Multi-Scale Imaging of Vascular Pathologies in Cardiovascular Disease

Cardiovascular disease entails systemic changes in the vasculature. The endothelial cells lining the blood vessels are crucial in the pathogenesis of cardiovascular disease. Healthy endothelial cells direct the blood flow to tissues as vasodilators and act as the systemic interface between the blood and tissues, supplying nutrients for vital organs, and regulating the smooth traffic of leukocytes into tissues. In cardiovascular diseases, when inflammation is sensed, endothelial cells adjust to the local or systemic inflammatory state. As the inflamed vasculature adjusts, changes in the endothelial cells lead to endothelial dysfunction, altered blood flow and permeability, expression of adhesion molecules, vessel wall inflammation, thrombosis, angiogenic processes, and extracellular matrix production at the endothelial cell level. Preclinical multi-scale imaging of these endothelial changes using optical, acoustic, nuclear, MRI, and multimodal techniques has progressed, due to technical advances and enhanced biological understanding on the interaction between immune and endothelial cells. While this review highlights biological processes that are related to changes in the cardiac vasculature during cardiovascular diseases, it also summarizes state-of-the-art vascular imaging techniques. The advantages and disadvantages of the different imaging techniques are highlighted, as well as their principles, methodologies, and preclinical and clinical applications with potential future directions. These multi-scale approaches of vascular imaging carry great potential to further expand our understanding of basic vascular biology, to enable early diagnosis of vascular changes and to provide sensitive diagnostic imaging techniques in the management of cardiovascular disease.

Sex-Specific ADHD-Like Behaviour, Altered Metabolic Functions, and Altered EEG Activity in Sialyltransferase ST3GAL5-Deficient Mice

A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5−/−) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5−/− mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5−/− mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5−/− mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5−/− mice. Together, St3gal5−/− mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.

Virtual embolization for treatment support of intracranial AVMs using an interactive desktop and VR application

Purpose The treatment of intracranial arteriovenous malformations (AVM) is challenging due to their complex anatomy. For this vessel pathology, arteries are directly linked to veins without a capillary bed in between. For endovascular treatment, embolization is carried out, where the arteries that supply the AVM are consecutively blocked. A virtual embolization could support the medical expert in treatment planning. Method We designed and implemented an immersive VR application that allows the visualization of the simulated blood flow by displaying millions of particles. Furthermore, the user can interactively block or unblock arteries that supply the AVM and analyze the altered blood flow based on pre-computed simulations. Results In a pilot study, the application was successfully adapted to three patient-specific cases. We performed a qualitative evaluation with two experienced neuroradiologist who regularly conduct AVM embolizations. The feature of virtually blocking or unblocking feeders was rated highly beneficial, and a desire for the inclusion of quantitative information was formulated. Conclusion The presented application allows for virtual embolization and interactive blood flow visualization in an immersive virtual reality environment. It could serve as useful addition for treatment planning and education in clinical practice, supporting the understanding of AVM topology as well as understanding the influence of the AVM’s feeding arteries.

Common Bean Baked Snack Consumption Reduces Apolipoprotein B-100 Levels: A Randomized Crossover Trial

Snack alternatives based on common beans (Phaseolus vulgaris L.) have been developed to promote pulse consumption. The purpose of this study was to evaluate the chemical composition, sensory acceptance and the effect of common bean baked snack (CBBS) consumption on blood lipid levels in participants with overweight and altered blood lipid levels. A sensory evaluation by 80 untrained judges was carried out using a hedonic scale. A randomized crossover 2 × 2 trial was performed, where 20 participants with overweight and one blood lipid alteration consumed 32 g of CBBS or did not consume it (control) for four weeks. Blood samples were taken to quantify the triglycerides, total cholesterol, LDL-c, HDL-c, ApoB-100, glucose and insulin. Furthermore, anthropometric, dietary and physical activity parameters were recorded. The overall acceptance of CBBS was similar compared to popcorn (p > 0.05). The consumption of CBBS reduced the apolipoprotein B-100 levels (p = 0.008). This reduction could be associated with the additional dietary fiber consumption during the CBBS period (p = 0.04). Although it did not improve any other blood lipid or glucose parameters (p > 0.05), it did not affect them either, which means that the CBBS could be consumed without compromising cardiovascular health.

Management of chronic subdural hematoma: our experience of last seven years

Background: Chronic SDH is collection of altered blood under dura mater which is variably more than 4-6 weeks old. It usually occurs in presence of atrophic brain which usually occurs in chronic alcoholics and in old age. Pathogenetic factors are mild trauma with or without some form of coagulopathy. There are various management options like twist drill and drainage, burr hole with evacuation with or without placement of drain and mini craniotomy. There are specific indications for each procedure with individual variations. We operated 74 patients of chronic SDH in last 7 years and are presenting analysis of our series.Methods: The study is retrospective. We studied records of 74 consecutive patients operated in single unit at our institute from February 2014 to December 2020. Patients with very poor GCS (less than 5) and children are not included in this study.Results: There was no benefit of drainage tube seen in our series of patients in decreasing incidence of residual collection.Conclusions: Timely intervention in case of chronic SDH is very gratifying in view of improvement of GCS and motor deficit without much effect of the type of procedure performed. Burr hole evacuation is the procedure of choice. Placement of drainage tube in subdural space is not effective in decreasing the incidence of residual collection. But it is very helpful in management of residual/recurrent collections.

1266 Digital Rectal Examination: Do You Still Put Your Foot in It If You Don’t Put Your Finger in It?

Introduction Most surgical trainees are familiar with the aphorism ‘if you don’t put your finger in it, you put your foot in it’, with regards to digital rectal examination (DRE). This commonly taught maxim, attributed to Bailey and Love in their Short Practice of Surgery, was coined to highlight the folly of neglecting DRE in patients with histories suggestive of malignant anorectal pathology. However, data are lacking on the diagnostic yield of DRE for detecting anorectal cancer in patients with lower gastrointestinal bleeding (LGIB), whilst advances in biomarker and imaging technology beg the question: is there still a role for DRE in the assessment of patients with LGIB? Method We designed a clinical coding search strategy to identify all adult patients with acute LGIB referred to general surgery at a UK university hospital from January to July 2020. Electronic patient records were interrogated to identify history and examination findings, diagnoses and clinical outcomes. Results 169 patients (median age 63 (16-94) years, 54.4% male) were identified, 74.6% (126/169) with bright red bleeding, 23.7% (40/169) with altered blood and 1.8% (3/169) with melaena. DRE was performed in 91.1% (154/169) of patients, identifying blood in 42.9% (66/154) of cases and suspicious lesions, which were subsequently confirmed as anorectal malignancy, in 1.3% (2/154). Conclusions DRE represents a possibly stigmatising and uncomfortable examination for patients and clinicians alike. These data support the utility of DRE in patients with LGIB and may inform the discussion at the bedside to facilitate the timely diagnosis of anorectal malignancy.

Thrombo-Inflammation: A Focus on NTPDase1/CD39

There is increasing evidence for a link between inflammation and thrombosis. Following tissue injury, vascular endothelium becomes activated, losing its antithrombotic properties whereas inflammatory mediators build up a prothrombotic environment. Platelets are the first elements to be activated following endothelial damage; they participate in physiological haemostasis, but also in inflammatory and thrombotic events occurring in an injured tissue. While physiological haemostasis develops rapidly to prevent excessive blood loss in the endothelium activated by inflammation, hypoxia or by altered blood flow, thrombosis develops slowly. Activated platelets release the content of their granules, including ATP and ADP released from their dense granules. Ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39 dephosphorylates ATP to ADP and to AMP, which in turn, is hydrolysed to adenosine by ecto-5′-nucleotidase (CD73). NTPDase1/CD39 has emerged has an important molecule in the vasculature and on platelet surfaces; it limits thrombotic events and contributes to maintain the antithrombotic properties of endothelium. The aim of the present review is to provide an overview of platelets as cellular elements interfacing haemostasis and inflammation, with a particular focus on the emerging role of NTPDase1/CD39 in controlling both processes.

SARS-CoV-2 Neurotropism and Single Cell Responses in Brain Organoids Containing Innately Developing Microglia

Neuropsychiatric manifestations are common in both acute and post-acute phase of SARS-CoV-2 infection, but the mechanism of these effects is unknown. Here, we derive human brain organoids with innately developing microglia to investigate the cellular responses to SARS-CoV-2 infection on a single cell level. We find evidence of limited tropism to SARS-CoV-2 and observe extensive neuronal cell death that also include non-infected cells. Single cell transcriptome profiling reveals distinct responses in microglia and astrocytes that share features with cellular states observed in neurodegenerative diseases, includes upregulation of genes with relevance for synaptic stripping, and suggests altered blood brain barrier integrity. Across all cell types, we observe a global translational shut-down as well as altered carbohydrate metabolism and cellular respiration. Together, our findings provide insights into cellular responses of the resident brain immune cells to SARS-CoV-2 and pinpoint mechanisms that may be of relevance for the neuropathological changes observed in COVID-19 patients.