Germaine Guèvremont (1900‑1968)

Éloge funèbre de Germaine Guèvremont, écrit en 1969 pour la Société royal

Low TLR7 gene expression in atherosclerotic plaques is associated with major adverse cardio- and cerebrovascular events

AIMS: Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome and to explore the mechanisms linked to TLR7 expression in atherosclerosis. METHODS AND RESULTS: Atherosclerotic plaques were removed by carotid endarterectomy (CEA) and subjected to gene array expression analysis (n = 123). Increased levels of TLR7 transcript in the plaques were associated with better outcome in a follow-up study over a maximum of 8 years. Patients with higher TLR7 transcript levels had a lower risk of experiencing major cardiovascular and cerebrovascular events (MACCE) during the follow-up period after CEA (hazard ratio: 2.38, P = 0.012, 95% CI 1.21–4.67). TLR7 was expressed in all plaques by T cells, macrophages and endothelial cells in capillaries, as shown by immunohistochemistry. In short-term tissue cultures, ex vivo treatment of plaques with the TLR7 ligand imiquimod elicited dose-dependent secretion of IL-10, TNF-α, GM-CSF, and IL-12/IL-23p40. This secretion was blocked with a TLR7 inhibitor. Immunofluorescent tissue analysis after TLR7 stimulation showed IL-10 expression in T cells, macrophages and vascular smooth muscle cells. TLR7 mRNA levels in the plaques were correlated with IL-10 receptor (r = 0.4031, P < 0.0001) and GM-CSF receptor A (r = 0.4354, P < 0.0001) transcripts. CONCLUSION: These findings demonstrate that TLR7 is abundantly expressed in human atherosclerotic plaques. TLR7 ligation elicits the secretion of pro-inflammatory and anti-inflammatory cytokines, and high TLR7 expression in plaques is associated with better patient outcome, suggesting that TLR7 is a potential therapeutic target for prevention of complications of atherosclerosis

Snow Buntings Maintain Winter-Level Cold Endurance While Migrating to the High Arctic

Arctic breeding songbirds migrate early in the spring and can face winter environments requiring cold endurance throughout their journey. One such species, the snow bunting (Plectrophenax nivalis), is known for its significant thermogenic capacity. Empirical studies suggest that buntings can indeed maintain winter cold acclimatization into the migratory and breeding phenotypes when kept captive on their wintering grounds. This capacity could be advantageous not only for migrating in a cold environment, but also for facing unpredictable Arctic weather on arrival and during preparation for breeding. However, migration also typically leads to declines in the sizes of several body components linked to metabolic performance. As such, buntings could also experience some loss of cold endurance as they migrate. Here, we aimed to determine whether free-living snow buntings maintain a cold acclimatized phenotype during spring migration. Using a multi-year dataset, we compared body composition (body mass, fat stores, and pectoralis muscle thickness), oxygen carrying capacity (hematocrit) and metabolic performance (thermogenic capacity – Msum and maintenance energy expenditure – BMR) of birds captured on their wintering grounds (January–February, Rimouski, QC, 48°N) and during pre-breeding (April–May) in the Arctic (Alert, NU, 82°). Our results show that body mass, fat stores and Msum were similar between the two stages, while hematocrit and pectoralis muscle thickness were lower in pre-breeding birds than in wintering individuals. These results suggest that although tissue degradation during migration may affect flight muscle size, buntings are able to maintain cold endurance (i.e., Msum) up to their Arctic breeding grounds. However, BMR was higher during pre-breeding than during winter, suggesting higher maintenance costs in the Arctic

Tractostorm 2 : Optimizing tractography dissection reproducibility with segmentation protocol dissemination

The segmentation of brain structures is a key component of many neuroimaging studies. Consistent anatomical definitions are crucial to ensure consensus on the position and shape of brain structures, but segmentations are prone to variation in their interpretation and execution. White-matter (WM) pathways are global structures of the brain defined by local landmarks, which leads to anatomical definitions being difficult to convey, learn, or teach. Moreover, the complex shape of WM pathways and their representation using tractography (streamlines) make the design and evaluation of dissection protocols difficult and time-consuming. The first iteration of Tractostorm quantified the variability of a pyramidal tract dissection protocol and compared results between experts in neuroanatomy and nonexperts. Despite virtual dissection being used for decades, in-depth investigations of how learning or practicing such protocols impact dissection results are nonexistent. To begin to fill the gap, we evaluate an online educational tractography course and investigate the impact learning and practicing a dissection protocol has on interrater (groupwise) reproducibility. To generate the required data to quantify reproducibility across raters and time, 20 independent raters performed dissections of three bundles of interest on five Human Connectome Project subjects, each with four timepoints. Our investigation shows that the dissection protocol in conjunction with an online course achieves a high level of reproducibility (between 0.85 and 0.90 for the voxel-based Dice score) for the three bundles of interest and remains stable over time (repetition of the protocol). Suggesting that once raters are familiar with the software and tasks at hand, their interpretation and execution at the group level do not drastically vary. When compared to previous work that used a different method of communication for the protocol, our results show that incorporating a virtual educational session increased reproducibility. Insights from this work may be used to improve the future design of WM pathway dissection protocols and to further inform neuroanatomical definitions.Peer reviewe

Using structured eradication feasibility assessment to prioritize the management of new and emerging invasive alien species in Europe

Prioritizing the management of invasive alien species (IAS) is of global importance and within Europe integral to the EU IAS regulation. To prioritize management effectively, the risks posed by IAS need to be assessed, but so too does the feasibility of their management. While the risk of IAS to the EU has been assessed, the feasibility of management has not. We assessed the feasibility of eradicating 60 new (not yet established) and 35 emerging (established with limited distribution) species that pose a threat to the EU, as identified by horizon scanning. The assessment was carried out by 34 experts in invasion management from across Europe, applying the Non‐Native Risk Management scheme to defined invasion scenarios and eradication strategies for each species, assessing the feasibility of eradication using seven key risk management criteria. Management priorities were identified by combining scores for risk (derived from horizon scanning) and feasibility of eradication. The results show eradication feasibility score and risk score were not correlated, indicating that risk management criteria evaluate different information than risk assessment. In all, 17 new species were identified as particularly high priorities for eradication should they establish in the future, whereas 14 emerging species were identified as priorities for eradication now. A number of species considered highest priority for eradication were terrestrial vertebrates, a group that has been the focus of a number of eradication attempts in Europe. However, eradication priorities also included a diverse range of other taxa (plants, invertebrates and fish) suggesting there is scope to broaden the taxonomic range of attempted eradication in Europe. We demonstrate that broad scale structured assessments of management feasibility can help prioritize IAS for management. Such frameworks are needed to support evidence‐based decision‐making

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes