The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs, and able to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials: they exhibit good features in terms of impermeability, deformability and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration: however, this kind of materials lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these mate-rials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields: in the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance and patency will be herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance will be been disclosed.

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.

Obturator herniæ are a quite rare type of abdominal hernia, accounting for less then 1% of all abdominal wall hernias and for 0.2-1.6% of patient with a small bowel obstruction. The obturator canal is the only portion of the obturator foramen that is not obliterated by the membrane of the same name and hosts the obturator neurovascular bundle; it is, for this reason, a locus minoris resistentiae, through which obturator hernias are formed, generally in elderly, multiparous women. Despite the fact that Computed Tomography offers the possibility of a quick, correct preoperative diagnosis, often signs and symptoms of obturator herniæ are quite unspecific; considering that, at the same time, patients with an obturator hernia are generally elderly, with concurrent conditions, this might cause delays in the diagnosis and treatment and produces the high postoperative mortality rates that obturator herniæ yield

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.

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although very limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which is able to stabilize the effector cells becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allows a great improvement in the management of asthma.

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<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.

The current systematic review examines whether there is an association between the genetic 5-HTTPLR pol-ymorphism and parenting and the mechanisms by which this association operates. The literature was searched in various databases such as PubMed, Scopus and ScienceDirect. In line with our inclusion criteria, nine articles were eligible out of 22. Most of the studies, analysed in this review, found an association between 5HTTLPR and parenting. Four studies found a direct association between 5-HTTLPR and parenting with conflicting findings: two studies found that mothers carrying the short variant were more sensitive to their infants, while two studies found that parents carrying the S allele were less sensitive. In addition, several studies found strong interaction between genetic and environmental factors, such as childhood stress and disruptive child behaviour, quality of early care experiences, poor parenting environment, and quality of environment. Only one study found an association between children’s 5HTTLPR and parenting. Parenting can be described as a highly complex construct influenced by multiple factors, including environmental, parenting and child charac-teristics. According to the studies, maternal 5-HTTLPR polymorphism is most likely associated with sensitive parenting.

Retroaortic left renal veins are an often overlooked, but no so rare anatomic anomaly that might cause a few aspecific symptoms and signs, especially flank or inguinal pain, microscopic or even gross hematuria; in the vast majority of cases it is, thought, totally asymptomatic. The nutcracker syndrome that might arise in the case of RLRV is mainly due to the re- duced space between aorta and the vertebral body and the consequent compression on the venal rein; this might in turn cause upstream hypertension, hematuria, varicocele, pain. The compression of RLRV leads to hematuria because of renal venous hypertension, consequent left renal congestion. This upstream venous congestion might result, in some cases, in left-sided varicocele in men and pelvic congestion syndrome in women. From a radiologic point of view, the presence of RLRV and the precise reporting its subtypes is mandatory.

Background: After the outbreak of a novel coronavirus (i.e. SARS COV2) in China and its diffusion around the world, great attentions was reserved to the increased incidence of venous thromboembolism in these patients. A specific antiviral action of heparins toward SARS COV2 has been reported in vitro such as a well know action of heparins to prevent VTE in inpatients with infective disease has already been reported since several years. Yet, because fondaparinux represent the pharmacological antithrombotic active sequence of all heparins and because its clinical indication o prevent VTE in inpatients is similar to heprains, we realized a retrospective analysis in inpatients with SARS COV2 on the incidence of VTE during pharmacological prophylaxis with enoxaparin or fondaparinux. This retrospective analysis was named FONDENOXAVID. Methods: We conducted a retrospective cohort study that used patients with SARS COV2 during the Italian outbreak from February 18, 2020 to April 30, 2020. Our aim was to compare the clinical characteristics, prophylactic treatment and outcomes in inpatients positive to SARS COV2 at risk to develop venous thromboembolism, in particular venous thrombosis with or without pulmonary embolism, during in-hospital primary thromboprophylaxis with enoxaparin (40 mg or 60 mg once daily) or fondaparinux (2.5 mg once daily). Statistical analysis was conducted with using MatLab R2016B and eventually ad hoc functions. Results: There were not significative differences in clinical characteristics between patients that used enoxaparin or fondaparinux as thromboprpophylaxis for SARS COV2. The cumulative incidence of thrombotic events was not different in patients that used enoxaparin or fondaparinux as thromboprpophylaxis. No differences were found also in d-dimer and fibrinogen levels test at the admission and after 3 weeks as markers of prolonged inflammation due to SARS COV2. Discussion: The increased incidence of VTE in vivo has been reported in several studies although prophylaxis with low molecular weight heparin was conducted in some of them. The clinical indication to prevent VTE was similar for heparins and fondaparinux. In our results a non-inferiority to prevent VTE was recorded when inpatients with SARS COV2 were treated with prophylactic doses of enoxaparin or fondaparinux according to international guidelines. The incidence of VTE in this retrospective analysis showed that Fondaparinux at fixed doses of 2.5 mg daily was not inferior to enoxaparin (4000 UI daily). Our results testify that fondaparinux and enoxaparin showed the same efficacy to reduce the incidence of VTE in inpatients with SARS COV2.

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.

Upper limb paresis is very common after stroke. An important tool to assess motor recovery is to use marker-based motion capture systems to measure the kinematic characteristics of patients’ movements in ecological scenarios. These systems are, however, very expensive and, as such, not readily available for many rehabilitation units. Here, we explored whether the markerless hand motion capabilities of the cost-effective Oculus Quest head-mounted display could be used to provide clinically meaningful measures. 14 stroke patients executed ecologically relevant upper limb tasks in an immersive virtual environment. During task execution, we recorded their hand movements simultaneously by means of the Oculus Quest’s and a marker-based motion capture system. Our results showed that the markerless estimates of the hand position and peak velocity provided by the Oculus Quest were in very close agreement with those provided by a marker-based commercial system with their regression line having a slope close to 1. Furthermore, the Oculus Quest had virtually the same sensitivity as that of a commercial system in distinguishing healthy from pathological kinematic measures. The Oculus Quest was as accurate as a commercial marker-based system in measuring clinically meaningful upper limb kinematic parameters in stroke patients.

Herein we present the biocatalysed preparation of mono-N-carbamate-protected precursor of antitumoral Nutlin-3a, through enantioselective alkoxycarbonylation of meso-1,2-disubstituted-1,2-diaminoethane, using enzyme lipases and dialkyl carbonates as acylating agents. A series of supported or free lipase enzymes were screened in combination with commercially available diallyl-, diethyl and dimethyl- carbonate. The reactions were conducted at different temperatures, reaction times and with variable co-solvent systems to evaluate the effect on the enzyme catalytic activity. The best results in terms of conversion, enantiomeric excess and yield were obtained when lipase from Candida antarctica B (CAL-B) was used with diallyl carbonate (DAC) conducting the reaction solventless at 75 °C.

Neuroblastoma is an embryonal tumor arising from the sympathetic central nervous system. The epidermal growth factor (EGF) plays a role in neuroblastoma growth and metastatic behavior. Recently, we have demonstrated that cathepsin D (CD) contrasts EGF-induced neuroblastoma cell growth in 2D by downregulating EGFR/MAPK signaling. Aggressive NB is highly metastatic to the bone and the brain. In the metastatic process, adherent cells detach to form clusters of suspended cells that once reached the metastatic site adhere and form secondary colonies. Whether CD involves in survival of metastatic NB clones is not known. Therefore, in this study we addressed how CD differentially affects cell growth in suspension versus adherent condition. To mimic tumor heterogeneity, we co-cultured transgenic clones silenced for or overexpressing CD. We compared the growth kinetics of such mixed clones in 2D and 3D models in response to EGF, and we found that Over CD clone was advantaged for the growth in suspension, while the CD knocked-down clone was favored for the adherent growth as 2D. The fact that CD plays a dual role in cancer cell growth in 2D and 3D conditions indicates that during clonal evolution subclones expressing different level of CD may arise, which confers survival and growth advantages depending on the metastatic step. Whether CD involves in survival of metastatic NB clones is not known. We propose that epigenetic regulation of CD expression could be an additional strategy to prevent NB metastases.

Wheat gluten contains epitopes that trigger celiac disease (CD). A life-long strict gluten-free diet is the only treatment accepted for CD. However, very low-gluten wheat may provide an alternative treatment to CD. Conventional plant breeding methods are not sufficient to produce celiac-safe wheat. RNA interference technology, to some extent, succeeded in the development of safer wheat varieties. However, these varieties had multiple challenges in their implementation. Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) is a versatile gene-editing tool that has the ability to edit the immunogenic gluten genes. So far, only a few studies have applied CRISPR/Cas9 to modify the wheat genome. In this article, we reviewed published literature that applied CRISPR/Cas9 in wheat genome editing to investigate the current status of the CRISPR/Cas9 system to produce a low-immunogenic wheat variety. We found that in recent years, the CRISPR/Cas9 system has been continuously improved to edit the complex hexaploid wheat genome. Although some reduced immunogenic wheat varieties have been reported, CRISPR/Cas9 has still not been fully explored in editing the wheat genome. We conclude that further studies are required to apply the CRISPR/Cas9 gene-editing system efficiently for the development of celiac-safe wheat variety and to establish it as a “tool to celiac safe wheat.”

Forest ecosystems are important providers of ecosystem functions and services belonging to four categories: supporting, provisioning, regulating, and cultural ecosystem services. Forest management, generally focused on timber production, has consequences on the ability of the system to keep providing services. Silviculture, in fact, may affect ecological structures and processes from which services arise. In particular, the removal of biomass causes a radical change in the stocks and flows of energy characterizing the system. Aiming at the assessment of differences in stored natural capital and ecosystem functions and services provision, three differently managed temperate forests of common beech (Fagus sylvatica) were considered: (1) a forest in semi-natural condition, (2) a forest carefully managed to get timber in a sustainable way and (3) a forest exploited without management. Natural capital and ecosystem functions and services are here accounted in biophysical terms. Specifically, all the resources used up to create the biomass (stock) and maintain the production (flow) of the different components of the forest system were calculated. Both stored emergy and empower decrease at increasing human pressure on the forest, resulting in a loss of natural capital and a diminished ability of the natural system to contribute to human well-being in terms of ecosystem services provision.

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.

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.

Facebook (FB) is the most popular online networking platform. There are several FB pages dedicated to spreading awareness about the Celiac disease (CD). To get the latest information, a huge number of CD patients follow Celiac disease Facebook (CD-FB) pages. Such pages frequently post beneficial information. However, very less is known if they provide appropriate information to CD patients. We conducted this study to know if CD-FB pages spread misleading information to CD patients. CD-FB pages from three celiac-influenced countries were explored using the FB platform and Google search engine. From October 2021 to April 2022, a total of 147 CD-FB, Italy (n=63), the USA (n=46), and India (n=38), were found eligible. Of them, 13% of pages (followers Mean±SD; Italy 2478±2011; USA 12635±12486; India 667±313) shared misleading information, particularly about gluten-free ingredients, and treatment of CD. In total,16% of CD-FB pages discussed alternative treatments option. Surprisingly, 7% of pages (followers Mean±SD; USA 23800±10465; India 628±333) supported alternative treatments for CD. CD-FB pages are useful for disseminating celiac-related information. While most of such pages provide useful information, a few pages sometimes contain misleading information. CD patients must consult their treating unit before following any uncertain information posted on CD-FB pages.

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.

Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, Middle East and USA areas. While in the ancient time pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, up to consider pomegranate as a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs) and its consumption appears to exert numerous healthy beneficial effects, in particular, in several pathological conditions, namely in patients affected by metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and in dentistry represents a promising field, as it could permit the development of innovative natural adjuvant therapies, able to empower the standard pharmaceutical therapies.

Renal cell carcinoma (RCC) is the second most common cancer of the urinary system. The current therapeutic strategies are based on partial or total nephrectomy and/or targeted therapies based on immune checkpoint inhibitors to which patients are often refractory. Preventive and screening strategies are not existing and the few available biomarkers for RCC are characterized by the lack of sensitivity, outlining the need of novel noninvasive and sensitive biomarkers for an early diag-nosis and a better disease monitoring. Blood liquid biopsy (LB) is a non- or minimally invasive procedure for a more representative view of tumor heterogeneity than the tissue biopsy, poten-tially allowing real-time monitoring of cancer evolution. Growing interest is focused on the extra-cellular vesicles (EVs) secreted by either healthy or tumoral cells and recovered in a variety of bio-logical matrices, blood included. EVs are involved in cell-to-cell crosstalk transferring their mRNAs, miRNAs, and proteins content. In particular, transferred miRNAs may regulate the tu-morigenesis and proliferation also impacting on resistance to apoptosis, thus representing poten-tial useful biomarkers. Here we present the latest efforts in the identification of circulating miR-NAs in blood samples, focusing on the potential use of EV derived miRNAs as RCC diagnostic, prognostic markers.

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.

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.

Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to its inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The previous COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances when vaccination is not accessible or in individuals with compromised immune systems, drugs can give additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds including anti-viral. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Epigenetic modifications in the genome can affect gene expression without altering DNA sequence. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses have recruited cellular epi transcriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells' epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we are exploring the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing modulation processes and anti-viral effects on DNA and RNA viruses, and addressing future research objectives in this rapidly emerging field.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Remotely Piloted Aircraft Systems (RPAS) are increasingly becoming relevant actors flying through the airspace and will assume much more importance in the future perspective. In order to allow their safe integration with manned conventional traffic in non-segregated airspaces, in accordance with the overall Air Traffic Management (ATM) paradigm, specific enabling technologies are needed. As well known, among the enabling technologies identified as crucial for RPAS integration into the overall ATM system, the Detect and Avoid (DAA) technology is fundamental. In the meantime, to support extended surveillance, the universal introduction on-board of aircraft of cooperative Automatic Dependent Surveillance – Broadcast (ADS-B) is increasingly implemented, having the potential to allow coverage of the whole airspace also in remote areas not usually covered by conventional radar surveillance. In this paper, the experimental results are presented and discussed that have been obtained through the real-time validation, with hardware and human in the loop (RTS-HIL) simulations, of an automatic ADS-B based Separation Assurance and Collision Avoidance System aimed to support RPAS automatic operations as well as remote pilot decision making. In the paper, after an introductory outline of the Concept of Operations (ConOps) of the system and of its architectural organization, while also providing basic information about the main system functionalities, the description is reported of the tests that have been carried out and the obtained results are described and discussed, in order to emphasize the performances and limitations of the proposed system. In particular, not only the quantitative performances obtained are reported and commented but also the feedbacks received by the pilots in order to improve the system are described, for instance in terms of preferred typology of conflict resolution manoeuver elaborated by the system.

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.

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.

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.

Background: The reference test for SARS-CoV-2 detection is the reverse transcriptase real time PCR (real time RT-PCR). However, evidences reported that real time RT-PCR has a lower sensitivity compared with the droplet digital PCR (ddPCR) leading to possible false negative in low viral load cases. Methods: We used ddPCR for viral genes N1 and N2 on 20 negative (no detection) samples from symptomatic hospitalized COVID-patients presenting fluctuating real time RT-PCR results and 10 suspected samples (Ct value>35) from asymptomatic not hospitalized subjects. Results: ddPCR performed on RNA revealed 65% of positivity for at least one viral target in the hospitalized patients group of samples (35% for N1 and N2, 10% only for N1 and 20% only for N2) and 50% in the suspected cases (30% for N1 and N2, while 20% only for N2). On hospitalized patients’ samples, we applied also a direct ddPCR approach on the swab material, achieving an overall positivity of 83%. Conclusion: ddPCR, in particular the direct quantitation on swabs, shows a sensitivity advantage for the SARS-CoV-2 identification and may be useful to reduce the false negative diagnosis, especially for low viral load suspected samples.

Background: Gender stereotypes and biases can influence perceptions of competence and suitability for certain medical specialties. Empathy is an important component of an optimal doctor-patient relationship. The scope of our study is to verify the correlation between “empathetic" behavioral style with attention and sensibility to the gender differences of patients of the medical students. Methods: An online survey was conducted using the Jefferson Scale for Empathy (JSE), to measure empathy in the context of health professions education and patient care; and the Nijmegen Gender Awareness in Medicine Scale (N-GAMS), which measures attitudes and assumptions about gender. A total of 234 students (52.1% M; mean age: 22.68±2.48) from Medicine and Surgery at the University of Salerno (Italy) participated, of whom n° 175 were third-year students and n° 59 were fifth-year students. Results: The JSE score shows that male students have higher scores (77.29±12.38) than females (75.91±10.39). Conversely, female students have higher perspective-taking (JSE Factor 1: Male= 51.26±11.84; Female= 52.72±11.88). In addition, third-year students are much more empathetic than their fifth-year colleagues (JSE Score: 3°ys= 77.35±11.46; 5°ys= 74.49±11.33). With reference to the GS, we found that male students have greater sensitivity than their female colleagues (GS: Male= 2.67±0.68; Female= 2.37±0.48); conversely, they have higher scores of gender stereotype towards patients (GRIP: Male= 2±0.88; Female= 1.59±0.61) and doctors (GRID: Male= 1.88±0.89; Female= 1.64±0.63). Also, the third-year students compared to their fifth-year colleagues are characterized by greater gender sensitivity (GS: 3°ys= 2.57±0.62; 5°ys= 2.42±0.57), less bias with respect to patients (GRIP: 3°ys= 1.77±0.79; 5°ys= 1.90±0.78) but, on the other hand, show more stereotypes and prejudices towards doctors (GRID: 3°ys= 1.77±0.81; 5°ys= 1.75±0.74). Conclusions: Humanistic attitudes, including empathy, should be instilled, and evaluated among trainees as an essential part of their postgraduate medical education.

The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10-15% of EGFR mutations). Predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions and exon 20 S768I. This group presents a heterogeneous prevalence, partly due to the different testing methods and to the presence of compound mutation, which in some cases leads to shorter overall survival and different sensitivity to different TKIs than simple mutations. EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain and the data of TKIs efficacy are founded of few prospective and some retrospective series. Newer investigational agents are still under study and there are no other approved specific treatment targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remain un unmet medical need. The objective of this review is to evaluate existing data on outcomes, epidemiology and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.

The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for biocrimes in several cases. Here, the main steps of ricin research are reported with particular regards to its enzymatic activity, structure and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation amongst bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been of great utility to develop a number of immunotoxins specific for the elimination of unwanted cells, mainly cancer cells; some of these immunotoxins gave promising results also in clinical trials.

The Coronavirus disease-19 (COVID-19) pandemic dramatically impacted on oncologic patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated also for oncologic population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy de-livery were not available. We aimed to evaluate potential factors influencing the outcome of COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing COVID-19 vaccination with gas-tro-entero-pancreatic and neuroendocrine neoplasms, treated at our Institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection 86.9% received two-doses of Pfizer-BioNTech and the remains Moderna vaccine. All patients obtained a subsequent im-mune-response. A significantly lower values of IgG for patients treated with chemotherapy versus other anti-cancer agents (p=0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs >7 days from the last systemic treatment (p=0.77) and lymphocytes count (p=0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue but rather the quality of the subset of lymphocytes before the vaccination to deter-mine the efficacy level of immune-response in this population.

Since January, the disease caused by the Sars Cov-2 virus has spread and following pandemic. In a few months, the virus is seriously affecting the health systems of the various countries of the world and placing people in difficult psychological conditions. Few scientific resources on mental health have been published but still no one has proposed an action plan to cope the future psychological problems.This manuscript provides a plan to easily frame the priorities of mental health area related to COVID-19 to be taken into consideration which should be disseminated and that should be known by all health professionals and also by the major administrators of public health.

Daridorexant, as the first Dual Orexin Receptor Antagonist (DORA) marketed in Europe, offers a novel therapeutic approach to insomnia. However, data regarding its real-world safety are scarce. Thus, the aim of this study was to assess its safety profile using a large-scale pharma-covigilance database. Daridorexant-related Adverse Drug Reaction (ADR) reports from the FDA Adverse Event Reporting System were scrutinized, and ADRs were selected using reporting odds ratio (ROR) as a measure of disproportionality. Frequencies of events related to daridorexant were compared to all other drugs (reference group, RG1) and only to other DORAs (RG2). Only significant disproportionalities to both RGs were evaluated in-depth. A total of 845 dari-dorexant-related reports were selected; nightmares (n = 146; Dari vs. RG1: ROR = 113.74; 95%CI[95.13, 136]; Dari vs. RG2: ROR = 2.35; 95CI%[1.93, 2.85]), depression (n = 22; Dari vs. RG1: 2.13; [1.39, 3.25]; Dari vs. RG2: ROR = 2.31; 95CI%[1.45, 3.67]), and hangover (n = 20; Dari vs. RG1: ROR = 127.92; 95CI%[81.98, 199.62]; Dari vs. RG2: 3.38; [2.04, 5.61]) were considered as safety signals. These data provide valuable insights into the real-world safety profile of dari-dorexant, supporting the existence of safety signals related to nightmares, depression, and hang-over.

Pediatric obesity management strategies suffer from a high rate of dropout and persistence of weight excess, despite the use of new tools, such as the automated mobile technology (MT). We aimed to compare the efficacy of two personalized MT protocols with/without monthly in-presence recalls in terms of better adherence to follow-up, and improved anthropometric and lifestyle parameters. MT contacts consisted in three not automated messages per week, inserted between three-monthly in-presence regular visits with (PediaFit 1.2) or without (PediaFit 1.1) monthly in-presence recalls. The sample included 103 children (mean age 10 years, range 6-14) recruited in the Pediatric Obesity Clinic between January 2017 and February 2019, randomized in Intervention group (IG) (n=24 PediaFit 1.1; n=30 PediaFit 1.2) and Control group (CG) (total n=49). Both IGs achieved significantly better results than the CGs for all considered parameters. Comparison of the two IGs at the 6th month showed that IG 1.2 had a statistically significant lower drop-out rate (10% vs. 62%), along with improved body mass index z-score, systolic blood pressure, sleep duration and physical activity. The study suggests that the hybrid association of messaging through personalized/not automated MT plus monthly in-presence recalls may be considered for a favorable outcome of pediatric obesity programs.

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.

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.

Cities have witnessed a booming interest in cycling in recent years. However, the implementation of cycling networks rarely followed a strategy to make them more accessible to specific social groups, such as women. To address this gap in knowledge, this paper provides a holistic perspective of women’s cycling mobility. Specifically, the study’s goal is to look into the social and environmental implications of cycling for women in Turin, Italy. Hence, this paper provides insights for ensuring a woman-friendly cycling system in a city and ensuring women’s participation as vital stakeholders in promoting a bike-friendly identity. We clarify women’s perceptions of cycling and outline the requirements for more inclusive bike infrastructures. Thus, we identify strategies to improve women’s access to bike lanes and investigate the environmental benefits of reduced air pollution by such a bike system. All this information is intended to define a more socially inclusive and environmental-friendly transport system in Turin for everyone, as depicted in Goal 11 of Sustainable Development Goals (SDGs).

Optimism and self-efficacy have been associated with psychological health. Empathy has also been found to promote positive functioning and to have a unique role in community health volunteering. This study investigated whether self-efficacy and optimism were associated with psychological and subjective well-being in a group of healthcare volunteers and whether empathy added incrementally to these associations. A sample of 160 Italian clown doctors volunteering in various hospitals completed self-report measures of self-efficacy, optimism, empathy, psychological well-being, and subjective well-being. Results indicated that self-efficacy and optimism were associated with both outcomes and that aspects of empathy, such as others’ perspective-taking and personal distress for others’ difficulties, incrementally added to these associations, although with opposite effects. The present study adds to previous research on the role of self-efficacy, optimism, and empathy for community health volunteers’ psychological health and offers suggestions regarding the training of this type of volunteer.

Accurately diagnosing specific variants of alopecia remains challenging for pathologists, potentially delaying appropriate therapeutic decisions by dermatologists. Issues such as limited knowledge on optimal biopsy types and processing methods add complexity. Understanding the normal histology of hair follicles and their changes throughout the follicular cycle further complicates microscopic evaluation. This paper aims to summarize these characteristics and highlight essential diagnostic clues for pathologists to confidently suggest a diagnosis, therefore playing a key role in alopecia diagnosis. Ongoing education, collaboration with dermatologists, and staying updated on advancements is crucial for accurate diagnosis and effective management of different types of alopecia.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nuclei are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved. We also call for a revised manner in which to think about choice during random X-inactivation.

Introduction. Bacterial resistance to antibiotics is estimated to cause the major number of deaths by 2050 if we do not find strategies to slow down the rise of drug resistance [1]. Reviews on Mediterranean Wild Edible Plants (MWEPs) with antimicrobial properties are scarce in the mean databases (Pubmed, Scopus and WoS). Hence, we proceeded to a new review of the studies on MWEPs. Methods. We used Wild Edible Plant and Antimicrobial as keywords. We only included the Mediterranean plants, and studies in non-Mediterranean countries, but for plants growing in Mediterranean basin. Exclusion criteria were the document type, studies not concerning plant, plants not edible, not antimicrobial properties, or totally out of topic. Results. Finally, the number of studies reviewed, starting from one hundred and ninety-two, was thirty-eight (19,8%), concerning the antimicrobial properties of seventy-four MWEPs species, be-longing to twenty-five Families. Fifty-seven (77%) out of seventy-four species, proved to be antimicrobial with a stringent threshold selection. Conclusions. The studies are still very heterogeneous. We still know too little about MWEPs properties, but what we already know seriously recommends continuing.

From a thermodynamic point of view, living cell life is no more than a cyclic process. It starts with the newly separated daughter cells and restarts when the next generations grow as free entities. In this cycle the cell changes its entropy. In cancer the growth control is damaged. In this paper we analyze the role of the volume-area ratio in cell in relation to the heat exchange between cell and its environment in order to point out the effect on the cancer growth. The result holds to a possible control of the cancer growth based on the heat exchanged by the cancer towards its environment, and the membrane potential variation, with the consequence of controlling the ions fluxes and the related biochemical reactions. This second law approach could represent a starting point for a possible future support for the anticancer therapies, in order to improve their effectiveness for the untreatable cancers.

The present days can be considered a crossroad in the history our word because the economic, social and ecological needs don't agree one another. The result is a continuous growth of poverty and an increase of the ecological degradation. This has generated the present difficult socio-economic state, and it seems very difficult to escape. A new viewpoint must be introduced, but it cannot based on the usual economic indicators. So, new indicators must be introduced. They must allow us to consider the technological level, the environmental impact and the socio-economic conditions. In this paper we suggest three indicators based on an engineering approach of irreversibility. Three applications are shown in order to highlight the possible interest from different scientists and researchers in engineering, economy, etc, in order to develop sustainable approaches and policies for decision makers.

Psychological wellbeing can be impacted substantially by changes in body image during youth, which can be a predictive factor for positive or negative attitudes, such as for self-esteem and satisfaction. In this study, adherence to the thinness model and to healthy behaviours were analysed in terms of the emotional patterns and body management of the young female Italian population (N = 2287). Skinny girls fitting better with the thinness model tended to develop higher positive emotional patterns, but their body management was low. Findings suggest the urgent need for preventive programmes to enhance awareness of healthy behaviours against appearance models.

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.

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.

Sudden unexpected death (SUD) is a fatal event that occurs in an apparently healthy subject so that such an abrupt outcome could have not been predicted. SUD - including sudden intrauterine unexplained death (SIUD), sudden neonatal unexpected death (SNUD), sudden infant death syndrome (SIDS), sudden unexpected death of the young (SUDY), sudden unexpected death in the adult (SUDA) - occurs as the first manifestation of an unknown underlying disease or within a few hours of presentation of a disease. SUD is a major unsolved, shocking form of death that occurs frequently and can happen at any time without warning. For each case of SUD, a review of clinical history data and performance of a complete autopsy, particularly focused on the study of the cardiac conduction system were carried out according to the necropsy protocol devised by the Lino Rossi Research Center, Università degli Studi di Milano, Italy. Research cases are represented by 75 SUD victims, subdivided into 15 SIUD, 15 SNUD, 15 SUDY, and 15 SUDA victims, collected and selected for this study. After the routine autopsy and clinical history analysis, the death remained unexplained and hence a diagnosis of SUD was assigned to the 75. subjects, which included45 females (60%) and 30 (40%) males, ranging in age from 27 gestational weeks to 76 years. Serial sections of the cardiac conduction system disclosed frequent congenital alterations, of the cardiac conduction system in fetuses and infants. An age-related significant difference in distribution among the 5 age-related groups was detected for the following anomalies of the conduction system: central fibrous body (CFB) islands of conduction tissue, fetal dispersion, resorptive degeneration, Mahaim fiber, CFB cartilaginous meta-hyperplasia, His bundle septation, sino-atrial node (SAN) artery fibromuscular thickening, atrio-ventricular junction hypoplasia, intramural right bundle branch, and SAN hypoplasia. The results data are useful to understand the cause of death for all SUD cases that were unexpected and would have otherwise remained unexplained, so to motivate medical examiners and pathologists to perform more in-depth studies.

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.

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.

Enamel erosion is a process which happens every time we eat and it may be accelerated by some particular acid foods, drinks or other agents. Dental enamel when damaged by low pH substances becomes chalky, rough, opaque, yellowed and it can be related to dentinal hypersensitivity. To the present day, several possible solutions are available, therefore the aim of this study was to evaluate the effect of a biocompatible minerals serum based on calcium silicate, sodium phosphate and fluoride (Regenerate™) on the damaged enamel by four different acid liquids. 135 ovine teeth were equally divided into 5 groups and submerged for one week into lemon juice, energy drink, coffee, tea and physiologic solution for the negative control. The first 4 groups were evaluated for their color with an analogical color scale (Vita® Scale) and for their surface assigning a qualitative aspect among opaque, rough, chalky or smooth. Then they were treated with hydroxyapatite gels and re-evaluated for the same parameters. Data were checked for the normal distribution with Shapiro-Wilk test and analyzed with dependent t-test or Wilcoxon Signed Rank test, every test with a p≤0.05. Both color and surface aspect showed a strongly significant improvement after the treatment. Biocompatible minerals serum based on hydroxyapatite is able to reverse teeth erosion, improve the color and restore the smoothness of the dental enamel.

In globe artichoke both the edible portion and the waste biomass are recognized as valuable sources of bioactive compounds. For this study, heads with 30 cm-long floral stems, including 2-3 leaves, were harvested from five genotypes which included two traditional vegetatively-propagated varietal types (‘Brindisino,’ and ‘Violetto di Foggia,’) and three "seed"-propagated hybrids (‘Tempo,’ ‘Opal,’ and ‘Madrigal’). The study aimed to determine the total and individual polyphenolic concentrations (measured spectrophotometrically and by HPLC) and antioxidant activity (AA) in different artichoke parts, namely the "hearts" (H), head waste (HW), stem waste (SW), and leaf waste (LW). ‘Brindisino’ SW exhibited the highest accumulation of luteolin (26,317 mg kg−1 F.W.), while ‘Tempo’ H displayed the highest cynarin content (190 mg kg−1 F.W.). ‘Tempo’ HW and H showed the highest levels of apigenin (640 mg kg−1 F.W.), and the greatest source of chlorogenic acid was found in the HW of ‘Opal’ and the H of ‘Brindisino’ (4,300 mg kg−1 F.W.). The hybrids generally exhibited lower total polyphenolic concentrations than the traditional genotypes, particularly evident in the LW. The SW demonstrated the highest concentration of total polyphenols (18,000 mg kg−1 F.W.), followed by the edible H and non-edible HW (12,000 mg kg−1 F.W.), while the LW exhibited the lowest concentration (2,000 mg kg−1 F.W.). Interestingly, the AA did not precisely align with the total polyphenolic concentration, showing slight variations between the examined parts and genotypes.

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.

Mitochondria are essential to cell homeostasis, and alterations in mitochondrial distribution, segregation or turnover have been linked to complex pathologies such as neurodegenerative diseases or cancer. Understanding how these functions are coordinated in specific cell types is a major challenge to discover how mitochondria globally shape cell functionality. In this review, we will first describe how mitochondrial transport and dynamics are regulated throughout the cell cycle in yeast and in mammals. Second, we will explore the functional consequences of mitochondrial transport and partitioning on cell proliferation, fate acquisition, stemness, and on the way cells adapt their metabolism. Last, we will focus on how mitochondrial clearance programs represent a further layer of complexity for cell differentiation, or in the maintenance of stemness. Defining how mitochondrial transport, dynamics and clearance are mutually orchestrated in specific cell types may help our understanding of how cells can transition from a physiological to a pathological state.

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.

Abstract: A. baumannii exhibits resilience in harsh environments and progressively develops resistance to diverse antibacterial agents over time. This adaptability poses a significant challenge in treating an infection caused by this bacterium within healthcare settings. The presence of peptidoglycan, a crucial precursor for cell wall synthesis, contributes to this challenge. Peptidoglycan serves not only as a structural support in bacterial cells but also provides protection against adverse environmental conditions. The synthesis of the peptidoglycan layer involves a group of substrates such as N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), within a three-partitioned process occurring in the membrane, periplasmic space, and cytoplasm of each bacterium. Initiated in the cytoplasm and extending to the inner cell membrane, this synthesis starts with the production of nucleotide precursors. The first step involves the synthesis of UDP-GlcNAc, orchestrated by Glm (GlmS, GlmM, and GlmU) enzymes using fructose-6-phosphate. Subsequently, enzymes from the Mur family, namely MurB, MurA, MurD, MurC, MurI, MurF, and MurE, synthesize UDP-N-acetylmuramyl-pentapeptide (UDP-Mpp) from UDP-GlcNAc. Concurrently, on the cytosolic side, the production of membrane-surrounded undecaprenyl phosphate occurs, involving membrane-side proteins MraY and MurG in the biosynthesis of peptidoglycan. This review emphasizes updated information on Mur family proteins, encompassing physicochemical properties, nature of binding site, number and type of binding site residues, functional domain details, three-dimensional structural aspects, and their functions within bacterial cells. Special attention is directed towards their enzymatic role in peptidoglycan biosynthesis due to the limited availability of precursors in the market. Additionally, the review provides a comprehensive summary of existing inhibitors and ongoing efforts in identifying new targeted inhibitors, recognizing these enzymes as potential candidates for antibacterial drug design and discovery.

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.

This work demonstrates that microbial fuel cells (MFCs), optimized for energy recovery, can be used as an effective tool to detect the presence of antibiotics in water-based environments. MFCs directly convert chemical energy of organic matter in electrical energy thanks to electroactive biofilms. The efficiency of the conversion process can be significantly affected by the presence of contaminants acting as toxicants for the biofilm. In the present work, we demonstrate that MFCs can successfully detect the presence of antibiotic residues in water and water-based electrolytes associated to the food industry, especially using honey as a new and more complex electron donor. The effectiveness of MFCs to sense antibiotics is here demonstrated for tetracycline that was added to both water and water/honey electrolytes with a minimum concentration close to 3.5 μg⁄kg. MFCs not only efficiently detect the presence of tetracycline in both the electrolytes, but also recover the same performance after each cycle of exposure, showing to a be very robust and reliable technology for both biosensing and energy recovery.

Infant cry is evolutionarily, psychologically, and clinically significant. During the last 60 years, several researchers and clinicians assessed the possibility of investigating the acoustical properties of cry for medical purposes. However, there is a lack of standardization in conducting and reporting cry-based studies. In this work, methodologies and procedures employed in infant cry analysis are reviewed, and best practices for reporting studies are provided. First, available literature on vocal and audio acoustic analysis have been examined to identify critical aspects of participant information, data collection, methods, and data analysis. Then, 180 peer-reviewed research articles have been assessed to certify the presence of identified critical information. Results show a general lack of critical description. Researchers in the field of infant cry need to agree on a standard set of criteria to report experimental studies, to better demonstrate the validity of the methods and obtained results.

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.

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.

Diabetes may cause an increase blood levels of cytokines inducing a rising of C reactive protein (PCR) and fibrinogen stimulating a subclinical inflammation which lead to adhesive molecules expression and to endothelial disfunction. A comprehensive panel of type 1 diabetes mellitus (T1DM) interleukins polymorphisms is not provided yet. As chronic periodontitis (CP) is considered the sixth complication of DM, a clarification is needed about the inflammatory role managed by single nucleotides polymorphisms (SNPs). The goal of this review is to focus on the significant diversity of SNPs in T1DM patients with and without CP. After a digital search on PubMed and Scopus with reference to the last 5 years, 21 items were enrolled. Several ILs were analyzed. T1DM still needs to be thoroughly explored regarding the ILs polymorphisms panel, however the last 5 years have led to the increased independence of this condition, causing autonomous inflammatory effects which requires further investigations. CP and T1DM association in children and adolescents represents a severe gap in literature that should be filled, the scarce presence of studies also about adults serves as a motivation for ulterior clinical researches

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.

The lipid fraction of margarines and fast-food French-fries, two types of foods traditionally high in trans fatty acids (TFA), is assessed. TFA data reported worldwide during the last 20 years have been gathered, and show that some countries still report high TFA amounts in these products. The content of TFA was analysed in margarines (2 store and 4 premium brands) and French-fries from fast-food restaurants (5 chains). Margarines showed mean values of 0.68% and 0.43% (gTFA/100g fat) for store and premium brands, respectively. French-fries values ranged from 0.49% to 0.89%. All samples were lower than the 2% set by some European countries as the maximum legal content of TFA in fats, and contained less than 0.5g/serving, so they could also be considered “trans free products”. This work confirmed that the presence of TFA is not significant in the two analysed products and contributes to update food composition tables, key tools for epidemiological and nutrition studies.

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.

Background: There is poor evidence about sensitivity to chemotherapy according to microsatellite instability (MSI)/mismatch repair (MMR) status in endometrial cancer (EC). Methodology: The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h) /deficient (d) MMR and MSI- low (l)/proficient (p)MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease. Results: 312 patients treated between 2010-2022 in 4 high volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (MITO) centers were selected. 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%). Median age was 65 (range 31–91) years. Among patients with localized disease, median RFS was 100.0 months (95%CI 59.4–140.7) for MSI-l/pMMR and 120.9 months (60.0-181.8) for MSI-h/dMMR (p=0.39). Seventy-seven patients received first-line chemotherapy for advanced/recurrent disease. Patients with MSI-h/dMMR ECs had a significantly worse OS (p=0.039). In patients receiving platinum-based chemotherapy, no statistically significant difference in PFS (p=0.21) and OS (p=0.057) were detected, although PFS and OS were numerically longer in the MSI-l/pMMR population. Conclusion: Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had a significantly worse OS.

The Munich ChronoType Questionnaire (MCTQ) has now been available for more than 15 years; its original publication has been cited 1,240 times (Google Scholar, May 2019); its online version, which was available until July 2017, has produced almost 300,000 entries from all over the world (MCTQ database). The MCTQ has gone through several versions, has been translated into 13 languages and has been validated against other more objective measures of daily timing in several independent studies. Besides being used as a method to correlate circadian features of human biology with other factors – ranging from health issues to geographical factors – the MCTQ gave rise to quantifying old wisdoms, like “teenagers are late” and has produced new concepts, like social jetlag. Some like the MCTQ’s simplicity and some view it critically; it is time to have a self-critical view on the MCTQ, to address some misunderstandings and give some definitions about MCTQ-derived chronotype and the concept of social jetlag.

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.

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as Lung Cancer associated with Cystic Airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs biennial pace of LDCT, choice between opportunistic or population-based recruitment and between uni or multi-center screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention and prospective validation of the biomarkers.

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.

The study investigated the chemical and functional characterization of propolis collected in southern Italy, in particular in Basilicata, a region rich in ecological and vegetative biodiversity. Sixteen samples of propolis, collected within a radius of 40 km from each other in the Basilicata region, showed significant differences between the chemical and functional parameters investigated: color index (L*, a*, b*; P<0.05), variation in chemical composition and antioxidant activities, by ABTS and FRAP assays. In general, Lucanian propolis had a low content of waxes (P<0.05) and a high content of resin (P<0.05) and balsams (P<0.05). The content of total phenolic compounds and flavonoids were highly variable, as was the biological capacity. In conclusion, Lucanian propolis showed a remarkable variability, highlighting a significant diversification according to the geographical position and the diversity of the flora surrounding the apiary of which the bees use as a source of resin. This study therefore contributes to the enhancement of the quality of propolis, laying the foundations for the production and marketing of propolis not only in the food industry, but also in the pharmaceutical and cosmetic industries.

Microplastics are widespread in freshwater environments and could impact these ecosystems. Bivalves are freshwater organisms that are particularly exposed to microplastic contamination. Therefore, in this preliminary study, the accumulation of microplastics, plasticizers, and additives in the freshwater bivalves Anodonta cygnea through active biomonitoring was investigated. Specimens commercially bought were exposed in three rivers in Central Italy for different exposure times: short (1 month) and long (3 months). The gills and the gastrointestinal tract (GIT) were analyzed separately to evaluate the possible uptake and ingestion of particles via Micro-FTIR. For the first time, small microplastics (SMPs, 5-100 µm), plasticizers, additives, and other micro-litter components, e.g., natural and non-plastic synthetic fibers (APFs) were identified in the bivalve A. cygnea. The most abundant polymer in the gills (94.4%), and GITs (66.1%) was polyamide, which had the highest concentration in each river. A decrease in SMPs' abundance was observed over time in the gills in each river, while the abundance in GIT increased. Compared to polymers, a greater variety of APFs was observed in rivers. The APFs changed during the time of exposure and between different rivers more evidently than polymers, allowing a clearer identification of the possible sources. These results highlighted plastic pollution by SMPs using freshwater bivalves as sentinel organisms and the need to investigate further the additives that can be proxies of the presence of microplastics in the environment and biota.

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.

APE1 is an essential endodeoxyribonuclease of the base excision repair pathway that maintains genome stability. It was identified as a pivotal factor favoring tumor progression and chemo-resistance through the control of gene expression by a redox-based mechanism. APE1 is overex-pressed and serum-secreted in different cancers, representing a prognostic and predictive factor, and a promising non-invasive biomarker. Strategies directly targeting APE1 funtions led to the identification of inhibitors showing a potential therapeutic value, which some of them are cur-rently in clinical trials. Interestingly, evidence indicates novel roles of APE1 in RNA metabolism still not fully understood, including its activity in processing damaged RNA in chemoresistant phenotypes, regulating oncomiRs maturation, and oxidized-RNA decay. Recent data point out a control role of APE1 in the expression and sorting of oncomiRs, within secreted extracellular vesicles (EVs). This review is focused on giving a portrait of the pros and cons of the last two decades of research aiming at the identification of inhibitors of the redox or the DNA-repair functions of APE1 for the definition of novel targeted therapies for cancer. We will discuss the new perspectives in cancer therapy coming from the unexpected finding of the APE1 role in miRNA processing for personalized therapy.

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.

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

Loss of photoreceptors in retinal degenerative diseases also impacts the inner retina: bipolar cell dendrites retract, neurons rewire and protein expression changes. ON-bipolar cells represent an attractive target for optogenetic vision restoration. However, above-described maladaptations may negatively impact the quality of restored vision. To investigate this question, we employed human post-mortem retinas and transgenic rd1_Opto-mGluR6 mice expressing the optogenetic construct Opto-mGluR6 in ON-bipolar cells and carrying the retinal degeneration rd1 mutation. We found significant changes in delayed rectifier potassium channel expression in ON-bipolar cells of degenerative retinas. In particular, we found an increase in Kv1.3 expression already in early stages of degeneration. Immunohistochemistry localized Kv1.3 channels specifically to OBC axons. In whole-cell patch-clamp experiments, ON-bipolar cells in the degenerated murine retina were less responsive, which could be reversed by application of the specific Kv1.3 antagonist Psora-4. Notably, Kv1.3 block significantly increased the amplitude and kinetics of Opto-mGluR6-mediated light responses in ON-bipolar cells of the blind retina and increased the signal-to-noise ratio of light-triggered responses in retinal ganglion cells. We propose that reduction of Kv1.3 activity in the degenerated retina, either by pharmacological block or by KCNA3 gene silencing, could improve the quality of restored vision.

Overimitation, the copying of causally irrelevant or non-functional actions, is well-known from humans but completely absent in other primates. Recent studies from our lab have provided evidence for overimitation in canines. Previously, we found that half of tested pet dogs copied their human caregiver's irrelevant action, while only few did so when the action was demonstrated by an unfamiliar experimenter. Therefore, we hypothesized that dogs show overimitation as a result of socio-motivational grounds. To test this more specifically, here we investigated how the relationship with the caregiver influenced the eagerness to overimitate. Given the high variability in the tendency to overimitate their caregiver, we hypothesized that not only familiarity, but also relationship quality influences whether dogs faithfully copy their caregiver. For this purpose, we measured on the one hand the overimitation tendency (with the same test as in the two studies before) and on the other hand the relationship quality between the dogs and their caregivers. Although not significant, results revealed that dogs who overimitated seemed to show more referential and affiliative behaviours towards the owner (like gazing, synchronization and greeting) than dogs who showed less or no copying of the irrelevant action. Possible reasons for these findings are discussed.

ATP is the most universal and essential energy molecule in the eukaryotic cell. This is due to its ability to store energy in form of high energy phosphate bonds, which are extremely stable and readily usable by the cell. This energy is key for a variety of biological functions such as cell growth and division, metabolism, signalling, and for the turnover of biomolecules. Understanding how ATP is produced and hydrolysed with a spatiotemporal resolution is necessary to understand its functions both in physiological and pathological contexts. In this review, we will first describe the ATP synthase, the main molecular motor for ATP production in mitochondria. Second, we will review the biochemical assays currently available to estimate ATP quantities in cells, and we will compare their readouts, strengths and weaknesses. Then, we will explore the palette of genetically-encoded biosensors designed for microscope-based approaches and show how their spatiotemporal resolution opened up the possibility to follow ATP levels and production in living cells. Finally, we will comment on how ATP monitoring is used in preclinical practices, and to what extent genetically-encoded sensors could be used as a promising tool to elucidate pathologies in which ATP is implicated.

The identification of the most rockfall-prone areas is the first step of the risk assessment procedure. In the case of land and urban planning, hazard and risk analyses involve large portions of territory and thus preliminary methods are preferred to define specific zones where more detailed computations are needed. To reach this goal, we developed the QGIS-based plugin QPROTO, able to quantitatively compute rockfall time-independent hazard over a three-dimensional topography on the basis of the Cone Method. This is obtained by combining kinetic energy, passing frequency and detachment propensity of each rockfall source. QPROTO requires the definition of few angles (i.e., the energy angle ϕ_p and the lateral angle α) that should take into account all the phenomena occurring during the complex block movement along the slope. The outputs of the plugin are a series of raster maps reporting the invasion zones and the quantification of both the susceptibility and the hazard. In this paper, we propose a method to relate these angles to some characteristics of the block (volume and shape) and the slope (inclination, forest density), to provide QPROTO users with a tool for estimating the input parameters. The results are validated on a series of case studies belonging to the North Western Italian Alps.

Unlike other SDGs, the SDG4 about quality education is not a goal in itself, but rather a tool to achieve different goals. Universities in this respect play a crucial role in the short-term implementation of SDGs for education, including new approaches and contents. Current academic debates explore the best practices via deductive-theoretical or inductive-experiential methods, yet not always considering the geographical, and therefore cultural and infrastructural factors affecting the success and the failure of such practices. In this paper, we systematize the implementation of SDGs in Italian universities from 2016 to 2019. Eighteen experiences have been collected after a national call by the Italian Network of Sustainable Universities (RUS) aimed at mapping the current landscape of SDG related actions. Results have been analyzed according to two criteria: 1- the educational "container" where the SDGs implementation takes place (from random workshops to dedicated courses); 2- the different organizational scales (from the foundation of a new department to the campaigns by local green teams). With this paper, we do not propose a total refunding or "deus-ex-machina" solutions, disregarding the local factors and the local resources in Italian universities. On the contrary, we draw a map to propose the reuse of an existing structure with adjustments, retrofitting and renewal actions towards holistic and coordinated sustainability efforts. Results show that, within the Italian context, SDGs implementation is still primarily understood as a strategic element for branding and promoting the green image of the Athenaeum. Secondarily, it is seen whether as a separate discipline to be inserted into existing curricula and original teachings or as a conceptual tool for remedying specific societal challenges through random workshops or fieldworks. Conclusions highlight the value of this first Country-wide systematization of the Italian Higher Education Institutions toward SDGs implementation. This exercise avoids individual experiences remaining isolated and self-concluded, and, most importantly, provides comparability and transferability criteria to help similar cases. Further works envisage the recognition of same elements in the broader European traditions, as well as the enhancement of stimuli for a personal and societal transformation generated by the partnership of all those people and institutions engaged in the exciting yet urgent defy of today's societal challenges.

Phytotherapy has long been a source of medicinal products and many attempts to use herbal medicine for the treatment of diabetes has been done over the years. Several medicinal plants and their preparations demonstrated to act in key points of glucidic metabolism. The most common mechanisms of action found include the inhibition of α-glucosidase and of AGE formation, the increase of GLUT-4 and PPARs expression and the antioxidant activity.Despite the large amount of literature available, the actual clinical effectiveness of medicinal plants in controlling diabetes related symptoms is still controversial and there is a crucial need for stronger evidence-based data. In this review, an overview of the medicinal plants, which use in the management of diabetes is supported by authoritative monograph, is provided. References to some species which are currently under growing clinical investigation are also reported.

Human induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them human attractive disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as source cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs. We also cover the phenotypic characteristics of the hiPSCs derived CMs, their ability to rescue injured CMs through paracrine effects, the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their potential use in biomedical applications.

Background and Objectives: Mucilaginous substances from plant extracts are known to be able to support the lubricating effect of hyaluronic acid (HA) in dry eye disease (DED). In this pilot study, the combined lubricating effect of HA and mallow extract (Malva sylvestris L.) in patients with DED was assessed. Materials and Methods: 20 patients at 5 ophthalmological practices in Italy were treated with eye drops, containing HA and mallow extract on the one hand, and with eye drops containing HA only, on the other hand, in a two-period crossover design. As primary endpoints, the tear film breakup time (TBUT), the reduction of lissamine green staining of the ocular surface (Oxford Scheme, OS), and the safety and efficacy assessment by the ophthalmologists were evaluated. As secondary variables, the patient symptom score, the ocular surface index (OSDI), and the satisfaction, preference and efficacy judgement by the patients were evaluated. All data were analysed descriptively in addition to an exploratory analysis of the target variables. Results: Both products were well tolerated. There were no statistically significant differences, with regard to the TBUT, OS and OSDI, between both treatments. Anyway, the efficacy and safety assessments by the ophthalmologists and the patients showed results in favour of the combined product. Conclusion: The addition of mallow extract to HA containing eye drops enhances the treatment of DED at least with respect to subjective measurements. Further assessments will have to be done to prove and explain this observation in terms of measurable parameters, e.g. markers for inflammatory cytokines.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

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.

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.

SARS-CoV-2 virulence is known to increase with lowering of environmental temperature and solar ultraviolet radiation; therefore, we have focused our real-world nationwide study concerning with COVID-19 trends and dynamics on the coldest seasons of the year in Italy, the Western country hardest hit at the onset of the pandemic, comparing the autumn-winter of 2020 (before mass vaccination but when the emergency machinery was fully operative in terms of tracing and swabs) with the autumn-winter of 2021 (after mass vaccination), and analyzing the mortality burden by age groups and life stages in the years 2019 (pre-COVID-19), 2020 (before mass vaccination) and 2021 (after mass vaccination). Methods: During the state of national health emergency, the Civil Defense Department released the aggregate data coming from the Higher Institute of Health, the Ministry of Health, the Italian Regions, and the Independent Provinces, to inform the population (58.85 million people) about the pandemic situation, daily. Among these data there were the number of contagions, performed swabs, hospitalizations in Intensive Care Units (ICU), non-ICU patients, and deaths. By means of a team effort, we have collected and elaborated all these data, comparing the COVID-19 pandemic in Italy during the autumn-winter of 2020 with the autumn-winter of 2021. Moreover, we have extracted from the database of the National Institute of Statistics the total number of annual deaths in Italy during the years 2019, 2020 and 2021, comparing them to each other in order to evaluate the mortality burden attributable to COVID-19. Results: From the autumn-winter of 2020 to the autumn-winter of 2021, the contagions increased by ≈285%, however against a ≈290% increase in the performed swabs; therefore, the mean positivity rate passed from 8.74% before mass vaccination to 8.59% after mass vaccination. The unprecedent vaccination campaign allowed a ≈251% abatement in COVID-19 deaths, and a reduction of ≈224% and ≈228% in daily ICU and non-ICU hospitalizations due to COVID-19, respectively. Regarding COVID-19 deaths, in 2020 there was a mortality excess of ≈14.3% quantifiable in 105,900 more deaths compared to 2019, the pre-COVID-19 year; 103,183 out of 105,900 deaths occurred in older adults (≥60 years), which is equivalent to ≈97.4%, while in adults over 50, the segment of population just below older adults, in 2020 there were 2807 more deaths than in 2019. Surprisingly, from the analysis of our data, it is emerged that under the age of 40 in the years 2019, 2020 and 2021 there were 7103, 6808 and 7165 deaths, respectively. This means that in subjects under 40 during 2020 there were 295 fewer deaths than in 2019, while during 2021 there were 357 more deaths than in 2020, equivalent to ≈5.2% more. Conclusions: COVID-19 is a potential life-threatening disease mainly in older adults, as they are the most vulnerable due to inherent immunosenescence and inflammaging. Extensive vaccination in this segment of population with up-to-date vaccines is the means to reduce deaths, hospitalizations, and ICU pressure in the public interest. In the event of future threats, a new mass vaccination campaign must not be implemented without taking into account the individual age; it should primarily be aimed at people over 60 and at patients of any age with immune deficits, and secondly at people over 50. COVID-19 vaccination shows a favorable benefit-risk balance in older adults, while this balance falls under the age of 40; this younger segment of population should be therefore exempt from any mandatory vaccination.

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.

Tissue bioengineering has been assuming a pivotal role in implementing alternatives to conven-tional ossicular middle ear replacement prostheses to overcome extrusion while preserving acoustic properties. This in vitro study aims to explore for the first time in current literature the feasibility of a biohybrid middle ear prosthesis composed of titanium surrounded by bone ex-tracellular matrix as bio-coating. We have hereby studied the adhesion and proliferation of human adipose-derived mesenchymal stem cells (hASC) on titanium scaffolds in vitro. Moreover, we identified the osteogenic differentiation of hASC using immunofluorescence assay to analyze osteoblasts gene expression profile (Alp, Runx2, Col1a1, Osx, and Bglap) and we accounted the presence of collagen as a marker of hASC ability to secrete extracellular matrix. We utilized scanning electron microscopy to evaluate the presence of extracellular matrix on the scaffolds. Our preliminary data demonstrated the titanium ability to support human adipose-derived mesenchymal stem cell colonization, proliferation, and osteoblastic differentiation, to obtain a biohybrid device. Our experience seems encouraging, we advocate further in vivo research to corroborate our results towards bone transplantation.