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

Functional disconnection of the substantia nigra pars compacta from the pedunculopontine nucleus impairs learning of a conditioned avoidance task

The pedunculopontine tegmental nucleus (PPTg) targets nuclei in the basal ganglia, including the substantia nigra pars compacta (SNc), in which neuronal loss occurs in Parkinson's disease, a condition in which patients show cognitive as well as motor disturbances. Partial loss and functional abnormalities of neurons in the PPTg are also associated with Parkinson's disease. We hypothesized that the interaction of PPTg and SNc might be important for cognitive impairments and so investigated whether disrupting the connections between the PPTg and SNc impaired learning of a conditioned avoidance response (CAR) by male Wistar rats. The following groups were tested: PPTg unilateral; SNc unilateral; PPTg-SNc ipsilateral (ipsilateral lesions in PPTg and SNc); PPTg-SNc contralateral (contralateral lesions in PPTg and SNc); sham lesions (of each type). SNc lesions were made with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine HCl (MPTP, 0.6micromol); PPTg lesions with ibotenate (24nmol). After recovery, all rats underwent 50-trial sessions of 2-way active avoidance conditioning for 3 consecutive days. Rats with unilateral lesions in PPTg or SNc learnt this, however rats with contralateral (but not ipsilateral) combined lesions in both structures presented no sign of learning. This effect was not likely to be due to sensorimotor impairment because lesions did not affect reaction time to the tone or footshock during conditioning. However, an increased number of non-responses were observed in the rats with contralateral lesions. The results support the hypothesis that a functional interaction between PPTg and SNc is needed for CAR learning and performance

Histoire du livre et de l'imprimé au Canada, Volume I

Étroitement liés à l'histoire du pays que deviendra le Canada, le livre et l'imprimé y ont fait leur apparition dès l'arrivée des premiers colons. Outils d'évangélisation, de colonisation, d'enseignement, de propagande religieuse et politique, mais aussi moyens d'exploration, de connaissance, de libération, le livre et l'imprimé ont contribué à la création d'une histoire nationale et à la construction de l'identité des peuples qui se côtoient désormais sur le territoire. Ce premier volume de l'Histoire du livre et de l'imprimé au Canada retrace le parcours de l'imprimé, depuis le débarquement des premiers colons en Nouvelle-France jusqu'aux Rébellions de 1837 et de 1838, en passant par l'apparition du premier imprimé à Halifax en 1752 et la constitution des premières bibliothèques publiques et privées. Il démontre avec clarté que l'imprimé sous toutes ses formes, que ce soit les placards, journaux, almanachs, illustrés, livres de cuisine ou ouvrages d'érudition, a fait partie intégrante de la vie quotidienne des Canadiens. Enfin, il dresse un portrait vivant de l'auteur et du lecteur, mais aussi de tous les artisans des métiers du livre et de l'imprimerie, de l'apprenti à l'éditeur imprimeur, en les replaçant dans leur contexte social et historique

A decade of changes in brain volume and cognition

Brain atrophy can occur several decades prior to onset of cognitive impairments. However, few longitudinal studies have examined the relationship between brain volume changes and cognition over a long follow-up period in healthy elderly women. In the present study we investigate the relationship between whole brain and hippocampal atrophy rates and longitudinal changes in cognition, including verbal episodic memory and executive function, in older women. We also examine whether baseline brain volume predicts subsequent changes in cognitive performance over a 10-year period. A total of 60 individuals from the population-based Women’s Healthy Ageing Project with a mean age at baseline of 59 years underwent 3T MRI. Of these, 40 women completed follow-up cognitive assessments, 23 of whom had follow-up MRI scans. Linear regression analysis was used to examine the relationship between brain atrophy and changes in verbal episodic memory and executive function over a 10-year period. The results show that baseline measurements of frontal and temporal grey matter volumes predict changes in verbal episodic memory performance, whereas hippocampal volume at baseline is associated with changes in executive function performance over a 10-year period of follow-ups. In addition, higher whole brain and hippocampal atrophy rates are correlated with a decline in verbal episodic memory. These findings indicate that in addition to atrophy rate, smaller regional grey matter volumes even 10 years prior is associated with increased rates of cognitive decline. This study suggests useful neuroimaging biomarkers for the prediction of cognitive decline in healthy elderly women

Histoire du livre et de l’imprimé au Canada, Volume II

Entre 1840 et 1918, l’imprimé et le livre, qui avaient déjà contribué à l’élaboration de l’histoire et de l’identité du peuple canadien, deviennent désormais les médias de communication prédominants. Plus que jamais la culture de l’imprimé participe aux transformations qui métamorphoseront la colonie en véritable État, unifiant les peuples qui le composent. C’est cette synergie qui constituera l’un des aspects historiques et culturels les plus fascinants de cette période qui est au centre de ce deuxième volume de l’Histoire du livre et de l’imprimé au Canada. L’expansion du territoire canadien grâce à l’immigration massive, sa traversée par le chemin de fer et par la télégraphie renouvellent entièrement la dynamique de l’imprimé, de Terre-Neuve à Dawson City. Après 1880, l’imprimé de masse voit le jour grâce à la nouvelle technologie qui permet d’imprimer plus rapidement et à moindre coût, et grâce à la constitution de nouveaux marchés desservis par les librairies. Du missel au journal en passant par le livre de recette, le catalogue d’Eaton et l’almanach, les Canadiens sont dorénavant en contact quotidien avec cet objet matériel qu’est l’imprimé. Dans ce contexte, l’auteur émerge lentement, soutenu par un marché de distribution à l’échelle nord-américaine, par un nombre croissant de bibliothèques publiques et par des droits conquis pour la protection de son œuvre et sa diffusion