Leptospirosis is a zoonotic disease that poses a significant threat to human and animal health worldwide. Among different animal species, pigs are known to play a crucial role in the transmission of the pathogenic Leptospira spp. This study aimed to investigate the prevalence of Leptospira spp. infection and associated risk factors in subsistence pig production in the state of Paraná, Brazil. A total of 1393 serum samples were collected from pigs on 188 subsistence properties in different regions of the state, and tested using the microscopic agglutination test (MAT) to detect antibodies against 24 different Leptospira spp serovars. The results revealed an overall seroprevalence of 68.78% for Leptospira spp. antibodies, with Icterohaemorrhagiae, Butembo, and Pomona being the most commonly detected serovars. Poor housing conditions, lack of rodent control, absence of veterinary assistance, and a history of reproductive problems were identified as significant risk factors associated with Leptospira spp. infection in the subsistence pig population. These findings highlight the urgent need for implementing effective control measures, such as improved housing conditions, rodent control, and veterinary assistance, to prevent the spread of this zoonotic disease in subsistence pig production systems in Paraná, Brazil.

This paper presents high-resolution digital measurements at low cost, combining oversample and averaging. Experiments of processing data between samples and between multiple temperature sensors in the same environment are conducted. They provide results with effective increase in the analog to digital converter bits, in correspondence with the minimization on the effects of noise. It is shown that averaging a set of small, low-cost sensors at a small microcontroller can give flexible access to improved measurement accuracy.

Glucose is a simple sugar molecule. The sugar molecule is chemically symbolised as C6H12O6. This means that the glucose molecule contains 6 carbon atoms (C), 12 hydrogen atoms (H) and 6 oxygen atoms (O). In human blood, the molecule glucose circulates as blood sugar. Normally after eating or drinking, our body breaks down the sugars in food and uses them to obtain energy for our cells. To do this, our pancreas produces insulin. Insulin "pulls" sugar from the blood and puts it into the cells for use. If someone has diabetes, their pancreas can't produce enough insulin. As a result, the level of glucose in the blood rises. This can lead one to many potential complications, including blindness, disease, nerve damage, amputation, stroke, heart attack and damage to blood vessels etc. In this study, a non-invasive method for monitoring blood glucose has been developed and is therefore easily usable. The device developed can measure the glucose level continuously and eliminates the disadvantages of the invasive system. Near-IR sensors (optical sensors) were used to estimate the concentration of glucose in the blood; these sensors have a wavelength of 940 nm. The sensor is placed on the tip of the finger and the output of the optical sensor is then connected to the microcontroller at the analogue input. Another sensor used, but only to provide more medical information was the heartbeat sensor. After processing and regression analysis, the glucose level is predicted, and data is sent via the Bluetooth network to a developed APP. The results of the implemented device were compared with available invasive methods. The study consists of a hardware platform inserted into an armband and then a small black parallelepiped-shaped box in which the optical sensors are inserted. The hardware consists of a microcontroller, a Near-IR optical sensor, a heartbeat sensor and a Bluetooth module.

Optical networks, characterized by using optical fibers as a transmission medium, constitute the fundamental infrastructure employed today by network operators to deliver services to users. As network capacity is one of the key factors influencing optical network performance, it is important to comprehend its limitations and have the capability to estimate its value. In this context, we revisit the concept of capacity from various perspectives, including channel capacity, link capacity, and network capacity, thus providing an integrated view of the problem. Hence, we review the fundamental concepts behind optical networks, along with the basic physical phenomena present in optical fiber transmission and provide methodologies for estimating the different types of capacities, mainly using simple formulations. In particular, we propose a method to evaluate the network capacity that relies on the optical reach to account for physical layer aspects, in conjunction with capacitated routing techniques for traffic routing. We apply this method to three reference networks and obtain capacities ranging from tens to hundreds of Terabits/s. Whenever possible, we also compare our results with published experimental data to understand how they relate.

Shared public buildings have become centers of innovation, integrating advanced technologies to meet evolving societal needs. With a heightened emphasis on occupants’ health and well-being, these buildings serve as hubs for technological convergence, facilitating seamless connectivity and intelligent data analysis and management. Within this context, environmental monitoring emerges as a foundational element, pivotal to all aspects of building management. This article provides findings from the nationally funded RE-START project, which focuses on shared public buildings, with special regard to educational and medical facilities. The project explores enhanced indoor air quality monitoring, focusing in particular on CO2 concentration that is directly correlated with occupancy, as a fundamental element for developing health and safety protocols, energy efficiency strategies, integration of smart building technologies, and data-driven energy management. The intersection of environmental monitoring, energy efficiency, security, and IoT technologies in in indoor spaces are relevant. The outcomes of the study reveal the delicate nature of all the involved components, that need to be carefully developed in an integrated manner.

The number of physical devices connected to the Internet such as vehicles, household appliances and other "things" has been steadily increasing in recent years, thus forming the basis for the Internet of Things (IoT). IoT ecosystem extends beyond country borders and application domains, combining thousands of versatile devices that differ in terms of their structures, capabilities, and available resources. It is therefore not surprising that the landscape of wireless communication technologies and the degree of IoT devices available today is excessively broad and diverse. Interference between networks leads to frame collisions and consequent packet loss. Frame collisions occur when two or more packets overlap in time and frequency and use the same LoRa parameters, i.e. the same spreading factor (SF), bandwidth (BW) and carrier frequency (CF). When most devices use the same configuration, collision probability is higher. The probability of frame collisions is also affected by traffic characteristics, particularly the periodicity of the transmission and the payload size. Larger payload sizes and more frequent transmissions accumulate with higher time on air (ToA) and channel occupancy [1]. Transmission powers and the location of the gateways also influences this situation. The aim of this experimental work is to verify the effects of collisions and interference in LoRaWAN, regarding the periodicity of transmissions and the payload sizes. The hardware used is an Arduino board programmed in C/C++, a LoRa Bee module operating at a frequency of 868 MHz and a LoRaWAN LG02 gateway. Different scenarios were tested in an outdoor environment, with Line of Sight and Non-Line of Sight, and different variables such as: SFs equal to 7, 9 and 12; distances of 20, 40 and 60 meters and different data sizes of 14, 32 and 51 bytes, over the same channel. The packets with different SF’s and different data sizes were transmitted in a (pseudo) random way, one after the other, overlapping different SFs in the same channel and testing this way (theoretical) orthogonality among them. By fixing the bandwidth in 125 kHz, and testing different SFs we intend to increase the probability of cause packet loss by applying to our connection a combination of emitted power/short distance that leaves an interference power received, strong enough [2] for the effect. We validate our conclusions by analyzing ToA according with RSSI and different data sizes, the RSSI for different SFs and different data sizes and finally the packet loss through the PDR-Packet Delivery Ratio for a better understanding of the reliability of packet transmission in our link.

The intensification of conflicts associated with the use of water in the transition region of the Cerrado and Amazon biomes caused by population and economic growth, combined with the interest in generating energy from hydroelectric plants, raise the need to quantify the surface water availability of rivers contributing with different drainage areas. The present study estimated and compared loco measurements of liquid flow (QL) and depth of rivers in the Teles Pires river basin by reference methods (MLN-7 hydrometric windlass and metal rod/winch) and by Acoustic Current Profiler by Doppler Effect (ADCP RiverRay), in addition, evaluated the total measurement time underestimation uncertainty by ADCP. Field measurements were carried out at monthly intervals between March 2020 and October 2021, seeking to represent the water seasonality and depth and QL variations in the cross-sections of the Caiabi 1 and 2, Celeste, Preto and Renato rivers. The evaluated rivers had a net flow between 3.48 and 60.78 m3 s-1 by the windlass and between 2.66 and 54.30 m3 s-1 by the ADCP, while the depths obtained were from 0.17 to 6.34 m by the rod/winch and from 0.65 to 6.20 m by the ADCP. The methods resulted in similar measurements of net flow and depth in each of the cross-sections, and the statistical performance of the linear regression model was satisfactory with a Willmott concordance index of 0.9977 and 0.9819 for estimates of QL and of the depth of the cross-sections, respectively. The ADCP accurately measured net discharge and depth in shallow (up to 6.5 m) cross-sections of Teles Pires River in relative to the reference method. Determining the total measurement time and pairs of transects to obtain accurate QL by ADCP depends on the hydraulic characteristics of the watercourses.

Optical backbone networks constitute the fundamental infrastructure employed today by network operators to deliver services to users. As network capacity is a key factor influencing optical network performance, it is important to understand how topological and physical properties impact its behavior and to have the capability to estimate its value. In this context, we propose here a method to evaluate the network capacity that relies on the optical reach to account for physical layer aspects, in conjunction with constrained routing techniques for traffic routing. As this type of routing can lead to traffic blocking, particularly due to the limitation on the number of wavelengths per fiber, we also propose a fiber assignment algorithm designed to deal with this problem. We apply this method to a set of randomly generated networks using a modified Waxman model, and for a network with 60 nodes, in a scenario without blocking, we obtain capacities of about 2.5 Pbit/s for a symbol rate of 64 Gbaud and about 5 Pbit/s for a symbol rate of 128 Gbaud. Remarkably, this duplication in the total network capacity is achieved by an increase in the total fiber length of only about 51%.

Affordances are an important concept in cognition, which can be applied to robots in order to perform a successful human-robot interaction (HRI). In this paper we explore and discuss the idea of emotional affordances and propose a viable model for implementation into HRI. We consider “2-ways” affordances: perceived object triggering an emotion, and perceived human emotion expression triggering an action. In order to make the implementation generic, the proposed model includes a library that can be customised depending on the specific robot and application’s scenario. We present the AAA (Affordance-Appraisal-Arousal) model, which incorporates Plutchik’s Wheel of Emotions, and show some examples of simulation and possible scenarios.

Integrated crop-livestock production (ILP) is an interesting alternative for more sustainable soil use. However, more studies are needed to analyze soil pore properties under ILP at the micrometer scale. Thus, this study proposes a detailed analysis of soil pore architecture at the micrometer scale in three dimensions. For this purpose, samples of an Oxisol under ILP subjected to minimum tillage (MT) and no-tillage (NT) with ryegrass as cover crop (C) and silage (S) were investigated. The soil micromorphological properties of the soil were analyzed using X-ray microtomography. The MT(C) system showed the highest values of porosity (c. 20.4%), connectivity (c. 32.8×103), volume (c. 26%), and number of pores (c. 32%) in a rod-like shape. On the other hand, the MT(S), NT(C), and NT(S) systems showed higher tortuosities (c. 2.2, c. 2.0, and c. 2.1) and lower pore connectivities (c. 8.3×103, c. 6.9×103, and c. 6.2×103), especially in S use. Ellipsoidal and rod-shaped pores predominated over spheroidal and disc-shaped pores in all treatments. The results of this study show that the use of ryegrass as a cover crop improves soil physical properties, especially in MT. For S use, the type of soil management (MT or NT) did not show any differences.

Menin inhibitors are new and promising agents currently in clinical development that target the HOXA/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemia. The mechanism of action of this new class of agents is based on the disruption of menin-KMT2A complex (constitute of chromatin remodelling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or mutated NPM1. This new class of drugs has been tested alone, or in combination with synergistic drugs, in phase I and II clinical trials (AUGMENT-01 and 02, KOMET-01 and 07, SAVE, COVALENT trial and others), showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this review, we summarise the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data of this emerging and promising class of agents, in particular revumenib and ziftomenib.

Adhesion of polymers to surfaces is of upmost importance in timely applications such as protective coatings, biomaterials, sensors, new power sources and soft electronics. In this context, this work examines the role of molecular interactions in the adhesion of polypyrrole thin films to flexible Indium Tin Oxide (ITO) electrodes grafted with aryl layers from various diazonium salts, namely 4-carboxybenzenediazonium (ITO-CO₂H), 4-sulfonicbenzenediazonium (ITO-SO₃H), 4-N,N dimethylbenzenediazonium (ITO-N(CH₃)₂), 4-aminobenzenediazonium (ITO-NH₂), 4-cyanobenzenediazonium (ITO-CN) and 4-N-phenylbenzenediazonium (ITO-NHPh). It was demonstrated that PPy thin layers were adherent to these surfaces, whereas adhesion failure was noted on bare ITO, following simple solvent washing or sonication. Adhesion of the polypyrrole was investigated in terms of the hydrophilic/hydrophobic character of the underlying aryl layer as probed by contact angle measurements. It was found that sulfonic acid doped polypyrrole (PPy-BSA) thin films were preferably deposited on the most hydrophobic surfaces. More importantly, the redox properties and electrochemical impedance of PPy were closely related to the hydrophobic character of the aryl layers. This work demonstrates that diazonium compounds are unique molecular glues for conductive polymers, and permit to tune their interfacial properties. With diazonium-based robust, architectured interfaces, one can design high performance materials for e.g.sensors, printed soft electronics and flexible thermoelectrics.

The primary objective of this experiment is to enhance road safety and mitigate the occurrence of accidents by leveraging Low Power Wide Area Networks (LPWAN), specifically focusing on the Long Range (LoRa) network. Through comprehensive research into LPWANs and their various applications, we have designed and implemented a novel approach employing two mobile robots. These robots are utilized to emulate a typical traffic scenario, with one robot leading the way, skillfully maneuvering around obstacles, while the other robot closely follows behind, tracing the same path. The leading robot is tasked with collecting data from its internal environment, the external surroundings, and its operator through an array of sensors. Subsequently, this data is transmitted to the trailing robot. The follower robot's role is to analyze the data received and formulate decisions based on this information. Its objective is to mimic safe driving behavior, particularly when the received data deviates from the expected norms. In such instances, the follower robot will opt to decelerate significantly, thereby minimizing the risk of collision. By implementing this innovative system, we aim to significantly enhance driving safety and reduce the occurrence of accidents on the road.

Mycobacterium tuberculosis (Mtb) the causative agent of human tuberculosis (TB) is one of the most successfully adapted-human pathogens. Human-to-human transmission occurs at high rates through aerosols containing bacteria, but the pathogen evolved prior to the establishment of crowded populations. Mtb has developed a particular strategy to ensure persistence in the host until an opportunity for transmission arise. It has refined its lifestyle to obviate the need for virulence factors such as capsules, flagella, pilli, or toxins to circumvent mucosal barriers. Instead, the pathogen uses host macrophages, where it establishes intracellular niches, for its migration into the lung parenchyma and other tissues and for the induction of long-lived latency in granulomas. Finally, at the end of the infection cycle Mtb induces necrotic cell death of macrophages to escape to extracellular milieu and instructs a strong inflammatory response required for progression from latency to disease and transmission. Common to all these events is ESAT-6, one of the major virulence factors secreted by the pathogen. This review highlights the recent advances in understanding the role of ESAT-6 in hijacking macrophage function to establish a successful infection and transmission and its use as a target for the development of diagnostic tools, and vaccines.

The outstanding occurrences of red wood ant nests (RWA; Formica rufa-group) at two study sites in the Oberpfalz, NE Bavaria, Germany, could be confirmed by the 2023 re-inventory (a total of 5,393 nests and an increase by ≈8 %). RWA nests preferred mature and medium mature pine-dominated forests. Standing and downed dead wood do not negatively influence nests. Nest counts with woodpecker cavities and the diversity of the herb layer increased. The highly clustered nests in NW-SE direction suggests a strong interaction between nests distributions and the tectonic environment. Our developed (re-)inventory approach in combination with the comprehensive photo database is a valuable tool for a) monitoring the entire forest habitat including woodpecker cavities and dead wood in, at and around nests, and b) identifying GeoBio-Interactions. Such a comprehensive approach leads to more accurate and realistic counts of RWA nests during (re-)inventories and provides scientific evidence of the status quo of RWA occurrence. Our results disproved the unfounded and scientifically unsubstantiated blanket statement by laymen of the ASW Landesverband Bayern e.V. that RWA nest numbers in the Oberpfalz or even in the entire Bavaria are in sharp decline. We suggest seven to eight years as a suitable time interval for re-inventories.

We re-inventoried red wood ant nests (RWA) in 12 study sites (≈1281 ha) in the Westeifel Volcanic Field, Germany, in an area-wide and integrated ecosystem approach after 12 years. Combined with the re-identification of previously mapped nests using a photo database, this approach leads to more accurate nest counts in (re)inventories. A total increase of nests from 1144 (2009) to 1252 (2021), and a dramatic one for the Heidberg site by 52-fold (2009) and 85-fold (2021) compared to a 1984 inventory was observed, contrasting with earlier postulations of a decline in RWA. Early to medium mature (41-80 years) and mature (³81–140 years) spruce forests were the preferred habitat. Large increase in small nest sizes suggests an increase in new nest settlements also in clearings, despite climate-induced forest dieback over the past decade. A decline in biodiversity in the herbaceous layer was observed; highly proliferating blackberries had no negative impact on RWA nests. Monitoring of woodpecker cavities in RWA nests is suggested as an indirect indicator tool for evaluating populations in forests. Positive ground movement rates caused by the Eifel plume are suggested another factor favoring nest settlements. This study contributes to the urgent update of statistically valid data required to a) effectively substantiate the status-quo of RWA occurrences, b) protect RWA as ecosystem engineers, c) advance understanding of Geo-Bio-Interactions in the wake of climate change, and c) contribute to the German government's Insect Conservation Action Program.

In the early 1980s it was well established that Leray solutions of the unforced Navier-Stokes equations in Rn decay in energy norm for large time. With the works of T. Miyakawa, M. Schonbek and others it is now known that the energy decay rate cannot in general be any faster than t^-(n+2)/4 and is typically much slower. In contrast, we show in this note that, given an arbitrary Leray solution u(.,t), the difference of any two Stokes approximations to the Navier-Stokes flow u(.,t) will always decay at least as fast as t^-(n+2)/4, no matter how slow the decay of || u(.,t) ||_L2 might happen to be.

Background: The mortality and severity in COVID-19 is increased in patients with comorbidities. The aim of this study was to evaluate the unknown risk of severity and mortality in COVID-19 patients with underlying kidney and liver diseases. Method: We retrieved data on the clinical features and primary composite end point of COVID-19 patients released from inception till 16^th of April 2020 from Medline and Embase. The data on two comorbidities, liver diseases and chronic kidney disease, present in COVID-19 were pooled and statistically analysed to explain the associated severity and mortality rate. Results: 142 abstracts were screened, and 41 full articles were then read. In total, 22 studies including 5595 COVID-19 patients were included in this study with case fatality rate of 16%. The prevalence of liver diseases and CKD were 3% (95%CI; 2%-3%) and 1% (95%CI; 1%-2%) respectively. In patients with COVID-19 and underlying liver diseases, 57.33% (43/75) cases were severe with 17.65% mortality. While in CKD patients with COVID-19, 83.93% (47/56) severity and 53.33% (8/15) mortality were reported. Conclusion: This study found an increased risk of severity and mortality in COVID-19 patients with liver diseases and CKD. This will allow for better clinical management and inform more stringent preventative measures for this group of patients.

Tributyltin (TBT) is an environmental contaminant present on all continents, including Antarctica, with a potent biocidal action. Its use began to be intensified during the 1970s, being effectively banned in 2003, but remaining in the environment to this day due to several factors that increase its half-life and misuse despite the bans. In addition to the endocrine disrupting effect of TBT, that may lead to imposex induction in some invertebrate species, there are several studies that demonstrated that TBT also has an immunotoxic effect. The immunotoxic effects that have been observed experimentally in vertebrates using in vitro and in vivo models involve different mechanisms, but mainly alterations in the expression and/or secretion of cytokines. In this review, we summarize and update the literature on the impacts of TBT on the immune system, as well as discuss what still needs to be done to fill the knowledge gaps regarding the impact of this endocrine disrupting-chemical on immune system homeostasis.

The ironstone outcrops in the rupestrian grasslands, known as cangas, are rich in species of endemic plants. This high endemism and the constant threat because of the area loss and fragmentation make the conservation of the rupestrian grasslands necessary. The rupestrian grasslands that host one of Brazil's largest iron-ore mining areas are Iron Quadrangle. About 89 rare and endangered species of the Iron Quadrangle are exclusive to cangas, including a threatened species Arthrocereus glaziovii. According to the International Union Conservation of Nature (IUCN), this species is considered micro-endemic and endangered and a priority for recovering the Iron Quadrangle's ferruginous rupestrian fields. This work aims to evaluate the potential distribution of A. glaziovii based on abiotic variables and soil elements and characterize the distribution of mining titles that may restrict the areas of occurrence of this species. We used five types of ecological niche model (ENM) algorithms (Bioclim, Domain, MaxEnt, GLM and RandomForest) in two sets of environmental variables for the modeling: 20 climatic variables and 18 edaphic variables. Our results showed that the area of the potential occurrence of A. glaziovii is more extensive and covers areas outside the Iron Quadrangle. However, mining titles currently licensed and in exploration correspond the entire identified area, threatening the species' survival.

The current manuscript presents a review on existing kiln burner technologies for the cement production process, in the context of the current climate of energy transition and environmental remediation. Environmental legislation has become ever stricter in response to global climate change, and cement plants need to adapt to this new reality in order to remain competitive in the market and ensure their longevity. The cement production process is a well-established technology with more than a century of existence. There are several plants in operation whose process is outdated by modern standards, particularly considering the current industry decarbonization needs. The cement process requires tremendous amounts of energy, mainly recovered from the combustion of solid, liquid or gaseous fuels, which yields massive emissions of greenhouse gases. Thus, an important onus is placed upon the minimization of pollutant emission in the combustion system, as well as a substitution of fossil fuels with more sustainable alternatives. One of the sus-tainable alternative fuels comes in the form of refuse derived fuels (RDF). These high caloric frac-tions of municipal solid waste present a double advantage by reducing the amount of fossil fuels used and reducing the landfilling fraction of waste. However, their use in rotary kiln burners comes with important limitations for burner operation, namely that a high degree of control over primary air supply is needed to ensure complete combustion with minimal pollutant emission.

This paper presents a new method to model the nonlinear behaviour of masonry double curvature structures, possibly reinforced by composite materials, by means of conventional elasto-plastic analyses. It is meant to be used in professional design, especially for assessment and retrofitting purposes, therefore based on the exploitation of the simplest nonlinear Finite Elements available in a commercial software, namely trusses with elasto-fragile and elasto-ductile behaviour (Cutoff Bars). The numerical static nonlinear analyses are carried out by considering elastic hexahedral elements for bricks and lumping nonlinearities on joints. These have been assumed in turn elastic-brittle and elastic-plastic by using 1D elements, respectively Point Contacts, under No-Tension Material hypothesis, and Cutoff Bars, assigning small tensile resistance to the material. The reinforcement, realised with FRP hooping strips, has been successfully modelled in a similar fashion, i.e. by applying perfectly bonded elastic-plastic Cutoff Bars at the extrados of the dome, where the debonding is accounted for in a conventional way limiting the tensile strength according to Italian Standards indications. The procedure is validated against benchmark models with the same geometry, using experimental data and more refined structural model results for comparison.

The peculiar physicochemical features of deep eutectic solvents (DESs), in particular their tunability, make them ideal media for various applications. Despite their ability to solubilize metal oxides, their use as rust removers from valuable substrates has not yet been thoroughly investigated. In this study we chosen three known DESs, consisting of choline chloride and acetic, oxalic or citric acid for evaluating their ability to remove corrosion products from a cellulose-based material as linen fabric and two different lithotypes, as travertine and granite. The artificial staining was achieved by placing a rusty iron grid on their surfaces. The DESs were applied by means of cellulose poultice on the linen fabrics, while on the rusted stone surfaces with a cotton swab. Macro- and microscopic observations, colorimetry and SEM/EDS analysis were employed to ascertain the cleaning effectiveness and the absence of side effects on the samples after treatment. Oxalic acid-based DES was capable of removing rust stains from both stone and cellulose-based samples, while choline chloride/citric acid DES was effective only on stone specimens. The results suggest a new practical application of DESs for the elimination of rust from lithic and cellulosic substrates of precious and artistic value.

The genus Clostridium is an important group of pathogenic and nonpathogenic Gram-positive anaerobic bacteria with sporulation capacity and wide distribution in different environments, including the gastrointestinal tract of healthy and diseased animals and humans. Among the pathogenic species of the genus, Clostridium chauvoei stands out as a histotoxic agent. It causes important myonecroses such as blackleg, a disease with high lethality and mortality, especially in young cattle, and is responsible for significant losses to livestock worldwide. The pathogenic-ity of the disease is complex and has not yet been fully elucidated. The hypotheses cover pro-cesses from the initial absorption to the transport and deposition of the agent in the affected tis-sues. The virulence factors of C. chauvoei were divided into somatic and flagellar antigens and soluble antigens/toxins, which are the main antigens involved in vaccines against blackleg in Brazil and worldwide. This review provides important information on the first and current ap-proaches to the agent C. chauvoei and its virulence factors, as well as provides a compilation of data on Brazilian studies related to blackleg.

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.

Polyphenols are well-known health promoting agents, but they have some limitations due to their spontaneous oxidation. This evidence has limited their use as drugs in the last years. In this field, several chemical modifications have been proposed to overcome these restrictions; among these, the esterification seems to be the preferred. Ester derivatives could be able to reduce the bioavailability problems connected to polyphenols. On the other hand, the presence of the esterase enzymes in the body guarantees the ester hydrolysis, which in turn frees the two molecules that make it up. Lipase-catalyzed esterifications afforded several derivatives of flavonoids glycosides, in green conditions. In this short note, pancreatic porcine lipase was firstly used as a cheap bio-catalyst, to synthesize oleoyl derivatives of quercetin in aglycone form. Results demonstrated how the enzyme acyl regioselective in position C-3, with high yields and easy purification processes

Highly sensitive multicomponent materials designed for the recognition of hazardous compounds request control over interfacial chemistry. The latter is key parameter in the construction of the sensing (macro)molecular architectures. In this work, multi-walled carbon nanotubes (in short, CNTs) were deposited on diazonium-modified flexible ITO electrodes prior to electropolymerization of pyrrole. This three step process, including diazonium electroreduction, deposition of CNTs and electropolymerization, provided adhesively bonded polypyrrole-wrapped CNT composite coatings on aminophenyl-modified flexible ITO sheets. The aminophenyl (AP) groups were attached to ITO by electroreduction of the in situ generated aminobenzenediazonium compound in aqueous, acidic medium. For the first time, polypyrrole (PPy) was electrodeposited in the presence of both benzenesulfonic acid (dopant) and ethylene glycol-bis(2-aminoethylether)-tetraacetic acid (EGTA) which acts as a chelator. The flexible electrodes were characterized by XPS, Raman and scanning electron microscopy (SEM) which provided strong supporting evidence for the wrapping of CNTs by the electrodeposited PPy. Indeed, the CNT average diameter increased from 182.6 nm to 274.8, 35.65.9 and 17520.1 after 1, 5 and 10 of electropolymerization of pyrrole. The PPy/CNT/NH2-ITO films generated by this strategy exhibit significantly improved stability and higher conductivity compared to a similar PPy coating without any embedded CNTs as assessed by from electrochemical impedance spectroscopy measurements. The potentiometric response was linear in the 10-83×10-7 mol.L-1 Pb(II) concentration range and the detection limit was 2.9×10-9 mol.L-1 at S/N=3. The EGTA was found to drastically improve selectivity for Pb(II) over Cu(II). To account for this improvement, density functional theory (DFT) was employed to calculate the EGTA-metal ion interaction energy which was found to be -374.6 and -116.4 kJ/mol for Pb(II) and Cu(II), respectively, considering solvation effects. This work demonstrates the power of a subtle combination of diazonium coupling agent, CNTs, chelators and conductive polymers to design high-performance electrochemical sensors for environmental applications.

The objective of this work was the use of goat and sheep liquid whey concentrates (LWCs) produced by ultrafiltration (UF) for the manufacture of frozen yoghurts with or without different concentrations of inulin. In a first step, natural yoghurts using only goat and sheep LWCs as raw material were obtained. One day after production, these yoghurts were used to produce frozen yoghurts with different concentrations of added inulin. The physicochemical charateristics of ewe´s and goat´s yoghurts were significantly different regarding dry matter, protein, fat and minerals. Ewe´s yoghurts were solids while goat´s yoghurts behaved as a viscous liquid. Frozen yoghurts with different levels of inulin addition also presented significant differences concerning physicochemical and microbiological characteristics. Overrun was similar for all formulations except for the one produced with ewe’s LWC containing 5.0% inulin, which presented a significantly higher value. Higher meltdown rates in goat’s whey frozen yoghurts were observed. The survival rates of lactic acid bacteria were lower than data reported for similar products. Concerning sensory acceptance, both products showed encouraging results. It can be considered that the production of frozen yoghurts by using LWCs as main ingredient can be an interesting option to broaden the product’s portfolio of small/medium scale dairy producers.

We investigated fault gases (helium, radon, CO₂) in two seismically active Cenozoic sedimentary environments: a) Meinweg (in 2015) at a tectonically quiet horst structure in the Lower Rhine Embayment and b) Bodanrück (in 2012; Lake of Constance) at the Molasse Basin and part of the Freiburg–Bonndorf–Bodensee Fault Zone (FBBFZ). Both study areas were selected because recent “GeoBio-Interactions” findings showed, that red wood ants (RWA) are biological indicators of otherwise undetected degassing systems. A total of 817 soil gas samples was analyzed. Currently, Meinweg can be considered “no ants land” due to the very low background-level geogas concentrations. Thus, anomalies (Rn-CO₂) weakly trending in NE-SW extension direction emerged. This could probably indicate the onset of (re)activation of the NE-SW trending (Variscan) structures or the development of new fractures as an aftershock process of the 1992 Roermond earthquake that occurred about 15 km to the west. Results at Bodanrück (3 RWA clusters and two RWA-free corridors) revealed degassing patterns in NW-SE and NNE-SSW directions in the clusters corresponding to re-activated and recent strike-slip fault systems. No gas anomalies were found in RWA-free corridors. The RWA nest distribution was shown to be a valuable tool for identifying areas of even actively degassing spotty anomalies caused by macro- and microscale brittle deformation masked by sediment cover.

The search for new food products that promote consumers health has always been of great interest. The dairy industry is perhaps the best example regarding the emergence of new products with claimed health benefits. Cheese whey (CW), the by-product resulting from cheese production, and second cheese whey (SCW), which is the by-product of whey cheese manufacture, have proven to be potential ingredients for the development of food products with improved nutritional characteristics and other functionalities. Nowadays, due to their nutritional quality, whey products have gained a prominent position among healthy food products. However, for long, CW and SCW were usually treated as waste or as animal feed. Due to their high organic content, these by-products can cause serious environmental problems if discarded without appropriate treatment. Small and medium size dairy companies do not have equipment and structure to process whey and second cheese whey. In these cases, generally, they are used for animal feed or discarded without an appropriate treatment, being the cause of several constraints. There are several studies regarding CW valorization and there is a wide range of whey products in the market. However, in the case of SCW remains a lack of studies regarding its nutritional and functional properties, as well as ways to reuse this by-product in order to create economic value and reduce environmental impacts associated to its disposal.

Despite the efforts made to stop the tuberculosis (TB) epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of DprE1 inhibitors, so, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties. Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester, or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused on nucleophilic addition/elimination reactions, SN2 reactions and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of the linker. The most interesting compounds exhibited activities comparable to isoniazid and DNB1. Computational studies were also performed aimed at understanding their possible interactions with DprE1. The most active compounds are a good starting point for further development, and we plan to study an extended family of compounds based in those structures.

The use of smartphones, coupled with different sensors, makes it an attractive solution for measuring different physical and physiological features, allowing for the monitoring of various parameters and even identifying some diseases. The BITalino device allows the use of different sensors, including Electroencephalography (EEG) and Electrocardiography (ECG) sensors, to study different health parameters. With these devices, the acquisition of signals is straightforward, and it is possible to connect them using a Bluetooth connection. With the acquired data, it is possible to measure parameters such as calculating the QRS complex and its variation with ECG data to control the individual's heartbeat. Similarly, by using the EEG sensor one could analyze the individual's brain activity and frequency. The purpose of this paper is to present a method for recognition of the diseases related to ECG and EEG data, with sensors available in off-the-shelf mobile devices and sensors connected to a BITalino device. The data were collected during the elderly's experiences, performing the Timed-Up and Go test, and the different diseases found in the sample in the study. The data were analyzed, and the following features were extracted from the ECG, including heart rate, heart rate variability, the average QRS interval, the average R-R interval, and the average R-S interval, and the EEG, including frequency and variability. Finally, the diseases are correlated with different parameters, proving that there are relations between the individuals and the different health conditions.

Smart living, a concept that has gained increasing attention in recent years, revolves around integrating advanced technologies in homes and cities to enhance the quality of life for citizens. Sensing and human action recognition are crucial aspects of this concept. Smart living applications span various domains, such as energy consumption, healthcare, transportation, and education, which greatly benefit from effective human action recognition. This field, originating from computer vision, seeks to recognize human actions and activities using not only visual data but also many other sensor modalities. This paper comprehensively reviews the literature on human action recognition in smart living environments, synthesizing the main contributions, challenges, and future research directions. This review selects five key domains: Sensing Technology, Multimodality, Real-time Processing, Interoperability, and Resource-Constrained Processing, as they encompass the critical aspects required for successfully deploying human action recognition in smart living. These domains highlight the essential role that sensing and human action recognition play in successfully developing and implementing smart living solutions. This paper serves as a valuable resource for researchers and practitioners seeking to explore further and advance the field of human action recognition in smart living.

Contamination with Arsenic, a toxic metalloid, is increasing in the marine environment. Additionally, global warming can alter metalloids toxicity. Polychaetes are key species in marine environments. By mobilizing sediments, they play vital roles in nutrient and element (including contaminants) cycles. Most studies with marine invertebrates focused on the effects of metalloids on either adults or larvae. Here we bring information on the effects of temperature increase and arsenic contamination on the polychaete Hediste diversicolor in different growth stages and water temperatures. Feeding activity and biochemical responses – neurotransmission, indicators of cell damage, antioxidant and biotransformation enzymes and metabolic capacity - were evaluated. Temperature rise combined with As imposed alterations on feeding activity and biochemical endpoints at different growth stages. Small organisms have their antioxidant enzymes increased, avoiding lipid damage. However, larger organisms are the most affected class due to inhibition of superoxide dismutase, which resulted in protein damage. Oxidative damage was observed on smaller and larger organisms exposed to As and 21 °C, demonstrating higher sensibility to the combination of temperature rise and As. The observed alterations may have ecological consequences, affecting the cycle of nutrients, sediment oxygenation and the food chain that depend on the bioturbation of this polychaete.

We investigate properties of strongly useful topologies, i.e. topologies with respect to which every weakly continuous preorder admits a continuous order-preserving function. In particular, we prove that a topology is strongly useful provided that the topology generated by every family of separable systems is countable. Focusing on normal Hausdorff topologies, whose consideration is fully justified and not restrictive at all, we show that strongly useful topologies are hereditarily separable on closed sets, and we identify a simple condition under which the Lindelöf property holds.

Users of meteorological forecasts are often faced with the question of whether to make a decision now based on the current forecast or whether to wait for the next and hopefully more accurate forecast before making the decision. One would imagine that the answer to this question should depend on the extent to which there is a benefit in making the decision now rather than later, combined with an understanding of how the skill of the forecast improves, and information about the possible size and nature of forecast changes. We extend the well-known cost-loss model for forecast-based decision making to capture an idealized version of this situation. We find that within this extended cost-loss model, the question of whether to decide now or wait depends on two specific aspects of the forecast, both of which involve probabilities of probabilities. For the special case of weather and climate forecasts in the form of normal distributions we derive a simulation algorithm, and equivalent analytical expressions, for calculating these two probabilities. We apply the algorithm to forecasts of temperature and find that the algorithm leads to better decisions relative to three simpler alternative decision-making schemes. Similar problems have been studied in many other fields, and we explore some of the connections.

A striking aspect of COVID-19 is the difference in the outcome of the infection between different countries, and different ethnic groups within one country. We surveyed the literature on SARS-CoV-2 complemented with comparative publications on SARS-CoV and other coronaviruses to capture the current understanding of virus – host interactions including virus subtypes, transmission, zoonotic aspects, and potential host determinants.

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.

Smart Living, an increasingly prominent concept, entails incorporating sophisticated technologies in homes and urban environments to elevate the quality of life for citizens. A critical success factor for Smart Living services and applications, from energy management to healthcare and transportation, is the efficacy of human action recognition (HAR). HAR, rooted in computer vision, seeks to identify human actions and activities using visual data and various sensor modalities. This paper extensively reviews the literature on HAR in Smart Living services and applications, amalgamating key contributions and challenges while providing insights into future research directions. The review delves into the essential aspects of Smart Living, the state of the art in HAR, and the potential societal implications of this technology. Moreover, the paper meticulously examines the primary application sectors in Smart Living that stand to gain from HAR, such as smart homes, smart healthcare, and smart cities. By underscoring the significance of the four dimensions of Context Awareness, Data Availability, Personalization, and Privacy in HAR, this paper serves as a valuable resource for researchers and practitioners striving to advance Smart Living services and applications.

This review covers the last 25 years literature on analogs of suberoylanilide hydroxamic acid (SAHA, known also as Vorinostat) acting as HDAC inhibitor. In particular, the topic has been focused on the synthesis and biological activity of compounds where the phenyl group (the surface recognition moiety, CAP) of SAHA has been replaced by an azaheterocycle through a direct bond with amide nitrogen atom, and the methylene chain in the linker region is of variable length. Most of the compounds reported displayed good to excellent inhibitory activity against HDACs and in many cases showed anti-proliferative activity against human cancer cell lines.

The emergence of antimicrobial resistance have represented a serious threats for public health and infections due to multidrug-resistant (MDR) microorganisms represent one of the most important causes of death worldwide. The renew of old antimicrobials, such as colistin, have been proposed as valuable therapeutic alternative to the emergence of the MDR microorganisms. Although colistin is well known to presents several adverse toxic effect, its usage in clinical practice have been reconsidered due to the broad spectrum of activity to gram-negative (GN) bacteria and to the important role of “last resort” agent against MDR-GN. Despite the revolutionary prospective of treatment of this old antimicrobial molecule, many questions remain open regarding the emergence of novel phenotypic traits of resistance and the optimal usage of the colistin in clinical practice. In the last years, several forward steps have been done in the understanding of resistance determinants, clinical usage and pharmacological dosage of this molecule, however, different points regarding the role of colistin in clinical practice and the optimal pharmacokinetic/pharmacodynamic targets are not well defined yet. In this review, we summarize the mode of action, the emerging resistance determinants and its optimal administration in the treatment of difficult-to-treat infections due to MDR Gram-negative bacteria.

Conclusions: It could be concluded that small/medium scale dairy plants can use UF equipment with the aim to valorize sheep´s and goat´s CW through the production of dairy formulations with added prebiotics and probiotics, while reducing the environmental impact of their activities.

So that the levels of water stress are not harmful to the development of the crop and affect its productivity, its detection and monitoring are necessary, and it can occur in different ways. One of them is through the Crop Water Stress Index (CWSI). This index quantifies water stress through the normalization of leaf temperature between the maximum and minimum plant temperatures as a function of evaporation conditions. The responses of a low-cost infrared (IR) sensor were crossed with image processing through segmentation by the Excess Green model to develop a water stress detection system using CWSI. A soil/plant temperature map was generated through a point-to-point scan of the IR sensor. And when it overlaid with a segmented image of the experimental area, only points identified as plants had their temperature values maintained. The Non-Water-Stressed Baseline (NWSB) equation was parameterized for the same conditions of the experiment and external environmental. The experimental area was divided into three different treatments, maintained under stable water conditions throughout the experiment and the system was able to identify stably different stress values between treatments. Although the relationship between crop and environment affected the results, this work showed that using an irrigation system based on CWSI is possible.

Syncope and presyncope occurring during work can affect safety and impair occupational performance. Few data are available regarding the prevalence of these events among workers. The possible role of sleep quality, mental stress and metabolic disorders in promoting syncope, presyncope and falls in workers is unknown. In the present study, 741 workers (male 35.4%; mean age 47±11 years), employed in different companies, underwent clinical evaluation and blood tests and completed questionnaires to assess sleep quality, occupational distress and mental disorders. The occurrence of syncope, presyncope and unexplained falls during their working life was assessed by an ad hoc interview. The prevalence of syncope, presyncope and falls of unknown origin was 13.9%, 27.0%, and 10.3%, respectively. The occurrence of syncope was associated with an increased risk of occupational distress (adjusted Odds Ratio aOR: 1.62, Confidence Intervals at 95%: 1.05-2.52), low sleep quality (aOR: 1.79 CI 95%: 1.16-2.77) and poor mental health (aOR: 2.43 CI 95%: 1.52-3.87). Presyncope was strongly associated with occupational distress (aOR: 1.77 CI 95%: 1.25-2.49), low sleep quality (aOR: 2.95 CI 95%: 2.08-4.18) and poor mental health (aOR: 2.61 CI 95%: 1.78-3.84), while no significant relationship was found between syncope or presyncope and metabolic syndrome. These results suggest that occupational health promotion interventions aimed at improving sleep quality, reducing stressors and increasing worker resilience might reduce syncope and presyncope events in the working population.

Sensors available on mobile devices allow the automatic identification of Activities of Daily Living (ADL). This paper describes an approach for the creation of a framework for the identification of ADL, taking in account several concepts, including data acquisition, data processing, data fusion, pattern recognition, and machine learning. These concepts can be mapped in a module of the framework, including the use and creation of several algorithms. For the development of a framework that works in several conditions, e.g., without Internet connection, these algorithms should take in account the hardware and software limitations of the mobile devices to run all main tasks locally. The main purpose of this paper is related to the presentation the sensors, algorithms, and architecture of the proposed approach.

: E-commerce sales surge represents a huge challenge for urban freight transport. Parcel lockers constitute a valid solution for addressing the challenges home deliveries imply. In fact, eliminating courier-consumer contact (also relevant for health-related issues, as made evident by COVID19 pandemic) and delivering in few predefined places might help coping with missed deliveries substantially. Furthermore, this option enables consolidated shipping and reducing delivery trip costs. This paper analyses and compares consumers’ preferences for alternative collection strategies. It investigates home delivery vs parcel locker use and forecasts their future market shares. This is performed based on both customers’ socio-economic variables and attributes characterising these alternative logistic fulfilment strategies. The case study considered rests upon a stated preference survey deployed in the city of Rome. The investigation specifically targets young people (i.e., population under 30 years) since they represent early adopters. Discrete choice models allow both quantifying the monetary value of parcel lockers attributes (i.e., willingness to pay measures) and estimating the potential demand for this innovative delivery scheme. Results show that distance and accessibility are the main choice determinants. Furthermore, there is an overall high propensity to adopt parcel lockers. This research can support policymakers when implementing such solutions.

Molecular mechanisms for N2 fixation (solar NH3) and CO2 conversion to C2+ products in enzymatic conversion (Nitrogenase), electrocatalysis, metal-complexes and plasma-catalysis are analysed and compared. It is evidenced that differently from what present in thermal and plasma-catalysis, the electrocatalysis path requires not only the direct coordination and hydrogenation of undissociated N2 molecule, but to realize a series of features present in the Nitrogenase mechanism. There is the need of i) a multi-electron and -proton simultaneous transfer, not as sequential steps, ii) forming bridging metal hydride species, iii) generate intermediates stabilized by bridging multiple metal atoms, iv) have the capability of the same sites to be effective both in N2 fixation and in COx reduction to C2+ products. Only iron oxide/hydroxide stabilized at defective sites of nanocarbons was found to have these features. This comparison of the molecular mechanisms in solar NH3 production and relations with CO2 reduction is proposed to be a source of inspiration to develop the next generation electrocatalysts to address the challenging transition to a future sustainable energy and chemistry beyond fossil fuels.

This study aimed to assess the physical characteristics of elite international soccer referees, compare them with other referee populations in the literature, and establish reference tolerance ellipses for the bioelectrical impedance vector analysis (BIVA) point graph. Forty-one elite international soccer referees (age 38.8 ± 3.6 years) participated in the study. the participants underwent body composition assessments, including dual-energy X-ray absorptiometry, BIVA, and somatotype. The Somatotype Attitudinal Distance (SAD), the two-sample Hotelling’s T2 test, and the Mahalanobis test were used to determine somatotype and bioelectrical vector differences with the literature. The average somatotype of the referees was a balanced mesomorph (2.8, 6.5, 2.8). Elite international referees significantly differed from other samples in the literature (SAD = 2.1, 2.6, 2.9 with respect to Zimbabwean, Brazilian, and South African referees, respectively). The bioelectrical vector was significantly different from the general population (T2  76.6; F = 38.8; D = 1.44; P < 0.001) and athletes (T2  25.3; F = 12.6; D = 0.8; P < 0.001). Somatotype values and tolerance ellipses from this study may be useful as a reference for developing training programs and improving the selection process of referees in soccer.

Cancer is a complex and heterogeneous disease, influenced by various factors that affect its progression and response to treatment. Although histopathological diagnosis is crucial for identifying and classifying cancer, it may not accurately predict the disease's development and evolution in all cases. To address this limitation, liquid biopsy has emerged as a valuable tool, enabling a more precise and non-invasive analysis of cancer. Liquid biopsy offers the ability to detect tumor DNA fragments, circulating tumor cells, and exosomes released by cancer cells into the bloodstream. Exosomes, in particular, have attracted significant attention in cancer research due to their specific protein composition, which can provide valuable insights into the disease. The protein profile of exosomes often differs from that of normal cells, reflecting the unique molecular characteristics of cancer. Analyzing these proteins can help identify cancer-associated markers that play critical roles in tumor progression, invasion, and metastasis. Ongoing research and clinical validation are essential to advance and effectively utilize protein biomarkers in cancer. Nevertheless, their potential to improve diagnosis and treatment is highly promising. This review discuss several exosome proteins of interest in breast cancer, particularly focusing on studies conducted in mammary tissue and cell lines in humans and experimental animals. Unfortunately, the studies conducted in the canine species are scarce. This emphasis sheds light on the limited research available in this field. Additionally, we present a curated selection of studies that have explored exosomal proteins as potential biomarkers, aiming to achieve the aforementioned benefits in breast cancer diagnosis, prognosis, monitoring, and treatment.

Canine mammary tumors (CMTs) are among the most common disease in female dogs and share similarities with human breast cancer, which have placed these animals as a model of study in comparative oncology. Metabolic reprogramming is one of them and is known as a hallmark of carcinogenesis whereby cells undergo adjustments to supply the high bioenergetic and biosynthetic demands of rapidly proliferating cells. However, such alterations are also vulnerabilities that may serve as therapeutic strategies which have been tested mostly in human clinical trials, but poorly explored in CMTs. In this dedicated review, we compilated the metabolic changes described for CMTs emphasizing the metabolism of carbohydrates, amino acids, lipids, and mitochondrial function. We observed here key factors associated with the presence and aggressiveness of CMTs, such as the increase in glucose uptake followed by enhanced anaerobic glycolysis via upregulation of glycolytic enzymes, changes in glutamine catabolism due to overexpression of glutaminases, raise in fatty acid oxidation and distinct effects depending on the lipid saturation, in addition to mitochondrial DNA which is a hotspot for mutations. Therefore, more attention should be paid to this topic given that targeting metabolic fragilities could improve the outcome of CMTs.

Worldwide anthropogenic activities result in the production and release of poten-tially damaging toxic pollutants into ecosystems, thereby jeopardizing their health and continuity. Research studies and biomonitoring programs attend to this emerging problematic by applying and developing statistically relevant indexes that integrate complex biomarker response data to provide an holistic approach reflecting toxically induced alterations at the organism’s or population level. Ultimately, indexes allow simple result communication, enhancing policy makers understanding, so contributing for better resource and environmental managing policies. In this study three indexes , the Integrated Biomarker Response index (IBR), the Bioeffects Assessment Index (BAI) and the Principal Components Analysis (PCA), were evaluated for their sensitivity in revealing toxically induced stress patterns in cells of the diatom Phaeodactylum tricornutum under contaminant exposure. The set of biomarkers selected for index construction comprise the anti-oxidant enzymes APX, CAT and SOD, and the lipid peroxidation marker TBARS. Several significant inverse correlations with the concentration gradients applied, , was noticed for all indexes, though, the IBR excels for its reliability in delivering statistically significant dose-response patterns for four out of the five compounds tested.

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

The mobile devices caused a constant struggle for the pursuit of data privacy. Nowadays, it appears that the number of mobile devices in the world is increasing. With this increase and technological evolution, thousands of data associated with everyone are generated and stored remotely. Thus, the topic of data privacy is highlighted in several areas. There is a need for control and management of data in circulation inherent to this theme. This article presents an approach of the interaction between the individual and the public environment, where this interaction will determine the access to information. This analysis was based on a data privacy management model in public environments created after reading and analyzing the current technologies. A mobile application based on location via Global Positioning System (GPS) was created to substantiate this model, which it considers the General Data Protection Regulation (GDPR) to control and manage access to the data of each individual.

Evaluation of drug permeability using cell monolayers is an important in vitro assay in the process of drug development, to identify compounds with favourable pharmacokinetics that may proceed to in vivo studies. When allowed to differentiate on permeable filters for at least 21 days, monolayers of Caco-2 cells develop morphological and functional properties similar to those of the intestinal epithelium. Permeability through Caco-2 monolayers is thus particularly relevant to assess drug absorption after oral administration. The major drawback of this assay is its very low throughput, with the cell monolayers being used in a single permeability assay. We have previously proposed a protocol to allow the re-use of the Caco-2 monolayer on additional permeability assays during the stable period and shown that cell monolayer integrity is maintained. In this work we evaluate the effect of re-use on the permeability of several reference compounds that permeate through passive pathways and show that the cell monolayers can be re-used twice in additional permeability assays. Preliminary results were also obtained regarding active transport pathways, and a new methodology is proposed to quantify the contribution from passive and active transport. This is a major step towards the full validation of the re-use methodology proposed, which at least triplicates the throughput of this important in vitro assay.

Background: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. Understanding their combined impact could enhance risk assessment and management strategies. Hypothesis: We hypothesized that the synergistic effects of hypertension and carotid plaques would increase the risk of both cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology department of Vilnius University Hospital Santaros klinikos between 2012 and 2021. The study recruited participants aged 40-60 who did not have overt CVD and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. The participants were monitored for 4-10 years for CVD events and all-cause mortality. Results: Among 6,138 participants, 954 (16%) experienced cardiovascular disease (CVD) events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events, stroke, or all-cause mortality. Conclusion: The combination of hypertension and carotid plaque did not significantly increase the risk of CVD events or all-cause mortality. CV events depend on the spread of the atherosclerosis process in the carotid vessels.

Epidemiological studies have shown that consuming olive oil rich in phenolic bioactive compounds is associated with a lower risk of neurodegenerative diseases and better cognitive performance in aged populations. Since oxidative stress is a common hallmark of age-related cognitive decline, incorporating exogenous antioxidants could have beneficial effects on brain aging. In this review, we firstly summarize and critically discuss the current preclinical evidence and the potential neuroprotective mechanisms. Existing studies indicates that olive oil phenolic compounds can modulate and counteract oxidative stress and neuroinflammation, two relevant pathways linked to the onset and progression of neurodegenerative processes. Secondly, we summarize the current clinical evidence. In contrast to preclinical studies, there is no direct evidence in humans of the bioactivity of olive oil phenolic compounds. Instead, we have summarized current findings regarding nutritional interventions supplemented with olive oil on cognition. A growing body of research indicates that high consumption of olive oil phenolic compounds is associated with better preservation of cognitive performance, conferring an additional benefit, independent of the dietary pattern. In conclusion, the consumption olive oil rich in phenolic bioactive compounds has potential neuroprotective effects. Further research is needed to understand the underlying mechanisms and potential clinical applications.

The mutualistic interactions between the oleaginous yeast Lipomyces starkeyi and the green mi-croalga Chloroidium saccharophilum in mixed cultures were investigated to exploit possible syner-gistic effects. As a matter of facts, microalga could act as an oxygen generator for the yeast, while the yeast could provide carbon dioxide to microalga. A lignocellulosic hydrolysate from steam exploded Arundo donax (Giant reed) was used as low cost feedstock. The overall lipid content and lipid productivity obtained in the mixed culture treating the hydrolysate of Arundo donax were equal to 0.081 glipid.gbiomass-1 and 37.2 mglipid.L-1.d-1, respectively. They represented promising re-sults if compared to the model systems where synthetic media were used. This study provided new input for the integration of Single Cell Oil (SCO) production with agro-industrial feedstock and the fatty acid distribution mainly consisting of stearic (C18:0) and oleic acid (C18:1) allows promising applications in biofuels, cosmetics, food additives and other products of industrial interest.

Background: In a Beveridgean decentralized healthcare system, like the Italian one, where regions are responsible for their own health planning and financing, the analysis of patients’ migration appears very interesting as it has economic and social implications. The study aims to analyze both patients’ migration for hospital rehabilitation and if the beds endowment is a driver for these flows; Methods: from 2011 to 2019, admissions data were collected from the Hospital Dis-charge Cards database of the Italian Ministry of Health, population data from Italian National Institute of Statistics and data of beds endowment from the Italian Ministry of Health website. To evaluate patients’ migration, we used Gandy’s Nomogram, while to assess if beds endowments are mobility drivers, we have created two matrices, one with attraction indexes (AI) and one with escape indexes (EI). The beds endowment, for each Italian region, were correlated with AI and EI. Spearman’s test was carried out through STATA software; Results: Gandy’s Nomogram showed that only some northern regions had good hospital planning for rehabilitation. A statistically significant correlation between beds endowment and AI was found for four regions, while with EI for eight regions. Conclusions: Only some northern regions appear able to satisfy the care needs of their residents, with an attraction minus escapes positive epidemiological balance. The beds endowment seems to be a driver of Patients’ migration, mainly for escapes. Certainly, the search for mobility drivers needs further investigation given the events in Molise and Basilicata.

Laser Powder Directed Energy Deposition (LP-DED) is an Additive Manufacturing process in which a laser beam is used to generate a melt pool onto a substrate. The additional material, in form of powder material, is fed into the generated melt pool and a raised track is obtained. The LP-DED process is very powerful for different applications such as the repair operations and the production of functionally graded material, however the application is still limited and one of the main reasons is related to the lack of knowledge in the physics of the process mechanisms. The process is influenced by a huge number of parameters and three main mechanisms can be identi-fied. These mechanisms are the powder flow, the generation of the molten pool and the solidifica-tion process and for each of these mechanisms the process parameters have a different relevance. In this paper, a review of the main mechanisms and the relationship between the process parame-ters and the outcome of each step of the process is presented.

The following article analyzes the determinants of e-government in 28 European countries between 2016 and 2021. The DESI-Digital Economy and Society Index database was used. The econometric analysis involved the use of the Panel Data with Fixed Effects and Panel Data with Variable Effects methods. The results show that the value of “e-Government” is negatively associated with “Fast BB (NGA) coverage”, “Female ICT specialists”, “e-Invoices”, “Big data” and positively associated with “Open Data”, “e-Government Users”, “ICT for environmental sustainability”, “Artificial intelligence”, “Cloud”, “SMEs with at least a basic level of digital intensity”, “ICT Specialists”, “At least 1 Gbps take-up”, “At least 100 Mbps fixed BB take-up”, “Fixed Very High Capacity Network (VHCN) coverage”. A cluster analysis was carried out below using the unsupervised k-Means algorithm optimized with the Silhouette coefficient with the identification of 4 clusters. Finally, a comparison was made between eight different machine learning algorithms using "augmented data". The most efficient algorithm in predicting the value of e-government both in the historical series and with augmented data is the ANN-Artificial Neural Network.

This article analyzes the determinants of the "Broadband Price Index" in Europe. The data used refer to 28 European countries between 2016 and 2021. The database used is the Digital, Economy and Society Index-DESI of the European Commission. The data were analyzed using the following econometric techniques, namely Panel Data with Random Effects, Panel Data with Fixed Effects, Pooled OLS, WLS and Dynamic Panel. The value of the "Broadband Price Index" is positively associated with the DESI Index, and "Connectivity" while it is negatively associated with "Fixed Broadband Take Up", "Fixed Broadband Coverage", "Mobile Broadband", "e-Government", "Advanced Skills and Development", "Integration of Digital Technology", "At Least Basic Digital Skills ", "Above Basic Digital Skills "," At Least Basic Software Skills ". A cluster analysis was carried out below using the k-Means algorithm optimized with the Silhouette coefficient. The analysis revealed the existence of three clusters. Finally, an analysis of the machine learning algorithms was carried out to predict the future value of the "Broadband Price Index". The result shows that the most useful algorithm for prediction is the Artificial Neural Network-ANN with an estimated value equal to an amount of 9.21%.

Laser-Powder Directed Energy Deposition (DED-LB/Powder) is an additive manufacturing process that is gaining popularity in the manufacturing industry due to its numerous advantages, particularly in repairing operations. However, its application is often limited to case studies due to some critical issues that need to be addressed, such as the degree of internal porosity. This paper investigates the effect of the most relevant process parameters of the DED-LB/Powder process on the level and distribution of porosity. Results indicate that, among the process parameters examined, porosity is less affected by travel speed and more influenced by powder mass flow rate and laser power. Additionally, a three-dimensional finite element transient model was introduced, which was able to predict the development and location of lack-of-fusion pores along the building direction.

Mitochondrial dysfunction plays a pivotal role in numerous complex diseases. Understanding the molecular mechanisms by which the “powerhouse of the cell” turns into the “factory of death” is an exciting yet challenging task that can unveil new therapeutic targets. The mitochondrial matrix protein CyPD is a peptidylprolyl cis-trans isomerase involved in the regulation of the permeability transition pore (mPTP). The mPTP is a multi-conductance channel in the inner mitochondrial membrane whose dysregulated opening can ultimately lead to cell death and whose involvement in pathology has been extensively documented over the past few decades. Moreover, several mPTP-independent CyPD interactions have been identified, indicating that CyPD could be involved in the fine regulation of several biochemical pathways. To further enrich the picture, CyPD undergoes several post-translational modifications that regulate both its activity and interaction to its clients. Here, we will dissect what is currently known about CyPD and critically review the most recent literature about its involvement in neurodegenerative disorders, focusing on Alzheimer’s Disease and Parkinson’s Disease, supporting the notion that CyPD could serve as a promising therapeutic target for the treatment of such conditions. Notably, significant efforts have been made to develop CyPD-specific inhibitors, which hold promise for the treatment of such complex disorders.

Radiotherapy commonly utilizes CBCT for patient positioning and treatment monitoring. CBCT is deemed to be secure for patients, making it suitable for the delivery of fractional doses. However, limitations such as a narrow field of view, beam hardening, scattered radiation artifacts, and variability in pixel intensity hinder the direct use of raw CBCT for dose recalculation during treatment. To address this issue, reliable correction techniques are necessary to remove artifacts and remap pixel intensity into HU values. This study proposes a deep-learning framework for calibrating CBCT images acquired with narrow FOV systems and demonstrates its potential use in proton treatment planning updates. Cycle-consistent GAN processes raw CBCT to reduce scatter and remap HU. Monte Carlo simulation is used to generate CBCT scans, enabling the possibility to focus solely on the algorithm’s ability to reduce artifacts and cupping effects without considering intra-patient longitudinal variability and producing a fair comparison between planning CT and calibrated CBCT dosimetry. To showcase the viability of the approach using real-world data, experiments were also conducted using real CBCT. Tests were performed on a publicly available dataset of 40 patients who received ablative radiation therapy for pancreatic cancer. The simulated CBCT calibration led to a difference in proton dosimetry of less than 2%, compared to the planning CT. The potential toxicity effect on the organs at risk decreased from about 50% (uncalibrated) up the 2% (calibrated). The gamma pass rate at 3%/2mm produced an improvement of about 37% in replicating the prescribed dose before and after calibration (53.78% vs 90.26%). Real data also confirmed this with slightly inferior performances for the same criteria (65.36% vs 87.20%). These results may confirm that generative artificial intelligence brings the use of narrow FOV CBCT scans incrementally closer to clinical translation in proton therapy planning updates.

The Urban Heat Island (UHI) is one of the more serious consequences of urbanization resulting in impacts on thermal comfort levels, heat stress, and even mortality. For Municipal Beirut, implementation of “cool” surface materials and green spaces have been recommended to counterbalance the UHI. This paper builds on previous findings on the topic of non-constructible parcels within the district of Bachoura in Municipal Beirut and examines the possibility of implementing “cool” surface or paving materials and urban vegetation which can improve thermal conditions especially during the summer period and with the viewto project the positive findings of this case study to the entire Municipal Beirut area. A numerical analysis using ENVI-met 4.0 investigates the thermal performance of these non-constructibles further to implementation of high reflective surfaces and urban vegetation within a broad neighborhood scale in Bachoura. Results show reductions in ambient temperatures up to 1K on a summer day.. Within the framework of an integrated approach to planning, this form of urban acupuncture aims for substantial UHI reduction. Energy performance of buildings further to implementation of these mitigation measures is also recommended for future studies and to validate the findings in this paper.

Cork oak tree (Quercus suber L.) symbolises Montado landscape in Portugal and is a central element in the country's social and economic history. In recent decades, the loss of thousands of cork oaks has been reported, revealing the ongoing decline of these agro-forestry ecosystems. This emblematic tree of the Mediterranean Basin is host to the soil-born root pathogen Phytophthora cinnamomi, an active cork oak decline driver. In this framework, the early diagnosis of trees infected by the oomycete by non-invasive methods should contribute to the sustainable management of cork oak ecosystems and motivated this work. Using leaf reflectance spectroscopy it was possible to distinguish plants inoculated with P. cinnamomi from non-inoculated plants in a long course assay and to argue about the factors contributing to this differentiation. Spectral acquisitions in the visible-near infrared (400–1100 nm) were performed at 63, 78, 91, 126 and 248 days after inoculation (DAI), on the abaxial and adaxial faces of the leaves, and the spectral data was arranged in a three-way array of samples × wavelengths × days. The separation of the two plant groups were attributed to variations in water content (4v (O−H)) and/or a shift in the red edge and to structural modifications in the epidermal layer and/or the mesophyll of the leaves observed in the visible range. These spectral signatures can assist in the field identification of cork oaks that are interacting with P. cinnamomi.

Data collection and analysis are becoming more and more important in a variety of application domains as long as the novel technologies advance. At the same time, we are experiencing a growing need for human-machine interaction with expert systems pushing research through new knowledge representation models and interaction paradigms. In particular, in the last years eHealth - that indicates all the health-care practices supported by electronic elaboration and remote communications - calls for the availability of smart environment and big computational resources. The aim of this paper is to introduce the HOLMeS (Health On-Line Medical Suggestions) framework. The introduced system proposes to change the eHealth paradigm where a trained machine learning algorithm, deployed on a cluster-computing environment, provides medical suggestion via both chat-bot and web-app modules. The chat-bot, based on deep learning approaches, is able to overcome the limitation of biased interaction between users and software, exhibiting a human-like behavior. Results demonstrate the effectiveness of the machine learning algorithms showing 74.65% of Area Under ROC Curve (AUC) when first-level features are used to assess the occurrence of different prevention pathways. When disease-specific features are added, HOLMeS shows 86.78% of AUC achieving a more specific prevention pathway evaluation.

Quality of life (QoL) assessments are integral to cancer care, yet their effectiveness in providing essential information for supporting survivors varies. This study aimed to elucidate key indicators of QoL among colorectal cancer survivors from the perspective of healthcare professionals, and to evaluate existing QoL questionnaires in relation to these indicators. Two studies were conducted: a Delphi study to identify key QoL indicators and a scoping review of questionnaires suitable for colorectal cancer survivors. Fifty-four healthcare professionals participated in the Delphi study's first round, with 25 in the second. The study identified two primary QoL domains (Physical and Psychological) and 17 subdomains deemed most critical. Additionally, a review of 12 questionnaires revealed two instruments assessing the most important general domains. Findings underscored a misalignment between existing assessment tools and healthcare professionals' clinical priorities in working with colorectal cancer survivors. To enhance support for survivors' QoL, efforts are needed to develop instruments that better align with the demands of routine QoL assessment in clinical practice.

Diabetes mellitus is a chronic disease, commonly associated with unhealthy habits and obesity, and it is becoming a serious health issue worldwide. As a result, new approaches to treat diabetes are required, and a movement towards more natural ones is emerging. Consuming fruit and vegetables is advised to prevent diabetes since they contain several bioactive compounds. A simple and ef-fective strategy to include them in the diets of diabetic and obese people is through beverages. This review aimed to report the anti-diabetic potential of different vegetable and fruit beverages. These functional beverages demonstrated in vitro potential to inhibit α-glucosidase and α-amylase en-zymes, and to improve glucose uptake. In vivo, the beverage consumption showed a reduction of blood glucose, increase of insulin tolerance, improvement of lipid profile, control of obesity, and reduction of oxidative stress. This suggests the potential of vegetable and fruit-based functional beverages to be a natural innovative therapy for the management of diabetes.

Ammonia is an atmospheric pollutant, predominantly emitted from agriculture, leading acidification and eutrophication of soil and water and contributing to secondary PM2.5. The implementation of accurate emission inventories with high spatial and time resolution plays a fundamental role in the development of air modelling simulation and in the impact assessment of actions for air quality improvement. The development and release of new algorithms and the increase of data availability are supporting the implementation of machine learning approaches in environmental and air quality data analysis. In this paper we present a methodology developed by the application of the Random Forest algorithm to bottom-up local emission inventories of ammonia to validate annual time series of ammonia emissions and calculate high resolution temporal profiles. The model has been trained and tested by the hourly measurements of ammonia concentrations and atmospheric turbulence parameters starting from a constant emission scenario. The initial values of emissions are calculated based on a bottom-up emission inventory detailed at the municipal basis and considering a circular area of about 4 km radius centered on measurement sites. By comparing predicted and measured concentrations, the emissions are modified, the model's training and testing are repeated, and the model converges to a very high performance in predicting ammonia concentrations and establishing an hourly time changing emission profile. The site-specific emissions profiles, estimated by the proposed methodology, clearly show a nonlinear relation with measured concentrations and allow to identify the effect of atmospheric turbulence on pollutant accumulation. The estimated time series well confirm the available data of the emission inventories and the monthly emission profiles have been compared with estimated data from satellite.

The use of convolutional neural networks (CNNs) in image classification has become the standard method of approaching computer vision problems. Here we apply pre-trained networks to classify images of non-breaking, plunging and spilling breaking waves. The CNNs are used as basic feature extractors and a classifier is then trained on top of these networks. The dynamic nature of breaking waves is exploited by using image sequences to gain extra information and improve the classification results. We also see improved classification performance in using pre-computed image features such as the optical flow between image pairs. The inclusion of the dynamic information improves the classification between breaking wave classes. We also provide corrections to the methodology from the article from which the data originates to achieve a more accurate assessment of performance.

The major stress-inducible Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending on its intracellular or membrane localization, Hsp70 either promotes tumor growth or serves as a target for NK cells. The kinetics of the membrane Hsp70 (mHsp70) density on human glioma cells (U87) was studied after different irradiation doses to define the optimal therapeutic window for Hsp70-targeting NK cells. To maintain the cells in the exponential growth phase during a cultivation period of 7 days different initial cell counts were seeded. Although cytosolic Hsp70 levels remained unchanged on days 4 and 7 after a sublethal irradiation with 2 Gy, 4 Gy and 6 Gy, a dose of 2 Gy resulted in an upregulated mHsp70 density in U87 cells which peaks on day 4 and starts to decline on day 7. Higher radiation doses (4 Gy, 6 Gy) resulted in an earlier and more rapid onset of the mHsp70 expression on days 2 and 1, respectively, followed by a decline on day 5. Membrane Hsp70 levels are higher in G2/M than in G1, however, an irradiation-induced cell cycle arrest on days 4 and 7, was not associated with an increase in the mHsp70 density. Extracellular Hsp70 concentrations increased significantly compared to sham (0 Gy) irradiated cells on days 4 and 7 but not on day 1. Functionally, elevated mHsp70 densities were associated with a significantly better lysis by Hsp70-targeting NK cells. In summary, the kinetics of changes in the mHsp70 density upon irradiation on tumor cells is time- and dose-dependent.

Nowadays, we can observe a worldwide trend towards the development of synthetic biomaterials. Numerous researches have been carried out in order to better understand the cellular behavior involved in the inflammation and bone healing processes related to living tissues. The aim of this study is to evaluate the tissue behavior of two different types of biomaterials: synthetic nano-hydroxyapatite / beta-tricalcium phosphate and hydroxyapatite in non-critical bone defects in rat calvaria. Twenty four rats underwent surgery in which two 3 mm defects in each cavity were performed. The rats were divided into 2 groups: Group 1, using xenogen hydroxyapatite (Bio oss ™); Group 2, using synthetic nano-hydroxyapatite / beta-tricalcium phosphate (Blue Bone ™). Sixty days after the surgery, the calvaria bone defect was filled with biomaterial, the animals were sacrificed and marked with Masson's trichrome and PAS staining, and immunohistochemistry (TNF-α, MMP-9) and electron microscopy analyzes were performed. Histomorphometric analysis indicates a greater presence in the protein matrix in Group 2, in addition to higher levels of TNF-α, MMP-9. The ultrastructural analysis shows an association of material with fibroblasts in the tissue regeneration stage. Paired statistical data indicates that Blue Bone ™ can improve bone formation / remodeling when compared to biomaterials of xenogenous origin.

Candida spondylodiscitis (CS) is a rare disease, for which therapeutic option are limited to fluconazole or echinocandins and the treatment should be administered up to 12 months. In case of reduced azole susceptibility, there is a scarcity of therapeutic options with adequate bone penetration and limited toxicity. We report the first case of successful use of rezafungin for a spondylodiscitis due to Candida parapsilosis with reduced susceptibility to azoles. The patient, affected by paraplegia and short bowel syndrome, was diagnosed with CS with culture on vertebral biopsy guided by a 18-FDG-PET/CT scan. He received rezafungin 200 mg weekly for 26 weeks, after 10 weeks of previous antifungal treatment. He had a full clinical, radiologic and biochemical response to the therapy with rezafungin, with no adverse effects. Rezafungin is a promising therapy for Candida osteomyelitis, especially when first line therapies are ineffective or contraindicated.

The targeted application of plant growth promoting rhizobacteria (PGPR) provides the key for a future sustainable agriculture with reduced pesticide application. PGPR interaction with the indigenous microbiota is poorly understood but essential to develop reliable applications. Therefore, Stenotrophomonas rhizophila SPA-P69 was applied as seed coating and in combination with a fungicide based on the active ingredients fludioxonil, metalaxyl-M, captan and ziram. Plant performance and rhizosphere composition of treated and non-treated maize plants of two field trials were analyzed. Plant health was significantly increased by treatment; however overall corn yield was not changed. By applying high-throughput amplicon sequencing of the 16S rRNA and the ITS genes, the bacterial and fungal changes in the rhizosphere due to different treatments were determined. Despite treatments had a significant impact on the rhizosphere microbiota (9- 12%), the field site was identified as main driver (27- 37%). Soil microbiota composition from each site was significantly different, which explains the site-specific effects. In this study we were able to show first indications how PGPR treatments increase plant health via microbiome shifts in a site-specific manner. This way first steps towards a detailed understanding of PGPRs and developments of consistently efficient applications in diverse environments are set.

Infertility” is a condition defined by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse or due to an impairment of a person’s capacity to reproduce either as an individual or with his/her partner’. The authors have set out to succinctly investigate, explore and assess infertility treatments harnessing the potential of stem cells to effectively and safely treat infertility, in addition to the legal and regulatory complexities at the heart of stem cell research, with an overview of the legislative state of affairs in six major European countries. In couples who cannot benefit from assisted reproductive technologies (ART) to treat their infertility, stem cells-based approaches have been shown to be a highly promising approach. Nonetheless, lingering ethical and immunological uncertainties require more conclusive findings and data before such treatment avenues can become mainstream and applied large scale. The isolation of human embryonic stem cells (ESCs) is ethically controversial, since their collection involves the destruction of human embryonic tissue. Overall, stem cell research has resulted in important new breakthroughs in the treatment of infertility. The effort to untangle the complex web of ethical and legal issues associated with such therapeutic approaches will have to rely on evidence-based, broadly shared standards, guidelines and best practices to make sure that the procreative rights of patients can be effectively reconciled with the core values at the heart of medical ethics.

Anthocyanins, the naturally occurring pigments responsible for most red to blue colours of flowers, fruits and vegetables, have also attracted interests because of their potential health effects. With the aim of contributing to major insights into their structure-activity relationship (SAR), we have evaluated the radical scavenging and biological activities of selected purified anthocyanin samples (PASs) from various anthocyanin-rich plant materials: two fruits (mahaleb cherry and blackcurrant) and two vegetables (black carrot and ‘Sun Black’ tomato). PASs from the above-mentioned plant material have been evaluated for their antioxidant capacity, using TEAC and ORAC assays. In human endothelial cells, we analysed the biological activity of different PASs by measuring their effects on the expression of endothelial inflammatory markers, including endothelial adhesion molecules VCAM-1 and ICAM-1. We demonstrated that all the different PASs showed biological activity. They exhibited antioxidant capacity of different magnitude, higher for samples containing non-acylated anthocyanins (typical for fruits) compared to samples containing more complex anthocyanins acylated with cinnamic acid derivatives (typical for vegetables), even though this order was slightly reversed when ORAC assay values were expressed on molar basis. Concordantly, PASs containing non-acylated anthocyanins reduced the expression of endothelial inflammatory antigens more than samples with aromatic acylated anthocyanins, suggesting the potential beneficial effect of structurally diverse anthocyanins in cardiovascular protection.

Soil texture is a key property influencing most soil physical, chemical, and biological processes and its catchment-scale spatial variation may yields insights for soil management. Texture data are generally available only at a few locations, since sampling and laboratory analyses are time consuming. Therefore, it is essential to predict soil size particles texture variability using appropriate methods. Moreover, soil texture distribution across a catchment is influenced by erosion and sedimentation processes controlled by hillslope morphology, which can be quantified through some topographic attributes. The study was aimed to evaluate the ability of a multivariate approach based on non-stationary geostatistics to merge remotely sensed high-resolution LiDAR-derived topographic attributes with Vis-NIR diffuse reflectance spectroscopy and laboratory analysis to produce high-resolution maps of soil sand content and estimation uncertainty in a forested catchment in southern Italy. Moreover, the proposed approach was compared with the commonly used univariate approach of ordinary kriging. Soil samples were collected at 135 locations within a 139 ha-forest catchment with granitic parent material and subordinately alluvial deposits, where soils classified as Typic Xerumbrepts and Ultic Haploxeralf crop out. A number of linear trend models coupled with different auxiliary variables were compared and the best one resulted the model using clay content as auxiliary variable. The improvement of estimation from using only LiDAR data (elevation) compared to the univariate (no trend) model was rather marginal.

Tropical forests constitute prolific sanctuary of unique floral diversity and potential medicinal sources, however, many of them remains unexplored. Herein, seven Mascarene endemic plants leaves were extracted and evaluated for their in vitro antioxidant properties and antiproliferative effects on a panel of cancer cell lines using MTT and clonogenic cell survival assay. Flow cytometry and comet assay were used to investigate the cell cycle and DNA damaging effects, respectively. Bioassay guided-fractionation coupled with LC-Mass spectrometry (MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopy analysis were used to identify the bioactive compounds. Among the seven plants tested, Terminalia bentzoë was comparatively the most potent antioxidant extract with significantly (p < 0.05) higher cytotoxic activities. T. bentzoë extract further selectively suppressed the growth of human hepatocellular carcinoma cells and significantly halted the cell cycle progression in G0/G1 phase, decreased the cells replicative potential and induced significant DNA damage. Ten phenolic compounds including punicalagin and ellagic acid were identified and likely contributed to the extract potent antioxidant and cytotoxic activities. These results established a promising basis for further in-depth investigations on the potential use of T. bentzoë as supportive therapy in cancer management.

Pulmonary hypertension (PH) has a high mortality, and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type 2 and type 17 responses in C57BL/6 mice. Here, we focused on type 2 response related cytokines, specifically Resistin-like-molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild type or RELMα-/- mice. Vascular remodeling was assessed by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were more prominent in the C57BL/6 strain. Compared to wild type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV ST2-IL-33-receptor were significantly increased in BALB/c wild type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild type or C57BL/6-RELMα-/- mice. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.

Machine Learning can be used for social good. In this paper, we discuss how it can be used to combat climate change and facilitate land management and farming in developing countries and in particular in Côte d’Ivoire. This paper explores models that improve land and water management and agricultural farming cultivation to contrast climate change. Côte d’Ivoire is the largest producer of cocoa beans (43%) in the world, but deforestation, lack of rainfall, drought, and climate change threaten crops and the already fragile economy of Ivorian farmers. It is important to combat climate change with methods and techniques that are affordable to the local farmers and also induce positive effects in production. We discuss the use of low-cost sensors to collect data on the soil and open data and open source software to develop AI tools. We show that using deep neural networks (YOLOv5m) is effective for detecting healthy plants and pods of cocoa from damaged ones only using mobile phone images. Focusing on a single land is not enough to combat climate change, which has different causes and involves also knowledge at a higher scale. We propose a new method of forecasting for the analysis of remote sensors. Remote sensor data come from GRACE NASA Mission and ERA5 produced by the Copernicus Climate Change Service at ECMWF. We implement a new deep neural network architecture named CIWA-net. It is based on a Fully Convolutional Neural Network (FCN) [ 1] and it is a U-net like architecture [2]. The aim of CIWA-net is to forecast Total Water Storage Anomalies (TWSA). We show the quality of our model with a comparison to a vanilla Convolutional Neural Network. CIWA-net could be used also for the detection of lands that interfere with agricultural work and yields, such as deserted areas, water-soaking soil areas, zones at risk of desertification, and poor land use. The employment of AI at the service of agriculture can decrease crop losses and waste, lower the inputs onto the soil of fertilizers, responsible for the increase of Greenhouse Gases. It could be useful to help the small farmers (at a local scale) and also the policy-makers and farmers’ cooperatives (at the regional scale) to take valid and coordinated countermeasures to improve the correct use of the lands, helping to contrast and adapt to climate change.

In the last decades, consumers are increasingly interested in organic products and they strongly demand for reliability of the traceability of the organic products they use to buy and eat. Different researches have been carried out over the years to investigate on new and reliable systems to test the authenticity of products obtained using organic cultivation methods. The monitoring of some chemical components, derived from primary and/or secondary metabolism, in horticultural organic and conventional products, has highlighted the diversity induced by the two production techniques while the difference in fertilization practices has been shown to impact on the isotopic distribution of some elements, with particular reference to nitrogen. An integrated system is proposed to validate, through the acquisition of isotopic data and other chemical and biochemical parameters, the authenticity of organic products. This approach is intended to be coupled to the application of chemometric multivariate analysis of isotopic data combined with other quality and nutraceutical parameters, giving the possibility to discriminate organic from conventional products, thanks to the different isotopic signature impressed by the different nitrogenous source combined with the qualitative pattern of the crops, significantly affected by the different treatments. The main perspectives of the presented integrated approach, based on the combined use of chemometric and analytical tools, are linked to the feasibility of applying a reliable system to authenticate productions obtained with organic fertilizers (organic agriculture) respect to those obtained with the use of synthetic fertilizers (conventional agriculture), protect and valorize virtuous farmers and support political stakeholders and decision makers to counteract food fraud.

This article presents an estimation of the hypertension risk based on a dataset on 1007 individuals. The application of a Tobit Model shows that “Hypertension” is positively associated to “Age”, “BMI-Body Mass Index”, and “Heart Rate”. The data show that the element that has the greatest impact in determining inflation risk is “BMI-Body Mass Index”. An analysis was then carried out using the fuzzy c-Means algorithm optimized with the use of the Silhouette coefficient. The result shows that the optimal number of clusters is 9. A comparison was then made between eight different machine-learning algorithms for predicting the value of the Hypertension Risk. The best performing algorithm is the Gradient Boosted Trees Regression according to the analyzed dataset. The results show that there are 37 individuals who have a predicted hypertension value greater than 0.75, 35 individuals who have a predicted hypertension value between 0.5 and 0.75, while 227 individuals have a hypertension value between 0.0 and 0.5 units.

The following article indicates the determinants of “Internet User Skills” among European countries based on the application of the database deriving from the DESI-Index. The data were analyzed using the following econometric models, namely: Panel Data with Fixed Effects, Panel Data with Random Effects, Pooled OLS, WLS, WLS corrected for heteroskedasticity. The Elbow method and the Silouette coefficient method were compared for the optimization of the number of clusters obtained by the k-Means algorithm. The result shows the presence of 5 clusters. A network analysis was carried out using the Euclidean distance with the result of identifying two network structures between some analyzed countries. subsequently a comparison was made between six different machine learning algorithms for the prediction of the future value of the variable of interest. The result shows that the best predictor algorithm is Gradient Boosted Tree Regression with an expected value of the predicted variable increasing by a value of 1.75%. Later a further comparison was made by comparing 6 algorithms with the increased data. The result shows that the best predictor is Simple Regression Tree. The interest variable is predicted to decrease by an amount equal to -6.099%. Statistical errors improve on average by 32.43% in the transition between the original data and the increased data.

The following article estimates the value of ICT Specialists in Europe between 2016 and 2021 for 28 European countries. The data were analyzed using the following econometric techniques, namely: Panel Data with Fixed Effects, Panel Data with Random Effects, WLS and Pooled OLS. The results show that the value of ICT Specialists in Europe is positively associated with the following variables: "Desi Index", "SMEs with at least a basic level of digital intensity", "At least 100 Mbps fixed BB take-up" and negatively associated with the following variables: "4G Coverage","5G Coverage", "5G Readiness", "Fixed broadband coverage", "e-Government", "At least Basic Digital Skills", "Fixed broadband take-up", "Broadband price index", "Integration of Digital Technology". Subsequently, two European clusters were found by value of "ICTG Specialists" using the k-Means clustering algorithm optimized by using the Silhouette coefficient. Finally, eight different machine learning algorithms were compared to predict the value of "ICT Specialists" in Europe. The results show that the best prediction algorithm is ANN-Artificial Neural Network with an estimated growth value of 12.53%. Finally, "augmented data" were obtained through the use of the ANN-Artificial Neural Network, through which a new prediction was made which estimated a growing value of the estimated variable equal to 3.18%.

Monitoring and measuring magnesium (Mg) values are essential to prevent the development of numerous complications in perioperative medicine and critically ill patients. Although previous studies suggest that measuring free ionized magnesium (iMg) is more useful for estimating Mg status, clinicians currently rely on measurement of total serum magnesium to determine if supplemental magnesium is needed. In this review, we analyzed the recent literature to decide whether it is better to measure ionized serum Mg or total serum Mg when assessing magnesium status, whether iMg predicts clinical outcome, and what are the difficulties in measuring serum iMg levels in intensive care patients and perioperative medicine.

The inhibition of heat shock protein 90 (Hsp90) a molecular chaperone for multiple oncogenic client proteins is considered as a promising approach to overcome radioresistance. Since most Hsp90 inhibitors activate HSF-1 that induces the transcription of cytoprotective and tumor-promoting stress proteins such as Hsp70 and Hsp27, a combined approach consisting of HSF-1 knockdown (k.d.) and Hsp90 inhibition was investigated. A specific HSF-1 k.d. was achieved in H1339 lung cancer cells using RNAi-Ready pSIRENRetroQ vectors with puromycin resistance. The Hsp90 inhibitor NVP-AUY922 was evaluated at low concentrations - ranging from 1-10nM - in control and HSF-1 k.d. cells. Protein expression (i.e., Hsp27/Hsp70, HSF-1, pHSF-1) and transcriptional activity was assessed by Western blot analysis and luciferase assays and radiosensitivity was measured by proliferation, apoptosis (Annexin V, active caspase 3), clonogenic cell survival, alkaline comet, γH2AX, 53BP1 and Rad51 foci assays. The k.d. of HSF-1 resulted in a significant reduction of basal and NVP-AUY922-induced Hsp70/Hsp27 expression levels. A combined approach consisting of HSF-1 k.d. and low concentrations of the Hsp90 inhibitor NVP-AUY922 potentiates radiosensitization which involves an impaired homologous recombination mediated by Rad51. Our findings are key for clinical applications of Hsp90 inhibitors with respect to adverse hepatotoxic effects.

Changes in food quality can dramatically impair zooplankton fitness, especially in eutrophic water bodies where cyanobacteria are usually predominant. Cyanobacteria are considered a food with low nutritional value, besides some species can produce bioactive secondary metabolites reported as toxic to zooplankton. Considering that cyanobacteria can limit survival, growth and reproduction of zooplankton, we hypothesized that the adverse effects of the dietary exposure of Daphnia species to saxitoxin-producing cyanobacteria depend on the relative abundance of nutitious food source in the diet. Life table experiments were conducted with different diets: 1) without nutritional restriction, where neonates were fed with diets at a constant green algae (Monoraphidium capricornutum) biomass as a nutritious food source, and increasing cyanobacterial concentration (STX-producing Raphidiopsis raciborskii), and 2) with diets consisting of different proportions of M. capricornutum (nutritious) and R. raciborskii (poor food) at a total biomass 1.0 mg C L 1. In general, the presence of high proportions of cyanobacteria promoted a decrease in Daphnia somatic growth, reproduction and intrinsic rate of population increase (r) in both diets with more pronounced effects in the nutritionally restricted diet (90% R. raciborskii). Two-way ANOVA revealed significant effects of species/clone and treatments in both assays, with significant interaction between those factors only in the second assay. Regarding the grazing assay, only D. laevis was negatively affected by increased cyanobacterial proportions in the diet. In the life table assay with constant edible food, a reduction in the reproduction parameters and the intrinsic rate of population increase (r) of all species was observed, In conclusion, we found adverse effects of the toxic cyanobacterial strain R. raciborskii on Daphnia fitness, regardless of the constant amount of nutritious food available, proving the toxic effect of R. raciborskii and the nutritional quality of the food has a greater influence on the fitness of these animals.

This review explores the transformative role of induced pluripotent stem cells (iPSCs) and organoids in advancing neuropathology research. Focused on Alzheimer's disease, epilepsy, Parkinson's disease, and spinal cord injury, iPSCs offer patient-specific disease modeling with regenerative therapy potential. The versatility of iPSCs, their ability to differentiate into the main neuronal cell types, and their integration into three-dimensional organoid models enable the recreation of complex tissues in vitro. Improvement of organoid and iPSCs generation protocols and the selection of appropriate donor cell types are highlighted as crucial steps toward the application of these new technologies to overcome tumorigenic potential and other challenges. iPSCs demonstrate promise in regenerative therapies, as evidenced by successful applications in animal models.

According to their nutritional value, their ability to adapt to the various environmental conditions, and their versatility, cereals are among the most cultivated plants in the world. However, the ongoing climate changes subject crops to important environmental stress that for some varieties leads to high production losses. Therefore, selection of species and varieties more versatile and adaptable to different environmental conditions can be important. However, the characteristics of some cereals are not completely known, this is a priority before to improve their cultivation. The aim of this study is to characterize select species of potential suitable for local environmental conditions, nutritional value.

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.

The following article presents an analysis of the determinants of diabetes using a dataset containing the surveys of 2000 patients from the Frankfurt Hospital in Germany. The data were analyzed using the following models, namely: Tobit, Probit, Logit, Multinomial Logit, OLS, WLS with heteroskedasticity. The results show that the presence of diabetes is positively associated with "Pregnancies", "Glucose", "BMI", "Diabetes Pedigree Function", "Age" and negatively associated with "Blood Pressure". A cluster analysis is realized using the fuzzy c-Means algorithm optimized with the Elbow method and three clusters were found. Finally a confrontation among eight different machine learning algorithms is realized to select the best performing algorithm to predict the probability of patients to develop diabetes.

The employment of clays in industry and on laboratory scale is still of interest, despite their long history. The chemical-physical characteristics of such material are strongly related to their geographical origin and the availability of proper characterization techniques is of great importance in order to gain as more information about their behavior when utilized as filling materials. In the present contribute a physical characterization by meaning of Thermogravimetry and N₂ physisorption, including a thermal stability evaluation, of samples of Sardinian bentonite collected from the Alghero area (Italy) is reported.

In the present study the effects of Origanum onites L. extract and essential oil of O. onites L. on the antioxidant status of the liver and brain of mice were investigated. Due to certain disadvantages of essential oils, such as poor solubility, high volatility, sensitivity to UV light and heat, formulation of liposomes with Oregano essentials (OE) was optimized and used in this study. The results demonstrated that the best composition of the lipid carriers and Oregano essentials were conducted in terms of the PDI, mean particle size and EE. The LE4 formulation contained Lipoid S100 of 45 mg, Lipoid S75 of 45 mg and 90 mg of EO. The administration of O. onites L. extract to mice for 21 days significantly decreased glutathione (GSH) level in the liver and brain of mouse as well as malondialdehyde (MDA) concentration in the liver. In the brain of mice MDA level significantly increased after this extract consumption. Whereas liposomes with OE significantly decreased GSH concentration in mouse brain and MDA concentration in mouse liver but increased (p&gt;0.05) GSH level in liver and MDA concentration in brain of mice compared with the control group. It was investigated that both, O. onites L. extract as well as liposomes with OE of this plant material make changes in the antioxidant status in the liver and brain of mice.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC₉₀ value of 1.5 μM.

Human factors are the most relevant issues contributing to adverse events in obstetrics. Specific training of Crisis Resource Management (CRM) skills (i.e., problem solving and team management, resource allocation, awareness of environment, and dynamic decision-making) are now widespread and are often based on High Fidelity Simulation. In order to be used as a guideline in simulated scenarios, they need to be translated into specific and observable behavioral markers. To this purpose, we developed a set of observable behaviors related to the main elements of CRM in the delivery room. The observational tool was then adopted in a two-days seminar on obstetric hemorrhage where teams working in obstetric wards of six Italian hospitals took part to simulations. The tool was used as guide for the Io and as a peer-to-peer feedback. It was then rated for its usefulness in facilitating the reflection upon one’s own behavior, its ease of use, and its usefulness for the peer-to-peer feedback. The ratings were highly positive, around 4 in a 5-point scale. The CRM observational tool is therefore a useful, quick and easy solution to facilitate the debriefing, the peer-to-peer feedback and, most of all, the transfer of safe behavior from simulation to everyday practice.

Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI<0.2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 ± 0.78 µg, 9.15 ± 1.23 µg and 1.42 ± 0.21 µg respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

According to the International Agency for Research on Cancer (IARC) of the World Health Organization (data of year 2020), Breast Cancer (BC) is one of the most common cancer types worldwide, with large geographical variations occurring between countries and world regions and highest incidence rates in countries that have undergone economic transition. The risk factors for BC include women ageing, genetic mutations, reproductive history, dense breast tissues, personal history of BC or specific non-cancerous breast diseases, family history of breast or ovarian cancer, previous treatment using radiation therapy, and exposure to hormone-like drugs such as diethylstilbestrol (DES). Additional risk factors include being overweight or having obesity after menopause, and taking hormones. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to the tumor development and angiogenesis process in different types of cancer, including BC. In the last years, the knowledge about miRNAs role in BC has significantly improved, and complex interactions among coding and non-coding RNA has been elucidated. In this context, an increasing number of papers had been published regarding the role of miR-125 in BC. In this review, we summarize the state-of-the-art about this research topic in addition to elaborating on the need to set novel ethical and legal standards for the governance of such innovations in healthcare.

The liver performs a fundamental role in the regulation of diverse physiological processes. Despite enormous advances in modern medicine, there are no completely effective drugs that stimulate hepatic function, offer complete protection to the organ, or aid in regenerating hepatic cells. Thus, it is necessary to identify alternative plant-origin pharmaceuticals more effective and less toxic for the treatment of hepatic diseases. The aim of this research was to establish the chemical composition of the American cranberry (Oxycoccus macrocarpus) leaves extract and its aminoacids preparations as well as their hepatoprotective activity. 19 phenolic compounds (8 flavonoids (flavones and flavonols), 4 anthocyanins, 2 catechins, and 3 hydroxycinnamic acids) and main amino acids (valine, arginine, glycine, histidine, aspartic acid, and taurine) were identified and quantified in the American cranberry (O. macrocarpus) leaves extract and its 7 aminoacids preparations. The therapeutic and prophylactic consumption of the American cranberry leaves extracts led to a decrease in the intensity of the lipid peroxidation process compared to the control pathology group in the experiment of acute toxic damage to the liver by tetrachloromethane on rats. The most pronounced hepatoprotective activity was established for the American cranberry leaves extracts’ preparations with arginine and valine.

The consumption of fiber in the human diet is a global recommendation to ensure a healthy diet. Quinoa (Chenopodium quinoa Willd.), a gluten-free grain, and chia (Salvia hispanica), a seed, contain high fiber content and both have the potential to be explored in the development of nutraceutical and pharmaceutical formulations. An interesting characteristic of chia is its ability to form viscous mucilage when in contact with water, bringing the prospect of a binder in solid formulations. To produce tablets with a high fiber content, it is more appropriate to transform the material into granules using a wet process, with the help of a tool that exploits this possibility. Therefore, the objective of the present work was to study, using the Mixer Torque Rheometer, the feasibility of using chia as a binder to produce granulated quinoa and the development of chewable tablets. To this end, an experimental design was carried out to evaluate the impact of variables on the rheometer results for subsequent granulation. It was possible to obtain the granulation point for the formulations and after producing the granules, physical tests were carried out in which we noticed improvements in the flow. In the end, a formulation was selected for the development of chewable tablets containing quinoa and chia fibers.