZ, starting before or after allodynia was established, or when administered alone after BTZ cessation. A certain degree of tolerance was seen after 7 days of administration, but only at the highest doses (20 and 60 mg/kg). Bupre was effective only acutely, since tolerance was evident from the fourth day onwards. Gaba showed a significant activity only at the fourth day of treatment. CR4056, over the range of concentrations of 3–30 µM, was unable to hinder BTZ cytotoxicity on several tumor cell lines, which could indicate that this substance does not directly interfere with BTZ antitumor activity. Therefore, CR4056 could represent a new treatment option for BTZ-induced neuropathic pain.Keywords: imidazoline I2 receptor ligand, antinociception, allodynia, neuropathic pain, bortezomib

Flora Ferrari1, Simonetta Fiorentino1, Laura Mennuni1, Paolo Garofalo1, Ornella Letari1, Stefano Mandelli2, Antonio Giordani3, Marco Lanza1, Gianfranco Caselli11Department of Pharmacology and Toxicology; 2Department of Medicinal Chemistry; 3R&D Chemistry Drug Development and OS, Rottapharm S.p.A., Monza (MB), ItalyAbstract: Two decades of investigations have failed to unequivocally clarify the functions and the molecular nature of imidazoline-2 receptors (I2R). However, there is robust pharmacological evidence for the functional modulation of monoamino oxidase (MAO) and other important enzyme activities by I2 site ligands. Some compounds of this class proved to be active experimental tools in preventing both experimental pain and opioid tolerance and dependence. Unfortunately, even though these compounds bind with high potency to central I2 sites, they fail to represent a valid clinical opportunity due to their pharmacokinetic, selectivity or side-effects profile. This paper presents the preclinical profile of a novel I2 ligand (2-phenyl-6-(1H-imidazol-1yl)quinazoline; [CR4056]) that selectively inhibits the activity of human recombinant MAO-A in a concentration-dependent manner. A sub-chronic four day oral treatment of CR4056 increased norepinephrine (NE) tissue levels both in the rat cerebral cortex (63.1% ± 4.2%; P

Recent advances in the stepwise multichannel quantum defect theory approach of electron/molecular cation reactive collisions have been applied to perform computations of cross sections and rate coefficients for dissociative recombination and electron-impact ro-vibrational transitions of H2+, BeH+ and their deuterated isotopomers. At very low energy, rovibronic interactions play a significant role in the dynamics, whereas at high energy, the dissociative excitation strongly competes with all other reactive processes.

Context. Gamma-ray bursts (GRBs) can be detected at cosmological distances, and therefore can be used to study the contents and phases of the early Universe. The 4−150 keV wide-field trigger camera ECLAIRs on board the Space-based multi-band Variable Object Monitor (SVOM) mission, dedicated to studying the high-energy transient sky in synergy with multi-messenger follow-up instruments, has been adapted to detect high-z GRBs. Aims. Investigating the detection capabilities of ECLAIRs for high-redshift GRBs and estimating the impacts of instrumental biases in reconstructing some of the source measured properties, focusing on GRB duration biases as a function of redshift. Methods. We simulated realistic detection scenarios for a sample of 162 already observed GRBs with known redshift values as they would have been seen by ECLAIRs. We simulated them at redshift values equal to and higher than their measured value. Then we assessed whether they would be detected with a trigger algorithm resembling that on board ECLAIRs, and derived quantities, such as T90, for those that would have been detected. Results. We find that ECLAIRs would be capable of detecting GRBs up to very high redshift values (e.g. 20 GRBs in our sample are detectable within more than 0.4 of the ECLAIRs field of view for zsim > 12). The ECLAIRs low-energy threshold of 4 keV, contributes to this great detection capability, as it may enhance it at high redshift (z > 10) by over 10% compared with a 15 keV low-energy threshold. We also show that the detection of GRBs at high-z values may imprint tip-of-the-iceberg biases on the GRB duration measurements, which can affect the reconstruction of other source properties. [ABSTRACT FROM AUTHOR]

Memristive devices made of multilayer hexagonal boron nitride are attracting much attention for information storage, computation, encryption, and communication. Generating multilevel operation in these memristors would be an important added value for the field of neuromorphic computation, but the main phenomenon producing it (i.e., conductance quantization) is not well understood for this material. Here, we analyze hexagonal boron nitride memristive devices with metal electrodes operating in their quasistatic and transient regimes. Conductance quantization effects were observed both in I-V curves measured under ramped voltage stress and in the reset processes driven by voltage pulse trains. Polar and time lag plots are employed to shed light on the physics behind the device resistive switching. A model is proposed to reproduce the electrical characteristics of progressive reset processes and the discretization of the device conductance linked to quantum effects. [ABSTRACT FROM AUTHOR]

Time series statistical analyses (TSSA) have been employed to evaluate the variability of resistive switching memories and to model the set and reset voltages for modeling purposes. The conventional procedures behind time series theory have been used to obtain autocorrelation and partial autocorrelation functions and determine the simplest analytical models to forecast the set and reset voltages in a long series of resistive switching processes. To do so, and for the sake of generality in our study, a wide range of devices have been fabricated and measured. Different oxides and electrodes have been employed, including bilayer dielectrics in devices such as Ni/HfO2/Si-n+, Cu/HfO2/Si-n+, and Au/Ti/TiO2/SiOx/Si-n+. The TSSA models obtained allowed one to forecast the reset and set voltages in a series if previous values were known. The study of autocorrelation data between different cycles in the series allows estimating the inertia between cycles in long resistive switching series. Overall, TSSA seems to be a very promising method to evaluate the intrinsic variability of resistive switching memories. [ABSTRACT FROM AUTHOR]

A 2 x 2 factorial experiment was carried out to evaluate the effect of herbage or concentrate feeding and dietary tannin supplementation on fatty acid metabolism and composition in sheep ruminal fluid, plasma, and intramuscular fat. Twenty-eight male lambs were divided into 2 equal groups at 45 d of age and kept in individual pens. One group was given exclusively fresh herbage (vetch), and the other group was fed a concentrate-based diet. Within each treatment, one-half of the lambs received supplementation of quebracho powder, providing 4.0% of dietary DM as tannins. Before slaughter, blood samples were collected. The animals were slaughtered at 105 d of age, and ruminal contents and LM were collected. Blood plasma, ruminal fluid, and LM fatty acid composition was determined by gas chromatography. Tannin supplementation reduced (P < 0.05) the concentration of stearic acid (-49%) and increased the concentration of vaccenic acid (+97%) in ruminal fluid from concentrate-fed lambs. Within concentrate- and herbage-based diets, tannin supplementation reduced the accumulation of SFA in blood (P < 0.05) compared with lambs fed the tannin-free diets. When tannins were included in the concentrate, the LM contained 2-fold greater concentrations of rumenic acid compared with the LM of the lambs fed the tannin-free concentrate (0.96 vs. 0.46% of total extracted fatty acids, respectively; P < 0.05). The concentration of PUFA was greater (P < 0.05) and SFA (P < 0.01) less in the LM from lambs fed the tannin-containing diets as compared with the animals receiving the tannin-free diets. These results confirm, in vivo, that tannins reduce ruminal biohydrogenation, as previously reported in vitro. This implies that tannin supplementation could be a useful strategy to increase the rumenic acid and PUFA content and to reduce the SFA in ruminant meats. However, the correct dietary concentration of tannins should be carefully chosen to avoid negative effects on DMI and animal performance. Key words: conjugated linoleic acid, fatty acid, feeding system, sheep, tannin