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The ever-increasing demand for water, food, and energy is putting unsustainable pressure on natural resources worldwide, often leading to environmental degradation that, in turn, affect water, food, and energy security. The recognition of the complex interlinkages between multiple sectors has led to the creation of various holistic approaches to environmental decision making such as Integrated Natural Resources Management (INRM), Integrated Water Resources Management (IWRM), Virtual Water (VW), Water Footprint (WF) and lately the Food-EnergyEnvironment-Water nexus (WE2F). All these approaches aim to increase resource use efficiency and promote sustainability by increasing the cooperation between traditionally disjoint sectors, and mainly differ by the number and relative weights of the sectors included in their framework. They also suffer from the same face and the same barriers for implementation, some of which may never be fully overcome. The paper discusses the benefits of adopting a WE2F nexus approach in the Upper Niger Basin (UNB) and the Inner Niger Delta (IND), but also the multiple difficulties associated with its practical implementation. IWRM/WE2F initiatives in the UNB/IND such as the BAMGIRE project piloted by Wetlands International and funded by the Dutch Embassy in Mali to secure livelihoods and biodiversity in a changing environment, is taken as an example of partial success in the use of a nexus approach to watershed management. It was shown there are multiple barriers to the operational implementation of the WE2F. However, while a full understanding of all interlinkage between sectors may never be possible, data collection, scientific research and model development can improve our ability to understand the complex system in which we live, and hence take better decisions

Over the last decade, the comorbidity between Autism Spectrum Disorder (ASD) and epilepsy has been widely demonstrated, and many hypotheses regarding the common neurobiological bases of these disorders have been put forward. A variable, but significant, prevalence of abnormalities on electroencephalogram (EEG) has been documented in non-epileptic children with ASD; therefore, several scientific studies have recently tried to demonstrate the role of these abnormalities as a possible biomarker of altered neural connectivity in ASD individuals. This narrative review intends to summarize the main findings of the recent scientific literature regarding abnormalities detected with standard EEG in children/adolescents with idiopathic ASD. Research using three different databases (PubMed, Scopus and Google Scholar) was conducted, resulting in the selection of 10 original articles. Despite an important lack of studies on preschoolers and a deep heterogeneity in results, some authors speculated on a possible association between EEG abnormalities and ASD characteristics, in particular, the severity of symptoms. Although this correlation needs to be more strongly elucidated, these findings may encourage future studies aimed at demonstrating the role of electrical brain abnormalities as an early biomarker of neural circuit alterations in ASD, highlighting the potential diagnostic, prognostic and therapeutic value of EEG in this field.

Background: The literature suggests the existence of an association between autism spectrum disorders (ASDs) and subclinical electroencephalographic abnormalities (SEAs), which show a heterogeneous prevalence rate (12.5–60.7%) within the pediatric ASD population. The aim of this study was to investigate the EEG findings in a cohort of ASD preschoolers and their correlation with the phenotypic characteristics. Methods: We retrospectively reviewed data on 141 ASD preschoolers evaluated in a tertiary care university hospital over the period 2008–2018. All participants underwent at least one standard polygraphic electroencephalogram (EEG) and a clinical multidisciplinary assessment with standardized instruments. Results: 77 patients (55%) showed SEAs, which were mainly represented by epileptiform discharges (p < 0.00001), especially focal and multifocal (p = 0.010). Abnormal EEG (p = 0.035) and epileptiform discharges (p = 0.014) were associated with seizure onset and were predominant in sleep (p < 0.00001). Patients with abnormal tracing (p = 0.031) and slow abnormalities (p < 0.001) were significantly younger. ASD severity was not found to be correlated with EEG results, which showed a potential, albeit non-significant, association with some psychometric parameters. Very similar results were found when patients were divided according to sex. Conclusions: EEG abnormalities appear to correlate more with ASD internalizing, externalizing and emotional comorbidities, rather than with ASD core symptoms; larger samples are needed to further investigate this association.

Hepatic metastases are a poor prognostic factor of colorectal carcinoma (CRC) and new strategies to reduce the risk of liver CRC colonization are highly needed. Herein, we used mouse models of hepatic metastatization to demonstrate that the continuous infusion of therapeutic doses of interferon-alpha (IFNα) controls CRC invasion by acting on hepatic endothelial cells (HECs). Mechanistically, IFNα promoted the development of a vascular antimetastatic niche characterized by liver sinusoidal endothelial cells (LSECs) defenestration extracellular matrix and glycocalyx deposition, thus strengthening the liver vascular barrier impairing CRC trans-sinusoidal migration, without requiring a direct action on tumor cells, hepatic stellate cells, hepatocytes, or liver dendritic cells (DCs), Kupffer cells (KCs) and liver capsular macrophages (LCMs). Moreover, IFNα endowed LSECs with efficient cross-priming potential that, along with the early intravascular tumor burden reduction, supported the generation of antitumor CD8 + T cells and ultimately led to the establishment of a protective long-term memory T cell response. These findings provide a rationale for the use of continuous IFNα therapy in perioperative settings to reduce CRC metastatic spreading to the liver. Colorectal cancer remains one of the most widespread and deadly cancers worldwide. Poor health outcomes are usually linked to diseased cells spreading from the intestine to create new tumors in the liver or other parts of the body. Treatment involves surgically removing the initial tumors in the bowel, but patient survival could be improved if, in parallel, their immune system was ‘boosted’ to destroy cancer cells before they can form other tumors. Interferon alpha is a small protein which helps to coordinate how the immune system recognizes and deactivates foreign agents and cancerous cells. It has recently been trialed as a colorectal cancer treatment to prevent tumors from spreading to the liver, but only with limited success. This partly because interferon-alpha is usually administered in high and pulsed doses, which cause severe side effects through the body. Instead, Tran, Ferreira, Alvarez-Moya et al. aimed to investigate whether continuously delivering lower amounts of the drug could be a better approach. This strategy was tested on mice in which colorectal cancer cells had been implanted into the wall of the large intestine. Continuous administration minimized the risk of the implanted cancer cells spreading to the liver while also creating fewer side effects. The team was able to identify an optimum delivery strategy by varying how much interferon-alpha the animals received and when. Further experiments also revealed a new mechanism by which interferon-alpha prevented the spread of colorectal cancer. Upon receiving continuous doses of the drug, a group of liver cells started to generate a physical barrier which stopped cancer cells from being able to invade the organ. The treatment also promoted long-term immune responses that targeted diseased cells while being safe for healthy tissues. If confirmed in clinical trials, these results suggest that colorectal patients undergoing tumor removal surgery may benefit from also receiving interferon-alpha through continuous delivery.

Mesenchymal stromal/stem cells (MSCs) are a fibroblast-like cell population with high regenerative potential that can be isolated from many different tissues. Several data suggest MSCs as a therapeutic tool capable of migrating to a site of injury and guide tissue regeneration mainly through their secretome. Pulmonary first-pass effect occurs during intravenous administration of MSCs, where 50 to 80% of the cells tend to localize in the lungs. This phenomenon has been exploited to study MSC potential therapeutic effects in several preclinical models of lung diseases. Data demonstrated that, regardless of the lung disease severity and the delivery route, MSCs were not able to survive longer than 24 h in the respiratory tract but still surprisingly determined a therapeutic effect. In this work, two different mouse bone marrow-derived mesenchymal stromal/stem cell (mBM-MSC) lines, stably transduced with a third-generation lentiviral vector expressing luciferase and green fluorescent protein reporter genes tracking MSCs in vivo biodistribution and persistency, have been generated. Cells within the engrafted lung were in vivo traced using the high-throughput bioluminescence imaging (BLI) technique, with no invasiveness on animal, minimizing biological variations and costs. In vivo BLI analysis allowed the detection and monitoring of the mBM-MSC clones up to 28 days after implantation independently from the delivery route. This longer persistency than previously observed (24 h) could have a strong impact in terms of pharmacokinetics and pharmacodynamics of MSCs as a therapeutic tool.

Congenital central nervous system (CNS) malformations in cattle are likely underreported, and their true incidence, clinical spectrum, and etiological factors remain poorly characterized. This study describes the clinical and pathological features of congenital structural brain anomalies in Piedmontese calves. In this prospective observational study (2021-2025), Piedmontese calves with suspected congenital CNS anomalies underwent clinical and neurological examinations, cerebrospinal fluid analysis, diagnostic imaging (CT/MRI in selected cases), molecular testing for regionally relevant teratogenic viral pathogens, and histopathology. The study population originated from the provinces of Cuneo and Turin (Italy), which together account for over 80% of Piedmontese cattle farms. Only calves with necropsy-confirmed structural brain anomalies were included. In total, 70 calves underwent necropsy for suspected CNS anomalies. Structural brain defects were confirmed in 11 calves. Hydrocephalus (6/11) was the most frequent finding and was commonly associated with cerebellar malformations. Isolated Dandy-Walker-like malformations were found in 2/11 and cerebral aplasia in 3/11. Molecular testing for bovine viral diarrhea virus, bluetongue virus, and Schmallenberg virus was negative in all cases. A severe medullary dysplastic anomaly was also observed. There was wide variability in the presentation of brain malformations in this sample of Piedmontese calves, in which the most common was hydrocephalus associated with cerebellar malformations. Since a viral etiology appeared unlikely, a genetic cause is suspected, and genomic analyses are currently ongoing to further investigate this hypothesis. These findings highlight the importance of considering congenital CNS malformations in the differential diagnosis of neurological disorders in neonatal calves, supporting earlier and more targeted diagnosis.

In the synthesis of nanostructures by pulsed laser deposition (PLD), a crucial role is played by the environmental deposition pressure and the substrate temperature. Due to the high temperature of nanoparticles (NPs) at landing, other factors may determine the structure of the resulting aggregates. Here, Au and TiO 2 nanostructures are obtained by non-thermal fs-PLD in ambient conditions. On Si(100), only TiO 2 NPs form fractals with areas up to ~ 1 × 10 6  nm 2 , while on quartz Au NPs also form fractals with areas up to ~ 5 × 10 3  nm 2 , a much smaller size with respect to the TiO 2 case. The aggregation is described by a simple diffusive model, taking into account isotropic diffusion of the NPs, allowing quantitative simulations of the NPs and fractal area. The results highlight the key role of substrate thermal conductivity in determining the formation of fractals. Graphical abstract ᅟ

IntroductionCluster seizures (CS) and status epilepticus (SE) in dogs are severe neurological emergencies that require immediate treatment. Practical guidelines call for constant rate infusion (CRI) of benzodiazepines or propofol (PPF) in patients with seizures not responding to first-line treatment, but to date only few studies have investigated the use of CRI in dogs with epilepsy.Study designRetrospective clinical study.MethodsDogs that received CRI of diazepam (DZP) or PPF for antiepileptic treatment during hospitalization at the Veterinary Teaching Hospital of the University of Turin for CS or SE between September 2016 and December 2019 were eligible for inclusion. Favorable outcome was defined as cessation of clinically visible seizure activity within few minutes from the initiation of the CRI, no seizure recurrence within 24 h after discontinuation of CRI through to hospital discharge, and clinical recovery. Poor outcome was defined as recurrence of seizure activity despite treatment or death in hospital because of recurrent seizures, catastrophic consequences of prolonged seizures or no return to an acceptable neurological and clinical baseline, despite apparent control of seizure activity. Comparisons between the number of patients with favorable outcome and those with poor outcome in relation to type of CRI, seizure etiology, reason for presentation (CS or SE), sex, previous AED therapy and dose of PPF CRI were carried out.ResultsA total of 37 dogs, with 50 instances of hospitalization and CRI administered for CS or SE were included in the study. CRI of diazepam (DZP) or PPF was administered in 29/50 (58%) and in 21/50 (42%) instances of hospitalization, respectively. Idiopathic epilepsy was diagnosed in 21/37 (57%), (13/21 tier I and 8/21 tier II); structural epilepsy was diagnosed in 6/37 (16%) of which 4/6 confirmed and 2/6 suspected. A metabolic or toxic cause of seizure activity was recorded in 7/37 (19%). A total of 38/50 (76%) hospitalizations were noted for CS and 12/50 (24%) for SE. In 30/50 (60%) instances of hospitalization, the patient responded well to CRI with cessation of seizure activity, no recurrence in the 24 h after discontinuation of CRI through to hospital discharge, whereas a poor outcome was recorded for 20/50 (40%) cases (DZP CRI in 12/50 and PPF CRI in 8/50). Comparison between the number of patients with favorable outcome and those with poor outcome in relation to type of CRI, seizure etiology, reason for presentation (CS or SE), sex and previous AED therapy was carried out but no statistically significant differences were found.ConclusionsThe present study is the first to document administration of CRI of DZP or PPF in a large sample of dogs with epilepsy. The medications appeared to be tolerated without major side effects and helped control seizure activity in most patients regardless of seizure etiology. Further studies are needed to evaluate the effects of CRI duration on outcome and complications.

Objective Postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) are the two main forms of functional dyspepsia (FD). Probiotics are a promising therapy for FD, but current data remains heterogeneous. This work aims to evaluate a probiotic combination of Lacticaseibacillus rhamnosus LR04 (DSM 16605), Lactiplantibacillus pentosus LPS01 (DSM 21980), Lactiplantibacillus plantarum LP01 (LMG P-21021), and Lactobacillus delbrueckii subsp. delbruekii LDD01 (DMS 22106), alone or together with other pharmacological therapies, for clinical improvement of symptoms associated with FD. Methods Patients with FD were enrolled and divided into two groups: PDS and EPS. Probiotic alone or combined with prokinetics, antacids, or proton-pump-inhibitors were administered for 30 days. A progressive-score scale was used to evaluate symptoms in all patients at the beginning of the trial and at 15 days after the end of treatment. Results A cohort of 2676 patients were enrolled (1 357 with PDS; 1 319 with EPS). All patients showed significant improvements in dyspeptic symptoms following treatment. In patients with PDS, probiotic alone resulted in the lowest prevalence of symptoms following treatment, while patients with EPS showed no clear between-treatment differences. Conclusions Dyspeptic symptoms were reduced following treatment in all patients.

Hepatic metastases are a poor prognostic factor of colorectal carcinoma (CRC) and new strategies to reduce the risk of liver CRC colonization are highly needed. Herein, we used mouse models of hepatic metastatization to demonstrate that the continuous infusion of therapeutic doses of interferon-alpha (IFN[alpha]) controls CRC invasion by acting on hepatic endothelial cells (HECs). Mechanistically, IFN[alpha] promoted the development of a vascular antimetastatic niche characterized by liver sinusoidal endothelial cells (LSECs) defenestration extracellular matrix and glycocalyx deposition, thus strengthening the liver vascular barrier impairing CRC trans-sinusoidal migration, without requiring a direct action on tumor cells, hepatic stellate cells, hepatocytes, or liver dendritic cells (DCs), Kupffer cells (KCs) and liver capsular macrophages (LCMs). Moreover, IFN[alpha] endowed LSECs with efficient cross-priming potential that, along with the early intravascular tumor burden reduction, supported the generation of antitumor CD8.sup.+ T cells and ultimately led to the establishment of a protective long-term memory T cell response. These findings provide a rationale for the use of continuous IFN[alpha] therapy in perioperative settings to reduce CRC metastatic spreading to the liver.