Marine Protected Areas (MPAs) are vital for biodiversity conservation, yet their effectiveness in preserving foundation seaweeds remains understudied. This study investigates the diversity and distribution of Cystoseira sensu lato (including Cystoseira, Ericaria and Gongolaria) populations in the an MPA located in the central Mediterranean Sea, comparing them with those in two unprotected control sites. We hypothesize that MPA Cystoseira s.l. populations will display higher diversity and structure compared to outside control sites. Results reveal a total of 19 Cystoseira s.l. species at depths of 0-20 m, with the MPA exhibiting a higher diversity than control sites. Thus, MPAs can play a crucial role in fostering the diversity of Cystoseira s.l. populations. However, no significant differences were observed among the MPA's protection zones, raising questions about the zoning effectiveness. Additionally, our survey uncovered a substantial presence of non-indigenous seaweeds within the MPA. In conclusion, while MPAs improve Cystoseira s.l. diversity compared to unprotected sites, the varying efficacy of protection within MPA zones suggests a necessity for site-specific conservation strategies. The presence of non-indigenous seaweeds emphasizes ongoing challenges. This study provides a baseline for understanding Cystoseira s.l. population dynamics, crucial for future monitoring and conservation efforts in the face of climate change.

The use of alternative synthetic methods, in the face of traditional processes that do not conform to the principles of Green Chemistry, represent a problem in the pharmaceutical industry. The procedures for the synthesis of benzimidazole derivatives have become a focus in synthetic organic chemistry, as they are building blocks of strong interest for the synthesis of compounds with pharmacological activity. Various benzimidazole derivatives have found very strong application in medicine and their synthesis is reported in the literature. A simple and environmental Montmorillonite K10 (MK10) catalyzed method for the synthesis of benzimidazole derivatives has been developed. The use of MK10 as heterogeneous catalysis provides various advantages in terms of yields, in the work up procedure of the reaction, selectivity and the possible recycle of catalyst without waste formation. The reactions were carried out in solvent free condition and in short reaction time using an inexpensive and environmentally friendly heterogeneous catalysis and it has been shown that the reaction process is applicable in the industrial field.

The simplest elasticity model of foundation underlying a slender beam under flexure was conceived by Winkler, requiring local proportionality between soil reactions and beam deflection. Such an approach leads to well-posed elastostatic and elastodynamic problems, but, as highlighted by Wieghardt, it provides elastic responses which are not technically significant for a wide variety of engineering applications. Thus, Winkler's model was replaced by Wieghardt himself by assuming that the beam deflection is the convolution integral between soil reaction field and an averaging kernel. Due to conflict between constitutive and kinematic compatibility requirements, the corresponding elastic problem of an inflected beam resting on Wieghardt foundation results to be ill-posed. Modifications of the original Wieghardt model were proposed by introducing fictitious boundary concentrated forces of constitutive type, which are physically questionable, being significantly influenced on prescribed kinematic boundary conditions. Inherent difficulties and issues are overcome in the present research using a displacement-driven nonlocal integral strategy got by swapping input and output fields involved in Wieghardt's original formulation. That is, nonlocal soil reaction fields are output of integral convolutions of beam deflection fields with an averaging kernel. Equipping the displacement-driven nonlocal integral law with the bi-exponential averaging kernel, an equivalent nonlocal differential problem, supplemented with non-standard constitutive boundary conditions involving nonlocal soil reactions, is established. As a key implication, the integro-differential equations governing the elastostatic problem of an inflected elastic slender beam resting on displacement-driven nonlocal integral foundation are replaced with much simpler differential equations supplemented with kinematic, static and new constitutive boundary conditions. The proposed nonlocal approach is illustrated by examining and analytically solving exemplar problems of structural engineering. Benchmark solutions for numerical analyses are also detected.

Keywords: Pain; Nociception; Disorders of Consciousness; Consciousness

Amyloids result from the aggregation of several unrelated proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being put in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms, and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which make it plausible that more effective drugs will be developed in the future.

The implications related to the fight against alien organisms often affect different sectors, from the economic to the landscape one or from the public health to the ecological one. This paper is an upgrade of our previous study focused on the evolution of the red palm weevil in a coastal urban area (central Italy); we investigate the evolution of this parasite in the following period (2013-2020), considering both the effectiveness of the chemicals used and their potential effects. With a multidisciplinary approach, on the one hand we carried out a spatio-temporal analysis to analyze the extent and mode of pest spread over time using historical aerial photos, freely available remote sensing images and field surveys, integrated in a GIS environment, and on the other hand we performed an assessment of the chemical risk associated with the substances used to protect the palms from the red weevil. The fight against weevil is now concentrated in specific areas (parks, relevant roads, villas, hotels, farmhouses, nurseries); the applied preventive chemical treatments are very effective in preserving the palms, but they show a toxic potential for all organisms. We discuss current local management of this pest focusing on the several aspects involve into the fight against this beetle in an urban area.

In the last decade, the drone market has grown rapidly for both civil and military purposes. Due to their versatility, drones demand is constantly increasing, with several industrial players joining the venture to transfer urban mobility to the air. This has exacerbated the problem of noise pollution, mainly due to the relatively lower altitude of these vehicles and to the proximity of their routes to extremely densely populated areas. In particular, both the aerodynamic and aeroacoustic optimization of the propulsive system and of its interaction with the airframe are key aspects of the design of aerial vehicles for the success or the failure of their mission. The industrial challenge involves finding the best performance in terms of loading, efficiency and weight, and, at the same time, the most silent configuration. For this reason, research has focused on an initial localization of the noise sources and, on further analysis, of the noise generation mechanism, focusing particularly on directivity and scattering. The aim of the present study is to review the noise source mechanisms and the state-of-the-art technologies available in literature for its suppression, focusing especially on the fluid-dynamic aspects of low Reynolds numbers of the propulsive system and on the interaction of the propulsive-system flow with the airframe.

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evalua-tion. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP, as-sessing its accuracy, timing, safety, and future technological improvement. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a cru-cial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visu-alization of the pancreas, biliary system, and adjacent structures. High accuracy of EUS is evident in detecting the actual causes of IAP such as microlithiasis, small bile duct stones, pancreas divisum, and small pancreatic tumors. Optimal timing for EUS is post-resolution of the acute phase of the disease. EUS, when conducted by experienced endoscopists, it boasts minimal safety concerns, and is crucial to prevent complications. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in cytological analy-sis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicenter prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.

Genetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. The present study aims at scanning 70 single-point mutations on the APP gene in a publicly available genetic dataset including 2.504 healthy individuals from 26 populations, and analyzing their distribution. Moreover, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations have been detected in the worldwide dataset, with several of them being specific for a single individual, population or macroarea. Patterns of segment sharing reflect recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups, and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementias.

The geographic variability of the dorsal pattern (DP) of the Italian wall lizard, Podarcis siculus, across its native range was studied with the aim to understand whether the distributions of this phenotypic trait were more shaped by allopatric differentiation rather than adaptive processes. A total of 1298 georeferenced observations scattered across the Italian peninsula and the main islands (Sicily, Corsica and Sardinia) were obtained from citizen science databases and five DPs were characterized by different shapes of the dark pattern (“reticulated”, “campestris”, “reticulated/campestris” and “striped”) or by absence of it (“concolor”). Frequencies of different DP phenotypes differ between the two main mtDNA lineages settled in central-northern and in southern Italy respectively. This pattern may be indicative of a role of long-term allopatric historical processes in determining the observed pattern. The analysis also identified a putative wide area of secondary contact, in central southern Italy, characterized by high diversity of the DP. Generalized Linear Models (GLMs), used to estimate a possible association between bioclimatic variables and the observed phenotypic variation, showed that each of the five DPs is correlated to different environmental factors and show different distribution of areas with high probability of occurrence. However, for all but one of the DPs, the area with the greatest probability does not correspond exactly to the real distribution of the DP. Conversely, the “concolor” phenotype does not seem related to any particular mtDNA lineage and it shows a preference for areas with high temperature and low rainfall. This is in agreement with the expectation of low amount of melanin of the dorsal pattern that, in the study areas, is characterized by a light uniform coloration which could confer a better thermoregulation ability in high temperatures environments avoiding overheating.

Climate change is one of the biggest challenges of our times. Its impact on human populations is not yet completely understood. Many studies have focused on single aspects with contradictory observations. However, climate change is a complex phoenomenon that cannot be adequately addressed from a single discipline's perspective. Hence, we propose a comprehensive conceptual framework on the relationships between climate change and human responses. This framework includes biological, psychological and behavioural aspects, and provides a multidisciplinary overview and critical information for focused interventions. The role of tipping points and regime shifts is explored, and a historical perspective is presented to describe the relationship between climate evolution and socio-cultural crisis. Vulnerability, resilience and adaptation are analyzed from an individual and a community point of view. Finally, emergent behaviours and mass effect phenomena are examined that account for mental maladjustment and conflicts.

The development of Artificial Intelligence-based tools is having a big impact on industry. In this context, the maintenance operations of important assets and industrial resources are deeply changing both from a theoretical and a practical perspective, even in the field of ship propulsion systems. Namely, conventional preventive maintenance schedules audits and checks at fixed times by using statistics on component failures, but it can be improved by a predictive maintenance based on the real component health status, which is inspected by proper sensors. In this way, time and costs are saved. More in details, data-driven models, through Machine Learning (ML) algorithms, generate the expected values of monitored variables for comparison with real measurements coming from the asset, hence for a diagnosis based on the difference between expectations and observations. Then, a ML-based fault detection starts with the choice of the ML algorithm. This process is often not the consequence of an in-depth deep analysis of the different algorithms available in the literature. For that reason, the authors propose a simple procedure to support a first implementation stage of the so-called Condition Based Maintenance (CBM): a quick benchmarking of the most suitable ML algorithms useful for fault detection. The algorithms are compared by taking into account not only the algorithm output error, shown by the Mean Squared Error between predictions and data, but also the response time, which is a crucial variable for maintenance purpose.

Relationships between geoheritage and cultural heritage are increasingly becoming a topic of study, especially in urban contexts. Their integrated reading adds value for educational and urban geotourism purpose, being the latter an emerging sector of sustainable tourism. The case study of the monumental complex of San Francesco le Moniche, built in the ancient Norman county Aversa, in the northern Campania (Italy), is analyzed here. The cultural heritage of the monumental complex and the additional value associated with the natural heritage (geological and geomorphological context, building stones) have been linked. The building stratification of the complex has been read not only from documentary sources, but also from the distribution and architecture of the existing underground cavities, the building stones, from ancient images and even postcards, integrating disciplines such as geosciences, architecture, archaeology, speleology, engineering. The results provide a clear example of a geoheritage-cultural heritage interface and the importance of an integrated approach in the valorization of the cultural and natural heritage of urban areas. The results allowed us to improve the knowledge of the study site and provide useful tools for the planning of future targeted investigations.

Listeria ivanovii and L. monocytogenes, are the only pathogenic species of the genus Listeria and share many virulence factors and mechanisms of pathogenicity. L. ivanovii shows host tropism towards small ruminants and rodents and much lower virulence for humans compared to L. monocytogenes. However, severe infections caused by L. ivanovii, resulting in bacteremia, abortion and stillbirth, occasionally occurred in immunocompromised persons and in pregnant women, while in immunocompetent hosts L. ivanovii can cause gastroenteritis. In this review the updated knowledge on virulence aspects and distribution of L. ivanovii in the environment and in food are summarized. Recent research on its virulence characters at genome level gave indications on how pathogenicity evolved in this bacterial species. As for L. monocytogenes, L. ivanovii infections occur after the ingestion of contaminated food, so an overview of reports regarding its distribution in the food products was carried out to obtain indications on the categories of foods exposed to contamination by L. ivanovii. It was found that a wide variety of food products can be a source of this microorganism and that, like L. monocytogenes, L. ivanovii is able to persist in the food production environment. Studies on its ability to grow in enrichment and isolation media suggested that its occurrence in nature might be underestimated. Moreover, virulence varies among strains for differences in virulence character regulation, presence/absence of genetic regions and the possible instability of a Listeria pathogenicity genomic island, LIPI-2, which is unique to L. ivanovii. We can conclude that L. ivanovii, as a possible pathogen for animals and humans, requires more focused investigations regarding its occurrence in the environment and in food and on intra-species variability of pathogenic potential.

Although the field of geomatics has seen multiple technological advances in the recent years which enabled new applications and simplified the consolidated ones, some tasks remain challenging, inefficient, and time- and cost-consuming. This is the case of accurate tridimensional surveys of narrow spaces. Static laser scanning is an accurate and reliable approach but impractical for extensive tunnel environments; portable laser scanning is on the other hand time-effective and efficient but not very reliable without ground control constraints. This paper describes the development process of a novel image-based multi-camera system meant to solve this specific problem: delivering accurate, reliable, and efficient results. The development is illustrated from the system conceptualization and initial investigations to the design choices and requirements for accuracy. The resulted working prototype has been put to the test to verify effectiveness of the proposed approach.

Background: Swimming and, specifically, front crawl, can be included among the "overhead" sports. Overhead sports are a risk factor for some problems of the musculoskeletal system, especially the shoulder. The aim of the study was assessing the incidence of shoulder and neck pain in a Masters Swimming Team and its correlation with the crawl stroke. Methods: It is an observational study through video-analysis of the stroke and a questionnaire. The participants are 61 athletes of a Master team, whose prevailing training stroke was the front crawl were selected for the present study. Their stroke was analyzed during training by a go-pro camera mounted on a sliding trolley on a track, evaluating with their trainer their technical defects. A questionnaire about frequency of shoulder and neck pain during the last five years was administered to all the participants at the study. Results: From the questionnaire, 45 and 55 out of 61 athletes had suffered from shoulder pain and cervical pain, respectively. Both types of pain were correlated with the weekly swimming volume. The swimmers with hyperflexion of the wrist and prolonged internal rotation in the pulling phase had shoulder problems. Those who suffered from current shoulder pain reduced the underwater time. The four swimmers with an excessive body roll during breathing and those who kept their heads extended, reported cervical pain. Conclusions: Shoulder and neck pain could be prevented with the correction of specific technical errors in crawl stroke.

Background: Restorative materials might significantly affect load transmission at peri-implant bone. The aim of the present study is to evaluate the shock absorption capacity of two different polymeric materials to be used as frameworks for implant-supported prostheses. Methods: A masticatory robot was used to compare the shock absorption capacity of polyether-ketoneketone (PEKK) Pekkton®ivory (Cendres+Mètaux) and glass fiber-reinforced composite (GFRC) TRINIATM (Bicon). Five identical sample crowns for each of the materials was tested un-der the same conditions described in previously published papers (Menini et al. 2013). Forces transmitted at the simulated periimplant bone were recorded and statistically analysed. Results: The statistical analysis of forces transmitted at the simulated dental implant revealed significant differences between all the materials tested and significant differences with the mate-rials tested in a previously published paper (Menini et al. 2013: zirconia, glass ceramic, composite resin, acrylic resin). Only differences between PEKK and veneered PEKK and between PEKK and one of the previously tested composite resins were not statistically significant. PEKK samples demonstrated significantly greater shock absorption capacity compared to GFRC. Conclusions: PEKK revealed optimal shock absorption capacity. Further studies are needed to evaluate its efficacy in case of long span prostheses with reduced prosthetic volume.

In the Republic of Moldova, nearly 90% of all deaths are due to noncommunicable diseases (NCDs), tha majority of which (58%) are caused by cardiovascular disease (CVD). Excess salt (sodium) and inadequate potassium intakes are associated with high CVD. Moreover, salt iodisation is the preferred policy to prevent iodine deficiency and associated disorders. However, there is no survey that has directly measured sodium, potassium and iodine consumption in adults in the Republic of Moldova. The aim is to estimate population sodium, potassium and iodine intakes and explore knowledge, attitudes and behaviour (KAB) towards the use of salt, amongst the adult population in the Republic of Moldova. Proportional random samples of adults were obtained from 28 of the 37 Districts and Municipalities and one Administrative Territorial Unit of Moldova. Participants attended a screening including demographic, anthropometric and physical measurements. Dietary sodium, potassium and iodine intakes were assessed by 24h urinary sodium (UNa), potassium (UK) and iodine (UI) excretions. Creatinine was measured. KAB was collected by questionnaire. Eight hundred and fifty-eight participants (326 men and 532 women, 18–69 years) were included in the analysis (response rate 66%). Mean age was 48.5 yrs (SD 13.8). Mean UNa was 172.7 (79.3) mmoL/day, equivalent to 10.8 g of salt/day and potassium excretion 72.7 (31.5) mmoL/day, equivalent to 3.26 g/day. Men ate more sodium and potassium than women. Only 11.3% of the sample had a salt intake below the World Health Organization (WHO) recommended target of 5 g/day and approximately 39% met WHO targets for potassium excretion (>90 mmoL/day). Whilst 81.7% declared limiting their consumption of processed food and over 70% declared not adding salt at the table, only 8.8% looked at sodium content of food, 31% still added salt when cooking and less than 1% took other measures to control salt consumption. Measures of awareness were significantly more common in urban compared to rural areas. Mean urinary iodine was 225 (SD: 152; median 196) mcg/24h, with no difference between sexes. According to WHO criteria, 41.0% had adequate iodine intake, 28.6% had intake below requirements and 17.8% and 12.6% had above requirement or excessive levels, respectively. Iodine content of salt table was 21.0 (SD: 18.6) mg/kg, with no difference between men and women. However, the content was lower in rural than urban areas (16.7 [SD: 18.6] vs 28.1 [SD: 16.5] mg/kg, p<0.001). There were weak or no correlations between urinary sodium and iodine excretions, and between urinary iodine excretion and iodine concentration in the table salt used in the participants’ households, indicating that in most cases participants were not using iodised salt as their main source of salt, more so in rural areas. In the Republic of Moldova, salt consumption is unequivocally high, potassium consumption is lower than recommended, both in men and in women, whilst iodine intake is still inadequate in 1 in 3 people, although severe iodine deficiency is rare. Salt consumed is often not iodised, with less iodised salt being used in rural areas.

The effects of the climate crisis are affecting ecosystems at different scales and magnitudes. This paper focuses on a massive Mediterranean mussel die-off observed along the middle Italian Adriatic coast in the summer of 2022. We considered the possible environmental causes of this phenomenon and carried out a climatic analysis of the last decade. We performed field surveys in different locations along a 16 Km coastal stretch (from Martinsicuro (TE) on the South, to Grottammare (AP) on the North). The study area includes two marine Sites of Community Importance under the European Natura 2000 network. The mussels die-off has interested practically all the natural mussel-beds colonizing the study area. Mussels are sessile filter-feeding organisms inhabiting the intertidal zone, therefore, are highly exposed to variations in environmental conditions such as temperature and nutrient load. We discuss the possible causes of this die-off, proposing that high temperature and the scarce availability of food acted simultaneously as stress factors, generating local unsustainable living conditions for this species.

Extracts from parts of coniferous trees have received increased interest due to their valuable bioactive compounds and properties, useful for plenty of experimental and consolidated applications, in fields comprising nutraceutics, cosmetics, pharmacology, food preservation, and stimulation of plant growth. However, the variability of the bioactive properties, the complexity of the extraction methods, and the use of potentially harmful synthetic chemicals, still represent an obstacle to the spreading of such valuable natural compounds. Hydrodynamic cavitation is emerging as a promising innovative technique for the extraction of precious food components and by-products from waste raw material of the agro-food production chain, which can improve processing efficiency, reduce resource consumption, and produce healthy, high-quality products. In this study, a process based on controlled hydrodynamic cavitation was applied for the first time to the production of aqueous solutions of silver fir (Abies Alba Mill.) needles with enhanced antioxidant activity. The observed levels of the in vitro antioxidant activity, comparable or higher than those found for reference substances, pure extracts, and other water extracts and beverages, highlight the very good potential of the HC process for the creation of solvent-free, aqueous solutions endowed with bioactive compounds extracted from silver fir needles.

A rather large portion of the population is sleep restricted in modern society, either by necessity or by choice. Epidemiological studies have observed that lack of sleep and poor sleep quality are associated with several pathological states, ranging from neuropsychiatric to metabolic diseases. To date, only a few studies have investigated the molecular consequences of sleep loss at the level of peripheral organs involved in maintaining metabolic homeostasis such as the white adipose tissue (WAT). From a molecular point of view, two key transcriptional regulators of WAT function are sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptors gamma (PPARγ). Both genes interact with specific targets involved in multiple metabolic processes, including adipocyte differentiation, browning and lipid metabolism. In this study, we assessed the effects of chronic sleep restriction (CSR) on the interplay between SIRT1 and PPARγ in mediating WAT metabolism in young adult mice. We found that CSR up-regulated expression of SIRT1 and some of its transcriptional targets involved in lipid metabolism and mitochondrial functions of adipocytes. Results suggest that CSR induces SIRT1-mediated metabolic remodeling of WAT to support an increased energy demand due to sleep loss.

In 2011 over 1.7 million people were hospitalized because of a fragility fracture, and direct costs associated with osteoporosis treatment exceeded 70 billion dollars in the United States. Failure to reach and maintain optimal peak bone mass during adulthood is a critical factor in determining fragility fracture risk later in life. Physical activity is a widely accessible, low cost, and highly modifiable contributor to bone health. Here, we will review the evidence linking exercise and physical activity to bone health in women. Bone structure and quality will be discussed, especially in the context of clinical diagnosis of osteoporosis. We will review the mechanisms governing bone metabolism in the context of physical activity and exercise. Questions such as, when during life is exercise most effective, and what specific types of exercises improve bone health, will be addressed. Finally, we will discuss some emerging areas of research on this topic, and will summarize areas of need and opportunity.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

Is the production of the “AnchoisFert” organic fertilizer via the circular economy process based on omega-3 lipid extraction of milled anchovy fillet leftovers with citrus limonene followed by mild drying economically and technically viable? This study answers this question and identifies the main obstacles, chiefly of economic and organizational nature, to be overcome prior to commercialization of this new organic fertilizer. Along with non-variable and proven efficacy, successful competition with conventional organic and inorganic fertilizers requires affordable cost and regular supply. This, inter alia, requires to establish new and mutually beneficial relationship between bioeconomy firms and fish processing companies.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., pro-NGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the “ideal” candidate in mediating Aβ-induced neuropathology. Besides pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.

Abandoned, lost, or otherwise discarded fishing gear (ALDFG) is a primary contributor to the entanglement of numerous marine species. Utilizing digital media platforms like Google, Facebook, and Instagram we conducted an assessment of the detrimental effects of ALDFG and plastic litter, on the biodiversity of Italy's marine ecosystem. Our investigation revealed that plastic litter has adverse consequences on various forms of marine life, including reptiles, mammals, birds, fish, crustaceans, and mollusks, along different Italian geographical sub-areas. Several records of interaction between plastic and endangered and vulnerable marine species have been described. Our reports even highlight the impact on marine turtles, mainly on Caretta caretta. This is the first report of entangled with fishing nets in Cetorhinus maximus, Oblada melanura, Serranus scriba, Homarus gammarus, Octopus vulgaris, and Phoenicopterus roseus. Furthermore, we identified that ghost nets have repercussions for endangered and vulnerable marine species. This update sheds light on the ongoing adverse effects of ghost nets on the Italian marine ecosystem, yet it is crucial to acknowledge that the true extent of the problem remains underestimated.

Background: Micro-RNAs (miRNA) are emerging as biomarkers in the detection and prognosis of cancers due to their inherent stability and resilience. Methods: To summarize evidence regarding urinary miRNA (umiRNAs) role in the detection, prognosis and therapeutic management of urological cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary mir-na)AND(prostate cancer); (urinary mirna)AND(bladder cancer); (urinary mirna)AND(renal cancer); (urinary mirna)AND(testicular cancer); (urinary mirna)AND(urothelial cancer). Results: Of all, 1364 articles were initially selected. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. Urinary miRNA (UmiRNAs) are downregulated in prostate cancers and may serve as potential non-invasive molecular biomarkers. Several umiR-NAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BCa), allowing to discriminate malignant from non-malignant forms of haematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle invasive BCa and could predict the aggressivity and prognosis of muscle-invasive BCa. In renal cell carcinoma, miRNAs have been identified as predictors of tumour detection, aggressiveness, and progression to metastasis. Conclusion: umiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique that modulates synaptic plasticity in the human motor cortex (M1). Since previous studies have primarily used motor evoked potentials (MEPs) as outcome measure, cortical correlates of PAS-induced plasticity remain unknown. Therefore, the aim of this observational study was to investigate cortical correlates of a standard PAS induced plasticity in the primary motor cortex by using a combined TMS-EEG approach in a cohort of eighteen healthy subjects. In addition to the expected long-lasting facilitatory modulation of MEPs amplitude, PAS intervention also induced a significant increase in transcranial magnetic stimulation evoked potentials (TEPs) P30 and P60 amplitude. No significant correlation between the magnitude of PAS-induced changes in TEP components and MEP amplitude were observed. However, the linear regression analysis revealed that the combined changes in P30 and P60 component amplitudes significantly predicted the MEP facilitation after PAS. The findings of our study offer novel insight into the neurophysiological changes associated with PAS-induced plasticity at M1 cortical level and suggest a complex relationship between TEPs and MEPs changes following PAS.

This paper is a thorough review of innovative architectures of electro-hydraulic servovalves that exploit actuation systems based on piezo-electric materials. The use of commercially available piezo-electric actuators, namely, piezo-stacks, amplified piezo-stacks, rectangular benders and ring benders, is very promising for the actuation of the main stages and of the pilot stages of servovalves, given the fast response and low weight of piezoelectric materials. The use of these actuators can also allow novel designs to be developed, thus helping manufacturers to overcome the typical drawbacks of commercial servovalves, such as the high complexity and the high internal leakage of the pilot stages of two stage servovalves, as well as the large size and weight of direct drive servovalves. Firstly, the piezoelectric actuators that can be used for driving servovalves are presented in the paper and their characteristics are thoroughly discussed. Then, the main novel architectures present in the literature are explained and compared with the commercial ones, and their performance parameters are discussed to draw conclusions on the prospect that some of these architectures can be used by manufacturers as future designs.

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p < 0.001). Its concentration >2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values >5.1 nmol/l and urine TIMP2*IGBP7 levels > 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

(1) Background: Mobile health (mHealth) solutions can become means of improving functional recovery and reducing the peri-operative burden and costs associated with arthroplasty procedures. Aim of this study is to explore the objectives, functionalities, and outcomes of a platform designed to provide personalized surgical experiences to qualified patients, along with the associated problems and opportunities. (2) Methods: A survey-based analysis was conducted on patients who were prescribed the use of a specific care management platform and underwent primary Robotic total knee arthroplasty (rTKA) between January 2021 and February 2023. (3) Results: Patients registered on the platform who have undergone primary Robotic TKA (rTKA) were considered. The mean age of registered patients is 68,6 years. The male (M) / female (F) ratio is 45.1% / 54.9%. The patients interviewed were at an average distance of 485 days from the intervention, with a standard deviation of 187.5. The survey highlighted appreciation for the App and its features but limits in its use and in its perception from the patients. All these data were evaluated according to the Wald principles and strategies to improve patient recruitment, enhance adherence, and create a comprehensive patient journey for optimized surgical experiences were analyzed. (4) Conclusions: This patient care platform may have the potential to impact surgical experiences by increasing patient engagement, facilitating remote monitoring, and providing personalized care. There is the need to emphasizes the importance of integrating the recruiting process, improving adherence strategies, and creating a comprehensive patient journey within the platform

-529391451442Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).0Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Abstract: SARS-CoV-2 vaccination offered the opportunity to get out of the pandemic and thereby worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe but side effects are being reported more frequently as more and more people around the world become treated. Myo-pericarditis is the major, but not the only cardiovascular complication of this vaccine, hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database emerged that heart rhythm disorders after Covid vaccination are not uncommon and deserve more clinical and scientific attention. Since Covid vaccine is the only vaccination to have been related to this side effect questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit is clearly in favor of vaccination heart rhythm disorders are not a negligible issue and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we investigated the potential mechanism for the Covid vaccine to impact on cardiac electrophysiology and cause heart rhythm disorders.

The biological heterogeneity of glioblastoma (GBM), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing the clinical progression over the time. The understanding and monitoring of the mutational profile is important not only to reveal novel therapeutic targets in this set of patients, but also to ameliorate the clinical stratification of subjects and the prognostic significance. As neurosurgery represents the primary technique to manage GBM, it is of outmost importance to optimize alternative and less invasive methods to monitor the dynamic mutation profile of these patients. Extracellular vesicles (EV) are included in the liquid biopsy analysis and have emerged as the biological mirror of escaping and surviving mechanisms by many tumors as well as glioblastoma. Very few studies have investigated the technical feasibility to detect and analyze the genomic profile by Next Generation Sequencing (NGS) in circulating EV of patients with grade IV glioblastoma. Here, we attempted to characterize and to compare with the corresponding matched tissue samples, potential variants with pathogenic significance of the DNA contained in peripheral blood derived EV. The NGS analysis has revealed that patients with grade IV glioblastoma, exhibited lesser DNA content in EV than controls and that both in EV and matched cancer tissues, the NF1 gene was consistently mutated in all patients with the c.2568C&gt;G as the most common pathogenic variant expressed. This study supports the clinical utility of the circulating EV in glioblastoma and as eligible tool for personalized medicine.

Background: Though tyrosine kinase inhibitors managed to reach outstanding responses in the treatment of Chronic Myeloid Leukemia, resistance is still a challenging point, occurring in approximately 10–20% of the cases, due to several mechanisms. STAT5 expression has been strictly linked to resistance and disease progression and may thus represent a significant target to overcome resistance to TKI in CML. The aim of the study is to explore the in vitro antineoplastic role of the STAT5 inhibitor Pimozide in association with 2nd and 3rd generation inhibitors on chronic myeloid leukemia cells. Methods: The cytotoxic effect was evaluated by the Trypan blue dye exclusion test. K562 cell lines were exposed to pimozide alone and in association with ponatinib and dasatinib at different concentrations to explore the drugs association effect and the in vitro cytotoxic concentrations. Conclusions: Pimozide showed a synergic effect when associated with ponatinib and dasatinib in survival inhibition of K562 cell lines. This results are of note and pave the way for a possible in vivo associations.

Background: Anthropometric measurements play a crucial role in medico-legal practices. Actually, several scanning technologies are employed in post-mortem investigations for forensic anthropological measurements. This study aims to evaluate the precision, in-ter-rater reliability, and accuracy of a hand-held scanner in measuring various body parts. Methods: Three independent raters measured seven longitudinal distances using an iPad Pro equipped with a LiDAR sensor and specific software. These measurements were sta-tistically compared to manual measurements conducted by an operator using a laser level and a meterstick (considered the gold standard). Results: The Friedman’s test revealed minimal intra-rater variability in digital measurements. Inter-rater variability analysis yielded an ICC=1, signifying high agreement among the three independent raters. Addi-tionally, the accuracy of digital measurements displayed errors below 2%. Conclusions: Preliminary findings demonstrate that the pairing of LiDAR technology with the Polycam app showcases high precision, inter-rater agreement, and accuracy. Hand-held scanners show potential in forensic anthropology due to their simplicity, affordability, and porta-bility. However, further validation studies under real-world conditions are essential to es-tablish the reliability and effectiveness of handheld scanners in medico-legal settings.

A renewable cyclic monoterpene obtained from citrus peel, limonene is widely used as a fra-grance, nutraceutical ingredient, antibacterial, biopesticide, and green extraction solvent. Indus-trial demand largely exceeds supply. After reviewing recent advances in the recovery of limonene from citrus peel and residues with a particular attention to benign-by-design extractive processes, we focus on the latest results in its dehydrogenation to p-cymene via heterogeneous catalysis.

This retrospective observational study describes the results of an ad-hoc designated prevention protocol aimed at containing the spread of the scabies infestation among healthcare workers (HCWs) of a large University Hospital in Italy. The outbreak started on October 2022 and a preventive protocol was set up thanks to a multidisciplinary approach. HCWs at high scabies risk were defined as subjects working in UOs with more than five confirmed cases of scabies, close contacts of a confirmed case of scabies, or HCWs with signs and symptoms of the disease. All cases of at high scabies risk underwent a dermatological examination and the infested HCWs were suspended from work until definitive healing. Mass prophylactic treatment was established for all HCWs working in UOs with more than five confirmed cases of scabies. Until March 2023, out of 183 screening dermatological examinations, 21 (11.5%) were diagnostic for scabies. We obtain a prevalence of scabies of 2.6% (21/800) and a duration of the outbreak of 14.7 weeks. Statistical analysis shows a significant association between scabies and being a nurse and have an allergy to dust mites. We obtained a low prevalence of scabies infection, limiting the duration of the outbreak and the related economic burden.

This study presents the results of a research project financed by the Lazio Regional Government. The research focused on defining an integrated model of recent alluvial deposits in the Tiber River. To achieve this objective, geological boreholes were made to monitor the aquifer and in situ and laboratory tests carried out. The data obtained was used to detail stratigraphic aspects and improve the comprehension of water circulation beneath the recent alluvial deposits of the Tiber River in the urban area of Rome, between the Ponte Milvio bridge and the Tiber Island. The stratigraphic intervals recognised in the boreholes were parameterised based on their litho-technical characteristics. The new data acquired, and integrated with existing data in the CNR IGAG database, made it possible to produce a three-dimensional model of the lithologies in the study area.The model of the subsoil, simplified for applied reasons, was described in hy-drostratigraphic terms: three different lithotypes were subjected to piezometric levels monitor-ing. Finally, the research generated a numerical hydrological level in a stationary regime. In general, this study demonstrates how a numerical hydrogeological model calibrated by piezo-metric monitoring data can support the construction of a geological model, discarding or con-firming certain hypotheses and suggesting other means of reconstructing sedimentary bodies.

This study evaluates for the first time the plastic litter occurrence in Posidonia spheroids of four Mediterranean sandy beaches at different anthropogenic impact. A total of 80 spheroids was analyzed and 202 plastic items were found. Spheroids entangled a high number of plastic litter (132 plastic items/kg) with significant differences between beaches. Our results highlight the importance to implement the beach cleaning plan for the removal of all spheroids in order to prevent them from flaking and releasing the marine litter trapped inside them again in the environment. Spheroids should be manually removed in order to protect the banquettes. The removal should be involved all spheroids, independently from their size. This study adds data for the implementation of the monitoring program of marine litter and contributes to the development of specific management measures as well as implement Mediterranean action plans.

Background: Patients with thromboembolic disease, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Although common professional oral hygiene might not represent a health concern for these patients, anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to investigate the bleeding time of different anticoagulants and antiplatelets during a professional hygiene session adapting the Ivy test to the oral environment; Methods: 93 consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn’s post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; Results: Control patients presented the lowest bleeding time 50 sec, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p=0.004), VKA (p&lt;0.001), DAPT (p&lt;0.001). Conclusions: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. However, bleeding did not interfere with the oral hygiene ses-sion The optimal period for dental treatment of these patients should be 2-3 hours before the next dose, without the need to temporarily suspend the medication.

In this study, 737 individual sheep milk samples were collected to evaluate the relationships between Brix refractometer measurements and milk constituents—particularly, protein and fat percentages—with the aim of verifying the ability of the refractometer to predict milk constituents. The Pearson's simple (rSP) and partial (rPP) correlations between milk constituents were calculated, and several first- and second-order regressions were tested to predict the protein and fat percentages. The results of the forecasts can be considered satisfactory only for the simple regression that predicted the percentage of milk protein through the measurements read with the Brix refractometer (PRT = -2.996 + 0.639*Brix), while the regression that predicted the percentage of fat + milk protein presented a weak forecasting capacity, which was probably due to the absence of partial correlations between the Brix refractometer measurements and the fat percentage.

Antibiotics have played a crucial role in the reduction of TB incidence globally as evidenced by the fact that before the mid-20th century, the mortality rate within five years of the onset of the disease was 50%. The use of antibiotics has eliminated TB as a devastating disease, but the challenge of resistance to anti-TB drugs, which had already been described at the time of the introduction of streptomycin, has become a major global issue in disease management. Mismanagement of multidrug-resistant tuberculosis (MDR-TB) cases, resulting from intermittent drug use, prescription errors and non-compliance of patients, has been identified as a critical risk factor for the development of extensively drug-resistant tuberculosis (XDR-TB). Antimicrobial resistance (AMR) in TB is a multi-factorial, complex problem of microbes evolving to escape antibiotics, the gradual decline of antibiotic development, and different economic and social conditions. In this review, we summarise recent advances in our understanding of how Mycobacterium tuberculosis evolves drug resistance. We also highlight the importance of developing shorter regimens that rapidly reach bacteria in diverse host environments, eradicating all mycobacterial populations and preventing the evolution of drug resistance. Lastly, we also emphasise that the current burden of this ancient disease is driven by a combination of complex interactions between mycobacterial and host factors, and that only a holistic approach that effectively addresses all the critical issues associated with drug resistance will limit the further spread of drug-resistant strains throught the community.

The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multiresistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.

This short review is aimed at giving an overview of catalytic carbonylative double cyclization reactions, which are processes in which suitable organic substrates and carbon monoxide are sequentially activated by a promoting catalyst to afford the formation of two new cycles with concomitant incorporation of carbon monoxide as a carbonyl function into the final product. Paradigmatic examples of this powerful synthetic methodology, which allows the one-step synthesis of complex molecular architectures from simple building blocks using the simplest and readily available C-1 unit (CO) are illustrated and discussed. The review is divided into five sections: 1) Introduction; 2) Functionalized Olefinic Substrates; 3) Functionalized Acetylenic Substrates; 4) Functionalized Halides; 5) Conclusions and Future Perspectives.

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as health care-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.

Objectives: To rate the effects of low molecular weight hyaluronic acid (LMWHA) solution and high concentration oxygen (HCO) through a specific medical device (Caress Flow©), compared to topical administration of hyaluronic acid (HA) alone on symptoms of mild and moderate stress and mixed urinary incontinence in women with genitourinary syndrome of menopause (GSM). Methods: A total of 68 postmenopausal women were enrolled (from October 2021 to September 2023). Patients were separated in two groups: one group used therapy with LMWHA solution and HCO combined and the second group used therapy with HA alone. Patient Global Impres-sion of Improvement (PGI-I) as the first outcome was used. As secondary outcomes International Consultation on Incontinence Questionnaire - short form (ICIQ-SF) questionnaire and Internation-al Quality of Life (IQoL) questionnaire were used. Results: Sixty-eight (68) women, 35 (51%) and 33 (49%), were treated with LMWHA solution and HCO combined and HA alone for 10 weeks, respectively. 28 (80%) versus 7 (20%) women reported an improvement (PGI-I score ≤3) of the symptoms in LMWHA solution and HCO com-bined group versus HA alone group. According to the ICIQ-SF, a statistically significant differ-ence was recorded after treatment between the two groups (median, 7 [5-11] vs 10 [8-11]; P = 0.03). According to the IQoL questionnaire, a statistically significantly lower median score was recorded in the LMWHA solution and HCO combined compared with the HA group, before (71 [IQR 55-81] vs 89 [IQR 67-94]; P < 0.01) and after (78 [IQR 65-86] vs 88 [IQR 72-99]; P = 0.04) treatment. Conclusions: LMWHA solution and HCO combined might improve the mild and moderate stress and mixed urinary incontinence in this set of women and that it is superior to HA therapy alone. However, these results need to be confirmed in further studies with a controlled design and a larger population.

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

In this study, we present a statistical forecasting framework and assess its efficacy using a range of established machine learning algorithms for predicting Particulate Matter (PM) concentrations in the Arctic, specifically in Pallas (FI), Reykjavik (IS), and Tromso (NO). Our framework leverages historical ground measures and 24-hour predictions from 9 models provided by the Copernicus Atmosphere Monitoring Service (CAMS) to provide PM predictions for the following 24 hours. Furthermore, we compare the performance of various memory cells based on artificial neural networks (ANN), including recurrent neural networks (RNNs), gated recurrent units (GRUs), long short-term memory networks (LSTMs), echo state networks (ESNs), and windowed multi-layer perceptrons (MLPs), which are commonly employed in time series forecasting tasks. Irrespective of the chosen memory cell type, our results demonstrate that the proposed framework consistently outperforms the CAM models in terms of mean squared error (MSE), with average improvements ranging from 25% to 40%. Additionally, we investigate the impact of outliers on the overall model performance.

The article focuses on the integrated environmental accounting model called 'eValue', developed for protected areas and applied in the research programme coordinated by the Italian Ministry of the Environment and aimed at implementing an environmental accounting system for Italian Marine Protected Areas (MPAs). eValue adopts a cost-benefit analysis approach. Financial accounting based on costs and revenues is integrated with environmental accounting, which reflects environmental costs and environmental revenues, i.e. environmental benefits. The environ-mental costs assess the impacts related to human activities in the MPA expressed by calculating the carbon footprint and the environmental benefits of the marine ecosystem services calculated by applying monetary valuation techniques. The values thus estimated flow into the annual flow account, where the value produced (or consumed) by the MPA is estimated by difference. The eValue model was applied to the Porto Cesareo MPA (Italy). eValue showed that the annual benefit-cost ratio reaches a value of 3.4. Furthermore, the ratio of net benefit to public funding is 3.7, completely covering the amount of public transfers and thus summarizing the MPA overall value for money.

Seizures are defined as a transient occurrence of signs and symptoms due to the abnormal, excessive or synchronous neuronal activity in the brain characterized by an abrupt and involuntary skeletal muscles activity. An early diagnosis, treatment and specific medical support must be performed to prevent Status Epilepticus (SE). Seizures’ onset, especially in children population, is related to specific risk factors like positive family history, fever, infections, neurological comorbidity, premature birth, mother’s alcohol abuse and smoke in pregnancy. Early death risk in children without neurological comorbidity is similar to the general population. Diagnosis is generally based on the identification of continuous or recurrent seizures but EEG evaluation could be useful if SE condition in suspected. The main goal of therapy is to contrast pathological mechanism which occurs in SE before neural cells are irreversibly damaged. According to latest International Guidelines and Recommendations of seizures’ related diseases, it is proposed a schematic and multi-stage pharmacological and diagnostic approach especially in the management of SE and its related causes in children. First measures should focus on early and appropriate drugs administration at adequate dosage, airway management, monitoring vital signs, PICU admission and management of parents’ anxiety.

Quantum chemical topology addresses the study of the chemical structure by applying the tools of differential topology to scalar and vector fields obtained by quantum mechanics. Here the magnetically induced isotropically averaged Lorentz force density has been computed and topologically analysed for 11 small molecules. Critical points (attractors, repellers and saddles) have been determined and trajectories connecting the attractors have been computed. It is shown that kinds and numbers of the critical points are rather transferable in similar molecules. CC bonds of different order are endowed with critical points of different kind close to their centre. The long range behaviour of the force allows understanding the value of the sum of topological indices of the isolated critical points.

Background: Sarcoma may show similarities to malignant melanoma in terms of morphologic and immunohistochemical aspects, hence making it difficult to differentiate between these two neoplasms during the diagnostic process. This systematic review aims to summarize available evidence on cases of sarcoma that were initially diagnosed as melanoma. Methods: A comprehensive search was conducted including MEDLINE/Pubmed, EMBASE and SCOPUS through March 2023. We included case series and case reports of sarcoma patients that were initially diagnosed as malignant melanoma. PRISMA guidelines were followed. Results: Twenty-three case reports and four case series with a total of 34 patients were included. The clinical presentation was heterogeneous, and the most involved anatomical regions were lower limbs (24%), head/neck (24%) and upper limbs (21%). IHC positivity was reported for S100 (69%), HMB45 (63%), MelanA (31%) and MiTF (3%). The main reasons for second assessment were unusual presentation (48%) and uncertain diagnosis (28%). EWSR1 translocation was investigated in 17/34 patients (50%) and found positive in 16/17 (94%). The final diagnosis was clear cell sarcoma (50%) or other soft tissue sarcomas (50%). Conclusions: Melanoma and some histotypes of sarcoma share many similarities. In case of atypical lesions, a second diagnosis should be considered, and ESWR1 translocation should be investigated.

Obesity and metabolic disorders can be risk factors for the onset and development of neurodegenerative diseases. The aim of the present study was to investigate the protective effects on dysmetabolism and neurodegeneration of a natural dietary supplement (NDS), containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin, on the brains of high fat diet (HFD)-fed mice. A decreased expression of FACL-4, CerS-1 and CerS-4, reduced cholesterol concentration, increased IR expression and insulin signaling activation, were found in brains of NDS-treated HFD mice, suggesting that NDS is able to prevent brain lipid accumulation and central insulin resistance. In the brains of NDS-treated HFD mice, the levels of RNS, ROS and lipid peroxidation, the expression of p-ERK, H-Oxy, i-NOS, HSP60, NF-kB, GFAP, IL-1β, IL-6, and CD4 positive cell infiltration were lower than in untreated HFD mice, suggesting antioxidant and anti-inflammatory effects of NDS. The decreased expression of p-ERK and GFAP in NDS-treated HFD mice was confirmed by immunofluorescence. Lastly, a lower number of apoptotic nuclei was found in cortical sections of NDS-treated HFD. All these data indicate that NDS exerts neuroprotective effects in HFD mice by reducing brain fat accumulation, oxidative stress and inflammation and improving brain insulin resistance.

Urinary tract infections (UTIs) are a prevalent bacterial infection in both community and healthcare settings. They account for approximately 40% of all bacterial infections and require around 15% of all antibiotic prescriptions. Although antibiotics have traditionally been used to treat UTIs for several decades, the significant increase in antibiotic resistance in recent years has made many previously effective treatments ineffective. Biofilm on medical equipment in healthcare settings creates a reservoir of pathogens that can be easily transmitted to patients. Urinary catheter infections are frequently observed in hospitals and are caused by microbes that form a biofilm after the catheter is inserted into the bladder. Managing infections caused by biofilms is challenging due to the emergence of antibiotic resistance. Biofilms enable pathogens to evade the host's innate immune defences, resulting in long-term persistence. The incidence of sepsis caused by urinary tract infections that have spread to the bloodstream is increasing, and drug-resistant infections may be even more prevalent. While the availability of upcoming tests to identify the bacterial cause of infection and its resistance spectrum is critical, it alone will not solve the problem; innovative treatment approaches are also needed. This review analyses the main characteristics of biofilm formation and drug resistance in recurrent uropathogen-induced UTI. The importance of innovative and alternative therapies to combat biofilm-caused UTI is emphasised.

Many historic buildings and monuments on the Salento Peninsula (Apulia, southern Italy) were built from locally quarried Miocene calcarenites belonging to the Pietra Leccese Formation (Late Burdigalian-early Messinian). The main facies consists of a homogeneous and porous biomicrite, pale yellow in color and fine- to medium-grained, very rich in planktonic Foraminifera and massive or thick-bedded in outcrop. Additionally, there are other facies among which Piromafo stands out for its aesthetic appearance, which is enhanced by its greenish-brown or greenish-grey colors. Its physical characteristics, in terms of thermal properties mainly due to the mineral content and fabric, make it a good refractory and insulation material. Piromafo occurs in the upper part of the Pietra Leccese Fm. and is repre-sented by a fine- to medium-grained glauconitic and phosphatic biomicrite with macrofossils, es-pecially Bivalves and Gastropods. Despite its important historical use as building and ornamental material, especially in the Roman and Baroque architecture, a research gap exists in the scientific literature describing the properties of the stone and their correlation. Therefore, the aim of this paper is to present a wide range of properties useful to explain the in-situ behavior and damage susceptibility of the stone in monu-ments and buildings, but also for selecting preservation treatments and strategies. Thus, an overall assessment of the main petrophysical and mechanical properties especially for restoration/conservation purposes was performed using both standard and unconventional tech-niques. Starting from rock fabric inspection, particular attention was given to the relationship be-tween pore-size distribution and, hydraulic and thermal properties of the material. Unconfined compressive strength, flexural strength and indirect tensile strength were also estimated.

Cars are a highly inefficient mode of urban transport with significant negative impacts. Electric vehicles make it possible to eliminate direct CO2 emissions (though the total over a vehicle’s entire life cycle greatly offsets the advantages) but leave unchanged – or even aggravate – all the other negative effects on the quality of urban environments. Three visions for urban transport were presented: automobility, multimodality and accessibility. The first dominates North American cities, the second European one. The anomalies of these two visions have been examined. The automobility cities cannot manage the congestion and the attempts are self- defeating. The anomalies of multimodality city are related to the public space consumption for mobility and the impossibility to plan spatial proximity. The sustainable vision, that resolve the anomalies, is represented by the accessibility city in the Triple Access System (TAS) version which, however, still has a long way to go to be accepted and implemented.

Overuse and misuse of antibiotics can pose the risks of spreading mutant strains that show antimicrobial resistance (AMR), with negative impact on management of bacterial infections and economic implications on healthcare systems. Research and development of natural antibacterial agents could be a priority in the next years to improve number of effective antibacterial molecules and to reduce AMR phenomenon and its development. The present study identified the most effective concentration and contact time of Thymus vulgaris L. essential oil (TEO) to obtain bactericidal effect in vitro against different Gram + and Gram – bacterial strains. Six clinically isolated (wild types) bacterial strains, (Citrobacter freundii, Enterococcus feciorum, Proteus mirabilis, Acinetobacter cioffi, Pasteurella putrefaciens, Klebsiella pneumoniae) and two ATCC (Staphylococcus aureus and Streptococcus mutans) were tested after 1min, 3min and 5min of contact with TEO. Preliminary results on S. aureus after 24h incubation revealed a TEO concentration of 9.28mg/mL (w/v) that completely inhibited bacteria growth keeping cell viability. Total suppression of bacterial growth at all tested contact times was observed for all tested bacterial strains and the results were confirmed after 48h incubation. Bacterial growth suppression was confirmed even with presence of organic component. These preliminary results showed in vitro antimicrobial efficacy of TEO against different Gram+ and Gram- bacterial strains. Future studies are necessary to confirm the reproducibility of these results even on other strains and to define exactly the molecular mechanisms of EOs, in order to consider TEO as a valid alternative of classic antibiotic therapies and subsequently to reduce the occurrence of AMR.

Despite the successes earned in cataloguing and finding the role of the most of molecular components in living matter, the “biochemical and molecular” perspective, popular in biology, medicine and genetics, is unable to give account for crucial topics as the faculty of living systems to “feel”, to “perceive” what a given stimulus implies (means, indeed) for their survival. Condensed matter physics too, if bounded to a local, short-range, and perturbative approach, fails dramatically. This is also due to the role commonly assigned to water – actually the main constituent of living matter – deemed for long time to be merely chemical (as “solvent” or a reactant/product). Nonetheless, today many evidences show how living matter can be right conceived as a super-structured coherent water-based matrix, suggesting that the characterization of bio(electro)chemical and physical processes undertaken at molecular level in living matter, would let us unable to answer a question like this: what allows an amoeba, moreover without any neurons, to “know” to get closer to a nutrient or escape away from a toxin? I propose that to pursue such a fundamental inquiry it’s necessary an essentially relational approach, that is: to consider the living being at its grounding as the outcome of a physical history of relationships where symmetry-breakings, dissipation and coherence yield the emergence of the living state of matter, conceivable only as a time-dependent open process, and not as a portraited “body”. The effective tools to build up such an approach may be retrieved in far-from-equilibrium thermodynamics (TD), symmetry-breakings and gauge-fields theory, science of complexity, within the framework of a Quantum Field Theory. Indeed, within a field-view of matter, and of water especially, as it has been developed by a Quantum Electrodynamic (QED) description of condensed matter, it’s possible to give account for a physical basis too such an epistemologically elusive, though crucial, feature of living systems (i.e.: perception and meaning). The emerging landscape allows some important meditations about adaptation, evolution, ecodynamics, and about different conceptions of complexity and “information” in living realm. Furthermore, some neuroscientific themes like consciousness, qualia and their links to artificial intelligence could be supplied with due insights.

Background The main aim of reconstructive surgery (RS) is to restore the integrity of soft tissues damaged by trauma, surgery, congenital deformity, burns or infection. Microsurgical techniques consist of harvesting tissues that are separated from the vascular sources of the donor site and anastomosed to the vessels of the recipient site. In these procedures, there are some preoperative modifiable factors that have the potential to influence the outcome of the flap transfer and its anastomosis. Methods Chronic inflammatory anaemia (ACD) is a constant condition in patients who have undergone RS and correlates with the perfusion of the free flap. In RS, it is important to maintain good tissue oxyporesis, avoiding blood hyperviscosity. From January 2017 to September 2019, we studied 16 patients (16 males, mean age 38 years) who underwent microsurgical procedures for RS. Haemoglobin (Hb) levels, Corpuscular Indexes, Transferring saturation (TSAT) ferritin concentrations and creatinine clearance have been measured the first day after surgery (T0), after the first week (T1) and after five weeks (T2). At T0 all patients showed low hemoglobin levels (average 7.4 g/dl, STD 0,71range 6,2-7,4 g dL-1), with an MCV of 72, MCH 28, MCHC 33, RDW 16, Sideremy 35, Ferritin 28, Ret% 1,36, TRF 277 and Creatinine Clearance 119. . We assessed all patients for clinical status, medical history and comorbidities before starting therapy. Results. In collaboration between the two departments, we started a therapeutic protocol with erythropoietic stimulating agents (ESAs) (Binocrit 6000 UI/week) and intravenous iron every other day, on the second day after surgery. Thirteen patients received ESAs and FCM (500-1000 mg per session), three patients received ESAs and iron gluconate (1 vial every other day). No patients received blood transfusions. No side effects were observed and, most importantly, no limb or flap rejection. Conclusions Preliminary data from our protocol show an optimal therapeutic response in a surgical setting with limited data in the scientific literature. The enrolment of further patients will allow us to validate this therapeutic protocol with statistically significant data.

Background: Kidney transplantation is considered the first-choice therapy in ESRD patients. Despite recent improvements in terms of outcomes and graft survival in recipients, postoperative complications still concern health-care providers involved in the management of those patients. Particularly challenging are cardiovascular complications. Perioperative goal-directed fluid-therapy (PGDT) and hemodynamic optimization are widely used in high-risk surgical patients, and are associated with a significant reduction in postoperative complication rates and length of stay (LOS). The aim of this work is to compare the effects of perioperative goal-directed therapy (PGDT) with conventional fluid therapy (CFT), and to determine whether there are any differences in major postoperative complications rates and delayed graft function (DGF) outcomes. Methods: Prospective study with historical controls. Two groups, a PGDT- and a CFT- group were used: the stroke volume (SV) optimization protocol was applied in PGDT group throughout the procedure. Conventional fluid therapy with fluids titration at a central venous pressure (CVP) 8-12 mmHg and mean arterial pressure (MAP) >80mmHg was applied to the control-group. Postoperative data collection including vital signs, weight, urinary output, serum creatinine, blood urea nitrogen, serum potassium, and assessement of volemic status and the signs and symptoms of major postoperative complications occurred at 24h, 72h, 7 days and 30 days after transplantation. Results: Among the 66 patients enrolled, 33 were in each group and both groups had similar physical characteristics. Good fuctional recovery was evident in the 94% of patients. The statistical analysis has showed a difference in postoperative complications as follows: significant reduction of cardiovascular complications, DGF episodes (p<0.05) and surgical complications (p<0.01). There were no significant differences in pulmonary or other complication. Conclusions: PGDT and SV optimization effectively influenced the rate of major postoperative complications, reducing the overall morbidity and thus the mortality in patients receiving kidney transplantation.

Nietzsche is almost always regarded as one of the thinkers who advocate extreme individualism, totally indifferent to or exclusively polemical towards the public human dimension. While this is very difficult to contradict, if we read his texts carefully we can see how his constant celebration of the individual runs parallel to an acute awareness of living in a new era, which he defined as ‘the century of the multitude and the masses’. The herd, conformism, mediocrity, public opinion: a civilisation in which community attempts suffocate all individual inspiration, and which therefore seems to row in the opposite direction. Although Nietzsche often uses collective life merely as a negative pole for more effectively emphasising the individual, his provocative words—pushed to the limits of the inexorable victory of the herd and of the paradoxical impossibility of all that is ‘public’—offer us a direct testimony of the tragic way of life of the man of his time. This provides us with an extremely clear and interesting phenomenological cross-section of the social sphere, as well as a very finely tuned and valuable seismograph for the continual monitoring of our everyday coexistence with and perception of the constantly incumbent dangers of its degeneration.

Umbria is an Italian region with a highly fragmented water supply, with many small water distribution systems fed by local sources. The chlorination in these small water systems faces many difficulties related to the high demand variation, low economic relevance, and access to infrastructures. As a result, there are many noncompliances with the quality of the supplied water, which causes a decrease in the performance indicators and tariff. This research investigates the possibility of using a low-cost chlorination system to consider different environmental conditions (e.g., temperature variations of water and environment, pH, ...) and discontinuous consumption. A device for this specific use is developed and tested by laboratory tests and is ready for use in the field.

Brain imaging studies have recently provided some evidence in favour of covert cognitive processes ongoing in patients with disorders of consciousness (DoC) (e.g., minimally consciousness states, vegetative state/unresponsive wakefulness syndrome) engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer’s motor system maps others’ actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, provided that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. Results indicate that some form of motor resonance is spared in a subset of patients with DoC with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials following the stimulation of the median nerve at the wrist (i.e., the temporal marker signalling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters.

Viscum album L., also known as “Mistletoe”, is a hemiparasitic plant native to the European continent that grows on various host trees. This plant contains a wide variety of active compounds that can be used for treat various diseases, such as diabetes, hypertension, as an anti- inflammatory and antioxidant. However, it is most indicated in human medicine for the adjuvant treatment of cancer patients. Both for its properties directed against neoplastic cells and for its antioxidant and anti-inflammatory properties. In Veterinary Medicine, I am very few studies are recorded for animals, although formulations are available for commercial use in oral and injectable form, mostly for homeopathic use. Many studies have been conducted on a large scale by groups of independent researchers and doctors in several countries, such as Switzerland, Germany and Brazil. Therefore, this review aimed to collect data on the use of Viscum album in Veterinary Medicine in order to encourage research in this sector not only in oncological diseases but in other directions in which Viscum can find use as an anti-pretensive and anti-diabetic agent. Introduction: Lectins, flavonoids, phenols such as phenylpropanoids, coumarins, sterols, lignans, terpenoids, phenylpropanoids, alkaloids, fatty acids and viscotoxins are among the main active ingredients present in the phytocomplexes of the Viscum album plant. In particular, Attention should be given to specific oligoproteins in consideration of their activity biological [1]. present in The foliage and fruits of V. album, as in other related species, contain low-weight proteins molecular type of thionin, called viscotoxins, as well as characteristic lectins, called viscolectins, both can contribute to its system defense and can be found in extracts and related products. These classes of Viscum microproteins have received considerable attention due to their contribution to effects cytotoxics and immunostimulants of mistletoe extracts used in medicine, as discussed later, including their mechanism of action [ 2–3] viscotoxins can increase the number of cells circulating naturalkillers and consequently improve the response host antitumor immunity [ 8]. Likewise, the a viscotoxin has an effective immunomodulatory impact on human and animal granulocytes [ 9, 10] and also acts on cellular apoptosis [11]. The cytotoxic action of viscotoxin is comparable to that of conventional chemotherapeutic agents [ 12].

Introduction Sepsis-associated encephalopathy (SAE) is common in sepsis and is linked to high mortality and impaired neurologic outcome. Brain ultrasonography (US), including transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS), is a non-invasive tool for cerebral monitoring and might be useful in sepsis. The aims of this review are: 1) to explore whether brain perfusion is altered in sepsis, 2) to determine the role of brain US in guiding resuscitation, and 3) its ability to predict neurological outcomes in septic patients. Materials and methods This scoping review adhered to the PRISMA-ScR protocol and JBI methodology. A comprehensive literature search was conducted across MEDLINE, Scopus, and Web of Science. The review included studies on adults with sepsis or septic shock in the ICU. Randomised controlled trials, clinical trials, observational studies and systematic reviews were included. All the data related to the review's key questions were extracted and charted independently by two authors. Results 625 articles were screened, and 34 were ultimately included after application of exclusion criteria. 85% of the studies were observational 15% were systematic reviews with or without meta-analysis. The studies primarily focused on cerebral blood flow (CBF) alterations in sepsis, reporting variable results. Findings showed variable cerebral autoregulation (CAR) impairment, with higher incidence in the early stages of sepsis and associations with poor neurological outcomes. However, while alterations in CAR and CBF are common in septic patients, their impact on neurological outcomes and mortality is not clear. Regarding resuscitation, only a paucity of studies were found and no conclusions can be drawn. Conclusions The current body of evidence has a poor grade, but it is possible to say that brain US can identify cerebral perfusions alterations. Its usage during resuscitation is feasible and warrants further investigations. Use of brain US during resuscitation and for prediction of outcome is not currently supported by evidence. Further studies on brain perfusion, acquisition of 2D images of parenchyma (TCCS) and application of a multimodal brain monitoring might be useful in these contexts.

The interaction of ultraviolet radiation with biological matter results in direct damage such as pyrimidine dimers in DNA. It also results in indirect damage provoked by the production of Reactive Oxygen Species (ROS) catalyzed by photo-sensitizers. Photosensitizers can be endogenous (e.g. Tryptophan) or exogenous (e.g. TiO2 and other photo-stable UVA sunscreens). Direct damage triggers an inflammatory response and the oxidative and proteolytic bursts that characterize its onset. The inflammatory reaction multiplies the effects of one single photon. Indirect damage, such as the peroxidative cascade in membrane lipids, can extend to thousands of molecular modifications per absorbed photon. Sunscreens should therefore be formulated in the presence of appropriate anti-oxidants. Superoxide and Singlet Oxygen are the main ROS that need to be tackled: this review describes some of the molecular, biochemical, cellular and clinical consequences of exposure to UV radiation as well as some results associated with scavengers and quenchers of Superoxide and Singlet Oxygen, as well as with inhibitors of singlet Oxygen production.

The investigation of submerged speleothems for sea level studies has made significant contributions to the understanding of the global and regional sea level variations during the Middle and Late Quateranry. This has been especially the case for the Mediterranean Sea, where more than 300 submerged speleothems sampled in 32 caves have been analysed so far. Here, we present a comprehensive review of the results obtained from the study of submerged speleothems since 1978. The studied speleothems cover the last 1.4 Ma and are focused mainly on Marine Isotope Stages (MIS) 1, 2, 3, 5.1, 5.3, 5.5, 7.1, 7.2, 7.3 and 7.5. Results reveal that submerged speleothems represent extraordinary archives providing accurate information on former sea level changes, also considering that the Mediterranean Sea is devoid of any tropical corals since the Miocene. New results from a stalagmite collected at Palinuro (Campania, Italy) characterized by marine overgrowth are also reported. The measured elevations of speleothems are contaminated by the local response to glacial- and hydro-isostatic adjustment (GIA), and thus might significantly deviate from the global eustatic signal. Age and altitude comparation between Mediterranean speleothems, flowstone from Bahamas with local GIA provide a new scenario for MIS 5 and 7 sea level reconstrutions.

Nowadays a recognized need for accurate observations of atmospheric aerosols (AEs) and reactive gases (RGs) exists in the framework of regional, national and global near-surface networks based on permanent or mobile measurement stations. In this context, a paramount and not-trivial issue is related to the correct execution of continuous sampling of ambient air and its subsequent distribution to measurement analyzers hosted inside the stations. Sampling artifacts must be minimized for obtaining reliable pictures of ambient air composition. To respond to this need, a suite of novel “smart” and relatively low-cost systems for the continuous sampling of ambient air was developed in the framework of the Project I-AMICA (2012 – 2015, www.i-amica.eu). These systems were designed to execute AE and RG measurements according with WMO/GAW and ACTRIS recommendations and standard operation procedures. A particular attention was dedicated to the stabilization and control of the sampling flow rates and temperatures. The analysis of one full year of operations at the WMO/GAW regional station of Capo Granitola (GAW ID: CGR, Italy), allowed to conclude that these systems are effective in meeting the technical requirements for correct execution of AE and RG measurements

CKD in HF patients is very common condition, their dysfunction is closely linked and influence each other, so their management required multidisciplinary and personalized approaches. The diagnosis of HF and CDK relies on signs and symptoms. Several tools, such as blood-based biomarkers and echography help us to clarify and discriminate the main characteristics of these patients. Evidence in improving survival due to new drug-employment in HF, has increasingly challenged physicians to manage patients with multiple diseases, especially in patients with CKD. The difficulty is in the safe administration of these drugs in patients with HF and CKD. Knowing up to which values ​​of creatinine or renal clearance any drug can be administered is fundamental. We wanted to summarize, on this sizable and complex topic, the experiences of various prior study to get clearer ideas and a more precise reference about the assessment and management of HF and CKD.

Analytical modeling has symmetries and aesthetic-mathematical characteristics that distinguish it from numerical computation. Nanoscience plays an extremely important role in unification efforts that also include holistic aspects of reality. In this paper I present new discovered results about the complete analytical quantum relativistic form of the mean square deviation of position false related to a lately appeared Drude-Lorentz-like model (DS model), already performed at classical, quantum and relativistic level. The function false gives precise information about the distance crossed by carriers (electrons, ions, etc.) inside a nanostructure, considering both quantum effects and relativistic velocities. The model has a wide scale range of applicability; the nanoscale is considered in this paper, but it holds from sub-pico-level to macro-level because of the existence of a gauge factor, making it applicable to every oscillating processes in Nature. Examples of application and suggestions supplement the paper, as well as interesting developments to be studied related to the model and to one of the basic elements of a current unified holistic approach based on the vacuum energy.

Background: Breast cancer is the most common cancer among women worldwide and remains the leading cause of death among Italian women. Despite increased breast cancer awareness and improved diagnostic techniques, mortality rates remains high globally. In Italy, despite the availability of screening programs by the National Health System (NHS) for all Italian women aged 50-69 every two years, the participation rate remains relatively low. The low uptake of screening may be attributed to a lack of general cancer knowledge among women, including awareness of risk factors, symptoms, and prevention measures. This study investigates the knowledge and misinformation in a population of Italian women regarding breast cancer risk factors, symptoms, and prevention. Methods: From March 2021 to January 2022, we conducted a survey targeting the female population in Italy, with a total of 2375 participants willingly participating in the study. To investigate factors linked to variations in attitudes toward breast cancer, the participants were categorized into two groups: the general population (Group A, n=2235) and women who have had or currently have breast cancer (Group B, n=140). Statistically significant differences were identified between these two groups. Results: The findings revealed considerable confusion regarding both the symptoms and causes associated with cancer, as well as prevention measures. This confusion was particularly prominent among women in the general population and those with lower levels of education. Conclusions: Given these insights, it remains crucial to promote accurate health information concerning risk factors, symptoms, and prevention strategies related to this devastating disease, emphasizing the ongoing importance of disseminating correct health information.

The decarbonization of the built environment, both in new construction and renovation, is crucial to mitigate its relevant impact on climate change and achieve the Paris agreement goals. This study presents a systematic LCA-based methodology to assess the whole life carbon emissions of buildings, applied to a proposal for the regeneration of one of Milan’s disused railway yards. As an entry for the 2020 Reinventing Cities competition, Scalo Lambrate is a project for a mainly residential neighborhood with a public park. Strategies to reduce carbon emissions deriving both from the operational energy and construction and maintenance were evaluated and their effects compared to a reference scenario over a time horizon of 100 years. The results show that, while the opportunities to reduce carbon emissions during the use phase are somehow limited due to the already stringent performance requirements for new builds, the use of fast-growing biogenic materials for construction materials, even if mixed with more traditional ones, can provide a significant reduction of the global warming potential over the whole life cycle, with a reduction of 70% over the baseline. The remaining emissions can be offset with afforestation initiatives that, however, must be assessed against land use issues.

A recent research has identified an inverse amplitude link between obliquity damping and short eccentricity amplification during Mid-Late Pleistocene based on LR04 δ18O and equatorial Pacific Site 846 sea surface temperature records, which is associated with the Earth's long-term cooling. In the present study, new evidence of this anticorrelation is presented from Antarctic D-CO2-CH4 records, global benthic-planktic δ18O, and regional (Atlantic, Pacific, Mediterranean, and Indian) climate-related proxies. Based on a critical review of theoretical constrains (Earth's oblateness changes and ice-volume phase lag in the obliquity band <5.0 kyr), this widespread and symmetric (bipolar) obliquity response damping has been interpreted as an effect of the obliquity-oblateness feedback, which could be the latent physical mechanism at the origin of the Mid-Pleistocene Transition (MPT). Indeed, results and considerations of the present work suggest that fast and positive/negative net variation of the Earth's oblateness in the obliquity band was controlled by dominant glacio-eustatic water mass component and, assuming a rapid response of the ice-volume to surface temperature changes, the mean obliquity lag response is estimated to be <5.0 kyr over the past 800 kyr. These elements may explain the interglacial/glacial damping observed in the obliquity response. The consolidation of the Earth's long-term icy-state in the subtrend IV, culminated with the post-MPT obliquity damping, might have contributed to the strengthening of the short eccentricity response by mitigating the obliquity ‘ice-killing’ during obliquity maxima (interglacials), favouring the obliquity-cycle skipping and a feedback amplified ice-growth in the short eccentricity band (obliquity damping hypothesis). This could suggest a different impact of the climate friction than what is generally believed, which is presumably the latent physical mechanism that triggers transient ‘competitive’ interaction between obliquity and short eccentricity started early during the Piacenzian.

To evaluate the nutrient load due to the grazing of laying hens in outdoor runs, soil characteristics were monitored in three Italian organic farms. For each farm, soil samples were taken from three increasing distances from the hen house and two depths and different chemical parameters were evaluated. The comparison among the results from the different distances shows that N-NO3 and Olsen P are the most affected parameters by hen faeces: both present high values with a statistically significant difference in the area close to the poultry house and for the most superficial layer. Even TKN and TOC show significant differences between the concentrations of the first layer (more concentrated) and those of the second layer (less concentrated). In general, the surface soil layer closest to the chicken house is the portion of the outdoor run most affected by chicken droppings and represents the most critical point in terms of potential environmental impact. Therefore, it is necessary to intensify the management of the outdoor run with tools that can facilitate the grazing of animals and with vegetation that can absorb nutrients by limiting leaching and run-off.

Background: Calcaneal fractures are the most frequent traumatic injuries of the hindfoot and can cause severe disability with social and economic sequelae; since 1980 an increasing number of studies and new technologies have led to an improvement in their management and complications but treatment is still controversial. The purpose of the study to review the secondary scientific literature looking for the optimal management of calcaneal fracture; Methods: through the PubMed MEDLINE database, 4856 articles were identified; only meta-analyses and systematic reviews were included in the study. Results: 59 reviews with more than 10,000 calcaneus fractures were examined and results were divided into various topics; the majority of articles agree on the superiority of surgical versus conservative treatment; minimally invasive access to the sinus tarsi shows better results and fewer complications than traditional extended lateral access; reduction and osteosynthesis with percutaneous and/or minimally invasive techniques seem to provide better outcomes if compared to open treatments. Conclusions: The management of calcaneus fractures requires an individualized planning based on the functional demands of the patient, the type of fracture and associated injuries. New technologies and further studies may still improve the management of these lesions.

The purpose of this paper is to examine the role and impact of public governance on European supranational public policies that seek to foster scientific and economic growth within innovation ecosystems (IEs) through the PITCCH initiative. The PITCCH is a European innovation development initiative funded by Horizon 2020 under the 'Innovation in SMEs' measure.The research methodology for this study is based on a 10-month real-time ethnographic field study of the PITCCH project, which allowed for the observation of the project governance and the capture of the perspectives of innovation-driven small and medium enterprises (i-SMEs) in their engagement with IE stakeholders.The findings of this research demonstrate the role of public governance in providing result-oriented practical support to the IE through the lens of i-SMEs, and they contribute to the existing literature on regional economic growth supported by supranational public policies. These findings have both academic and practical applications. They enrich the current literature on this topic and provide insights for policymakers and governing representatives seeking to implement effective public policies.

Several criteria exist to diagnose pulmonary aspergillosis with varying degrees of certainty in specific populations, including oncohaematological patients (EORTC/MSG), ICU patients (AspICU) and Covid-19 patients (ECMM). At the beginning of the pandemic, however, the diagnosis of Covid-19 Associated Pulmonary Aspergillosis (CAPA) could not be performed easily, and the decision to treat (DTT) was empirical. In this cross-sectional retrospective study including patients with SARS-CoV-2 infection and a suspicion of CAPA, we studied the concordance between the DTT and the three diagnostic criteria using Cohen’s coefficient, then we identified the factors associated with the DTT and we corrected by treatment to study the influence of the diagnostic criteria on survival. We showed good concordance of DTT and AspICU and ECMM criteria, with “compatible signs”, “positive culture” and “positive galattomannan” influencing the DTT. Treatment also showed a positive effect on survival once corrected for a putative, possible or probable diagnosis of CAPA using AspICU and ECMM criteria. We conclude that EORTC/MSGERC are not considered applicable in clinical practice due to lack of inclusion of signs and symptoms and do not lead to improved survival. AspICU and ECMM criteria showed a good degree of agreement with the DTT and a positive correlation with patient recovery.

Aims. In a male Italian cohort (initially aged 40-59, n=1712) followed-up during 61 years and reaching practical extinction, the natural history of major CVD mortality categories including coronary heart disease (CHD), stroke and other Heart Diseases of Uncertain Etiology (HDUE, including congestive heart failure) were studied along with their risk factor relationships. Methods and Results. Cox models were run with 12 covariates measured at entry as possible predictors. About 93% of all CVD deaths were covered by the 3 major groups selected here (N=751): 37.4% of them were diagnosed as CHD, 30.6% as stroke and 28.5 % as HDUE. CHD declined in the last 20 years of follow-up, while a sharp increase of HDUE mortality was seen. Baseline mean levels of serum cholesterol were 209.6, 204.2 and 198.0 mg/dl respectively for CHD, stroke and HDUE deaths: the multivariable coefficients of serum cholesterol were positive and significant for CHD (p<0.0001) and stroke (p=0.0203) and not significant for HDUE (p=0.3467). In Fine-Gray models, the algebraic signs of cholesterol coefficients were opposite for CHD versus the other mortality categories (t=3.13). The predictive performances of remaining risk factors were varied whereas that of Cox models was not very good, probably due to the attrition phenomenon and possible competing risks. Conclusion. Large differences in natural history and risk factors were found comparing the 3 CVD conditions, potentially indicating different etiologies and pointing to the need of not mixing them up in a grouped CVD category.

A Digital Twin (DT) refers to a virtual representation or digital replica of a physical object, system, process, or entity. This concept involves creating a detailed, real-time digital counterpart that mimics the behavior, characteristics, and attributes of its physical counterpart. DTs have the potential to improve efficiency, reduce costs, and enhance decision-making by providing a detailed, real-time understanding of the physical systems they represent. While this technology is finding application in numerous fields, such as energy, healthcare, transportation, it appears to be a key component of the digital transformation of industries. In this paper, we present the research results achieved by IoTwins, a European research project aimed at investigating opportunities and issues of adopting DTs in the fields of industrial manufacturing and facility management. Particularly, we discuss a DT model and a reference architecture for use by the research community to implement a platform for the development and deployment of industrial DTs in the cloud continuum. Guided by the devised architectures’ principles, we implemented an open platform and a development methodology to help companies build DT-based industrial applications and deploy them in the so-called Edge/Cloud continuum. To prove the research value and the usability of the implemented platform, we discuss a simple yet practical development use case.

This paper aims to raise awareness on certain interoperability issues as we intend to shape industry 5.0 in order to enable a human-centric resilient society. We advocate that the need of sharing small and specific data will become more intensive as AI-based solutions will become more pervasive. Consequently, dataspaces should be carefully designed to address this need. We advance the conversation by presenting a case study from HR demonstrating how to predict the possibility of an employee experiencing attrition. Our experimental results show that we need more than 500 samples for developing a machine learning model to be sufficiently capable to generalize the problem. Consequently, our experimental results show the feasibility of the idea. However, in small and medium sized companies this approach cannot be implemented due to the limited number of samples. At the same time, we advocate that this obstacle may be overcome if multiple companies will join a shared dataspace, thus raising interoperability issues

Polar stratospheric clouds (PSCs) form in polar regions typically between 15 and 25 km, when the local temperature is sufficiently low. PSCs play an important role in the ozone chemistry and the dehydration and denitrification of the stratosphere. Lidars with a depolarization channel may be used to detect and classify different classes of PSCs. The main PSC classes are water ice, nitric acid trihydrate (NAT) and supercooled ternary solutions (STS), the latter being liquid droplets consisting of water, nitric acid and sulphuric acid. PSCs have been observed at the lidar observatory at Concordia Station from 2014 on. The harsh environmental conditions at Concordia during winter render successful lidar operation difficult. In order to facilitate the operation of the observatory several measures have been put in place to achieve an almost complete remote control of the system. PSC occurrence is strongly correlated with local temperatures and is affected by dynamics, as the PSC coverage during the observation season shows.

A methodological similarity between Thomas Hobbes and Pëtr Kropotkin is the intention to spread a theoretical foundation to everyone, in the sense that they are willing to give to all the people a clear description of the reality and a subsequent political view. To do so, they use a scientific method, deductive (starting from empirical observations) in the case of Hobbes, inductive-deductive in the case of Kropotkin. Kropotkin underlines the educational value of the scientific method.In this work we want to highlight that, although they both start their argumentations from a materialist ontology, Hobbes and Kropotkin conjecture two completely different states of nature. Hobbes describes the state of nature through the two famous metaphors homo homini lupus (citing Plautus) and bellum omnium contra omnes, while Kropotkin introduced the theory of mutual aid. Both the theory of a state of war by Hobbes and the theory of mutual aid by Kropotkin have been revolutionary. Hobbes has been influenced by the scientific revolution initiated by Francis Bacon, one of his mentors, and Galileo Galilei, together with a criticism towards the ancient Greece philosophers, in particular Aristotle. Kropotkin has been influenced by the ground-breaking writings of Charles Darwin together with a very fruitful Russian scientific environment.We want to stress here that the disenchanted view of the human nature in Hobbes, a state of war due to the fact that everyone has rights on everything, helps him to legitimate sovereignty, while the positive view of human nature in Kropotkin, a spontaneous mutual aid among people in a community, helps him to legitimate anarchy. Therefore, the fascinating scientific methods of the two materialists Hobbes and Kropotkin to structure a solid political theory cannot neglect different views on human nature due to their historical contexts.

For its microtubule-binding properties, the expression level of the neurodegeneration-associated protein Tau is pondered as a potential modifier of cancer resistance to chemotherapy since decades. Indeed, Tau binds microtubules at the same site as taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network in order to stall cell division and to induce tumor cell death. Whilst independent studies report the association between low Tau expression and superior taxane response, the data were refused by a meta-analysis, suggesting interference of other parameters. Unpredictably, Tau expression level was identified as a prognostic cancer marker, whereby its positive or negative predictive value for survival depended on the cancer type. With recent experimental evidence linking Tau to P53 signaling, DNA stability and protection and to the implication of Tau in cancer is strengthened. The identification of a role of Tau at the interface between two major aging-related disorder families, neurodegeneration and cancer, offers clues for the epidemiological observation inversely correlating these disorders. Elucidating how Tau is mechanistically implicated in cellular pathways common to these devastating illnesses may extend the Tau-targeting therapeutic opportunities to cancer.

Meat loss and waste are estimated at each stage along the food chain, but the methods used are complex and the data needed often fragmented. We, therefore, evaluated the feasibility of estimating meat loss and waste using a simpler method comparing meat availability and consumption, using Swiss meat consumption according to a national nutrition survey and Swiss meat availability according to food balance sheets. As availability is reported at the fresh meat level and consumption as consumed, items of the latter were converted to fresh meat equivalents before comparing consumption with availability. Consumed unprocessed meat was directly converted to fresh meat equivalents and consumed meat products after having identified their meat ingredients. Meat availability, meat consumption as consumed and as fresh meat equivalent were 138.4 g/d, 105.5 g/d, and 112.1 g/d, respectively. The resulting total meat loss and waste was 19% and varied from −36% to 38% for the different meat types. Estimating meat loss and waste based on meat availability and consumption derived from a national nutrition survey yielded results varying to such an extent that the evaluated method to estimate meat loss and waste cannot be recommended.

This paper discusses complexity theory, that is, the many theories that have been proposed for emergence of complexity from the underlying physics. Our aim is to identify which aspects have turned out to be the more fundamental ones as regards the emergence of biology, engineering, and digital computing, as opposed to those that are in fact more peripheral in these contexts. In the cases we consider, complexity arises via adaptive modular hierarchical structures that are open systems involving broken symmetries. Each emergent level is causally effective because of the meshing together of upwards and downwards causation that takes place consistently with the underlying physics. Various physical constraints limit the outcomes that can be achieved. The underlying issue concerns the origin of consciousness and agency given the basis of life in physics, which is structured starting from symmetries and variational principles with no trace of agency. A possible solution is to admit that consciousness is an irreducible emergent property of matter.

In the last two centuries, land use change (LUC) has been the most important direct changes driver for terrestrial ecosystems. To contrast the consequent ecosystems degradation, forward-looking spatial policies and target landscape and land-use planning processes, promoting a sustainable land use change, are needed. The present paper proposes a framework of action including different landscape planning and ecological approaches: from the spatial modelling to recognize the LUC and build different scenarios, to the ecosystem services (ESs) assessment to evaluate the possible environmental impacts. Three different scenarios were built: Trend, No-Tillage and Energy crops. The Sediment Delivery Ratio and Carbon Storage and Sequestration ESs were assessed and compared for each scenario. The aim of the paper is to support decision-makers and local communities into the landscape planning process. Results show that a regional development in line with past trend could lead to further land degradation. Instead, the two scenarios proposed in compliance with EU policies, could bring benefits only if related to moderate LUCs and respecting the naturally grass-vegetated land. From the local to global scale, a guided and shared LUC management allows implementing sustainable development, basing on a deep knowledge of physical-environmental but also social and economic issues.

During the 3rd millennium cal BC, the Indus communities exploited great quantities of chert from the Rohri Hills mines in Upper Sindh for making different types of artefacts. This paper discusses the way chert was transported to the Indus Civilization centres and the problems related to the type, quantity and quality of raw material and artefacts that were transported, when, why, and where. This paper raises the question of land and water transport. Both these methods were probably used according to the landscape location of the Indus sites. Another problem regards the landscape characteristics of the Indus Valley during the Bronze Age before the climate changes which took place around the end of the 3rd millennium cal BC, and the disappearance of the Hakra River, which was an important watercourse during the Indus phase. What do we know of the way the Indus communities exploited, transported, and circulated knappable chert? Why the Indus settlements excavated around the Rohri Hills, the largest chert mines of the Indian Subcontinent, have yielded little evidence of chert artefacts and nodules? What do we know of this important problem which is strictly related with the everyday life of the Indus communities and their economy? Why this problem has been systematically neglected by most archaeologists despite its importance?

This work describes and compares the backpropagation algorithm with the Extended Kalman filter, a second-order training method which can be applied to the problem of learning neural network parameters and is known to converge in only a few iterations. The algorithms are compared with respect to their effectiveness and speed of convergence using simulated data for both, a regression and a classification task.

The interplay between thrombosis and inflammation, known as thromboinflammation, is a significant pathway driving cardiovascular and autoimmune diseases, as well as COVID-19. Key modulators of this process have emerged as innate immune cells. Strategically positioned to promote thromboinflammation are neutrophils, the most predominant white blood cells in humans. Neutrophils can trigger an organized cell death pathway by releasing decondensed chromatin structures known as neutrophil extracellular traps. These structures are decorated with histones, cytoplasmic, and granular proteins, and have cytotoxic, immunogenic, and prothrombotic effects, which can accelerate disease progression. The activities of PAD4, which catalyses the citrullination of histones, and the neutrophil inflammasome are required for distinct steps leading to extracellular DNA release (NETosis). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. We will discuss how vascular blockages in thromboinflammation occur due to the interaction between neutrophil extracellular traps and ultra-large VWF (von Willebrand Factor). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. It will also review the mechanisms whereby vaso-occlusive events in thrombo-inflammation depend on the interaction of neutrophil extracellular traps with von Willebrand factor and suggest the importance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thrombo-inflammatory diseases such as atherosclerosis and CVD.

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

Objectives: In December 2019 a novel human-infecting coronavirus, SARS-CoV-2, has emerged. The WHO has stated the epidemic as a “public health emergency of international concern”. A dramatic situation has emerged with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a severe deficiency in nutrients as fatsoluble and hydrosoluble vitamins. Design: In this second part of the review about Cov2 in aged people, we searched for studies describing the possible efficacy of vitamins A, D, E and C in improving the immune system function and their possible activities against viruses. Results: Vitamins may shift the proinflammatory Th17 mediated immune-response arising in the autoimmune diseases towards a T-cell regulatory phenotype. These diseases may serve as a paradigm for the study of CRS emerging in the course of SARS CoV-2 infection. Conclusion: This review discusses about the possible activity of Vitamin A, D, E and C in restoring normal antiviral Immune System function or the potential therapeutic role of these micronutrients as a part of a multi-treatment strategy against SARS-CoV-2 infection.

Objectives: In December 2019 a novel human-infecting coronavirus, SARS-CoV-2, has emerged. The WHO has stated the epidemic as a “public health emergency of international concern”. A drammatic situation has emerged with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a severe deficiency in nutrients as fatsoluble and hydrosoluble vitamins. Design: In this first part of the review about Cov2 in aged people, we searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We sed them as a paradigm with the purpose to retrieve pathogenetic mechanisms in common among these pathological conditions and SARS-CoV-2 infection, as well as the alteration induced in immune system function by this virus, or by its homologous SARS-CoV. Results: SARS-CoV-2 infection induces an important immune system dysfunction with the development of an exhuberant proinflammatory response in the host, and with the development of a life-threatening condition defined as Cytokine Release Syndrome (CRS). This leads to the Acute Respiratory Syndrome (ARDS), mainly in the aged people. High mortality and lethality rates have been observed in the elderly subjects with CoV-2-related infection. Conclusion: These diseases may serve as a paradigm for the study of CRS emerging in the course of SARS CoV-2 infection. This review discusses about the possible activity of Vitamin A, D, E and C in restoring normal antiviral Immune System function or the potential therapeutic role of these micronutrients as a part of a multi-treatment strategy against SARS- CoV-2 infection.

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

Coronaviruses (CoVs) are a well-known group of viruses in veterinary medicine. We currently know four genera of Coronavirus, alfa, beta, gamma and delta. Wild, farmed and pet animals are infected with CoVs belonging to all four genera. Seven human respiratory coronaviruses have still been identified, four of which cause upper respiratory tract diseases, specifically, the common cold, and the last three that have emerged cause severe acute respiratory syndromes, SARS-CoV-1, MERS-CoV and SARS-CoV-2. In this review we briefly describe animal coronaviruses and what we actually know about SARS-CoV-2 infection in farm and domestic animals.

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease among people over the age of 50 and occurs with symptoms such as musculoskeletal pain and stiffness in the neck, shoulders and hips. To date, corticosteroids represent the cornerstone of PMR treatment, although it is well known that their prolonged use is associated with several adverse effects, making it crucial to find therapeutic alternatives to their use. The purpose of this case report was to describe the effectiveness of 10 whole-body cryostimulation (WBC) sessions on a 74-year-old woman suffering from PMR. An improvement in disease impact, fatigue, pain, quality of sleep and total physical activity was observed after WBC. Moreover, the patient reduced her daily drug intake by 67% following WBC treatments. Given the increasing prevalence of PMR and considering the side effects that drug treatments can lead to, WBC could represent a valuable adjuvant and well-tolerated alternative for the treatment of PMR.

Our aim was to compare the inter-rater agreement of Transvaginal ultrasonography (TVS) with Magnetic Resonance Imaging (MRI) regarding diagnosing adenomyosis and for various predefined imaging features of adenomyosis in the same set of women. MRIs were assessed by four experienced radiologists and 2D TVS videoclips and 3D ultrasound volumes were assessed by five experienced sonographers. Each rater subjectively evaluated the presence or absence of adenomyosis, assessed various imaging. Fleiss kappa (κ) was used to reflect inter-rater agreement for categorical data and the Intraclass correlation coefficient (ICC) to reflect the reliability of quantitative data. Agreement between raters for diagnosing adenomyosis was higher for TVS than for MRI (κ =0.42 vs.0.28). MRI had a higher inter-rater agreement in assessing wall asymmetry irregular Junctional Zone (JZ) presence of myometrial cysts, while TVU had a better agreement for globular shape. MRI showed a moderate-good reliability for measuring the JZ (ICC=0.57-0.82). For TVS, JZ was unmeasurable in &gt; 50% of cases and the remaining cases had a low reliability (ICC=-0.31-0.08). We found that Inter-rater agreement for diagnosing adenomyosis was higher for TVS than for MRI, despite that MRI showed a higher inter-rater agreement in most specific features. Measurements of JZ in the coronal plane with 3D TVS were unreliable and thus unlikely to be useful for diagnosing adenomyosis.

In recent years, photobiomodulation (PBM) has been recognized as a physical therapy in wound management. Despite several published research papers, the mechanism underlying photobiomodulation is still not completely understood. The investigation about application of blue light to improve wound healing is a relatively new research area. Tests in selected patients evidenced a stimulation of the healing process in superficial and chronic wounds treated with a blue LED light emitting at 420 nm; a study in animal model pointed out a faster healing process in superficial wound, with an important role of fibroblasts and myofibroblasts. Here we present a study aiming at evidencing the effects of blue light on the proliferation and metabolism in fibroblasts and keratinocytes. Different light doses were used to treat the cells, evidencing inhibitory and stimulatory effects. Electrophysiology was used to investigate the effects on membrane currents, while Raman spectroscopy revealed the mitochondrial Cytochrome C (Cyt C) oxidase dependence on blue light irradiation. In conclusion, we observed that the blue LED light can be used to modulate the activity of human fibroblasts, and the effects in wound healing are particularly evident when studying the fibroblasts and keratinocytes co-cultures.

The evaluation of the piezoelectric properties of ferroelectric ceramics generally has a high level of uncertainty, due to incomplete poling, porosity, domain wall clamping and other effects. In addition, the poling process is often difficult and dangerous, due to the risk of breaking or damaging the sample. A method is described for the evaluation of the potential intrinsic piezoelectric response that a ceramic would have after full poling, without poling it. The method relies on the fact that any material undergoes an elastic softening below the ferroelectric transition temperature, whose magnitude can be expressed in terms of the intrinsic piezoelectric and dielectric coefficients of the material. Such a softening is equivalent to an electromechanical coupling, averaged over all the components due to the unpoled state of the sample, and can be deduced from a single temperature scan of an elastic modulus of a ceramic sample, spanning the ferroelectric and paraelectric states. The strengths, limits and possible applications of the method are discussed.

Rapid haemostasis during surgery is essential when one wants to reduce the duration of opera-tions, reduce the need for transfusions, and above all when one wants to achieve better patient management. The use of haemostatic agents, sealants and adhesives improves the haemostatic process by offering several advantages, especially in vascular surgery. These agents vary widely in their mechanism of action, composition, ease of application, adhesion to wet or dry tissue, im-munogenicity and cost. The most used are cyanoacrylate-based glues (Glubran 2) or polysaccharide hydrogel-microsphere powder (AristaTMAH). This work is based on a retrospective study carried out on a sample of patients with different vascular diseases (FAV, pseudoaneurysm and PICC application) in which two different haemostatic sealants were used. The aim was to assess the safety, the advantages and the ability of both sealants to activate the haemostatic process at the affected site, also in relation to their chemical-physical characteristics. The obtained results showed that the application of Glubran 2 and AristaTMAH as surgical wound closure systems is effective and safe as the success achieved was ≥94% on anastomoses of FAV; 100% on stabilization of Picc catheters; ≤95% on pseudoaneurysms.