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

A simple procedure to obtain 1,5-disubstituted 1,2,3-triazoles, using the catalytic system erbium(III) trifluoromethanesulfonate, 1-methyl pyridinium trifluoromethanesulfonate and water is described. The reaction proceeds through an eliminative azide–olefin cycloaddition (EAOC) offering a highly regioselective approach and good yields (81–94%). The advantages of this method include simple operations of work-up and the ability of the catalytic system to be re-used five times without an evident loss in yield.

An efficient, eco-compatible and very cheap method for the construction of triazoles via eliminative azide–olefin cycloaddition (EAOC) reaction has been developed by a catalytic system IL/FeCl3, offering an highly regioselective approach to structurally diverse 1,5-disubstituted 1,2,3-triazoles in up to 95% yield. This strategy features the reuse of catalytic system through simple operations. Mechanistic studies indicated that an asynchronous concerted dipolar cycloaddition-elimination process might be involved.

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

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

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

Since the first description of COVID-19 infection, among clinical manifestations of the disease including fever, dispnea, cough, fatigue, it was observed a high incidence of thromboembolic events potentially evolving towars ARDS and COVID-associated-coagulopathy (CAC).The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status in COVID-19 disease can be explained by the increase of coagulation levels of D-dimer, lymphocytes, fibrinogen, IL-6 and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

Cigarette butts (CBs) are the most diffuse waste in the world, often abandoned in the environment without proper disposal. They are dangerous because of the numerous harmful chemicals poten-tially released in the environment. There are, in literature, several technological options for CB recycling, but some critical concerns could affect their effectiveness due to the quality and quantity of CB litter collected in the proper way. The present paper focuses on policy framework social behavior, waste collection and transport and technological processes. The Extended Producer Responsibility scheme for CBs is proposed at European level as an action to tackle CB litter and encourage sustainable product development. The CB waste collection and transport is a key step for bringing CB to the recycling process. The main concern is the small quantity of CBs collected: 0.06 % of the municipal waste and 0.18 % of the unsorted waste in the administrative area of Pe-rugia. Another crucial issue is the need for behavioral interventions to increase education and awareness of smoker citizens, addressing the discrepancy between smokers’ behaviors and beliefs.

In Italy, the number of buildings that have fallen into disuse is huge; also the normative and regulative framework promoting public portfolio’s re-use and revitalisation is still unclear and blurred. Nevertheless, in the last ten years, these buildings have become fertile ground for innovation and creative experiences by civic actors. The rise of this new category of civic actors plays an important role, both from the institutional side and the kind of initiatives and practices they process. They act in different manners but according to an in-depth analysis they share similar patterns of behaviour. What has emerged is that, although the different contexts, where they operate, the institutional performances might be successful if only certain kinds of conditions are taken into consideration. Based on some basic features, civic actors and their dynamics with public administrations are analysed to understand conditions that allow revitalisation processes to be successful in unused public buildings.

This study examined the tail dependency structure of sovereign credit risk and three global risk factors in BRICS countries using copulas approach, which is known for its ability to provide the “true” tail correlation based on the correct marginal distribution. The empirical results show that global market risk sentiment comoves with sovereign CDS spreads across BRICS countries under extreme market events, with Brazil having the highest co-dependency followed by China, Russia, and South Africa. Furthermore, oil price volatility is the second biggest risk factor correlated with sovereign CDS spreads for Brazil and South Africa while exchange rate risk exhibits very small co-dependence with sovereign CDS spreads under extreme market conditions dominated by tail events. On the contrary, exchange rate risk is the second largest risk factor co-moving with China and Russia’s sovereign CDS spreads while oil price volatility exhibits the lowest co-dependence to CDS in these countries. Between oil price and currency risk, evidence of single risk factor dominance is found for Russia where exchange rate risk is largely dominant. These results suggest that BRICS policymakers might consider financial sector regulations that mitigate risks spill-over such as targeted capital controls when markets are distressed.

Metal foams are widely studied as possible tools for the enhancement of heat transfer from hot bodies. The basic idea is that a metal foam tends to increase significantly the heat exchange area between the hot solid body and the external cooling fluid. For this reason, this class of porous materials are considered as good candidates for an alternative to finned surfaces, with different pros and cons. Among the pros, we mention the generally wider area of contact between solid and fluid. Among the cons is the difficulty of producing different specimens with the same inner structure, with the consequence that their performance may be significantly variable. This paper will offer a survey of the literature with a focus on the main heat transfer characteristics of the metal foams. Then, a numerical simulation of the heat transfer at the pore scale level for an artificial foam with a spatially periodic structure will be discussed. Finally, these numerical results will be employed to assess the macroscopic modelling of the flow and heat transfer in a metal foam.

Atherosclerotic cardiovascular disease, a leading cause of morbidity and mortality worldwide, is a chronic inflammatory disease, linked to a state oxidative stress, with several well-identified culprits, of which low-density-lipoprotein cholesterol (LDL-C) and lipoprotein(a). No specific treatment is currently available to lower lipoprotein(a). It is, therefore, of paramount importance to identify nutritional factors that could lower lipoprotein(a). Growing evidence shows that although reducing saturated fatty acid (SFA) intake decreases LDL-C, it could increase lipoprotein(a). Optimal dietary recommendations may therefore differ depending on an in-dividual’s baseline lipoprotein(a) and LDL-C levels. Assessing the diet-induced true LDL-C response and net balance of these two atherogenic entities is difficult because LDL-C measurement is confounded by lipoprotein(a) cholesterol content. We have estimated, for the first time, the net atherogenic result of diet-induced variations of both LDL-C and lipoprotein(a), thanks to our new concept of LDLapoB risk equivalent=apoB+lp(a)x5 (in nmol/L). This is illustrated, via the rare case of a physician with very high lipoprotein(a) and hypobetalipoproteinemia. She experiences twice a considerable lipoprotein(a) increase (+32%, + 28mg/dL, + 67nmol/L) and higher LDLapoB risk equivalent (138mg/dL versus 123mg/dL) on a mediterranean diet, low in SFA. A reasonable SFA intake, despite causing marginal LDL-C increase, may be advisable in patients with high lipoprotein(a) who need personalized dietary recommendations.

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

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected 21 sources referring to 14 studies focused on KarXT, out of which only four have published results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data is needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

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

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

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

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

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

This research examines the impact of social equity on energy consumption. We constructed a digital twin for residential energy consumption by enriching the synthetic population with real-world surveys and feeding them with other environmental and appliance data to the energy modeling framework. We analyzed household hourly energy consumption data from Albemarle County and Charlottesville City in Virginia, USA, for the year 2019. We used clustering analysis to identify patterns in social equity and energy consumption. The results demonstrated the impact of different residential attributes on energy poverty. Statistical analyses, including ANOVA and Chi-Squared tests, were conducted to test for significant differences between racial groups in quantitative and categorical variables. The study found that race is significant in determining the location and quality of housing. People of color often live in areas with higher pollution and less access to green spaces. Additionally, income levels and the age of the house are influential factors in determining energy efficiency. Future work should focus on collecting and analyzing data at the country level and using qualitative data collection methods to gain a more comprehensive understanding of social equity issues concerning energy consumption. Overall, this study provides valuable insights into the relationship between different residential attributes and energy consumption, which can inform policy development to promote more equitable and sustainable communities.

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

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

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and Impella 2.5 device may have a role to play for this group of patients. A simulation approach may help with a quantitative as-sessment of the achievable degree of assistance. In this paper, we analyse the interaction be-tween Impella 2.5 pump applied as LVAD and IABP using the numerical simulator of the cardi-ovascular system developed in our laboratory. Starting with pathological conditions reproduced using literature data, the simulations were performed setting different rotational speeds for the LVAD and driving the IABP in full mode (1:1) or partial mode (1:2, 1:3 and 1:4). The effects in-duced by drug administration during the assistance were simulated too. The haemodynamic pa-rameters under investigation were: mean aortic pressure, systolic and diastolic aortic pressure, mean pulmonary arterial pressure, mean left and right atrial pressure, cardiac output, cardiac index, left and right ventricular end-systolic volume, left ventricular end-diastolic volume and mean coronary blood flow. The energetic variables considered in the study were: left and right ventricular external work and left and right atrial pressure-volume area. The outcome of our simulations shows that the combined use of IABP and Impella 2.5 achieves adequate support in the acute phase of cardiogenic shock compared to each standalone device. This would allow fur-ther stabilisation and transfer to a transplant centre should escalation of treatment be required.

Among many other themes, Leonardo da Vinci’s Manuscript B contains several drawings of centrally planned churches, some of which are represented using a plan view paired with a bird’s-eye view. The use of a bird’s-eye instead of an elevation represents an innovative depiction technique, which allows to combine the immediacy of the perspective view with the measurability of the façades, and therefore to describe the three-dimensionality of the buildings. To understand the reasons behind the use of this original technique, the edifices’ shape and classify them we decided to use 3D digital reconstruction techniques, for their ability to avoid misunderstandings in the reconstruction process and in the results. This article describes the method to create the digital models of sixteen churches. A Visual programming language (VPL) script was used as 3D base for modelling the churches achieved from a classification code expressing the aggregative rules of the churches. Then, the geometric process for the construction of the plan and its relationship with the elevation measures was studied for each church. Finally, this information was used for the completion of the 3D models, distinguishing more output variants each time there was an inconsistency between plan and perspective view, a variability of one architectural element or an uncertainty.

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

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

The onset of neurodegenerative diseases involves a complex interplay of pathological mecha-nisms, including protein aggregation, oxidative stress, impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disor-ders, highlighting autophagy as pivotal in disease pathogenesis. Reactive oxygen species (ROS) play dual roles in cellular homeostasis and autophagy regulation, with disruptions of redox sig-naling contributing to neurodegeneration. The activation of the Nrf2 pathway represents a criti-cal antioxidant mechanism, while autophagy maintains cellular homeostasis by degrading al-tered cell components. The interaction between p62/SQSTM1, Nrf2 and Keap1 forms a regulatory pathway essential for cellular stress response, whose dysregulation leads to impaired autophagy and aggregate accumulation. Targeting the Nrf2-p62/SQSTM1 pathway holds promise for thera-peutic intervention, mitigating oxidative stress and preserving cellular functions. Additionally, the review explores the potential synergy between the endocannabinoid system and Nrf2 signal-ing for neuroprotection. Further research is needed to elucidate the involved molecular mecha-nisms and develop effective therapeutic strategies against neurodegeneration.

Climate variability and change has been found to be one of the factors that affect economies leading to food insecurity in various parts of the world. Kenya is no exception. This study looks at how climate variability has contributed to food insecurity in Kisii County, Kenya. The objectives of this study is therefore to, (i) to examine the rainfall and temperature trends in Kisii County for a period of approximately 30 years, (ii) to examine the effect of climate variability on food production and (iii) to assess the perception of local farmers on weather and climate information, (iv) to evaluate the coping strategies adopted at to bridge the gap on food deficit at different household level and (v) to assess the nutritional status of children and the elderly. The study was conducted in two sub-counties of Kisii County; Marani and Bomachoge Chache. The data used was mainly rainfall and temperature data from meteorological stations and sample data gathered from selected groups. The study population comprised of children between 6 months and 59 months, household heads, elderly people and agricultural officers. Purposive sampling was used to select agricultural officers while multistage sampling was used to select respondents at household level. Data was collected by use of a pre-tested questionnaire. The MUAC tape was used to collect nutritional status of children while BMI data was obtained from elderly people. Mann Kendall statistic was used to determine whether the trend of rainfall and temperature observed is significant while Chi-square test was used to determine whether the coping strategies observed varied significantly at household level. From the analysis, rainfall has not shown any significant change in Kisii County while temperature trend has been significantly increasing over the years at 95% confidence level. This could explain the observed reduction in river levels. Analysis of crop production and price trends of major food crops in Kisii County showed a decreasing trend of food production leading to increase in price over the years. This meant that farmers could not produce enough to take them to the next harvesting season making farmers to adopt different coping strategies at household level which differed significantly according to Chi-Square test. Malnutrition status of both elderly people above 59 years and children between 6-59 months were similar with 23% of both children/elderly being severely malnourished/malnourished. This study has only looked at climatic factors such as rainfall and temperature. Other aspects such as depth of underground water, ph level of soil and the effects of land fragmentation also need to be looked at. This study is important to both farmers in choosing the right crop to plant, and policy makers and planners in formulating the best mitigation and intervention strategies for Kisii County food insecurity problem. This will further contribute to national efforts towards achievement of vision 2030.

Wearable sensors have become increasingly popular for assessing athletic performance, but the optimal methods for processing and analysing the data remain unclear. This study investigates the efficacy of discrete and continuous feature extraction methods, separately and in combination, for modelling countermovement jump performance using wearable sensor data. We demonstrate that continuous features, particularly those derived from Functional Principal Component Analysis, outperform discrete features in terms of model performance, robustness to variations in data distribution and volume, and consistency across different datasets. Our findings underscore the importance of methodological choices, such as signal type, alignment methods, and model selection, in developing accurate and generalisable predictive models. We also highlight the potential pitfalls of relying solely on domain knowledge for feature selection and the benefits of data-driven approaches. Furthermore, we discuss the implications of our findings for the broader field of sports biomechanics and provide practical recommendations for researchers and practitioners aiming to leverage wearable sensor data for athletic performance assessment. Our results contribute to the development of more reliable and widely applicable predictive models, facilitating the use of wearable technology for optimising training and enhancing athletic outcomes across various sports disciplines.

The COVID-19 pandemic had a wide-ranging impact, resulting in a global recession due to weakened purchasing power. This circumstance necessitates business organizations adapting to developments and being more conscious of the risk of financial statement fraud. The intention of this research is to investigate the way corporate governance affected financial statement fraud during the COVID-19 pandemic. To acquire empirical data for examining corporate governance variables on financial statement fraud, the research was examined using quantitative methods. The study takes advantage of secondary data acquired from annual reports of companies under special monitoring listed on the Indonesia Stock Exchange of 2020-2021. The logistic regression method was used to evaluate 134 data sets, and financial statement fraud was measured using the Z-Score and F-Score models. The results indicate that using the Z-score, only the board size has a negative effect on financial statement fraud during the COVID- 19 pandemic. Meanwhile, using the F-Score, the corporate governance variables studied are not proven to have an influence on financial statement fraud during the COVID 19 pandemic.

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

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody-drug conjugates,chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients.

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

Growth monitoring of crops is a crucial aspect of precision agriculture, essential for optimal yield prediction and resource allocation. Traditional crop growth monitoring methods are labor-intensive and prone to errors. This study introduces an automated segmentation pipeline utilizing multi-date aerial images and orthomosaics to monitor the growth of cauliflower crops (Brassica Oleracea var. Botrytis). The methodology employs YOLOv8, Grounding DINO, and the Segment Anything Model (SAM) for automatic annotation and segmentation. The YOLOv8 model was trained using initial datasets, which then facilitated the training of the Grounded SAM framework. This approach generated automatic annotations and segmentation masks, classifying crop rows for temporal monitoring and growth estimation. The study's findings highlight the efficiency of this automated system in providing accurate crop growth analysis, promoting informed decision-making in crop management and sustainable agricultural practices. Results indicate consistent and comparable growth patterns between aerial images and orthomosaics, with significant periods of rapid expansion and minor fluctuations over time. The integration of these advanced techniques demonstrates the potential for enhancing precision agriculture through reduced labor and increased accuracy in crop growth monitoring.

Abstract: Background: Vasoplegic shock syndrome(VSS) after an off-pump coronary artery bypass graft (OPCABG) is an extremely rare condition. Inotropic support is usually the first-line therapy though it can precipitate several complications or be ineffective. We report the first case of severe refractory VSS after OPCABG successfully treated with hydroxycobalamin. Methods: A 77-year-old gentleman underwent OPCABG for three vessels coronary artery disease. Preoperative LV ejection fraction was 28%, and the patient before surgery started sacubi-tril/valsartan titrated, then, to the highest dose. Surgery was uneventful and, by the end of the procedure, TEE showed improved biventricular contractility. Results: The patient was transferred to the ICU without inotropic support but he developed soon hypotension. TEE ruled out pericardial tamponade and confirmed fair contractility. Norepineph-rine was titrated to a medium-high dose, vasopressin was started and a Swan-Ganz catheter was placed. SVR was 480 dyn·s·cm−5. Despite aggressive pharmacologic treatment (including Methylprednisolone and Methylene blue), no improvements were noticed. 10 g of hydroxycobalamin were administered. One hour later hemodynamic status re-assessment showed SVR > 800 dyn·s·cm−5. Afterward, vasopressors were gradually reduced. Conclusions: Our case demonstrated the importance of adequate early treatment in VSS after OPCABG. For the first time, hydroxycobalamin was effectively used to restore homeostasis.

This scoping review investigated how consumers perceive and interpret serving size information on food packages. A search of seven databases (2010 to September 2017) was followed by title and abstract screening, with relevant articles assessed for eligibility in full-text. Fourteen studies met inclusion criteria, with relevant data extracted by one reviewer and checked for consistency by a second reviewer. Five studies reported poor understanding of nutrition facts labelling and portion size, with information to ‘benchmark’ serving size against reported as helpful in two studies. Consumer attitudes towards serving size labelling were measured in six studies and identified that serving size information was interpreted as indicative of nutrient intake regardless of portion size recommendations. Increased labelled serving sizes resulted in increased portion sizes in three studies, with three studies reporting the opposite or neutral effect for discretionary food portion sizes. The influence of labelled serving size on consumer attitudes and consumption is complex and sometimes counterintuitive. As labelled serving size can impact on consumption, any changes may result in unintended public health consequences. The effects of labelled serving size format changes should be tested carefully within experimental and ecological contexts and accompanied by tailored, comprehensive and serving size-specific food literacy initiatives.

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

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

Motivated by the increasing need of optimised micro-devices for droplets production in medical and biological applications, this paper introduces an integrated approach for the study of the liquid-liquid droplet creation in flow-focusing micro cross-junctions. The micro-junction considered is characterised by a restriction of the channels cross-sections in the junction, which has the function of focusing the flow in the region of the droplet formation. The problem is studied numerically in OpenFOAM environment and validated by the comparison with experimental results obtained by high-speed camera images and micro-PIV measurements. The analysis of the forces acting on the dispersed phase during the droplet formation and the diameter of the droplets obtained numerically are considered for the development of a model of the droplet breakup under the squeezing regime. On the basis of energy balancing during the breakup, a relation between interfacial tension, the size of the cross-sections in the junction, and the time interval needed for droplet creation is obtained, which yields a novel correlation between the dimensionless length of the droplet and the dimensionless flow rate. This correlation is general and can be used to predict the droplet diameters produced by similar micro-junctions with different aspect ratios and extended to different geometries of flow-focusing micro-junctions.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

Tuberculosis (TB) remains the leading cause of death from a single infectious agent. Among children, TB can have a wide range of non-specific clinical and radiological manifestations becoming a challenging diagnosis, particularly in areas with a low prevalence. We present the case of a 14 month-old female with a history of fever of unknown origin (FUO) and later diagnosed with miliary tuberculosis.

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

Italian Directives recommends the good quality of natural mineral waters but literature data assert a potential risk from several microorganisms colonizing wellsprings and mineral water bottling plants. Aim of study is the identification of microorganisms from spring waters (SW) and bottled mineral waters (BMW) samples. Methods: Routine microbiological indicators, Legionella spp., Nontuberculous mycobacteria (NTM), protozoa (FLA) and physical-chemical parameters were assessed in 24 SW and 10 BMW samples performing culture methods and molecular tests as PCR and qPCR. Results: In 33 out of 34 samples no cultivable bacteria were isolated with the exception of 83 CFU/L of Mycobacterium gilvum, detected in one warm rich-mineralized SW. qPCR showed the presence of Legionella genomic units in 24% of samples (mean 2,9x10²±1,7x10² GU/L) and NTM genomic units in 18% of samples (mean 5,7x10^3±4,1x10³ GU/L). Vermamoeba vermiformis and Acanthamoeba polyphaga were recovered respectively in 70% of BMW samples (counts from 1,3x10³ to 1,2x10⁵) and 42% of SW samples (counts from 1,1x10³ to 1,3x10⁴). Vahlkampfia spp. was detected in 42% of SW and 70% of BMW samples (mean 1,3x10⁴ ±2,9x10³ GU/L). Conclusion: The study highlights a low rate of microbial risk and the importance of risk assessment in natural mineral waters.

The crosstalk between gut microbiota, intestinal epithelial cells, and innate and adaptive immune system governs the maintenance of the intestinal homeostasis. Any interference in this tight dialogue and in the processes preserving cellular homeostasis (e.g., autophagy) may dysregulate the immune response and impair the clearance of harmful bacteria favoring the dysbiotic alteration of the microbic flora that leads to chronic inflammation. Gut dysbiosis is strongly associated with gastrointestinal inflammatory disorders, among them the inflammatory bowel disease (IBD). This review discusses the current knowledge on IBD, from the genetic background of high-risk patients to the molecular mechanisms underlying the disease, the contribution of the microbic flora, and the role of autophagy in intestinal epithelial cells and provides the state of art regarding the targeted-nutritional approaches aimed to restore the beneficial crosstalk between an “anti-inflammatory” microbiota and the host. Analysis of the molecular pathogenesis of IBD will help identify genetic and diet-associated risk factors and thus suggest personalized strategies to prevent and manage the disease to improve quality of life with long-term maintenance of the remission phase.

The incidence of cutaneous melanoma has been increasing in the last decades among fair-skinned population. Despite etiology is complex and multifactorial, the exposure to ultraviolet radiation (UVR) is the most consistent modifiable risk factor associated with melanoma. Several factors influence the amount of UVR reaching Eart’s surface. The aim of our study is to explore the association between melanoma and altitude in an area characterized by a mixed geographic morphology, such as in the Veneto region. For this purpose, 2752 melanoma patients, who referred to our attention between 1998 and 2014, were included in this study. For each patient we extracted demographic, histological and clinical-survival data. Head/neck and acral melanoma were more common in patients from the hills and the mountains, while the prevalence of limb and trunk melanoma was higher in patients living in plain and coastal areas. With increase of altitude, the Breslow thickness, ulceration and mitotic rate get worse but no significant difference was observed in overall and disease free-survival. Geographical area of origin of melanoma patients and the “coast-plain-hill gradient” could help to estimate the influence of different sun exposure and to explain the importance of vitamin D level in skin-cancer control.

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

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

Aortic disease has a significant impact on quality of life. Involvement of the aortic arch requires preservation of blood supply to the brain during surgery. Deep hypothermic circulatory arrest is an established technique for this purpose although neurological injury remains high. Additional techniques have been used to reduce the risk although controversy still remains. A three-way cannulation approach, including both carotid arteries and the femoral artery or the ascending aorta, has been used successfully for aortic arch replacement and redo procedures. We have de-veloped circuits of the circulation to simulate blood flow during this type of cannulation set up. The aim is to analyse using CARDIOSIM© cardiovascular simulation platform, how the haemodynamic and energetic parameters are affected and the benefit derived with particular reference to the cerebral circulation.

Bemisia tabaci (Gennadius) is a polyphagous, highly destructive pest capable of vectoring viruses in most agricultural crops. Currently, information on the distribution and genetic diversity of B. tabaci in South Sudan is not available. The objectives of this study were to investigate the genetic variability of B. tabaci infesting sweet potato and cassava in South Sudan. Field surveys were conducted between August 2017 and July and August 2018 in 10 locations in Juba County, Central Equatoria State, South Sudan. Sequences of mitochondrial DNA cytochrome oxidase I (mtCOI) were used to determine the phylogenetic relationships between sampled B. tabaci. Six distinct genetic groups of B. tabaci were identified including three non-cassava haplotypes (Mediterranean (MED), Indian Ocean (IO) and Uganda) and three cassava haplotypes (Sub-Saharan Africa 1 sub-group 1 (SSA1-SG1), SSA1-SG3 and SSA2). MED predominated on sweet potato and SSA2 on cassava in all the sampled locations. The Uganda haplotype was also widespread, occurring in five of the sampled locations. This study provides important information on the diversity of B. tabaci species in South Sudan. A comprehensive assessment of the genetic diversity, geographical distribution, population dynamics and host range of B. tabaci species in South Sudan is vital for its effective management.

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

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

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

In recent years, the treatment of locally-advanced rectal cancer (LARC) has been spotlighted in a number of landmark, practice-changing trials, heralding in the age of so-termed “total neoadjuvant therapy” (TNT). However, the lack of a common control arm, standard inclusion criteria, or, indeed, definition of TNT necessitates further study in this field, particularly using real-world data. We conducted a retrospective analysis of all patients treated for LARC at a single Canadian academic cancer centre between July 1st 2019 and July 14th 2022. This includes the June 2020 incorporation of TNT. 290 patients were included in the final analysis, and 124 variables were collected on each patient, including demographics, treatment type, adverse events, response to treatment, surgery versus watchful waiting and survival. Our findings demonstrate that both TNT and non-TNT regimens are highly toxic, with regards to both overall toxicity and grade 2+ adverse effects. 62 (96.9%) of patients on TNT experienced toxicities, compared to 186 (82.3%) of the non-TNT patients. Grade 2+ toxicities were 46 (71.9%) and 143 (63.3%), respectively. TNT, however, was associated with improved rates of complete response, compared to non-TNT treatment regimens (44% vs 24%). These findings suggest that TNT harbours both benefit and risk in a real-world population, and both of these aspects should be considered when deciding on a treatment approach for an individual patient. More work in the area is needed to determine longer term survival, as well as impact of surgery versus organ preservation approach on patient outcomes.

In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul." The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability," on which the heartbeat depended and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of ARIs (acute respiratory infections) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 ARIs.

The Infectious and Tropical Diseases Department of University of Brescia organized free rapid screening tests for HIV and HCV as part of the Fast Track City commitment. A cross-sectional study was conducted, consisting of an anonymous, multiple-choice questionnaire that was administered to individuals who underwent the screening or consultation. The study aimed to compare knowledge and attitudes towards HIV and HCV between age groups (18-40 vs. >40) and sexual orientations (heterosexual vs. LGBTQ+). Overall, 333 questionnaires were completed. Individuals over the age of 40 and those who identified as heterosexual had the lowest level of knowledge about HIV transmission (7.9% and 30% respectively), undetectable=untransmittable (19.7% and 39.4% respectively) and PrEP (9.2% and 18.2% respectively). They were also less willing to cohabit with people with HIV (PLHIV). Only 9.6% of the population demonstrated high levels of knowledge for both HIV and HCV. People over the age of 40 had the largest gaps in knowledge and would benefit the most from educational and prevention interventions.

Klebsiella pneumoniae is a leading cause of healthcare acquired infections. The severity of the infections is multifactorial including virulence and antimicrobial resistance properties. The objective of the study was to investigate the virulence determinants of K. pneumoniae strains colonizing patients hospitalized in the intensive care units (ICU) of a tertiary hospital in Uganda. A hospital based cross-sectional study involving 103 patients admitted in the ICU of Mulago National Referral hospital was conducted from January 2022 to April 2022. A total of 31 identified clinical strains of K. pneumoniae isolated from rectal swabs of the same number of patients were characterized. Susceptibility testing of colistin was performed by broth microdilution method, thereafter, 5 colistin resistant K. pneumoniae were purposefully selected for whole genome sequencing. Bioinformatics analysis was performed using established web-based tools to detect virulence genes, sequence type and other genomic features. Numerous virulence factor genes related to pathogenicity of K. pneumoniae were identified. They ranged from those related to colonization to those of persistence and dissemination including capsule genes (wzi), siderophore systems; yersiniabactin (ybt15), aerobactin (iutA), enterobactin (entC, entD, entF, entS, fepB, fepD, fepG, fes), and salmochelin (iroN), secretion systems; type II (T2SS) and type VI (T6SS-1). Furthermore, the isolates harbored outer membrane protein (ompA) gene, biofilm synthesis gene (fimH) and several adhesion genes. The results demonstrate the dual-risk of K. pneumoniae strains combining high level of virulence and colistin resistance which is a great concern as it leads to unmanageable infection outbreaks with high morbidity and mortality.

It is important to be able to detect and differentiate between distinct porcine enteric coronaviruses that can cause similar diseases. However, the existence of naturally occurring recombinant coronaviruses such as swine enteric coronavirus (SeCoV) can give misleading results with currently used diagnostic methods. Therefore, we have developed and validated three duplex real-time quantitative RT-PCR assays for the simultaneous detection of, and differentiation between, porcine epidemic diarrhea virus (PEDV) and SeCoV. Transmissible gastroenteritis virus (TGEV) is also detected by two out of these three assays. In addition, a novel triplex assay was set up that was able to detect and differentiate between these alphacoronaviruses and the porcine deltacoronavirus (PDCoV). The validated assays have low limits of detection, close to 100% efficiency and were able to correctly identify the presence of PEDV and SeCoV in 55 field samples, while 20 samples of other pathogens did not give a positive result. Implementing one or more of these multiplex assays into the routine diagnostic surveillance for PEDV will ensure that the presence of SeCoV, TGEV and PDCoV will not go unnoticed.

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

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

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

Plant-based insecticides are considered among the most economical and eco-friendly chemicals for the protection of field plants and even stored grains. The sweet melon (Cucumis melo L.) insect pest causes more than 90% damage to most melon leaves, vines, and balls at its growth stage. The study looked at how effective the plant extract from Africa Basil and the synthetic insecticide Cymbush were at killing insects on sweet melon (Cucumis melo L.). The study explored four different concentrations (2.5, 50, 75, and 100%) and a synthetic insecticide, Cymbush, against insect pests of sweet melon and compared the effects of distilled water, which is used as a control in a Randomized Complete Block Design (RCBD). The toxicity percentage levels of the African basil extracts against field pests of sweet melon were 25, 50, 75, and 100%. Maximum plant protection of the crop was achieved by the synthetic insecticide Cymbush (3.0 pest point), followed by Africa basil extract B100 (3.3 pest point), whereas weak and minimum insect pest protection were observed in the control (5.53 pest point). In conclusion, these results indicate the utility of African basil plant extracts against field insect pests of sweet melon as potential botanicals to control field insect pests and mitigate the hazardous use of synthetic insecticides on humans, animals, and the environment

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

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

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

The study investigated the impact of traditional medicine on life expectancy in Nasarawa State, Nigeria. The study adopted a quantitative research approach. Purposive or judgmental sampling was used to elucidate the data set used for the study. Cross-sectional data were gathered with the help of a well-designed questionnaire from a total of three hundred and fifty-seven (357) respondents who were available for the survey. The data set collected was analysed using descriptive and linear regression using Ordinary Least Squares (OLS). From the results, 53%, 87%, and 56% were male, below 50 years old, and in the low-income class, respectively, suggesting that the bulk of the respondents under investigation were male, young, and had rather modest incomes. Also, 53% were married, and all had one form of formal education. 67% of respondents acknowledge using traditional medicine; however, the majority of respondents preferred Orthodox medical care over alternative kinds of care. Traditional medicine (TM) and factors that contribute to the advancement of traditional medicine (FITM) have a negative impact on life expectancy, according to the regression analysis. On the other hand, TM has no statistically significant impact on life expectancy, despite FITM having a statistically significant effect at the 5% level. All available data, however, indicates that TM and FITM have an impact on life expectancy, either directly or indirectly. Based on the results, this study concluded that traditional medicine has the potential to significantly increase life expectancy in Nasarawa State and throughout Nigeria. The study recommends that traditional health professionals, stakeholders, and concerned government agencies should put efforts in place to improve and promote modern traditional medicine among the people, especially its effectiveness and medicinal quality, increase its accessibility to people, and efficiently regulate its prices to increase its affordability for low-income earners

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

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

ADHD is a neurodevelopmental disorder that children and also adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls.We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p=0.02 and p=0.03, respectively), instead the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p=0.0002 and p=0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highligted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness then, suggesting that these genotypes maybe protective towards specific changes in behavior (p=0.05). Interestingly, an increase of the GG genotype of rs6323 (p=0.01) and a decrease of GT genotype (p=0.0005) was also found in patients without aggressive behavior compared with controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help to early detect those patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

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

Antioxidants reduce arterial stiffness but the effects previously reported are weak. The present study evaluated the effects of 2 weeks of therapy with a combination of antioxidants (l-cysteine, thiamine, pyridoxine and ascorbic acid) compared to placebo on stiffness index (SI) a measure of arterial stiffness that is strongly correlated with central pulse wave velocity (PWV), using a Pulse Trace recorder in a diverse group of 78 volunteers. SI fell by 1.7 m/sec relative to placebo (95% confidence intervals 0.6 to 2.7 m/sec), a reduction of 19% (95% confidence intervals 9% to 31%). The Glass effect size was 1.4, indicating a very strong treatment effect which was substantially greater than found in previous studies of the effects of antioxidant therapy on arterial stiffness. The magnitude of reduction in SI was positively correlated with increasing age (r = 0.362 P = 0.02). The change in RI, a measure of compliance of small to medium size arteries, did not differ between the antioxidant and placebo groups The combination of antioxidants studied reduced PWV to a much greater extent than reported for other antioxidants. This combination may be of value in the treatment of cardiovascular disease.

Cardiogenic shock (CS) is part of a clinical syndrome consisting of acute left ventricular failure causing severe hypotension leading to inadequate organ and tissue perfusion. The most com-monly used devices to support patients affected by CS are Intra-Aortic Balloon Pump (IABP), Impella 2.5 pump and Extracorporeal Membrane Oxygenation. The aim of this study is the com-parison between Impella and IABP using CARDIOSIM© software simulator of the cardiovascular system. The results of the simulations included baseline conditions from a virtual patient in CS followed by IABP assistance in synchronized mode with different driving and vacuum pressures. Subsequently, the same baseline conditions were supported by the Impella 2.5 with different ro-tational speeds. The percentage variation with respect to baseline conditions was calculated for hemodynamic and energetic variables during IABP and Impella assistance. Impella pump driven with a rotational speed of 50000 rpm increased the total flow by 4.36% with a reduction in left ventricular end diastolic volume (LVEDV) by ≅15% to ≅30%. A reduction in left ventricular end systolic volume (LVESV) by ≅10% to ≅18% (≅12% to ≅33%) was observed with IABP (Impella) as-sistance. Taking into account the limitations of a simulation setting, this study highlights that assistance with the Impella device leads to higher reduction in LVESV, LVEDV, left ventricular external work and left atrial pressure-volume loop area compared to IABP support.

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

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

(1) Context: Cancer triggers significant changes in family dynamics. It is noteworthy that coping and problem-solving skills, particularly in situations involving cancer in children and adolescents, have not been adequately explored in the context of family adaptation. This study aims to analyze the effectiveness of family interventions in coping to improve problem-solving skills in parents and/or caregivers of children and adolescents during and after oncological treatment. (2) Methods: This is a scoping review following the recommendations of the Joanna Briggs Institute and the Systematic Reviews and Meta-Analyses Extension for Scoping Review (PRISMA-ScR), from 2014 to 2024, in the databases LILACS, CINAHL, SCOPUS, Web of Science, and PUBMED. (3) Results: Forty-five studies were eligible. Coping strategies were categorized as follows: (1) positive attitudes (including a sense of courage and hope, family support to enhance resilience, and future planning), (2) caregiver empowerment (involving acceptance of diagnosis, emotional distancing, and coping through religiosity), and (3) communication skills (encompassing professional communication, horizontal dialogue with healthcare teams, and sincere communication with friends and family). (4) Conclusions: Over time, families develop coping and problem-solving strategies that influence changes in family functioning patterns, aiding them in accepting, reinterpreting, and reframing ideas and feelings associated with neoplasia.

Takotsubo syndrome (TTS), recognized as stress’s cardiomyopathy, or better as left ventricular apical balloon syndrome in the recent years, is a rare pathology, described for the first time by Japanese researchers in 1990. TTS is characterized by an interindividual heterogeneity in onset and progression, and by the strong predominance in postmenopausal women. The clear causes of these TTS features are uncertain, given the reduced understanding of this intriguing syndrome until now. However, the increasing frequency of TTS cases in the last years, and particularly correlated to SARS-CoV-2 pandemic, leads us to imperative necessity both of a complete knowledge of TTS pathophysiology for identifying biomarkers facilitating its management, and targets for specific and effective treatments. The suspect of a genetic basis in TTS pathogenesis has been evidenced. Accordingly, familial form of TTS has been described. But a systematic and comprehensive characterization of the genetic or epigenetic factors significantly associated with TTS is lacking. Thus, we, here, conducted a systematic review of literature before June 2021, to contribute to identify potential genetic and epigenetic factors associated with TTS. Interesting data were evidenced, but of reduced number and with diverse limitations. Consequently, we concluded further work is needed to address the gaps discussed, and probably a clear evidence may arrive using multi-omics investigations.

This study aims to assess and identify the role of disruptive/digital technologies in financial innovation strategies as part of social innovations at both firm and country level. There are few studies of this type that "cross-examine" technical/social innovative capacity at the firm level vs. the same innovative capacity at the level of the world's major countries. Our proposed study brings some novel elements to the literature on this topic. First, the study synthesizes the factors/variables explaining technical/social innovative capacity as ranked by the GCI (Global Competitiveness Index) and GII (Global Innovation Index) at the country level and then correlates these variables with the factors explaining innovative capacity for the 50 companies in the BCG (Boston Consulting Group) ranking. Second, the study identifies three "driving forces" (digital technologies, managers and the market) as the main variables determining financial innovativeness at firm level. Third, based on the "cross" analysis of the information/data provided by the BCG study vs. the GII and GCI studies, the study suggests some ways to delineate and quantify financial innovation as part of social innovation (e.g., it is argued that 80% of the social innovation achieved annually by a firm relates to the financial relationships engaged by the firm with various categories of stakeholders). Finally, the study is also important from a pragmatic point of view as it suggests/proposes a number of principles that can be considered by managers for building a KM (knowledge management) and continuous innovation strategy. From a theoretical perspective, the study provides a starting point for further research aimed at explaining firm-level financial innovation through the massive use of disruptive technologies.

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

Background: Ultraviolet (UV) radiation from the sunlight can harm skin cells, causing short-term effects, such as sunburns and long-term effects, such as pigmentation changes, changes in the skin's immune responses, and increased risk of skin cancer. These conditions can be largely prevented with proper sun protection measures and behavioural changes. This study aims to assess the knowledge on sun protection behaviour and baseline knowledge of medical students from the “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania. Methods: Data in this cross-sectional study were collected through a Google Forms questionnaire, which was distributed from November 2023 to December 2023 via digital communication channels to students across all academic years. STROBE guidelines were consulted for data synthesis; Results: A total of 668 stu-dents responded. The student cohort demonstrated a commendable level of awareness of the risks associated with sun exposure and the advantages of employing sun protection factor (SPF); how-ever, the incidence of sunburns remained notably elevated (72.3%). Further analysis revealed cor-relations among gender, academic year, presence of photosensitizing conditions, and adherence to SPF application. Additionally, there is a need to improve understanding of the appropriate appli-cation techniques for SPF, as only 11.5% of the students exhibited proficiency in this regard; Con-clusions: As future healthcare providers, medical students hold significance in promoting healthy behaviours in the broader community. This study indicates that while their knowledge about sun protection is satisfactory, there is scope for enhancement.

This review is devoted to present the history of CARDIOSIM© software simulator platform, which was developed in Italy to simulate the human cardiovascular and respiratory system. The first version of CARDIOSIM© was developed at the Institute of Biomedical Technologies of the National Research Council in Rome. The first platform version published in 1991 ran on PC with disk operating system (MS-DOS) and was developed using the Turbo Basic language. The last version runs on PC with Microsoft Windows 10 operating system; it is implemented in Visual Basic and C++ languages. The platform has a modular structure consisting of seven different general sections, which can be assembled to reproduce different pathophysiological conditions. The software simulator can reproduce the most important circulatory phenomena in terms of pressure and volume relationships. It represents the whole circulation using a lumped-parameter model and enables the simulation of different cardiovascular conditions according to Starling’s law of the heart and a modified time-varying elastance model. Different mechanical ventilatory and circulatory devices have been implemented in the platform including thoracic artificial lung, ECMO, IABP, pulsatile and continuous right and left ventricular assist devices, biventricular pacemaker and biventricular assist devices. CARDIOSIM© is used in clinical and educational environment.

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

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

Listeria monocytogenes is a Gram-positive pathogenic bacterium which can be found in soil or water. Infection with the microorganism can occur after ingestion of contaminated food products. Small and large outbreaks of listeriosis have been described in the past. L. monocytogenes can cause a number of different clinical syndromes, most frequently sepsis, meningitis, and rhombencephalitis, particularly in immunocompromised hosts. L. monocytogenes systemic infections can develop following tissue penetration across the gastrointestinal tract or to hematogenous spread to sterile sites, possibly evolving towards bacteremia. L. monocytogenes only rarely causes bone or joint infections, usually in the context of prosthetic material that can provide a site for bacterial seeding. We describe here the clinical findings of invasive listeriosis, mainly focusing on diagnosis, clinical management and treatment of bone and vertebral infections occurring in the context of invasive listeriosis.

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

The target area of the present study is the entrance to the Sulina channel in the Black Sea, the zero-kilometer of the Danube River. This represents the southern gate of the seventh Pan-European transport corridor and is subjected to high navigation traffic. The coastal environment at the Danube’s mouth is very often subjected to strong environmental conditions inducing high risks for navigation hazards. From this perspective, the objective of the present work is to provide a more comprehensive picture concerning the past and future expected dynamics of the environmental matrix in this area, including especially wind and wave conditions. An analysis of some in situ measurements performed at the zero kilometer of the Danube is first carried out for the 15 years 2009-2023. A second analysis is based on data provided by regional climate wind models. Two 30-year periods are considered, the recent past (1976-2005), when also comparisons with ERA5 reanalysis data were performed, and the near future (2041-2070), when two different models and three climate scenarios were considered. Finally, using as a forcing factor each of the wind fields before analyzed, simulations with a spectral wave model were carried out and the nearshore wave conditions were evaluated. The results show that both extreme wind and wave conditions are expected to be slightly enhanced in the future. Strong wind fields are characteristic in this area, with wind gusts exceeding on average with more than 70% the maximum hourly averaged wind speed. As regards the waves, due to the complex nearshore phenomena, considerable enhancements in terms of significant wave heights are induced. Furthermore, there is also a high risk of rogue wave’s occurrence.

Dealing with and maintaining high-quality standards in the design and construction phases is challenging, especially for on-site construction. Issues like improper implementation of building components and poor communication can widen the gap between design specifications and actual conditions. To prevent this, particularly for energy-efficient buildings, it's vital to develop resilient, sustainable strategies. These should optimize resource use, minimize environmental impact, and enhance livability, contributing to carbon neutrality by 2050 and climate change mitigation. Traditional post-occupancy evaluations, which identify defects after construction, are impractical for addressing energy performance gaps. A new, real-time inspection approach is necessary throughout the construction process. This paper suggests an innovative guideline for prefabricated buildings, emphasizing digital 'self-instruction' and 'self-inspection'. These procedures ensure activities impacting quality adhere to specific instructions, drawings, and 3D models, incorporating relevant acceptance criteria to verify completion. This methodology, promoting alignment with planned energy-efficient features, is supported by BIM-based software and Augmented Reality (AR) tools, embodying Industry 4.0 principles. BIM and AR bridge the gap between virtual design and actual construction, improving stakeholder communication and enabling real-time monitoring and adjustments. This integration fosters accuracy and efficiency, key for energy-efficient and Nearly Zero-Energy Buildings, marking a shift towards a more precise, collaborative, and environmentally sensible construction industry.

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

The global malaria community has picked up the theme of malaria elimination in greater than 90 % of the world’s population in the next decade. The recent reports of P. vivax in all sub-Saharan Africa, including Duffy negative individuals, threaten the efforts to achieve elimination. This is not only in view of strategies that are tailored only to P. falciparum elimination, but also due to currently revealed biological characteristics of P. vivax concerning the relapse patterns of hypnozoites and conservation of a large biomass at cryptic sites in the bone marrow and spleen. A typical scenario has been observed in Botswana from the period between 2008 to 2018, which palpably projects how P. vivax could endanger efforts at malaria elimination where the two parasites co-exist. The need for the global malaria community, NMPs, funding agencies and relevant stakeholders to engage in a forum to discuss and recommend clear pathways for sub-Saharan Africa regarding malaria elimination including P. vivax, is warranted.

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

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

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

Multidrug resistance (MDR) among gram-negative bacteria is a global public health threat because it has exhausted all standard therapeutic options. This has necessitated clinicians to reconsider colistin, an “old sort” antibiotic which was deemed toxic for clinical use. Unfortunately, swift resistance towards colistin by K. pneumoniae has been reported in different parts of the world. The study aimed at investigating the genetic determinants of colistin resistance in K. pneumoniae isolated from patients admitted in a tertiary care hospital in Kampala, Uganda. 31 archived multidrug resistant K. pneumoniae isolates obtained from rectal swabs of patients admitted to the Mulago Hospital ICU were retrieved. From this collection, we selected 7 colistin resistant K. pneumoniae isolates for whole genome sequencing and molecular profile analysis. In silico sequence data analyses were performed using established web-based bioinformatics tools. The sequence analysis of the genes involved in colistin resistance revealed several non-synonymous mutations in nucleotide sequences of pmrA, pmrB, phoP, phoQ and mgrB genes. Insertion transposase genes for the insertion sequences IS1 and IS5 which are highly implicated in colistin resistance via modification or inactivation of mgrB gene were identified in all isolates and were located in the chromosomal DNA at different genomic positions. No plasmid-borne mcr genes were detected. More so, the strains harbored numerous multidrug resistant genes. This study underscores the need of genomic surveillance of K. pneumoniae strains to limit further spread of colistin resistance genes to avert the potential risk of pandrug resistance. And high throughput sequencing is imperative.

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

Optical characterization and thermal aging tests are performed on a sputter-deposited coating, consisting of SiO₂/Cr₂O₃/Cr/Cr₂O₃ layers, designed and developed as a selective solar absorber to be used for unconcentrated solar thermal applications. Both measurements are performed by using a home-made apparatus, which mimics a flat plate collector under high vacuum. A Performance Criterion (PC_η(T)), based on absorber efficiency is proposed, and a forecast of service lifetime is obtained. As a result of the thermal aging tests, the selective solar absorber under study appears to be highly efficient at mid temperatures (up to 573 K) and thermally stable at temperatures (up to 690 K).

The Vitamin D Receptor (VDR) mediates the actions of vitamin D, which has important roles in bone homeostasis, growth/differentiation of cells, immune functions and reduction of inflammation. Emerging evidences suggest that epigenetic modifications of the VDR gene, particularly DNA methylation, may contribute to the onset and progression of many human disorders. This review aims to summarize the available information on the role of VDR methylation signatures in different pathological contexts, including autoimmune diseases, infectious diseases, cancer and others. The reversible nature of DNA methylation could enable the development of therapeutic strategies, offering new avenues for the management of these worldwide diseases.

For a mobile robot, navigation in a densely crowded space can be a challenging and sometimes impossible task, especially with traditional techniques. In this paper, we present a framework to train neural controllers for differential drive mobile robots which must safely navigate a crowded environment while trying to reach a target location. To learn the robot’s policy, we train a convolutional neural network using two reinforcement learning algorithms, Deep Q-Networks (DQN) and Asynchronous Advantage Actor Critic (A3C), and develop a training pipeline that allows to scale the process to several compute nodes. We show that the asynchronous training procedure in A3C can be leveraged to quickly train neural controllers and test them on a real robot in a crowded environment.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

We present the case of a 35-year-old patient without pathological history who developed hemopneumothorax due to altitude barotrauma during a commercial airline flight. The computed tomography of the chest identified the presence of emphysema "blebs" and bubbles, and the histopathological examination of the lung fragment obtained during the diagnostic and therapeutic thoracoscopy identified elements suggestive for the diagnosis of respiratory bronchiolitis associated with desquamative interstitial pneumonia (DIP).

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

The human T-cell leukemia virus type 1 (HTLV-1) is the only known human oncogenic retrovirus. HTLV-1 can cause a cancer called adult T-cell leukemia/lymphoma (ATL). The virus is transmitted through body fluids of infected individuals, primarily breast milk, blood, and semen. At least 5–10 million people in the world are infected with HTLV-1. In addition to ATL, HTLV-1 infection can also cause HTLV-I-associated myelopathy (HAM /TSP). ATL is characterized by low viral ex-pression and poor prognosis. The oncogenesis triggered by HTLV-1 is extremely complex and the molecular mechanisms are not fully understood. However, viral regulatory proteins Tax and HTLV-1 bZIP factor (HBZ) have been shown to play key roles in the transformation of HTLV-1-infected T cells. Moreover, several studies have shown that the final fate of HTLV-1-infected transformed T cell clones is the result of a complex interplay of HTLV-1 oncogenic protein expression with cellular transcription factors that subvert the cell cycle and disrupt reg-ulated cell death, thereby exerting their transforming effects. This review provides updated in-formation on the mechanisms underlying the transforming action of HTLV-1 and the potential therapeutic targets to combat ATL.

Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological aims, were presently tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues, and to assess calcium antagonism in comparison to amiodarone, lidocaine, procainamide, and quinidine. All compounds, but two, compared favorably with the reference drugs. Potent antiarrhythmic activity was observed for compounds (in increasing order) 4, 1, 6 and 5. The last compound N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC50 = 0.017 µM) for the increase of threshold of ac-arrhythmia, and being devoid of antihypertensive activity against spontaneously hypertensive rats.