Vein graft disease in a knockout mouse model of hyperhomocysteinaemia

A major reason for vein graft failure after coronary artery bypass grafting is neointimal hyperplasia and thrombosis. Elevated serum levels of homocysteine (Hcy) are associated with higher incidence of cardiovascular disease, but homocysteine levels also tend to increase during the first weeks or months after cardiac surgery. To investigate this further, C57BL/6J mice (WT) and cystathionine‐beta‐synthase heterozygous knockout mice (CBS+/?), a mouse model for hyperhomocysteinaemia, underwent interposition of the vena cava of donor mice into the carotid artery of recipient mice. Two experimental groups were examined: 20 mice of each group underwent bypass surgery (group 1: WT donor and WT recipient; group 2: CBS+/? donor and CBS+/? recipient). After 4 weeks, the veins were harvested, dehydrated, paraffin‐embedded, stained and analysed by histomorphology and immunohistochemistry. Additionally, serum Hcy levels in CBS knockout animals and in WT animals before and after bypass surgery were measured. At 4 weeks postoperatively, group 2 mice showed a higher percentage of thrombosis compared to controls, a threefold increase in neointima formation, higher general vascularization, a lower percentage of elastic fibres with shortage and fragmentation in the neointima, a lower percentage of acid mucopolysaccharides in the neointima and a more intense fibrosis in the neointima and media. In conclusion, hyperhomocysteinaemic cystathionine‐beta‐synthase knockout mice can play an important role in the study of mechanisms of vein graft failure. But further in vitro and in vivo studies are necessary to answer the question whether or not homocysteine itself or a related metabolic factor is the key aetiologic agent for accelerated vein graft disease.     

Simulation of dental collisions and occlusal dynamics in the virtual environment

Semi‐adjustable articulators have often been used to simulate occlusal dynamics, but advances in intra‐oral scanning and computer software now enable dynamics to be modelled mathematically. Computer simulation of occlusal dynamics requires accurate virtual casts, records to register them and methods to handle mesh collisions during movement. Here, physical casts in a semi‐adjustable articulator were scanned with a conventional clinical intra‐oral scanner. A coordinate measuring machine was used to index their positions in intercuspation, protrusion, right and left laterotrusion, and to model features of the articulator. Penetrations between the indexed meshes were identified and resolved using restitution forces, and the final registrations were verified by distance measurements between dental landmarks at multiple sites. These sites were confirmed as closely approximating via measure‐ments made from homologous transilluminated vinylpolysiloxane interocclusal impressions in the mounted casts. Movements between the indexed positions were simulated with two models in a custom biomechanical software platform. In model DENTAL, 6 degree‐of‐freedom movements were made to minimise deviation from a straight line path and also shaped by dynamic mesh collisions detected and resolved mathematically. In model ARTIC, the paths were further constrained by surfaces matching the control settings of the articulator. Despite these differences, the lower mid‐incisor point paths were very similar in both models. The study suggests that mathematical simulation utilising interocclusal ‘bite’ registrations can closely replicate the primary movements of casts mounted in a semi‐adjustable articulator. Additional indexing positions and appropriate software could, in some situations, replace the need for mechanical semi‐adjustable articulation and/or its virtual representation.     

The Hea/r/tist Part: Turning the Point of Mothering Toward 100%

In this Defining Moments essay, I story the a/r/tographical practice of coming to understand who I am as a mother, artist, researcher, and teacher in the face of my experiences with infertility, pregnancy loss, and the death of my son Milo. Through living inquiry and artistically capturing the turning points that have defined me over time, I make sense of what it means to do hea/r/t work as I engage compassionate love alongside those I mother.     

Highly accelerated,real‐time phase‐contrast MRI using radial k‐space sampling and GROG‐GRASP reconstruction: a feasibility study in pediatric patients with congenital heart disease

Retrospective electrocardiogram‐gated, 2D phase‐contrast (PC) flow MRI is routinely used in clinical evaluation of valvular/vascular disease in pediatric patients with congenital heart disease (CHD). In patients not requiring general anesthesia, clinical standard PC is conducted with free breathing for several minutes per slice with averaging. In younger patients under general anesthesia, clinical standard PC is conducted with breath‐holding. One approach to overcome this limitation is using either navigator gating or self‐navigation of respiratory motion, at the expense of lengthening scan times. An alternative approach is using highly accelerated, free‐breathing, real‐time PC (rt‐PC) MRI, which to date has not been evaluated in CHD patients. The purpose of this study was to develop a 38.4‐fold accelerated 2D rt‐PC pulse sequence using radial k‐space sampling and compressed sensing with 1.5 × 1.5 × 6.0 mm³ nominal spatial resolution and 40 ms nominal temporal resolution, and evaluate whether it is capable of accurately measuring flow in 17 pediatric patients (aortic valve, pulmonary valve, right and left pulmonary arteries) compared with clinical standard 2D PC (either breath‐hold or free breathing). For clinical translation, we implemented an integrated reconstruction pipeline capable of producing DICOMs of the order of 2 min per time series (46 frames). In terms of association, forward volume, backward volume, regurgitant fraction, and peak velocity at peak systole measured with standard PC and rt‐PC were strongly correlated (R² > 0.76; P < 0.001). Compared with clinical standard PC, in terms of agreement, forward volume (mean difference = 1.4% (3.0% of mean)) and regurgitant fraction (mean difference = ?2.5%) were in good agreement, whereas backward volume (mean difference = ?1.1 mL (28.2% of mean)) and peak‐velocity at peak systole (mean difference = ?21.3 cm/s (17.2% of mean)) were underestimated by rt‐PC. This study demonstrates that the proposed rt‐PC with the said spatial resolution and temporal resolution produces relatively accurate forward volumes and regurgitant fractions but underestimates backward volumes and peak velocities at peak systole in pediatric patients with CHD.     

Migraine and the Risk for Stroke and Cardiovascular Disease

Numerous data have pointed to an association between migraine and cardiovascular diseases. The majority of the available data have indicated that migraine with aura can be considered a risk factor for ischemic stroke, whereas migraine without aura cannot be reliably considered as such. High frequency of attacks and a recent onset of migraine have been related to an increased ischemic stroke risk. In addition, in young subjects with ischemic stroke migraine with aura represents an independent risk factor of overall recurrent vascular events and of recurrent ischemic stroke. Also the risk of transient ischemic attack seems to be increased in migraineurs, although this issue has not been extensively investigated. Several studies have also addressed the possible association between migraine and hemorrhagic stroke. Although the results of these individual studies were conflicting, their meta-analysis showed that migraine is associated with a 1.5-fold increase in the risk of hemorrhagic stroke (including intracerebral and subarachnoid hemorrhage). Some studies have identified migraine also as a possible risk factor for cardiac vascular events while others have yielded negative results. A meta-analysis did not show an increased risk of myocardial infarction in subjects with any migraine vs no migraine but subsequently, data has pointed to an association between any migraine with cardiac ischemic disease. Migraine has also been associated by some studies with vascular mortality and with vascular diseases in regions other than the brain and the heart. Several studies have also indicated that compared with nonmigraineurs, migraineurs have a higher burden of asymptomatic white matter brain lesions and, according to some studies, also infarct-like lesions at brain magnetic resonance. The mechanisms underlying the relationship between migraine and cardiovascular disease are still unclear. The possible explanation may rely on a peculiar vascular vulnerability of migraineurs that may contribute to the pathogenesis of migraine and, in the presence of some other unknown factors may also contribute, over time, to the development of cardiovascular disease. At the moment, there are no reliable features that may indicate which subjects, across the overall migraine population, will develop vascular events and so far, no drugs are recommended for the vascular prevention in migraineurs unless other clear indications are present. In general, the acute treatment and the secondary prevention measures of a patient with stroke who has a history of migraine do not differ from that of other stroke patients. There is currently no direct evidence to support that a migraine prophylactic treatment will reduce future stroke risk in secondary prevention.     

Neuroarchitecture of the central complex of the desert locust: Tangential neurons

The central complex (CX) comprises a group of midline neuropils in the insect brain, consisting of the protocerebral bridge (PB), the upper (CBU) and lower division (CBL) of the central body and a pair of globular noduli. It receives prominent input from the visual system and plays a major role in spatial orientation of the animals. Vertical slices and horizontal layers of the CX are formed by columnar, tangential, and pontine neurons. While pontine and columnar neurons have been analyzed in detail, especially in the fruit fly and desert locust, understanding of the organization of tangential cells is still rudimentary. As a basis for future functional studies, we have studied the morphologies of tangential neurons of the CX of the desert locust Schistocerca gregaria. Intracellular dye injections revealed 43 different types of tangential neuron, 8 of the PB, 5 of the CBL, 24 of the CBU, 2 of the noduli, and 4 innervating multiple substructures. Cell bodies of these neurons were located in 11 different clusters in the cell body rind. Judging from the presence of fine versus beaded terminals, the vast majority of these neurons provide input into the CX, especially from the lateral complex (LX), the superior protocerebrum, the posterior slope, and other surrounding brain areas, but not directly from the mushroom bodies. Connections are largely subunit- and partly layer-specific. No direct connections were found between the CBU and the CBL. Instead, both subdivisions are connected in parallel with the PB and distinct layers of the noduli.