Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

We have studied the very large amount of literary works written by the Italian mystic Maria Valtorta to assess similarities and differences in her writings because she claims that most of them are due to mystical visions. We have used mathematical and statistical tools developed for specifically studying deep linguistic aspects of texts. The general trend indicates that the literary works explicitly attributable to Maria Valtorta differ significantly from her other literary works, that she claims are attributable to the alleged characters Jesus and Mary. Mathematically, they seem to have been written by different authors. The comparison with the Italian literature is very striking. A single author, namely Maria Valtorta, seems to be able to write texts so diverse to cover the entire mathematical range (suitable defined) of the Italian literature of seven centuries.

Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer Disease will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed focussing on Alzheimer Disease pathogenesis.

Flavonoids are polyphenolic phytochemical compounds found in many plants, fruits, vegetables, and leaves. They have a multitude of medicinal applications due to their anti-inflammatory, anti-oxidative, anti-viral, and anti-carcinogenic properties. Furthermore, they also have neuroprotective and cardioprotective effects. Their biological properties depend on the chemical structure of flavonoids, their mechanism of action, and their bioavailability. The flavonoid’s beneficial effects have been proven for a variety of diseases. In the last few years, it is demonstrated that flavonoids’ effects are mediated by inhibiting the NF-κB (Nuclear Factor-κB) pathway. In this review, we have summarized the effects of some flavonoids on the most common diseases such as cancer, cardiovascular, and neurodegenerative human diseases. In particular, here we collected all recent studies describing plant-derived flavonoids’ protective and prevention role, by specifically focusing their action on the NF-κB signaling pathway.

Background: Patients with allergic rhinitis (AR) have bothersome symptoms that may assess using the visual analog scale (VAS). Asthma frequently is associated with AR. The present study investigated the role of VAS in children with newly-diagnosed AR. Methods: Parameters were VAS for nasal and asthma symptoms, and doctor’s perception of these diseases, medication use, and asthma comorbidity. Results: 67% of AR children had asthma. Severity of perceived nasal symptoms was associated with more intense asthma symptoms and doctor’s perception of disease severity (p<0.001 and p=0.02, re-spectively. Conclusions: Allergic rhinitis frequently is associated with asthma in child-hood. Symptom perception assessment using VAS is a simple tool for assessing their intensity. Moreover, the severity of nasal symptoms is associated with asthma symptom severity. Therefore, asthma should be carefully considered in AR children and require appropriate symptom perception assessment.

The impact of controlled breathing on cognitive and affective processing has been recognized since ancient times, giving rise to multiple practices aimed at achieving different psychophysical states, mostly related to mental clarity and focus, stress reduction and relaxation. Previous scientific research explored the effects of unilateral nostril breathing (UNB) over brain activity, emotional and cognitive functions. Most evidence concluded for a contralateral effect, but many other controversial results make it difficult to come to an unambiguous interpretation. In the present study, we invited a pilot sample of 20 participants to take part in an 8-days breathing training, assigned either to the right nostril (URNB) or the left nostril breathing condition (ULNB). Then, each day, we assessed participants’ well-being indices with mood and mind-wandering scales. Results revealed that, after the daily practice, both groups reported improved well-being perception. However, the effect was specifically related to the nostril involved. URNB produced more benefits in terms of stress reduction and relaxation, while ULNB significantly reduced mind-wandering occurrences, increasingly over time. Our results are only partially in agreement with previous evidence, indicating the need for a more complex interpretive model that considers multiple brain networks and integrates central and peripheral nervous systems.

The unresolved territories are privileged places for the proliferation of degradation phenomena that affect the environment and human well-being. The impacts of their critical conditions go beyond the limits of the damaged urban fragments, involving the built environment, society, economy, culture and conditioning quality of life. This paper proposes a methodological approach to landscape design supported by an evaluation framework to orient strategic design planning with specific attention to unresolved territories consistent with circular economy perspective. The circular city principles are applied to spatial planning of landscape, by operationalising Ecosystem Services, Landscape Services, and Ecosystem Disservices, as interpretative categories for multi-dimensional regenerative strategies. Starting from the theoretical framework, the objective of the analysis is to implement an approach to the regenerative design of landscapes of waste, defined wastescapes. The industrial area of East Naples is the case study where an incremental evaluative approach has been defined to design scenarios to provide services and values, aimed to drive the conversion in a regenerativescape. A multi-criteria analysis through PROMETHEE-GAIA method has been implemented to compare the base case scenario with two incremental new scenarios and identify situated sustainable priorities.

Wetlands are complex ecosystems, considered among the most productive environments of the world. They contain major biodiversity hotspots, providing the resources upon which countless species of plants and animals depend and they perform important environmental and economic functions. Wetlands reduce flooding events, improve water quality and represent a valuable cultural and natural heritage. It is estimated that 2/3 of Europe wetlands have disappeared since the beginning of the 20th Century, mainly lost through development processes which did not take their functions and values adequately into account. The European Directive (2000/60/EC) re-quires to foster an integrated approach for wetland management through collaborative governance processes. The Wetland Contract is a tool that has been developed and implemented to set the ground for voluntary-based commitments for the sustainable governance of water systems. Among the Mediterranean countries, Italy and Croatia count on a rich variety of coastal wetlands that, together with the plants and animals inhabiting and crossing them, constitute an extremely precious natural heritage. The aim of this paper is to present and discuss, whit a critical approach, the output of the Interreg Project CREW that, between 2018-21, contributed to the drafting of seven new Wetland Contracts.

New digital interventions have shown potential in managing asthma and improving patients' quality of life compared with conventional interventions. Our objective was to conduct an exhaustive survey of the application of digital health technologies in evaluating, treating, and self-managing psychological and psychopathological elements linked to asthma. We analyzed a compendium of research papers and systematic reviews pertaining to asthma, encompassing themes such as outdoor air pollution, early life wheezing disorders, atopic dermatitis, digital strategies for asthma self-management, psychiatric conditions and asthma, familial impacts on pediatric asthma, and the utilization of mobile health apps for managing asthma. We scrutinized eight chosen studies to evaluate the capacity of digital health technologies to enhance the man-agement and treatment outcomes of psychological factors related to asthma. The studies under review indicate that eHealth interventions, mixed reality instruments, mHealth technolo-gy-augmented nurse-led interventions, and smartphone apps incorporating Bluetooth-enabled sensors for asthma inhalers can markedly enhance self-management of symptoms, quality of life, and mental health outcomes, particularly in children and adolescents with asthma. Nonetheless, additional research is required to ascertain their efficacy and practicability across diverse populations and environments. Customized interventions that cater to the unique needs and preferences of asthma patients and associated psychological elements are vital to ensure the persistent and equitable adoption of these technologies. We underscore the significance of addressing psychological elements in the management and treatment of asthma and advocate for ongoing research and development in this domain.

Dynamic virtual testing by Hardware in the Loop (HIL) real time simulation systems is common to minimize physical tests to validate and verify control algorithms, logics and software, under normal and emergency conditions. The accurate but costly HIL models setup activities could have an extended use to simulate faulty conditions that are seldom observable in the real system, yet they must be detected in advance and recognized. Data driven diagnostic methods have reached a mature development, in various sectors, proving effective in early detecting slowly varying deviations from nominal patterns of signals, even without a priori knowledge of their nature and behavior. These methods rely on vast amount of data logged from real systems that are ever and ever richer of monitoring telemetries that are worth being exploited. However, due to the usually reliable and safe systems being managed, it is often difficult to collect enough data on anomalous situations to validate fault detection and isolation and limit false positives. HIL model-based simulations allow generating and observing operational domains or transients rarely observed in real operations. This allows identifying the signals that are most correlated to faults and that could be selected to setup data-based diagnostic models of parts or subsystems, which are more suitable than the whole HIL model for online diagnostics, as well as to identify the features and trends that are most symptomatic of anomalous conditions.

Sulfenic acids as small molecules are too unstable to be isolated and their transient nature offers the possibility to involve them in concerted processes that lead to the obtainment of functional groups such as sulfoxides, sulfones and disulfides. All these functions are present in a number of natural and synthetic drugs and can represent structural motives inducing biological relevant properties. In this small review the generation and reactions of sulfenic acid bearing naturally occurring residues are described. Carbohydrate and aminoacid-derived sulfenic acids have been used in concerted addition to triple bonds to obtain alliin derivatives and thiosugars in enantiomerically pure form. Glycoconjugates with sulfinyl, sulfonyl and disulfane functional groups and pyridine-derived disulfides have been obtained from bis and tris-sulfinyl precursors of sulfenic acids. Small families of such compounds have been subjected to preliminary biological tests. Starting from the evidence that the control of molecular architecture and the presence of suitable functional groups can play a significant role on the exhibition of biological properties, apoptotic effects on malignant cells by glycoconjugates and inhibitory activity against the important human pathogen S. aureus by pyrimidine-derived disulfides have been found.

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer associated to asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and the Epithelial Mesenchymal Transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos related primary oxidative damage is counteracted in the lung by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet fully understood. Moreover, asbestos exposure has been associated to induced EMT event, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in a possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells: as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Take as a whole, these results show, for the first time, a crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, so improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.

Deep learning image reconstruction (DLIR) algorithms employs convolutional neural networks (CNNs) for CT image reconstruction to produce CT images with a very low noise level, even at low radiation dose. The aim of this study was to assess whether the DLIR algorithm reduces the CT effective dose (ED) and im-proves CT image quality in comparison with filtered back projection (FBP) and iterative reconstruction (IR) algorithms in intensive care unit (ICU) patients. We identified all consecutive patients referred to the ICU of a single hospital who underwent at least two consecutive chest and/or abdominal contrast-enhanced CT scans within a time period of 30 days using DLIR and subsequently FBP or IR algorithm (Advanced Mod-eled Iterative Reconstruction model-based algorithm [ADMIRE], or Adaptive Iterative Dose Reduction 3D [AIDR 3D]) for CT image reconstruction. The radiation ED, noise level, and signal-to-noise ratio (SNR) were compared between the different CT scanners. The non-parametric Wilcoxon test was used for statistical comparison. Statistical significance was set at p < 0.05. A total of 83 patients (mean age, 59 ± 15 years [standard deviation]; 56 men) were included. DLIR vs FBP reduced ED (18.45 ± 13.16 mSv vs 22.06 ± 9.55 mSv, P < 0.05), while DLIR vs FBP and vs ADMIRE and AIDR 3D IR algorithms reduced image noise (8.45 ± 3.24 vs 14.85 ± 2.73 vs 14.77 ± 32.77 and 11.17 ± 32.77\, P < 0.05) and increased SNR (11.53 ± 9.28 vs 3.99 ± 1.23 vs 5.84 ± 2.74 and 3.58 ± 2.74, P < 0.05). CT scanners employing DLIR reduced radiation ED and im-proved SNR compared to CT scanners using FBP, whereas CT scanners using DLIR improved SNR com-pared to CT scanners using FBP or IR algorithms in ICU patients.

Several chronic diseases derive from metabolic, genetic, or inflammatory causes and often these causes are interconnected. Pharmacological treatments, although effective, often lead to unpleasant side effects. In this context, preventive approaches are of growing interest. The literature data of recent years support that the dietary intake of bioactive compounds can positively influence the biological functions of an organism. Among the bioactive compounds in the diet, polyphenols are widely recognized for their beneficial effects on health, as useful compounds for preventing/combating a series of pathologies related to lifestyle, metabolism, and aging. The artichoke (Cynara scolymus L.), a member of the Asteraceae family, is widely used in the food and herbal medicine fields for its beneficial properties. Artichokes are rich in polyphenols (including cynarin), flavonoids and their derivatives, and, for this reason, they have aroused interest in their pharmacological properties. The best-known activity of polyphenols is antioxidant activity. Through it, they help to neutralize free radicals, preventing cellular damage and the subsequent risk of conditions such as cancer, diabetes, and heart disease. Related to the antioxidant action we find the anti-inflammatory activity. This is an important benefit since chronic inflammation is a cause or contributory cause of many chronic diseases. Although many scientific results are of great interest and potential, there are still gaps to be filled. In this review, we report and discuss new insights providing documented evidence regarding the benefits of the artichoke compounds and their possible use to support the pharmacological treatment of pathologies associated with inflammation.

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy, its effectiveness in increasing bone mineral density (BMD) and in modulating biochemical skeletal markers upon previous treatments with bisphosphonates in a group of post-menopausal women affected by osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray Absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased effectiveness in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

The efficacy of chemotherapy depends on sensitivity and intrinsic or acquired drug resistance of cancer cells. The n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic mechanisms. The specific mechanisms are not fully understood, but nowadays, it is widely accepted that there are a complex network of mechanisms, including alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species and lipid peroxidation. A crucial mechanism in the control of cell drug uptake and efflux is related to n-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, n-3 LCPUFAs often impact on the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting their adjuvant role in cancer treatment.

A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices which have been classified as “possibly carcinogenic”, however their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (RE) may promote genomic instability, here we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of RE, such as long interspersed nuclear element1s (LINE-1), Alu short interspersed nuclear element and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM-modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE1 and ribosomal repeats in terms of both average profiles and organization of methylated and un-methylated CpG sites, in different ways in each of the three cell lines studied.

Among the components of a healthy life, sexuality is an essential part, contributing not only to psychophysical well-being, but also to the social well-being of women and, consequently to their quality of life. A poorly investigated standpoint is the acceptability of a contraceptive method, not only in terms of tolerability and metabolic neutrality, but also concerning the impact that it can have on sexual life. In this context, we will provide an overview of the different methods of contraception and their effects on female sexuality from the biological changes, to organic, social, and psychological factors, which can all shape sexuality.A MEDLINE/PUBMED review of the literature between 2010 and 2021 was conducted using the following key words/phrases: hormonal contraception, contraceptives, female sexual function, libido, sexual arousal and desire, and sexual pain. Recent studies have supported the effects of contraceptives on women’s sexuality, describing a variety of positive and negative events on several domains of the sexual function (desire, arous-al, orgasm, pain, enjoyment). However, satisfaction with sexual activity depends on factors that extend beyond sexual functioning alone. A more holistic approach is needed to better under-stand the multitude of factors linked to women’s sexuality and contraception. Contraceptive counselling must necessarily consider these important elements since they are closely related to good compliance.

Vulnerability is the big issue of the small inland urban centers exposed to the risk of depopulation. In the climate and in the context of an increasing seismic risk in the center-northern part of Italy, seismic vulnerability can become the determinant cause of the final abandonment of a small town. In some Italian regions, as well as Emilia Romagna, municipalities are implementing seismic vulnerability reduction policies based on the Emergency Limit Condition that has become a basic reference for ordinary land planning. This study proposes a valuation planning approach to the seismic vulnerability reduction carried out within the general planning framework concerning the Faentina Union, a group of five small towns located in the south-western part of the Province of Ravenna, Italy. The approach consists of three main stages: knowledge – the typological, constructive and technological description of the buildings specifically concerning their vulnerability degree; interpretation – the analyses aimed to outline a range of hypotheses about the damages in case of seism; planning – identifying the works intended to definitely reduce the vulnerability of the buildings. This stage includes a cost modelling tools aimed at outlining the trade-off between the extension and the intensity of the vulnerability reduction works, given the budget.

The aim of this study was to evaluate the effect of dietary supplementation with Olea europaea L. extract on the animal welfare and milk quality of lactating Italian Holstein-Friesian dairy cows at different calving orders. Cows in mid lactation phase received, for 60 days, the natural olive extract Phenofeed Dry® (500 mg/cow/day) with high antioxidant power. Hormonal and metabolic parameters were determined through ELISA assays, the milk fatty acid profile through gas chromatography, chemical-nutritional and hygienic-sanitary parameters through ultrasonic analyses. The milk lysozyme content was measured through a specific ELISA assay. The administration of the enriched feed did not alter the hormonal balance. Primiparous cows were more sensitive to the treatment and showed a better general health status compared to other calving orders. The enriched feed resulted in a reduction of saturated fatty acids (SFAs) and an increase of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), ensuring an adequate nutritional content and, above all, a significantly higher content of the antibacterial protein, lysozyme. Overall, our study demonstrate that the inclusion of natural bioactive molecules such as Olea europaea L. polyphenols contributes to improving the welfare status of dairy cows and ensuring high nutritional and functional quality of animal productions.

In horses, quantitative assessment of gait parameters, as the use of inertial measurement units system (IMUs), might help in the decision-making process. However, it requires financial investment, is time-consuming, and lacks accuracy if displaced. An innovative Artificial Intelligence marker-less Motion Tracking System (AI-MTS) may overcome these limitations in the field. Our aim was to compare the level of agreement and accuracy between both systems and visual clinical assessment. Twenty horses underwent locomotion analysis by visual assessment, IMUs and AI- MTS systems, in the following conditions: straight hard (SH), straight soft (SS), left and right circle hard (LCH, RCH) and soft (LCS, RCS). A greater number of horses were considered sound by clinical examination, compared to those identified as symmetric by the two gait analysis systems. More limbs were considered asymmetric by the AI-MTS compared to IMUs, suggesting its greater sensitivity. The greatest agreement between the two systems was found for the difference between two minima in vertical head position in SH, while the lowest for the difference between two minima in vertical pelvis position in SS, reflecting the difficulties in assessing asymmetry of hindlimbs. Some degree of asymmetry may be clinically relevant, suggesting its regular use in training horses.

Personalized treatment based on driver molecular alterations, such as ALK rearrangement, has revolutionized the therapeutic management of advanced oncogene addicted NSCLC patients. Multiple effective ALK tyrosine kinase inhibitors (TKIs), with the amelioration of the activity at central nervous system level, are now available, leading to substantial prognosis improvement. The exposure to TKIs triggers resistance mechanisms and the sequential administration of other TKIs and chemotherapy is, for the most part, not targeted. In this context, extending the benefit deriving from precision medicine is paramount, above all when disease progression occurs in a limited number of sites. Retrospective data indicate that, in oligoprogressive disease, targeted therapy beyond progression combined with definitive local treatment of the progressing site(s) is an effective alternative. In these cases, multidisciplinary approach becomes essential for an integrated treatment strategy, depending on the site of disease progression, in order to improve not only survival, but also quality of life. In this review we provide an updated and comprehensive overview of the main treatment strategies in case of ALK rearranged oligoprogression, including systemic treatment as well as local therapy, and report real-world clinical stories, with the final aim of identifying the most promising management for this subset of patients.

Intense physical efforts performed at maximal or near-maximal speeds and the ability to recover among sprint are important characteristics of soccer player. Considering that women's soccer is a markedly growing sport, the aim of the study was to analyse the performance (total time –TT-; fatigue index percentage -IF%) and physiological (aerobic and anaerobic) responses to Repeated Sprint Ability Test (RSA, 7×30 m sprints with 25 s of active recovery among sprints) in an elite female player (age: 30 yrs; BMI: 20.3 kg/m²). A repeated measure MANOVA over the 7 sprints time series was applied (p < 0.05). Results showed that TT was 58.71 s (Ideal Time: 56.98 s) with IF% of 3.0%. Energy contributions were given for 80.3% by aerobic, 19.2% by anaerobic lactid, and 0.5% by anaerobic alactid sources. Considering that 1) we have different kinetics in heart rate (HR) and maximum oxygen uptake with oxygen uptake that reach the peak when HR is still rising, and 2) the energy consumption during intermittent exercises requires different metabolism as a result of physiological stimuli proposed, the present findings substantiate the need to choose specific and adequate training methods for female soccer players that aim at increasing their RSA performances.

Introduction: This study aims to investigate the activity of the remdesivir-nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination. Methods: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir-nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration. The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic. Results: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h with an HSA score of 52.8 and 28.6, respectively (p<0.0001). This data has been confirmed performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone. An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab, and dexamethasone, with an excellent clinical-radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir up to the negativization. Conclusion: Remdesivir-nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.

Palmitoylethanolamide (PEA) has been prescribed for neuropathic pain for several years. This study is mainly addressed to summarize what has been published on the topic in the last decades, and how appropriate the numerous prescriptions are. Among others, it examines the innovative EquiPEA^® patent, which aims to address obstacles encountered with conventional PEA formulations. EquiPEA^® seems to partially ameliorate the bioavailability and the targeted distribution. It seems to introduce novel advancements that have the potential to enhance the therapeutic effectiveness of PEA in terms of its anti-inflammatory, antioxidant, and analgesic properties. The deep literature analysis aims to examine the potential advantages of this innovative formulation, in the context of several pathological conditions that may benefit from this molecule. In particular, it investigates the potential enhanced bioavailability and targeted delivery system of EquiPEA^®. Also, it tries to understand if it can modernize the field of therapy based on PEA, thus offering a better treatment option for individuals with long-term inflammation, oxidative stress, and neuropathic or mixed pain with a neuropathic component. The study examines the possible impact of EquiPEA^® on personalized medicine strategies and its potential for translation into clinical practice. It analyses the possibilities that EquiPEA^® has in enhancing patient outcomes in a range of central nervous system and inflammatory conditions. This narrative review makes a valuable contribution to the ongoing comprehension of PEA therapy. It establishes a foundation for further exploration in research and potential uses in clinical settings.

A Brewer Spent Grain (BSG), the most abundant by-product of the brewing process, is mainly used in animal feed and biogas production. The aim of the present work is BSG valorization by yeast fermentation to produce carotenoids. R. mucilaginosa CBS316 was cultured on BSG syrups, supplemented or not with YE and PEP (s-Fsa and Fsa). The biomass and carotenoid production were optimized in flasks and then scaled-up in bioreactor. In flask tests, the maximum biomass concentration was 5.3 and 6.2 g/L for Fsa and s-Fsa cultures, respectively. The maximum carotenoid production was 833 μg/L in Fsa and 1159 μg/L in s-FSA. Considering that the highest specific productivity value (P 7.16 μg/g*h) was obtained with Fsa syrup, this medium was selected for the process scale-up. In bioreactor tests, the maximum concentrations of biomass (4.29 g/L) and carotenoid (396 ug/L) was reached at 72 hours of fer-mentation, 24 h later than in flask. The total carotenoid produced was 524 and 150 ug in bioreactor and flask cultures, respectively. The carotenoids production by R. mucilaginosa was obtained both in Fsa and s-Fsa syrups. The results confirm the possibility to use the syrup as it is, Fsa, thus limiting the process costs.

We study the work fluctuations in ergotropic heat engines, namely two-strokes quantum Otto engines where the work stroke is designed to extract the ergotropy (the maximum amount of work by a cyclic unitary evolution) from a couple of quantum systems at canonical equilibrium at two different temperatures, whereas the heat stroke thermalizes back the systems to their respective reservoirs. We provide an exaustive study for the case of two qutrits whose energy levels are equally spaced at two different frequencies by deriving the complete work statistics. By varying the values of temperatures and frequencies, only three kinds of optimal unitary strokes are found: the swap operator U1, an idle swap U2 (where one of the qutrits is regarded as an effective qubit), and a non trivial permutation of energy eigenstates U3, which indeed corresponds to the composition of the two previous unitaries, namely U3 = U2U1. While U1 and U2 are Hermitian (and hence involutions), U3 is not. This point has an impact on the thermodynamic uncertainty relations (TURs) which bound the signal-to-noise ratio of the extracted work in terms of the entropy production. In fact, we show that all TURs derived from a strong detailed fluctuation theorem are violated by the transformation U3.

Cestrum parqui L'Herit. (Solanaceae family) is a species of forest shrub, self-incompatible and specialized in pollination, widespread in the subtropical area of the planet and now widely dis-tributed also in the Mediterranean area. The constituents of its leaves have antimicrobial, anti-cancer, insecticidal, antifeedant, and herbicidal properties. The spread of this species represents a valuable source of compounds with high biological value. Research on potential uses, under-standing of the nutritional and functional composition, and applications of C. parqui extracts is important and very promising for its commercial use. To date, there are some reports on the potential applications of C. parqui extracts as selective natural pesticides and for their potential phytotoxic role. Scientific knowledge and the use of extraction techniques for these components are essential for commercial applications. This article summarizes the research and recent studies available on the botany, phytochemistry, functional properties, and commercial applications of C. parqui as a biopesticide.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

The work consisted in identifying possible effects from heavy metals (HMs) pollution due to waste disposal activities in three potentially polluted sites located in Basilicata (Italy), where a release of pollutants with values over the thresholds allowed by the Italian legislation was detected. The potential variations in the physiological efficiency of vegetation have been analyzed through the multitemporal processing of satellite images. In detail, Landsat 5 Thematic Mapper (TM) and Landsat 8 Operational Land Imager (OLI) images were used to calculate the Normalized Difference Vegetation Index (NDVI) trend over the years. Then, the multitemporal trends were analyzed using the median of Theil-Sen, a non-parametric estimator particularly suitable for the treatment of remote sensing data, being able to minimize the outlier effects due to exogenous factors. Finally, the subsequent application of the Mann-Kendall test on the trends identified by Theil-Sen slope allowed the evaluation of trends significance and, therefore, the areas characterized by the effects of contamination on vegetation. The application of the procedure to the three survey sites led to the exclusion of the presence of significant effects of HMs contamination on the vegetation surrounding the sites during the years of waste disposal activities.

The last decade was characterized by the reduction of hospital beds throughout Europe. When facing Covid pandemic, this has been an issue of major importance as hospitals were seriously overloaded with an unexpected growth in demand. The dichotomy formed by the scarcity of beds and the need for acute care was handled by the Bed Management (BM) function. This study explores how BM was able to help the solidness of the healthcare system, managing hospital beds at best and recruiting others in different set-tings as intermediate care, in a large Local Health Authority (LHA) in central Italy. Ad-ministrative data show how the provision of appropriate care was achieved recruiting approximately 500 beds belonging to private healthcare facilities affiliated with the re-gional healthcare system and exercising at best the BM function. The ability of the system to absorb the extra demand caused by Covid was made possible using intermediate care beds, which allowed to stretch the logistic boundaries of the hospitals, and by the promptness of Bed Management in converting beds in Covid beds and reconverting them and timely managing internal patient logistic, thus creating space according to the healthcare demand.

Augmented Reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications is driving new perspectives in improving diagnostic accuracy and sensitivity in the field of traumatology. Currently, however, it is still difficult to quantify the value and impact in the medical-scientific field especially in the improvement of diagnostic in complex fractures. Acetabulum fractures have always been a challenge among orthopedics, for volumetric complexity and low diagnostic reliability.Background/Objectives: The goal of this study is to determine whether these methods can improve the learning aspect and diagnostic accuracy of complex acetabulum fractures compared to gold standard CT (computed tomography). Methods: Orthopedic residents of our department have been selected and divided into Junior (JUN) and Senior (SEN) groups. Associated fractures of acetabulum have been included in the study, obtaining : CT-scans, 3DP model, and AR model displayed on a tablet screen. In a double-blind questionnaire, each resident classified every fracture according to methods. Diagnostic accuracy (DA), response time (RT), agreement (R), and confidence (C) were measured. Results: 20 residents (JUN=10, SEN=10) classified five fractures. Overall DAs were 26% (CT), 18% (3DP), and 29% (AR). AR-DA resulted to be superior to 3DP-DA (p=0,04). DA means (JUN vs SEN respectively) were :CT-DA was 20% vs 32% (p&lt;0.05), 3DP-DA was 12% vs 24% (p=0.08), and AR-DA was 28% vs 30% (p=0,80). Overall RT was 61.2 sec (±24,6) for CT, 35.8 sec (±20,1) for 3DP, and 46,7 sec (±20,8) for AR. R was fairly poor between methods and groups. 3DPs resulted to have superior overall C (65%). Conclusions: AR resulted to have the same Overall DA as CT, independent from experience, 3DP has minor DA and R, but it resulted to be the most confident and fast method. Intra and interobserver R between methods remain very poor in residents.

A new chiral Mn-salen catalyst, functionalized with a long aliphatic chain and a choline group, able to act as surfactant catalyst for green epoxidation in water, is here described. This catalyst was employed with a commercial surfactant (CTABr) leading to a nanoreactor for the enantioselective epoxidation of some selected alkenes in water, using NaClO as oxidant. This is the first example of nanoreactor for enantioselective epoxidation of non-functionalized alkenes in water.

Biosurfactants (BSs) are microbial compounds that have emerged as potential alternatives to chemical surfactants due to their multifunctional properties, sustainability, and biodegradability. Owing to their amphipathic nature and distinctive structural arrangement, biosurfactants exhibit a range of physicochemical properties, including excellent surface activity, efficient critical micelle concentration, humectant properties, foaming and cleaning abilities and the capacity to form microemulsions. Furthermore, numerous biosurfactants display additional biological characteristics, such as antibacterial, antifungal, and antiviral effects, antioxidant, anticancer, and immunomodulatory activities. Over the past two decades, numerous studies have explored their potential applications, including pharmaceuticals, cosmetics, antimicrobial and antibiofilm agents, wound healing, anticancer treatments, immune system modulators and drug/gene carriers. These applications are particularly important in addressing challenges such as antimicrobial resistance and biofilm formation in clinical, hygiene, and therapeutic settings. They can also serve as coating agents for surfaces, enabling antiadhesive, suppression, or eradication strategies. Not least importantly, biosurfactants have shown compatibility with various drug formulations, including nanoparticles, liposomes, micro and nanoemulsions, and hydrogels, improving drug solubility, stability, and bioavailability and enabling targeted and controlled drug release. These qualities make biosurfactants promising candidates for the development of next-generation antimicrobial, antibiofilm, anticancer, wound healing, immunomodulating, drug or gene delivery agents, as well as adjuvants to other antibiotics. Analyzing recent literature, this review aims to provide insights into the present understanding, highlight emerging trends, identify promising directions and advancements in the utilization of biosurfactants within the pharmaceutical and biomedical fields.

The global process of urbanization, and the modification of social interaction determined by the pandemic crisis poses the issue of the place of vulnerable users, and in particular children, within the contemporary city. This research aims to elaborate a theoretical and methodological framework, based on the concepts of affordance and capability, for analyzing the potential of public spaces to enable and support children’s independent activities. This potential, or meaningful usefulness, is expressed by the Index of Meaningful Usefulness of public Urban Spaces (IUIS). The latter is calculated via the tool ‘Opportunities for Children in Urban Spaces’ (OCUS). This methodology is applied to the analysis of significant public spaces within the historic center of the city of Iglesias in Sardinia, Italy. The results reveal adequate usefulness of the selected spaces, while underlining criticalities related to intrinsic spatial and physical attributes. The application to the case study confirms the validity of the theoretical and methodological framework embodied in the OCUS tool for supporting urban design and planning by orienting place-shaping processes towards the acknowledgement of children’s needs.

SARS-CoV-2 attachment and entry inside mammalian cells is mainly mediated by human angiotensin-converting enzyme 2 (ACE2) and its interaction with spike protein. However, it is well known that spike protein also interacts with other molecules like glycosaminoglycans (GAG), e.g., heparan sulfate (HS) or Enoxaparin (EX), which are linear, anionically charged polysaccharides known for their biological activities. The mode of action of these two polysaccharides is to bind spike protein to block the interaction with ACE2 receptors. This study aimed to assess a model capable of confirming the activity of these GAGs in both the wild-type strain of SARS-CoV-2 and its variants, such as the highly variable BA.2.86. This was achieved by combining in silico modeling with in vitro determination using BacMam technology. The results showed the antiviral activity of HS and EX both in vitro and through the in-silico analysis, reconciling conflicting findings from recent studies on the cellular entry of SARS-CoV-2. In conclusion, it is possible to highlight the ability of these molecules to circumvent the high variability of SARS-CoV-2, providing valuable insights into intervention strategies targeting cell entry mechanisms and establishing a safe in vitro model.

: Organic poultry need high-quality proteins in their diet. The EU’s organic regulation forbids synthetic amino acids; therefore, soybean, with its balanced essential amino acid content, has become the most used protein source, though much of it is imported from non-EU countries. Soybean, however, has some important problems related to sustainability and crop competition; therefore, it must be substituted with a high-protein-value alternative such as insect meal. In this study, 900 Aviagen Savanna broilers were reared using three different organic diets. The diets used the following as protein feed material: soybean only (S100), 50% black soldier fly larvae meal (BSL) and 50% soybean (BSL50), and 100% BSL only (BSL100). Broiler performance, welfare, and fatty acids (FA) in the thigh and breast were analyzed. BSL50 and BSL100 negatively affected growth performance, while BSL100 worsened all of the market-related measures of performance. Meat quality was worse in BSL50 and BSL100, with a significant increase in saturated FA (SFA) and a corresponding decrease in polyunsaturated FA (PUFA). Among SFA, lauric acid (C12:0) more notably increased. The increase in SFA represents a negative aspect of BSL meal inclusion, namely the production of lauric acid; however, this trend could have a beneficial effect, which will be more deeply explored with regard to its impact on animal and human health.

Equine Asthma Syndrome (EAS) is a common respiratory problem that affects horses of any age. In the severe EAS form (historically referred to as recurrent airway obstruction or RAO) the diagnosis, based mainly on history and clinical signs, it is definitively confirmed by the cytological examination of the bronchoalveolar lavage (BAL), also very useful in monitoring lower airway inflammation in response to environmental management and medication. Cytocentrifugated preparation is usually the staging method for the BAL cytological interpretation. To evaluate whether the BAL cytology in horses with severe EAS under different environmental conditions and before and after treatment can undergo significant changes, and at the same time to investigate whether in the cytological evaluation of the BAL there are interpretative differences between two methods of smear preparation of the collected fluid, a study was carried out on a series of BAL samples (n=48) collected in 8 withdrawals from 6 EAS-affected horses subjected to process exacerbation through environmental stimuli and then to pharmacological treatment. Each BAL fluid collected was equally divided into duplicate portions: one set up by cytocentrifugation and one by sediment from simple centrifugation. The cytological examination revealed any significant difference between the EAS-affected horses in all experimental phases (asymptomatic, early exacerbation phase, late exacerbation phase, and remission phase). Diagnostic interpretive comparison between the two BAL preparations then showed no significant differences in results, suggesting how they can be used indifferently in the evaluation of BAL under conditions of airway inflammation in the horse. Thus, the concentrated smear preparation appears to be an equally diagnostically useful method in conditions where there is no possibility of using an appropriate cytocentrifuge.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the key regulator of low-density lipoprotein cholesterol (LDL-C) plasma levels. We previously observed that treatment of dyslipidemic subjects with nutraceutical combination containing red yeast rice (monacolin K 3.3 mg), Berberis aristata cortex extract (Berberine 531.25 mg) and Morus alba leaves extract (1-deoxynojirimycin 4 mg) (LopiGLIK®) did not alter the plasma PCSK9 levels. Thus, the aim of the present study was to investigate the effect of these three components on PCSK9 expression in HepG2 cell line in relationship to their effects on LDL-C cellular uptake. HepG2 cell line were incubated with Berberis aristata cortex extract (BCE), red yeast rice (RYR) and Morus alba leaves extract (MLE) alone or in combination for 24 h. RYR (50 µg/mL) increased PCSK9 protein expression (WB and ELISA assays), PCSK9 mRNA and its promoter activity. BCE (40 µg/mL) reduced PCSK9 expression, mRNA levels and promoter activity. MLE determined a concentration-dependent inhibition of PCSK9 at mRNA and protein levels, with a maximal reduction at 1 mg/mL; no significant changes in PCSK9 promoter activity were found. MLE also downregulates the expression of fatty acid synthase and HMG-CoA reductase mRNA levels. The combination of RYR, BCE and MLE reduced PCSK9 at mRNA, protein, and promoter activity. Finally, this combination induced the LDL receptor and LDL-C uptake by HepG2 cells. In conclusion, the positive effect of MLE on PCSK9 supports the rational of using this nutraceutical combination to control hyperlipidemic conditions.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

Despite laws and directives for the regulation and restriction of pesticide in farming, the large use of Plant Protection Products (PPPs) in paddy fields is a relevant worldwide cause of contamination of the environment. The aim of this work is to evaluate the environmental impact due to the use of PPPs by using an integrated approach based on chemical analyses and ecotoxicological hazard assessment, supported by statistical tools, in order to overcome the issues related to the traditional tabular evaluation. Samples of soil and water of seven conventional and organic paddies located in Northern Italy have been examined for two years by extensive chemical and ecotoxicological analyses. The results evidenced a direct relationship between the presence of Oxadiazon in water and bioassays responses as the main cause of the toxicity measured. This phenomenon affected both biological and conventional rice fields, due to the free circulation of water through irrigation canals. Therefore, the implementation of organic districts with a water circulation isolated from conventional fields represents a simple and effective countermeasure to safeguard the agricultural practices of organic crops.

Terpenoids are toxic compounds produced by plants as a defense strategy against insect herbivores. We tested the effect of Origanum vulgare terpenoids on the generalist herbivore Spodoptera littoralis and the response of the plant to herbivory. Terpenoids were analyzed by GC-FID and GC-MS and quantitative gene expression (qPCR) was evaluated on selected plant genes involved in both terpene biosynthesis. The insect detoxification response to terpenes was evaluated by monitoring antioxidant enzymes activity and expression of insect genes involved in terpene detoxification. O. vulgare terpenoid biosynthesis and gene expression was modulated by S. littoralis feeding. The herbivore-induced increased level of terpenoids (particularly carvacrol and p-cymene) interacted with the herbivore by decreasing larval survival and growth rate. The assimilation by S. littoralis of more than 50% of ingested terpenes correlated with the possible toxic effects of O. vulgare terpenoids. In choice test experiments, carvacrol and γ-terpinene mediated the larval feeding preferences, wherease the prolonged feeding on O. vulgare terpenoids (particularly on γ-terpinene) exerted relevant antinutritional effects on larvae. S. littoralis was found to react to O. vulgare terpenoids by increasing its antioxidant enzymes activities and gene expression, although this was not sufficient to sustain the toxicity of O. vulgare terpenoids.

Nowadays, there is evidence that bacteria can contribute to cancer formation and interfere with therapy by mediating its carcinogenesis and related infection. Moreover, it is acknowledged that microbial infections and antibiotic resistance represent severe economic and health risks to society. These facts have led to the developing of several new techniques for impeding crucial biological processes in microbial cells. One of these techniques centers on using metal-chelating agents, which can disrupt the microorganism's vital metal metabolism by obstructing metal uptake and bioavailability for critical reactions. Additionally, nanotechnology has made a wide range of nanomaterials available for possible uses in the antibacterial industry. This complex field is shaped by antimicrobial nanoparticles, also investigated as therapeutic and drug-delivery tools. Halloysite nanotubes (HNTs) are naturally occurring tubular clay nanomaterials consisting of aluminosilicate kaolin sheets rolled up several times. The aluminon and siloxane groups on the surface of HNTs facilitate the formation of hydrogen bonds with biomaterials on their surface. These properties make HNTs crucial in a wide range of applications, such as in environmental sciences, wastewater treatment, dye removal, nanoelectronics and nanocomposite fabrication, catalytic studies, coatings for glass or anti-corrosive coatings, cosmetics, flame retardants, stimulus-response, and in forensic sciences. This work aimed to produce an antibacterial material by combining the properties of halloysite nanotubes with the ability of kojic acid to chelate iron. Starting from kojic acid, a simple nucleophilic substitution involving the hydroxyl groups on the surface of the nanotubes was performed. The obtained material was characterized by IR and SEM, and its ability to chelate iron was evaluated. Finally, the capacity to load drugs such as resveratrol and curcumin was also evaluated by UV analysis. In this way, a new bio-based material that can be used as a drug carrier and antimicrobial was produced.

A new coronavirus (SARS-CoV-2) have determined a pneumonia outbreak in China (Wuhan and Hubei) on December 2019. While pharmaceutical and non-pharmaceutical intervention strategies are strengthened worldwide, the scientific community has been studying the risk factors associated with SARS-Cov-2, to enrich epidemiological information. For a long time, before the industrialized era, air pollution has been a real and big health concern and it is today a very serious environmental risk for many diseases and anticipated deaths in the world. It has long been known that air pollutants increasing the invasiveness of pathogens for humans by acting as a carrier and making people more sensitive to pathogens through a negative influence on the immune system. Based on scientific evidences, the hypothesis that air pollution, resulting from a combination of factors such as meteorological data, level of industrialization as well as regional topography, can acts both as an infection carrier as a harmful factor of the health outcomes of COVID-19 disease has been raised recently. This hypothesis is turning in scientific evidence, thanks to the numerous studies that have been launched all over the world. With this review, we want to provide a first unique view of all the first epidemiological studies relating the association between air pollution and SARS-CoV-2. Major findings are consistent, highlighting the important contribution of air pollution on the COVID-19 spread and with a less extent also PM₁₀.

The meridian line is a basic instrument for positional astronomy, it was used to study the motion of Sun, Moon, planets and the position of stars by measuring position and time of their passage through the meridian plane. The accuracy of such positions was dependent on precise theories of the atmospheric refraction (Cassini, 1655 and Laplace, 1825) and by the use of reference marks present originally on the meridian line, and now cancelled by the centuries. From October 27, 2018 the new pinhole of the meridian line in the Basilica of S. Maria degli Angeli in Rome (1702) is a circle 25 mm wide and 6.11 mm thick and its position is fixed, in order to perform a series of observations of astrometric quality, the IGEA campaign. The comparison of the observed positions of the meridian passages of the Sun, Southern and Northern limbs, with the ephemerides of Calsky.org and Stellarium 0.20.2 for the Sun are examined for the dates of the ingresses into the zodiacal signs, when the ecliptic longitude is exactly 0°/180° (Aries and Libra, spring and fall equinox), 30°/150° (Taurus, Virgo), 60°/120° (Gemini, Leo), 90° (Cancer), 330°/210° (Pisces, Scorpio), 300°/240° (Aquarius/Sagittarius), 270° (Capricorn). The former geometrical calibration of the marks present on the line, with a total station, is compared with another calibration done with a metal and laser meter. The first star on the floor of the Basilica representing the position of the Sun on August 20, 1702 when the pope Clement XI visited the meridian line, financed by him, has been calibrated with the solar image. The present pinhole is 4.4±0.1 mm South with respect to the original one of 1702.

The COVID-19 pandemic has had a profound impact on the mental health, adjustment, and psychological well-being of young adults. Despite extensive research conducted in this area, eudaimonic well-being, one specific form of psychological well-being focusing on self-knowledge and self-realization within existential challenges, has received comparatively less attention. The current study aimed to investigate the potential linkages between two key psychological factors, psychological inflexibility and fear of death, with eudaimonic well-being among young adults in the context of the Covid-19 pandemic. One year after the outbreak, 317 young Italian adults (18-34 yrs.) participated in an online survey, including measures of psychological inflexibility (AAQ-II), fear of death (CL-FODS), and eudaimonic well-being (PWB). Results showed that psychological inflexibility was negatively associated with all the dimensions of Ryff’s model of eudaimonic well-being, while fear of death of others was found to be associated with three of these dimensions (autonomy, environmental mastery, and self-acceptance). Results also indicated a mediation role of psychological inflexibility in the association between fear of death and eudaimonic well-being. These findings expand our knowledge of the potential factors that may influence eudaimonic well-being and provide insights for clinical work with young adults challenged by uncertain times.

Microbiota plays a key role in various body’s functions, physiological, metabolic and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Several evidences indicate that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that resides on the mucosal surface or within the mucus layer participate in interactions with the host immune system, and a healthy gut microbiota is essential for the development of mucosal immunity. The immunomodulatory activity of probiotics has been proposed in several bowel disorders or in aging-related dysfunctions. In HIV infected patients, the intestinal immune system is affected and inflammation persists during ART therapy too. Several studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition and microbial translocation in HIV infection. This mini-review aims to suggest how the use of probiotics is beneficial not only in maintaining a healthy status but also to improve conditions in HIV subjects.

The maintenance of traditional agricultural practices in protected small islands is closely linked to the preservation of the land, the protection of natural resources, and the conservation of local traditions. For this purpose, the Tuscan Archipelago National Park promoted the census of ancient horticultural varieties preserved by some farmers on the island of Elba. The survey revealed a deep-rooted historical, cultural, social, and economic link between this germplasm and the island’s territory. A scientific characterization of the landrace under ethnobotanical, morphological, and genetic aspects was carried out. Among these local varieties, two landraces of the Brassica species and three landraces of the Phaseolus species were identified and analyzed in this study. To ascertain their distinguishability and uniqueness, similar varieties were also identified based on morpho-physiological characteristics or territorial proximity and compared with the Elban landraces. Morpho-phenological data were collected, and molecular analyses were carried out using Simple Sequence Repeats (SSR) markers. Ten different SSR loci were considered for the Phaseolus species and nine for the Brassica species. The Tuscan Archipelago landraces showed a high level of internal variability but were clearly distinct from each other and from the analyzed varieties, as shown by AMOVA (Analysis of Molecular Variance). Their distinctness was further highlighted by the UPGMA dendrogram obtained from the genetic distance matrix. The same results were confirmed by Principal Coordinate Analysis (PCoA). This study confirms the peculiarity of the Elban landraces, their biodiversity is a heritage to be safeguarded, which can also be used in future breeding programs. These ancient Elban landraces were allocated to local farmers (most were young farmers) to protect them from extinction and to promote more resilient varieties cultivation compared to commercial hybrids widely spread in the area. Local farmhouses also play a strategic role in safeguarding the germplasm and dissemination of sustainable agricultural practices. There is high demand for ancient Elban landraces, this has led to the development of a new local economy balanced between agricultural tradition and innovation.

Superconducting split ring resonator arrays allow to overcome two main limitations affecting metallic metamaterial resonating in the Terahertz (THz) range: Ohmic losses and tunability of their optical response. In this work, we design and experimentally realize direct and complementary square arrays of superconducting YBa2Cu3O7 (YBCO) split ring resonators working in the THz spectral range. The main purpose of this paper is to show how the metamaterial resonances can be tuned by temperature (T) when crossing the superconducting transition temperature Tc of YBCO. The tuning property can be quantified by describing the THz transmittance of the patterned YBCO films vs. T through a model of coupled resonators. This model allows us to estimate the THz resonances of split-ring arrays and their interaction, showing how the kinetic inductance Lk in the superconducting state is the main parameter affecting the metamaterial properties.

Indoleamine 2,3-dioxygenase 2 (IDO2) is a paralogue of IDO1, a tryptophan-degrading enzyme producing immunomodulatory molecules. However, the two proteins are unlikely to carry out the same functions. IDO2 shows little or no tryptophan catabolic activity and exerts contrasting immunomodulatory roles in a context-dependent manner, in both cancer and autoimmune diseases. The recently described potential non-enzymatic activity of IDO2 has suggested its possible involvement in alternative pathways resulting in either pro- or anti-inflammatory effects in different models. In a previous study on non-small cell lung cancer (NSCLC) tissues, we found that IDO2 expression, revealed at the plasma membrane level of tumor cells, was significantly associated with poor prognosis. In this study, the A549 human cell line, basally expressing IDO2, was used as an in vitro model of human lung adenocarcinoma to gain more insights on a possible alternative function of IDO2, different from the catalytic one. In these cells, immunocytochemistry and isopycnic sucrose gradient analyses confirmed the IDO2 protein localization in the cell membrane compartment, and immunoprecipitation of tyrosine-phosphorylated proteins revealed that IDO2 can be targeted by kinase activities. The different localization than the cytosolic one and the phosphorylation state are the first indications for the signaling function of IDO2, suggesting that the IDO2 non-enzymatic role in cancer cells is worthy of deeper understanding.

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

In the dynamic and complex environment of industrial control rooms, operators are often inundated with a multitude of tasks and alerts, which can lead to an overwhelming situation known as task overload. This state can precipitate decision fatigue and a heavier reliance on cognitive biases, potentially compromising the decision-making process. To mitigate such risks, the implementation of decision support systems becomes crucial. These systems are designed to assist operators in making swift and well-informed decisions, particularly when they sense their own judgment may be faltering. Our research introduces an AI-based framework that leverages dynamic influence diagrams and reinforcement learning to construct an effective decision support system. The cornerstone of this framework is the creation of a robust, interpretable, and efficient tool that supports control room operators during critical process disturbances. By integrating expert knowledge, the dynamic influence diagram forms a comprehensive model that captures the uncertainties inherent in complex industrial processes. It is adept at anomaly detection and recommending optimal actions. Moreover, this model is enhanced through a strategic partnership with reinforcement learning algorithms, which fine-tune the recommendations to be more context-specific and precise. The ultimate goal of our framework is to provide operators with a live, reliable decision support system that can significantly improve their response during process upsets. This paper outlines the development of our AI framework and its application within a simulated control room environment. Our findings indicate that the use of decision support systems can lead to improved operator performance and reduced cognitive workload. However, it also reveals a trade-off with situation awareness, which tends to diminish as operators may become overly reliant on the system’s guidance. Trust emerges as a critical factor in the adoption and effectiveness of decision support systems. Our research underscores the importance of balancing the benefits of decision support with the need for maintaining operator engagement and comprehension during process operations.

The outbreak of coronavirus disease 2019 (COVID-19) was identified in Wuhan, China, in December 2019. As of April 17, 2020, more than 2 million cases of COVID-19 have been reported worldwide. Northern Italy is one of the world’s centers of active coronavirus cases. In this study, we predicted the spread of COVID-19 and its burden on hospital care under different conditions of social distancing in Lombardy and Emilia-Romagna, the two regions of Italy most affected by the epidemic. To do this, we used a Susceptible-Exposed-Infectious-Recovered (SEIR) deterministic model, which encompasses compartments relevant to public health interventions such as quarantine. A new compartment L was added to the model for isolated infected population, i.e., individuals tested positives that do not need hospital care. We found that in Lombardy restrictive containment measures should be prolonged at least until early July to avoid a resurgence of hospitalizations; on the other hand, in Emilia-Romagna the number of hospitalized cases could be kept under a reasonable amount with a higher contact rate. Our results suggest that territory-specific forecasts under different scenarios are crucial to enhance or take new containment measures during the epidemic.

Background: Dual disorders (DD) involve the coexistence of substance use disorder (SUD) with another mental illness, often from psychotic and affective categories. This study explores the ef-fectiveness of brexpiprazole, a third-generation antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder (DSM-V) and comorbid AUD/SUD (DSM-V). Methods: Eighteen enrolled patients underwent psychometric assessments at baseline and one month into brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (PANSS total score, p=0.004), improved CGI total score (p=0.042), and decreased MOAS total score (p=0.012). Quality of life improved in SF-36 subscales (p<0.05). Substance craving reduction, though observed, did not reach statistical significance. Conclusions: This study provides initial evidence supporting brexpiprazole's efficacy and safety with positive effects on psychopathology and quality of life, emphasizing the need for tailored, comprehensive treatment strategies in this complex patient population.

Objectives Listeria monocytogenes (LM), the etiological agent of Listeriosis, can cause foodborne zoonosis. In this study, we characterized 23 strains that caused human listeriosis in Palermo (Sicily, Italy) during the period 2018-2020. In addition, we assessed the phenotypic susceptibility of clinical isolates to antibiotics in accordance with EUCAST guidelines. Methods The serogroup was determined by PCR. While MLST and MVLST were identified through the sequencing of housekeeping genes. Finally, susceptibility to antibiotics was assessed by means of the Phoenix automatic system. Results Patients hospitalized with listeriosis were predominantly males (56% vs. 44% of females). The cases were not associated with pregnancy included patients >65 years of age (60%), two of whom were affected by cancer, while cases associated with pregnancy included two pregnant women and three preterm infants. Data collected found that the main pathologies shown by patients were meningitis (60,9%) and bacteremia (39,1%). The LM strains were isolated from blood (52%), cerebrospinal fluid (26%), cerebrospinal fluid + blood (13%), blood + nasal swab (4%), and ascitic fluid (4%). The predominant serogroup was IVb (96%), whereas only one strain belonged to serogroup IIa (4%). Among the strains with serotype 4b, 4d, 4e, ST 2/VT 21 (92%) and ST6/VT19 (4%) were determined, while only isolates with serotype 1/2a, 3a show ST155/VT45 (CC155). Conclusion This study revealed the widespread circulation of a single clinical strain (ST2/VT21) associated with suspected food contamination, demonstrating the importance of carrying out molecular epidemiological surveillance. Our clinical isolates were susceptible to the assayed beta-lactams, in agreement with the literature data.

Socio-demographic factors are responsible of health inequalities also in vaccination. The aim of this study was to evaluate their role at population level through a population-based study performed on the whole population entitled to receive COVID-19 vaccines in Umbria Region, Italy, and registered to the Regional Healthcare Service as of February 28th, 2021. Socio-demographic characteristics and vaccination status in terms of uptake at least one dose of any available vaccine, completion of the primary vaccination cycle and uptake of the booster doses as of February 28th, 2022 were col-lected from the Umbria regional database. The percentage of eligible population who did not initiate the COVID-19 vaccination, complete the full vaccination cycle and get the booster dose was 11.8%, 1.2% and 21.5% respectively. A younger age, being a not-Italian citizen, and not holding an ex-emption for chronic disease/disability and a GP/FP were associated to all the endpoints. Females, as compared to males, were more likely to not initiate the vaccination but less likely to not receive the booster dose. On the contrary, results on the deprivation index were not conclusive. The findings, beyond confirming current knowledge at population level, provide new inputs for better tailoring vaccination campaigns.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

In the area of dental healthcare services, where patients and professionals deal with multiple auditory stimuli, this cross-sectional study reports on the intricate dynamics of sound preferences, noise obstacles, and the profound impact of music on anxiety reduction within dental office set-tings. The sample comprises of 134 dental patients, primarily females (56.7%), with varying age groups, education levels, and therapy durations in the university clinics of the department of Dentistry, National and Kapodistrian University of Athens and four private dental offices at the metropolitan area of Athens, Greece. Notably, 92.5% of the participants report no hearing loss, and 56.7% exhibit some level of noise sensitivity. The study reveals a moderate to good perceived health status (M=3.84, SD=0.95) among participants, with low perceived noise disturbance in university dental clinics. Preferences for instrumental music, foreign pop, and classical music are prominent during waiting times. Potential irritations include impersonal treatment (44%) and staff behavior (41.8%). Music player usage within the settings of the dental clinic involves radios (49.3%) and headphones (41.0%). Correlations and predictors indicate associations between health status, music preferences, and noise disturbances. More specifically, visiting the university dental clinics (β = .300, p = .005) as well as younger age (β = .300, p = .034) were significant predictors of better perceived health status. Clearer perception of external sounds while using the music player (β = .190, p = .039) was a significant predictor of better perceived health status, while poorer health was predicted by the preference of Greek folk songs (β = -.200, p = .030). Also, the use of smartphones for playing music was related to poorer health (β = -.370, p < .001). Following, younger age (β = -.270, p = .015), lower education (β = -.210, p = .035), higher noise sensitivity (β = .190, p = .027), as well as feelings of anxiety and nervousness due to ambient noise from people and machines (β = .510, p = .027) were significant predictors of noise disturbance from machines. Also, visiting private clinics (β = .240, p = .018), preferences of specific playlist (β = .310, p = .012), no music (β = .280, p = .016) and use of smartphones to play music (β = .230, p = .029) were significant predictors of noise disturbance from patients or staff. Finally, the preference of listening to a specific playlist was related to better health status (r = .190, p < .05). Findings aim to optimize eco-soundscapes in dental offices, con-tributing to enhanced patient well-being. The research underscores the potential of music inter-ventions to alleviate dental anxiety and improve the overall dental experience and quality care.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Sleep is a fundamental human need: sleep disruption, in fact, causes an increase in the activity of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms and pro-inflammatory responses. Sci-entific literature is finally starting to pay attention to the central role of sleep-wake rhythm alterations for patients health. Oxaliplatin is used extensively for the treatment of gastrointestinal cancer and other malignancies, with increased frequency of use in recent years. This study aims to understand the effects of sleep-wake rhythm alterations on health and quality of life on cancer patients treated with oxaliplatin. Study has been conducted through the creation and distribution of questionnaires to patients to inves-tigate the potential alteration of the sleep-wake quality. Evaluating the influence of the collected variables on sleep quality, only liver and biliary tract and pancreas tumor lo-calization, in males, and previous difficulty sleeping, and anxiety, worries and stress, in females, resulted statistically significant. The results obtained may serve as foundation for designing awareness campaigns and updating of patients, healthcare personnel and caregivers, to improve health and quality of patients life.

When we are asleep we lose the ability to promptly respond to external stimuli and yet we spend many hours every day in this inherently risky behavioral state. This simple fact strongly suggests that sleep must serve essential functions that rely on the brain going offline, on a daily basis, and for long periods of time. If these functions did not require partial sensory disconnection, it would be difficult to explain why they are not performed during waking. Paradoxically, despite its central role in defining sleep and what sleep does, sensory disconnection during sleep remains a mystery. We have a limited understanding of how it is implemented along the sensory pathways, we do not know whether the same mechanisms apply to all sensory modalities, nor do we know to which extent these mechanisms are shared between non-rapid eye movement (NREM) sleep and REM sleep. The main goal of this contribution is to review some knowns and unknowns about sensory disconnection during sleep as a first step to fill this gap.

Cooperation is widely recognized to be challenging for the well-balanced development of human societies. The emergence of cooperation in populations has been largely studied in the context of the Prisoner's Dilemma game, where temptation to defect and fear to be betrayed by others often activate defective strategies. In this paper we analyze the decision making mechanisms fostering cooperation in the two-strategy Stag-Hunt and Chicken games, which include the mixed strategy Nash equilibrium, describing partially cooperative behavior. We find the conditions for which cooperation is asymptotically stable in both full and partial cases, and we show that the partially cooperative steady state is also globally stable in the simplex. Furthermore, we show that the last can be more rewarding than the first, thus making the mixed strategy effective, although people cooperate at a lower level with respect to the maximum allowed, as it is reasonably expected in real situations. Our findings highlight the importance of Stag-Hunt and Chicken games in understanding the emergence of cooperation in social networks.

Our work is regarding the analysis of land use changes, in the light of “saving soil” against the expansion due to unearned plus value of land: The loss of natural and agricultural surface in front of the expanding urban environment is a critical aspect of unsustainability of urban development, especially in the way it was carried out in the past decades. The measure of the physical transition of land use and characters from a more natural condition of land surface to a new artificial one, joint with a parallel analysis of the increase of land value due to such change is nowadays a major land-policy tool. The interplay of urban economics regulation with planning, reveals new key issues in urban governance and environmental preservation. In this paper it will be shown some experiment about the impact assessment of soil take, related with the seek of valorization of property inside the planning process. Our paper reports as well about the experimental activity carried out inside the MITO Lab of the Polytechnic of Bari, where reports about property values and environmental values have been produced, specially looking at the reality of the Apulia, a southern Italian Region, that is rich of farmlands and coastlines, often invaded by constructions with a severe loss of nature, landscape and ecosystems services.

Opuntia sp. contain antioxidant phytochemicals resistant to ROS damage, whose excess negatively affect fertilization. We investigate the activity of fruit extracts of O. dillenii and O. ficus indica (cv red and yellow) on sperm quality and cryopreservation. In the first experiment, we exposed the samples to extracts (50 µl) for 1 hour to then evaluate semen parameters (vitality, motility, acrosome reaction, DNA fragmentation and oxidative stress). The results showed a significant increase in the motility (86%±0.19 for OFI cv yellow, 82%±0.15 for OFI cv red and 90%±0.08 for O. dillenii) compared to the control (80%±0.17). Moreover, we noted a reduction of DNA fragmentation on treated (3%±0.03 in OFI cv yellow, 7%±0.09 in OFI cv red and 5%±0.07 in O. dillenii) than the control (40%±0.14). Furthermore, the oxidative stress was reduced after exposure to solutions (3.15mV in the control and 2.94mV in the treated). In the second experiment, 50 µl of solutions were added to the Freezing medium. After thawing, we observed an improvement in vitality and the number of intact acrosomes. Our results suggest that Opuntia sp. fruit extracts improve sperm quality, both before and after cryopreservation, optimizing the potential of fertilization of sperm cells.

In the Emergency Department (ED), pain is one of the symptoms that is most frequently reported, making it one of the most significant issues for the emergency physician, but is frequently under treated. Intravenous (IV), oral (PO), and intramuscular (IM) delivery are the standard methods for administering acute pain relief. Firstly, we compared the safety and efficacy of IN analgesia to other conventional routes of analgesia to assess if IN analgesia may be an alternative for the management of acute pain in ED. Secondary, we analyzed the incidence and severity of adverse events (AEs) and rescue analgesia required. We performed a systematic review-based keywords in Pubmed/Medline, Scopus, EMBASE, the Cochrane Library and Controlled Trials Register finding only twenty randomized Clinical trials eligible in the timeline 1992-2022. A total of 2098 patients were analyzed and compared to intravenous analgesia showing no statistical difference in adverse effects. In addition, intranasal analgesia also has a rapid onset and quick absorption. Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while providing effective pain relief. IN is simple to administer, non-invasive, rapid onset and quick absorption; it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management. Analgesia needs to be tailored to each patient's features and type of pain: IN Fentanyl and Ketamine look promising and may be administered easily and safely while providing effective pain relief.

Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. TILs has a strong prognostic role in triple negative breast cancer (TNBC). Little is known about his interaction with Androgen receptor (AR) and Forkhead box A1 (FOXA1). We analyzed the relationships between TIL levels, AR and FOXA1 expression and their clinical significance in TNBC patients. Further, we investigated their interaction with other biomarkers like programmed cell death ligand-1 (PD-L1), Breast Cancer Type 1 susceptibility protein (BRCA1), Poly [ADP-Ribose] Polymerase 1 (PARP1) and Na+/H+ Exchanger Regulatory Factor 1 (NHERF1). The expression of the proteins was evaluated by immunohistochemistry in 124 TNBC samples. TILs were performed adhering to International TILs Working Group 2014 criteria. Cox proportional hazards models were also used to identify risk factors associated with poor prognosis. Multivariate analysis identified TILs as independent prognostic factor of disease free survival (DFS) (p=0.045). A Kaplan-Meyer analysis revealed that the patients with high TILs had a better DFS compared to patients with low TILs (p=0.037), and the phenotypes TILs-/AR+ and TILs-/FOXA1- had a worse DFS (p=0.032, p=0.001 respectively). AR was associated with FOXA1 expression (p=0.007), and the tumors FOXA1+ presented low levels of TILs (p=0.028). A poor DFS was observed for AR+/FOXA1+ tumors compared to other TNBCs (p=0.0117). Low TILs score was associated with poor patients’ survival, and TILs level in combination with AR or FOXA1 expression affected patient’s clinical outcome. In addition, AR+/FOXA1+ phenotype identified a specific subgroup of TNBC patients with poor prognosis. These data may suggest new ways of therapeutic intervention to support current treatments.

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

This contribution illustrates the training evaluation system developed within the Master’s Program in Family and Community Mediation at Università Cattolica del Sacro Cuore in Milan. This is an interim evaluation, which focuses on the training process and which considers fundamental the collaboration with the subjects of the training. The peculiarity of this work concerns the possibility of inserting research within the training process, following a logic of mutual enrichment both in terms of content and learning. The contribution illustrates in detail the outcome and the process evaluation system, defining the perspective, the objectives, and the methodology of implementation. In particular, the outcome evaluation focuses on the distal and proximal outcomes of the training, while the process analysis focuses on the dynamics within the group of participants. Although further evaluations involving different training groups and other training processes are needed, this training evaluation system allows to shed light on both the topic and the context in which training is delivered. The integration between different points of view and several levels of analysis allows the researchers to deepen the individual path of each participant as well as to have feedbacks on the progress of the training group as a whole.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Reducing GHG emissions is a crucial challenge in urban areas, characterized by high energy consumption and reduced exposure to nature. In this context, the urban green system could play a pivotal role. In the literature, scholars analyzed both the ability of species-specific and layout-specific green infrastructures to increase carbon sequestration and the best location sites of new green infrastructures, to increase the provision of overall ecosystem services. There is a lack of studies helping green urban planners and designers choose where and which green infrastructure to implement, based on vegetation species-specific performance and local carbon emissions of city components. This paper uses tree inventory data from a medium-sized city in central Italy (Perugia) to develop a spatial analysis of the urban parks' performance in carbon sequestration. Then, the method evaluates the carbon emission of a public city building to generate a spatialized balance between buildings’ demand and trees’ supply, to support local decisions about the best locations for new green infrastructures and the choice between species. The paper contributes to GIS-based tools that vary the recommended location sites and species for new green infrastructures based on the demanded ecosystem service.

Background: Heat waves are correlated with increased mortality in the aged population. Social isolation is known as a vulnerability factor. This study aims at evaluating the correlation between an intervention to reduce social isolation and the increase in mortality in the population over 80 during heat waves. Methods: The study adopts a retrospective ecologic design. We compared the excess mortality rate (EMR) in the over 80 population during heat waves in urban areas of Rome (Italy), where a program to reduce social isolation was implemented compared to others where it was not implemented. We measured mortality of the summer periods from 2015 to 2019 compared with 2014 (a year without heat waves). Winter mortality, cadastral income and proportion of over 90 were included in the multivariate Poisson regression. Results: The EMR in the intervention and controls was 2.70% and 3.81%, respectively. Rate ratio 0.70 (c.i. 0.54 - 0.92, p-value 0.01). The Incidence Rate Ratio (IRR) of the interventions with respect to the controls is 0.76 (c.i. 0.59 - 0.98). After adjusting for other variables, the IRR was 0.44 (c.i. 0.32 - 0.60). Conclusions: Reducing social isolation could limit the impact of heat waves on the mortality of the elderly population.

Extracellular vesicles (EVs) are involved in intercellular communication during carcinogenesis and cancer cells are able to secrete EVs, in particular exosomes containing molecules, that can be transferred to recipient cells to induce pathological processes and significant modifications, as metastasis, increase of proliferation and carcinogenesis evolution. FZD proteins, a family of receptors comprised in the Wnt signaling pathway, play an important role in carcinogenesis of gastroenteric tract. Here, a still unrecognized role of Frizzled 10 (FZD10) protein was identified. In particular, the presence of FZD10 and FZD10-mRNA in exosomes extracted from culture medium of the untreated colorectal, gastric, hepatic and cholangio cancer cell lines, was detected. A substantial reduction in the FZD10 and FZD10-mRNA level was achieved in FZD10-mRNA silenced cells and in their corresponding exosomes and, concomitantly a significant decrease in viability of the silenced cells compared to their respective controls was observed. Interestingly, the incubation of silenced cells with exosomes extracted from culture medium of the same untreated cells promoted a remarkable restoration of the cell viability and, also, of the FZD10 and FZD10-mRNA level, thus indicating that the FZD10 and FZD10-mRNA delivering exosomes may be potential messengers of cancer reactivation and play an active role in long-distance metastatization

Food production is a complex matter, affecting people’s lives, organizations’ profits, and the well-being of the whole planet and has multifaceted ethical considerations surrounding its production, distribution, and consumption. This paper addresses the pressing need to confront ethical challenges within the food system, encompassing issues such as environmental sustainability, food security, and individual food choices for better oral and systemic health of all individuals around the globe. From agricultural practices to global trade and food waste, ethical implications are addressed across various domains, highlighting the interconnectedness of ethical decision-making in the food industry. Central themes explored include the ethical dimensions of food production methods, the impact of global trade on food ethics, and the role of individuals in making ethically informed food choices. Additionally, the paper dives into the spiritual and physical significance of food, particularly through the lens of oral health as a gateway to holistic well-being. Recognizing the complexity of the food ecosystem, the paper calls for serious interventions in legislation and economics to promote ethical protocols and techniques for sustainability reasons. It emphasizes the importance of ethical considerations in food safety management systems, regulatory frameworks, and quality standards. Moreover, the paper underscores the need for a comprehensive approach to address ethical dilemmas and moral values inherent in the food industry and oral health policies, advocating for the adoption of the precautionary principle and ethical decision-making frameworks. The article aims to serve as a call to action for stakeholders across the food industry and the healthcare sector, to prioritize ethical practices, promote transparency, rearrange economic parameters and work towards a more sustainable and equitable food system for inner and outer oral and systemic health and human sustainability for all.

Cochlear implantation is the therapy used for patients with severe to profound sensorineural hearing loss. For the success of the surgery, it is important that each surgical step is performed with meticulous precision, starting from the correct patient’s position on the operating table. In elderly or obese patients, this can be difficult to achieve due to cervical rigidity. In these cases, the orthopedic position is an excellent choice to perform a mastoidectomy accurately, ensuring a safe procedure and avoiding unpleasant complications.

The stochastic modelling of chemical physical processes is essentially based on a coarse-grained formulation of fluctuations, usually described by means of Wiener processes. By taking the paradigmatic example of chemical reaction kinetics, we propose a simple representation of microscopic stochastic dynamics grounded on the use of distributional derivatives of counting processes that account for elementary reactive events. This approach is consistent with the statistical analysis based on the Chemical Master Equation, and provides the formal setting for the existing algorithmic approaches (Gillespie algorithm). Some practical advantages of this formulation are addressed, and several other examples are discussed in connection with cluster formation, velocity fluctuations in liquid systems, and quantum transitions (radiative interactions) at the molecular level.

Trauma is one of the most common causes of death or permanent disability in young people, so a timely diagnostic approach is crucial. In polytrauma patients, CEUS has been shown to be more sensitive than US for the detection of solid organ injuries, improving the identification and grading of traumatic abdominal lesions with levels of sensitivity and specificity similar to those seen with MDCT. CEUS is recommended for the diagnostic evaluation of hemodynamically stable patients with isolated blunt moderate-energy abdominal traumas and for the diagnostic follow-up of conservatively managed abdominal traumas. In this pictorial review we illustrate the advantages and disadvantages of CEUS and the procedure details with tips and tricks during investigation of blunt moderate-energy abdominal trauma as well as during follow-up in non-operative management.

Evaluation of biliary strictures remains a challenge due to the low sensitivity of standard diagnostic work up, but the introduction of direct single-operator cholangioscopy (DSOC) changed this paradigm. Aim of our study was to evaluate diagnostic performance of DSOC and DSOC-targeted biopsies, intraductal ultrasound (IDUS) and brush cytology in patients with indeterminate biliary stricture (IBS). We evaluated patients who underwent advanced diagnostic work up for IBS in our endoscopy unit from ‘01/2018 to ‘12/2022; all patients had at least one previous attempt to characterize the biliary stricture. Final diagnosis was based on surgical pathology and/or clinical and radiological follow-up of at least 12 months. A total of 57 patients with a mean age of 67.2 ± 10.0 years were included, with a mean follow up of 18.2 ± 18.1 months. IBS were mostly located in the distal common bile duct (45.6%) and final diagnosis was consistent with malignancy in 35 patients (61.4%). DSOC and IDUS showed a significantly higher accuracy (89.5% and 82.7% respectively) compared to standard cytology (61.5%, p <0.05). In our experience, DSOC visualization and IDUS both demonstrated an optimal diagnostic yield in the differentiation of IBS, with an acceptable safety profile both quantitatively and qualitatively.

Saliva is a promising matrix with several purposes. Our aim is to verify if salivary anti-SARS-CoV-2 antibody determination is suitable for monitoring immune response. One-hundred eighty-seven subjects were enrolled at University-Hospital Padova: 105 females (56.1%) and 82 males (43.9%), 95 (50.8%) children and 92 (49.2%) adults. Subjects self-collected saliva using Salivette; nineteen subjects collected three different samples within the day. A serum sample was obtained for all individuals. The N/S anti-SARS-CoV-2 salivary IgG (sal-IgG) and serum anti-SARS-CoV-2 S-RBD IgG (ser-IgG) were used for determining anti-SARS-CoV-2 antibodies. The mean (min-max) of age was 9.0 (1–18) for children and 42.5 (20–61) for adults. Of 187 samples, 63 were negative for sal-IgG (33.7%), while 7 were negative for ser-IgG (3.7%). Spearman’s correlation was 0.56 (p&lt;0.001). Sal-IgG and ser-IgG levels were correlated with age, but not with gender, comorbidities, prolonged therapy, previous SARS-CoV-2 infection or time from last COVID-19 infection/vaccination. The repeatability ranged from 23.8% (7.4kAU/L) to 4.0% (3.77kAU/L). Linearity of the assay missed in 4/6 samples. No significant intra-subject differences were observed in sal-IgG across samples collected at different time points. Sal-IgG have a good agreement with ser-IgG. Non-invasive saliva collection represents an alternative method for antibody measurement, especially in children.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Electrospinning is known to be an effective and straightforward technique to fabricate polymer non woven matrices made of nano and microfibers. Micro patterned morphology of electrospun matrices results to be outmost advantageous in the biomedical field, since it is able to mimic extracellular matrix (ECM), and favors cell adhesion and proliferation. Controlling electrospun fibers alignment is crucial for the regenerative purposes of certain tissues, such as neuronal and vascular. In this study we investigated the impact of electrospinning process parameters on fiber alignment in tubular nanofibrous matrices made of Poly (L-lactide-co-ε-caprolactone) (PLA-PCL); a Design of Experiments (DoE) approach is here proposed in order to statistically set up the process parameters. The DoE was studied keeping constants the previously set material and environmental parameters; voltage, flow rate and mandrel rotating speed were the process parameters here investigated as variables. Orientation analysis was based on ImageJ and plugin Orientation J analysis of SEM images. The results show that voltage combined with flow rate has significant impact on electrospun fiber orientation, and the greatest orientation is achieved when all the three input parameters (voltage, flow rate and mandrel rotation speed) are at their maximum value.

The aims of this study were: (1) to analyze the level of agreement of a sample of Italian people with the rights of people with physical and psychical disabilities (PwPHDs and PwPSYDs) to have satisfying sexuality, to marry, to adopt a child; (2) to inquire if PwPSYDs were subject to less recognition than PwPHDs; (3) to verify if socio-demographic characteristics, such as age, sex, education, occupation, geographical origin, relational status, sexual orientation, and religiosity, associated with being against these sexual and parenting rights (SPRs). An online anonymous questionnaire inquired the level of agreement or disagreement with statements regarding the SPRs of PwPHDs and PwPSYDs. 973 participants, aged 18 – 84 years (71.1% females) were considered for analyses; At least 7 out of 10 participants declared in favor of the SPRs of PwPHDs, while the SPRs of PwPSYDs were always subjected to higher underrecognition. Religiosity almost invariably associated to being against the SPRs of PwDs. Being male, of higher age and lower education also associated with lower recognition. A better identification of the less tolerant respondents and of the less recognized categories may allow for specific strategies for promoting the recognition of the SPRs for PwDs.

The strictness of the result of an excavation, whether mechanical or by means of explosives, is naturally conditioned by the objective, and therefore by the type of technique applied to achieve it. To attain the best results in terms of rock breakage and respect of the final profile, it’s important to evaluate the excavation specific energy and its optimization. This research focuses on evaluating the effects of different techniques on the quality of final walls in open-pit and underground operations. Different geometries and configurations can be applied to both quarrying and tunnelling blasts. The research is aimed to push contour blasts to their limits, and the main aspects are discussed in order to improve the blast parameters in the daily practice.

Comprehensive understanding of tree characteristics and conditions holds paramount importance for the precise management of hazelnut orchards. It facilitates the determination of tree vigor, pruning requirements, phytosanitary interventions, and plant water consumption. The primary objective of this study was to explore, for the first time on a fruit tree with a bushy structure and across trees of four Italian distinct hazelnut cultivars, the efficacy of multispectral and thermal UAV (Unmanned Aerial Vehicle) technologies in assessing canopy attributes, vegetative growth, and predicting abiotic stresses. These technologies serve as tools for precision agriculture, enabling the computation of various indices such as the Normalized Difference Vegetation Index (NDVI) and crop water stress index (CWSI). The study of water content is of particular importance at this time, especially considering the increasing water stress levels in Europe as well as globally. While Red Green Blue (RGB) and thermal imagery collectively demonstrated superior performance in model reconstruction, the multispectral UAV remained more adept at characterizing size traits of hazelnut plants. Thermal images alone proved inadequate for accurately reconstructing hazelnut biometric characteristics. Furthermore, all indices were found to be cultivar-specific, underscoring the importance of conducting studies across different cultivars. The utilization of two UAVs, namely multispectral and thermal, facilitated the examination of the relationship between NDVI and CWSI across tree species.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Altered metabolism is a common feature of many cancers and in some cases is a consequence of mutation in metabolic genes, such as the ones involved in Krebs cycle. Isocitrate dehydrogenase (IDH) gene is mutated in many gliomas and other cancers. Physiologically IDH converts isocitrate to αketoglutarate (αKG), but when mutated, IDH reduces αKG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at high levels in IDH mutant cancers, and in the last decade, a massive effort has been done to develop small inhibitors targeting mutant IDH. In this review, we summarize current knowledge about the cellular and molecular consequences of IDH mutations, and the therapeutic approached developed to target IDH mutant tumours, with a focus on gliomas.

In the last two decades, the development of high-throughput diagnostic methods and availabil-ity of effective treatments has increased interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report our 8-year experience of screening and follow up on about 250,000 neonates screened for four lysosomal storage diseases (Pompe disease, mucopolysaccharidosis type I, Fabry dis-ease, Gaucher disease), using enzyme activity assay by tandem mass spectrometry, and bi-omarker quantification as second tier test. Among the 126 positive newborns (0.051%), 51 infants were confirmed as affected (positive pre-dictive value 40%), with an overall incidence of 1:4,874. Of these, 3 infantile-onset Pompe dis-ease, 2 neonatal-onset Gaucher disease and 4 mucopolysaccharidosis type I patients were imme-diately treated. Furthermore, another four Gaucher disease patients needed treatment in the first years of life. Our study demonstrated the feasibility and effectiveness of newborn screening for lysosomal storage diseases. Early diagnosis and treatment allow the achievement of better patient out-comes. Challenges such as false positive rates, the diagnosis of variants of uncertain significance or late-onset forms, and the lack of treatment for neuronopathic forms, should be addressed.

Food allergy (FA) affects approximately 6–8% of children worldwide causing a significant impact on the quality of life of children and their families. In the years, the possible role of weaning in the development of FA has been studied. According to recent studies, the role of weaning in its development is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collected the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food.

In this study, we conducted a comprehensive analysis of the spatial distribution of soil organic carbon stock (SOC stock) and the associated uncertainties in two soil layers (0–10 cm and 0–30 cm; SOC stock 10 and SOC stock 30 respectively), in Valchiavenna, an alpine valley located in northern Italy . We employed the digital soil mapping (DSM) approach within different machine learning models, including multivariate adaptive regression splines (MARS), random forest (RF), support vector regression (SVR), and elastic net (ENET). Our dataset comprised soil data from 110 profiles, with SOC stock calculations for all sampling points based on bulk density (BD), whether measured or estimated, considering the presence of rock fragments. As environmental covariates for our research we utilized environmental variables, in particular geomorphometric parameters derived from a digital elevation model (with a 20 m pixel resolution), land cover data, and climat-ic maps. To evaluate the effectiveness of our models, we evaluated their capacity to predict SOC stock 10 and SOC stock 30 using the coefficient of determination (R2). The results for the SOC stock 10 were as follows: MARS 0.39, ENET 0.41, RF 0.69, and SVR 0.50. For the SOC stock 30, the corresponding R2 values were: MARS 0.45, ENET 0.48, RF 0.65, and SVR 0.62. Additionally, we calculated the Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) for further assessment. To map the spatial distribution of SOC stock and address uncertainties in both soil layers, we chose the RF model, due to its better performance, as indicated by the highest R2 and the lowest RMSE and MAE. The resulting SOC stock maps using the RF model demonstrated an accuracy of RMSE = 1.35 kg.m-2 for the SOC stock 10 and RMSE= 3.36 kg.m-2 for the SOC stock 30. To further evaluate and illustrate the precision of our soil maps, we conducted an uncertainty assessment and mapping by analyzing the standard deviation (SD) from 50 iterations of the best-performing RF model. This analysis effectively highlighted the high accuracy achieved in our soil maps. The maps of uncertainty demonstrated that the RF model better predicts the SOC stock 10 compared to the SOC stock 30.

Heart transplantation (HT) represents the mainstream therapy of end-stage heart failure for selected patients with a median survival of more than 10 years after surgery and substantial improvement in quality of life. Current guidelines suggest a variety of examinations including invasive (coronary angiography and endomyocardial biopsy (EBM) and non-invasive methods (echocardiography, stress echocardiography, computed tomography, PET and MRI) to monitor HT patients. Guidelines do not specify the timing of echocardiographic evaluations and do not recommend echocardiography as an alternative to serial EMB in rejection monitoring [2]. They still recommend as gold standard coronary angiography to be done 1 year after surgery and every 2 years after. In this review we will discuss the advantages of non-invasive techniques over the invasive ones for an adequate follow-up of HT patients.

Tyrosine Kinase Inhibitors work by blocking the tyrosine kinases responsible of the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patient and most of them were paediatrics. The 82.4% of patients were men; however, sex-related differences in drugs pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated: as patients ages increased, drug levels decreased. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that Therapeutic Drug Monitoring is a useful method for adjusting a patient treatment schedule depending on drug concentrations in biological fluids. The use of Therapeutic Drug Monitoring in conjunction with Tyrosine Kinase Inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, Tyrosine Kinase Inhibitors Therapeutic Drug Monitoring classification needs to be refined in terms of factors like sexes and ages.

Continuous technological progress places significant demands on the materials used in increasingly modern devices. An important parameter is often the long-term thermal resistance of the material. The use of heat-resistant polymer materials worked well in technologically advanced products. An economically justified direction in searching for new materials is the area of polymer nanocomposite materials. It is necessary to appropriately select both the polymer matrix and the nanofillers best able to demonstrate the synergistic effect. A promising area of exploration for such nanocomposites is the use of organosilicon polymers, which results from the unique properties of these polymers related to their structure. This review presents the results of the analysis of the most important literature reports regarding organosilicon polymer nanocomposites with increased thermal resistance. Particular attention was paid to modification methods of silicone nanocomposites focused on the increase of their thermal resistance related to the modification of siloxane molecular structure and by making nanocomposites using inorganic additives, carbon nanomaterials. Attention was also paid to such important issues as the influence of the dispersion of additives in the polymer matrix on the thermal resistance of silicone nanocomposites and the possibility of modifying the polymer matrix and permanently introducing nanofillers thanks to the presence of various reactive groups. The thermal stability mechanism of these nanocomposites was also analysed.

Monitoring of clients living with HIV encompasses a specific array of activities that routinely check on various aspects of ART following its initiation depending on the availability of resources in that particular state, among other factors as per guidelines from the World Health Organisation. This is a significant practice as it promotes positive health outcomes for patients and efficient utilisation of ART regimens to reduce resistance to the medication – hence it is a measure to guard avoidable costs. It also forms a basis on which decisions are made from. It can be done clinically by assessing for signs e.g., skin rash and symptoms e.g., nausea and vomiting, checking vital organ function and measuring weights across all populations, or can be also be done by assessing specimens for their respective viral loads, white blood cell count, pregnancy status or other infections such as hepatitis B. There have not been any special indications required for one to be eligible for monitoring during ART in developing countries; all qualify for routine monitoring even though some may be more frequent than others in cases of comorbidities such as renal failure where medications can be attributed to exacerbating the condition.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

Research on bidirectional human-machine interfaces will enable the smooth interaction with robotic platforms in contexts ranging from industry to tele-medicine and rescue. This paper introduces a bidirectional communication system to achieve multisensory telepresence during the gestural control of an industrial robotic arm. We complement the gesture-based control by means of a tactile-feedback strategy grounding on a spiking artificial neuron model. Force and motion from the robot are converted in neuromorphic haptic stimuli delivered on the user’s hand through a vibro-tactile glove. Untrained personnel participated in an experimental task benchmarking a pick-and-place operation. The robot end-effector was used to sequentially press six buttons, illuminated according to a random sequence, and comparing the tasks executed without and with tactile feedback. The results demonstrated the reliability of the hand tracking strategy developed for controlling the robotic arm, and the effectiveness of a neuronal spiking model for encoding hand displacement and exerted forces in order to promote a fluid embodiment of the haptic interface and control strategy. The main contribution of this paper is in presenting a robotic arm under gesture-based remote control with multisensory telepresence, demonstrating for the first time that a spiking haptic interface can be used to effectively deliver on the skin surface a sequence of stimuli emulating the neural code of the mechanoreceptors beneath.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Background: Interstitial lung disease (ILD) is a frequent complication in systemic sclerosis (SSc). So, an increased awareness of this complication is a real need in the clinical setting, because it may affect the prognosis of patients. In particular, an accurate strategy is desirable in order to detect ILD in its stages. So, we investigate the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to determine its potential in disease progression. Methods: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), pulmonary auscultation, chest radiographs and respiratory function tests (RFT) were performed. An expert rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. After the baseline assessment, the patients were followed every 3 months for 12 months. Results: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p=0.0001). The clinical and laboratory variables associated with ILD were anti-centromere antibodies (p=0.005) and RSS (p=0.004). A positive correlation was demonstrated between the US and HRCT findings (p=0.001). Sensitivity and specificity of US in detecting ILD was 91.2% and 88.6% respectively. A good inter-observer reliability was observed (k = 0.72). In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. Conclusions: US showed a high prevalence of subclinical ILD in SSc patients. It demonstrated to be a valid, reliable and feasible tool to detect ILD in SSc and to monitoring the disease progression.

Starting from the analysis of the lack of positivity of the Cattaneo heat equation, the article addresses the thermodynamic relevance of the positivity constraint in irreversible thermodynamics, than is at least as important as the entropic constraints. The fulfillment of this condition in hyperbolic models leads to the parametrization of the concentration fields with respect to internal variables associated with the microscopic dynamics. Using Brownian motion theory as a landmarking example for deriving macroscopic transport equations from the equations of motion at the particle/molecular level, we discuss two typical problems involving hydrodynamic interactions at microscale: surface chemical reactions at a solid interface of a diffusing reactant, and mass-balance equations in a complex viscoelastic fluid, in which the physics of the interaction leads either to the overcome the parabolic diffusion model or to consider the parametrization of the concentration with respect to the degrees of freedom associated with the relaxation dynamics of the solvent fluid.

The aim of the present study is to investigate themes related to visitors’ perceptions of captive wildlife in particular, attitudes towards non-human primates (henceforth, primates). This research took place in free-roaming, multi-species primate sanctuary, Monkeyland (South Africa), where 400 visitors were interviewed using an anonymous survey both before and after attending a guided tour. The answers were divided into different categories, in order to standardize the motivations behind tourists’ choices. The results of the survey demonstrated that most visitors agree that a primate would not be a good companion animal. Visitors’ desire to touch primates was found to be positively correlated with desire for companion primates and inversely associated with visitor age. In response to: “would you like to touch a monkey?”, the majority of tourists who expressed this desire seemed aware that such interactions are not appropriate, with concern for animal welfare and human health. Of the various primate species present in the sanctuary, visitors preferred the ring-tailed lemur (Lemur catta) and, generally speaking, expressed appreciation for primates’ “cuteness”. Our results indicate a general awareness by the visitors on the importance of animal welfare in the human interactions with captive wildlife, in agreement with the “hands-off” policy of Monkeyland primate sanctuary. We discuss the findings from a general to zooanthropological point of view, proposing some reflections on the attitudes of visitors toward non-human primates.

In the twenty-first century– an era of increasing domestic and international tourism- there are boundless opportunities to encounter wild animals both in their home countries and ex situ in zoological facilities around the world. Tourism activity– especially at accredited zoos and sanctuaries –plays a crucial role in the conservation of wild animal populations, and influences the welfare of individuals within involved species. Unfortunately, not all zoos and sanctuaries prioritize the conservation and welfare of their animals, such as those who promote irresponsible and mutually-harmful visitor-animal encounters for economic profit. While the relationship between visitors and animals at zoological facilities has shifted over time to match evolving morals and sentiments towards animals, there is still a storied tendency of visitors preferring close encounters with charismatic wild species. Since the 1970s, researchers’ attention has increasingly focused on assessing the influence of the visitor effect, which refers to the impact that viewing, touching, feeding, holding, and riding captive wildlife has on the animals. Many wildlife attractions promote such encounters, despite research suggesting that close interactions with visitors can cause stress and harm to involved species. Such activities are further promoted through the “selfie tourism” phenomenon, in which visitors capture images of themselves in too-close proximity to wild animals to be shared on social media. In this commentary, we consider the challenge of “selfie tourism”, and how it can promote unethical relationships between humans and wildlife and lead to deleterious implications for the animals’ conservation and welfare.