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A simple and sustainable propylphosphonic anhydride (T3P)-assisted methodology for the synthesis of N-acyl tryptamines, an interesting class of gut microbiota-derived endocannabinoid-like lipid mediators, was proposed. This protocol is characterized by great operational simplicity, and all products were obtained at room temperature, without the use of an inert atmosphere and by using limited amounts of non-halogenated solvents. Finally, the possibility to realize the reaction under mechanochemical conditions was explored with interesting results. [ABSTRACT FROM AUTHOR]

Sound planning for urban mobility is a key facet of securing a sustainable future for our urban systems, and requires the careful and comprehensive assessment of its components, such as the status of the cities' public transportation network, and how urban planners should invest in developing it. We use agent-based modelling, a tried and true method for such endeavours, for studying the history, planned future works and possible evolution of the tram line network in the Greater Geneva region. We couple these models with knowledge graphs, in a way that both are able to mutually enrich each other. Results show that the information organisation powers of knowledge graphs are highly relevant for effortlessly recounting past events and designing scenarios to be directly incorporated inside the agent-based model. The model features all 5 tram lines from the current real-world network, servicing a total of 15 communes. In turn, the model is capable of replaying past events, predicting future developments and exploring user-defined scenarios. It also harnesses its self-organisation properties to autonomously reconstruct an artificial public transportation network for the region based on two different initial networks, servicing up to 29 communes depending on the scenario. The data gathered from the simulation is effortlessly imported back into the initial knowledge graphs. The artificial networks closely resemble their real-world counterparts and demonstrate the predictive and prescriptive powers of our agent-based model. They constitute valuable assets towards a comprehensive assessment of urban mobility systems, compelling progress for the agent-based modelling field, and a convincing demonstration of its technical capabilities. [ABSTRACT FROM AUTHOR]

Background and purpose: Preclinical studies of amyotrophic lateral sclerosis (ALS) have shown altered endocannabinoid (eCB) signalling that may contribute to the disease. Results from human studies are sparse and inconclusive. The aim of this study was to determine the association between serum levels of eCBs or their congeners, the so‐called endocannabinoidome, and disease status and activity in ALS patients. Methods: Serum concentrations of 2‐arachidonoylglycerol and N‐arachidonoylethanolamine (AEA), and AEA congeners palmitoylethanolamide (PEA), oleoylethanolamide (OEA), eicosapentaenoylethanolamide (EPEA), 2‐docosahexaenoylglycerol (2‐DHG) and docosahexaenoylethanolamide (DHEA) were measured in samples from 65 ALS patients, 32 healthy controls (HCs) and 16 neurological disease controls (NALS). A subset of 46 ALS patients underwent a longitudinal study. Disease activity and progression were correlated with eCB and congener levels. Results: Most circulating mediators were higher in ALS than HCs (all p < 0.001), but not NALS. Across clinical stages, ALS patients showed increased levels of PEA, OEA and EPEA (all p < 0.02), which were confirmed by the longitudinal study (all p < 0.03). Serum PEA and OEA levels were independent predictors of survival and OEA levels were higher in patients complaining of appetite loss. Cluster analysis revealed two distinct profiles of circulating mediators associated with corresponding patterns of disease activity (severe vs. mild). Patients belonging to the 'severe' cluster showed significantly higher levels of OEA and PEA and lower levels of 2‐DHG compared to NALS and HCs. Conclusion: Circulating endocannabinoidome profiles are indicative of disease activity, thus possibly paving the way to a personalized, rather than a 'one‐fits‐all', therapeutic approach targeting the endocannabinoidome. [ABSTRACT FROM AUTHOR]

Sustainability in cities, and its accurate and exhaustive assessment, represent a major keystone of environmental sciences and policy making in urban planning. This study aims to provide methods for a reproducible, descriptive, predictive and prescriptive analysis of urban residential choices and mobility, which are key components of an urban system's sustainability. Using the DPSIR framework for building agent evolution rules, we design an agent-based model of the canton of Geneva, Switzerland. The model leverages real geographical data for the canton of Geneva and its public transportation network. The resulting simulations show the dynamics of the relocation choices of commuters, in terms of the function of their travel time by public transportation to their workplace. Results show that areas around the city centre are generally preferred, but high rent prices and housing availability may prevent most residents from relocating to these areas. Other preferred housing locations are distributed around major tram and train lines and where rent prices are generally lower. The model and its associated tools are capable of spatialising aggregated statistical datasets, inferring spatial correlations, and providing qualitative and quantitative analysis of relocation dynamics. Such achievements are made possible thanks to the efficient visualisation of our results. The agent-based modelling methodology represents an adequate solution for understanding complex phenomena related to sustainability in urban systems, which can be used as guidance for policy making. [ABSTRACT FROM AUTHOR]

Simple Summary: Screening for breast, colorectal, and cervical cancer is correlated with diagnosis at an earlier stage, less extensive surgery, and reduced mortality and fewer complications. Adherence rates to cancer screening are lower for individuals with low socio-economic conditions and educational attainment. These social disparities are only partially reduced by free screening through national initiatives. Education and information and appropriate expenditure for preventive care have the potentials to increase adherence to screening for colorectal, breast, and cervical cancer with the possibility of reduced cancer mortality. The findings of our study highlight the importance of the implementation of nationally organized screening programs for several other types of cancers that are often detected after the occurrence of symptoms. Nationally organized screening programs for several types of cancers, like esophageal, gastric, and pancreatic cancer, in regions with a high prevalence may increase the possibility of diagnosis at earlier stages and improved early and late results. The objective of this study was to determine the correlation between adherence to cancer screening programs and earlier diagnosis of the 14 most common types of cancers in the adult population, before and during the COVID-19 pandemic. National data concerning number of admissions and operations in Italy for adult patients admitted with oncologic problems during the COVID-19 pandemic (2020 to 2022) and in the pre-pandemic period (2015 to 2019) were analyzed. We selected 14 types of cancer that present the most common indications for surgery in Italy. This study included 1,365,000 adult patients who had surgery for the 14 most common types of cancer in the period 2015–2022, and interviews concerning adherence rates to screening for breast, colorectal, and cervical cancer were conducted for 133,455 individuals. A higher decrease in the number of operations for the 14 types of cancer (−45%) was registered during the first three acute phases of the pandemic, and it was more evident for screenable cancers like breast, colorectal, and cervical cancer (p < 0.001). During the first year of the COVID-19 pandemic, the number of screened individuals for breast, colorectal, and cervical cancer decreased by 33.8% (from 7,507,893 to 4,969,000) and the number of diagnoses and operations for these three types of cancer decreased by 10.5% (from 107,656 to 96,405). The increase and return to normality of the number of screened individuals in the last year of the pandemic (2022) and in the first post-pandemic year (2023) was associated with a return to the pre-pandemic levels of diagnoses and operations. The adherence rates were lower for individuals living in rural areas, with low socio-economic status, and unmarried persons; however, the most statistically significant factor for reduced adherence was a lower level of educational attainment. Free screening through nationally organized programs reduced social disparities. There were no significant differences between the pre-pandemic and pandemic periods for several types of cancers (stomach, esophagus, pancreas, liver) that are diagnosed for the occurrence of symptoms and for which nationally organized programs might increase the possibility of earlier diagnosis and improved clinical outcomes. Education, information, and appropriate expenditure for preventive care have the potential to reduce cancer mortality. Nationally organized screening programs for several types of cancers, which are often detected for the occurrence of symptoms, may increase the possibility of diagnosis at earlier stages. [ABSTRACT FROM AUTHOR]

The synthesis of some N-(3-acyloxyacyl)glycines, an interesting class of bioactive gut microbiota metabolites, is described. This procedure involves seven reaction steps using the commercially available Meldrum's acid to obtain highly pure products, in normal or deuterated form. The key point of the synthetic strategy was the use of commendamide t-butyl ester as a synthetic intermediate, a choice that allowed the removal of the protecting group at the end of the synthetic procedure without degrading of the other ester bond present in the molecule. The developed synthetic sequence is particularly simple, uses readily available reagents and involves a limited number of purifications by chromatographic column, with a reduction in the volume of solvent and energy used. [ABSTRACT FROM AUTHOR]

Background: Endovascular treatment of popliteal aneurysms (PA) has increased in the last few years, quickly becoming the main treatment performed in many vascular centers, based on the acceptable and promising outcomes reported in the literature. However, endograft infections after endovascular popliteal aneurysm repair (EPAR) are the most dangerous complications to occur as they involve serious local compromise and usually require open surgical conversion and device explantation to preserve the affected extremity. Case report: We report two patients who were admitted to the emergency room of our hospital for pain and edema in the lower leg. Both patients had undergone exclusion of a ruptured PA a few years before by endovascular graft. CTA testing showed a significant volume of fluid-corpuscular collection related to perianeurysmal abscess collection in both cases. Blood cultures and drained material cultures were positive for Staphylococcus capitis in the first case and S. aureus in the second. Prophylactic antibiotics were administered for 10 days, then patients underwent an open surgical conversion with the complete explantation of endovascular material and a femoro-popliteal bypass using an autologous vein in the first case and a biological bovine pericardium prosthesis in the second case. The infective department of our hospital had defined a discharged specific antibiotic therapy for each patient, based on intraoperative microbiological samples. Furthermore, we have examined the literature and found six more cases described in case report articles that refer to popliteal graft infections by different microorganisms, mostly presenting acute limb ischemia as the first symptom and suggesting endograft explantation with open conversion and autologous vein bypass as the commonest therapeutic choice. Conclusions: The open surgical conversion of popliteal endograft infection is the best strategy to manage peripheral infection after an endovascular popliteal aneurysm repair procedure. [ABSTRACT FROM AUTHOR]

Organisations heavily dependent on paper documents still spend a significant amount of time managing a large volume of documents. An intelligent document management system (DMS) is presented to automate the processing of tax and administrative documents. The proposed system fills a gap in the landscape of practical tools in the field of DMS and advances the state of the art. This system represents a complex process of integrated AI-powered technologies that creates an ontology, extracts information from documents, defines profiles, maps the extracted data in RDF format, and applies inference through a reasoning engine. The DMS was designed to help all those companies that manage their clients' tax and administrative documents daily. Automation speeds up the management process so that companies can focus more on value-added services. The system was tested in a case study that focused on the preparation of tax returns. The results demonstrated the efficacy of the system in providing document management service. [ABSTRACT FROM AUTHOR]

The emergence of inflammatory diseases is a heavy burden on modern societies. Cannabis has been used for several millennia to treat inflammatory disorders such as rheumatism or gout. Since the characterization of cannabinoid receptors, CB1 and CB2, the potential of cannabinoid pharmacotherapy in inflammatory conditions has received great interest. Several studies have identified the importance of these receptors in immune cell migration and in the production of inflammatory mediators. As the presence of the CB2 receptor was documented to be more predominant in immune cells, several pharmacological agonists and antagonists have been designed to treat inflammation. To better define the potential of the CB2 receptor, three online databases, PubMed, Google Scholar and clinicaltrial.gov, were searched without language restriction. The full texts of articles presenting data on the endocannabinoid system, the CB2 receptor and its role in modulating inflammation in vitro, in animal models and in the context of clinical trials were reviewed. Finally, we discuss the clinical potential of the latest cannabinoid-based therapies in inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Despite extensive studies on the neurobiological correlates of traumatic brain injury (TBI), little is known about its molecular determinants on long-term consequences, such as dementia and Alzheimer's disease (AD). Methods: Here, we carried out behavioural studies and an extensive biomolecular analysis, including inflammatory cytokines, gene expression and the combination of LC-HRMS and MALDI-MS Imaging to elucidate the targeted metabolomics and lipidomics spatiotemporal alterations of brains from wild-type and APP-SWE mice, a genetic model of AD, at the presymptomatic stage, subjected to mild TBI. Results: We found that brain injury does not affect cognitive performance in APP-SWE mice. However, we detected an increase of key hallmarks of AD, including Aβ1-42 levels and BACE1 expression, in the cortices of traumatized transgenic mice. Moreover, significant changes in the expanded endocannabinoid (eCB) system, or endocannabinoidome (eCBome), occurred, including increased levels of the endocannabinoid 2-AG in APP-SWE mice in both the cortex and hippocampus, and N-acylserotonins, detected for the first time in the brain. The gene expression of enzymes for the biosynthesis and inactivation of eCBs and eCB-like mediators, and some of their main molecular targets, also underwent significant changes. We also identified the formation of heteromers between cannabinoid 1 (CB1) and serotonergic 2A (5HT2A) receptors, whose levels increased in the cortex of APP-SWE mTBI mice, possibly contributing to the exacerbated pathophysiology of AD induced by the trauma. Conclusions: Mild TBI induces biochemical changes in AD genetically predisposed mice and the eCBome may play a role in the pathogenetic link between brain injury and neurodegenerative disorders also by interacting with the serotonergic system. [ABSTRACT FROM AUTHOR]

Background. Homicide by burning is rare, involving victims exposed to direct flames, often with accelerants. This demonstrates excessive force by the assaulter. A thorough investigation is vital as fire can conceal pathological findings. This study presents two emblematic cases of intentional burning. Case report. Two cases of homicide by fire are detailed. The first involves a male found dead in a fire-damaged apartment, doused with flammable liquid and set on fire by his partner. The autopsy showed heat hematoma and soot in the trachea and large bronchi. The second case involves a female set on fire with gasoline by an acquaintance, sustaining burns over 90% of her body and dying from hypovolemic shock. The autopsy revealed effusions in pleural and peritoneal cavities and a hyperaemic trachea. Conclusions. Intentional burnings are sporadic and difficult to classify without testimonial evidence. The difference between homicide and accidental burns relies on circumstantial evidence and antemortem injuries. Vital reactions to thermal lesions include red-base blisters, dilated capillaries, leukocyte infiltration, coagulative necrosis, heat hematoma, and soot in the airways. High carboxyhemoglobin levels indicate vitality. The first case showed heat hematoma and tracheal soot, while the second exhibited severe burns leading to hypovolemic shock. Testimonial evidence and crime scene examination were crucial in determining the homicidal nature. Forensic investigation of charred corpses requires a comprehensive evaluation of all available data. Crime scene analysis, combined with autopsy, toxicological tests, and post-mortem CT scans, helps establish the cause of death and differentiate between ante- and postmortem injuries. [ABSTRACT FROM AUTHOR]

Palmitoylethanolamide (PEA) is a pleiotropic lipid mediator with established anti-inflammatory and anti-hyperalgesic activity. Ultramicronized PEA (PEA-um) has superior oral efficacy compared to naïve (non-micronized) PEA. The aim of the present study was two-fold: (1) to evaluate whether oral PEA-um has greater absorbability compared to naïve PEA, and its ability to reach peripheral and central tissues under healthy and local inflammatory conditions (carrageenan paw edema); (2) to better characterize the molecular pathways involved in PEA-um action, particularly at the spinal level. Rats were dosed with 30 mg/kg of [13C]4-PEA-um or naïve [13C]4-PEA by oral gavage, and [13C]4-PEA levels quantified, as a function of time, by liquid chromatography/atmospheric pressure chemical ionization/mass spectrometry. Overall plasma levels were higher in both healthy and carrageenan-injected rats administered [13C]4-PEA-um as compared to those receiving naïve [13C]4-PEA, indicating the greater absorbability of PEA-um. Furthermore, carrageenan injection markedly favored an increase in levels of [13C]4-PEA in plasma, paw and spinal cord. Oral treatment of carrageenan-injected rats with PEA-um (10 mg/kg) confirmed beneficial peripheral effects on paw inflammation, thermal hyperalgesia and tissue damage. Notably, PEA-um down-regulated distinct spinal inflammatory and oxidative pathways. These last findings instruct on spinal mechanisms involved in the anti-hyperalgesic effect of PEA-um in inflammatory pain. [ABSTRACT FROM AUTHOR]

Objective: Endocannabinoids and their N-acyl-ethanolamines (NAEs) and 2monoacyl-glycerols (2-MAGs) congeners are involved in the central and peripheral regulation of energy homeostasis, they are present in human milk and are associated with obesity. Infants exposed in utero to gestational diabetes mellitus (GDM) are more likely to develop obesity. The objective of this crosssectional study is to compare the profile of eCBome mediators in milk of women with gestational diabetes (GDM+) and without (GDM-) and to assess the association with offspring growth. The hypothesis is that the eCBome of GDM+ human milk is altered and associated with a difference in infant growth. Methods: Circulating eCBome mediators were measured by LC-MS/MS in human milk obtained at 2 months postpartum from GDM+ (n=24) and GDM- (n=29) women. Infant weight and height at 2 months were obtained from the child health record. Z-scores were calculated. Results: Circulating Npalmitoylethanolamine (PEA) was higher in human milk of GDM+ women than in GDM-women (4.9 ± 3.2 vs. 3.3 ± 1.7, p=0.04). Higher levels were also found for several 2monoacyl-glycerols (2-MAGs) (p<0.05). The levels of NAEs (b=-4.6, p=0.04) and especially non-omega-3 NAEs (B=-5.6, p=0.004) in human milk were negatively correlated with weight-for-age z-score of GDM+ offspring. Conclusion: The profile of eCBome mediators in human milk at 2 months postpartum was different in GDM+ compared to GDM-women and was associated with GDM+ offspring growth at 2 months. [ABSTRACT FROM AUTHOR]

Introduction: Popliteal artery entrapment syndrome (PAES) is a rare disease of the lower limbs, mainly affecting young patients, due to extrinsic compression of the neurovascular bundle at the popliteal fossa. The aim of this study was to describe our experience during a median 15-year period. Methods: Patients treated for PAES in our institution from 1979 to 2024 were included. Preoperative, intraoperative, and postoperative data were analyzed. Results: A total of 47 patients with a total of 78 limbs were treated. Duplex ultrasound with active maneuvers was performed in all limbs (100%). Angiography was performed in almost all patients (97.4%), computed tomography angiography in 56 (71.8%), and magnetic resonance angiography in 22 (28.2%). Concerning surgical treatment, musculotendinous section was performed in 60 limbs (76.9%), and autologous venous bypass was achieved in 18 limbs (23.1%). The rates for freedom from target lesion revascularization—meaning that no significant stenosis or occlusion during follow-up required revascularization—and 15-year primary patency were 92.4% and 98%, respectively. Conclusion: Long-term results of surgical treatment for PAES seem to be very satisfying. Myotomy with or without arterial reconstruction using venous bypass can lead to good patency at 15 years of follow-up. [ABSTRACT FROM AUTHOR]

Despite the non-contact underwater explosion phenomena (UNDEX) have been studied for decades and several numerical methods have been proposed in literature, its effects on military structures, especially composite ones, are even nowadays matter of research. In early design phases, it is not always possible to verify the shock resistance of hull structures modelling the whole phenomenon, in which fluid, gas and solid properties must be properly set in a fully coupled fluid-structure interaction (FSI) numerical model. These ones are extremely complex to set, computationally demanding and certainly not suitable for everyday design practice. In this paper, a simplified finite element (FE) model, easy to use in an early design phase, is proposed. Both, the structure and the fluid are simulated. In this approximation, the fluid behaviour is simplified, using special finite elements, available in a commercial software environment. This choice reduces the computational time and numerical efforts avoiding the problem of combining computational fluid dynamics (CFD) and FE domains and equations in a fully coupled fluid-structure interaction model. A typical parallel body block of a minesweeper is modelled, using two-dimensional multi-layered shell elements to properly account for the composite materials behaviour. For the fluid instead, three dimensional volumetric elements, directly coupled to the structural elements, are placed. In addition, the same calculation is performed, modelling separately fluid in the CFD environment and structures in the finite element one. Thus, realizing a fully coupled fluid-structure interaction model. The results obtained by applying both numerical models are compared with the structural response measured on board of a composite ship during a full-scale shock test. The simplified proposed procedure provides results in satisfactory agreement with experiments, allowing the validation of the model. Approximations are discussed and differences with the real phenomenon and fully coupled CFD+FE method are shown, providing a better understanding of the phenomena. Eventually, the modelling strategy has been considered a valuable and cost-effective tool for the concept and preliminary design of composite structures subject to underwater explosions. [ABSTRACT FROM AUTHOR]

In engineering applications, it is standard to consider modal parameters (e.g. natural frequencies and mode shapes), to obtain measurable changes induced by damage events. However, such changes are often too subtle to detect and interpret accurately. In order to overcome this limitation and enhance the efficacy of damage detection, this study introduces an innovative technique inspired by Prof. Lekszycki, outlined prior to his untimely departure. This technique is designed to highlight the influence of structural damage on natural frequencies. In other words, we add an external mass in a general point of a structure and calculate the set of natural frequencies before and after the occurrence of a damage event. We, therefore, repeat this procedure for all the points of the structure. The hypothesis we have verified in this paper is that if the mass is posed in the neighborhood of the place where the damage is considered, then it interacts with the undamaged and with the damaged structure in a different way. In particular, the changes of the natural frequencies between the undamaged and the damaged structure are emphasized. We verify the correctness of this idea for selected and simple examples in both 2D and 3D environments. [ABSTRACT FROM AUTHOR]

Fuel level gauging in aircraft presents a significant flight mechanics challenge due to the influence of aircraft movements on measurements. Moreover, it constitutes a multidimensional problem where various sensors distributed within the tank must converge to yield a precise and single measurement, independent of the aircraft's attitude. Furthermore, fuel distribution across multiple tanks of irregular geometries complicates the readings even further. These issues critically impact safety and economy, as gauging errors may compromise flight security and lead to carrying excess weight. In response to these challenges, this research introduces a multi-stage project in aircraft fuel gauging systems, as a continuum of studies, where this first article presents a computational tool designed to simulate aircraft fuel sensor data readings as a function of fuel level, fuel tank geometry, sensor location, and aircraft attitude. Developed in an open-source environment, the tool aims to support the statistical inference required for accurate modeling in which synthetic data generation becomes a crucial component. A discretization procedure accurately maps fuel tank geometries and their mass properties. The tool, then, intersects these geometries with fuel-level planes and calculates each new volume. It integrates descriptive geometry to intersect these fuel planes with representative capacitive level-sensing probes and computes the sensor readings for the simulated flight conditions. The method is validated against geometries with analytical solutions. This process yields detailed fuel measurement responses for each sensor inside the tank, and for different analyzed fuel levels, providing insights into the sensors' signals' non-linear behavior at each analyzed aircraft attitude. The non-linear behavior is also influenced by the sensor saturation readings at 0 when above the fuel level and at 1 when submerged. The synthetic fuel sensor readings lay the baseline for a better understanding on how to compute the true fuel level from multiple sensor readings, and ultimately optimizing the amount of used sensors and their placement. The tool's design offers significant improvements in aircraft fuel gauging accuracy, directly impacting aerostructures and instrumentation, and it is a key aspect of flight safety, fuel management, and navigation in aerospace technology. [ABSTRACT FROM AUTHOR]

Background: Accessory renal arteries (ARAs) frequently coexist with abdominal aortic aneurysms (AAA) and can influence treatment. This study aimed to retrospectively analyze the ARA's exclusion effect on patients undergoing standard endovascular aneurysm repair for AAA. Methods: The study focused on medium- and long-term outcomes, including type II endoleak, aneurysmal sac changes, mortality, reoperation rates, renal function, and infarction post-operatively. Results: 76 patients treated with EVAR for AAA were included. One hundred and two ARAs were identified: 69 originated from the neck, 30 from the sac, and 3 from the iliac arteries. The ARA treatment was embolization in 15 patients and coverage in 72. Technical success was 100%. One-month post-operative computed tomography angiography (CTA) revealed that 76 ARAs (74.51%) were excluded. Thirty-day complications included renal deterioration in 7 patients (9.21%) and a blood pressure increase in 15 (19.73%). During follow-up, 16 patients (21.05%) died, with three aneurysm-related deaths (3.94%). ARA-related type II endoleak (T2EL) was significantly associated with the ARA's origin in the aneurysmatic sac. Despite reinterventions were not significantly linked to any factor, post-operative renal infarction was correlated with an ARA diameter greater than 3 mm and ARA embolization. Conclusion: ARAs can influence EVAR outcomes, with anatomical and procedural factors associated with T2EL and renal infarction. Further studies are needed to optimize the management of ARAs during EVAR. [ABSTRACT FROM AUTHOR]

The projected population increase and drastic climate changes are a great setback to food security through sustainable agriculture. However, governments need to play key roles in supporting the agriculture sector, which creates considerable employment and contributions to most countries' Gross Domestic Product (GDP) outcomes. In many countries, the governments already support the agriculture sector with services based on Information and Communication Technology (ICT) to reach many stakeholders, including smallholder farmers. This paper investigated the status of e-Government services in the agriculture sector for farmers in order to understand the functions and scope of e-services, the challenges faced by farmers, both addressed and unaddressed, and the challenges of ICT-based services for farmers and other stakeholders in Tanzania. We used a qualitative research approach to interview the Ministry of Agriculture, farmers, extension workers, and agriculture processing industries. The main finding reveals that e-government services play a major role in the agriculture sector in Tanzania. Our results show that the pre-existing ICT services identified for farmers cannot meet the needs of farmers in a complete farming cycle. Moreover, lack of awareness, digital illiteracy, and poor infrastructure are the major challenges faced by farmers and other stakeholders when it comes to ICT-based services. These results justify the need for a comprehensive digital platform, particularly the proposed Farmers Digital Information System (FDIS) to enable farmers and other stakeholders to access essential services in a complete farming cycle for a more sustainable agriculture. [ABSTRACT FROM AUTHOR]

The health and balance of the gut microbiota are known to be linked to diet composition and source, with fermented products and dietary proteins potentially providing an exceptional advantage for the gut. The purpose of this study was to evaluate the effect of protein hydrolysis, using a probiotic beverage enriched with either cricket protein (CP) or cricket protein hydrolysates (CP.Hs), on the composition of the gut microbiota of rats. Taxonomic characterization of the gut microbiota in fecal samples was carried out after a 14-day nutritional study to identify modifications induced by a CP- and CP.H-enriched fermented probiotic product. The results showed no significant differences (p > 0.05) in the diversity and richness of the gut microbiota among the groups fed with casein (positive control), CP-enriched, and fermented CP.H-enriched probiotic beverages; however, the overall composition of the microbiota was altered, with significant modifications in the relative abundance of several bacterial families and genera. In addition, fermented CP.H-enriched probiotic beverages could be related to the decrease in the number of potential pathogens such as Enterococcaceae. The association of gut microbiota with the nutritional parameters was determined and the results showed that digestibility and the protein efficiency ratio (PER) were highly associated with the abundance of several taxa. [ABSTRACT FROM AUTHOR]

In the context of the COVID-19 pandemic, the global healthcare landscape has undergone significant transformations, particularly impacting the management of complex medical conditions such as aortic aneurysms. This study focuses on a 76-year-old female patient with a history of extensive cardiovascular surgeries, including aortic valve replacement, Bentall operation, and Frozen Elephant Trunk procedure, who presented with a type II thoracoabdominal aortic aneurysm post-COVID-19 recovery. A comprehensive frailty assessment using the Modified Frailty Index and a two-phase endovascular approach for aneurysm treatment, considering the patient's frailty and complex medical history was performed. Upon successful aneurysm management, the patient's postoperative course was complicated by COVID-19 reinfection and Enterococcus faecalis superinfection, highlighting the increased risk of bacterial superinfections and the challenges posed by antimicrobial resistance in COVID-19 patients. The study underscores the necessity of vigilant postoperative surveillance and a multidisciplinary approach in managing such complex cases, highlighting the importance of personalized care strategies, integrating cardiovascular and infectious disease management, and adapting healthcare practices to the unique challenges of the pandemic. This case contributes to the evolution of knowledge on managing aortic aneurysms in the COVID-19 era, advocating for patient-centric treatment approaches and continuous research into long-term patient outcomes. [ABSTRACT FROM AUTHOR]

The mechanism underlying the transition from the pre-symptomatic to the symptomatic state is a crucial aspect of epileptogenesis. SYN2 is a member of a multigene family of synaptic vesicle phosphoproteins playing a fundamental role in controlling neurotransmitter release. Human SYN2 gene mutations are associated with epilepsy and autism spectrum disorder. Mice knocked out for synapsin II (SynII KO) are prone to epileptic seizures that appear after 2 months of age. However, the involvement of the endocannabinoid system, known to regulate seizure development and propagation, in the modulation of the excitatory/inhibitory balance in the epileptic hippocampal network of SynII KO mice has not been explored. In this study, we investigated the impact of endocannabinoids on glutamatergic and GABAergic synapses at hippocampal dentate gyrus granule cells in young pre-symptomatic (1–2 months old) and adult symptomatic (5–8 months old) SynII KO mice. We observed an increase in endocannabinoid-mediated depolarization-induced suppression of excitation in young SynII KO mice, compared to age-matched wild-type controls. In contrast, the endocannabinoid-mediated depolarization-induced suppression of inhibition remained unchanged in SynII KO mice at both ages. This selective alteration of excitatory synaptic transmission was accompanied by changes in hippocampal endocannabinoid levels and cannabinoid receptor type 1 distribution among glutamatergic and GABAergic synaptic terminals contacting the granule cells of the dentate gyrus. Finally, inhibition of type-1 cannabinoid receptors in young pre-symptomatic SynII KO mice induced seizures during a tail suspension test. Our results suggest that endocannabinoids contribute to maintaining network stability in a genetic mouse model of human epilepsy. [ABSTRACT FROM AUTHOR]

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within—and across—countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation. [ABSTRACT FROM AUTHOR]

(1) Background: Spontaneous isolated intramural hematoma of the superior mesenteric artery (SIHSMA) is a rare entity often considered as a subset of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). It is characterized by a completely thrombosed false lumen with or without an ulcer-like projection with computed tomography (CT) imaging. The recent literature describes few reports with a relatively short-term follow-up. The natural course, prognosis, and treatment options for SIHSMA still lack consensus. We present two cases of acute abdominal pain in a young man due to IMH of the superior mesenteric artery with an extensive literature review. (2) Case report: A 46-year-old male patient was submitted to an urgent CTA for acute abdominal pain, showing the presence of an isolated dissection of the superior mesenteric artery, determining significant stenosis of the vessel with collateral vessel patency. The patient referred to a recent COVID-19 infection, whose course was paucisymptomatic. He was conservatively treated with antiplatelet therapy and corticosteroid treatments, and, after a few days, the symptomatology completely regressed; also, the 2-month-control CTA showed complete IMH regression and the absence of any signs of residual stenosis. The second patient was a 61-year-old male patient who was submitted to an urgent CTA for acute abdominal pain, showing the presence of an isolated dissection of the superior mesenteric artery, not determining significant vessel stenosis. He was conservatively treated with antiplatelet therapy and corticosteroid treatment, and after a few days, the symptomatology completely regressed and the radiological control showed complete dissection regression. (3) Conclusion: SISHSMA is a rare entity of vascular pathology, and conservative management represents the best medical strategy. We propose corticosteroid treatment as one of the most appropriate tools in the conservative treatment of SISHSMA. [ABSTRACT FROM AUTHOR]

Smart grids play an important role for energy management by directly supporting the socio-ecological transition of neighbourhoods. This research provides the design of a coordination model to enable the management and exchange of electrical energy between producers and consumers at a micro-grid level. This model, which derives from the SAPERE coordination model, allows the intelligent digital twins to interact and generate services on the fly to meet different needs in real time. We have designed producer and consumer digital twins, which autonomously generate supply contracts in the form of a transaction, and supervisor digital twins, which regulate energy at the node level, managing threshold violations and proactively avoiding future threshold violations by using predictions. This coordination model allows energy exchanges in a single node and in a micro-grid structure that contains several neighbouring nodes. We have implemented and tested the platform with realistic data, based on the consumption statistics of a real household, and with real data, collected in the living-lab of "Les Vergers" located near Geneva. The results show that the combination of a coordination model and intelligent digital twins actually supports self-adaptive energy management in a smart grid. Such approaches are fundamental to develop efficient and reliable smart grids. [ABSTRACT FROM AUTHOR]

Smallholder farmers produce about 70% of the world's food and employ more than one billion people. They therefore have an important role to play in eradicating food insecurity and poverty among the world's growing population. Although there are different digital services for smallholder farmers, the existing services lack sustainability in the agriculture context and hardly meet their needs. Data management and sharing among different agriculture stakeholders has the potential to make agriculture sustainable, but there is a need to enable access to digital services in an entire farming cycle under one roof. This paper aims to propose the design of a comprehensive data management digital framework to solve common challenges of smallholder farmers in Tanzania and other countries' agricultural systems. We follow the design science research (DSR) method to develop an artifact that interacts with the problem context. To illustrate the framework's applicability, we use different case studies in Tanzania. [ABSTRACT FROM AUTHOR]

The vascular endothelium is key target for immune and thrombotic responses that has to be controlled in successful xenotransplantation. Several genes were identified that, if induced or overexpressed, help to regulate the inflammatory response and preserve the transplanted organ function and metabolism. However, few studies addressed combined expression of such genes. The aim of this work was to evaluate in vivo the effects of the simultaneous expression of three human genes in a mouse generated using the multi-cistronic F2A technology. Male 3-month-old mice that express human heme oxygenase 1 (hHO-1), ecto-5′-nucleotidase (hE5NT), and ecto-nucleoside triphosphate diphosphohydrolase 1 (hENTPD1) (Transgenic) were compared to wild-type FVB mice (Control). Background analysis include extracellular nucleotide catabolism enzymes profile on the aortic surface, blood nucleotide concentration, and serum L-arginine metabolites. Furthermore, inflammatory stress induced by LPS in transgenic and control mice was used to characterize interleukin 6 (IL-6) and adhesion molecules endothelium permeability responses. Transgenic mice had significantly higher rates of extracellular adenosine triphosphate and adenosine monophosphate hydrolysis on the aortic surface in comparison to control. Increased levels of blood AMP and adenosine were also noticed in transgenics. Moreover, transgenic animals demonstrated the decrease in serum monomethyl-L-arginine level and a higher L-arginine/monomethyl-L-arginine ratio. Importantly, significantly decreased serum IL-6, and adhesion molecule levels were observed in transgenic mice in comparison to control after LPS treatment. Furthermore, reduced endothelial permeability in the LPS-treated transgenic mice was noted as compared to LPS-treated control. The human enzymes (hHO-1, hE5NT, hENTPD1) simultaneously encoded in transgenic mice demonstrated benefits in several biochemical and functional aspects of endothelium. This is consistent in use of this approach in the context of xenotransplantation. [ABSTRACT FROM AUTHOR]

Introduction: The endocannabinoid system (ECS) plays an integral role in maintaining metabolic homeostasis, where an hyperactivation has been related with serum lipid alterations. The biological effects of ECS are limited by the activation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) and by polyunsaturated fatty acid (PUFA) intake as precursors. The FAAH Pro129Thr variant has been associated with obesity in some populations. However, the association with metabolic phenotypes in the Mexican population has not been studied. This study aimed to analyze the association of the FAAH Pro129Thr variant with serum lipids and diet in Mexican adults with different metabolic phenotypes. Methods: This is a cross-sectional study with 306 subjects between 18 and 65 years of age. They were classified with normal weight (NW) or excess weight (EW) according to their body mass index (BMI). The EW group included individuals with overweight or obesity (BMI 25–39.9 kg/m2). The individuals were classified into two metabolic phenotypes, metabolically healthy and metabolically unhealthy (MUH), using the homeostatic model assessment of insulin resistance and the National Cholesterol Education Program-adenosine triphosphate III cutoff points for blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting glucose. Subjects with ≥2 of 5 altered parameters were classified as MUH. The FAAH Pro129Thr variant was determined by allelic discrimination with TaqMan® probes. Results: The total cholesterol and very low-density lipoprotein cholesterol levels were associated with the FAAH Pro129Thr variant in NW-MUH subjects. Moreover, a lower PUFA intake was found in EW-MUH subjects with the FAAH variant. Conclusions:FAAH Pro129Thr variant has an important role in lipid metabolism, especially in NW-MUH subjects. By contrast, a low dietary intake of endocannabinoid PUFA precursors may partly counteract the development of the altered lipid profile associated with overweight/obesity. [ABSTRACT FROM AUTHOR]

The gut microbiota and the endocannabinoidome (eCBome) play important roles in regulating energy homeostasis, and both are closely linked to dietary habits. However, the complex and compositional nature of these variables has limited our understanding of their interrelationship. This study aims to decipher the interrelation between dietary intake and the gut microbiome–eCBome axis using two different approaches for measuring dietary intake: one based on whole food and the other on macronutrient intakes. We reveal that food patterns, rather than macronutrient intakes, were associated with the gut microbiome–eCBome axis in a sample of healthy men and women (n = 195). N-acyl-ethanolamines (NAEs) and gut microbial families were correlated with intakes of vegetables, refined grains, olive oil and meats independently of adiposity and energy intakes. Specifically, higher intakes in vegetables and olive oil were associated with increased relative abundance of Clostridiaceae, Veillonellaceae and Peptostreptococaceae, decreased relative abundance of Acidominococaceae, higher circulating levels of NAEs, and higher HDL and LDL cholesterol levels. Our findings highlight the relative importance of food patterns in determining the gut microbiome–eCBome axis. They emphasize the importance of recognizing the contribution of dietary habits in these systems to develop personalized dietary interventions for preventing and treating metabolic disorders through this axis. [ABSTRACT FROM AUTHOR]

N-oleoylglycine (OlGly), a lipid derived from the basic component of olive oil, oleic acid, and N-oleoylalanine (OlAla) are endocannabinoid-like mediators. We report that OlGly and OlAla, by activating the peroxisome proliferator-activated receptor alpha (PPARα), reduce the rewarding properties of a highly palatable food, dopamine neuron firing in the ventral tegmental area, and the obesogenic effect of a high-fat diet rich in lard (HFD-L). An isocaloric olive oil HFD (HFD-O) reduced body weight gain compared to the HFD-L, in a manner reversed by PPARα antagonism, and enhanced brain and intestinal OlGly levels and gut microbial diversity. OlGly or OlAla treatment of HFD-L mice resulted in gut microbiota taxonomic changes partly similar to those induced by HFD-O. We suggest that OlGly and OlAla control body weight by counteracting highly palatable food overconsumption, and possibly rebalancing the gut microbiota, and provide a potential new mechanism of action for the obeso-preventive effects of olive oil-rich diets. In mice, lipoamino acids activate the peroxisome proliferator-activated receptor alpha, thus reducing the rewarding properties of palatable food, dopamine neuron firing and the obesogenic effect of a high-fat diet. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a complex illness marked by aberrant cellular behaviors and genetic variances, resulting in tumor heterogeneity that presents challenges in cancer prognosis and treatment. This review underscores the significance of comprehending tumor heterogeneity, offering perspectives on its attributes and the intricacies involved in its quantification. By emphasizing the need for effective therapies targeting tumor heterogeneity, this work contributes to raising awareness about this elusive characteristic of cancer. Cancer manifests as a multifaceted disease, characterized by aberrant cellular proliferation, survival, migration, and invasion. Tumors exhibit variances across diverse dimensions, encompassing genetic, epigenetic, and transcriptional realms. This heterogeneity poses significant challenges in prognosis and treatment, affording tumors advantages through an increased propensity to accumulate mutations linked to immune system evasion and drug resistance. In this review, we offer insights into tumor heterogeneity as a crucial characteristic of cancer, exploring the difficulties associated with measuring and quantifying such heterogeneity from clinical and biological perspectives. By emphasizing the critical nature of understanding tumor heterogeneity, this work contributes to raising awareness about the importance of developing effective cancer therapies that target this distinct and elusive trait of cancer. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major worldwide neurological disorder with no neuroprotective treatment available. Three-dimensional (3D) in vitro models of brain contusion serving as a screening platform for drug testing are lacking. Here we developed a new in vitro model of brain contusion on organotypic cortical brain slices and tested its responsiveness to mesenchymal stromal cell (MSC) derived secretome. A focal TBI was induced on organotypic slices by an electromagnetic impactor. Compared to control condition, a temporal increase in cell death was observed after TBI by propidium iodide incorporation and lactate dehydrogenase release assays up to 48 h post-injury. TBI induced gross neuronal loss in the lesion core, with disruption of neuronal arborizations measured by microtubule-associated protein-2 (MAP-2) immunostaining and associated with MAP-2 gene down-regulation. Neuronal damage was confirmed by increased levels of neurofilament light chain (NfL), microtubule associated protein (Tau) and ubiquitin C-terminal hydrolase L1 (UCH-L1) released into the culture medium 48 h after TBI. We detected glial activation with microglia cells acquiring an amoeboid shape with less ramified morphology in the contusion core. MSC-secretome treatment, delivered 1 h post-injury, reduced cell death in the contusion core, decreased NfL release in the culture media, promoted neuronal reorganization and improved microglia survival/activation. Our 3D in vitro model of brain contusion recapitulates key features of TBI pathology. We showed protective effects of MSC-secretome, suggesting the model stands as a tractable medium/high throughput, ethically viable, and pathomimetic biological asset for testing new cell-based therapies. [ABSTRACT FROM AUTHOR]

Background. Mesotherapy is a technique through which active ingredients are administered into the thickness of the skin in order to increase the local analgesic effect. Methods. 141 patients with spinal pain not responding to systemic therapy with NSAIDs were randomized to receive one or more intracutaneous drugs on a weekly basis. Results. All patients achieved a pain reduction of at least 50% compared to baseline, and all tolerated the therapy without having to resort to systemic drug dose increases. Conclusions. The data from our study show that the active ingredients infiltrated into the skin induce a mesodermal modulation between the infiltrated liquid and the cutaneous nervous and cellular structures from which the typical drug-saving effect of mesotherapy arises. Although further studies are needed to establish how to integrate mesotherapy in various clinical settings, it appears to be a useful technique available to the practicing physician. This research is also useful in guiding future clinical research. [ABSTRACT FROM AUTHOR]

We investigated a novel dedicated Prostate Imaging for Local Recurrence Reporting and Data System (PI-RRADS) in biochemical recurrence after radiotherapy (RT) and radical prostatectomy (RP) evaluating biparametric magnetic resonance imaging (bpMRI) exams, at 3T MRI of 55 patients. Associating bpMRI and biochemical recurrence data, we calculated bpMRI diagnostic accuracy. Four probability categories, from 1 (very low) to 4 (very high), were distinguished. In 20 patients with radiotherapy, 25% and 75% of lesions were reported as PI-RRADS 3, and 4, respectively. In 35 patients with radical prostatectomy, 7.7% of lesions were included in PI-RRADS 1-2, whereas 40.4% and 51.9% in PI-RRADS 3 and 4 categories, respectively. Excellent agreement and significant correlation between bpMRI and biochemical recurrence were found. BpMRI showed sensitivity, specificity, positive predictive value, negative predictive value, false-positive value, false-negative value, and total diagnostic accuracy of 96.15%, 86.7%, 97.4 %, 81.25%, 13.3%, 3.8% and 94.6%, respectively. BpMRI-based PI-RRADS allows the detection and localization local recurrence in biochemical recurrence after RT and RP contributing in clinical management and treatment. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) was first reported thousands of years ago, yet there is still a shortage of biomarkers to determine the severity and type of PE. The importance of the expanded endocannabinoid system, or endocannabinoidome (eCBome), has emerged recently in placental physiology and pathology, though the potential alterations of the eCBome in PE have not been fully explored. Analysis by qRT‐PCR using placental samples of normotensive and PE women demonstrate for the first time the presence of ABHD4, GDE1, and DAGLβ in both normotensive and PE placental tissues. Interestingly, NAPE‐PLD, FAAH‐1, DAGLα, MAGL, and ABHD6 mRNA levels were increased in the placental tissues of PE patients. Quantification in plasma and placental tissues showed a decrease for anandamide (AEA), N‐oleoylethanolamine (OEA), and N‐docosahexaenoylethanolamine (DHEA) in the placenta, accompanied only by a decrease in plasma levels of AEA. In addition, a strong negative correlation was obtained between OEA and the biomarker of PE, soluble fms‐like tyrosine kinase‐1. Given the inflammatory nature of PE and the anti‐inflammatory role of OEA and DHEA, the decrease in the local levels of these mediators may underlie the inflammatory component of this pathology. Additionally, lower AEA levels in both placenta and plasma may contribute to the atypical alterations of the spiral arteries in PE due to the vasorelaxation effects of AEA. These results add new information to the role of the eCBome members in placental development, while also pointing to a potential role as biomarkers of PE. [ABSTRACT FROM AUTHOR]

Dacarbazine is an important drug in the therapeutic landscape of leiomyosarcoma (LMS). Alkylating agents are subjected to resistance mechanisms based on anti-apoptotic pathways and repair mechanisms, including the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). In this retrospective study, the methylation status of the MGMT promoter in histological tumor samples from patients with LMS, dacarbazine-based regimens-treated, was measured and correlated with clinical outcomes aimed at optimizing the use of dacarbazine in soft tissue sarcomas. The patients with unmethylated MGMT had better outcomes than those with methylated MGMT. Patients without MGMT methylation had better Progression Free Survival (PFS) when aged ≥62 years compared to those aged <62 years, while PFS of patients with methylated MGMT was less favorable independently of age (p = 0.0054). The patients without a methylated MGMT gene had higher Disease control rate (DCR). These results are not in agreement with the role of the methylated MGMT gene in other tumors, and with this study, we demonstrated the correlation between methylated MGMT and poor prognosis; despite that, sample smallness, heterogeneity of LMS and of treatment history could be selection bias. Predictive markers of response to chemotherapies in sarcomas remain an unmet need. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota are involved in the onset and development of chronic intestinal inflammation. The recently described endocannabinoidome (eCBome), a diverse and complex system of bioactive lipid mediators, has been reported to play a role in various physio-pathological processes such as inflammation, immune responses and energy metabolism. The eCBome and the gut microbiome (miBIome) are closely linked and form the eCBome - miBIome axis, which may be of special relevance to colitis. Methods: Colitis was induced in conventionally raised (CR), antibiotic-treated (ABX) and germ-free (GF) mice with dinitrobenzene sulfonic acid (DNBS). Inflammation was assessed by Disease Activity Index (DAI) score, body weight change, colon weight-length ratio, myeloperoxidase (MPO) activity and cytokine gene expression. Colonic eCBome lipid mediator concentrations were measured by HPLC-MS /MS. Results: GF mice showed increased levels of anti-inflammatory eCBome lipids (LEA, OEA, DHEA and 13- HODE-EA) in the healthy state and higher MPO activity. DNBS elicited reduced inflammation in GF mice, having lower colon weight/length ratios and lower expression levels of Il1b, Il6, Tnfa and neutrophil markers compared to one or both of the other DNBS-treated groups. Il10 expression was also lower and the levels of several N-acyl ethanolamines and 13-HODE-EA levels were higher in DNBS-treated GF mice than in CR and ABX mice. The levels of these eCBome lipids negatively correlated with measures of colitis and inflammation. Conclusions: These results suggest that the depletion of the gut microbiota and subsequent differential development of the gut immune system in GF mice is followed by a compensatory effect on eCBome lipid mediators, which may explain, in part, the observed lower susceptibility of GF mice to develop DNBS-induced colitis. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal dementia (FTD) is a heterogeneous group of early onset and progressive neurodegenerative disorders, characterized by degeneration in the frontal and temporal lobes, which causes deterioration in cognition, personality, social behavior and language. Around 45% of the cases are characterized by the presence of aggregates of the RNA-binding protein TDP-43. Methods: In this study, we have used a murine model of FTD that overexpresses this protein exclusively in the forebrain (under the control of the CaMKIIα promoter) for several biochemical, histological and pharmacological studies focused on the endocannabinoid system. Results: These mice exhibited at postnatal day 90 (PND90) important cognitive deficits, signs of emotional impairment and disinhibited social behaviour, which were, in most of cases, maintained during the first year of life of these animals. Motor activity was apparently normal, but FTD mice exhibited higher mortality. Their MRI imaging analysis and their ex-vivo histopathological evaluation proved changes compatible with atrophy (loss of specific groups of pyramidal neurons: Ctip2- and NeuN-positive cells) and inflammatory events (astroglial and microglial reactivities) in both cortical (medial prefrontal cortex) and subcortical (hippocampus) structures at PND90 and also at PND365. The analysis of the endocannabinoid system in these mice proved a decrease in the hydrolysing enzyme FAAH in the prefrontal cortex and the hippocampus, with an increase in the synthesizing enzyme NAPE-PLD only in the hippocampus, responses that were accompanied by modest elevations in anandamide and related N-acylethanolamines. The potentiation of these elevated levels of anandamide after the pharmacological inactivation of FAAH with URB597 resulted in a general improvement in behaviour, in particular in cognitive deterioration, associated with the preservation of pyramidal neurons of the medial prefrontal cortex and the CA1 layer of the hippocampus, and with the reduction of gliosis in both structures. Conclusions: Our data confirmed the potential of elevating the endocannabinoid tone as a therapy against TDP-43-induced neuropathology in FTD, limiting glial reactivity, preserving neuronal integrity and improving cognitive, emotional and social deficits. [ABSTRACT FROM AUTHOR]

The endocannabinoid system (ECS) refers to a complex cell-signaling system highly conserved among species formed by numerous receptors, lipid mediators (endocannabinoids) and synthetic and degradative enzymes. It is widely distributed throughout the body including the CNS, where it participates in synaptic signaling, plasticity and neurodevelopment. Besides, the olfactory ensheathing glia (OEG) present in the olfactory system is also known to play an important role in the promotion of axonal growth and/or myelination. Therefore, both OEG and the ECS promote neurogenesis and oligodendrogenesis in the CNS. Here, we investigated if the ECS is expressed in cultured OEG, by assessing the main markers of the ECS through immunofluorescence, western blotting and qRT-PCR and quantifying the content of endocannabinoids in the conditioned medium of these cells. After that, we investigated whether the production and release of endocannabinoids regulate the differentiation of oligodendrocytes co-cultured with hippocampal neurons, through Sholl analysis in oligodendrocytes expressing O4 and MBP markers. Additionally, we evaluated through western blotting the modulation of downstream pathways such as PI3K/Akt/mTOR and ERK/MAPK, being known to be involved in the proliferation and differentiation of oligodendrocytes and activated by CB1, which is the major endocannabinoid responsive receptor in the brain. Our data show that OEG expresses key genes of the ECS, including the CB1 receptor, FAAH and MAGL. Besides, we were able to identify AEA, 2-AG and AEA related mediators palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in the conditioned medium of OEG cultures. These cultures were also treated with URB597 10-9 M, a FAAH selective inhibitor, or JZL184 10-9 M, a MAGL selective inhibitor, which led to the increase in the concentrations of OEA and 2-AG in the conditioned medium. Moreover, we found that the addition of OEG conditioned medium (OEGCM) enhanced the complexity of oligodendrocyte process branching in hippocampal mixed cell cultures and that this effect was inhibited by AM251 10-6 M, a CB1 receptor antagonist. However, treatment with the conditioned medium enriched with OEA or 2-AG did not alter the process branching complexity of premyelinating oligodendrocytes, while decreased the branching complexity in mature oligodendrocytes. We also observed no change in the phosphorylation of Akt and ERK 44/42 in any of the conditions used. In conclusion, our data show that the ECS modulates the number and maturation of oligodendrocytes in hippocampal mixed cell cultures. [ABSTRACT FROM AUTHOR]

Atherosclerotic plaque in the carotid artery is the main cause of ischemic stroke, with a high incidence rate among people over 65 years. A timely and precise diagnosis can help to prevent the ischemic event and decide patient management, such as follow up, medical, or surgical treatment. Presently, diagnostic imaging techniques available include color-Doppler ultrasound, as a first evaluation technique, computed tomography angiography, which, however, uses ionizing radiation, magnetic resonance angiography, still not in widespread use, and cerebral angiography, which is an invasively procedure reserved for therapeutically purposes. Contrast-enhanced ultrasound is carving out an important and emerging role which can significantly improve the diagnostic accuracy of an ultrasound. Modern ultrasound technologies, still not universally utilized, are opening new horizons in the arterial pathologies research field. In this paper, the technical development of various carotid artery stenosis diagnostic imaging modalities and their impact on clinical efficacy is thoroughly reviewed. [ABSTRACT FROM AUTHOR]

Background/Aim: Breast angiosarcoma is a rare and aggressive disease with a poor prognosis. Two subtypes have been identified: primary angiosarcoma (PBA) and secondary breast angiosarcoma (SBA). In this retrospective analysis, we describe and compare our institute experience with the data existing in the literature. Materials and Methods: We included in our analysis 29 patients who received a diagnosis of PBA or SBA between 2006 and 2019. Results: All patients received surgery as frontline treatment, but only 6 patients underwent to adjuvant treatment. Neoadjuvant chemotherapy was administered 2 patients. The preferred chemotherapeutic regimen was taxanes with or without gemcitabine and associated with anthracyclines. A lower median RFS and OS were reported in patients with PBA compared to those with SBA, but the difference observed was not statistically significant. Patients with PBA had a lower median age at the diagnosis (38 vs. 75). Conclusion: In our analysis, we have shown a lower median RFS and OS in patients with PBA compared with those with SBA, and a significantly younger age at diagnosis in patients affected by PBA. [ABSTRACT FROM AUTHOR]

Background and Purpose: Psychedelics elicit prosocial, antidepressant and anxiolytic effects via neuroplasticity, neurotransmission and neuro‐immunomodulatory mechanisms. Whether psychedelics affect the brain endocannabinoid system and its extended version, the endocannabinoidome (eCBome) or the gut microbiome, remains unknown. Experimental Approach: Adult C57BL/6N male mice were administered lysergic acid diethylamide (LSD) or saline for 7 days. Sociability was assessed in the direct social interaction and three chambers tests. Prefrontal cortex and hippocampal endocannabinoids, endocannabinoid‐like mediators and metabolites were quantified via high‐pressure liquid chromatography with tandem mass spectrometry (HPLC‐MS/MS). Neurotransmitter levels were assessed via HPLC‐UV/fluorescence. Gut microbiome changes were investigated by 16S ribosomal DNA sequencing. Key Results: LSD increased social preference and novelty and decreased hippocampal levels of the N‐acylethanolamines N‐linoleoylethanolamine (LEA), anandamide (N‐arachidonoylethanolamine) and N‐docosahexaenoylethanolamine (DHEA); the monoacylglycerol 1/2‐docosahexaenoylglycerol (1/2‐DHG); the prostaglandins D2 (PGD2) and F2α (PGF2α); thromboxane 2 and kynurenine. Prefrontal eCBome mediator and metabolite levels were less affected by the treatment. LSD decreased Shannon alpha diversity of the gut microbiota, prevented the decrease in the Firmicutes:Bacteroidetes ratio observed in saline‐treated mice and altered the relative abundance of the bacterial taxa Bifidobacterium, Ileibacterium, Dubosiella and Rikenellaceae RC9. Conclusions and Implications: The prosocial effects elicited by repeated LSD administration are accompanied by alterations of hippocampal eCBome and kynurenine levels, and the composition of the gut microbiota. Modulation of the hippocampal eCBome and kynurenine pathway might represent a mechanism by which psychedelic compounds elicit prosocial effects and affect the gut microbiome. [ABSTRACT FROM AUTHOR]