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There is currently no clinically valid biomarker for predicting the growth and prognosis of abdominal aortic aneurysms (AAA). The most promising candidates with the highest diagnostic values are plasma D-dimers and markers of activated neutrophils, i.e., myeloperoxidase (MPO) or cell-free DNA. So far, case-control studies on these markers have been performed almost exclusively using healthy individuals as controls. To validate the value of these markers in the clinical setting of a vascular surgery department, we analysed the diagnostic and prognostic potential of plasma D-dimers and MPO in 177 AAA patients versus 138 non-AAA patients with different vascular diseases. Significantly elevated levels of D-dimers were recorded for AAA patients compared with non-AAA patients, although the difference between the two groups was significantly smaller than that in other studies comparing AAA patients with healthy controls. Surprisingly, MPO levels were significantly higher in non-AAA patients than in those with AAA. After adjusting for the confounding factors of sex, peripheral artery disease (PAD) and internal carotid stenosis in multivariate regression models, neither D-dimers nor MPO remained independent correlates of AAA. In contrast, D-dimer plasma levels correlated well with the maximal aortic diameter. Combined analysis of D-dimers and circulating cell-free DNA levels derived from a previous study failed to improve the predictive values for the maximal aortic diameter. In conclusion, our data show that D-dimers and MPO are not suitable biomarkers for monitoring AAA in a real-world setting of mixed vascular surgery patients.

Purpose: This study evaluates a deep learning-based denoising algorithm to improve the trade-off between radiation dose, image noise, and motion artifacts in TIPSS procedures, aiming for shorter acquisition times and reduced radiation with maintained diagnostic quality. Methods: In this retrospective study, TIPSS patients were divided based on CBCT acquisition times of 6 s and 3 s. Traditional weighted filtered back projection (Original) and an AI denoising algorithm (AID) were used for image reconstructions. Objective assessments of image quality included contrast, noise levels, and contrast-to-noise ratios (CNRs) through place-consistent region-of-interest (ROI) measurements across various critical areas pertinent to the TIPSS procedure. Subjective assessments were conducted by two blinded radiologists who evaluated the overall image quality, sharpness, contrast, and motion artifacts for each dataset combination. Statistical significance was determined using a mixed-effects model (p ≤ 0.05). Results: From an initial cohort of 60 TIPSS patients, 44 were selected and paired. The mean dose-area product (DAP) for the 6 s acquisitions was 5138.50 ± 1325.57 µGy·m2, significantly higher than the 2514.06 ± 691.59 µGym2 obtained for the 3 s series. CNR was highest in the 6 s-AID series (p < 0.05). Both denoised and original series showed consistent contrast for 6 s and 3 s acquisitions, with no significant noise differences between the 6 s Original and 3 s AID images (p > 0.9). Subjective assessments indicated superior quality in 6 s-AID images, with no significant overall quality difference between the 6 s-Original and 3 s-AID series (p > 0.9). Conclusions: The AI denoising algorithm enhances CBCT image quality in TIPSS procedures, allowing for shorter scans that reduce radiation exposure and minimize motion artifacts.

A growing body of evidence has shown the influence that religion and spirituality have on individuals duelling with illness, especially at advanced stages of disease. It is often vital for such individuals to have their spiritual and religious beliefs respected and, potentially, integrated in a compassionate caregiving setting for healthcare systems. However, given the diversity in religions and spiritual practices, healthcare professionals ought to approach such cultural significance with cultural humility, i.e., approaching differences in beliefs without relying on stereotypes or assumptions. This process requires sufficient training and communication skills among healthcare providers, as well as a successful medico-pastoral partnership. The aim of this review is to provide insight into one specific religion, Eastern Orthodoxy, and discuss current evidence of the religion’s influence on healthcare and medicine. Within this review, we aim to provide a summary on religion and spirituality specific to the Eastern Orthodox identity and religious practices, along with providing clinical guidance on approaching people who identify with this faith in certain healthcare settings in a manner compatible with the principles of cultural humility. The review will discuss important key elements of religious belief and practice of Εastern Orthodoxy that may influence health and healthcare decisions by patients.

The reaction of sodium 2,2-dicyanoethene-1,1-bis(thiolate) with bromine (2 equiv.) in CCl4 gave 3,5-dibromoisothiazole-3-carbonitrile and 5,5′-thiobis(3-bromoisothiazole-4-carbonitrile) in 7% and 18% yields, respectively. The latter novel compound was fully characterized.

Treatment of the most aggressive and deadliest form of skin cancer, the malignant melanoma, still has room for improvement. Its invasive nature and ability to rapidly metastasize and to develop resistance to standard treatment often result in a poor prognosis. While the highly effective standard chemotherapeutic agent doxorubicin (DOX) is widely used in a variety of cancers, systemic side effects still limit therapy. Especially, DOX-induced cardiotoxicity remains a big challenge. In contrast, the natural chalcone cardamonin (CD) has been shown to selectively kill tumor cells. Besides its anti-tumor activity, CD exhibits anti-oxidative, anti-inflammatory and anti-bacterial properties. In this study, we investigated the effect of the combinational treatment of DOX with CD on A375 melanoma cells compared to normal human dermal fibroblasts (NHDF) and rat cardiac myoblasts (H9C2 cells). DOX-induced cytotoxicity was unselective and affected all cell types, especially H9C2 cardiac myoblasts, demonstrating its cardiotoxic effect. In contrast, CD only decreased the cell viability of A375 melanoma cells, without harming normal (healthy) cells. The addition of CD selectively protected human dermal fibroblasts and rat cardiac myoblasts from DOX-induced cytotoxicity. While no apoptosis was induced by the combinational treatment in normal (healthy) cells, an apoptosis-mediated cytotoxicity was demonstrated in A375 melanoma cells. CD exhibited thiol reactivity as it was able to directly interact with N-acetylcysteine (NAC) in a cell-free assay and to induce heme oxygenase-1 (HO-1) in all cell types. And that took place in a reactive oxygen species (ROS)-independent manner. DOX decreased the mitochondrial membrane potential (Δψm) in all cell types, whereas CD selectively decreased mitochondrial respiration, affecting basal respiration, maximal respiration, spare respiratory capacity and ATP production in A375 melanoma cells, but not in healthy cardiac myoblasts. The DOX-induced cytotoxicity seen in melanoma cells was ROS-independent, whereas the cytotoxic effect of CD was associated with CD-induced ROS-formation and/or its thiol reactivity. This study highlights the beneficial properties of the addition of CD to DOX treatment, which might protect patients from DOX-induced cardiotoxicity. Future experiments with other tumor cell lines or a mouse model should substantiate this hypothesis.

Nowadays, one of the greatest challenges in data meshes revolves around detecting and creating data domains and data products for providing the ability to adapt easily and quickly to changing business needs. This requires a disciplined approach to identify, differentiate and prioritize distinct data sources according to their content and diversity. The current paper tackles this highly complicated issue and suggests a standardized approach that integrates the concept of data blueprints with data meshes. In essence, a novel standardization framework is proposed that creates data products using a metadata semantic enrichment mechanism, the latter also offering data domain readiness and alignment. The approach is demonstrated using real-world data produced by multiple sources in a poultry meat production factory. A set of functional attributes is used to qualitatively compare the proposed approach to existing data structures utilized in storage architectures, with quite promising results. Finally, experimentation with different scenarios varying in data product complexity and granularity suggests a successful performance.

3,5-Diphenyl-4H-1,2,6-thiadiazin-4-one treated with meta-chloroperoxybenzoic acid undergoes an oxidative ring contraction to give 2-benzoyl-4-phenyl-1,2,5-thiadiazol-3(2H)-one 1,1-dioxide in a 29% yield, the structure of which is supported by single-crystal X-ray diffraction analysis and the available spectroscopic data.

Stille coupling between 5,5′-dibromo-4,4′-diphenyl-2,2′-bithiazole and 9-(2-ethylhexyl)-3-(tributylstannyl)-9H-carbazole in the presence of Pd(Ph3P)2Cl2 in toluene, heated at reflux for 2 h, gave 5,5′-bis[9-(2-ethylhexyl)-9H-carbazol-3-yl]-4,4′-diphenyl-2,2′-bithiazole in 85% yield.

Data meshes are an approach to data architecture and organization that treats data as a product and focuses on decentralizing data ownership and access. It has recently emerged as a field that presents quite a few challenges related to data ownership, governance, security, monitoring, and observability. To address these challenges, this paper introduces an innovative algorithmic framework leveraging data blueprints to enable the dynamic creation of data meshes and data products in response to user requests, ensuring that stakeholders have access to specific portions of the data mesh as needed. Ownership and governance concerns are addressed through a unique mechanism involving Blockchain and Non-Fungible Tokens (NFTs). This facilitates the secure and transparent transfer of data ownership, with the ability to mint time-based NFTs. By combining these advancements with the fundamental tenets of data meshes, this research offers a comprehensive solution to the challenges surrounding data ownership and governance. It empowers stakeholders to navigate the complexities of data management within a decentralized architecture, ensuring a secure, efficient, and user-centric approach to data utilization. The proposed framework is demonstrated using real-world data from a poultry meat production factory.

Coronary artery ectasia (CAE) is defined as abnormal dilation of a coronary artery with a diameter exceeding that of adjacent normal arterial segment by >1.5 times. CAE is a pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE frequently coexists with coronary artery disease (CAD). While inflammation appears to be involved, the pathophysiology of CAE remains unclear. Damage-associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue, are deemed as alarm signals by the innate immune system. Inflammatory agents can generate DAMPs and DAMPs can create a pro-inflammatory state. In a prospective cross-sectional study, we enrolled 29 patients with CAE and non-obstructive CAD, 19 patients with obstructive CAD without CAE, and 14 control subjects with normal (control) coronary arteries age- and sex-matched with the CAE patients, to investigate the differential expression of plasma DAMPs. Patients with CAE and non-obstructive CAD had increased plasma levels of the DAMPs S100B, S100A12, HMGB1, and HSP70, the DAMPs receptor TLR4, and miR328a-3p compared to CAD and controls. Plasma levels of the mir328a-3p target the protective soluble form of the DAMPs receptor for advanced glycation end products (sRAGE), and the antioxidant DJ-1 was decreased in both CAE and CAD compared to controls. In an in vitro human umbilical vein endothelial cells model, circulating levels of S100B, HMGB1, HSP70 as well as CAE patient plasma induced inflammatory responses. The differential expression of the DAMPs S100B, HSP70, HMGB1, and their receptors TLR4 and sRAGE in CAE versus CAD makes them attractive novel biomarkers as therapeutic targets and therapeutics.

Background: Polycystic ovary syndrome (PCOS) is closely related to various adverse cardiovascular manifestations and increased cardiovascular risk. However, atrial fibrillation (AF) development and atrial conduction abnormalities have not been thoroughly studied in patients with PCOS. Methods: This meta-analysis (CRD42021261375) was conducted in accordance with the PRISMA guidelines. Our aim was to investigate associations between PCOS and disorders in atrial conduction parameters linked with an increased risk for AF occurrence. Results: Five cohort studies with aggregate data on 406 adult women (229 with PCOS and 177 age-matched without PCOS) were included in this analysis. Our results showed a significantly increased mean difference in P-wave maximum duration (+7.63 ± 7.07 msec; p < 0.01) and P-wave dispersion (+11.42 ± 5.22 msec; p = 0.03) of patients with PCOS compared to healthy women. The mean difference in P-wave minimum duration (−2.22 ± 2.68 msec; p = 0.11) did not reach the statistical threshold between the compared groups. Echocardiographic measurements of atrial electromechanical delay (AED) also indicated a statistically significant mean difference in favour of the PCOS group in all assessed parameters, except for atrial electromechanical coupling (PA) in the tricuspid annulus. Particularly, PCOS was associated with increased lateral PA, septal PA, inter- and intra-AED durations (mean difference: +17.31 ± 9.02 msec; p < 0.01, +11.63 ± 7.42 msec; p < 0.01, +15.31 ± 9.18 msec; p < 0.01, +9.31 ± 6.85 msec; p < 0.01, respectively). Conclusions: PCOS is strongly associated with alterations in several electrocardiographic and echocardiographic parameters indicating abnormal atrial conduction. Therefore, PCOS could be considered as a causal or triggering factor of AF. Larger studies are needed to confirm these results and investigate direct associations between PCOS and AF.

(1) This study evaluates the impact of an AI denoising algorithm on image quality, diagnostic accuracy, and radiological workflows in pediatric chest ultra-low-dose CT (ULDCT). (2) Methods: 100 consecutive pediatric thorax ULDCT were included and reconstructed using weighted filtered back projection (wFBP), iterative reconstruction (ADMIRE 2), and AI denoising (PixelShine). Place-consistent noise measurements were used to compare objective image quality. Eight blinded readers independently rated the subjective image quality on a Likert scale (1 = worst to 5 = best). Each reader wrote a semiquantitative report to evaluate disease severity using a severity score with six common pathologies. The time to diagnosis was measured for each reader to compare the possible workflow benefits. Properly corrected mixed-effects analysis with post-hoc subgroup tests were used. Spearman’s correlation coefficient measured inter-reader agreement for the subjective image quality analysis and the severity score sheets. (3) Results: The highest noise was measured for wFBP, followed by ADMIRE 2, and PixelShine (76.9 ± 9.62 vs. 43.4 ± 4.45 vs. 34.8 ± 3.27 HU; each p < 0.001). The highest subjective image quality was measured for PixelShine, followed by ADMIRE 2, and wFBP (4 (4–5) vs. 3 (4–5) vs. 3 (2–4), each p < 0.001) with good inter-rater agreement (r ≥ 0.790; p ≤ 0.001). In diagnostic accuracy analysis, there was a good inter-rater agreement between the severity scores (r ≥ 0.764; p < 0.001) without significant differences between severity score items per reconstruction mode (F (5.71; 566) = 0.792; p = 0.570). The shortest time to diagnosis was measured for the PixelShine datasets, followed by ADMIRE 2, and wFBP (2.28 ± 1.56 vs. 2.45 ± 1.90 vs. 2.66 ± 2.31 min; F (1.000; 99.00) = 268.1; p < 0.001). (4) Conclusions: AI denoising significantly improves image quality in pediatric thorax ULDCT without compromising the diagnostic confidence and reduces the time to diagnosis substantially.

Low back pain (LBP) is associated with the degeneration of human intervertebral discs (IVDs). Despite progress in the treatment of LBP through spinal fusion, some cases still end in non-fusion after the removal of the affected IVD tissue. In this study, we investigated the hypothesis that the remaining IVD cells secrete BMP inhibitors that are sufficient to inhibit osteogenesis in autologous osteoblasts (OBs) and bone marrow mesenchymal stem cells (MSCs). A conditioned medium (CM) from primary human IVD cells in 3D alginate culture was co-cultured with seven donor-matched OB and MSCs. After ten days, osteogenesis was quantified at the transcript level using qPCR to measure the expression of bone-related genes and BMP antagonists, and at the protein level by alkaline phosphatase (ALP) activity. Additionally, cells were evaluated histologically using alizarin red (ALZR) staining on Day 21. For judging ALP activity and osteogenesis, the Noggin expression in samples was investigated to uncover the potential causes. The results after culture with the CM showed significantly decreased ALP activity and the inhibition of the calcium deposit formation in alizarin red staining. Interestingly, no significant changes were found among most bone-related genes and BMP antagonists in OBs and MSCs. Noteworthy, Noggin was relatively expressed higher in human IVD cells than in autologous OBs or MSCs (relative to autologous OB, the average fold change was in 6.9, 10.0, and 6.3 in AFC, CEPC, and NPC, respectively; and relative to autologous MSC, the average fold change was 2.3, 3.4, and 3.2, in AFC, CEPC, and NPC, respectively). The upregulation of Noggin in residual human IVDs could potentially inhibit the osteogenesis of autologous OB and MSC, thus inhibiting the postoperative spinal fusion after discectomy surgery.

Detecting micron-sized particles is an essential task for the analysis of complex plasmas because a large part of the analysis is based on the initially detected positions of the particles. Accordingly, high accuracy in particle detection is desirable. Previous studies have shown that machine learning algorithms have made great progress and outperformed classical approaches. This work presents an approach for tracking micron-sized particles in a dense cloud of particles in a dusty plasma at Plasmakristall-Experiment 4 using a U-Net. The U-net is a convolutional network architecture for the fast and precise segmentation of images that was developed at the Computer Science Department of the University of Freiburg. The U-Net architecture, with its intricate design and skip connections, has been a powerhouse in achieving precise object delineation. However, as experiments are to be conducted in resource-constrained environments, such as parabolic flights, preferably with real-time applications, there is growing interest in exploring less complex U-net architectures that balance efficiency and effectiveness. We compare the full-size neural network, three optimized neural networks, the well-known StarDist and trackpy, in terms of accuracy in artificial data analysis. Finally, we determine which of the compact U-net architectures provides the best balance between efficiency and effectiveness. We also apply the full-size neural network and the the most effective compact network to the data of the PK-4 experiment. The experimental data were generated under laboratory conditions.

(1) To investigate whether interventional cone-beam computed tomography (cbCT) could benefit from AI denoising, particularly with respect to patient body mass index (BMI); (2) From 1 January 2016 to 1 January 2022, 100 patients with liver-directed interventions and peri-procedural cbCT were included. The unenhanced mask run and the contrast-enhanced fill run of the cbCT were reconstructed using weighted filtered back projection. Additionally, each dataset was post-processed using a novel denoising software solution. Place-consistent regions of interest measured signal-to-noise ratio (SNR) per dataset. Corrected mixed-effects analysis with BMI subgroup analyses compared objective image quality. Multiple linear regression measured the contribution of “Radiation Dose”, “Body-Mass-Index”, and “Mode” to SNR. Two radiologists independently rated diagnostic confidence. Inter-rater agreement was measured using Spearman correlation (r); (3) SNR was significantly higher in the denoised datasets than in the regular datasets (p < 0.001). Furthermore, BMI subgroup analysis showed significant SNR deteriorations in the regular datasets for higher patient BMI (p < 0.001), but stable results for denoising (p > 0.999). In regression, only denoising contributed positively towards SNR (0.6191; 95%CI 0.6096 to 0.6286; p < 0.001). The denoised datasets received overall significantly higher diagnostic confidence grades (p = 0.010), with good inter-rater agreement (r ≥ 0.795, p < 0.001). In a subgroup analysis, diagnostic confidence deteriorated significantly for higher patient BMI (p < 0.001) in the regular datasets but was stable in the denoised datasets (p ≥ 0.103).; (4) AI denoising can significantly enhance image quality in interventional cone-beam CT and effectively mitigate diagnostic confidence deterioration for rising patient BMI.

Infrared radiation (IR) is a promising complementary treatment for musculoskeletal conditions and chronic pain. By means of a systematic review, we evaluated the contribution of IR to the management of these ailments. PubMed-MEDLINE, Scopus, and Cochrane Library–Cochrane Central Register of Controlled Trials were systematically searched until 20 December 2021. The literature search yielded 233 relevant records. Following the screening of titles and abstracts, 42 full-texts were evaluated. As per inclusion/exclusion criteria, 13 publications were entered into the qualitative assessment. These studies described the effects of IR in humans: three studies focused on osteoarthritis, four studies on fibromyalgia, and six encompassed a wider range of diseases (ankylosing spondylitis, recovery from sports injuries, myofascial pain syndrome). Based on the findings of our systematic review, we noted a decrease in pain levels, as evaluated by the visual analog scale (VAS), in patients suffering from musculoskeletal disorders treated with IR. In addition, IR use led to a decrease in Fibromyalgia Impact Questionnaire (FiQ) scores in subjects diagnosed with fibromyalgia. Nevertheless, IR has failed to facilitate muscle recovery following athletic injuries.

(1) To explore the potential impact of an AI dual-energy CT (DECT) prototype on decision making and workflows by investigating its capabilities to differentiate COVID-19 from immunotherapy-related pneumonitis. (2) Methods: From 3 April 2020 to 12 February 2021, DECT from biometrically matching patients with COVID-19, pneumonitis, and inconspicuous findings were selected from our clinical routine. Three blinded readers independently scored each pulmonary lobe analogous to CO-RADS. Inter-rater agreement was determined with an intraclass correlation coefficient (ICC). Averaged perfusion metrics per lobe (iodine uptake in mg, volume without vessels in ml, iodine concentration in mg/mL) were extracted using manual segmentation and an AI DECT prototype. A generalized linear mixed model was used to investigate metric validity and potential distinctions at equal CO-RADS scores. Multinomial regression measured the contribution “Reader”, “CO-RADS score”, and “perfusion metrics” to diagnosis. The time to diagnosis was measured for manual vs. AI segmentation. (3) Results: We included 105 patients (62 ± 13 years, mean BMI 27 ± 2). There were no significant differences between manually and AI-extracted perfusion metrics (p = 0.999). Regardless of the CO-RADS score, iodine uptake and concentration per lobe were significantly higher in COVID-19 than in pneumonitis (p < 0.001). In regression, iodine uptake had a greater contribution to diagnosis than CO-RADS scoring (Odds Ratio (OR) = 1.82 [95%CI 1.10–2.99] vs. OR = 0.20 [95%CI 0.14–0.29]). The AI prototype extracted the relevant perfusion metrics significantly faster than radiologists (10 ± 1 vs. 15 ± 2 min, p < 0.001). (4) Conclusions: The investigated AI prototype positively impacts decision making and workflows by extracting perfusion metrics that differentiate COVID-19 from visually similar pneumonitis significantly faster than radiologists.

A reaction of 3-chloroisothiazole-5-carbonitrile with 1-iodo-4-methylbenzene (2 equiv.) produced 3-chloro-4-(p-tolyl)isothiazole-5-carbonitrile in a 60% yield. The compound was fully characterized.

Reactions of 3-bromo-4-phenylisothiazole-5-carboxamide and 3-bromoisothiazole-5-carboxamide with NaNO2 (4 equiv.), in TFA, at ca. 0 °C gave the carboxylic acid products in 99% and 95% yields, respectively. The two compounds were fully characterized.

Reaction of methyl 3-bromo-5-cyanoisothiazole-4-carboxylate with conc. H2SO4 gave methyl 3-bromo-5-carbamoylisothiazole-4-carboxylate in 93% yield. The compound was fully characterized.

PET/CT scanners with a long axial field-of-view (LAFOV) provide increased sensitivity, enabling the adjustment of imaging parameters by reducing the injected activity or shortening the acquisition time. This study aimed to evaluate the limitations of reduced [18F]FDG activity doses on image quality, lesion detectability, and the quantification of lesion uptake in the Biograph Vision Quadra, as well as to assess the benefits of the recently introduced ultra-high sensitivity mode in a clinical setting. A number of 26 patients who underwent [18F]FDG-PET/CT (3.0 MBq/kg, 5 min scan time) were included in this analysis. The PET raw data was rebinned for shorter frame durations to simulate 5 min scans with lower activities in the high sensitivity (HS) and ultra-high sensitivity (UHS) modes. Image quality, noise, and lesion detectability (n = 82) were assessed using a 5-point Likert scale. The coefficient of variation (CoV), signal-to-noise ratio (SNR), tumor-to-background ratio (TBR), and standardized uptake values (SUV) including SUVmean, SUVmax, and SUVpeak were evaluated. Subjective image ratings were generally superior in UHS compared to the HS mode. At 0.5 MBq/kg, lesion detectability decreased to 95% (HS) and to 98% (UHS). SNR was comparable at 1.0 MBq/kg in HS (5.7 ± 0.6) and 0.5 MBq/kg in UHS (5.5 ± 0.5). With lower doses, there were negligible reductions in SUVmean and SUVpeak, whereas SUVmax increased steadily. Reducing the [18F]FDG activity to 1.0 MBq/kg (HS/UHS) in a LAFOV PET/CT provides diagnostic image quality without statistically significant changes in the uptake parameters. The UHS mode improves image quality, noise, and lesion detectability compared to the HS mode.

With a global increase in chronic kidney disease patients, alternatives to dialysis and organ transplantation are needed. Stem cell-based therapies could be one possibility to treat chronic kidney disease. Here, we used multipotent urine-derived renal progenitor cells (UdRPCs) to study nephrogenesis. UdRPCs treated with the JNK inhibitor—AEG3482 displayed decreased proliferation and downregulated transcription of cell cycle-associated genes as well as the kidney progenitor markers—SIX2, SALL1 and VCAM1. In addition, levels of activated SMAD2/3, which is associated with the maintenance of self-renewal in UdRPCs, were decreased. JNK inhibition resulted in less efficient oxidative phosphorylation and more lipid peroxidation via ferroptosis, an iron-dependent non-apoptotic cell death pathway linked to various forms of kidney disease. Our study is the first to describe the importance of JNK signalling as a link between maintenance of self-renewal and protection against ferroptosis in SIX2-positive renal progenitor cells.

Despite great efforts to develop new therapeutic strategies to combat melanoma, the prognosis remains rather poor. Artesunate (ART) is an antimalarial drug displaying anti-cancer effects in vitro and in vivo. In this in vitro study, we investigated the selectivity of ART on melanoma cells. Furthermore, we aimed to further elucidate the mechanism of the drug with a focus on the role of iron, the induction of oxidative stress and the implication of the enzyme heme oxygenase 1 (HO-1). ART treatment decreased the cell viability of A375 melanoma cells while it did not affect the viability of normal human dermal fibroblasts, used as a model for normal (healthy) cells. ART’s toxicity was shown to be dependent on intracellular iron and the drug induced high levels of oxidative stress as well as upregulation of HO-1. Melanoma cells deficient in HO-1 or treated with a HO-1 inhibitor were less sensitive towards ART. Taken together, our study demonstrates that ART induces oxidative stress resulting in the upregulation of HO-1 in melanoma cells, which subsequently triggers the effect of ART’s own toxicity. This new finding that HO-1 is involved in ART-mediated toxicity may open up new perspectives in cancer therapy.

Asthma is a heterogeneous disease, characterized by chronic inflammation and oxidative stress of the airways. Several inflammatory pathways including activation of the receptor for advanced glycation end products (RAGE) have been described in the course of the disease. DJ-1 is a redox-sensitive protein with multifaceted roles in mast cell homeostasis and an emerging role in the pathogenesis of asthma. Moreover, cardiac function abnormalities have been described via echocardiography in patients with asthma. The main aim of this study was to investigate the plasma levels of RAGE, its ligands and DJ-1 in asthmatic patients pre- and post-treatment along with echocardiographic indices of cardiovascular function. The study population was divided into two groups. Group A included 13 patients with newly diagnosed bronchial asthma who were free of treatment for at least two weeks and Group B included 12 patients without asthma. An echocardiography examination was performed on all patients. The plasma levels of RAGE, its ligands (AGEs, S100A12, S100B, S100A8/A9), the interleukins (IL-6, IL-1β) and DJ-1 were measured. No differences were noted among the two groups for baseline characteristics and echocardiographic indices of cardiac function. In Group A, 31% suffered from mild asthma, 54% from moderate asthma and 15% from severe asthma. Plasma levels of IL-6, AGEs and AGE/RAGE ratio were increased and those of S100A12 and DJ-1 were decreased in asthmatics. Pharmacotherapy with corticosteroids/β2-agonists decreased IL-6, and AGEs, and increased DJ-1. In search of novel approaches in diagnosing and treating patients with asthma, S100A12, ratio AGE/sRAGE, and DJ-1 in addition to IL-6 may prove to be useful tools.

Radial access has largely substituted femoral access for coronary interventions. Nevertheless, the femoral artery remains indispensable for gaining access to structural and complex percutaneous coronary interventions such as transcatheter aortic valve implantation and chronic total occlusion interventions, respectively. Ultrasound-guided femoral puncture is a broadly available, inexpensive, and relatively easy-to-learn technique. According to the existing evidence, ultrasound guidance for gaining femoral access has improved the effectiveness and safety of the technique. In the present paper, we sought to review the current literature in order to provide the reader with up-to-date data regarding the benefits of ultrasound-guided femoral access compared with the conventional technique as well as describing the state-of-the-art technique for gaining femoral access under ultrasound guidance.

Reaction of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with 2-mercaptoethan-1-ol (1 equiv.) gave 6,10-dichloro-1-oxa-4,8-dithia-7,9-diazaspiro[4.5]deca-6,9-diene in 12% yield. The compound was fully characterized.

(1) Background: Low back pain (LBP) is often associated with intervertebral disc degeneration (IVDD). Autochthonous progenitor cells isolated from the center, i.e., the nucleus pulposus, of the IVD (so-called nucleus pulposus progenitor cells (NPPCs)) could be a future cell source for therapy. The NPPCs were also identified to be positive for the angiopoietin-1 receptor (Tie2). Similar to hematopoietic stem cells, Tie2 might be involved in peroxisome proliferator-activated receptor delta (PPARδ) agonist-induced self-renewal regulation. The purpose of this study was to investigate whether a PPARδ agonist (GW501516) increases the Tie2+ NPPCs’ yield within the heterogeneous nucleus pulposus cell (NPC) population. (2) Methods: Primary NPCs were treated with 10 µM of GW501516 for eight days. Mitochondrial mass was determined by microscopy, using mitotracker red dye, and the relative gene expression was quantified by qPCR, using extracellular matrix and mitophagy-related genes. (3) The NPC’s group treated with the PPARδ agonist showed a significant increase of the Tie2+ NPCs yield from ~7% in passage 1 to ~50% in passage two, compared to the NPCs vehicle-treated group. Furthermore, no significant differences were found among treatment and control, using qPCR and mitotracker deep red. (4) Conclusion: PPARδ agonist could help to increase the Tie2+ NPCs yield during NPC expansion.

Reaction of 4,5-dichloro-1,2,3-dithiazolium chloride with 2-[amino(methylthio)methylene])malononitrile (1 equiv) in the presence of pyridine (2 equiv) gave (Z)-2-{[(4-chloro-5H-1,2,3-dithiazol-5-ylidene)amino](methylthio)methylene}malononitrile in 20% yield. The compound was fully characterized.

The 1,2,3-dithiazole is an underappreciated scaffold in medicinal chemistry despite possessing a wide variety of nascent pharmacological activities. The scaffold has a potential wealth of opportunities within these activities and further afield. The 1,2,3-dithiazole scaffold has already been reported as an antifungal, herbicide, antibacterial, anticancer agent, antiviral, antifibrotic, and is a melanin and Arabidopsis gibberellin 2-oxidase inhibitor. These structure activity relationships are discussed in detail, along with insights and future directions. The review also highlights selected synthetic strategies developed towards the 1,2,3-dithiazole scaffold, how these are integrated to accessibility of chemical space, and to the prism of current and future biological activities.

The aim of this study was to investigate histopathological differences in abdominal aortic aneurysms (AAAs) between patients with multiple and single arterial aneurysms, as we suspect that there are different underlying mechanisms in aneurysm formation. Analysis was based on a previous retrospective study on patients with multiple arterial aneurysms (mult-AA; defined as at least four, n = 143) and a single AAA (sing-AAA, n = 972) who were admitted to our hospital for treatment between 2006 and 2016. Available paraffin-embedded AAA wall specimens were derived from the Vascular Biomaterial Bank Heidelberg (mult-AA, n = 12 vs. sing-AAA, n = 19). Sections were analyzed regarding structural damage of the fibrous connective tissue and inflammatory cell infiltration. Alterations to the collagen and elastin constitution were assessed by Masson–Goldner trichrome and Elastica van Gieson staining. Inflammatory cell infiltration, response and transformation were assessed by CD45 and IL-1β immunohistochemistry and von Kossa staining. The extent of aneurysmal wall alterations was assessed by semiquantitative gradings and was compared between the groups using Fisher’s exact test. IL-1β was significantly more present in the tunica media in mult-AA compared to sing-AAA (p = 0.022). The increased expression of IL-1β in mult-AA compared to sing-AAA indicates inflammatory processes play a role in aneurysm formation in patients with multiple arterial aneurysms.

Low back pain is often due to degeneration of the intervertebral discs (IVD). It is one of the most common age- and work-related problems in today’s society. Current treatments are not able to efficiently restore the full function of the IVD. Therefore, the aim of the present work was to reconstruct the two parts of the intervertebral disc—the annulus fibrosus (AF) and the nucleus pulposus (NP)—in such a way that the natural structural features were mimicked by a textile design. Silk was selected as the biomaterial for realization of a textile IVD because of its cytocompatibility, biodegradability, high strength, stiffness, and toughness, both in tension and compression. Therefore, an embroidered structure made of silk yarn was developed that reproduces the alternating fiber structure of +30° and −30° fiber orientation found in the AF and mimics its lamellar structure. The developed embroidered ribbons showed a tensile strength that corresponded to that of the natural AF. Fiber additive manufacturing with 1 mm silk staple fibers was used to replicate the fiber network of the NP and generate an open porous textile 3D structure that may serve as a reinforcement structure for the gel-like NP.

3,5-Dichloro-4H-1,2,6-thiadiazin-4-one reacts with benzo[d]thiazole-2-thiol (1 equiv) and triethylamine (1 equiv) to give 3-(benzo[d]thiazol-2-ylthio)-5-chloro-4H-1,2,6-thiadiazin-4-one in 71% yield. The reactivity of this compound with methoxide is explored and compared with that of 3-chloro-5-(phenylthio)-4H-1,2,6-thiadiazin-4-one.

The reaction of 4,5-dichloro-1,2,3-dithiazolium chloride with 2-(phenylsulfonyl)acetonitrile (1 equiv) in the presence of pyridine (2 equiv) gave S-(3-chloro-5-cyanoisothiazol-4-yl)benzenesulfonothioate and (Z)-2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-2-(phenylsulfonyl)acetonitrile in 19% and 23% yield, respectively. The compounds were fully characterized and the mechanistic rationale is proposed for the formation of the benzensulfonate.

Due to its high morbidity and mortality, myocardial infarction is the leading cause of death worldwide. Against this background, rapid diagnosis is of immense importance. Especially in case of an atypical course, the correct diagnosis may be delayed and thus lead to increased mortality rates. In this report, we present a complex case of acute coronary syndrome. A triple-rule-out CT examination was performed in dual-energy CT (DECT) mode. While pulmonary artery embolism and aortic dissection could be ruled out with conventional CT series, the presence of anterior wall infarction was only detectable on DECT reconstructions. Subsequently, adequate and rapid therapy was then initiated leading to survival of the patient.

Purpose: The purpose of this study was to test the technical feasibility and the impact on the image quality of a deep learning-based super-resolution reconstruction algorithm in 1.5 T abdominopelvic MR imaging. Methods: 44 patients who underwent abdominopelvic MRI were retrospectively included, of which 4 had to be subsequently excluded. After the acquisition of the conventional volume interpolated breath-hold examination (VIBEStd), images underwent postprocessing, using a deep learning-based iterative denoising super-resolution reconstruction algorithm for partial Fourier acquisitions (VIBESR). Image analysis of 40 patients with a mean age of 56 years (range 18–84 years) was performed qualitatively by two radiologists independently using a Likert scale ranging from 1 to 5, where 5 was considered the best rating. Results: Image analysis showed an improvement of image quality, noise, sharpness of the organs and lymph nodes, and sharpness of the intestine for pre- and postcontrast images in VIBESR compared to VIBEStd (each p < 0.001). Lesion detectability was better for VIBESR (p < 0.001), while there were no differences concerning the number of lesions. Average acquisition time was 16 s (±1) for the upper abdomen and 15 s (±1) for the pelvis for VIBEStd, and 15 s (±1) for the upper abdomen and 14 s (±1) for the pelvis for VIBESR. Conclusion: This study demonstrated the technical feasibility of a deep learning-based super-resolution algorithm including partial Fourier technique in abdominopelvic MR images and illustrated a significant improvement of image quality, noise, and sharpness while reducing TA.

Reaction of 4-oxo-3,4-dihydroquinazoline-2-carbaldehyde with hydroxylamine hydrochloride (1.1 equiv) in the presence of K2CO3 (1 equiv) gave (E)-4-oxo-3,4-dihydroquinazoline-2-carbaldehyde oxime (8) in 58% yield. The compound was fully characterized and the conformation of the oxime was supported by single crystal x-ray diffractometry.

Developing risk assessment tools for CAD prediction remains challenging nowadays. We developed an ML predictive algorithm based on metabolic and clinical data for determining the severity of CAD, as assessed via the SYNTAX score. Analytical methods were developed to determine serum blood levels of specific ceramides, acyl-carnitines, fatty acids, and proteins such as galectin-3, adiponectin, and APOB/APOA1 ratio. Patients were grouped into: obstructive CAD (SS > 0) and non-obstructive CAD (SS = 0). A risk prediction algorithm (boosted ensemble algorithm XGBoost) was developed by combining clinical characteristics with established and novel biomarkers to identify patients at high risk for complex CAD. The study population comprised 958 patients (CorLipid trial (NCT04580173)), with no prior CAD, who underwent coronary angiography. Of them, 533 (55.6%) suffered ACS, 170 (17.7%) presented with NSTEMI, 222 (23.2%) with STEMI, and 141 (14.7%) with unstable angina. Of the total sample, 681 (71%) had obstructive CAD. The algorithm dataset was 73 biochemical parameters and metabolic biomarkers as well as anthropometric and medical history variables. The performance of the XGBoost algorithm had an AUC value of 0.725 (95% CI: 0.691–0.759). Thus, a ML model incorporating clinical features in addition to certain metabolic features can estimate the pre-test likelihood of obstructive CAD.

Reaction of 4,5,6-trichloropyrimidine-2-carbonitrile (1) with concentrated sulfuric acid at ca. 20 °C gave 4,5,6-trichloropyrimidine-2-carboxamide (5) in 91% yield. The new compound was fully characterized by IR, MALDI-TOF, NMR and elemental analysis.

The reaction of tetracyanoethylene (TCNE) with HCl (g) in the presence of Sn (1 equiv) and AcOH resulted in 2-amino-5-chloro-1H-pyrrole-3,4-dicarbonitrile in a 74% yield. The compound was fully characterized.

The reaction of 3,5-dichloro-4H-1,2,6-thiadiazin-4-one with (R) and (S)-1,3-dimethylpiperazines (1 equiv), in THF, at ca. 20 °C gives (R) and (S)-3-chloro-5-(2,4-dimethylpiperazin-1-yl)-4H-1,2,6-thiadiazin-4-ones in 70% and 68% yields, respectively. The new compounds were fully characterized.

Reaction of 3,5-dichloro-4H-1,2,6-thiadiazin-4-one with (R) and (S)-3-methylmorpholines (2 equiv), in THF, at ca. 20 °C gave (R) and (S)-3-chloro-5-(3-methylmorpholino)-4H-1,2,6-thiadiazin-4-ones in 95 and 97% yields, respectively. The new compounds were fully characterized.

MicroRNAs (miRNAs) create systems networks and gene-expression circuits through molecular signaling and cell interactions that contribute to health imbalance and the emergence of cardiovascular disorders (CVDs). Because the clinical phenotypes of CVD patients present a diversity in their pathophysiology and heterogeneity at the molecular level, it is essential to establish genomic signatures to delineate multifactorial correlations, and to unveil the variability seen in therapeutic intervention outcomes. The clinically validated miRNA biomarkers, along with the relevant SNPs identified, have to be suitably implemented in the clinical setting in order to enhance patient stratification capacity, to contribute to a better understanding of the underlying pathophysiological mechanisms, to guide the selection of innovative therapeutic schemes, and to identify innovative drugs and delivery systems. In this article, the miRNA–gene networks and the genomic signatures resulting from the SNPs will be analyzed as a method of highlighting specific gene-signaling circuits as sources of molecular knowledge which is relevant to CVDs. In concordance with this concept, and as a case study, the design of the clinical trial GESS (NCT03150680) is referenced. The latter is presented in a manner to provide a direction for the improvement of the implementation of pharmacogenomics and precision cardiovascular medicine trials.

The implications of the adult congenital heart disease anatomic and physiological classification (AP-ACHD) for risk assessment have not been adequately studied. A retrospective cohort study was conducted using data from an ongoing national, multicentre registry of patients with ACHD and atrial arrhythmias (AA) receiving apixaban (PROTECT-AR study, NCT03854149). At enrollment, patients were stratified according to Anatomic class (AnatC, range I to III) and physiological stage (PhyS, range B to D). A follow-up was conducted between May 2019 and September 2021. The primary outcome was a composite of death from any cause, any major thromboembolic event, major or clinically relevant non-major bleeding, or hospitalization. Cox proportional-hazards regression modeling was used to evaluate the risks for the outcome among AP-ACHD classes. Over a median 20-month follow-up period, 47 of 157 (29.9%) ACHD patients with AA experienced the composite outcome. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for the outcome in PhyS C and PhyS D were 1.79 (95% CI 0.69 to 4.67) and 8.15 (95% CI 1.52 to 43.59), respectively, as compared with PhyS B. The corresponding aHRs in AnatC II and AnatC III were 1.12 (95% CI 0.37 to 3.41) and 1.06 (95% CI 0.24 to 4.63), respectively, as compared with AnatC I. In conclusion, the PhyS component of the AP-ACHD classification was an independent predictor of net adverse clinical events among ACHD patients with AA.

Recent studies support that acylcarnitines exert a significant role in cardiovascular disease development and progression. The aim of this metabolomics-based study was to investigate the association of serum acylcarnitine levels with coronary artery disease (CAD) severity, as assessed via SYNTAX Score. Within the context of the prospective CorLipid trial (NCT04580173), the levels of 13 circulating acylcarnitines were accurately determined through a newly developed HILIC-MS/MS method in 958 patients undergoing coronary angiography in the AHEPA University Hospital of Thessaloniki, Greece. Patients presenting with acute coronary syndrome had significantly lower median acylcarnitine C8, C10, C16, C18:1 and C18:2 values, compared to patients with chronic coronary syndrome (p = 0.012, 0.007, 0.018, 0.011 and p = 0.026), while median C10, C16, C18:1 and C18:2 levels were higher in stable angina compared to STEMI (p = 0.019 p = 0.012, p = 0.013 and p < 0.001, respectively). Moreover, median C2, C3, C4 and C8 levels were significantly elevated in patients with diabetes mellitus (p < 0.001, p-values less than 0.05). With regard to CAD severity, median C4 and C5 levels were elevated and C16 and C18:2 levels were reduced in the high CAD complexity group with SYNTAX Score > 22 (p = 0.002, 0.024, 0.044 and 0.012, respectively), indicating a potential prognostic capability of those metabolites and of the ratio C4/C18:2 for the prediction of CAD severity. In conclusion, serum acylcarnitines could serve as clinically useful biomarkers leading to a more individualized management of patients with CAD, once further clinically oriented metabolomics-based studies provide similar evidence.

(1) Background: To evaluate the effects of an AI-based denoising post-processing software solution in low-dose whole-body computer tomography (WBCT) stagings; (2) Methods: From 1 January 2019 to 1 January 2021, we retrospectively included biometrically matching melanoma patients with clinically indicated WBCT staging from two scanners. The scans were reconstructed using weighted filtered back-projection (wFBP) and Advanced Modeled Iterative Reconstruction strength 2 (ADMIRE 2) at 100% and simulated 50%, 40%, and 30% radiation doses. Each dataset was post-processed using a novel denoising software solution. Five blinded radiologists independently scored subjective image quality twice with 6 weeks between readings. Inter-rater agreement and intra-rater reliability were determined with an intraclass correlation coefficient (ICC). An adequately corrected mixed-effects analysis was used to compare objective and subjective image quality. Multiple linear regression measured the contribution of “Radiation Dose”, “Scanner”, “Mode”, “Rater”, and “Timepoint” to image quality. Consistent regions of interest (ROI) measured noise for objective image quality; (3) Results: With good–excellent inter-rater agreement and intra-rater reliability (Timepoint 1: ICC ≥ 0.82, 95% CI 0.74–0.88; Timepoint 2: ICC ≥ 0.86, 95% CI 0.80–0.91; Timepoint 1 vs. 2: ICC ≥ 0.84, 95% CI 0.78–0.90; all p ≤ 0.001), subjective image quality deteriorated significantly below 100% for wFBP and ADMIRE 2 but remained good–excellent for the post-processed images, regardless of input (p ≤ 0.002). In regression analysis, significant increases in subjective image quality were only observed for higher radiation doses (≥0.78, 95%CI 0.63–0.93; p < 0.001), as well as for the post-processed images (≥2.88, 95%CI 2.72–3.03, p < 0.001). All post-processed images had significantly lower image noise than their standard counterparts (p < 0.001), with no differences between the post-processed images themselves. (4) Conclusions: The investigated AI post-processing software solution produces diagnostic images as low as 30% of the initial radiation dose (3.13 ± 0.75 mSv), regardless of scanner type or reconstruction method. Therefore, it might help limit patient radiation exposure, especially in the setting of repeated whole-body staging examinations.

Micro-computed tomography (micro-CT) is a promising novel medical imaging modality that allows for non-destructive volumetric imaging of surgical tissue specimens at high spatial resolution. The aim of this study is to provide a comprehensive assessment of the clinical applications of micro-CT for the tissue-based diagnosis of lung diseases. This scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews, aiming to include every clinical study reporting on micro-CT imaging of human lung tissues. A literature search yielded 570 candidate articles, out of which 37 were finally included in the review. Of the selected studies, 9 studies explored via micro-CT imaging the morphology and anatomy of normal human lung tissue; 21 studies investigated microanatomic pulmonary alterations due to obstructive or restrictive lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis; and 7 studies examined the utility of micro-CT imaging in assessing lung cancer lesions (n = 4) or in transplantation-related pulmonary alterations (n = 3). The selected studies reported that micro-CT could successfully detect several lung diseases providing three-dimensional images of greater detail and resolution than routine optical slide microscopy, and could additionally provide valuable volumetric insight in both restrictive and obstructive lung diseases. In conclusion, micro-CT-based volumetric measurements and qualitative evaluations of pulmonary tissue structures can be utilized for the clinical management of a variety of lung diseases. With micro-CT devices becoming more accessible, the technology has the potential to establish itself as a core diagnostic imaging modality in pathology and to enable integrated histopathologic and radiologic assessment of lung cancer and other lung diseases.

The rat model is a common model for intervertebral disc (IVD) and spinal research. However, complications remain challenging. Standard Operating Procedures (SOPs) are validated methods to minimize complications and improve safety and quality of studies. However, a SOP for rat spinal fusion surgery has been missing until now. Therefore, the aim of the study was to develop a SOP for spinal tail disc surgery in elderly Wistar rats (419.04 ± 54.84 g). An initial preoperative, intraoperative, and postoperative surgical setup, including specific anaesthesia and pain management protocols, was developed. Anaesthesia was induced by subcutaneous injection of a pre-mixture of fentanyl, midazolam, and medetomidin with the addition of 0.5% isoflurane in oxygen and caudal epidural analgesia. The surgery itself consisted of the fixation of a customized external ring fixator with ⌀ 0.8 mm Kirschner wires at the proximal rat tail and a discectomy and replacement with bone morphogenetic protein coated beta-tricalcium-phosphate carrier. The postoperative setup included heating, analgesia with buprenorphine, and meloxicam, as well as special supplementary food. Anaesthesia, surgery, and pain management were sufficient. In the presented optimized SOP, no animals developed any complications. A SOP for spinal surgery in elderly rats in an in vivo spinal fusion model was developed successfully. This novel protocol can improve transparency, reproducibility, and external validity in experimental rat spinal surgery experiments.

Apart from its beneficial effects on cardiovascular risk factors, an anti-inflammatory effect of exercise is strongly implicated. Yet, data regarding the effect of an exercise intervention on healthy individuals are limited and contradictory. The present study aimed to investigate the effects of a physical activity intervention on the soluble form of the receptor for advanced glycation end products (sRAGEs) and its ligands S100A8/A9. A total of 332 young army recruits volunteered and 169 completed the study. The participants underwent the standard basic training of Greek army recruits. IL-6, IL-1β, S100A8/A9, and sRAGEs were measured at the beginning and at the end of the training period. Primary rodent adult aortic smooth muscle cells (ASMCs) were analyzed for responsiveness to direct stimulation with S100A8/A9 alone or in combination with sRAGEs. At the end of the training period, we observed a statistically significant reduction in S100A8/A9 (630.98 vs. 472.12 ng/mL, p = 0.001), IL-1β (9.39 [3.8, 44.14] vs. 5.03 [2.44, 27.3] vs. pg/mL, p = 0.001), and sRAGEs (398.38 vs. 220.1 pg/mL, p = 0.001). IL-6 values did not change significantly after exercise. S100A8/A9 reduction was positively correlated with body weight (r = 0.236 [0.095, 0.370], p = 0.002) and BMI (r = 0.221 [0.092, 0.346], p = 0.004). Direct stimulation of ASMCs with S100A8/A9 increased the expression of IL-6, IL-1β, and TNF-α and, in the presence of sRAGEs, demonstrated a dose-dependent inhibition. A 4-week military training resulted in significant reduction in the pro-inflammatory cytokines IL-1β and S100A8/A9 complex. The observed reduction in sRAGEs may possibly reflect diminished RAGE axis activation. Altogether, our findings support the anti-inflammatory properties of physical activity.

Aortic diseases comprise aneurysms, dissections, and several other pathologies. In general, aging is associated with a slow but progressive dilation of the aorta, along with increased stiffness and pulse pressure. The progression of aortic disease is characterized by subclinical development or acute presentation. Recent evidence suggests that inflammation participates causally in different clinical manifestations of aortic diseases. As of yet, diagnostic imaging and surveillance is mainly based on ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Little medical therapy is available so far to prevent or treat the majority of aortic diseases. Endovascular therapy by the introduction of covered stentgrafts provides the main treatment option, although open surgery and implantation of synthetic grafts remain necessary in many situations. Because of the risks associated with surgery, there is a need for identification of pharmaceutical targets interfering with the pathophysiology of aortic remodeling. The participation of innate immunity and inflammasome activation in different cell types is common in aortic diseases. This review will thus focus on inflammasome activities in vascular cells of different chronic and acute aortic diseases and discuss their role in development and progression. We will also identify research gaps and suggest promising therapeutic targets, which may be used for future medical interventions.

Several imaging techniques are used in biological and biomedical studies. Micro-computed tomography (micro-CT) is a non-destructive imaging technique that allows the rapid digitisation of internal and external structures of a sample in three dimensions and with great resolution. In this review, the strengths and weaknesses of some common imaging techniques applied in biological and biomedical fields, such as optical microscopy, confocal laser scanning microscopy, and scanning electron microscopy, are presented and compared with the micro-CT technique through five use cases. Finally, the ability of micro-CT to create non-destructively 3D anatomical and morphological data in sub-micron resolution and the necessity to develop complementary methods with other imaging techniques, in order to overcome limitations caused by each technique, is emphasised.