(1) Background: Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airways involvement. Reduction in CO diffusing capacity and functional alterations in small airways have been described. The extended analysis of Fractional Exhaled Nitric Oxide (FeNO), may distinguish the sites of production and the presence of small airways inflammation being a useful, non-invasive marker for these patient’s follow up. The aim of our study was to compare PFTs, FeNO and CANO values of UC patients with different clinical disease activity and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. (2) Methods: We enrolled 42 adult outpatients with different clinical activity stages of UC (mean age 39±13 years) and a healthy control group of 41 subjects (mean age 29±3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100 and 200 ml/sec) were collected. All patients performed pulmonary function tests (PFT’s) with static volumes and diffusing capacity (DLCO). (3) Results: FENO, CANO and CRP values were significantly increased in UC patients when compared with controls (p=0.02 and p<0.0001, respectively) and proportionally to the disease activity (FeNO class 3: 27.1 ppb vs class 1-2: 6.2 ppb; CANO values class 3: 8.1 ppb vs class 1-2: 2.0 ppb (p < 0.0001). TLC and DLCO were significantly reduced in UC patients compared to controls (p=0.011 and p<0.0001, respectively). (4) The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with the disease activity suggesting an integrated approach in routine assessment.

This lack of information is due to the primary role of HSTs in fungal pathogenesis, which often masks the functions of NSTs and CWDEs. So, the toxic effects of A. alternata metabolites due to NSTs and CWDEs have received minor attention than those reported for HSTs mycotoxins [11]. A wider study of the activity of isolated fungal metabolites can allow the identification of compounds directly related to the pathogenic activity of the fungus, making it possible to create chemo libraries that facilitate the linking of the structure of the compounds with the species that produce it and its effect on host and non-host crops, as well as with biosynthetic features [12]. In this context, our work reports a study focused on NSTs and CWDEs used by an A. alternata strain isolated from infected pears in Italy. To this aim, the characterization of hydrolytic enzyme activities of A. alternata and the identification of the metabolites produced in vitro were performed. Furthermore, the phytotoxic activity of the isolated compounds was evaluated on pear (host and non-host varieties) and lemon fruits [13]. Finally, the competition of A. alternata with other pathogens was evaluated to investigate the role of NSTs on co-infections.

(1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective is to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1, 48 h or continuously with 10-7 M Nicotine, a concentration mimicking human exposure to a cigarette. Cell viability and proliferation were evaluated by trypan blue dye exclusion and cell counting, migration by cell migration assay, senescence by SA-beta-Gal activity, and anchorage-independent growth by cloning in soft agar. Expression of Ki67, p53/phospho-p53, VEGF, EGFR/pEGFR, phospho-p38, intracellular Ca+2, ATP and EMT were evaluated by ELISA and/or western blotting. (3) Results: Nicotine induced through α7-nAChR (i) increase in cell viability (ii) cell proliferation; (iii) Ki67 over-expression, (iv) phospho-p38 up-regulation (v) EGFR/pEGFR over-expression; (vi) increase in basal Ca+2 concentration, (vii) reduction of ATP production; (viii) decreased level of p53/phospho-p53, (ix) delayed senescence, (x) VEGF increase, (xi) EMT and consequent (xii) enhanced migration, and (xiii) ability to grow independently of the substrate. (4) Conclusions: Based on our results and on evidence showing that Nicotine potentiates viral infection it is likely that Nicotine is involved in SARS-CoV-2 infection and severity

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

The Active Distribution Networks (ADNs) are Multi-Input Multi-Output (MIMO) systems with coupled dynamics which cause interactions among the control loops of the Distributed Energy Resources (DERs). This undesired effect lead to performance degradation in the voltage control. To mitigate the effects of these unavoidable coupling, the present paper proposes a systematic design procedure based on the analysis of the interaction's sources. In details, each DER is equipped with a double loop PI to control the active and reactive powers output by the Voltage Source Converter (VSC) which connects the DER to the network's node. Furthermore, to guarantee Ancillary Services (ASs), the two loops are coupled by a simple mechanism of cooperation of the active power to voltage regulation realized by a filtered droop law. To achieve voltage regulation with reduced loop interactions, the PI parameters and the filter's pulse are designed according to a two sequential steps procedure based on the (Internal Model Control) IMC technique. Simulation studies are finally presented to demonstrate that the proposed design method achieves both reduction of the loop interaction and robust voltage control in presence of model parameter uncertainty in the MIMO model.

The paper proposes, through an experimental method, a conceptualisation of theoretical-methodological and practical guidelines for the project on the system of collective open spaces, residual areas, abandoned areas that characterise the contemporary city, both in the urban contexts of the historical city, and in the more marginal areas of the modern suburbs. This methodology was experimented on an historical neighbourhood in Rome (San Lorenzo discrict) starting from the results of some researches conducted in collaboration between Sapienza University of Rome and the Escuela de Architettura, Universidad San Jorge and some design experiments conducted by Gràvalosdimonte design studio. This methodology and experimentation combines the theme of the inter-scalarity of the project (territorial, urban and local scale) with the themes of the flexibility and proximity of functions with respect to local instances and contingencies caused by the pandemic situation and by the sustainability perspectives, with particular reference to the need for urban health, the dialectic between public and private space in the perspective of the notion of common good, the bottom-up project for the construction of proximity spaces and plurality in the decision-making process.

SerpinB3, a member of the serine-protease inhibitor family, has emerged as a crucial player in various physiological and pathological processes. Initially identified as an oncogenic factor in squamous cell carcinomas, SerpinB3's intricate involvement extends from fibrosis progression and cancer to cell protection in acute oxidative stress conditions. This review explores the multi-faceted roles of SerpinB3, focusing on its implications in fibrosis, metabolic syndrome, carcino-genesis, and immune system impairment. Furthermore, its involvement in tissue protection from oxidative stress and wound healing underscores its potential as diagnostic and therapeutic tool. Recent studies have described the therapeutic potential of targeting SerpinB3 through its upstream regulators, offering novel strategies for cancer treatment development. Overall, this review underscores the importance of further research to fully elucidate the mechanisms of ac-tion of SerpinB3 and to exploit its therapeutic potential across various medical conditions.

Background: COPD is characterized by dyspnea, chronic cough, sputum production and extra pulmonary multimorbidity including depression, anxiety and cognitive problems. Methods: Cognitive and psychological clinical alterations/disorders; QoL/Health-related QoL; and Coping strategies were evaluated in 71 COPD patients characterized for FKBP5 gene (rs4713916). Instruments: MMSE, MoCA, ROCF, BDI-II, CES-D, SAS, SF-36, ADL, IADL, SGRQ, MRF 26, CIRS, Brief COPE. Results: Carriers of the rs4713916 polymorphisms (G:A) show better cognitive performances, higher degree of independence in the ADL and IADL, better QoL before and after rehabilitation, no presence of depressive mood and anxiety symptoms, no family history of psychiatric disorder, more ability to cope with stressors by avoiding emotions but demanding emotional support, and lesser use of anti-anxiety, anti-depressant anti-psychotic, hypnotic-sedative drugs. On the other hand, no difference was found as regards the number of comorbidities. Conclusions: Our study shows that rs4713916 is positively associated with better outcome for COPD. These results offer valuable insights into the role of FKBP5 in the complex network of mechanisms associated to clinical and behavioral features of COPD patients.. Our data may be used as initial benchmark for future clinical studies.

Traditional methodologies for measuring combat effectiveness rely on various contribution factors, where the main challenge lies in the complexity and subjectivity of these factors. Using frontline variation to measure combat effectiveness circumvents the limitations of many previous methods regarding complexity and subjectivity. Employing this methodology, we have quantitatively measured the combat effectiveness of both parties in the Russo-Ukrainian War across various temporal scales. Utilizing the time series data derived from our measurements, we constructed Daily, Weekly, Monthly, and Annual Candlestick Charts to illustrate the variation trends in combat effectiveness between the two sides across different temporal scales. This comprehensive approach facilitated a nuanced and all-encompassing analysis of the conflict, capturing the intricate dynamics of individual military engagements and the broader strategic operations' context. This case underscores the distinctive utility of our method in quantifying combat effectiveness, offering detailed and strategically significant insights.

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts and provides data suggesting that the topical administration of melatonin as eye drops is a real possibility. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. Standard treatment of HF includes angioten-sin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorti-coid-receptor antagonists, beta-blockers, and sodium-glucose co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with de-creased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of HFrEF therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater num-ber of medications for the management of these patients. This review covers vericiguat's metab-olism, molecular mechanisms, and drug-drug interactions.

Background: DNA-RNA compounds have shown promising protection against cell oxidative stress. This study aimed to assess the cytotoxicity, protective, or preventive effect of different experimental formulations on oral epithelia’s oxidative stress in vitro. Methods: Reconstituted human oral epithelia (RHOE) were grown air-lifted in a continuous-flow bioreactor. Mouthwash and gels containing DNA-RNA compounds and other bioactive molecules were tested on a model of oxidative stress generated by hydrogen peroxide treatment. Epithelia viability was evaluated using a biochemical MTT-based assay and confocal microscopy; structural and ultrastructural morphology was evaluated by light microscopy and TEM. Results: DNA-RNA showed non-cytotoxic activity and effectively protected against oxidative stress, but not in its prevention. Gel formulation did not express adequate activity compared to the mouthwash. Excipients played a fundamental role in enhancing or even decreasing the bioactive molecules’ effect. Conclusion: A mouthwash formulation with hydrolyzed DNA-RNA effectively protected against oxidative stress without additional enhancement by other bioactive molecules. Active compounds such as hyaluronic acid, β-Glucan, allantoin, bisabolol, ruscogenin, and essential oils showed a protective effect against oxidative stress, which was not synergistic with the one of DNA-RNA. Surfactant agents showed harmful activity against oral epithelia.

Tourism may not sustainably support territories with limited natural resource stock as islands. The volume in visitor arrivals and the industry investments can increase the pressure even beyond sustainable levels. There is an evident and unresolved tension between these two great polarities, sustainability and economic growth driven by tourism. The aim for policymakers is to find an acceptable equilibrium between these two dimensions. This paper investigates the tourism evolution between 2007 and 2019 in 15 Mediterranean islands, comparing the tourism pressures through statistical indicators. The analysis will compare tourism demand and supply trends in these contexts. The performances will be evaluated to identify the Islands positioning between sustainability needs and tourism development opportunities considering post-covid-19 challenges.

The agricultural sector, even though it has been greatly reduced and is in constant transformation, continues to be of strategic importance. Although it does not represent a quantitatively relevant employment sector, the dynamics are interesting because they reflect the structural, economic and social transformations that are affecting the sector in recent years; there is a growing need for external labour that corresponds to a massive recourse of foreigners to work. Innovative approaches are required to explore the capacity of social farming to create a sustainable and inclusive workplace for migrant. The overall methodological approach of the paper seeks to synthesize fieldwork research and qualitative interviewing to validate the Italian inclusive model. To do this, we have selected four experiences of Italian social agriculture in which migrants are included.

Microwave Power Modules (MPM) are high power devices largely used for radar applications. An MPM is a hybrid combination of a Solid-State Power Amplifier (SSPA) as a driver and a Traveling wave tube amplifier (TWT) as the final high power stage. Power equalizer is often used to flat the TWT output power gain owing to its big gain fluctuations in the operating frequency range. This paper deals with an optimal design and development of a fully-coaxial easy-tunable power equalizer for an X-band MPM. The structure utilizes a coaxial waveguide as the main transmission line and a coaxial cavity loaded with absorbing material as the resonant unit. A sensitivity analysis of the coaxial cavity length, the thickness of the absorbing disc and inserted depth of the probe on the attenuation amplitude and resonant frequency is carried out. The transmission characteristic curves and the voltage standing wave ratio curves show a good compromise in terms of transferred power and adaptive matching impedance at the input and output ports. The measured results show that the equalization curve meets the requirements well and prove that this structure is practical and effective.

Multirotors are gaining great importance in the layout of innovative and more agile mobility. In this framework, a possible solution to developing an aircraft complying with the stringent size requirements characterizing this type of application can be a coaxial rotor configuration. To exploit the several possibilities linked to coaxial rotors, a scaled experimental model is designed to evaluate the performances of the counter-rotating propellers system, concerning the distance between the two propellers. Both thrust and noise are considered as parameters of interest. Two brushless motors are deployed whereas the propellers' angular velocity, in terms of round per minute (rpm), is controlled by an external control system. Tests are conducted on both single isolated propellers as well as on the counter-rotating system: the two propellers and their respective motors have been characterized concerning the thrust. Furthermore, a comparison with a numerical model is performed. Noise evaluation on the single propeller has shown a motor contribution prevalence at a low rpm regime (1140-1500 rpm) and a propeller prevalence for angular velocities higher than 1860 rpm. By varying the distances between the propellers a sensitivity analysis is performed with the aim of identifying the optimum configuration taking into account both noise and thrust performances.

The use of Attitude and Heading Reference Systems (AHRS) for orientation estimation is now common practice in a wide range of applications, e.g., robotics and human motion tracking, aerial vehicles and aerospace, gaming and virtual reality, indoor pedestrian navigation and maritime navigation. The integration of the high-rate measurements can provide very accurate estimates, but these can suffer from errors accumulation due to the sensors drift over longer time scales. To overcome this issue, inertial sensors are typically combined with additional sensors and techniques. As an example, camera-based solutions have drawn a large attention by the community, thanks to their low-costs and easy hardware setup; moreover, impressive results have been demonstrated in the context of Deep Learning. This work presents the preliminary results obtained by DOES , a supportive Deep Learning method specifically designed for maritime navigation, which aims at improving the roll and pitch estimations obtained by common AHRS. DOES recovers these estimations through the analysis of the frames acquired by a low-cost camera pointing the horizon at sea. The training has been performed on the novel ROPIS dataset, presented in the context of this work, acquired using the FrameWO application developed for the scope. Promising results encourage to test other network backbones and to further expand the dataset, improving the accuracy of the results and the range of applications of the method.

The idea of an extension of life for CubeSats is proposed to reduce space debris in a low-earth orbit. In this work, a gripper is designed for geometry-based grasping in berthing tasks. The grasping operation is outlined for square- and rectangle-profiled CubeSats. Equilibrium conditions are used to choose fingertips shape and parameters for grasping the CubeSat body. A design scheme is proposed to provide the required accuracy. A design concept is developed into a lab prototype by using low-cost 3D printing technique, and a mock-up grasping task that is representative of the berthing operation is evaluated with the lab prototype. Center-mass hanging setup for the prototype and grasped body is used to evaluate the impact of grasping, partially replicating the conditions in space by reducing the effect of gravity on the system.

Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customized biomaterials able to mimic ECM functionalities represent one of the major strategy to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review new strategies and future perspectives of such synthetic cell microenvironment will be highlighted.

In European Seveso Legislation for the control of the hazard of major accidents (Directive 2015/12/UE), the Safety Management System SMS is an essential obligation for managers and the authorities are required to periodically verify its adequateness through periodical inspections at Seveso sites. One of the pillars of the SMS is the collection and analysis of documents on accidents, near misses and possibly anomalies, in order to identify weaknesses and implement continuous improvement. In Italy, for a few years, the documents, gathered from all Italian Seveso sites by the inspectors, have been archived and used for research purposes. The archive currently contains some 4000 reports, collected in five years by some 100 inspectors throughout Italy. The paper discusses in the detail the challenges faced to extract the knowledge hidden in the documents and make it usable through the design of a robust model. For this aim, Machine Learning techniques have been used as a preprocessing of the reports for extracting the concepts and their relations, organized into an entity-relation model. The effectiveness of this methodology and its potentiality are pointed out by investigating a few hot topics, exploiting the information contained in the repository.

Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

Heavy metals are dangerous contaminants constituting a threat to human health because they persist in soils and are easily transferred into the food chain, causing damages to human health. Among heavy metals, nickel appears to be one of the most dangerous responsible for different disorders. Public health protection requires nickel detection in environment and food chains; a simple, rapid and sensitive method to detect nickel contamination is represented by biosensors. In this paper we report the setup of a whole-cell based system, in which protoplasts, obtained from Nicotiana tabacum leaves, were used as transducers to detect the presence of heavy metal ions and, in particular, nickel ions. Protoplasts were genetically modified with a plasmid containing the GFP reporter gene under the promoter region of a sunflower small HSP gene control. By this device the presence of heavy metal ions was detected. Thus, the possibility to use this whole-cell system as a novel tool to detect the presence of nickel ions in food matrices was assessed.

In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

In numerous instances, the fate of a single cell not only represents its peculiar outcome but also contributes to the overall status of an organism. In turn, cell division cycle and its control strongly influence cell destiny playing a critical role in targeting it towards a specific phenotype. Several factors participate to the control of growth and among them p27 and p57, two proteins modulating various transitions of cell cycle, appear to play key functions. In this review, the major features of p27 and p57 will be described, focusing in particular on their recently identified roles not directly correlated to cell cycle modulation. Then, their possible role as molecular effectors of polyphenols activities are discussed. Polyphenols represent a large family of natural bioactive molecules that have been demonstrated to play promising protective activities against several human diseases. Their use has also been proposed in association with classical therapies for ameliorating their clinical effects and for diminishing their negative side activities. The importance of p27 and p57 in polyphenol cellular effects will be discussed with the aim of identifying novel therapeutic strategies for the treatment of important human diseases, such as cancers, characterized by an altered control of growth.

The contents of Education for Sustainable Development (ESD) should be included in teachers’ initial and advanced training programs. In order to determine the key competences for sustainability, creating a Sustainable Consciousness is one of the main foundations. However, there are not many empirical studies that deal with consciousness from education. In this context, e-portfolio appears as a tool that promotes reflection and critical thinking, key competences for consciousness development. This work intends to propose a categorization system to extract types of consciousness and identify trainee teachers’ levels of consciousness. For this research work, of an eminently qualitative nature, we have selected twenty-five portfolios of students in the last year of the School of Education at the University of Macerata (Italy). The qualitative methodological procedure followed allowed to deduce three bases that shape trainee teachers’ consciousness: thinking, representation of reality and type of consciousness. We concluded that the attainment of a Sustainable Consciousness in teachers requires activating and developing higher levels of thinking, as well as a projective and macrostructural representation of reality.

In the last decades, studies on the inflammatory signaling pathways in multiple pathological contexts revealed new targets for novel therapies. Among the family of G-protein-coupled Proteases Activated Receptors, PAR2 was identified as a driver of the inflammatory cascade in many pathologies, ranging from autoimmune disease to cancer metastasis. For this reason, many efforts have been focused on the development of potential antagonists of PAR2 activity. This work focuses on a small molecule, 1-Piperidine Propionic Acid (1-PPA), previously described to be active against inflammatory processes, but whose target is still unknown. Stabilization effects observed by cellular thermal shift assay coupled to in-silico investigations, including molecular docking and Molecular Dynamics simulations, suggested that 1-PPA binds PAR2 in an allosteric pocket of the receptor inactive conformation. In addition, this compound was found able to inhibit platelet aggregation, a process mediated by PAR family members, including PAR2. Since the allosteric pocket binding 1-PPA is highly conserved in all the members of the PAR family, the evidence reported here suggests that 1-PPA could represent a promising new small molecule targeting PARs with antagonistic activity.

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

The range of interactions between Cladosporium, an ubiquitous fungal genus, and insects, a class including about 60% of the animal species, is extremely diverse. The broad case history of antagonism and mutualism connecting Cladosporium and insects is reviewed in this paper based on the examination of the available literature. Certain strains establish direct interactions with pest or beneficial insects, or indirectly influence them through their endophytic development in plants. Entomopathogenicity is often connected to the production of toxic secondary metabolites, although there is a case where these compounds have been reported to favor pollinators attraction, suggesting an important role in angiosperm reproduction. Other relationships include mycophagy, which on the other hand may reflect an ecological advantage for these extremely adaptable fungi using insects as carriers for spreading in the environment. Several Cladosporium species colonize insect structures, such as galleries of ambrosia beetles, leaf-rolls of attelabid weevils and galls formed by cecidomyid midges, playing a still uncertain symbiotic role. Finally, the occurrence of Cladosporium in the gut of several insect species has intriguing implications in pest management, also considering that some strains have proven to be able to degrade insecticides. These interactions especially deserve further investigation to understand the impact of these fungi on pest control measures and strategies to preserve beneficial insects.

Paper is one of the most promising materials for food packaging and wrapping due to its low environmental impact, but surface treatments are often needed to improve some performance, e.g. the resistance to fats and oils. In this context, this research is focused on the formulation of a new paper bio-coating. Paper was coated with liquids containing Poly(hexano-6-lactone) (PCL), Glycerol and variable percentages of starch (5 - 10% w/w PCL dry weight), agar agar (0 - 1.5% w/w PCL dry weight) and PEG (5% or 15% w/w PCL dry weight) to improve coating uniformity and diffusion. A Design of Experiments approach was implemented to find statistically reliable results in terms of best coating formulation. Coated paper was characterized through mechanical and physical properties. Results showed that agar content (1.5% w/w PCL dry weight) has a beneficial effect on increasing the resistance to oil. Furthermore, the best coating composition has been calculated, and it is: 10% w/w PCL dry weight of Starch, 1.5% w/w PCL dry weight of agar and 15% w/w PCL dry weight of PEG.

Microglial cells, the resident macrophages of the CNS, exist in a process-bearing, ramified/surveying phenotype under resting conditions. Upon activation by cell damaging factors they get transformed to an amoeboid phenotype releasing various cell products including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen/nitrogen species and the excytotoxic ATP and glutamate. In addition, they engulf pathogenic bacteria or cell debris and phagocytose them. However, already resting/surveying microglia has a number of important physiological functions in the CNS; they e.g. shield small disruptions of the blood-brain barrier by their processes, dynamically interact with synaptic structures and clear surplus synapses during development. In neurodegenerative illnesses they aggravate the original disease by a microglia-based compulsory neuroinflammatory reaction. Therefore, the blockade of this reaction improves the outcome of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. The function of microglia is regulated by a whole array of purinergic receptors classified as P2Y12, P2Y6, P2Y4, P2X4, P2X7, A2A, A3, and being targets for endogenous ATP, ADP, or adenosine. ATP is sequentially degraded by the ecto-nucleotidases and 5’-nucleotidase enzymes to the weak adenosine agonist inosine as an end-product. The appropriate selective agonists/antagonists for purinergic receptors as well as the respective enzyme inhibitors may profoundly interfere with microglial functions and reconstitute the homeostasis of the CNS disturbed by neuroinflammation.

Italy is the leading European producer of rice. The transition to organic farming could represent a solution for environmental protection, as well as for the economic sustainability of farms, consumer safety and as a measure of climate mitigation, but it currently displays several weaknesses in the control and certification system. The objective of the current study is to propose advice for improving the control and certification scheme in the organic rice sector. To achieve this aim, we adopted a qualitative methodology based on participant observation at stakeholders’ meetings, focus groups, community-led workshops and deep interviews with relevant local actors. Findings show that there are some solutions to mitigate the weakness of the Italian certification scheme. The study also produces managerial implications to improve the Italian organic rice system.

One of the main issues for underwater robots navigation is represented by the accurate vehicle positioning, which heavily depends on the orientation estimation phase. The systems employed to this scope are affected by different noise typologies, mainly related to the sensors and to the irregular noise of the underwater environment. Filtering algorithms can reduce their effect if opportunely configured, but this process usually requires fine techniques and time. This paper presents DANAE++, an improved denoising autoencoder based on DANAE, which is able to recover Kalman Filter IMU/AHRS orientation estimations from any kind of noise, independently of its nature. This deep learning-based architecture already proved to be robust and reliable, but in its enhanced implementation significant improvements are obtained both in terms of results and performance. In fact, DANAE++is able to denoise the three angles describing the attitude at the same time, and that is verified also on the estimations provided by the more performing Extended KF. Further tests could make this method suitable for real-time applications on navigation tasks.

Spatial attentional biases can be observed during the processing of linguistic material. For example, we previously reported that healthy subjects overestimate the semantic distance between word stimuli in the right vs left space. Here we explored whether attentional biases are also observed in tasks requiring evaluation of phonological distance between words in the right and left hemispace. Forty-one healthy subjects were presented with triplets of words arranged in space and were asked to indicate the side of space in which the phonological distance between the middle word and an outer word was smaller. In Experiment 1 real words and pseudowords were used, while in Experiment 2 only pseudowords and consonant strings were used. Subjects overestimated the phonological distance between the middle and outer words in the right space. These findings were specific to word stimuli. These results are consistent with the idea that semantic and phonological information may be internally mapped onto spatial representations.

The European system of indicators is the result of the European Union sustainable development strategy, based on the objectives of economic prosperity, social equity, cohesion and environmental protection. In 2010 the EC defined four strategic priorities: encourage competitiveness in the tourism sector, promote sustainable high-quality tourism, strengthen the image of Europe as a tourism destination, and finally, improve EU financial policies and instruments. This paper aims to analyze in a positive critical perspective the experience done during the period 2013-2014 in the Italian destination Visit South Sardinia. This experience is in one hand an important primacy in Italy and in Europe, but in the other hand has not reached the expected objectives. Many difficulties were encountered both for data collection and for stakeholder involvement. Also the complexity of the indicators tool kit is relevant. Even if the experience of VSS did not produce the expected results, we believe that the analysis carried out in this paper can help and support other countries and or other destination in Europe in the process of implementation of the ETIS indicators tool kit in order to adapt the system itself to the needs that are encountered locally.

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.

Critical sized bone defects and articular cartilage injuries resulting from trauma, osteonecrosis or age-related degeneration are often nonhealing by the physiological repairing mechanisms, thus representing a clinic issue due to the relevant epidemiological incidence. Current treatment approaches consist of autologous or allogenic grafting, which are associated with painfulness, morbidity, risk of infections and rejection. Novel tissue-engineering approaches, aiming at the reconstruction of damaged tissues, have been proposed as alternative solutions to these conven-tional methods. These approaches are based on the combination of three fundamental compo-nents: autologous or allogenic cells, a scaffold and growth-stimulating signals, which are gener-ally referred to as the tissue engineering triad. Three-dimensional polymer networks are fre-quently used as scaffolds to allow cell proliferation and tissue regeneration. In this scenario, cryogels are giving promising results as cell scaffolds over other polymer networks, thanks to their peculiar properties. In particular, cryogels possess an interconnected porous structure and a typical sponge-like behaviour, which facilitate the cellular infiltration and ingrowth. Their properties can be appropriately adjusted to match the requirements of the specific tissue or or-gan that it is intended to regenerate. In this review it is reported the state of the art on the fabri-cation and employment of cryogels in supporting osteo or chondro-genic differentiation for the re-building of more organized tissues. Moreover, it will highlight current progress and future perspectives in the implementation of this technology in the clinical practice.

Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a rare form of necrotizing granulomatous inflammation that predominantly affects medium and small size vessels. Generally respiratory tracts and kidneys are the most affected organs. Neurological manifestations of GPA usually involve the peripheral nervous system causing mononeuritis multiplex or and cranial nerve palsies. Central nervous system (CNS) involvement is rare and characterized by cerebral vasculitis, meningeal inflammation, or mass lesions. The CNS involvement is often linked to Ear Nose Throat (ENT) system disease. In this report, we present two cases of patients diagnosed with GPA who exhibit CNS involvement as first symptom. In the first one with an ischemic stroke while in the second with an atypical headache. In the first patient, a positive medical history indicating involvement of the Ear, Nose, and Throat (ENT) facilitated a precise diagnosis through the prompt execution of autoimmune screening. This, in turn, enabled a timely commencement of treatment, resulting in neurological improvement. In the second case, the significance of ENT involvement was initially overlooked in the context of pathological definition, leading to a substantial delay in diagnosis and an ultimately grim prognosis for the patient. The ENT involvement could be an easy marker to suspect GPA in patient with atypical CNS presentation and could help to make a prompt diagnosis.

Circular Economy (CE) is a growing topic among scholars, industry and government aiming at decoupling economic growth and development from the consumption of finite resources. CE incorporates different meanings, from reduce, reuse and recycle activities to environmental degradation or resource scarcity, and supported by specific indicators to attain sustainable development. However, so far, there has been no agreement to measure how effective an industry/product is in making the transition from linear to circular approaches, particularly those affected the society. This research work aims to perform a systematic literature review (n=60) to analyze and discuss how social aspects have been considered and integrated in the CE research so far. Moreover, this review provides and overview of the literature on social impact within CE, that resulted in three main outputs: a knowledge map of the CE, an analysis of social aspects within CE, and the theories/frameworks used to evaluate social impact of CE. Finally, this study brings to light how CE implementation can affect society and highlights the importance of social dimension in the domains of CE and policy-making community, which could help moving CE towards a sustainable development.

Vaccination has been the most effective way to control the outbreak of the Covid pandemic. The numbers and types of vaccines have reached considerable proportions, even if the question of vaccine procedures and frequency still needs to be resolved. We learn the necessity of defining a vaccination distribution strategies with regard to Covid that could be used for any future pandemics of similar gravity. In fact, vaccine monitoring implies the existence of a strategy that should be measurable in terms of input and output, based on a mathematical model, including death rates, spread of infections, symptoms, hospitalization and so on. This paper addresses the issue of vaccine diffusion and strategies for monitoring the pandemic. It provides a description of the importance and take up of vaccines and the links between procedures and the containment of Covid variants, as well as the long-term effects. Finally, the paper focuses on the global scenario in a world undergoing profound social and political change, with particular attention on current and future health provision. This contribution would represent an example of vaccination experiences which can be useful in other pandemic or epidemiological contexts.

Background: Post-delivery period could be characterized by psychological distress (e.g., anxiety, sadness, and irritability), leading to post-partum depression (PPD). Objective: The present clinical study assess the effect of probiotic supplementation containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) on mother’s mood and breastfeeding quality during the first trimester after delivery. Methods: A Randomized Double Blind Controlled (RDBPC) trial has been carried out in 200 healthy new mothers divided into an active group taking a supplement containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) plus multivitamins, and a control group (multivitamin complex only) for 90 days. Symptoms related to maternal depression and breastfeeding quality were evaluated at days 45 and 90 by Edinburgh Postnatal Depression Scale (EPDS) and Breastfeeding Self-Efficacy Scale Short-Form (BSES-SF). Results: At days 45 and 90, probiotic treatment significantly ameliorated the mothers’ mood compared to the control treatment (p<0.001). Likewise, breastfeeding quality and baby’s cries significantly improved in the probiotic group (p<0.001). Conclusions: Microbiota alterations could influence post-delivery woman’s mental state. According to our results, L. reuteri PBS072 and B. breve BB077 are potential candidates able to improve stress resilience in the post-partum period.

The present study aims to evaluate the ability of peonidin and petunidin-3-glucoside (Peo and Pet-3-glc) and their metabolites (vanillic acid; VA and methyl-gallic acid; MetGA), to prevent monocyte (THP-1) adhesion to endothelial cells (HUVECs), and to reduce the production of VCAM-1, E-selectin and VEGF in a stimulated pro-inflammatory environment, a pivotal step of atherogenesis. Tumor necrosis factor-α (TNF-α; 100 ng mL-1) was used to stimulate the adhesion of labelled monocytes (THP-1) to endothelial cells (HUVECs). Successively, different concentrations of Peo-3-glc and Pet-3-glc (0.02, 0.2, 2 and 20 µM) and VA and MetGA (0.05, 0.5, 5 and 50 µM) were tested. After 24 h, the production of VCAM-1, E-selectin and VEGF was quantified by ELISA kits, while the adhesion process was measured spectrophotometrically. Peo-3-glc and Pet-3-glc (from 0.02 to 20 µM) significantly (p<0.0001) decreased THP-1 adhesion to HUVECs at all concentrations (-37%, -24%, -30% and -47% for Peo-3-glc; -37%, -33%, -33% and -45% for Pet-3-glc). VA, but not MetGA, reduced the adhesion process at 50 µM (-21%; p<0.001). At the same concentrations, a significant (p<0.0001) reduction of E-selectin, but not VCAM-1, was documented. In addition, anthocyanins and their metabolites significantly decreased (p<0.001) VEGF production. The present findings suggest, that while Peo-3-glc and Pet-3-glc, but not their metabolites, reduced monocyte adhesion to endothelial cells through suppression of E-selectin production, VEGF production was reduced by both anthocyanins and their metabolites suggesting a role in regulation of angiogenesis.

Traditional dry fermented meat products are obtained artisanally in many countries, where they represent a gastronomic heritage well distinguished from industrial counterparts. This food category is most often obtained from red meat, a food commodity that is under attack because of evidences of increased risk of cancer and degenerative diseases with high consumption. However, traditional fermented meat products are intended for moderate consumption and gastronomic experience and, as such, their production must be continued also to safeguard culture and economy of the geographical areas of origin. In this review, the main risks attributed to these products are considered and how these risks are minimized by following precise production norms, respectful of the ancient manufacturing processes is described. Moreover, results obtained in studies reporting use of autochthonous microbial cultures of lactic acid bacteria (LAB), coagulase negative staphylococci (CNS), Debaryomyces hansenii and Penicillium nalgiovense to improve safety and quality of traditional fermented meats are summarized. The role of these products as a source of microorganisms that can be beneficial to the host are also considered. From the results of the studies reviewed here it appears that the development of autochthonous cultures for these foods ensure safety and stabilize sensory characteristics with possibility to be extended to the large variety of traditional productions.

High Vacuum Flat Plate Collectors (HVFPCs) are the only type of Flat Plate Thermal Collectors capable of producing thermal energy for middle-temperature applications (until 180 °C). As the trend of research plans to develop new Selective Solar Absorbers to extend the range of HVFPC application until 250 °C, it is necessary to correctly evaluate the collector efficiency up to such temperature to predict the energy production accurately. We propose an efficiency model for these collectors based on the selective absorber optical properties. The proposed efficiency model explicitly includes the radiative heat exchange with the ambient, which is the main source of thermal losses for evacuated collectors at high temperatures. It also decouples the radiative losses that depend on the optical properties of the absorber adopted from the other thermal losses due to HVFPC architecture. The model has been validated by applying it to MT-Power HVFPC manufactured by TVP-Solar, and it has been used to predict the efficiency and energy production of HVFPC equipped with new, optimized selective solar absorbers developed in recent years.

Matrix metalloproteases (MMPS) are a family of well-known enzymes which operate prevalently in the extracellular domain, where they fulfil the function of remodeling the extracellular matrix. Within the about 26 family members, encoded by 24 genes in humans, MMP-2 and MMP-9, have been regarded as the primary responsibility for the basement membrane and pericellular ECM rearrangement. In cases of infiltrating carcinomas, which arise from the epithelial tissues of a gland or of an internal organ, a marked alteration of the expression and the activity levels of both MMPs is known to occur. Present investigation represents the continuation and upgrading of our previous studies, now focusing on the occurrence and intensity levels of MMP-2 and -9, and their proteomic correlations, in a cohort of 80 breast cancer surgical tissues

In Parkinson's disease, neuroinflammation is a complex defense mechanism. Activated microglia and Proteinase-activated receptor-2 (PAR2) are key points in the regulation of neuroinflammation. 1-Piperidin Propionic Acid (1-PPA) has been recently described as a novel inhibitor of PAR2. The aim of our study was to evaluate the effect of 1-PPA in neuroinflammation and microglial activation in Parkinson's disease. Protein aggregates and PAR2 expression were analyzed by thioflavin S assay and immunofluorescence in cultured human fibroblasts from Parkinson's patients, treated or not with 1-PPA. A significant decrease of amyloid aggregates and expression of PAR2 were observed after 1-PPA treatment in all patients. A parallel decrease of PAR2 expression, that was higher in sporadic Parkinson’s patients, was also observed both at transcriptional and protein level. In addition, in mouse LPS-activated microglia, the inflammatory profile was significantly downregulated after 1-PPA treatment, with a remarkable decrease of IL-1, IL-6 and TNF-togheter with PAR2 decreased expression.In conclusion, 1-PPA determines reduced neuroglia inflammation and amyloid aggregates formation, suggesting that pharmacological inhibition of PAR2 could be proposed as a novel strategy to control neuroinflammation.

Large volume bone defect regeneration is complex and demands time to complete. Several regeneration phases with unique characteristics including immune responses follow, overlap, and interdepend on each other and, if successful, lead to the regeneration of the organ bone's form and function. However, during traumatic, infectious, or neoplastic clinical cases, the intrinsic bone regeneration capacity may exceed, and surgical intervention is indicated. Scaffold-guided bone regeneration (SGBR) has recently shown efficacy in preclinical and clinical studies. To investigate different SGBR strategies over periods of up to 3 years we have established a well characterized large segmental tibial bone defect ovine model, for which we have developed and optimized immunohistochemistry (IHC) protocols. We present an overview of the immunohistochemical characterization of different experimental groups in which all ovine segmental defects were treated with a bone grafting technique combined with a three-dimensionally printed medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold. The qualitative data set is based on osteoimmunological findings gained from IHC analyses of over &gt;350 sheep surgeries over the past two decades. Our systematic and standardized IHC protocols enabled us to gain further insight into the complex and long-drawn-out bone regeneration processes, which ultimately proved to be a critical element for successful translational research.

In the dairy cattle sector, the evaluation of the effects induced by heat stress is still one of the most impactful and investigated aspects as it is strongly connected to both sustainability of the production and animal welfare. On the other hand, more recently, the possibility of collecting large dataset made available by the increasing technology diffusion is paving the way for the application of advanced numerical techniques based on machine learning or big data approaches. In this scenario driven by rapid change there could be the risk of dispersing the relevant information represented by the physiological animal component, which should maintain the central role in the development of numerical models and tools. In the light of this, the present literature review aims to consolidate and synthesize existing research on the physiological consequences of heat stress in dairy cattle. The present review provides, in a single document, an overview as complete as possible of the heat stress-induced responses in dairy cattle with the intent of filling the existing research gap for extracting the veterinary knowledge present in the literature and make it available to those who are developing numerical models and tools.

In the present study, the performance of a 70 L photobioreactor, operating outdoors, was investigated using a purple bacterial strain as Rhodopseudomonas sp. S16-VOGS3 for producing poly-3-hydroxybutyrate (PHB). The novel photobioreactor was equipped with 5L-shaped rows; the bottom of every row was placed in a stainless-steel tank containing water with controlled temperature. The photofermentation trials were carried out under fed-batch mode and under a semi-continuous regimen using lactic acid as carbon source. The effect of the irradiance and the C/N ratio on the PHB accumulation was investigated, in order to evaluate the optimal bacterial growth. The results showed the feasibility of the prototype photobioreactor for the production of PHB by Rhodopseudomonas sp. S16-VOGS3 under the natural light/dark cycle. During the fed-batch growth (144 h long), the cumulative PHB increased quickly reaching the maximum value of 377 mg/L and decreased to 255 mg/L during the semi-continuous regimen (336 h long).

A growing body of evidences is showing that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, with reduction of host damage. Herein, we discuss how diagnostic parasitology may contribute to design clinical metagenomics pipelines and FMT programs, especially in pediatric subjects. The consequences of a more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.

Pain is a complex multidimensional feeling combined with sensorial and emotional features. The majority of patients undergoing orthodontic treatment reported various degrees of pain, which is perceived as widely variable between individuals, even when the stimulus is the same. Orthodontic pain is considered the main cause of poor-quality outcomes, patients' dissatisfaction, and lack of collaboration up to the interruption of the therapy. A deep understanding of pain and how it influences the patient’s daily life is fundamental to establishing proper therapeutic procedures and obtaining the correct collaboration. Because of its multifaced and subjective nature, pain is a difficult dimension to measure. The use of questionnaires and their relative rating scales is actually considered the gold standard for pain assessment. Depending on the patient’s age and cognitive abilities is possible to choose the most appropriate instrument for self-reported pain records. Although several scales have been proposed and a lot of them are applied, it remains uncertain which of these tools represents the standard and performs the most precise, universal, and predictable task. This review aims to give an overview of the aspects which describe pain, specifically the pain experienced during orthodontic treatment, the main tool to assess self-perceived pain in a better and more efficient way, the different indications for each of them, and their correlated advantages or disadvantages.

We measured the anelastic, dielectric and structural properties of the metal-free molecular perovskite (ABX$_{3}$) (MDABCO)(NH$_{4}$)I$_{3}$, which has already been demonstrated to become ferroelectric below $T_{\text{C}}=$ 448~K. Both the dielectric permittivity measured in air on discs pressed from powder and the complex Young's modulus measured on resonating bars in vacuum show that the material starts deteriorating with loss of mass just above $T_{\text{C}}$, introducing defects and markedly lowering $T_{\text{C}}$. The elastic modulus softens of 50\% when heating through the initial $T_{\mathrm{C}}$, contrary to usual ferroelectrics, which are stiffer in the paraelectric phase. This suggests improper ferroelectricity, where the primary order parameter of the transition is not the electric polarization, but the orientational order of the MDABCO molecules. The degraded material presents thermally activated relaxation peaks in the elastic energy loss, whose intensities increase together with the decrease of ~$T_{\mathrm{C}}$. The peaks are much broader than pure Debye, due to the general loss of crystallinity, also apparent from X-ray diffraction, but their relaxation times have parameters typical of point defects. It is argued that the major defects should be of the Schottky type, mainly due to the loss of (MDABCO)$^{2+} $ and I$^{-}$, leaving charge neutrality, and possibly also (NH$_{4}$)$^{+}$ vacancies. The focus is on an anelastic relaxation process peaked around 200~K at $\sim 1$~kHz, whose relaxation time follows the Arrhenius law with $\tau $$_{0}$~$\sim $\ $10^{-13}$\ s and $E\simeq 0.4$~eV. This peak is attributed to I vacancies (V$_{\text{X}}$) hopping around MDABCO vacancies (V$_{\text{A}}$) and its intensity presents a peculiar dependence on temperature and content of defects. The phenomenology is thoroughly discussed in terms of lattice disorder introduced by defects and of partition of V$_{\text{X}}$ among sites that are far from and close to the cation vacancies. A method is proposed for calculating the relative concentrations of V$_{\text{X}}$, that are untrapped, paired with V$_{\text{A}}$ or forming V$_{\text{X}}$--V$_{\text{A}}$--V$_{\text{X}}$ complexes.

The paper addresses the problem of a statistically significant numerical evaluation of the biomechanics of respiration using the motion of the ribcage through the identification of the kinematics of the sixth rib. We report the results of an experimental campaign conducted using a RESPIRholter device prototype for efficient, comfortable, and numerical monitoring on two groups of volunteers, namely with healthy people and with chest operated patients. The results are reported in terms of statistical processing of the data extracted from the monitoring which are represented in plots of acquired motion characteristics with movement graphs in terms of angles and accelerations. This experimental campaign can be considered a first result for the construction of a database useful for a reference of diagnostics as reported by the discussed example case study.

This work deals with the performance evaluation of novel flat photovoltaic-thermal (PV-T) modules under vacuum. Through a 1D (dimensional) steady-state-energy-balance numerical model developed in MATLAB, two different layouts are studied: the first consisting of a photovoltaic (PV) cell installed just below the glass encapsulating the flat panel, and the second where the PV cell is placed on the selective solar absorber (SSA). In both cases the thermal and electrical efficiencies have been evaluated at different SSA operating temperatures, in the range of 323 K to 423 K. The analysis has been conducted at different energy bandgap (E_bg) of the PV cell and assuming a variable transmittance or emittance of the PV cell, depending on the design. The two systems efficiency comparison has been carried out at the same operating temperature. Overall, this work highlights the importance of high vacuum insulation, which guarantees the reduction of convective thermal losses, and shows that the maximum energy is produced for PV cells with E_bg ≈1.5-1.7 eV, depending on layout and operating temperature, by including the thermal output in the PV-T optimization. The energy and exergy efficiencies obtainable using the proposed PV-T systems are considerably improved compared to the results previously reported in the literature.

Background: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations and lipid profile, blood pressure and body mass index (BMI) in highly exposed adolescents and children. Methods: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA) perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC) high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic blood pressure (BP) were measured and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. Analyses were stratified by gender and adjusted for potential confounders. Results: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a fewer extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Increased serum concentrations of PFAS, particularly PFOS, were associated with decreased BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. Conclusions: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.

This study aims to develop a hybrid approach based on backpropagation Artificial Neural Network (ANN) and spatial analysis techniques to predict particulate matter of size 2.5 µm (PM2.5) from vehicle exhaust emissions in the State of California using Aerosol Optical Depth (AOD) and several climatic indicators (relative humidity, temperature, precipitation, and wind speed). The PM2.5 data were generated using Motor Vehicle Emission Simulator (MOVES), the measured climatic variables and AOD were obtained from the California Irrigation Management Information System (CIMIS), and NASA’s Moderate Resolution Spectroradiometer (MODIS). The data were resampled to a seasonal format and downscaled over grids of 10 by 10 to 150 by 150, and precipitation was determined to be the most important independent variable. Coefficient of determination ( ), Mean Absolute Percentage Error (MAPE), and Root Mean Square Error (RMSE) were used to assess the quality of the ANN prediction model. The model peaked at winter seasons with = 0.984, RMSE = 0.027, and MAPE = 25.311, whereas it had the lowest performance in summer with = 0.920, RMSE = 0.057, and MAPE = 65.214. These results indicate that the ANN model can accurately predict the PM2.5 concentration and can be used to forecast future trends.

Cystic artery bleeding (CAB), a relatively uncommon entity, can arise from both traumatic and non-traumatic etiologies. This pictorial essay aims to elucidate the computed tomography (CT) findings associated with CAB in these distinct contexts. In traumatic CAB, particularly blunt or penetrating trauma, a cystic artery lesion is the culprit behind the hemoperitoneum characteristically located within the gallbladder fossa. Prompt diagnosis is crucial. Fortunately, trans-arterial embolization offers a successful treatment option for traumatic cystic artery lesions, especially in settings where non-operative management is preferred. Non-traumatic CAB, on the other hand, often stems from inflammation in the hepatobiliary and pancreatic system, gallbladder tumours, or iatrogenic injuries. The underlying mechanism typically involves cystic artery wall damage, either due to inflammation or procedural complications, leading to the formation of a cystic artery pseudoaneurysm (CAP). Notably, CAP bleeding can manifest long after the causative event, posing a diagnostic challenge with a variable clinical presentation. This pictorial essay serves to illustrate the CT signs and features of CAB in both traumatic and non-traumatic scenarios. Additionally, it will delve into the characteristic CT appearance of CAP.

We developed a novel approach in the field of spatiotemporal modelling, based on the spatialisation of time: the Timescape algorithm. It is especially aimed at sparsely distributed datasets in ecological research, whose spatial and temporal variability is strongly entangled. The algorithm is based on the definition of a spatiotemporal distance that incorporates a causality constraint and that is capable of accommodating the seasonal behaviour of the modelled variable as well. The actual modelling is conducted exploiting any established spatial interpolation technique, substituting the ordinary spatial distance with our Timescape distance, thus sorting, from the same input set of observations, those causally related to each estimated value at a given site and time. The notion of causality is expressed topologically and it has to be tuned for each particular case. The Timescape algorithm originates from the field of stable isotopes spatial modelling (isoscapes), but in principle it can be used to model any real scalar random field distribution.

Asphaltenes constitute a heavy fraction of fossil fuels and their characterization is still a very difficult and challenging issue due to their complex and variable composition. Asphaltene components are highly condensed aromatic molecules having some heteroatom and aliphatic functionalities. Their molecular weights distribution span a wide range, from hundreds to millions of units, in dependence on the diagnostic used, leading to speculation about possible occurrence of self-aggregation. In the present work, mass spectrometry, with properly developed mathematical methods, size ex-clusion chromatography and X-ray diffraction analysis have been applied to asphaltenes for giving some further insight on their MW distribution and characteristics. The results here reported give further quantitative support to the experimental data interpretation already reported in previous works.

Irrigated agriculture determines large blue water withdrawals, and it is considered a key intervention area to reach sustainable development objectives. Precision agriculture technologies have the potential to mitigate water resource depletion that often characterizes conventional agricultural approaches. This study investigates the factors influencing farmers' intentions to adopt variable rate irrigation (VRI) technology. The Technology Acceptance Model 3 (TAM-3) was employed as a theoretical framework to design a survey to identify the factors influencing farmers' decision-making process when adopting VRI. Data were gathered through quantitative face-to-face interviews with a sample of 138 fruit and grapevine producers from the Northeast of Italy (Veneto, Emilia-Romagna, Trentino-Alto Adige, Friuli-Venezia Giulia). Data were analyzed using partial least squares path modelling (PLS-PM). The results highlight that personal attitudes, such as perceived usefulness and subjective norm, positively influence the intention to adopt VRI. Also, the perceived ease of use positively affects intention, but it is moderated by subject experience.

Amitriptyline is a tricyclic antidepressant commonly used for depressive disorders and pre-scribed off-label for several neurological conditions like neuropathic pain, migraine and anxiety. Amitriptyline potentiates the monoaminergic transmission by blocking the reuptake of norepi-nephrine and serotonin. However, antidepressants also act on additional targets that contribute to either therapeutic or adverse effects and may suggest new indications for their repurposing. Furthermore, since depression is often a co-morbidity in patients with chronic conditions (i.e. cancer, neurodegenerative diseases) the use of antidepressants interfering with pathways in-volved in cell homeostasis may affect the progression and outcome of these pathologies. Here we investigate the effects of amitriptyline on proliferation and autophagy in human SH-SY5Y neuroblastoma cells. Dose and time-dependent upregulation of the autophagy markers LC3II and autophagy receptor p62, with accumulation of LAMP1 positive compartments, were observed in SH-SY5Y cells exposed to amitriptyline. Alteration of autophagy was accompanied by reduced cell viability and decreased clonogenic capacity, without a significant induction of apoptosis. Decrease viability and clonogenic activity were still observed in autophagy deficient Atg5 -/- MEF and following pre-treatment of SH-SY5Y culture with the autophagy inhibitor chloroquine suggesting that the amitriptyline’s effects on cell proliferation were not caused by the modulation of autophagy. Our findings demonstrate that amitriptyline acts on pathways that are crucial for cell and tissue homeostasis and pose the basis for further studies on the potential application of these effects and the consequences during long-term antidepressant treatment.

Tomato quality is intricately regulated by a combination of factors, including the presence of bioactive compounds referred to as secondary metabolites and various organoleptic characteristics. These attributes are notably influenced and harmonized by the specific growing conditions, with a particular emphasis on the type of fertilization employed. Traditionally, chemical fertilizers have been favoured in crop cultivation due to their cost-effectiveness and ability to accelerate crop growth. However, in pursuit of sustainable and intelligent agricultural practices, there is a growing need for alternative fertilizers. In this context, the present study aimed to assess the impact of fertilizers derived from waste materials, specifically sulphur bentonite and orange residue (referred to as SB), on tomato quality. This assessment extended to examining qualitative and quantitative alterations in aroma-related volatile compounds and the antioxidant systems of tomatoes, in comparison to the conventional use of fertilizers such as horse manure and NPK (nitrogen, phosphorus, and potassium). The results obtained revealed distinct effects of different fertilizers on tomato quality. Notably, parameters such as TPRO (total protein), TCARB (total carbohydrate), LIC (lycopene content), TCAR (total carotenoid content), total phenols, total flavonoids, and aroma profiling exhibited significantly superior values in the group treated with SB fertilizer. These findings strongly suggest that the novel fertilizer functioned as a bio-stimulant, enhancing the nutraceutical and sensory attributes of tomatoes, with a pronounced impact on the synthesis of secondary metabolites and the aroma profile of the fruits.

Soot is characterized by a multiscale structural organization and Transmission Electron Microscope (TEM) is the only diagnostic tool giving access to it. However, being a diffraction-based technique, TEM images only aromatic systems and thus, it is particularly useful to combine it with electron energy-loss spectroscopy (EELS), able to provide quantitative information about the relative abundance of sp3 and sp2 hybridized carbon. In this paper a method for the EELS spectrum analysis of carbonaceous materials recently developed for electron-irradiated graphite and glassy carbon composition analysis has been applied for the first time on soot samples, in order to test its performance in soot nanostructure study in combination with TEM and High Resolution TEM (HRTEM). Soot samples here analysed were collected in the soot inception region of premixed flames of different hydrocarbon fuels. EELS, in agreement with TEM and HRTEM, showed a quite disordered and heterogeneous structure for young soot, without any significant distinction between soot formed from methane and ethylene fuels.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

The COVID19 pandemic tested the performance of hospitals and intensive care units around the world. Health care workers (HCWs) have been used to develop mental symptoms, but this was especially true during the COVID19 pandemic when HCWs must deal with many other sources of stress and anxiety that can usually be avoided, and long-term shifts and unprecedented population restrictions have weakened people's ability to cope with stress. The research aims to observe the dynamic interplay between burnout, depression, distress, and anxiety in HCWs working in various settings, with specific a focus on Emotional exhaustion, depersonalization, and a diminished sense of personal achievement in mediating a worst mental health status during the first wave of the COVID19 pandemic in Italy. To analyze that we performed a mediation analysis, from which resulted a strong correlation among depression, psychological distress, health perception and anxiety, and the impact of job burnout on anxiety, depression, and distress. Gender seemed to have a strong correlation with burnout, anxiety, and distress; the impact of COVID19 pandemic on Quality of Life seemed to affect anxiety and depression; the changing of mansion influenced depression and job burnout. Encouraging supportive and educational strategies would certainly be recommended to policy makers.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

The aim of this study was to measure the effects on 3D active cervical Range of Motion (ACROM) and perceived pain of a n elastic taping (ET) application in the cervical area. Thirty participants (n: 22M and 8F, age 35.4±4.4 years; body height 173.1±8.4 cm; body mass 73.5±12.8 kg) for the study group (SG) and twenty subjects (n: 11M and 9F, age 32.6±3.9 years; body height 174.9±10.9 cm; body mass 71.2±12.9 kg) for the control group (CG) were recruited. All subjects were symptomatic for neck and cervical pain in baseline condition. Each group performed on ACROM test and the perceived pain on neck basing as Numerical Rating Scale (NRS 0-10, a.u.): at the baseline (T0); after 20' from ET application (T1); after three days of wearing the ET application (T2). Between T0 and T1 an ET was applied on the cervical area of the SG participants. Statistical analysis did not show any significant change in CG in any measurement session for ACROM and neck pain parameters. Conversely, the SG showed significant improvements for ACROM rotation left (T0 64.8 ± 7.7° - T2 76.0 ± 11.1° p &lt; 0.000) and right (T0 66.0 ± 11.9° - T2 74.2 ± 9.6° p &lt; 0.000); lateral inclination left (T0 37.5 ± 6.9° - T2 40.6 ± 10.8° p &lt; 0.000) and right (T0 36.5 ± 7.9° - T2 40.9 ± 5.2° p &lt; 0.000); flexion posterior (T0 47.0 ± 12.9° - T2 55.1 ± 12.3° p &lt; 0.001) and anterior (T0 55.0 ± 3.6° - T2 62.9 ± 12.0° p &lt; 0.006). A significant decrease was measure also in SG for pain NRS between T0 and T2 (T0 7.5 ± 1.0° - T1 5.5 ± 1.4 - T2 1.4 ± 1.5° p &lt; 0.000). In conclusion, the results of this study underline the usefulness of a bilateral and symmetrical ET cervical application in terms to enhance multiplanar ACROM and to reduce subjective self-perceived cervical pain when it is needed. These findings can be applied for managing musculoskeletal health of different kind of individuals.

Scaffolds for tissue engineering are expected to respond to a challenging combination of physical and mechanical requirements, guiding the research towards the development of novel hybrid materials. This study introduces innovative three-dimensional bioresorbable scaffolds, in which a stiff poly(lactic acid) lattice structure is meant to ensure temporary mechanical support, while a bioactive gelatin-chitosan hydrogel is incorporated to provide a better environment for cell adhesion and proliferation. The scaffolds present a core-shell structure, in which the lattice core is realized by additive manufacturing, while the shell is nested throughout the core by grafting and crosslinking a hydrogel forming solution. After subsequent freeze-drying, the hydrogel network forms a highly interconnected porous structure that completely envelops the poly(lactic acid) core. Thanks to this strategy, it is easy to tailor the scaffold properties for a specific target application, by properly designing the lattice geometry and the core/shell ratio, which are found to significantly affect the scaffold mechanical performance and its bioresorption. Compression stiffness and strength provided by poly(lactic acid) lattices are overall within the range of values displayed by human bone tissue and remain stable after prolonged immersion in water at body temperature for several weeks. On the other hand, the hydrogel undergoes gradual and homogeneous degradation over time, but the core-shell integrity and structural stability are nevertheless maintained during at least 7-week hydrolytic degradation tests. In vitro experiments with human mesenchymal stromal cells reveal that the core-shell scaffolds are biocompatible and their physical-mechanical properties and architecture are suitable to support cell growth and osteogenic differentiation, as demonstrated by hydroxyapatite formation. These results suggest that the bioresorbable core-shell scaffolds can be considered, and further studied, in view of clinically relevant endpoints in bone regenerative medicine.

nutrition, macro and micronutrients, bone health, exercise, exogenous and endogenous microRNA, epigenetics

Pregnancy in women with Sickle Cell Disease (SCD) is a high-risk situation, especially during the third trimester of gestation and in the post-partum period, due to chronic hypoxia and vaso-occlusive phenomena occurring in the maternal-fetal microcirculation: as a result, unfavorable outcomes, such as intra-uterine growth restriction, prematurity or fetal loss are more frequent in SCD pregnancies. Therefore, there is a consensus on the need for a strict and multidisciplinary follow-up within specialized structures. Transfusion support remains the mainstay of treatment of SCD pregnancies, although most appropriate modalities are still controversial: the benefit of prophylactic management, either by simple transfusions or by automated Red Blood Cell Exchange (aRBCX), is not unanimously recognized. We illustrate the cases of three SCD pregnant patients who underwent aRBCX procedures at our institution in different clinical scenarios. Moreover, we carried out a careful literature revision to investigate the management of pregnancy in SCD, particularly regarding the practice of aRBCX. Our experience and current literature support using aRBCX in pregnancy as a feasible and safe procedure provided that specialized equipment and an experienced apheresis team are available. However, further research in this high-risk population, with appropriately powered prospective trials, will be desirable to refine indications and timing of aRBCX and confirm this approach's advantages on other transfusion modalities.

Modern drugs have changed epilepsy, which affects people of all ages. But for young people with epilepsy, the framework of drug development has stalled. In the wake of the thalidomide catastrophe, the misconception emerged that for people <18y antiseizure medications (ASMs) need separate proof of efficacy and safety (E&S), overall called “pediatric drug development.” This has been corrected to some extent. Authorities accept that ASMs are effective in <18y as well, but they still require "extrapolation of efficacy," as if minors were another species. In our view, the real problem is less that relevant parts of pediatric clinical epilepsy research over the past decades were useless, but that this has hampered research on meaningful challenges. We do not need to show that ASMs work also before the 18th birthday. But we need to learn how to best use ASMs to prevent brain damage in young patients and optimize ASMs use considering a broader range of aspects

Brimonidine, a selective alpha-2 adrenergic agonist, used for treatment of open-angle glaucoma, has been shown to cause neurological side effects such as unresponsiveness, lethargy, hypoventilation, and stupor, mimicking opioid toxicity. We report one case of transient encephalopathy in a toddler, in whom brimonidine accidental toxicity was sus-pected and then confirmed by a toxicology study. The 8-month-old healthy girl child was taken to the pediatric ER since she was drowsy and hypotonic, with miosis. Brain CT scan and toxicological work-up on blood and urine were negative. Starting from hour +4, the child progressively improved, and by hour +6, she recovered to a normal state of consciousness. A survey of available drugs at the child’s reach showed the presence of brimonidine. Thus, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to quantify brimonidine in urine and plasma samples, showing 8.40 ng/mL level and 0.79 ng/mL, respectively. To our knowledge, this is the first report for determining brimonidine levels in urine and plasma by UPLC-MS/MS. Insufficient knowledge of the family members about the potential hazards of an apparently innocuous, topical medication such as eye drops may put children at a greater risk of poisoning. Necessary warnings should be better given to parents when prescribing this medication.

Coagulase-Negative Staphylococci (CoNS) are commensal on human body surfaces and for years, they were not considered a cause of bloodstream infection and were often regardered as contamination. However, the association of CoNS with nosocomial infection is increasingly recognized. The insertion of cannulas and intravascular catheters represents the first source of CoNS entry into the bloodstream, causing bacteremia and sepsis. They owe their pathogenic power to their ability to produce biofilms on surfaces, such as medical devices. In this study, we evaluate the adhesive capacity of CoNS isolated from blood cultures by comparing spectrophotometric phenotypic assay with genotypic analysis based on the evidence of the ica operon. We retrospectively reviewed the database of CoNS isolated from blood cultures, that were considered to be responsible for 361 bloodstream infections. Among them, we selected 89 ones who had full records. Our data show that S. epidermidis was the predominant species isolated, and with greater adhesive capacities, especially those with the complete operon. Knowing the adhesive capabilities of a microorganism responsible for sepsis can be useful in implementing appropriate corrective and preventive measures, as conventional antibiotic therapy cannot effectively eradicate biofilms.

This literature review was aimed to collect investigations on the in vivo evidences for bacteria associated to fermented dairy foods to behave as probiotics with beneficial effects in the prevention and treatment of various diseases. All main bacterial groups commonly present in high numbers in fermented milks or cheeses were taken into account, namely starter lactic acid bacteria (SLAB) Lactobacillus delbrueckii subsp. bulgaricus and lactis, L. helveticus, Lactococcus lactis, Strepto-coccus thermophilus, non starter LAB (NSLAB) Lacticaseibacillus spp., Lactiplantibacillus plantarum, dairy propionibacteria and other less frequently encountered species. Only studies regarding strains of proven dairy origin were considered. Studies in animal models and clinical studies showed that dairy bacteria ameliorate symptoms of inflammatory bowel disease (IBD), mucositis, metabolic syndrome, aging and oxidative stress, cancer, bone diseases, atopic dermatitis, allergies, infections and damages caused by pollutants, mild stress and depression. Immunomodulation and changes in the intestinal microbiota were the mechanisms most often involved in the observed effects. The results of the studies considered indicated that milk and dairy products are a rich source of beneficial bacteria that should be further exploited to the advantage of human and animal health.

The production of bio-chemicals requires the use of microbial strains with efficient substrate conversion and excellent environmental robustness, such as Bacillus coagulans spp. So far the genomes of about 50 strains have been sequenced. Herein, we report a comparative genomic analysis of nine strains on the full repertoire of CAZymes, secretion systems, and resistance mechanisms to environmental challenges. Moreover, B. coagulans Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) immune system along with CRISPR-associated Cas) genes, was also analysed. Overall, this study expands our understanding of the strains genomic diversity of B. coagulans to fully exploit its potential in biotechnological applications.

Temporomandibular disorders (TMDs) refer to a group of conditions that affect the temporomandibular joint, causing pain and dysfunction in the jaw joint and related muscles. The diagnosis of TMDs typically involved clinical assessment through operator-based physical examination, self-reported questionnaire and imaging studies. To objectivize the measurement of TMD, this study aims at investigating on the feasibility to use machine-learning algorithms fed with data gathered from low-cost and portable instruments to discriminate the presence of TMD in adult subjects. Through this aim, the experimental protocol involved fifty participants, equally distributed between TMD and healthy subjects, acting as control group. The diagnosis of TMD has been performed by a skilled operator through the typical clinical scale. Participants underwent to a baropodometric analysis by using a pressure matrix and the evaluation of the cervical mobility through inertial sensors. Nine machine-learning algorithms belonging to support vector machine, k-nearest neighbours and decision tree were compared. The k-nearest neighbours based on cosine distance was found as the best performing, achieving performance of 0.94, 0.94 and 0.08 for the accuracy, F1-score and G-index, respectively. These findings open the possibility to use such methodology to support the diagnosis of TMDs in clinical environments.

The microbiota in the oral cavity has a strict connection to its host. Its unbalance may determine oral diseases and can also have an impact on the systemic health. Probiotic strains may help in the restoration of a balanced condition. For this purpose, we screened the antibacterial and antiadhesive activities of many viable probiotic strains (Lactobacillus acidophilus PBS066, Lactobacillus crispatus LCR030, Lactobacillus gasseri LG050, Lactiplantibacillus plantarum PBS067, Limosilactobacillus reuteri PBS072, Lacticaseibacillus rhamnosus LRH020, Bifidobacterium animalis subsp. lactis BL050, Lacticaseibacillus paracasei LPC 1101, L. paracasei LPC 1082, and L. paracasei LPC 1114) against two main oral pathogens, Streptococcus mutans and Aggregatibacter actinomycetemcomitans, involved in dental caries and periodontal disease development and progression. Our results, obtained through agar overlay assay, plate count method, and scanning electron microscope imaging, indicate that the tested probiotics prevent the growth and adhesion of oral pathogens in a strain-specific manner, improving oral health. L. plantarum PBS067, L. rhamnosus LRH020, L. paracasei LPC 1101, L. paracasei LPC 1082, and L. paracasei LPC 1114 performed in a significant way against both pathogens in all the tests used. They can be considered as an effective adjuvant to guarantee oral and systemic well-being.

As of today, 20 disease modifying drugs (DMD) have been approved for the treatment of relapsing multiple sclerosis (MS) and, based on their efficacy, they can be grouped into moderate-efficacy DMDs and high-efficacy DMDs. The choice of the drug mostly relies on the judgement and experience of neurologists and the evaluation of therapeutic response can only be obtained by monitoring clinical and magnetic resonance imaging (MRI) status during follow up. In an era where therapies are focused on personalization, the aim of this study is to develop a modeling infrastructure to predict the evolution of relapsing MS and the response to treatments. We built a computational modeling infrastructure named UISS (Universal Immune System Simulator) able to simulate the main features and dynamics of the immune system activities. We extended UISS to simulate all the underlying MS pathogenesis and its interaction with the host immune system. This simulator is a multi-scale, multi-organ, agent based simulator with an attached module capable of simulating the dynamics of specific biological pathways at the molecular level. We simulated six MS patients with different relapsing-remitting courses. These patients were characterized on the basis of their age, sex, presence of oligoclonal bands, therapy and MRI lesion load at onset. The simulator framework is made freely available and can be used following the links provided in the availability section. Even though the model can be further personalized employing immunological parameters and genetic information, based on the available data we generated a few simulation scenarios for each patient, including those who matched the real clinical and MRI history. Moreover, for two patients, the simulator anticipated the timing of subsequent relapses, which really occurred, suggesting that UISS may have the potential to assist MS specialists in predicting the course of the disease and the response to treatment.

Outdoor exercise is beneficial for psychophysical well-being. Limited studies have compared outdoor and virtual reality (VR) indoor physical activities, especially in coastal settings. Therefore, this study aimed to assess the impact of outdoor coastal walking and indoor walking in a VR simulation with a similar environment on physiological and psychological variables in healthy adults. Twenty-six subjects (14M and 12F; age 25.2 ± 2.5 years) voluntarily participated in this crossover randomized controlled and counterbalanced study and were allocated under three conditions: VR indoor walking (INVR), outdoor walking (OUT) and standard indoor walking (IN). IN and INVR conditions were performed on a treadmill (speed 4.5 Km/h) and the OUT was per-formed on a seaside pedestrian road. The same outdoor environment was displayed in the visor during the INVR. Heart rate (HRmean/max), Physical Activity Enjoyment (PACES-It) and State of Mindfulness for Physical Activity (SMS-PA) were assessed at the end of each condition. The OUT condition showed significantly greater PACES-It scores and HRmean than IN and INVR (p<0.001) and greater SMS-PA scores and HRmax than IN (p<0.01 and p<0.05, respectively). No significant dif-ferences were found between OUT and INVR regarding HRmax and SMS-PA scores (p>0.05). Findings suggest that physical activity in an immersive technology may lead to physiological loads comparable to the outdoor environment. OUT is more enjoyable than IN and INVR but exhibits a mindfulness response comparable to INVR. Therefore, INVR could be an alternative to OUT for those who cannot engage in outdoor activities for various reasons.

This study refers to the optimization of a Selective Solar Absorber to improve the Sun-to-thermal conversion efficiency at mid temperatures in high vacuum flat thermal collectors. Efficiency has been evaluated by using analytical formula and a numerical thermal model. Both results have been experimentally validated using a commercial absorber in a custom experimental set-up. The optimization procedure aimed at obtaining Selective Solar Absorber is presented and discussed in the case of a metal dielectric multilayer based on Cr2O3 and Ti. The importance of adopting a real spectral emissivity curve to estimate high thermal efficiency at high temperatures in selective solar absorber is outlined. Optimized absorber multilayers can be 8% more efficient than the commercial alternative at 250 °C operating temperatures and up to 27% more efficient at 300 °C. Once the multilayer has been optimized the choice of a very low emissivity substrate such as copper allows to further improve efficiency and to reach stagnation temperature higher than 400 °C without Sun concentration.

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain com-pounds with fewer side effects, at the same time effectively overcoming the problem of antimi-crobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important sup-port for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of FT-ICR and LTQ mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribu-tion and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

Recent omics technologies have revolutionized the study of molecular plant responses to air pollution, overcoming previous limitations. This review synthesizes the latest advancements in molecular plant responses to major air pollutants, emphasizing ozone (O3), nitrogen oxides (NOX) and particulate matter (PM) research. These pollutants induce stress responses common to other abiotic and biotic stresses, including the activation of reactive oxygen species (ROS)-scavenging enzymes and hormone signaling pathways. New evidence showed the central role of antioxidant phenolic compound biosynthesis via phenylpropanoids pathway in air pollution stress responses. Transcription factors like WRKY, AP2/ERF, and MYB, which connect hormones signaling to antioxidant biosynthesis, were also affected. To date, research has predominantly focused on laboratory studies analyzing individual pollutants. This review highlights the need for comprehensive field studies and the identification of molecular tolerance traits, which are crucial for the identification of tolerant plant species aimed to the development of sustainable Nature Based Solutions (NBS) to mitigate urban air pollution.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamin-ergic neurons responsible for unintended or uncontrollable movements. Mutations in leu-cine-rich repeat kinase 2 locus, contributes to genetic forms of PD. The fruit fly Drosophila mela-nogaster carrying this mutation (LRRK2-Dm), is an in vivo model of PD that develops motor impairment and stands for an eligible non mammalian paradigm to test novel therapeutic ap-proaches. Dehydrozingerone (DHZ) is a natural phenolic compound isolated from ginger. Pre-sents anti-inflammatory, antioxidant and neuroprotective properties making it a potential therapeutic target for PD. We administered DHZ and its C2-symmetric dimer (DHZ-DIM) at 0.5 and 1mM, for 14 and 21 days, in the LRRK2-Dm, with the aim to assess changes for rescuing motor behavior, brain dopaminergic neurons, mitochondria and synapses (T-Bars). The shorter treat-ment with both molecules revealed efficacy at the higher dose improving climbing behavior with a prevention of dopaminergic neuronal demise. After 21 days, a recovery of the motor disability, dopaminergic neuron loss, mitochondrial damage and T-Bars failure was observed with the DHZ-DIM. Our data indicates that the DHZ-DIM exerts a more potent neuroprotective effect respect to the monomer in LRRK2-Dm, prompting further investigation of these compounds in rodent models of PD.

Aims: To date, precision medicine plays a pivotal role in the clinical administration of solid tumor patients. In this scenario, a rapidly increasing number of predictive biomarkers have been approved in diagnostic practice or are currently investigated in clinical trials. A pitfall in the molecular tests is the diagnostic routine sample available to analyze predictive biomarkers; scant tissue sample often represents the only diagnostical source of nucleic acids to assess molecular analysis. At the sight of these critical issues, Next Generation Sequencing (NGS) platforms emerged as referral testing strategy for molecular analysis of predictive biomarkers in routine practice but high-skilled personnel, extensive working-time drastically impact on the widespread diffusion of this technology in diagnostic setting. Here, we technically validate a fully integrated NGS platform on diagnostic routine tissue samples previously tested with NGS based diagnostic workflow by a referral institution. Methods: A retrospective series of n=64 samples (n=32 DNA, n=32 RNA samples), previously tested using a customized NGS assay (SiRe™ and SiRe fusion) were retrieved from internal archive of University of Naples Federico II. Each sample was tested by adopting Oncomine Precision Assay (OPA), able to detect 2769 molecular actionable alterations [hot spot mutations, copy number variations (CNV) and gene fusions on fully integrated NGS platform (Genexus, Thermofisher Scientifics. (26,27) Concordance rate between these technical approaches was carried out. Results: Genexus system successfully carried out molecular analysis in all instances. A concordance rate of 96.9% (31 out of 32) was observed between OPA and SiRe™ panel both for DNA and RNA based analysis. A negative predictive value of 100% and a positive predictive value of 96.9% (62 out of 64) was assessed. Conclusions: Fully automatized Genexus system combined with OPA (Thermofisher Scientifics) may be considered a technically valuable, saving time sequencing platform to test predictive biomarkers in diagnostic routine practice.

The liver health of Gilthead sea bream and European sea bass fed fishmeal-free diets including various proportions of plant proteins, insect and poultry by-product meals, was investigated through biochemical and histological analyses using a new Liver Index (LI) formula. Four isoproteic (45% DM) and isolipidic (20% DM) diets were compared: a control, plant-based diet (CV) and other three test ones where 40% of a plant protein-rich ingredient mixture was replaced by Hermetia illucens (H40) or poultry by-product (P40) meals alone or in combination (H10P30). The trials lasted 12 and 18 weeks for sea bream and sea bass, respectively. The results so far ob-tained highlighted species-specific differences in the physiological response to dietary changes. In sea bream, the biochemical and histological responses suggest favorable physiological status and liver health, with higher serum cholesterol (CHO) and triglyceride (TAG) levels and moderate hepatocyte lipid accumulation with the H10P30 diet compared to CV (p<0.05). In sea bass, all diets resulted in elevated serum TAG levels and liver lipid accumulation particularly in fish fed the P40 one (p<0.05) which resulted in the highest LI, coupled with higher frequency of severe lipid accumulation, hypertrophy, cord loss, peripheral nuclei displacement and pyknosis. In conclusion sea bream well adapted to the test diets, while sea bass exhibited altered hepatic lipid metabolism leading to incipient liver steatosis, likely due to the high lipid content of the diets including the insect and poultry meals. The LI developed in this study proved to be a reliable tool for assessing the effects of dietary changes on liver health of sea bream and sea bass, consistent with biochemical and histological findings.

A new Pd(II) complex of the previously reported ligand N,N′-bis[(2,2′-dihydroxybiphen-3-yl)methyl]-N,N′-dimethylethylenediamine (L) was obtained from a DMF/H2O mixture. It differs from a Pd(II) complex of L previously obtained by sole DMF. The roles in the solid state assembly of solvent molecules and molecular conformation (driven by specific transition metal ions) were studied by comparing six complexes of L containing different metal centers (Ni(II), Cd(II), Cu(II), Pd(II)). Hirshfeld surface analysis, 2D fingerprint plots and energy frameworks calculations were used to investigate the intermolecular interactions within the crystal packing of the six complexes. As suggested by interaction energies, Pd(II) and Ni(II) complexes arrange to form ribbons, while Cd(II) and Cu(II) complexes form 3D networks. Interactions between complexes and solvent molecules in the previous Pd(II) complex are replaced by complex-complex interactions in the new Pd(II) complex, while BuOH and MeOH are interchangeable in the interactions within the crystal packing of the two Ni(II) complexes. Finally, solvent molecules are not involved in the crystal packing of the Cu(II) complex. The present study suggested that the solid state assembly of these systems is mainly driven by the molecular conformation, that depends in turn by the metal ion involved, while the solvent only plays a minor role.

In this study electrophoretic deposition (EPD) technique is used to prepare chitosan-based coatings with enhanced antibacterial activity suitable for bone implants applications. We designed, prepared and compared physic-chemical and biological properties of coatings obtained with commercial chitosan, chitosan enriched with silver nanoparticles and chitosan obtained from insects. With the aim to consider the sustainability issue, silver nanoparticles were directly prepared in the chitosan solution by laser ablation in liquid technique, avoiding the use of chemicals and limiting the production of wastes. Moreover, a sustainable source of chitosan such as Hermetia Illucens exuviae was considered. The EPD process was optimized by adjusting parameters like voltage and deposition time to achieve ideal coating thickness and adhesion. The prepared films were characterized by spectroscopic and microscopic techniques such as SEM, XRD, and FTIR. Antimicrobial tests against E. coli and S. aureus revealed that silver nanoparticles enhanced the antibacterial properties of the polymer, whereas biological evaluation using the WST8 test on MG63 human osteoblasts-like cells showed that all coatings are non-toxic. Finally, chitosan obtained from insect showed comparable properties with respect to the commercial polymer, suggesting it could replace seafood-derived chitosan in biomedical applications, whereas the Ag@chitosan composite demonstrated superior antibacterial activity without compromising its biocompatibility.

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

(1) Background: A wide literature based on loading and unloading bending tests has been carried out over the half past century for assessing the force released by superelastic wires. The aim of this investigation is not only to characterize a broadly described superelastic NiTi and a novel CuNiTi archwire, but also to provide novel insights into the load vs deflection profiles. A harmonic scenario for superelastic wires will be shown as temperature is kept constant at 37°C. However, a completely different picture will be highlighted as a temporary heating step up to 50°C is introduced within the force vs deflection profiles. (2) Methods: A variety of NiTi and a novel CuNiTi round and rectangular cross-section archwires have been investigated. Static 3-point bending tests up to a deflection level of 3.0 mm have been carried out for detecting the unloading force plateau levels occurring at 37°C. A hold deflection step of 5 min at deflection levels occurring along the unloading plateau extension is introduced. The effect of a temporary heating up to 50°C on the force plateau level released by the investigated wires is analyzed. (3) Results: Mechanical profiles suggest that the plateau force levels detected at 37°C are consistent with those broadly reported in the literature, but they only represent a single block puzzle of the force scenario that a superelastic wire releases during the orthodontic treatment. (4) Conclusions: Once a superelastic wire is bent and clinically applied, the effect of a temporary heating up to 50°C (e.g. hot food or drink ingestion) produces a significant plateau force increase whose magnitude depends on the deflection level. The highest force increase of about 50% and 40% have been detected at deflection levels located at the beginning of the unloading plateau extension for NiTi and CuNiTi wires, respectively.

Abdominal entry is the critical initial step of laparoscopic surgery as it is associated with unexpected complications. Acceptable working space is a prerequisite for safe minimal access surgery. Direct trocar insertion (DTI) technique has been often reported to be time-consuming and capable of causing injuries. We aim to facilitate conventional DTI employing an easy-to-use self-designed abdominal wall-lifting device, OneShot-M. We tested its safety in a porcine model. 18 pigs were randomized into three groups (n=6): open laparoscopy (Group A), DTI (Group B), DTI using OneShot-M (Group C), suitable for a 5-mm trocar. Outcomes were access time, entry-related minor and major complications. Median access time was shorter in C (43 seconds; range: 35-49 seconds), followed by B (82.5; 72-90) and A (190.5; 182-240). Statistically significant differences in procedural time between techniques were detected (p-value = 0.0005). Pairwise comparisons exhibited a statistically significant difference between A and C in terms of access time. Only one difficulty in entry was seen in C; pigs experienced several occurrences in A and B. This pilot study suggests that OneShot-M appears to be a technically feasible, fast and safe method for pneumoperitoneum induction in a porcine model, as it provides sufficient exposure of the operative field without access-related complications. Further clinical studies are needed.

Background: Fabry disease cardiomyopathy (FDCM) has manifested some resistance to enzyme replacement therapy (ERT) particularly in its advanced phase. Recently myocardial inflammation of autoimmune origin has been demonstrated in FDCM. Aims: Aim of the study is the assessment of circulating anti-globotriaosylceramide (GB3) antibody as biomarker of myocardial inflammation in FDCM. Its sensitivity was based on the evidence of overlapping myocarditis at left ventricular endomyocardial biopsy. Methods and Results: From January 1996 to December 2021, 85 patients received in our Department the histological diagnosis of FDCM and 48 (56.5%) of them had an overlapping myocardial inflammation with negative PCR for the common cardiotropic viruses, positive anti-heart and anti-myosin abs. The presence of anti-GB3 antibodies was evaluated with an Elisa assay (BioGeM scarl Medical Investigational Research, MIR - Ariano Irpino, Italy) in the FDCM patients and compared with controls of healthy individuals. Circulating levels of anti-GB3 autoantibodies were compared with the presence or absence of myocardial inflammation at histology and with the severity of FDCM. The assay results showed that 42 out of 48 FDCM subjects with myocarditis were positive for anti-Gb3 antibodies while 30 out of 37 FDCM patients without myocarditis had negative anti-GB3 antibodies, with a sensitivity of 87.5 % and a specificity of 83.5%. Conclusions: The present study suggests a potential positive role of antiGB3 antibodies as marker of overlapping cardiac inflammation in patients with FDCM.

Chorioamnionitis (CA) at term of pregnancy can have infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (Intrauterine Inflammation, Infection or both, TI) has been proposed to reduce the overdiagnosis of infection and the neonatal overtreatment. The aim of the study is to identify clinical and histological variables predicting adverse outcomes when TI has been suspected and/or confirmed. This retrospective cohort study included 404 pregnancies ≥37 g.a. that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to NICHD definition of 2015 and it could be confirmed (TI+) or not (TI-) by histological examination. Signs of infection/inflammation not respecting the definition of TI were classified as “Clinical suspicion”, supported (CS+) or not (CS-) by histology. Histological chorioamnionitis (HCA) without clinical manifestation represented fifth group. Whole Placental Involvement (WPLI), was defined as a histological inflammation involving maternal and fetal side. There were 113 TI+, 30 TI-, 186 CS+, 35 CS- and 40 isolated HCA. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). TI+ compared to CS+ was more predictive of CNO (p=0.001), CMO (p<0.001) and WPLI (p=0.005). WPLI was related both to CNO (p<0.001) and CMO (p=0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p=0.001) and by WPLI (OR 2.23; p=0.001). TI, compared to CS, is a better predictor of CNO and can be useful for the identification of newborns at risk.

Although decision making strategy based on clinico-histopathological criteria is well established, renal cell carcinoma (RCC) represents a spectrum of biological ecosystems characterized by distinct genetic and molecular alterations, diverse clinical courses and potential specific therapeutic vulnerabilities. Given the plethora of drugs available, the subtype-tailored treatment to RCC subtype holds the potential to improve patient outcome, shrinking treatment-related morbidity and cost. The emerging knowledge of the molecular taxonomy of RCC is evolving, whilst the antiangiogenic and immunotherapy landscape maintained and reinforced their potential. Although several prognostic factors of survival in patients with RCC have been described, no reliable predictive biomarkers of treatment individual sensitivity or resistance have been identified. In this review, we summarize the available evidence able to prompt more precise and individualized patient selection in well-designed clinical trials, covering the unmet need of medical choices in the era of next-generation anti-angiogenesis and immunotherapy.

Durum wheat is an important staple food used to obtain several products. At first the wheat is milled to obtain different products: bran, semolina and flour. These products are the base of several artifacts with varying properties both from a nutritional point of view and flavoring characteristics. It is known that most elements concentrate in the outer layers of the wheat seed (pericarp and aleurone) so that the content of the elements vary a lot in the ground products. The present study investigates the characterizing elements of the milled products and the effect of cultivation protocol applied. We measured, by ICP-OES, the concentration of 28 elements in the whole seed and in any grinding products; the results show that only few elements characterize each product. Few elements, but different for each product, permit to disclose the kind of agri-cultural method used: organic or conventional protocol. Five elements: B, Cd, Cu, K, Se, are the most important to distinguish between organic and conventional agriculture by PCA and PLS analysis; these elements also permit some differentiation of products.

Cancer cells show an increased glutamine consumption. The glutaminase (GLS) enzyme controls a limiting step in the glutamine catabolism. Breast tumors, especially the triple negative subtype, have a high expression of GLS. Our recent study demonstrated that GLS activity and ammonia production are inhibited by Sirtuin 5 (SIRT5). We have developed MC3138, a selective SIRT5 activator. Treatment with MC3138 mimicked the deacetylation effect mediated by SIRT5 overexpression. Moreover, GLS activity is regulated by inorganic phosphate (Pi). Considering the interconnected role of GLS, SIRT5 and Pi for cancer growth, our hypothesis is that activation of SIRT5 and reduction of Pi could represent a valid anti-tumoral strategy. Treating cells with MC3138 and lanthanum acetate, a Pi chelator, decreased cell viability and clonogenicity. We also observed a modulation of LC3 and ULK1 with MC3138 and lanthanum acetate. Interestingly, inhibition of mitophagy marker BNIP3 was observed only in the presence of MC3138. Such autophagy and mitophagy modulation was accompanied by an increase of cytosolic and mitochondrial reactive oxygen species (ROS). In conclusion, our results show how SIRT5 activation and/or Pi binding can represent a valid strategy to inhibit cell proliferation by reducing glutamine metabolism and mitophagy leading to a deleterious accumulation of ROS.

A bread wheat line (N11) and a disomic 2D(2R) substitution triticale line have been crossed and backrossed four times. At each step electrophoretic selection for the seeds that possessed, simultaneously, the complete set of high molecular weight glutenin subunits of N11 and the two high molecular weight secalins of rye, present in the 2D(2R) line, was carried out. Molecular cytogenetic analyses of the BC4F5 generation have revealed that the selection carried out had produced a disomic addition line (2n=44). The pair of additional chromosomes consisted of the long arm of chromosome 1R (1RL) from rye fused with the satellite body of the wheat chromosome 6B. Rheological analyses revealed that the dough obtained by the new addition line had higher quality characteristics when compared with the two parents. The role of the two additional high molecular weight secalins, present in the disomic addition line, in influencing improved dough characteristics is discussed.

Seafood products are the main dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, due to the widespread use of processed fish products, the presence of these n-3 PUFAs may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, with a focus on n-3 polyunsaturated fatty acids (n-3 PUFAs), in different processed fish and shellfish food of EU and non-EU origin purchased in supermarkets and ethnic food shops in Messina (Italy), using gas chromatography with flame-ionization detector (GC-FID). From the fatty acid profile, the atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.31-9.84 (TI) and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids had the following ranges: 13.55-50.48%, 18.91-65.58%, 13.84-52.73%, respectively. All samples showed a good presence of PUFAs and, in particular, eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were the main n-3 polyunsaturated fatty acids (n-3 PUFA).

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is commonly enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer causing viruses.

Despite the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitor-urinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response as PD-L1 expression, tumor mutational burden, and clinical features. In addition to the identification of the patients with a high sensibility to immune checkpoint inhibitors, another approach currently under intensive investigation is the use of therapeutics in a combinatory manner with immune checkpoint inhibitors to obtain an enhancement of efficacy through the modification of the tumor immune microenvironment. In addition to the abscopal effect induced by radiotherapy, a lot of studies are evaluating several drugs able to improve response rate to immune checkpoint inhibitors, including microbiota modifiers, drugs targeting co-inhibitors receptors, anti-angiogenic therapeutics, small molecules, and oncolytic viruses. In view of the rapid and extensive development of this research field, we conducted a systematic review of the literature identifying which of these drugs are closer to achieving validation in the clinical practice.