RADIATION CROSSLINKED ADVANCED WOUND DRESSING CONTAINING EGG WHITE PROTEINS

During the past decades, the use of antibiotics has grown worldwide in different fields, from medicine to agriculture, leading to antibiotic resistance of microbes, which is the cause of thousands of deaths every year worldwide. [1, 2] Finding new antibiotics is becoming more and more difficult because their development is no longer convenient in term of the cost–benefit ratio for the pharmaceutical industry. The interest in egg white proteins, such as ovoalbumin, ovotransferrin and lysozyme, has risen especially because of their demonstrated antimicrobial activities. [3] These antimicrobial proteins can then be used to enrich wound dressing films that requires a high level of control of microbial colonization. Wound dressing films can be easily produced crosslinking polymers, such as polyvinyl alcohol (PVA) or polyvinyl pyrrolidone, by high-energy radiation. [4] This technique does not require expensive initiators and catalysts and, depending on the irradiation doses, it can guarantee simultaneous product sterilization. PVA hydrogels obtained by irradiation are also transparent, a desirable property for wound dressings. When PVA is mixed with selected polysaccharides, the dressings have shown faster healing rates and scarless healing, probably due to antioxidant properties of polysaccharide fragments produced upon irradiation. [4] Therefore, the aim of this work is to develop hydrogel would dressings based on the irradiation of PVA and xyloglucan (XG) blends and to investigate the antibacterial properties of the films due to the incorporation of egg white proteins

Carcinoid Syndrome. Preclinical Models and Future Therapeutic Strategies

Carcinoid syndrome represents a debilitating paraneoplastic disease, caused by the se- cretion of several substances, occurring in about 10–40% of patients with well-differentiated neu- roendocrine tumors (NETs). The main signs and symptoms associated with carcinoid syndrome are flushing, diarrhea, hypotension, tachycardia, bronchoconstriction, venous telangiectasia, dyspnea and fibrotic complications (mesenteric and retroperitoneal fibrosis, and carcinoid heart disease). Although there are several drugs available for the treatment of carcinoid syndrome, the lack of therapeutic response, poor tolerance or resistance to drugs are often reported. Preclinical models are indispensable tools for investigating the pathogenesis, mechanisms for tumor progression and new therapeutic approaches for cancer. This paper provides a state-of-the-art overview of in vitro and in vivo models in NETs with carcinoid syndrome, highlighting the future developments and therapeutic approaches in this field

Variability in genes regulating vitamin D metabolism is associated with vitamin D levels in type 2 diabetes

Mortality rate is increased in type 2 diabetes (T2D). Low vitamin D levels are associated with increased mortality risk in T2D. In the general population, genetic variants affecting vitamin D metabolism (DHCR7 rs12785878, CYP2R1 rs10741657, GC rs4588) have been associated with serum vitamin D. We studied the association of these variants with serum vitamin D in 2163 patients with T2D from the "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes". Measurements of serum vitamin D were centralised. Genotypes were obtained by Eco™ Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 x 10-4) and GC rs4588 (p = 1 x 10-6) but not CYP2R1 rs10741657 (p = 0.31) were significantly associated with vitamin D levels. One unit of a weighted genotype risk score (GRS) was strongly associated with vitamin D levels (p = 1.1 x 10-11) and insufficiency (<30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, p = 1.1 x 10-7). In conclusion, DHCR7 rs12785878 and GC rs4588, but not CYP2R1 rs10741657, are significantly associated with vitamin D levels. When the 3 variants were considered together as GRS, a strong association with vitamin D levels and vitamin D insufficiency was observed, thus providing robust evidence that genes involved in vitamin D metabolism modulate serum vitamin D in T2D

Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells

The chiral cationic complex [Ru(η1-OAc)(CO)((R,R)-Skewphos)(phen)]OAc (2R), isolated from reaction of [Ru(η1-OAc)(η2-OAc)(R,R)-Skewphos)(CO)] (1R) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)-Skewphos)(phen)]Y (X=Y=OPiv 3R; X=SAc, Y=OAc 4R). The corresponding enantiomers 2S-4S have been obtained from 1S containing (S,S)-Skewphos. Reaction of 2R and 2S with (S)-cysteine and NaPF6 at pH=9 gives the diastereoisomers [Ru((S)-Cys)(CO)(PP)(phen)]PF6 (PP=(R,R)-Skewphos 2R-Cys; (S,S)-Skewphos 2S-Cys). The DFT energetic profile for 2R with (S)-cysteine in H2O indicates that aquo and hydroxo species are involved in formation of 2R-Cys. The stability of the ruthenium complexes in 0.9 % w/v NaCl solution, PBS and complete DMEM medium, as well as their n-octanol/water partition coefficient (logP), have been evaluated. The chiral complexes show high cytotoxic activity against SW1736, 8505 C, HCT-116 and A549 cell lines with EC50 values of 2.8–0.04 μM. The (R,R)-Skewphos derivatives show higher cytotoxicity compared to their enantiomers, 4R (EC50=0.04 μM) being 14 times more cytotoxic than 4S against the anaplastic thyroid cancer 8505 C cell line

Xerostomia, gustatory and olfactory dysfunctions in patients with COVID-19

Background The novel Coronavirus Disease-19 (COVID-19) continues to have profound effect on global health. Our aim was to evaluate the prevalence and characterize specific symptoms associated with COVID-19. Methods This retrospective study included 326 patients with confirmed SARS-CoV-2 infection evaluated at the Emergency Department of the Umberto I Polyclinic Hospital, Rome, Italy between March 6th and April 30th, 2020. In order to assess xerostomia, olfactory and gustatory dysfunctions secondary to COVID-19, a telephone-based a modified survey obtained from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 for taste and smell disorders and the Fox Questionnaire for dry mouth were administered to 111 patients (34%) after discharge between June 4th and June 12th. Results Taste dysfunction was the most common reported symptom (59.5%; n = 66), followed by xerostomia (45.9%; n = 51) and olfactory dysfunctions (41.4%; n = 46). The most severe symptom was olfactory dysfunction with a median severity score of 8.5 (range: 5–10). Overall 74.5% (n = 38) of patients with xerostomia, 78.8% (n = 52) of patients with gustatory dysfunctions and 71.1% (n = 33) of patients with olfactory dysfunctions reported that all symptoms appeared before COVID-19 diagnosis. Overall, the majority of patients reported one symptom only (45.9%, n = 51), 37 (33.3%) reported the association of two symptoms, and 23 (20.7%) patients reported the association of three symptoms at the same time. Conclusion Xerostomia, gustatory and olfactory dysfunctions may present as a prodromal or as the sole manifestation of COVID-19. Awareness is fundamental to identify COVID-19 patients at an early stage of the disease and limit the spread of the virus

Autobiographical memory in contact tracing: evidence from the COVID-19 pandemic

IntroductionThe recent COVID-19 pandemic has compelled various governments to trace all contacts of a confirmed case, as well as to identify the locations visited by infected individuals. This task, that requires the activation of our autobiographical memories, can make a difference in the spread of the contagion and was based primarily on telephone interviews with infected people. In this study, we examined whether participants were able to provide contact tracing information and whether their memories were influenced by salient events occurring during the initial phases of the pandemic.MethodsParticipants were asked to fill in an online standardized form in which they recounted every day of the 2 weeks before, reporting as much information as possible. The time period selected included, among other things, the day on which the Italian government issued the decree initiating the COVID-19 lockdown. The task was completed twice, the first time relying solely on their memory, and the second time using external aids (diaries, mobile phones etc.). Reports were then coded using a scheme that segmented accounts into informational details, divided into two broad categories, internal and external.ResultsOur findings showed that (i) the use of external aids was effective only when participants had to recall the day furthest away or if to-be-recalled events have low distinctiveness, and (ii) memories of internal details were recalled better than memories of external details. Participants were overall accurate and reported a large amount of information about people and places. However, because of the connection with key pandemic-related events, the effect was somewhat stronger on specific days (e.g., the day in which the lockdown was announced).DiscussionThe results of this work could provide a useful tool for improving the design of contact tracing procedures in the event of an unwanted future public health crisis caused by a highly infectious agent

Psychopathological Burden and Quality of Life in Substance Users During the COVID-19 Lockdown Period in Italy

Background Following the development of the COVID-19 pandemic, a rigid public health strategy of reduced social contact and shelter-in-place has been adopted by the Italian Government to reduce the spread of the virus. In this paper, we aim at evaluating the impact that the COVID-19 pandemic, and the relative containment measures, have had on a real-life sample of patients suffering from substance use disorders (SUDs) and/or behavioral addictions. Methods An anonymous questionnaire was filled out by 153 addicted patients, both outpatients and residential inpatients, recruited across Italy and highly representative of the current Italian population suffering from addictions. Psychopathological burden (anxiety and depressive symptomatology, somatization, irritability, and post-traumatic symptoms), quality of life, and craving changes in daily habits were assessed. Results In our sample, we found moderate rates of depression (22.9%), anxiety (30.1%), irritability (31.6%), and post-traumatic stress (5.4%) symptoms. Psychopathological burden was globally higher among residential patients. Reported levels of craving were generally low. Discussion This study is the first attempt to collect Italian data regarding the effects of the rigid quarantine period, during the COVID-19 pandemic, on patients suffering from a SUD and/or behavioral addictions. The presence of a moderate psychopathological burden correlated to poor quality of life and low craving scores represented the main outcomes. Long-term studies, with follow-up after the end of the restrictive measures, should be considered to implement our findings

Location of primary tumor and benefit from anti-epidermal growth factorreceptor monoclonalantibodies in patients with RAS and BRAF wild-typemetastatic colorectal cancer

Introduction. Right- and left-sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right-sided tumors derive less benefit from anti-epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive. Patients and Methods. Patients with RAS and BRAF wild-type metastatic CRC (mCRC) who were treated with single-agent anti-EGFRs or with cetuximab-irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right- and left-sided tumors were investigated. Results. Of 75 patients, 14 and 61 had right- and left-sided tumors, respectively. None of the right-sided tumors responded according to RECIST, compared with 24 left-sided tumors (overall response rate: 0% vs. 41%; p 5 .0032), and only 2 patients with right-sided tumors (15%) versus 47 patients with left-sided tumors (80%) achieved disease control (p, .0001). The median duration of progression-free survival was 2.3 and 6.6 months in patients with right-sided and left-sided tumors, respectively (hazard ratio: 3.97;95%confidence interval: 2.09–7.53; p,.0001). Conclusion. Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti- EGFRs

An IoT Toolchain Architecture for Planning, Running and Managing a Complete Condition Monitoring Scenario

Condition Monitoring (CM) is an extremely critical application of the Internet of Things (IoT) within Industry 4.0 and Smart City scenarios, especially following the recent energy crisis. CM aims to monitor the status of a physical appliance over time and in real time in order to react promptly when anomalies are detected, as well as perform predictive maintenance tasks. Current deployments suffer from both interoperability and management issues within their engineering process at all phases – from their design to their deployment, to their management –, often requiring human intervention. Furthermore, the fragmentation of the IoT landscape and the heterogeneity of IoT solutions hinder a seamless onboarding process of legacy devices and systems. In this paper, we tackle these problems by first proposing an architecture for CM based on both abstraction layers and toolchains, i.e., automated pipelines of engineering tools aimed at supporting the engineering process. In particular, we introduce four different toolchains, each of them dedicated to a well-defined task (e.g., energy monitoring). This orthogonal separation of concerns aims to simplify both the understanding of a complex ecosystem and the accomplishment of independent tasks. We then illustrate our implementation of a complete CM system that follows said architecture as a real Structural Health Monitoring (SHM) pilot of the Arrowhead Tools project, by describing in detail every single tool that we developed. We finally show how our pilot achieves the main objectives of the project: the reduction of engineering costs, the integration of legacy systems, and the interoperability with IoT frameworks

Quality assurance for automatically generated contours with additional deep learning

Objective: Deploying an automatic segmentation model in practice should require rigorous quality assurance (QA) and continuous monitoring of the model’s use and performance, particularly in high-stakes scenarios such as healthcare. Currently, however, tools to assist with QA for such models are not available to AI researchers. In this work, we build a deep learning model that estimates the quality of automatically generated contours. Methods: The model was trained to predict the segmentation quality by outputting an estimate of the Dice similarity coefficient given an image contour pair as input. Our dataset contained 60 axial T2-weighted MRI images of prostates with ground truth segmentations along with 80 automatically generated segmentation masks. The model we used was a 3D version of the EfficientDet architecture with a custom regression head. For validation, we used a fivefold cross-validation. To counteract the limitation of the small dataset, we used an extensive data augmentation scheme capable of producing virtually infinite training samples from a single ground truth label mask. In addition, we compared the results against a baseline model that only uses clinical variables for its predictions. Results: Our model achieved a mean absolute error of 0.020 ± 0.026 (2.2% mean percentage error) in estimating the Dice score, with a rank correlation of 0.42. Furthermore, the model managed to correctly identify incorrect segmentations (defined in terms of acceptable/unacceptable) 99.6% of the time. Conclusion: We believe that the trained model can be used alongside automatic segmentation tools to ensure quality and thus allow intervention to prevent undesired segmentation behavior