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Purpose: Vertebral fractures (VFs), the hallmark of skeletal fragility, have been reported as an emerging complication in patients with pituitary diseases associated with hormonal excess and/or deficiency, independently from bone mineral density. Non-functioning pituitary adenoma (NFPA) is amongst the most frequent pituitary adenomas; however, skeletal health in this context has never been investigated. We aimed at assessing the prevalence and the determinants of morphometric VFs in patients with NFPA., Methods: We enrolled 156 patients (79 M/77F, mean age 55.75 ± 12.94 years) at admission in Neurosurgery Unit before trans-sphenoidal surgery and compared them with an age and sex-matched control group of subjects with neither history/risk factors for secondary osteoporosis nor pituitary disorders. We performed a vertebral morphometric evaluation of the thoracic spine on pre-operative X-ray images (MTRx) and collected biochemical, demographic, and clinical data from the entire cohort., Results: The prevalence of thoracic VFs in patients with NFPA was significantly higher than the control group (26.3% vs. 10.3%; p < 0.001). In the NFPA group, 20 patients (48.8% of the fractured patients) showed multiple VFs, 14 (34.1% of them) showed moderate/severe VFs. Patients with VFs were significantly older and had lower serum free triiodothyronine (fT3) levels than non-fractured ones (p = 0.002 and p = 0.004; respectively). The prevalence of secondary male hypogonadism was higher among men with VFs as compared to those with no VFs (72% vs. 48.1%; p = 0.047). Consistently, total testosterone levels in males were significantly lower in fractured patients than in non-fractured ones (p = 0.02). The prevalence of gonadotroph adenomas was significantly higher among patients with VFs (p = 0.02). In multiple logistic regression analysis, older age and lower serum fT3 levels were independent factors predicting the risk for VFs., Conclusions: For the first time, we reported a high prevalence of thoracic radiological VFs in patients with NFPAs. Our data should prompt clinicians to proceed with a clinical bone fragility evaluation already during the diagnostic work-up, particularly in those with concomitant hypogonadism, or in those with older age and/or with lower fT3., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The importance of non-human DNA in the forensic field has increased greatly in recent years, together with the type of applications. The molecular species identification of animal and botanical material may be crucial both for wildlife trafficking and crime scene investigation. However, especially for forensic botany, several challenges slow down the implementation of the discipline in the routine.Although the importance of molecular analysis of animal origin samples is widely recognized and the same value is acknowledged to the botanical counterpart, the latter does not find the same degree of application.The availability of molecular methods, especially useful in cases where the material is fragmented, scarce or spoiled preventing the morphological identification, is not well known. This work is intended to reaffirm the relevance of non-human forensic genetics (NHFG), highlighting differences, benefits and pitfalls of the current most common molecular analysis workflow for animal and botanical samples, giving a practical guide. A flowchart describing the analysis paths, divided in three major working areas (inspection and sampling, molecular analysis, data processing and interpretation), is provided. More real casework examples of the utility of non-human evidence in forensic investigations should be shared by the scientific community, especially for plants. Moreover, concrete efforts to encourage initiatives in order to promote quality and standardization in the NHFG field are also needed., (© 2024. The Author(s).)

In our continuing effort devoted at developing agents targeting the EphA2 receptor by means of protein-protein interaction (PPI) inhibitors, we report here the design and synthesis of a new class of l-β-homotryptophan conjugates of 3-β-hydroxy-Δ 5 -cholenic acid bearing a set of arylsulfonyl substituents at the indole nitrogen atom. An extensive structure-activity relationship (SAR) analysis indicates that the presence of a bulky lipophilic moiety at the indole nitrogen is fundamental for improving potency on the EphA2 receptor, while abrogating activity on the EphB1-EphB3 receptor subtypes. A rational exploration, guided by the combined application of an experimental design on σ p and π physicochemical descriptors and docking simulations, led to the discovery of UniPR1454, a 1-(4-(trifluoromethyl)phenyl)sulfonyl derivative acting as potent and competitive EphA2 antagonist able to inhibit ephrin-A1 dependent signals and to reduce proliferation of glioblastoma (U251) cell line at micromolar concentration., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Massimiliano Tognolini reports financial support was provided by Italian Association for Cancer Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The aim of this study was to compare the fracture strength of two different Ribbond Fiber (Ribbond, Ribbond Inc., Seattle, WA, USA) restoration strategies in 5 mm deep standardized MOD cavities without interaxial dentin., Material and Methods: 34 extracted human molars were randomly divided into two groups and restored as follows: Group 1 restoration with Ribbond Fiber placed at the cavity floor incorporated in Estelite Bulk-Fill Flow Universal composite (Tokuyama Dental Corporation Inc., Tokyo, Japan); Group 2 restoration with RF placed at 3 mm from the occlusal plane over a 2mm layer of Estelite Bulk-Fill Flow. The occlusal plane in both groups was restored with Ceram.x Spectra ST (Dentsply Sirona, Ballantyne Corporate Pl, Charlotte, NC, USA). The restored teeth were subjected to thermal cycling by immersing them for 30 seconds in hot water (55±2°C) followed by 30 seconds in cold water (5±2°C), for 2000 cycles.Their fracture strength was then evaluated using an Instron device. Data were analyzed with Two-sample T Test statistical test to compare fracture strength among groups. Finally, a descriptive analysis of the failure location was performed., Results: A statistically significant difference was found between groups 1 and 2 ( P <0.001) in terms of fracture strength. Group 2 exhibited a higher percentage of recoverable fractures compared to group 1. Group 1 had a mean fracture load of 833N and a SD of 248 while group 2 had a mean fracture load of 1286N and SD of 447., Conclusions: RF placed at 3 mm depth from the occlusal plane, on a 2 mm layer Estelite Bulk-Fill Flow Universal composite (Tokuyama Dental Corporation Inc., Tokyo, Japan) contributes to improve fracture resistance in vital teeth without interaxial dentin and reduces the risk of non-recoverable fractures compared to when it is placed at a 5 mm depth. Key words: Ribbond fiber, composite restoration, fracture resistance, Instron machine., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Medicina Oral S.L.)

Purpose: Hashimoto thyroiditis and Graves's disease are two related autoimmune disorders, representing the leading causes of hypothyroidism and hyperthyroidism. Autoimmune hypothyroidism is generally irreversible but very rarely, some patients would shift to hyperthyroidism. The aim of the study was to seek for possible clinical predictors of the transition from hypo to hyperthyroidism in patients with Hashimoto thyroiditis and to outline their clinical phenotype., Methods: Twelve patients with overt autoimmune hypothyroidism who had at least one transition from hypothyroidism to autoimmune hyperthyroidism were compared with 294 consecutive patients with autoimmune hypothyroidism and 69 consecutive patients with autoimmune hyperthyroidism that accessed the outpatient clinic over six months. Demographic, hormonal data and autoantibodies titers were compared., Results: Prevalence of smoking habit was significantly higher in switchers compared to controls. Switchers showed a significantly higher prevalence of personal and familial history of non-thyroidal autoimmune disorders. TSH levels were significantly lower in the switcher group during the hypothyroid phase and levothyroxine dose required was lower. TSH concentrations were significantly lower while free fT4 and free fT3 values were higher in GD patients compared to switchers during the hyperthyroid phase despite comparable TRAb levels. Prevalence and type of hyperthyroid symptoms and orbitopathy were similar between switchers and GD group. Mean dose of anti-thyroid drugs was significantly higher in GD patients compared to switchers. No differences were observed in the remission rate from hyperthyroidism between the two groups, despite switchers showed a significantly lower time-to-remission., Conclusions: Conversion of Hashimoto Thyroiditis towards Graves' disease is a rare phenomenon which can occur almost at any time after the development of autoimmune hypothyroidism. Our findings suggest active surveillance of hypothyroid patients who require frequent reduction of levothyroxine during follow up and testing for TSHR antibodies in these patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Due to the importance of joint disease and ostearthritis (OA) in equine athletes, new regenerative treatments to improve articular cartilage repair after damage are gaining relevance. Chondrocyte de-differentiation, an important pathogenetic mechanism in OA, is a limiting factor when differentiated articular chondrocytes are used for cell-based therapies. Current research focuses on the prevention of this de-differentiation and/or on the re-differentiation of chondrocytes by employing different strategies in vitro and in vivo. Articular chondrocytes normally live in a condition of higher osmolarity (350-450 mOsm/L) compared to normal physiological fluids (~ 300 mOsm/L) and some studies have demonstrated that osmolarity has a chondroprotective effect in vitro and in vivo. Therefore, the response of horse articular chondrocytes to osmolarity changes (280, 380, and 480 mOsm/L) was studied both in proliferating, de-differentiated chondrocytes grown in adhesion, and in differentiated chondrocytes grown in a 3D culture system. To this aim, cell proliferation (cell counting), morphology (optical microscopy), and differentiation (gene expression of specific markers) were monitored along with the expression of osmolyte transporters involved in volume regulation [betaine-GABA transporter (BGT-1), taurine transporter (SLC6A6), and neutral amino acid transporter (SNAT)] real-time qPCR. Proliferating chondrocytes cultured under hyperosmolar conditions showed low proliferation, spheroidal morphology, a significant reduction of de-differentiation markers [collagen type I (Col1) and RUNX2] and an increase of differentiation markers [collagen type II (Col2) and aggrecan]. Notably, a persistently high level of BGT-1 gene expression was maintained in chondrocyte cultures at 380 mOsm/L, and particularly at 480 mOsm/L both in proliferating and differentiated chondrocytes. These preliminary data encourage the study of osmolarity as a microenvironmental co-factor to promote/maintain chondrocyte differentiation in both 2D and 3D in vitro culture systems., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Functional Neurological Disorders are characterized by sensory-motor or cognitive symptoms. Recent research has revealed their complex nature involving biological, psychological, and social factors. Care requires a multidisciplinary approach, which, to date, has yet to be considered. A Constructivist Grounded Theory study was conducted to understand the reasons behind this, exploring Functional Neurological Disorders diagnosis, communication, and understanding from multiple perspectives (patients and healthcare professionals). The core category was "negotiating Functional Neurological Disorders meanings and care amid a dissatisfying dichotomy," with sub-categories: i) seeking to "word" the disease, ii) exposing reductionism, and iii) a pluralist vision emerging. Diagnosing and communicating Functional Neurological Disorders is a process of negotiating meanings and care that hinges on participants' diverse ontological perspectives regarding the condition. Results highlight the difficulty in finding common ground and achieving mutual understanding among the various viewpoints, creating a challenge in establishing a unified approach to Functional Neurological Disorders care. In this context, only a few healthcare professionals emphasized the potential benefits of increased integration. A shift is required from a reductionist to an integrated biopsychosocial perspective to develop a more cohesive approach. Defining a medical paradigm through dialogue with teams and patients is essential in addressing Functional Neurological Disorders effectively. Furthermore, the required interdisciplinary approach holds the potential to mitigate the dissatisfaction arising from fragmented and compartmentalized care (the "dissatisfying dichotomy") experienced by our participants. It signifies a comprehensive strategy that could address the concerns of all involved parties and enhance the overall quality of care provided., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

With the aim of identifying novel antagonists selective for the EphA receptor family, a combined experimental and computational approach was taken to investigate the molecular basis of the recognition between a prototypical Eph-ephrin antagonist (UniPR1447) and two representative receptors of the EphA and EphB subfamilies, namely, EphA2 and EphB2 receptors. The conformational free-energy surface (FES) of the binding state of UniPR1447 within the ligand binding domain of EphA2 and EphB2, reconstructed from molecular dynamics (MD) simulations performed on the microsecond time scale, was exploited to drive the design and synthesis of a novel antagonist selective for EphA2 over the EphB2 receptor. The availability of compounds with this pharmacological profile will help discriminate the importance of these two receptors in the insurgence and progression of cancer.

Beer bagasse is a residue waste produced in great amounts; nevertheless, it is still underestimated in the industry. The aim of this paper is to develop an innovative and efficient methodology to recycle the beer bagasse by producing Poly-lactic acid(PLA)-based bio-composites, in the forms of pellets and filaments, to be used in additive manufacturing processes. To assess the suitability of beer bagasse for extrusion-based 3D printing techniques, it was, firstly, physically and chemically characterized. Then, it was added in combination with different kinds of plasticizers to PLA to make bio-composites, analyzing their thermal and physical properties. The results prove the great potential of bagasse, evidencing its printability. Both composites' pellets and filaments were used in two different 3D printing machines and the mechanical properties of the 3D-printed models were evaluated as a function of the composition and the kind of technology used. All the used plasticizers improved processability and the polymer-bagasse interface. Compared to neat PLA, no changes in thermal properties were detected, but a lowering of the mechanical properties of the 3D-printed composites compared to the neat polymers was observed. Finally, a comparison between the efficiency of the two 3D printing techniques to be used with the bio-based composites was performed.

It is well demonstrated the key role of Eph-ephrin system, specifically of EphA2 receptor, in supporting tumor growth, invasion, metastasis and neovascularization. We previously identified FXR agonists as eligible antagonists of Eph-ephrin system. Herein we characterize new commercially available FXR (Farnesoid X Receptor) agonists as potential Eph ligands including Cilofexor, Nidufexor, Tropifexor, Turofexorate isopropyl and Vonafexor. Our exploration based on molecular modelling investigations and binding assays shows that Cilofexor binds specifically and reversibly to EphA2 receptor with a Ki value in the low micromolar range. Furthermore, Cilofexor interferes with the phosphorylation of EphA2 and the cell retraction and rounding in PC3 prostate cancer cells, both events depending on EphA2 activation. In conclusion, we can confirm that target hopping can be a successful approach to discover new moiety of protein-protein inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Prevention of preterm birth (PTB) with progestogens after an episode of threatened preterm labour is still controversial. As different progestogens have distinct molecular structures and biological effects, we conducted a systematic review and pairwise meta-analysis to investigate the individual role played by 17-alpha-hydroxyprogesterone caproate (17-HP), vaginal progesterone (Vaginal P) and oral progesterone (Oral P)., Methods: The search was performed in MEDLINE, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials (CENTRAL) up to 31 October 2021. Published RCTs comparing progestogens to placebo or no treatment for maintenance tocolysis were considered. We included women with singleton gestations, excluding quasi-randomized trials, studies on women with preterm premature rupture of membrane, or receiving maintenance tocolysis with other drugs. Primary outcomes were preterm birth (PTB) < 37 weeks' and < 34 weeks'. We assessed risk of bias and evaluated certainty of evidence with the GRADE approach., Results: Seventeen RCTs including 2152 women with singleton gestations were included. Twelve studies tested vaginal P, five 17-HP, and only 1 oral P. PTB < 34 weeks' did not differ among women receiving vaginal P (RR 1.21, 95%CI 0.91 to 1.61, 1077 participants, moderate certainty of evidence), or oral P (RR 0.89, 95%CI 0.38 to 2.10, 90 participants, low certainty of evidence) as opposed to placebo. Instead, 17-HP significantly reduced the outcome (RR 0.72, 95% CI 0.54 to 0.95, 450 participants, moderate certainty of evidence). PTB < 37 weeks' did not differ among women receiving vaginal P (RR 0.95, 95%CI 0.72 to 1.26, 8 studies, 1231 participants, moderate certainty of evidence) or 17-HP (RR 0.86, 95%CI 0.60 to 1.21, 450 participants, low certainty of evidence) when compared to placebo/no treatment. Instead, oral P significantly reduced the outcome (RR 0.58, 95% CI 0.36 to 0.93, 90 participants, low certainty of evidence)., Conclusions: With a moderate certainty of evidence, 17-HP prevents PTB < 34 weeks' gestation among women that remained undelivered after an episode of threatened preterm labour. However, data are insufficient to generate recommendations in clinical practice. In the same women, both 17-HP and vaginal P are ineffective in the prevention of PTB < 37 weeks'., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ferrari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: During the Sars-CoV-2 virus pandemic, Italy faced an unrivaled health emergency. Its impact has been significant on the hospital system and personnel. Clinical neurophysiology technicians played a central role (but less visibly so compared to other healthcare workers) in managing the COVID-19 pandemic. This research aims to explore the experiences of clinical neurophysiology technicians during the pandemic and contribute to the debate on the well-being of healthcare workers on the front line., Methods: We implemented a cross-sectional survey across Italy. It contained questions that were open-ended for participants to develop their answers and acquire a fuller perspective. The responses were analyzed according to the framework method., Results: One hundred and thirty-one responses were valid, and the following themes were generated: technicians' experiences in their relationship with patients, technicians' relationship with their workgroup and directors, and technicians' relationship with the context outside of their work. The first theme included sub-themes: fear of infection, empathy, difficulty, a sense of obligation and responsibility, anger, and sadness. The second theme contained selfishness/solidarity in the workgroup, lack of protection/collaboration from superiors, stress, and distrust. The last theme included fear, stress/tiredness, serenity, sadness, and anger., Conclusion: This study contributes to building a humanized perspective for personnel management, bringing attention to the technical work of healthcare professionals in an emergency and the emotional and relational dimensions. These are the starting points to define proper, contextually adequate support., (© 2022. Fondazione Società Italiana di Neurologia.)

Bio-based polymers, obtained from natural biomass, are nowadays considered good candidates for the replacement of traditional fossil-derived plastics. The need for substituting traditional synthetic plastics is mainly driven by many concerns about their detrimental effects on the environment and human health. The most innovative way to produce bioplastics involves the use of raw materials derived from wastes. Raw materials are of vital importance for human and animal health and due to their economic and environmental benefits. Among these, wood waste is gaining popularity as an innovative raw material for biopolymer manufacturing. On the other hand, the use of wastes as a source to produce biopolymers and biocomposites is still under development and the processing methods are currently being studied in order to reach a high reproducibility and thus increase the yield of production. This study therefore aimed to cover the current developments in the classification, manufacturing, performances and fields of application of bio-based polymers, especially focusing on wood waste sources. The work was carried out using both a descriptive and an analytical methodology: first, a description of the state of art as it exists at present was reported, then the available information was analyzed to make a critical evaluation of the results. A second way to employ wood scraps involves their use as bio-reinforcements for composites; therefore, the increase in the mechanical response obtained by the addition of wood waste in different bio-based matrices was explored in this work. Results showed an increase in Young's modulus up to 9 GPa for wood-reinforced PLA and up to 6 GPa for wood-reinforced PHA.

Background: Cervical blood and cerebrospinal fluid (CSF) flow rates can be quantified with Phase-contrast (PC) MRI, which is routinely used for clinical studies. Previous MRI studies showed that venous and CSF flow alterations are linked to various pathological conditions. Since it is well known that, besides the heart beating, the thoracic pump influences the blood and CSF dynamics, we studied the effect of different respiration modes on blood and CSF flow rates using a real-time (RT)-PC prototype., Methods: Thirty healthy volunteers were examined with a 3 T scanner. A RT-PC sequence was acquired at the first cervical level to quantify the flow rates of internal carotid arteries, internal jugular veins (IJVs) and CSF. Each RT-PC acquisition was repeated three times, while the subjects were asked to breathe in three different ways for 60 s each: freely (F), with a constant rate (PN) and with deep and constant respiration rate (PD). The average flow rates were computed, they were removed from the respective signals and integrated in the inspiratory and expiratory phases (differential volumes). Finally, the power spectral density was computed for each detrended flow rate. High- and very-high frequency peaks were identified on the spectra while their frequencies were compared to the respiratory and cardiac frequencies estimated using a thoracic belt and a pulse oximeter. The area under the spectra was computed in four 0.5 Hz-wide ranges, centered on the high-frequency peak, on very-high frequency peak and its 2nd and 3rd harmonics, and then they were normalized by the flow rate variance. The effect of breathing patterns on average flow rates, on systolic and diastolic peaks, and on the normalized power was tested. Finally, the differential volumes of inspiration were compared to those of expiration., Results: The frequencies of the high- and very-high spectral peaks corresponded to the respiratory and cardiac frequencies. The average flow rate progressively decreased from F to PN to PD breathing, and the cardiac modulations were less predominant especially for the IJVs. The respiratory modulation increased with PD breathing. The average volumes displaced in the inspiratory phases were not significantly different from those of the expiratory one., Conclusions: The spectral analyses demonstrated higher respiratory modulations in PD compared to free breathing, even prevailing the cardiac modulation in the IJVs, showing an increment of the thoracic pump affecting the flow rate shape., (© 2022. The Author(s).)

Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia and high-permeability pulmonary edema. A hallmark of the disease is the presence of lung inflammation with features of diffuse alveolar damage. The molecular pathogenetic mechanisms of COVID-19-associated ARDS (CARDS), secondary to SARS-CoV-2 infection, are still not fully understood. Here, we investigate the effects of a cytokine-enriched conditioned medium from Spike S1-activated macrophage on alveolar epithelial A549 cells in terms of cell proliferation, induction of autophagy, and expression of genes related to protein degradation. The protective effect of baricitinib, employed as an inhibitor of JAK-STAT, has been also tested. The results obtained indicate that A549 exhibits profound changes in cell morphology associated to a proliferative arrest in the G0/G1 phase. Other alterations occur, such as a blockade of protein synthesis and the activation of autophagy, along with an increase of the intracellular amino acids content, which is likely ascribable to the activation of protein degradation. These changes correlate to the induction of IFN-regulatory factor 1 (IRF-1) due to an increased secretion of IFN-γ in the conditioned medium from S1-activated macrophages. The addition of baricitinib prevents the observed effects. In conclusion, our findings suggest that the IFN-γ-IRF-1 signaling pathway may play a role in the alveolar epithelial damage observed in COVID-19-related ARDS.

Objective: HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown., Design: We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother., Methods: Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA., Results: Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU., Conclusion: In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

The purpose of this study was to examine the effect of the JAK-STAT inhibitor baricitinib on the inflammatory response of human monocyte-derived macrophages (MDM) and endothelial cells upon exposure to the spike S1 protein from SARS-CoV-2. The effect of the drug has been evaluated on the release of cytokines and chemokines from spike-treated MDM, as well as on the activation of endothelial cells (HUVECs) after exposure to conditioned medium collected from spike-activated MDM. Results obtained indicate that, in MDM, baricitinib prevents the S1-dependent phosphorylation of STAT1 and STAT3, along with the induction of IP-10- and MCP-1 secretion; the release of IL-6 and TNFα is also reduced, while all other mediators tested (IL-1β, IL-8, RANTES, MIP-1α and MIP-1β) are not modified. Baricitinib is, instead, poorly effective on endothelial activation when HUVECs are exposed to supernatants from S1-activated macrophages; the induction of VCAM-1, indeed, is not affected by the drug, while that of ICAM-1 is only poorly inhibited. The drug, however, also exerts protective effects on the endothelium by limiting the expression of pro-inflammatory mediators, specifically IL-6, RANTES and IP-10. No effect of baricitinib has been observed on IL-8 synthesis and, consistently, on neutrophils chemiotaxis. Our in vitro findings reveal that the efficacy of baricitinib is limited, with effects mainly focused on the inhibition of the IL-6-mediated inflammatory loop.

Epoxy-based composites are designed for long-lasting applications, though their wide use is in contrast with their poor recyclability, which poses serious end-of-life issues. In order to reduce their environmental impact, precursors derived from fossil fuel based raw materials should be replaced with eco-friendly sources. This can be attained by using naturally derived epoxy matrices, or by finding a suitable solution for recycling at the end of life. In this paper, both strategies were analyzed, by replacing traditional monomers with epoxidized waste flour (EWF), an innovative bio-precursor derived from the organic waste stream, and a cleavable hardener, which allowed the recyclability of the matrix. The recyclable matrix was reinforced with recycled carbon fibers, derived from pyrolysis. DSC measurements were carried out in order to optimize the curing steps of the matrix, then flexural tests were performed in order to evaluate the mechanical response of the composite. A green recycling procedure was then investigated, which involved the use of non-toxic solvents and mild working conditions, and allowed recovery of the matrix while still preserving the properties of the carbon fibers. The components obtained after recycling were analyzed by FTIR analysis, which revealed the presence of the epoxy ring on the recycled waste flour. Hence, recycled waste flour was again used as a precursor and mixed with the cleavable hardener, thus, obtaining a closed-loop recycling.

ATP-binding cassette (ABC) transporters are a large superfamily of membrane transporters that facilitate the translocation of different substrates. While ABC transporters are clearly expressed in various tumor cells where they can play a role in drug extrusion, the presence of these transporters in normal lung tissues is still controversial. Here, we performed an analysis of ABC transporters in EpiAlveolar TM , a recently developed model of human alveoli, by defining the expression and activity of MDR1, BCRP, and MRPs. Immortalized primary epithelial cells hAELVi (human alveolar epithelial lentivirus-immortalized cells) were employed for comparison. Our data underline a close homology between these two models, where none of the ABC transporters here studied are expressed on the apical membrane and only MRP1 is clearly detectable and functional at the basolateral side. According to these findings, we can conclude that other thus-far-unidentified transporter/s involved in drug efflux from alveolar epithelium deserve investigations.

The availability of a reliable molecular assay in species recognition in forensic cases is of paramount importance when visual inspection or morphological methods are not exhaustive, especially from challenging samples. Here, two different caseworks involving bone samples founded during medico-legal outdoor investigations are presented. In order to exclude the human nature of the specimens and to determine the exact species they belong to, we proceeded with the molecular approach trying to generate sequences from the classical mtDNA markers cyt b and COI. However, they both gave critical results. For this reason, a short amplicon of ~ 150 bp of the 12S rRNA gene was used as an alternative.This short fragment was sufficient to identify the biological origin of the bone specimens with a high degree of certainty leading to the exclusion of their human nature. This work highlights the utility of the 12S rRNA and underlines the importance of deepen the choice of alternative shorter markers with respect to the classical ones, in order to achieve species identification even from challenging and degraded material in forensic criminal and wildlife caseworks., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Childhood obesity is a high prevalence condition that causes a high burden of disease in adulthood. Mobile phone app are increasingly used to prevent it. We summarized the evidence on the effectiveness of mobile apps for devices used by parents to prevent and treat childhood and adolescent obesity. An update of a systematic review of the literature (De Lepeleere et al., 2017) was carried out. PubMed, Embase, Cochrane, CINAHL, PsycINFO, Scopus, and ERIC were searched up to 2020. The included studies should target children 1-18 years, compare an app aimed at preventing or treating overweight and obesity, as stand-alone intervention or as part of a complex program, installed on parents' mobile devices, to no intervention or an intervention without the app. Outcomes related to weight status, diet, and physical activity (PA) behaviors were considered. Nineteen studies (14 RCTs and 5 non-randomized trials) were included. The app was mainly used to record food consumption and PA, to set goals, to view progress, and send health promotion messages. One study reported a significant decrease and one a suggestive decrease in anthropometric measures in obese and overweight children, while other studies observed no effect. One study reported a significant increase in PA. Six interventions proved to be effective in changing dietary behaviors. Interventions targeting overweight and/or obese children had the most positive results. All studies reported high acceptability and feasibility of interventions. The differences between interventions and the small sample size of the studies did not allow this review to reach conclusion on effectiveness., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

The study of brain venous drainage has gained attention due to its hypothesized link with various neurological conditions. Intracranial and neck venous flow rate may be estimated using cardiac-gated cine phase-contrast (PC)-MRI. Although previous studies showed that breathing influences the neck's venous flow, this aspect could not be studied using the conventional segmented PC-MRI since it reconstructs a single cardiac cycle. The advent of real-time PC-MRI has overcome these limitations. Using this technique, we measured the internal jugular veins and superior sagittal sinus flow rates in a group of 16 healthy subjects (12 females, median age of 23 years). Comparing forced-breathing and free-breathing, the average flow rate decreased and the respiratory modulation increased. The flow rate decrement may be due to a vasoreactive response to deep breathing. The respiratory modulation increment is due to the thoracic pump's greater effect during forced breathing compared to free breathing. These results showed that the breathing mode influences the average blood flow and its pulsations. Since effective drainage is fundamental for brain health, rehabilitative studies might use the current setup to investigate if respiratory exercises positively affect clinical variables and venous drainage.

This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth. Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0-12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A < 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to -2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %. This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications., (Copyright © 2022 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Clinical and experimental evidence point to a dysregulated immune response caused by SARS-CoV-2 as the primary mechanism of lung disease in COVID-19. However, the pathogenic mechanisms underlying COVID-19-associated ARDS (Acute Respiratory Distress Syndrome) remain incompletely understood. This study aims to explore the inflammatory responses of alveolar epithelial cells to either the spike S1 protein or to a mixture of cytokines secreted by S1-activated macrophages., Methods and Results: The exposure of alveolar A549 cells to supernatants from spike-activated macrophages caused a further release of inflammatory mediators, with IL-8 reaching massive concentrations. The investigation of the molecular pathways indicated that NF-kB is involved in the transcription of IP-10 and RANTES, while STATs drive the expression of all the cytokines/chemokines tested, with the exception of IL-8 which is regulated by AP-1. Cytokines/chemokines produced by spike-activated macrophages are also likely responsible for the observed dysfunction of barrier integrity in Human Alveolar Epithelial Lentivirus-immortalized cells (hAELVi), as demonstrated by an increased permeability of the monolayers to mannitol, a marked decrease of TEER and a disorganization of claudin-7 distribution., Conclusion: Upon exposure to supernatants from S1-activated macrophages, A549 cells act both as targets and sources of cytokines/chemokines, suggesting that alveolar epithelium along with activated macrophages may orchestrate lung inflammation and contribute to alveolar injury, a hallmark of ARDS.

Desmopressin (dDAVP) is the best characterized analogue of vasopressin, the endocrine regulator of water balance endowed with potent vasoconstrictive effects. Despite the use of dDAVP in clinical practice, ranging from the treatment of nephrogenic diabetes insipidus to bleeding disorders, much remains to be understood about the impact of the drug on endothelial phenotype. The aim of this study was, thus, to evaluate the effects of desmopressin on the viability and function of human pulmonary microvascular endothelial cells (HLMVECs). The results obtained demonstrate that the vasopressor had no cytotoxic effect on the endothelium; similarly, no sign of endothelial activation was induced by dDAVP, indicated by the lack of effect on the expression of inflammatory cytokines and adhesion molecules. Conversely, the drug significantly stimulated the production of nitric oxide (NO) and the expression of the inducible isoform of nitric oxide synthase, NOS2/iNOS. Since the intracellular level of cAMP also increased, we can hypothesize that NO release is consequent to the activation of the vasopressin receptor 2 (V2R)/guanylate cyclase (Gs)/cAMP axis. Given the multifaceted role of NOS2-deriving NO for many physio-pathological conditions, the meanings of these findings in HLMVECs appears intriguing and deserves to be further addressed.

Fragment-based lead discovery (FBLD) is one of the most efficient methods to develop new drugs. We present here a new computational protocol called High-Throughput Supervised Molecular Dynamics (HT-SuMD), which makes it possible to automatically screen up to thousands of fragments, representing therefore a new valuable resource to prioritise fragments in FBLD campaigns. The protocol was applied to Bcl-X L , an oncological protein target involved in the regulation of apoptosis through protein-protein interactions. Initially, HT-SuMD performances were validated against a robust NMR-based screening, using the same set of 100 fragments. These independent results showed a remarkable agreement between the two methods. Then, a virtual screening on a larger library of additional 300 fragments was carried out and the best hits were validated by NMR. Remarkably, all the in silico selected fragments were confirmed as Bcl-X L binders. This represents, to date, the largest computational fragments screening entirely based on MD.

Alveolar epithelium, besides exerting a key role in gas exchange and surfactant production, plays important functions in host defense and inflammation. Pathological conditions associated to alveolar dysfunction include Acute Respiratory Distress Syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). The use of predictive in vitro models of human alveolar epithelium is nowadays required for the study of disease mechanisms, as well as of pharmacokinetic parameters of pulmonary drugs delivery. Here, we employed a novel 3D model of human alveoli, namely EpiAlveolar™, consisting of primary alveolar epithelial cells, pulmonary endothelial cells and fibroblasts, that reflects properly the in vivo-like conditions. In EpiAlveolar™ we performed a characterization of Organic Cation Transporters (OCTs and OCTNs) expression and activity and we found that OCTN2, OCT1 and OCT3 are expressed on the basolateral membrane; instead, ATB 0,+ transporter for cationic and neutral amino acids, which shares with OCTN2 the affinity for carnitine as substrate, is readily detectable and functional at the apical side. We also show that these transporters differentially interact with anticholinergic drugs. Overall, our findings reveal close similarities of EpiAlveolar™ with the tracheal/bronchial epithelium (EpiAirway™ model) and entrust this alveolar tissue as a potential tool for the screening of biopharmaceuticals molecules., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Emerging evidences suggest that in severe COVID-19, multi-organ failure is associated with a hyperinflammatory state (the so-called "cytokine storm") in combination with the development of a prothrombotic state. The central role of endothelial dysfunction in the pathogenesis of the disease is to date accepted, but the precise mechanisms underlying the associated coagulopathy remain unclear. Whether the alterations in vascular homeostasis directly depend upon the SARS-CoV-2 infection of endothelial cells or, rather, occur secondarily to the activation of the inflammatory response is still a matter of debate. Here, we address the effect of the SARS-CoV-2 spike S1 protein on the activation of human lung microvascular endothelial cells (HLMVEC). In particular, the existence of an endothelium-macrophage crosstalk in the response to the spike protein has been explored., Methods and Results: The effect of the spike protein is addressed in human lung microvascular endothelial cells (HLMVEC), either directly or after incubation with a conditioned medium (CM) of human monocyte-derived macrophages (MDM) previously activated by the spike S1 protein (CM-MDM). Both MDM and HLMVEC are activated in response to the S1 protein, with an increased expression of pro-inflammatory mediators. However, when HLMVEC are exposed to CM-MDM, an enhanced cell activation occurs in terms of the expression of adhesion molecules, pro-coagulant markers, and chemokines. Under this experimental condition, ICAM-1 and VCAM-1, the chemokines CXCL8/IL-8, CCL2/MCP1, and CXCL10/IP-10 as well as the protein tissue factor (TF) are markedly induced. Instead, a decrease of thrombomodulin (THBD) is observed., Conclusion: Our data suggest that pro-inflammatory mediators released by spike-activated macrophages amplify the activation of endothelial cells, likely contributing to the impairment of vascular integrity and to the development of a pro-coagulative endothelium.

Organic wastes represent an increasing pollution problem due to the exponential growth of their presence in the waste stream. Among these, waste flour cannot be easily reused by transforming it into high-value-added products. Another major problem is represented by epoxy-based thermosets, which have wide use but also poor recyclability. The object of the present paper is, therefore, to analyze both of these problems and come up with innovative solutions. Indeed, we propose a completely new approach, aimed at reusing the organic waste flour, by converting it into high-value epoxy-based thermosets that could be fully recycled into a reusable plastic matrix when added to the waste epoxy-based thermosets. Throughout the research activity, the organic waste was transformed into an epoxidized prepolymer, which was then mixed with a bio-based monomer cured with a cleavable ammine. The latter reactant was based on Recyclamine™ by Connora Technologies, and in this paper, we demonstrate that this original approach could work with the synthetized epoxy prepolymers derived from the waste flour. The cured epoxies were fully characterized in terms of their thermal, rheological, and flexural properties. The results obtained showed optimal recyclability of the new resin developed.

Objective: To present the changes in 5-year relative survival of patients with breast and colorectal cancer in a northern Italian province in the 2000-2012 period. Changes are presented in relation to stage, period, and age in the screening population., Methods: A total of 5073 breast cancer and 4093 colorectal cancer cases were registered. Breast cancer was divided into 5 age groups: <45, 45-49, 50-69, 70-74 (the target screening population is ages 45-74), and >74 years. Colorectal cancers were classified into 3 age groups: <50, 50-69 (screening target population), and >69 years. Survival was analysed by stage, period, and screening program., Results: Five-year breast cancer relative survival was 92.9% overall, with 100%, 91.9%, 78.8%, 34.2%, and 76.4% for stages I, II, III, IV, and unknown, respectively. Survival increased from 89.7%, 91.8%, and 93.4%, respectively, in the periods 2000-2005, 2006-2009, and 2010-2012. Breast cancer survival was stable in early stages (although already high); a slight improvement was seen for stages III and IV. Five-year colorectal cancer relative survival was 63.6% overall, with 93.3%, 78.6%, 69.8%, 13.2%, and 55.8% for stages I, II, III, IV, and unknown, respectively. No improvement in survival was seen in the periods analysed, although the introduction of screening in 2005 did lead to a sharp decrease in incidence and mortality., Conclusions: For breast cancer, extending the screening target age led to an improvement in survival; for colorectal cancer, the best impact was on incidence and mortality rate.

Purpose: Laser-evoked potentials (LEPs) are useful neurophysiological tools for investigating the A-delta sensory peripheral fibers and the central nociceptive pathway. The current investigation aims to obtain normative values of LEPs via pudendal nerve stimulation in healthy adult volunteers., Methods: Laser-evoked potentials were recorded in 16 men and 22 women, 22 to 75 years of age, using neodymium and yttrium and aluminum and perovskite laser bilateral stimulation to the pudendal nerve-supplied skin and the dorsal surface of the hands and feet. We assessed the perceptive threshold, latency, and amplitude of the N1 component and main vertex N2-P2 complex. The relationship between gender, age, height, and site of stimulation was statistically analyzed., Results: Both in men and in women, laser perceptive threshold increased from genitalia to foot and from hand to foot (P ≤ 0.001). N1 and N2-P2 latencies progressively increased from pudendal area to hand to foot (P ≤ 0.008). N1 and N2-P2 complex LEP amplitudes progressively decreased from hand to genitalia to foot (P ≤ 0.04). The latencies of N1 component and N2-P2 complex of LEPs correlated with body height, whereas the amplitude of the N2-P2 complex correlated negatively with age; no correlations were observed between the latencies and amplitudes with gender., Conclusions: This study provides normative data on pudendal LEPs versus hand and foot LEPs. Incorporation of pudendal LEPs into clinical practice could provide a valuable neurophysiological tool for the study of pelvic pain syndromes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

In this work, we studied the transport properties (thermal and electrical conductivity) of smart fabric materials treated with graphite nanomaterial stacks-acetone suspensions. An innovative and easy method to produce graphite nanomaterial stacks-acetone-based formulations, starting from a low-cost expandable graphite, is proposed. An original, economical, fast, and easy method to increase the thermal and electrical conductivity of textile materials was also employed for the first time. The proposed method allows the impregnation of smart fabric materials, avoiding pre-coating of the fibers, thus reducing costs and processing time, while obtaining a great increase in the transport properties. Two kinds of textiles, cotton and Lycra ® , were selected as they represent the most used natural and artificial fabrics, respectively. The impact of the dimensions of the produced graphite nanomaterial stacks-acetone-based suspensions on both the uniformity of the treatment and the transport properties of the selected textile materials was accurately evaluated using several experimental techniques. An empirical relationship between the two transport properties was also successfully identified. Finally, several theoretical models were applied to predict the transport properties of the developed smart fabric materials, evidencing a good agreement with the experimental data.

At present, the central role played by arginine in the modulation of the inflammatory cellular responses is well-recognized, and many pro-inflammatory stimuli are known to modulate the expression and activity of its transmembrane transporters. In this regard, we have addressed the effects of bacterial flagellin from Pseudomonas aeruginosa (FLA-PA) on the uptake of the amino acid in human epithelial respiratory cells. Among the arginine transporters, only ATB 0,+ , y + L, and y + were operative in bronchial epithelial Calu-3 cells under control conditions; however, only the expression and activity of ATB 0,+ were stimulated upon incubation with flagellin, whereas those of systems y + L and y + were not stimulated. As a result, this induction, in turn, led to an increase in the intracellular content of arginine without making any change to its metabolic pathway. In addition, flagellin upregulated the amount of other amino acids substrates of ATB 0,+ , in particular, all the essential amino acids, such as valine, isoleucine, and leucine, along with the non-essential glutamine. At the molecular level, these effects were directly referable to the stimulation of a toll-like receptor-5 (TLR5) signaling pathway and to the induction of nuclear factor-κB (NF-κB) transcription factor. An induction of ATB 0,+ expression has been observed also in EpiAirway™, a model of primary human normal tracheal-bronchial epithelial cells that mimics the in vitro pseudostratified columnar epithelium of the airways. In this tissue model, the incubation with flagellin is associated with the upregulation of messenger RNAs (mRNAs) for the chemokine IL-8 and for the cytokines IL-6 and interleukin-1β (IL-1β); as for the latter, a marked secretion in the extracellular medium was also observed due to the concomitant activation of caspase-1. The overall findings indicate that, in human respiratory epithelium, flagellin promotes cellular responses associating the increase of intracellular amino acids through ATB 0,+ with the activation of the inflammasome. Given the role of the ATB 0,+ transporter as a delivery system for bronchodilators in human airway epithelial cells, its induction under inflammatory conditions gains particular relevance in the field of respiratory pharmacology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barilli, Visigalli, Ferrari, Borsani, Dall'Asta and Rotoli.)

SARS-CoV-2 virus infection is responsible for coronavirus disease (COVID-19), which is characterised by a hyperinflammatory response that plays a major role in determining the respiratory and immune-mediated complications of this condition. While isolating peripheral blood mononuclear cells (PBMCs) from whole blood of COVID-19 patients by density gradient centrifugation, we noticed some changes in the floating properties and in the sedimentation of the cells on density medium. Investigating this further, we found that in early phase COVID-19 patients, characterised by reduced circulating lymphocytes and monocytes, the PBMC fraction contained surprisingly high levels of neutrophils. Furthermore, the neutrophil population exhibited alterations in the cell size and in the internal complexity, consistent with the presence of low density neutrophils (LDNs) and immature forms, which may explain the shift seen in the floating abilities and that may be predictive of the severity of the disease. The percentage of this subset of neutrophils found in the PBMC band was rather spread (35.4 ± 27.2%, with a median 28.8% and IQR 11.6-56.1, Welch's t-test early phase COVID-19 versus blood donor healthy controls P < 0.0001). Results confirm the presence of an increased number of LDNs in patients with early stage COVID-19, which correlates with disease severity and may be recovered by centrifugation on a density gradient together with PBMCs.

Stroke patients often have difficulty completing motor tasks even after substantive rehabilitation. Poor recovery of motor function can often be linked to stroke-induced damage to motor pathways. However, stroke damage in pathways that impact effective integration of sensory feedback with motor control may represent an unappreciated obstacle to smooth motor coordination. In this study we investigated the effects of augmenting movement proprioception during a reaching task in six stroke patients as a proof of concept. We used a wearable neurorobotic proprioceptive feedback system to induce illusory kinaesthetic sensation by vibrating participants' upper arm muscles over active limb movements. Participants were instructed to extend their elbow to reach-and-point to targets of differing sizes at various distances, while illusion-inducing vibration (90 Hz), sham vibration (25 Hz), or no vibration was applied to the distal tendons of either their biceps brachii or their triceps brachii. To assess the impact of augmented kinaesthetic feedback on motor function we compared the results of vibrating the biceps or triceps during arm extension in the affected arm of stroke patients and able-bodied participants. We quantified performance across conditions and participants by tracking limb/hand kinematics with motion capture, and through Fitts' law analysis of reaching target acquisition. Kinematic analyses revealed that injecting 90 Hz illusory kinaesthetic sensation into the actively contracting (agonist) triceps muscle during reaching increased movement smoothness, movement directness, and elbow extension. Conversely, injecting 90 Hz illusory kinaesthetic sensation into the antagonistic biceps during reaching negatively impacted those same parameters. The Fitts' law analyses reflected similar effects with a trend toward increased throughput with triceps vibration during reaching. Across all analyses, able-bodied participants were largely unresponsive to illusory vibrational augmentation. These findings provide evidence that vibration-induced movement illusions delivered to the primary agonist muscle involved in active movement may be integrated into rehabilitative approaches to help promote functional motor recovery in stroke patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ferrari, Shell, Thumser, Clemente, Plow, Cipriani and Marasco.)

In our previous study, an innovative method for sterilization, inertization, and valorization of the organic fraction of municipal solid waste (OFMSW), to be recycled in the production of composite panels, was developed. In this follow-up work, the effects of fire retardants on fire performance, durability, and the mechanical properties of the composite panels based on OFMSW and melamine-formaldehyde resin were investigated. The performance of panels without fire retardants (control panels) was compared to panels containing either mono-ammonium phosphate (PFR) or aluminium trihydrate (ATH) at a mass fraction of 1% and 10% (modified panels). As shown by cone calorimetry, the total heat released was already low (about 31 MJ/m 2 at 50 kW/m 2 ) in the control panels, further decreased in the modified panels with the addition of fire retardants, and reached the lowest value (about 1.4 MJ/m 2 ) with 10% mass fraction of PFR. Hence, the addition of fire retardants had a beneficial effect on the response to fire of the panels; however, it also reduced the mechanical properties of the panels as measured by flexural tests. The deterioration of the mechanical properties was particularly obvious in panels containing 10% mass fraction of fire retardants, and they were further degraded by artificial accelerated weathering, carried out by boiling tests. Ultimately, the panels containing PFR at a mass fraction of 1% offered the best balance of fire resistance, durability, and mechanical performance within the formulations investigated in this study.

Background: Between 2000 and 2020, Europe experienced an annual net arrival of approximately 1.6 million immigrants per year. While having lower mortality rates, in the setting of severe diseases, immigrants bear a greater cancer-related burden due to linguistic and cultural barriers and socio-economic conditions. Professionals face a two-fold task: managing clinical conditions while considering the social, economic, cultural, and spiritual sphere of patients and their families. In this regard, little is known about the care provision to low-income immigrant cancer patients in real contexts., Aim: To investigate the perspective of professionals, family members, and stakeholders on the caring process of low-income immigrant cancer patients at the end of life., Design: A Constructivist Grounded Theory study., Setting/participants: The study, conducted at a Hospital in Northern Italy, involved 27 participants among health professionals, family caregivers, and other stakeholders who had recently accompanied immigrant cancer patients in their terminal phase of illness., Results: Findings evidenced that professionals feel they were not adequately trained to cope with immigrant cancer patients, nonetheless, they were highly committed in providing the best care they could, rushing against the (short) time the patients have left. Analyses evidenced four main categories: "providing and receiving hospitality," "understanding each other," "addressing diversity," and "around the patient," which we conceptualized under the core category "Achieve the best while rushing against time.", Conclusions: The model reveals the activation of empathic and compassionate behavior by professionals. It evidences the need for empowering professionals with cultural competencies by employing interpreters and specific training programs.

This work is aimed at proposing demonstrative actions devoted to show reprocessing and recyclability of PET originating from bottles collected from the seaside, in order to increase the consumer awareness on the importance of recycling plastics. To this purpose, collected bottles were washed, cut, grinded, extruded in the form of a thin wire adopting different cooling rates, which leads to a modulation of the crystallinity content. Once having optimized the processing parameters, the extruded wire was used to produce 3D printed samples through the fused deposition modelling (FDM). The changes in the crystalline structure due to the different processing conditions were assessed by DSC and XRD analyses, while rheological tests were performed in order to evaluate any modification in the viscosity of PET after repeated processing cycles. The reduction in thermal stability was confirmed by TGA analysis, which showed a progressive decrease in the degradation temperature as processing cycles increased. Finally, tensile tests highlighted the difference in the mechanical response due to the predominance of the crystalline or amorphous phase in the tested sample. In particular, a good mechanical behavior was found for the 3D-printed samples.

Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30-40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNFα, IL-23, IL-1β and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNFα, IL-1β, IFNγ and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes' cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay.

Aim: To evaluate the epidemiology of male breast cancer (MBC) in Italy and to describe incidence and survival data in relation to age, morphology, year of incidence, geographic area, and possible association with other cancers compared with female BC., Methods: Cases were extracted from 40 Italian Cancer Registries. Standardized incidence rates (SIR), age-specific rates, and 5-year survival were calculated. The association with second tumors was also evaluated. All data were compared with data from female BCs., Results: In the 2000-2014 period, 2175 new cases of MBC were registered, with an SIR of 1.7 × 100,000. The incidence showed a slight upward trend and increased with increasing age. The 5-year survival was 82% in the first two periods (2000-2004, 2005-2009), lower than in females (87%). The most frequent morphology was the ductal carcinoma (84%). Stage at diagnosis was 39.5% stage I, 33.1% stage II, 20.9% in stage III, and 6.4% in stage IV. Concerning receptor status, 96.4% had ER+ and 82.5% PR+; 46.5% had high Ki67 and 14.7% HER2 amplified. The risk of BC increased if the man had already had a previous tumor in any site (excess absolute risk, EAR = 2.7) and especially if he had had prostate cancer (EAR = 5.1). Instead, males with a previous diagnosis of BC had an increased risk of testicular, kidney and lung cancer., Conclusions: MBC requires more attention in terms of diagnosis and treatment as clinicians tend to follow the guidelines that have been developed for female BC management.

This work represents an innovative study that, for the first time, explores the possibility to use waste flours to produce thermoplastic polymeric bio-films. To the best of our knowledge, this is the first time that waste flours, derived from bakeries, pizzerias or pasta factories, have been proposed for the production of bio-polymers, as a replacement of neat starch. To this aim, durum waste flour derived from a pasta factory, soft waste flour derived from pizzerias and neat maize starch used as control material were firstly analyzed from dimensional, morphological and chemical points of view. Afterwards, waste flour films were produced by the addition of a nature-based plasticizer, glycerol. Mechanical characterization of the plasticized thermoplastic films, produced by compression molding, evidenced low performances, even in the case of the neat maize starch. In order to improve the mechanical properties, the possibility to include polylactic acid and cardanol-based plasticizer was also investigated. Mass transport properties of all the produced bio-films were investigated by measuring their water vapor permeability and hygroscopic absorption. The durability properties of the bio-films were assessed by accelerated ageing tests, while the bio-degradability of the waste-based films was evaluated by measuring the solubility and the degradation in water. The physicochemical analyses of the novel bio-films evidenced good mechanical properties; specifically, the waste-based films showed a lower hygroscopic absorption and water solubility than those of the blends containing neat starch.

Background: Childhood obesity prevention is a public health priority in industrialized countries. The Reggio Emilia Local Health Authority has implemented a program involving primary and secondary prevention as well as the care of obese children. There are many health-promoting mobile apps, but few are targeted to children and very few are sponsored by public health agencies., Objective: The goal of the research was to describe the process and tools adopted to cocreate a mobile app sponsored by the Reggio Emilia Local Health Authority to be installed in parents' phones aimed at promoting child health and preventing obesity., Methods: After stakeholder mapping, a consulting committee including relevant actors, stakeholders, and users was formed. Key persons for childhood obesity prevention were interviewed, focus groups with parents and pediatricians were conducted, and community reporting storytelling was collected. The results of these activities were presented to the consulting committee in order to define the functionalities and contents of the mobile app., Results: Three key trends emerged from community reporting: being active, playing, and being outdoors; time for oneself, family, and friends; and the pressures of life and work and not having time to be active and socialize. In focus groups, interviews, and labs, mothers showed a positive attitude toward using an app to manage their children's weight, while pediatricians expressed concerns that the app could increase their workload. When these findings were explored by the consulting committee, four key themes were extracted: strong relationships with peers, family members, and the community; access to safe outdoor spaces; children's need for age-appropriate independence; and professional support should be nonjudgmental and stigma-free. It should be a dialogue that promotes family autonomy. The app functions related to these needs include the following: (1) newsletter with anticipatory guidance, recipes, and vaccination and well-child visit reminders; (2) regional map indicating where physical activity can be done; (3) information on how to manage emergencies (eg, falls, burns, fever); (4) module for reinforcing the counseling intervention conducted by pediatricians for overweight children; and (5) a function to build a balanced daily diet., Conclusions: The pilot study we conducted showed that cocreation in health promotion is feasible, with the consulting committee being the key co-governance and cocreation tool. The involvement of stakeholders in this committee made it possible to expand the number of persons and institutions actively contributing to the project., (©Paolo Giorgi Rossi, Francesca Ferrari, Sergio Amarri, Andrea Bassi, Laura Bonvicini, Luca Dall'Aglio, Claudia Della Giustina, Alessandra Fabbri, Anna Maria Ferrari, Elena Ferrari, Marta Fontana, Marco Foracchia, Teresa Gallelli, Giulia Ganugi, Barbara Ilari, Sara Lo Scocco, Gianluca Maestri, Veronica Moretti, Costantino Panza, Mirco Pinotti, Riccardo Prandini, Simone Storani, Maria Elisabeth Street, Marco Tamelli, Hayley Trowbridge, Francesco Venturelli, Alessandro Volta, Anna Maria Davoli, Childhood Obesity Prevention Working Group. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 08.06.2020.)

Organic cation transporters (OCTs) and novel organic cation transporters (OCTNs) are responsible for drug delivery in the intestine and kidney; in the lung, OCTs mediate inhaled drugs' transport, although their physiological role in airways remains poorly understood. The studies addressing OCTs/OCTNs in human airways were mostly performed in immortal or transformed cell lines; here, we studied OCTs in EpiAirway™, a recently developed in vitro model of normal bronchial epithelium. Calu-3 monolayers were used for comparison. The activity of OCTs was evaluated by measuring the uptake of 1-methyl-4-phenylpyridinium (MPP + ) at the apical and basolateral side of monolayers and protein expression through Western Blot analysis. OCTs and OCTNs expression, along with that of Amino acid Transporter B 0,+ (ATB 0,+ )transporter, was determined by measuring the number of mRNA molecules through quantitative Polymerase Chain Reaction (qPCR). The interaction of the transporters with bronchodilators was also assessed. Results highlight significant differences between Calu-3 cells and EpiAirway™, since, in the latter, OCTs are active only on the basolateral membrane where they interact with the bronchodilator ipratropium. No activity of OCTs is detectable at the apical side; there, the most abundant carrier is, instead, SLC6A14 /ATB 0,+ , that can thus be potentially listed among organic cation transporters responsible for drug delivery in the lung.

This paper reports the preparation of newly synthesized bio-epoxy monomers, suitable for replacing petrochemical-derived epoxy resins. An original green method able to produce epoxy monomers starting from neat carbohydrates, waste flours, and even from the organic fraction of municipal solid waste (OFMSW), was here proposed. Hence, for the first time, the epoxidation of carbohydrates was attained only through the exposition to UV and ozone radiation, without using any organic solvent to carry out the reaction. Besides the innovation in the epoxidation method, this work explored the possibility of valorizing waste materials, by recycling carbohydrate scraps; in particular, the exposition of waste flours and municipal solid waste to UV and ozone and their consequent epoxidation allowed obtaining green precursors for the production of a bio-based epoxy resin. Applicability and suitability of the synthesized compounds for epoxy monomers were investigated by curing experiments with a selected amount of a model cycloaliphatic amine-type hardener, i.e. isophorodiamine (IPDA)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Childhood obesity is a major public health problem in industrialized countries. The aim of this study was to estimate the risk of obesity at age 5 based on BMI categories at age 3 and changes in BMI z-score from birth to 3 years of age. In this population-based study BMI data of 5173 children were collected at ages 3 and 5 and were linked to information relative to birth weight. The prevalence of obesity at age 5 was 3.8%. The risk of obesity for children born large for gestational age was 6.5%, while it was 18.6% for children overweight at age 3 and 62% for children who were obese at 3. An increase in BMI z-score from birth to 3 years increases the risk of obesity at age 5 (OR for increase of one standard deviation 2.8%; 95% CI: 2.46-3.20), but adjusting for BMI z-score at age 3, the effect of trajectory disappears (OR 1.08 95% CI: 0.9-1.29). In other words, if one targeted early preventive interventions to 3-year-olds affected by overweight/obesity (only 9.8% of the study cohort), one could possibly address 71% of children potentially affected by obesity at age 5., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The ATP-binding cassette (ABC) transporters P-glycoprotein (MDR1/ ABCB1 ), multidrug resistance-associated protein 1 (MRP1/ ABCC1 ), and breast cancer resistance protein (BCRP/ ABCG2 ) play a crucial role in the translocation of a broad range of drugs; data about their expression and activity in lung tissue are controversial. Here, we address their expression, localization and function in EpiAirway™, a three-dimensional (3D)-model of human airways; Calu-3 cells, a representative in vitro model of bronchial epithelium, are used for comparison. Transporter expression has been evaluated with RT-qPCR and Western blot, the localization with immunocytochemistry, and the activity by measuring the apical-to-basolateral and basolateral-to-apical fluxes of specific substrates in the presence of inhibitors. EpiAirway™ and Calu-3 cells express high levels of MRP1 on the basolateral membrane, while they profoundly differ in terms of BCRP and MDR1: BCRP is detected in EpiAirway™, but not in Calu-3 cells, while MDR1 is expressed and functional only in fully-differentiated Calu-3; in EpiAirway™, MDR1 expression and activity are undetectable, consistently with the absence of the protein in specimens from human healthy bronchi. In summary, EpiAirway™ appears to be a promising tool to study the mechanisms of drug delivery in the bronchial epithelium and to clarify the role of ABC transporters in the modulation of the bioavailability of administered drugs.

The aim of this work is the development and characterization of biodegradable thermoplastic recycled carbon ashes/maize starch (TPAS) composite films for agricultural applications. A proper plasticizer, that is, glycerol, was added to a commercial maize starch in an amount of 35 wt.%. Carbon-based ashes were produced by the biomass pyro-gasification plant CMD ECO 20, starting from lignocellulosic wastes. The ashes were added to glycerol and maize native starch at different amounts ranging from 7 wt. % to 21 wt.%. The composite was mixed at 130 °C for 10 min and then molded. The effect of the different amounts of carbon based ashes on the thermal and physical-mechanical properties of the composite was assessed by using several techniques, such as rheology, wide- angle X-ray diffraction (WAXD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), moisture absorption, degradation and mechanical tests. The presence of the carbon waste ashes allows to improve thermal and durability performances of the thermoplastic starch (TPS) films. It reduces the water absorption of starch matrix and strongly decreases the deterioration of starch, independently from fillers amount, enhancing the lifetime of the TPS films in outdoor conditions. In addition, the waste carbon ashes/maize starch films present an advantage in comparison to those of neat starch; it can biodegrade, releasing the plant nutrients contained in the ashes into the soil. In conclusion, this approach for recycling carbon waste ashes increases the efficiency of industrial waste management, along with a reduction of its impact on the environment., Competing Interests: The authors declare no conflict of interest.

In human, OCTN2 (SLC22A5) and ATB0,+ (SLC6A14) transporters mediate the uptake of L-carnitine, essential for the transport of fatty acids into mitochondria and the subsequent degradation by β-oxidation. Aim of the present study was to characterize L-carnitine transport in EpiAirway™, a 3D organotypic in vitro model of primary human tracheal-bronchial epithelial cells that form a fully differentiated, pseudostratified columnar epithelium at air-liquid interface (ALI) condition. In parallel, Calu-3 monolayers grown at ALI for different times (8d or 21d of culture) were used as comparison. OCTN2 transporter was equally expressed in both models and functional at the basolateral side. ATB0,+ was, instead, highly expressed and active on the apical membrane of EpiAirway™ and only in early-cultures of Calu-3 (8d but not 21d ALI). In both cell models, L-carnitine uptake on the apical side was significantly inhibited by the bronchodilators glycopyrrolate and tiotropium, that hence can be considered substrates of ATB0,+; ipratropium was instead effective on the basolateral side, indicating its interaction with OCTN2. Inflammatory stimuli, such as LPS or TNFα, caused an induction of SLC6A14/ATB0,+ expression in Calu-3 cells, along with a 2-fold increase of L-carnitine uptake only at the apical side; on the contrary SLC22A5/OCTN2 was not affected. As both OCTN2 and ATB0,+, beyond transporting L-carnitine, have a significant potential as delivery systems for drugs, the identification of these transporters in EpiAirway™ can open new fields of investigation in the study of drug inhalation and pulmonary delivery., Competing Interests: The authors have declared that no competing interests exist.