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Abstract Calciprotein particles (CPPs) are an endogenous buffering system, clearing excessive amounts of Ca2+ and PO4 3- from the circulation and thereby preventing ectopic mineralization. CPPs circulate as primary CPPs (CPP1), which are small spherical colloidal particles, and can aggregate to form large, crystalline, secondary CPPs (CPP2). Even though it has been reported that CPPs are toxic to vascular smooth muscle cells (VSMC) in vitro, their effect(s) on the vasculature remain unclear. Here we have shown that CPP1, but not CPP2, increased arterial stiffness ex vivo. Interestingly, the effects were more pronounced in the abdominal infrarenal aorta compared to the thoracic descending aorta. Further, we demonstrated that CPP1 affected both endothelial and VSMC function, impairing vasorelaxation and contraction respectively. Concomitantly, arterial glycosaminoglycan accumulation was observed as well, which is indicative of an increased extracellular matrix stiffness. However, these effects were not observed in vivo. Hence, we concluded that CPP1 can induce vascular dysfunction.

Abstract Background Doxorubicin (DOX) is used for breast cancer and lymphoma, but can cause cardiotoxicity, arterial stiffness, and endothelial dysfunction. We recently reported SERPINA3N as biomarker of cardiovascular toxicity in patients and mice. Dexrazoxane (DEXRA) is an FDA-approved drug that prevents DOX-induced cardiac toxicity in high-risk patients. However, the effect of DEXRA on vascular dysfunction during DOX treatment has not been documented. Therefore, here we investigated whether DEXRA protects against DOX-induced arterial stiffness, endothelial dysfunction, and SERPINA3N upregulation in tissue and plasma from mice. Methods Male C57BL6/J mice were treated with DOX (4 mg/kg), DEXRA (40 mg/kg), a combination (DEXRA + DOX), or VEHICLE (0.9% NaCl) weekly i.p. for 6 weeks (n = 8 per group). Cardiovascular function was measured in vivo by ultrasound imaging at baseline, weeks 2 and 6. Vascular reactivity was analyzed ex vivo in the thoracic aorta at week 6 and molecular analysis was performed. Results DEXRA prevented left ventricular ejection fraction decline by DOX (DEXRA + DOX: 62 ± 2% vs DOX: 51 ± 2%). Moreover, DEXRA prevented the increase in pulse wave velocity by DOX (DEXRA + DOX: 2.1 ± 0.2 m/s vs DOX: 4.5 ± 0.3 m/s) and preserved endothelium-dependent relaxation (DEXRA + DOX: 82 ± 3% vs DOX: 62 ± 3%). In contrast to DOX-treated mice, SERPINA3N did not increase in the DEXRA + DOX group. Conclusion Our results not only confirm the cardioprotective effects of DEXRA against DOX-induced cardiotoxicity but also add preservation of vascular endothelial cell function as an important mechanism. Moreover, the study demonstrates the potential of SERPINA3N as a biomarker for monitoring cardiovascular complications of DOX in high-risk patients.

Abstract Arterial stiffness, a key indicator of vascular health, encompassing active (vascular tone) and passive (extracellular matrix) components. This study aims to address how these different components affect arterial stiffness along the aorta and the influence of aging. Aortic segments of 12 week and 24 month old (both n = 6) male C57BL/6J mice were mounted in a Rodent Oscillatory Set-up to study Arterial Compliance, in order to measure arterial stiffness and vascular reactivity. Regional variations in arterial stiffness were evident, with abdominal infrarenal aorta (AIA) exhibiting highest stiffness and smallest diameters. AIA displayed both the highest amount of collagen and collagen:elastin ratio. Regional ex vivo vascular reactivity revealed heightened AIA contractions and lowered NO availability. Aging is a significant factor contributing towards vessel remodelling and arterial stiffness. Aging increased arterial stiffness, aortic diameters, collagen content, and reduced VSMC contraction. The results of this study could identify specific regions or mechanisms to target in the development of innovative therapeutic interventions aimed at enhancing overall vascular health.

Abstract Background The anthracycline doxorubicin (DOX) is a highly effective anticancer agent, especially in breast cancer and lymphoma. However, DOX can cause cancer therapy-related cardiovascular toxicity (CTR-CVT) in patients during treatment and in survivors. Current diagnostic criteria for CTR-CVT focus mainly on left ventricular systolic dysfunction, but a certain level of damage is required before it can be detected. As diastolic dysfunction often precedes systolic dysfunction, the current study aimed to identify functional and molecular markers of DOX-induced CTR-CVT with a focus on diastolic dysfunction. Methods Male C57BL/6J mice were treated with saline or DOX (4 mg/kg, weekly i.p. injection) for 2 and 6 weeks (respectively cumulative dose of 8 and 24 mg/kg) (n = 8 per group at each time point). Cardiovascular function was longitudinally investigated using echocardiography and invasive left ventricular pressure measurements. Subsequently, at both timepoints, myocardial tissue was obtained for proteomics (liquid-chromatography with mass-spectrometry). A cohort of patients with CTR-CVT was used to complement the pre-clinical findings. Results DOX-induced a reduction in left ventricular ejection fraction from 72 ± 2% to 55 ± 1% after 2 weeks (cumulative 8 mg/kg DOX). Diastolic dysfunction was demonstrated as prolonged relaxation (increased tau) and heart failure was evident from pulmonary edema after 6 weeks (cumulative 24 mg/kg DOX). Myocardial proteomic analysis revealed an increased expression of 12 proteins at week 6, with notable upregulation of SERPINA3N in the DOX-treated animals. The human ortholog SERPINA3 has previously been suggested as a marker in CTR-CVT. Upregulation of SERPINA3N was confirmed by western blot, immunohistochemistry, and qPCR in murine hearts. Thereby, SERPINA3N was most abundant in the endothelial cells. In patients, circulating SERPINA3 was increased in plasma of CTR-CVT patients but not in cardiac biopsies. Conclusion We showed that mice develop heart failure with impaired systolic and diastolic function as result of DOX treatment. Additionally, we could identify increased SERPINA3 levels in the mice as well as patients with DOX-induced CVT and demonstrated expression of SERPINA3 in the heart itself, suggesting that SERPINA3 could serve as a novel biomarker.

The impact of α-tocopherol on atherosclerosis is unclear and controversial. While some studies suggest potential benefits, such as antioxidant properties that may reduce oxidative stress, other studies indicate no significant preventive effects. The intricate interplay of various factors, including dosage, individual differences, and study methodologies, contributes to the ongoing uncertainty surrounding α-tocopherol’s role in atherosclerosis. Further research is needed to clarify its impact and establish clearer guidelines. Therefore, we aimed to evaluate the impact of α-tocopherol on atherogenesis in ApoE−/− fibrillin (Fbn)1C1039G/+ mice, which is a unique mouse model of advanced atherosclerosis with typical features, such as large necrotic cores, high levels of inflammation, and intraplaque neovascularization, that resemble the unstable phenotype of human plaques. ApoE−/− Fbn1C1039G+/− mice were fed a western-type diet (WD) supplemented with a high dose of α-tocopherol (500 mg/kg diet), while control mice were fed a WD containing a low dose of α-tocopherol (50 mg/kg diet). The high dose of α-tocopherol reduced plaque thickness and necrotic core area in the right common carotid artery (RCCA) after 24 weeks WD. Moreover, α-tocopherol decreased plaque formation and intraplaque neovascularization in the RCCA. In addition to its antiatherogenic effect, chronic supplementation of α-tocopherol improved cardiac function in ApoE−/− Fbn1C1039G/+ mice. However, chronic supplementation of α-tocopherol did not decrease lipid peroxidation. On the contrary, α-tocopherol acted as a prooxidant by increasing plasma levels of oxidized LDL and plaque malondialdehyde, an end product of lipid peroxidation. Our data indicate that α-tocopherol inhibits atherogenesis and improves cardiac function independent of its antioxidant properties.

Ferroptosis is a type of regulated necrosis that is associated with iron-dependent accumulation of lipid hydroperoxides. Given that iron deposition and lipid peroxidation initiate ferroptosis in atherosclerosis and contribute to further plaque development, we hypothesized that inhibition of ferroptosis could be of value in the treatment of atherosclerosis. Glutathione peroxidase 4 (GPX4) is the only enzyme known capable of reducing lipid hydroperoxides. Previous studies have demonstrated that inactivation of GPX4 results in ferroptosis, while overexpression of GPX4 confers resistance to ferroptosis. In the present study, we examined the impact of GPX4 overexpression on the development of atherosclerotic plaques. GPX4-overexpressing mice (GPX4Tg/+) were crossbred with ApoE−/− mice and fed a western-type diet for 16 weeks. Atherosclerotic plaques of GPX4Tg/+ ApoE−/− mice showed increased GPX4 expression and a reduced amount of lipid hydroperoxides. However, plaque size and composition were not different as compared to control animals. Similarly, GPX4-overexpressing vascular smooth muscle cells and bone marrow-derived macrophages were not protected against lipid peroxidation and cell death triggered by the ferroptosis inducers erastin and 1S,3R-RSL3. We concluded that GPX4 overexpression reduces lipid peroxidation in plaques of ApoE−/− mice, yet GPX4 overexpression is not sufficiently powerful to change plaque size or composition.

BackgroundA type 3 medication review (MR3) is a patient-centred medication service primarily provided by pharmacists and is presently employed routinely in several countries. In this process, pharmacists interview patients and collaborate with the treating physician to optimize the patient’s pharmacotherapy, taking into account the patient’s medication history and other medical data including laboratory values. The need to maintain the quality of such interventions during and after their initial implementation cannot be overstated.AimThe objective of this study was to refine and assess a scoring table to evaluate the quality of MR3 conducted in Belgian community pharmacies.MethodsThe comprehensive quality of MR3s was assessed by scoring its various components using a previously developed scoring table, called BRANT-MERQS, Brussels Antwerp Medication Review Quality Score. MR3s were analysed from an implementation study with patients suffering from rheumatoid arthritis (RA, subproject 1) and type 2 diabetes mellitus (T2DM, subproject 2). Additional information was obtained during a telephone call with a subset of participating pharmacists of subproject 1 who finalized their first MR3.ResultsIn subproject 1, a total of 21 MR3s of patients with RA were examined. The assessment showed favourable scores for elements such as a well-organized medication schedule, treatment adherence, and the elaboration of specific interventions. However, certain other quality criteria posed challenges in the evaluation, for example, the use of simple and understandable language. Pharmacists faced time constraints, and elderly general practitioners (GPs) displayed limited enthusiasm, which were notable barriers observed for this subproject. In the context of subproject 2 that investigated 41 MR3s in patients with T2DM, the quality criteria of interaction between pharmacist and GP, and used sources and tools received high scores. However, there was still room for improvement, especially in areas such as accurate dosing, handling kidney function, QT prolongation, correctly associating laboratory values with relevant drugs and medical conditions, and optimisation of medication schedules for patients.ConclusionThis study demonstrated the feasibility of MR3 quality assessment through a scoring system. However, it also unveiled the tool’s current imperfections and highlighted the ongoing need for refinement, something expected of a new service in an implementation phase.

Background The noninvasive magnetic resonance direct thrombus imaging (MRDTI) technique can be used to diagnose acute deep vein thrombosis (DVT), without the use of intravenous contrast. MRDTI holds the potential to differentiate between acute and chronic DVT and could be helpful when diagnosing thrombosis is challenging.

The current standard technique for vascular grafting in cerebral revascularization surgery employs the interposition of an autologous blood vessel. Technical complications have necessitated the development of a synthetic alternative, but classical biomaterials are not suited for small caliber vascular grafting due to the resulting neointimal hyperplasia and thrombosis. The electrospinning of polymers is a promising technique for the development of small vascular grafts. The in vivo performance and efficacy of electrospun polyurethane (ePU) grafts with an internal diameter of

Proteasome inhibitors such as bortezomib and carfilzomib induce apoptosis and are a cornerstone in the treatment of relapsed or refractory multiple myeloma. However, concerns have emerged concerning their link to cancer therapy-related cardiovascular dysfunction (CTRCD). Bortezomib, a reversible first-generation inhibitor, and carfilzomib, a second-generation irreversible inhibitor, are associated with hypertension, heart failure, and cardiac arrhythmias. The current study investigated the effects of bortezomib and carfilzomib on cardiac (left ventricular ejection fraction, LVEF) and vascular (arterial stiffness, vascular reactivity) function. Cardiac function assessment aimed to build upon existing evidence of proteasome inhibitors CTRCD, while arterial stiffness served as an early indicator of potential vascular remodeling. Groups of 12-week-old C57BL/6J male mice (n = 8 per group) were randomly assigned to receive vehicle, carfilzomib (8 mg/kg I.P.), or bortezomib (0.5 mg/kg I.P.). Additionally, proteasome inhibition was assessed in mice treated with L-NAME (0.5 mg/kg) to induce hypertension. Cardiac and vascular parameters were evaluated via echocardiography on days 0 and 3. On day 6, mice were sacrificed for ex vivo analysis of arterial stiffness and vascular reactivity. Overall, no changes in arterial stiffness were detected either in vivo or ex vivo at basal pressures. However, a steeper pressure–stiffness curve was observed for carfilzomib in normotensive (p < 0.01) and hypertensive (p < 0.0001) mice ex vivo. Additionally, in hypertensive mice, carfilzomib decreased LVEF (p = 0.06), with bortezomib exhibiting similar trends. Vascular reactivity remained largely unchanged, but proteasome inhibition tended to enhance endothelial-independent relaxations in both control and hypertensive mice. In conclusion, short-term treatment with carfilzomib and bortezomib is considered relatively safe for the protocols assessed in the study.

Pine nut skin (Pinus pinea L.) is a poorly explored industrial byproduct with potential to be utilized as a food ingredient. Subcritical water extraction (SWE), an eco-friendly extraction technique with higher efficiency than hot-water extraction (HWE), was studied to evaluate its suitability in producing extracts rich in soluble fiber and phenolic compounds. For this, a factorial design was developed considering temperature (120–180 °C), time (2–10 min), and mass/volume ratio (1–3 g/60 mL) under microwave irradiation. This design aimed to maximize the extraction of carbohydrates, while achieving the highest content of phenolic compounds and antioxidant activity. SWE produced higher yields (2.6-fold in relation to HWE) of extracts rich in polysaccharides, determined by methylation analysis, oligosaccharides, determined by GC-qMS as alditol acetates, and phenolic compounds, determined by HPLC-ESI-MS. SWE increased the recovery of pectic oligosaccharides (10-fold) and xyloglucans (2-fold), and allowed to recover pectic polysaccharides, type II arabinogalactans and insoluble-bound phenolic compounds. Mono-, oligo- and polysaccharides were not hydrolyzed during in vitro gastrointestinal digestion, showing potential prebiotic functionality. Although phenolic compounds suffered a 23 % (gallic acid equivalents) decrease, phenolic acids and aldehydes were released or conserved upon intestinal phase. These results highlight the potential of PNS valorization as functional food ingredients through the subcritical water solubilization of polysaccharides and phenolic compounds.

Due to global population growth, age-related disorders like cardiovascular disease and dementia are anticipated to increase. Recent data suggests a connection between cardiovascular disease and neurodegeneration, especially focusing on arterial stiffness (AS) and Alzheimer’s disease (AD). In light of this, we conducted a study to explore the impact of long-term nitric oxide synthase (NOS) isoform inhibition, which leads to AS, on neurobehavioral performance. We also compared these effects in an AD model and control mice. C57BL/6 and hAPP23+/− mice (an established AD model) were given 0.5 mg/mL N(G)-Nitro-L-Arginine Methyl Ester (L-NAME) in their drinking water for 16 weeks. Our findings indicate that chronic non-selective NOS inhibition increased AS and reduced spatiotemporal learning and memory in both C57BL/6 and hAPP23+/− mice. These effects were consistent across both groups, emphasizing the role of neuronal NOS (nNOS) in cognitive aging, regardless of genetic predisposition to AD.

Abstract Dihydroquercetin (DHQ) is a natural occurring dihydroflavonol that has strong antioxidant and antibacterial activities. However, its application is limited due to its poor solubility. This study aims to improve the aqueous solubility of DHQ by complexing DHQ with β-cyclodextrin (β-CD) to boost its biological activity. DHQ was encapsulated with β-CD by freeze drying at a 1:1-M ratio. The structure of DHQ/β-CD complex prepared was elucidated by using Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and 1H nuclear magnetic resonance (1H NMR). In addition, molecular docking further revealed two energetically favorable conformations of the DHQ/β-CD complex, in which DHQ interacted with β-CD via hydrogen bonds. Experimental results showed that the solubility of the DHQ increased 22.63-fold by encapsulating with β-CD. Also the dissolution rate, antioxidant activity and antibacterial activity of the DHQ were significantly improved by encapsulating. The encapsulating with β-CD solves the problem of the poor aqueous solubility of DHQ, and broadens the path for a more optimal use of the health promoting effect of DHQ in pharmaceutical and food products.

Tropical savannas and grasslands are the most frequently burned biome in the world, and fire has an important role in sustaining ecosystem processes. Modern management of fires in savannas has roots in traditions stretching back centuries, and nowadays earth observation data is incorporated extensively in fire management practices. In tropical savannas in particular strongly seasonal monsoonal climates allow relatively low severity prescribed burning in the early part of the dry season (EDS) with the goal of preventing more destructive late dry season (LDS) fires. In many regional contexts it is common that a specific, fixed date is used officially to indicate when the window of safe burning has expired and the EDS transitions to the LDS, based on the experience of local or regional fire management authorities. This approach, while practical, neglects inter-annual variability in meteorological conditions and timing of onset of more dangerous fire weather. In this study, we pro-pose a remote sensing-based method for determining when this EDS window expires for five savanna-dominated continental-scale regions. By taking ad- vantage of the fact that conditions allowing night-time burning occur later in the dry season, we use day and night-time active fire detections from the MODerate Resolution Imaging Spectroradiometer (MODIS) instruments to set a flexible date of transition between the EDS and LDS. The vast majority of tropical savannas have very variable (std. dev. ≈ 20–40 days) transition dates, though this is somewhat modulated by fire frequency. Fuel connectivity rather than fuel condition appears to be a strong driving factor behind this variability. We find that especially national parks and protected areas have a high proportion of potentially more severe burning in the LDS, though areas with well-established EDS burning programmes are reducing this impact.

Background: Medication reviews are a structured evaluation of a patient’s pharmacotherapy with the aim of optimizing medicines use and improving health outcomes. This entails detecting drug related problems and recommending interventions. A high level of quality is essential for the successful implementation of this service in community pharmacies but currently there is no instrument or tool to assess that overall quality.Aim: This study investigated the development of quality criteria of type 3 medication reviews (MR3s).Methods: After surveying the literature, an electronic questionnaire was developed to gather information about quality criteria for MR3. This survey, in Dutch, was distributed electronically. Four groups were queried: 1) pharmacists, mainly working in the Netherlands, involved in practice research and contacted through the PRISMA (Practice Research In Collaboration With Pharmacists) foundation, 2) Belgian pharmacy academics and pharmacists active in professional associations (APA), 3) Belgian pharmacists trained in medication review (MR) by the Royal Pharmacists Association of Antwerp (KAVA) and 4) Belgian pharmacy students. The survey included 57 criteria, divided into eight domains, which were ranked according to their importance by the participants. The results were analyzed statistically using the nonparametric Kruskal–Wallis test.Results: The survey was completed by 95 participants, including 42 PRISMA pharmacists, 19 APA pharmacists, 18 KAVA pharmacists and 16 pharmacy students. Opinions from participants from the different groups overlapped significantly. The use of simple and understandable language in the conversation with the patient was considered essential by the majority. Discussing the usefulness and purpose of a MR3 with the patient was also rated highly by all groups. Differences of opinion were present in aspects about laboratory values, the use of specific tools, and reporting to and consultation with the treating physician. The participants themselves formulated a limited number of additional assessment criteria.Conclusion: There was widespread agreement on the hierarchy of the quality assessment criteria for MR3s. Minor differences were related to the experience of the participants. With these results and a small number of suggested extra criteria, a quality assessment instrument for MR3 can be created.

Error attribution based on modelled relationships and satellite observations suggests that errors in global models are more important and require more concerns than emission errors in creating the overall uncertainties for biomass burning aerosols.

Due to its viscoelastic properties, the aorta aids in dampening blood pressure pulsatility. At the level of resistance-arteries, the pulsatile flow will be transformed into a continuous flow to allow for optimal perfusion of end organs such as the kidneys and the brain. In this study, we investigated the ex vivo viscoelastic properties of different regions of the aorta of healthy C57Bl6/J adult mice as well as the interplay between (altered) cyclic stretch and viscoelasticity. We demonstrated that the viscoelastic parameters increase along the distal aorta and that the effect of altered cyclic stretch is region dependent. Increased cyclic stretch, either by increased pulse pressure or pulse frequency, resulted in decreased aortic viscoelasticity. Furthermore, we identified that the vascular smooth muscle cell (VSMC) is an important modulator of viscoelasticity, as we have shown that VSMC contraction increases viscoelastic parameters by, in part, increasing elastin fiber tortuosity. Interestingly, an acute increase in stretch amplitude reverted the changes in viscoelastic properties induced by VSMC contraction, such as a decreasing contraction-induced elastin fiber tortuosity. Finally, the effects of altered cyclic stretch and VSMC contraction on viscoelasticity were more pronounced in the abdominal infrarenal aorta, compared to both the thoracic ascending and descending aorta, and were attributed to the activity and stability of VSMC focal adhesion. Our results indicate that cyclic stretch is a modulator of aortic viscoelasticity, acting on VSMC focal adhesion. Conditions of (acute) changes in cyclic stretch amplitude and/or frequency, such as physical exercise or hypertension, can alter the viscoelastic properties of the aorta.

Background: Medication review is a multifaceted service aimed at optimizing the use of medicines and enhancing the health outcomes of patients. Due to its complexity, it is crucial to clearly describe the service, its variants, and its components to avoid confusion and ensure a better understanding of medication review among healthcare providers. Aim: This study aims to bring clarity to the origins, definitions, abbreviations, and types of medication reviews, together with the primary criteria that delineate key features of this service. Method: A narrative review approach was employed to clarify the diverse terminology associated with “medication review” services. Relevant references were initially identified through searches on PubMed and Google Scholar, complementing the existing literature known to the authors. Results: The study uncovers a complicated and sometimes convoluted history of “medication review” in different regions around the world. The initial optimization of medicine use had an economic purpose before evolving subsequently into a more patient-oriented approach. A selection of abbreviations, definitions, and types were outlined to enhance the understanding of the service. Conclusions: The study underscores the urgent need for comprehensive information and standardization regarding the content and quality of the services, collectively referred to as “medication review”.

The negative impacts of mining operations are generally intensified by the lack of preventive measures in the management of mining waste, one of them being the disposal of waste rock that generates drainage depending on its geology, mineralogical composition, geochemistry and solubility of the metals present. The objective of the research was to simulate the weathering of waste rock from mining activities in a wet column under controlled laboratory conditions. The physicochemical parameters were evaluated for 20 weeks. Results were obtained on leachate acidity as one of the main parameters, the pH was found to be between 6.0 and 7.5; this was due to the presence of carbonates as a neutralizer. The results allow taking measures to plan efficient waste management throughout the mining operation process, especially at mine closure, contributing to the control of negative impact.

In Latin America, a deficit in wastewater treatment translates into the degradation of the environmental quality of other ecological spaces. Due to this problem, the effect of the use of a biofilter on the treatment of domestic wastewater was investigated. In this research was evaluated the parameters of turbidity, dissolved oxygen, COD, BOD5, total solids, dissolved solids, and total suspended solids and mainly the parameter of oils and fats (determined by the Soxhlet method). The water sample was obtained from the peri-urban area of San Benito at the Carabayllo district. The treatment unit used two residual inputs: biochar that was made from shell residues of Carya illinoinensis and hydrogel that was made with Caesalpinia spinosa gum; previously were determined the physical-chemical parameters of these inputs. The following configuration was used in the treatment unit: an 80 L tank to deposit domestic wastewater, the biofilter made up of 3 beds of biochar (+/- 12 mesh) of 700 g, 800 g, and 700 g respectively, a flocculation tank of 20 L to which was added the Caesalpinia spinosa gel, another biofilter with 2 beds of 600 g and 700 g respectively and, finally, a tank to receive the treated water. The process carried out during the implementation of the test was characterized by being continuous: On every 30 minutes was adding 500 ml of hydrogel for 5 times and at the same process, the treated water samples were collected in an amount of 2 L every 25 minutes. On a removal process of 3 hours and 20 minutes, the final results showed a reduction of oils and fats from an initial value of 906 mg/l to 277 mg/l (69.43% reduction); Additionally, other physicochemical parameters were also reduced, obtained a final values of 80.70 NTU of turbidity, 2.53 mg/l of dissolved oxygen, 548.3 mg/l of COD, 4.17 BOD5, 1,211 mg/l of total solids, 948 mg/l of dissolved solids and 233 mg /l of total suspended solids. This research proves the positive effect of this biofilter for the removal of oils and fats, so it can be considered an alternative solution in wastewater sanitation problems.

A 24-month aging study in male C57Bl/6 mice reveals that aortic aging precedes cardiovascular disease and is due to changes in the extracellular matrix and vascular smooth muscle cell signaling.

Apart from cardiotoxicity, the chemotherapeutic agent doxorubicin (DOX) provokes acute and long-term vascular toxicity. Dexrazoxane (DEXRA) is an effective drug for treatment of DOX-induced cardiotoxicity, yet it remains currently unknown whether DEXRA prevents vascular toxicity associated with DOX. Accordingly, the present study aimed to evaluate the protective potential of DEXRA against DOX-related vascular toxicity in a previously-established in vivo and ex vivo model of vascular dysfunction induced by 16 hour (h) DOX exposure. Vascular function was evaluated in the thoracic aorta in organ baths, 16h after administration of DOX (4 mg/kg) or DOX with DEXRA (40 mg/kg) to male C57BL6/J mice. In parallel, vascular reactivity was evaluated after ex vivo incubation (16h) of murine aortic segments with DOX (1 μM) or DOX with DEXRA (10 μM). In both in vivo and ex vivo experiments, DOX impaired acetylcholine-stimulated endothelium-dependent vasodilation. In the ex vivo setting, DOX additionally attenuated phenylephrine-elicited vascular smooth muscle cell (VSMC) contraction. Importantly, DEXRA failed to prevent DOX-induced endothelial dysfunction and hypocontraction. Furthermore, RT-qPCR and Western blotting showed that DOX decreased the protein levels of topoisomerase-IIβ (TOP-IIβ), a key target of DEXRA, in the heart, but not in the aorta. Additionally, the effect of N-acetylcysteine (NAC, 10 μM), a reactive oxygen species (ROS) scavenger, was evaluated ex vivo. NAC did not prevent DOX-induced impairment of acetylcholine-stimulated vasodilation. In conclusion, our results show that DEXRA fails to prevent vascular toxicity resulting from 16h DOX treatment. This may relate to DOX provoking vascular toxicity in a ROS- and TOP-IIβ-independent way, at least in the evaluated acute setting. However, it is important to mention that these findings only apply to the acute (16h) treatment period, and further research is warranted to delineate the therapeutic potential of DEXRA against vascular toxicity associated with longer-term repetitive DOX dosing.

Summary: Insights into the evolution of non-model organisms are limited by the lack of reference genomes of high accuracy, completeness, and contiguity. Here, we present a chromosome-level, karyotype-validated reference genome and pangenome for the barn swallow (Hirundo rustica). We complement these resources with a reference-free multialignment of the reference genome with other bird genomes and with the most comprehensive catalog of genetic markers for the barn swallow. We identify potentially conserved and accelerated genes using the multialignment and estimate genome-wide linkage disequilibrium using the catalog. We use the pangenome to infer core and accessory genes and to detect variants using it as a reference. Overall, these resources will foster population genomics studies in the barn swallow, enable detection of candidate genes in comparative genomics studies, and help reduce bias toward a single reference genome.

Abstract In vivo angiotensin II (AngII)‐treatment is a widely used experimental model to induce cardiovascular disease and results in a high likelihood of abdominal aorta aneurysm (AAA) formation. This involves progressive and irreversible focal dilation of the abdominal aorta and induces adverse aortic connective tissue remodeling contributing to aortic wall stiffening through inflammation, elastin degradation, and collagen restructuring. Hence, the present study aimed to investigate how AAA formation in AngII‐treated mice affects aortic function and biomechanics. To this end, C57Bl/6J mice were treated with AngII (1000 ng/[kg.min]) or PBS infusion for 28 days. Peripheral blood pressure, echocardiography, and aortic pulse wave velocity were measured in vivo. Thoracic aorta rings were studied ex vivo in organ chambers, while aortic vascular smooth muscle cell (VSMC) phenotype was investigated histologically. We confirmed peripheral hypertension, cardiac hypertrophy, aortic stiffening, and increased VSMC proliferation and migration after AngII‐treatment. Abdominal aorta aneurysm formation was observed in 8/13 AngII‐treated mice. Ex vivo thoracic aortic rings of both aneurysmal and non‐aneurysmal AngII‐treated mice showed high isobaric aortic stiffness, endothelial dysfunction, heightened α1‐adrenergic contractility, and altered VSMC contractile calcium signaling. However, aortic biomechanics were differently affected, with heightened α1‐adrenoreceptor mediated aortic stiffening in non‐aneurysmal mice, whereas contraction‐dependent stiffening was impaired in aneurysmal mice. In conclusion, although aneurysmal and non‐aneurysmal 4‐week AngII‐treated mice displayed similar changes in aortic physiology, aortic biomechanics were dissimilarly affected.

Non-invasive routes for insulin delivery are emerging as alternatives to currently painful subcutaneous injections. For pulmonary delivery, formulations may be in powdered particle form, using carriers such as polysaccharides to stabilise the active principle. Roasted coffee beans and spent coffee grounds (SCG) are rich in polysaccharides, namely galactomannans and arabinogalactans. In this work, the polysaccharides were obtained from roasted coffee and SCG for the preparation of insulin-loaded microparticles. The galactomannan and arabinogalactan-rich fractions of coffee beverages were purified by ultrafiltration and separated by graded ethanol precipitations at 50% and 75%, respectively. For SCG, galactomannan-rich and arabinogalactan-rich fractions were recovered by microwave-assisted extraction at 150 °C and at 180 °C, followed by ultrafiltration. Each extract was spray-dried with insulin 10% (w/w). All microparticles had a raisin-like morphology and average diameters of 1–5 µm, which are appropriate for pulmonary delivery. Galactomannan-based microparticles, independently of their source, released insulin in a gradual manner, while arabinogalactan-based ones presented a burst release. The microparticles were seen to be non-cytotoxic for cells representative of the lung, specifically lung epithelial cells (A549) and macrophages (Raw 264.7) up to 1 mg/mL. This work shows how coffee can be a sustainable source of polysaccharide carriers for insulin delivery via the pulmonary route.

Introduction and Aims: Endothelial nitric oxide synthase (eNOS) knockout mice develop pronounced cardiovascular disease. In the present study, we describe the alterations in aortic physiology and biomechanics of eNOS knockout and C57Bl/6 control mice at 2–12 months of age, including a thorough physiological investigation of age and cyclic stretch-dependent VSMC contractility and aortic stiffness.Methods and Results: Peripheral blood pressure and aortic pulse wave velocity were measured in vivo, and aortic biomechanical studies and isometric contractions were investigated ex vivo. Age-dependent progression of aortic stiffness, peripheral hypertension, and aortic contractility in eNOS knockout mice was absent, attenuated, or similar to C57Bl/6 control mice. Voltage-gated calcium channel (VGCC)-dependent calcium influx inversely affected isometric contraction and aortic stiffening by α1-adrenergic stimulation in eNOS knockout mice. Baseline aortic stiffness was selectively reduced in eNOS knockout mice after ex vivo cyclic stretch exposure in an amplitude-dependent manner, which prompted us to investigate cyclic stretch dependent regulation of aortic contractility and stiffness. Aortic stiffness, both in baseline conditions and after activation of vascular smooth muscle cell (VSMC) contraction, was reduced with increasing cyclic stretch amplitude. This cyclic stretch dependency was attenuated with age, although aged eNOS knockout mice displayed better preservation of cyclic stretch-dependency compared to C57Bl/6 control mice. Store operated calcium entry-medicated aortic stiffening as induced by inhibiting sarcoplasmic reticulum calcium ATPase pumps with 10 µM CPA was most pronounced in the aorta of aged mice and at low cyclic stretch amplitude, but independent of eNOS. Basal aortic tonus and VSMC depolarization were highly dependent on eNOS, and were most pronounced at low cyclic stretch, with attenuation at increasing cyclic stretch amplitude.Conclusion: eNOS knockout mice display attenuated progression of arterial disease as compared to C57Bl/6 control mice. Basal VSMC tone in eNOS knockout mice could be reduced by ex vivo exposure to cyclic stretch through stretch-dependent regulation of cytosolic calcium. Both baseline and active aortic stiffness were highly dependent on cyclic stretch regulation, which was more pronounced in young versus aged mice. Other mediators of VSMC contraction and calcium handling were dependent on cyclic stretch mechanotransduction, but independent of eNOS.

The recovery of biomolecules from food industry by-products is of major relevance for a circular economy strategy. However, by-products’ contamination with mycotoxins represents a drawback for their reliable valorization for food and feed, hampering their application range, especially as food ingredients. Mycotoxin contamination occurs even in dried matrices. There is a need for the implantation of monitoring programs, even for by-products used as animal feed, since very high levels can be reached. This systematic review aims to identify the food by-products that have been studied from 2000 until 2022 (22 years) concerning mycotoxins’ contamination, distribution, and prevalence in those by-products. PRISMA (“Preferred Reporting Items for Systematic Reviews and MetaAnalyses”) protocol was performed via two databases (PubMed and SCOPUS) to summarize the research findings. After the screening and selection process, the full texts of eligible articles (32 studies) were evaluated, and data from 16 studies were considered. A total of 6 by-products were assessed concerning mycotoxin content; these include distiller dried grain with solubles, brewer’s spent grain, brewer’s spent yeast, cocoa shell, grape pomace, and sugar beet pulp. Frequent mycotoxins in these by-products are AFB1, OTA, FBs, DON, and ZEA. The high prevalence of contaminated samples, which surpasses the limits established for human consumption, thus limiting their valorization as ingredients in the food industry. Co-contamination is frequent, which can cause synergistic interactions and amplify their toxicity.

Resistance against anti-cancer therapy is one of the major challenges during treatment of multiple cancers. Gemcitabine is a standard first-line chemotherapeutic drug, yet autophagy is highly activated in the hypoxic microenvironment of solid tumors and enhances the survival of tumor cells against gemcitabine chemotherapy. Recently, we showed the add-on effect of autophagy inhibitor UAMC-2526 to prevent HT-29 colorectal tumor growth in CD1-/- Foxn1nu mice treated with oxaliplatin. In this study, we aimed to investigate the potential beneficial effects of UAMC-2526 in a syngeneic Panc02 mouse model of pancreatic ductal adenocarcinoma (PDAC). Our data showed that UAMC-2526 combined with gemcitabine significantly reduced tumor growth as compared to the individual treatments. However, in contrast to in vitro experiments with Panc02 cells in culture, we were unable to detect autophagy inhibition by UAMC-2526 in Panc02 tumor tissue, neither via western blot analysis of autophagy markers LC3 and p62, nor by transmission electron microscopy. In vitro experiments revealed that UAMC-2526 enhances the potential of gemcitabine to inhibit Panc02 cell proliferation without obvious induction of cell death. Altogether, we conclude that although the combination treatment of UAMC-2526 with gemcitabine did not inhibit autophagy in the Panc02 mouse model, it has a beneficial effect on tumor growth inhibition.

Measuring arterial stiffness has recently gained a lot of interest because it is a strong predictor for cardiovascular events and all-cause mortality. However, assessing blood vessel stiffness is not easy and the in vivo measurements currently used provide only limited information. Ex vivo experiments allow for a more thorough investigation of (altered) arterial biomechanical properties. Such experiments can be performed either statically or dynamically, where the latter better corresponds to physiological conditions. In a dynamic setup, arterial segments oscillate between two predefined forces, mimicking the diastolic and systolic pressures from an in vivo setting. Consequently, these oscillations result in a pulsatile load (i.e., the pulse pressure). The importance of pulse pressure on the ex vivo measurement of arterial stiffness is not completely understood. Here, we demonstrate that pulsatile load modulates the overall stiffness of the aortic tissue in an ex vivo setup. More specifically, increasing pulsatile load softens the aortic tissue. Moreover, vascular smooth muscle cell (VSMC) function was affected by pulse pressure. VSMC contraction and basal tonus showed a dependence on the amplitude of the applied pulse pressure. In addition, two distinct regions of the aorta, namely the thoracic descending aorta (TDA) and the abdominal infrarenal aorta (AIA), responded differently to changes in pulse pressure. Our data indicate that pulse pressure alters ex vivo measurements of arterial stiffness and should be considered as an important variable in future experiments. More research should be conducted in order to determine which biomechanical properties are affected due to changes in pulse pressure. The elucidation of the underlying pulse pressure-sensitive properties would improve our understanding of blood vessel biomechanics and could potentially yield new therapeutic insights.

The antineoplastic activity of the thioredoxin reductase 1 (TrxR) inhibitor, auranofin (AF), has already been investigated in various cancer mouse models as a single drug, or in combination with other molecules. However, there are inconsistencies in the literature on the solvent, dose and administration route of AF treatment in vivo. Therefore, we investigated the solvent and administration route of AF in a syngeneic SB28 glioblastoma (GBM) C57BL/6J and a 344SQ non-small cell lung cancer 129S2/SvPasCrl (129) mouse model. Compared to daily intraperitoneal injections and subcutaneous delivery of AF via osmotic minipumps, oral gavage for 14 days was the most suitable administration route for high doses of AF (10–15 mg/kg) in both mouse models, showing no measurable weight loss or signs of toxicity. A solvent comprising 50% DMSO, 40% PEG300 and 10% ethanol improved the solubility of AF for oral administration in mice. In addition, we confirmed that AF was a potent TrxR inhibitor in SB28 GBM tumors at high doses. Taken together, our results and results in the literature indicate the therapeutic value of AF in several in vivo cancer models, and provide relevant information about AF’s optimal administration route and solvent in two syngeneic cancer mouse models.

Background: Neutrophil extracellular traps (NET) are extracellular fibers produced by activated neutrophils to kill bacteria. NET was recently found to be associated with several diseases, such as autoimmune diseases. NET formation, called NETosis, is reactive oxygen species (ROS) dependent, thereby, prompting us to study its inhibition by potent antioxidant monoHER as well as to study monoHER protection against NET toxicity caused by NET constituent histone 3 on endothelial cells. Methods: Freshly isolated neutrophils from male donors were stimulated with PMA to induce NET formation. The effect of monoHER (50 µM) on oxidative burst (O2●− production) and NET formation was determined by fluorescence microscopy. Flow cytometry was used to determine the protective effect of monoHER against NET toxicity constituent histone 3 in EA.hy926 cells. Data was evaluated using ANOVA followed by the Bonferroni post-hoc test. Results: MonoHER significantly reduced (p < 0.01) O2●− production of PMA-stimulated neutrophils and consequently inhibited NET formation. MonoHER could also counteract histone 3 toxicity in EA.hy926 cells. Conclusions: MonoHER might inhibit ROS-dependent NETosis pathway and also protect the endothelial cells against NET toxicity.

In school buildings high levels of Indoor Air Quality are required for the specific susceptibility to airborne pollution of occupants, but most of the data published in the scientific literature indicate that classroom ventilation in many schools is still inadequate. The low investment costs and the easy implementation of the Building Automation Systems allow a widely application in the existing buildings. This work studies the natural ventilation mechanisms based mainly on the stack effect of the central atrium and of the stairwells in order to design the building automation control systems.

Nitric oxide (NO) is a small gaseous signaling molecule responsible for maintaining homeostasis in a myriad of tissues and molecular pathways in neurology and the cardiovasculature. In recent years, there has been increasing interest in the potential interaction between arterial stiffness (AS), an independent cardiovascular risk factor, and neurodegenerative syndromes given increasingly epidemiological study reports. For this reason, we previously investigated the mechanistic convergence between AS and neurodegeneration via the progressive non-selective inhibition of all nitric oxide synthase (NOS) isoforms with N(G)-nitro-L-arginine methyl ester (L-NAME) in C57BL/6 mice. Our previous results showed progressively increased AS in vivo and impaired visuospatial learning and memory in L-NAME-treated C57BL/6 mice. In the current study, we sought to further investigate the progressive molecular signatures in hippocampal tissue via LC–MS/MS proteomic analysis. Our data implicate mitochondrial dysfunction due to progressive L-NAME treatment. Two weeks of L-NAME treatment implicates altered G-protein-coupled-receptor signaling in the nerve synapse and associated presence of seizures and altered emotional behavior. Furthermore, molecular signatures implicate the cerebral presence of seizure-related hyperexcitability after short-term (8 weeks) treatment followed by ribosomal dysfunction and tauopathy after long-term (16 weeks) treatment.

The average age of the world’s elderly population is steadily increasing. This unprecedented rise in the aged world population will increase the prevalence of age-related disorders such as cardiovascular disease (CVD) and neurodegeneration. In recent years, there has been an increased interest in the potential interplay between CVDs and neurodegenerative syndromes, as several vascular risk factors have been associated with Alzheimer’s disease (AD). Along these lines, arterial stiffness is an independent risk factor for both CVD and AD. In this review, we discuss several inflammaging-related disease mechanisms including acute tissue-specific inflammation, nitro-oxidative stress, impaired autophagy, and insulin resistance which may contribute to the proposed synergism between arterial stiffness and AD.

The diagnosis of cerebral vein thrombosis (CVT) can be difficult. Patients with suspected CVT, in whom venous sinuses are affected by intracranial tumours or after intracranial surgery constitutes a particular challenging setting. Magnetic resonance non-contrast thrombus imaging (MR-NCTI) is a new magnetic resonance imaging (MRI) technique that has previously been shown to be accurate in the diagnosis of a first CVT and difficult-to-diagnose venous thrombosis in other anatomical locations. In this case report, a patient with a medical history of craniotomy for parieto-occipital meningioma was suspected of an acute CVT, but had an inconclusive computed tomography (CT) and MRI venography. MR-NCTI showed no abnormalities diagnostic for (sub)acute CVT and thus cerebral sinus occlusion was most likely a chronic thrombus or a result of residual meningioma tissue. Anticoagulant treatment was discontinued and she was discharged from hospital in good health. This case shows that MR-NCTI may be a valuable additional imaging test in complex cases in whom CT and MRI venography could not exclude acute CVT.

Distraction osteogenesis is a clinically established technique for lengthening, molding and shaping bone by new bone formation. The experimental evaluation of this expensive and time-consuming treatment is of high impact for better understanding of tissue engineering but mainly relies on a limited number of histological slices. These tissue slices contain two-dimensional information comprising only about one percent of the volume of interest. In order to analyze the soft and hard tissues of the entire jaw of a single rat in a multimodal assessment, we combined micro computed tomography (µCT) with histology. The µCT data acquired before and after decalcification were registered to determine the impact of decalcification on local tissue shrinkage. Identification of the location of the H&E-stained specimen within the synchrotron radiation-based µCT data collected after decalcification was achieved via non-rigid slice-to-volume registration. The resulting bi- and tri-variate histograms were divided into clusters related to anatomical features from bone and soft tissues, which allowed for a comparison of the approaches and resulted in the hypothesis that the combination of laboratory-based µCT before decalcification, synchrotron radiation-based µCT after decalcification and histology with hematoxylin-and-eosin staining could be used to discriminate between different types of collagen, key components of new bone formation.

Gasdermin D (GSDMD) is the key executor of pyroptotic cell death. Recent studies suggest that GSDMD-mediated pyroptosis is involved in atherosclerotic plaque destabilization. We report that cleaved GSDMD is expressed in macrophage- and smooth muscle cell-rich areas of human plaques. To determine the effects of GSDMD deficiency on atherogenesis, ApoE−/− Gsdmd−/− (n = 16) and ApoE−/−Gsdmd+/+ (n = 18) mice were fed a western-type diet for 16 weeks. Plaque initiation and formation of stable proximal aortic plaques were not altered. However, plaques in the brachiocephalic artery (representing more advanced lesions compared to aortic plaques) of ApoE−/− Gsdmd−/− mice were significantly smaller (115 ± 18 vs. 186 ± 16 × 103 µm2, p = 0.006) and showed features of increased stability, such as decreased necrotic core area (19 ± 4 vs. 37 ± 7 × 103 µm2, p = 0.03) and increased αSMA/MAC3 ratio (1.6 ± 0.3 vs. 0.7 ± 0.1, p = 0.01), which was also observed in proximal aortic plaques. Interestingly, a significant increase in TUNEL positive cells was observed in brachiocephalic artery plaques from ApoE−/− Gsdmd−/− mice (141 ± 25 vs. 62 ± 8 cells/mm2, p = 0.005), indicating a switch to apoptosis. This switch from pyroptosis to apoptosis was also observed in vitro in Gsdmd−/− macrophages. In conclusion, targeting GSDMD appears to be a promising approach for limiting the transition to an inflammatory, vulnerable plaque phenotype.

RIPK1 (receptor-interacting serine/threonine-protein kinase 1) enzymatic activity drives both apoptosis and necroptosis, a regulated form of necrosis. Because necroptosis is involved in necrotic core development in atherosclerotic plaques, we investigated the effects of a RIPK1S25D/S25D mutation, which prevents activation of RIPK1 kinase, on atherogenesis in ApoE−/− mice. After 16 weeks of western-type diet (WD), atherosclerotic plaques from ApoE−/− RIPK1S25D/S25D mice were significantly larger compared to ApoE−/− RIPK1+/+ mice (167 ± 34 vs. 78 ± 18 × 103 µm2, p = 0.01). Cell numbers (350 ± 34 vs. 154 ± 33 nuclei) and deposition of glycosaminoglycans (Alcian blue: 31 ± 6 vs. 14 ± 4%, p = 0.023) were increased in plaques from ApoE−/− RIPK1S25D/S25D mice while macrophage content (Mac3: 2.3 ± 0.4 vs. 9.8 ± 2.4%, p = 0.012) was decreased. Plaque apoptosis was not different between both groups. In contrast, pharmacological inhibition of RIPK1 kinase with GSK’547 (10 mg/kg BW/day) in ApoE−/− Fbn1C1039G+/− mice, a model of advanced atherosclerosis, did not alter plaque size after 20 weeks WD, but induced apoptosis (TUNEL: 136 ± 20 vs. 62 ± 9 cells/mm2, p = 0.004). In conclusion, inhibition of RIPK1 kinase activity accelerated plaque progression in ApoE−/− RIPK1S25D/S25D mice and induced apoptosis in GSK’547-treated ApoE−/− Fbn1C1039G+/− mice. Thus, without directly comparing the genetic and pharmacological studies, it can be concluded that targeting RIPK1 kinase activity does not limit atherogenesis.

Abstract Fire emissions of gases and aerosols alter atmospheric composition and have substantial impacts on climate, ecosystem function, and human health. Warming climate and human expansion in fire‐prone landscapes exacerbate fire impacts and call for more effective management tools. Here we developed a global fire forecasting system that predicts monthly emissions using past fire data and climate variables for lead times of 1 to 6 months. Using monthly fire emissions from the Global Fire Emissions Database (GFED) as the prediction target, we fit a statistical time series model, the Autoregressive Integrated Moving Average model with eXogenous variables (ARIMAX), in over 1,300 different fire regions. Optimized parameters were then used to forecast future emissions. The forecast system took into account information about region‐specific seasonality, long‐term trends, recent fire observations, and climate drivers representing both large‐scale climate variability and local fire weather. We cross‐validated the forecast skill of the system with different combinations of predictors and forecast lead times. The reference model, which combined endogenous and exogenous predictors with a 1 month forecast lead time, explained 52% of the variability in the global fire emissions anomaly, considerably exceeding the performance of a reference model that assumed persistent emissions during the forecast period. The system also successfully resolved detailed spatial patterns of fire emissions anomalies in regions with significant fire activity. This study bridges the gap between the efforts of near‐real‐time fire forecasts and seasonal fire outlooks and represents a step toward establishing an operational global fire, smoke, and carbon cycle forecasting system.

Autophagy is an important cellular survival process that enables degradation and recycling of defective organelles and proteins to maintain cellular homeostasis. Hence, defective autophagy plays a role in many age-associated diseases, such as atherosclerosis, arterial stiffening and hypertension. Recently, we showed in mice that autophagy in vascular smooth muscle cells (VSMCs) of large elastic arteries such as the aorta is important for Ca2+ mobilization and vascular reactivity. Whether autophagy plays a role in the smaller muscular arteries, such as the femoral artery, and thereby contributes to for example, blood pressure regulation is currently unknown. Therefore, we determined vascular reactivity of femoral artery segments of mice containing a VSMC specific deletion of the essential autophagy gene Atg7 (Atg7F/F SM22α-Cre+) and compared them to femoral artery segments of corresponding control mice (Atg7+/+ SM22α-Cre+). Our results indicate that similar to the aorta, femoral artery segments showed enhanced contractility. Specifically, femoral artery segments of Atg7F/F SM22α-Cre+ mice showed an increase in phasic phenylephrine (PE) induced contractions, together with an enhanced sensitivity to depolarization induced contractions. In addition, and importantly, VSMC sensitivity to exogenous nitric oxide (NO) was significantly increased in femoral artery segments of Atg7F/F SM22α-Cre+ mice. Notwithstanding the fact that small artery contractility is a significant pathophysiological determinant for the development of hypertension, 7 days of treatment with angiotensin II (AngII), which increased systolic blood pressure in control mice, was ineffective in Atg7F/F SM22α-Cre+ mice. It is likely that this was due to the increased sensitivity of VSMCs to NO in the femoral artery, although changes in the heart upon AngII treatment were also present, which could also be (partially) accountable for the lack of an AngII-induced rise in blood pressure in Atg7F/F SM22α-Cre+ mice. Overall, our study indicates that apart from previously shown effects on large elastic arteries, VSMC autophagy also plays a pivotal role in the regulation of the contractile and relaxing properties of the smaller muscular arteries. This may suggest a role for autophagy in vascular pathologies, such as hypertension and arterial stiffness.

Introduction Timely diagnosis and treatment of portal vein thrombosis (PVT) is crucial to prevent morbidity and mortality. However, current imaging tests cannot always accurately differentiate acute from chronic (nonocclusive) PVT. Magnetic resonance noncontrast thrombus imaging (MR-NCTI) has been shown to accurately differentiate acute from chronic venous thrombosis at other locations and may also be of value in the diagnostic management of PVT. This study describes the first phase of the Rhea study (NTR 7061). Our aim was to select and optimize MR-NCTI sequences that would be accurate for differentiation of acute from chronic PVT. Study Design The literature was searched for different MRI sequences for portal vein and acute thrombosis imaging. The most promising sequences were tested in a healthy volunteer followed by one patient with acute PVT and two patients with chronic PVT, all diagnosed on (repetitive) contrast-enhanced computed tomography (CT) venography to optimize the MR-NCTI sequences. All images were evaluated by an expert panel. Results Several MR-NCTI sequences were identified and tested. Differentiation of acute from chronic PVT was achieved with 3D T1 TFE (three-dimensional T1 turbo field echo) and 3D T1 Dixon FFE (three-dimensional T1 fast field echo) sequences with best image quality. The expert panel was able to confirm the diagnosis of acute PVT on the combined two MR-NCTI sequences and to exclude acute PVT in the two patients with chronic PVT. Conclusion Using 3D T1 TFE and 3D T1 Dixon FFE sequences, we were able to distinguish acute from chronic PVT. This clinical relevant finding will be elucidated in clinical studies to establish their test performance.

A 43-year-old man complaining of abdominal angina for several months showed a large suprarenal aneurysm of the abdominal aorta with extensive circumferential wall thrombosis, complete occlusion of the right renal artery and a critically stenosed left renal artery on CT angiography. He suffered from severe hypertension and renal failure. A percutaneous transluminal angioplasty (PTA) was planned. After the PTA procedure, which was complicated by the development of left renal artery occlusion, successful rescue revascularization surgery was performed. Since we were hesitant to start anticoagulant treatment because of a high bleeding risk, magnetic resonance direct thrombus imaging was performed to assess the age of the extensive arterial thrombosis. The aortic thrombus showed a low signal intensity, which is indicative of chronic rather than acute thrombosis. Therefore, oral anticoagulant treatment was not started. The patient recovered without major complications.

Mycoplasmas cause some of the most economically important diseases of sheep and goats, including diseases listed by the World Organisation for Animal Health (OIE) such as contagious caprine pleuropneumonia (CCPP) and contagious agalactia (CA). Other important mycoplasma diseases include chronic respiratory and arthritic syndrome (CRAS) and atypical pneumonia, both present on all continents where small ruminants are farmed. Unfortunately, owing to a lack of investment, most commercial vaccines for these diseases are of poor quality, being mostly composed of killed bacteriocins of dubious or unknown efficacy. Several Mediterranean laboratories produce autogenous vaccines, but these can only be used on farms where outbreaks have been officially declared, and consequently have limited impact on disease nationally. Effective live vaccines are available, but their use is often restricted because of safety concerns. With the necessary safeguards in place, we argue for their greater use. This review examines reported vaccines for mycoplasma diseases of small ruminants and attempts to identify new candidate antigens that may enable the development of improved products. Vaccines for CCPP are covered elsewhere.

Abstract. Climate change is increasing the frequency and intensity of wildfires globally, with significant impacts on society and the environment. However, our understanding of the global distribution of extreme fires remains skewed, primarily influenced by media coverage and regional research concentration. This inaugural State of Wildfires report systematically analyses fire activity worldwide, identifying extreme events from the March 2023–February 2024 fire season. We assess the causes, predictability, and attribution of these events to climate change and land use, and forecast future risks under different climate scenarios. During the 2023–24 fire season, 3.9 million km2 burned globally, slightly below the average of previous seasons, but fire carbon (C) emissions were 16 % above average, totaling 2.4 Pg C. This was driven by record emissions in Canadian boreal forests (over 9 times the average) and dampened by reduced activity in African savannahs. Notable events included record-breaking wildfire extent and emissions in Canada, the largest recorded wildfire in the European Union (Greece), drought-driven fires in western Amazonia and northern parts of South America, and deadly fires in Hawai’i (100 deaths) and Chile (131 deaths). Over 232,000 people were evacuated in Canada alone, highlighting the severity of human impact. Our analyses revealed that multiple drivers were needed to cause areas of extreme fire activity. In Canada and Greece a combination of high fire weather and an abundance of dry fuels increased the probability of fires by 4.5-fold and 1.9–4.1-fold, respectively, whereas fuel load and direct human suppression often modulated areas with anomalous burned area. The fire season in Canada was predictable three months in advance based on the fire weather index, whereas events in Greece and Amazonia had shorter predictability horizons. Formal attribution analyses indicated that the probability of extreme events has increased significantly due to anthropogenic climate change, with a 2.9–3.6-fold increase in likelihood of high fire weather in Canada and a 20.0–28.5-fold increase in Amazonia. By the end of the century, events of similar magnitude are projected to occur 2.22–9.58 times more frequently in Canada under high emission scenarios. Without mitigation, regions like Western Amazonia could see up to a 2.9-fold increase in extreme fire events. For the 2024–25 fire season, seasonal forecasts highlight moderate positive anomalies in fire weather for parts of western Canada and South America, but no clear signal for extreme anomalies is present in the forecast. This report represents our first annual effort to catalogue extreme wildfire events, explain their occurrence, and predict future risks. By consolidating state-of-the-art wildfire science and delivering key insights relevant to policymakers, disaster management services, firefighting agencies, and land managers, we aim to enhance society’s resilience to wildfires and promote advances in preparedness, mitigation, and adaptation.

Increasing epidemiological and experimental evidence points to a link between arterial stiffness and rapid cognitive decline. However, the underlying mechanism linking the two diseases is still unknown. The importance of nitric oxide synthases in both diseases is well-defined. In this study, we introduced arterial stiffness in both genetic (eNOS−/−, endothelial nitric oxide synthase knockout) and pharmacological (N(G)-nitro-L-arginine methyl ester (L-NAME) treatment) NO dysfunction models to study their association with cognitive decline. Our findings demonstrate that the non-selective inhibition of NOS activity with L-NAME induces cardiac dysfunction, arterial stiffness, and a decline in hippocampal-dependent learning and memory. This outcome demonstrates the importance of neuronal NOS (nNOS) in both cardiovascular and neurological pathophysiology and its potential contribution in the convergence between arterial stiffness and cognitive decline.

The aim of this preliminary study was to investigate the presence of Mycoplasma agalactiae (Ma) or other Contagious Agalactia (CA) causative organisms, in hard ticks infesting milking sheep and goats in endemic areas for CA in Sicily (South-Italy). Although there is accumulating evidence to support the role of ticks in the transmission of blood-borne haemoplasmas, information regarding their role in the transmission of CA, remains scarce. Ticks (n = 152) were collected from 25 lactating sheep and goats from three farms with previous outbreaks of CA. Microbiological and biomolecular, as well as serological analysis were performed on milk, tick, and serum samples, respectively. Rhipicephalus bursa species predominated, comprising 84.8% of the sampled ticks. Mycoplasma-like colonies were isolated from 5/56 (8.9%) tick pools and were identified as Ma by specific PCR and 16S rRNA gene sequencing. Unexpectedly, the organism was isolated from R. bursa ticks recovered only from animals whose milk tested negative for the pathogen. This preliminary demonstration suggests the potential role for ticks to act as a reservoir for the organisms, with potential involvement in the spread and maintenance of CA. Further work is required to determine the location of the organisms within the body of the ticks and to assess transmission potential.

Single-dose coffee capsules have revolutionized the coffee market, fueling espresso coffee popularity and offering access to a wide selection of coffee blends. Nevertheless, scarce information related to coffee powder and brew’s combined volatile characterization is available. In this study, it is hypothesized that coffee brew aroma characteristics can be predicted based on coffee powder’s volatile composition. For this, headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry detection (GC × GC-ToFMS) was used. The data were combined via chemometric tools to characterize in depth the volatile composition of eight blends of capsule-coffee powder and respective espresso brews, simulating the consumer’s perception. A total of 390 volatile compounds were putatively identified, 100 reported for the first time in roasted coffee or brews. Although the same chemical families were determined among the coffee powders and espresso brews, a different volatile profile was determined for each matrix. The Pearson correlation of coffee powders and respective brews allowed to identify 15 volatile compounds, mainly terpenic and esters recognized by their pleasant notes, with a strong relationship between the amounts present in both matrices. These compounds can be key markers to predict the volatile aroma potential of an espresso brew when analyzing the coffee powder.

The data presented here are related to the research paper entitled “Structural features of spent coffee grounds water-soluble polysaccharides: towards tailor-made microwave assisted extractions” [1]. Microwave assisted extraction conditions were applied to spent coffee grounds for recovery of polysaccharides, namely arabinogalactans and galactomannans. Following an experimental design testing temperature, time, and alkali conditions as influence factors during microwave assisted extraction, this article reports the response data for the total extracted mass, sugars yield (including arabinogalactans and galactomannans total content, and mass ratio), and structural features (including degree of polymerization and degree of branching) for each set of operating conditions. In addition, it provides gas chromatography–mass spectrometry (GC–MS) chromatograms (and respective GC–MS spectra) of arabinogalactan and galactomannan mixtures with different structural features corresponding to representative microwave treatment conditions. Keywords: Coffee residue, Arabinogalactans, Galactomannans, Polysaccharides, Methylation analysis, Microwave assisted extraction

Atherosclerosis is a chronic inflammatory disorder characterized by the gradual build-up of plaques within the vessel wall of middle-sized and large arteries. Over the past decades, treatment of atherosclerosis mainly focused on lowering lipid levels, which can be accomplished by the use of statins. However, some patients do not respond sufficiently to statin therapy and therefore still have a residual cardiovascular risk. This issue highlights the need for novel therapeutic strategies. As macrophages are implicated in all stages of atherosclerotic lesion development, they represent an important alternative drug target. A variety of anti-inflammatory strategies have recently emerged to treat or prevent atherosclerosis. Here, we review the canonical mechanisms of macrophage death and their impact on atherogenesis and plaque stability. Macrophage death is a prominent feature of advanced plaques and is a major contributor to necrotic core formation and plaque destabilization. Mechanisms of macrophage death in atherosclerosis include apoptosis, passive or accidental necrosis as well as secondary necrosis, a type of death that typically occurs when apoptotic cells are insufficiently cleared by neighboring cells via a phagocytic process termed efferocytosis. In addition, less-well characterized types of regulated necrosis in macrophages such as necroptosis, pyroptosis, ferroptosis, and parthanatos may occur in advanced plaques and are also discussed. Autophagy in plaque macrophages is an important survival pathway that protects against cell death, yet massive stimulation of autophagy promotes another type of death, usually referred to as autosis. Multiple lines of evidence indicate that a better insight into the different mechanisms of macrophage death, and how they mutually interact, will provide novel pharmacological strategies to resolve atherosclerosis and stabilize vulnerable, rupture-prone plaques.