Phenotype Presentation and Molecular Diagnostic Yield in Non-5q Spinal Muscular Atrophy

BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) is mainly caused by homozygous SMN1 gene deletions on 5q13. Non-5q SMA patients' series are lacking, and the diagnostic yield of next-generation sequencing (NGS) is largely unknown. The aim of this study was to describe the clinical and genetic landscape of non-5q SMA and evaluate the performance of neuropathy gene panels in these disorders. METHODS: Description of patients with non-5q SMA followed in the different neuromuscular reference centers in France as well as in London, United Kingdom. Patients without a genetic diagnosis had undergone at least a neuropathy or large neuromuscular gene panel. RESULTS: Seventy-one patients from 65 different families were included, mostly sporadic cases (60.6%). At presentation, 21 patients (29.6%) showed exclusive proximal weakness (P-SMA), 35 (49.3%) showed associated distal weakness (PD-SMA), and 15 (21.1%) a scapuloperoneal phenotype (SP-SMA). Thirty-two patients (45.1%) had a genetic diagnosis: BICD2 (n = 9), DYNC1H1 (n = 7), TRPV4 (n = 4), VCP, HSBP1, AR (n = 2), VRK1, DNAJB2, MORC2, ASAH1, HEXB, and unexpectedly, COL6A3 (n = 1). The genetic diagnostic yield was lowest in P-SMA (6/21, 28.6%) compared with PD-SMA (16/35, 45.7%) and SP-SMA (10/15, 66.7%). An earlier disease onset and a family history of the disease or consanguinity were independent predictors of a positive genetic diagnosis. Neuropathy gene panels were performed in 59 patients with a 32.2% diagnostic yield (19/59). In 13 additional patients, a genetic diagnosis was achieved through individual gene sequencing or an alternative neuromuscular NGS. DISCUSSION: Non-5q SMA is genetically heterogeneous, and neuropathy gene panels achieve a molecular diagnosis in one-third of the patients. The diagnostic yield can be increased by sequencing of other neuromuscular and neurometabolic genes. Nevertheless, there is an unmet need to cluster these patients to aid in the identification of new genes

Development of a primary cell model derived from porcine dorsal soft palate for foot-and-mouth disease virus research and diagnosis

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals that has a significant socio-economic impact. One concern associated with this disease is the ability of its etiological agent, the FMD virus (FMDV), to persist in its hosts through underlying mechanisms that remain to be elucidated. While persistence has been described in cattle and small ruminants, it is unlikely to occur in pigs. One of the factors limiting the progress in understanding FMDV persistence and, in particular, differential persistence is the lack of suitable in vitro models. A primary bovine cell model derived from the dorsal soft palate, which is the primary site of replication and persistence of FMDV in cattle, has been developed, and it seemed relevant to develop a similar porcine model. Cells from two sites of FMDV replication in pigs, namely, the dorsal soft palate and the oropharyngeal tonsils, were isolated and cultured. The epithelial character of the cells from the dorsal soft palate was then assessed by immunofluorescence. The FMDV-sensitivity of these cells was assessed after monolayer infection with FMDV O/FRA/1/2001 Clone 2.2. These cells were also grown in multilayers at the air-liquid interface to mimic a stratified epithelium susceptible to FMDV infection. Consistent with what has been shown in vivo in pigs, our study showed no evidence of persistence of FMDV in either the monolayer or multilayer model, with no infectious virus detected 28 days after infection. The development of such a model opens up new possibilities for the study and diagnosis of FMDV in porcine cells

The prevention and management of chronic disease in primary care: recommendations from a knowledge translation meeting

BACKGROUND: Seven chronic disease prevention and management programs were implemented across Quebec with funding support from a provincial-private industry funding initiative. Given the complexity of implementing integrated primary care chronic disease management programs, a knowledge transfer meeting was held to share experiences across programs and synthesize common challenges and success factors for implementation. METHODS: The knowledge translation meeting was held in February 2014 in Montreal, Canada. Seventy-five participants consisting of 15 clinicians, 14 researchers, 31 knowledge users, and 15 representatives from the funding agencies were broken up into groups of 10 or 11 and conducted a strengths, weaknesses, opportunities, and threats analysis on either the implementation or the evaluation of these chronic disease management programs. Results were reported back to the larger group during a plenary and recorded. Audiotapes were transcribed and summarized using pragmatic thematic analysis. RESULTS AND DISCUSSION: Strengths to leverage for the implementation of the seven programs include: (1) synergy between clinical and research teams; (2) stakeholders working together; (3) motivation of clinicians; and (4) the fact that the programs are evidence-based. Weaknesses to address include: (1) insufficient resources; (2) organizational change within the clinical sites; (3) lack of referrals from primary care physicians; and (4) lack of access to programs. Strengths to leverage for the evaluation of these programs include: (1) engagement of stakeholders and (2) sharing of knowledge between clinical sites. Weaknesses to address include: (1) lack of referrals; (2) difficulties with data collection; and (3) difficulties in identifying indicators and control groups. Opportunities for both themes include: (1) fostering new and existing partnerships and stakeholder relations; (2) seizing funding opportunities; (3) knowledge transfer; (4) supporting the transformation of professional roles; (5) expand the use of health information technology; and (6) conduct cost evaluations. Fifteen recommendations related to mobilisation of primary care physicians, support for the transformation of professional roles, and strategies aimed at facilitating the implementation and evaluation of chronic disease management programs were formulated based on the discussions at this knowledge translation event. CONCLUSION: The results from this knowledge translation day will help inform the sustainability of these seven chronic disease management programs in Quebec and the implementation and evaluation of similar programs elsewhere

Towards the development of ecosystem-based indicators of mangroves functioning state in the context of the EU water framework directive

European Water Framework Directive is enforced in five tropical French Oversea Territories where mangroves are present. Developing bioindication tools to support the ecosystem-based management approach of the Directive is needed. A series of expert workshops was organized and led to the proposal of a strategy and of an applied research program to develop bioindication tools. The proceedings of the workshops are presented as a case study, as this is the first time such an integrative ecosystem-based approach is proposed in mangroves, combining structural and functional aspects, from forest structure to benthic community functioning

Sources manuscrites/sources publiées: La mission de la CMS au Buganda (1876-1900)

Note : la présentation de ce travail lors du séminaire du 2 décembre était plus illustrée – j’avais pu montrer les photos des sources manuscrites, ce que je ne peux pas faire sur le blog, en raison des droits d’images qui ne m’ont toujours pas été accordés par la CMS. Je souhaite dans ce billet détailler comment la confrontation de deux types de sources, les sources manuscrites et les sources publiées, a orienté la problématique de mon sujet thèse, fait jaillir de nouveaux thèmes et a posé de..

Les usages de la malédiction de Cham dans les débats sur l’abolition de l’esclavage

L’histoire des usages de la malédiction de Cham permet de suivre les itinéraires sinueux qu’a pu prendre l’idée d’un « lignage stigmatisé » dans les discours coloniaux, notamment dans les débats sur l’abolition de l’esclavage qui ont secoué l’espace anglophone au XIXe siècle. La malédiction de Cham fit l’objet d’interprétations diverses dès l’Antiquité et le Moyen-Âge, de la part d’intellectuels chrétiens, juifs et musulmans. Comme le résume Benjamin Braude dans un article de 2002 qui s’app..

« Missionnaires britanniques et race : la Church Missionary Society au Buganda, ca. 1860-ca. 1910 »

International audienc

Tutoriels Zotero

Des tutoriels vidéo pour nous apprendre à installer et utiliser le logiciel bibliographique gratuit Zotero: http://alopensource.blogspot.com/2010/11/zotero-en-video.htm

The Missionary and the Anthropologist: The Intellectual Friendship and Scientific Collaboration of the Reverend John Roscoe (CMS) and James G. Frazer, 1896–1932

International audienc

Sources manuscrites/sources publiées: La mission de la CMS au Buganda (1876-1900)

Note : la présentation de ce travail lors du séminaire du 2 décembre était plus illustrée – j’avais pu montrer les photos des sources manuscrites, ce que je ne peux pas faire sur le blog, en raison des droits d’images qui ne m’ont toujours pas été accordés par la CMS. Je souhaite dans ce billet détailler comment la confrontation de deux types de sources, les sources manuscrites et les sources publiées, a orienté la problématique de mon sujet thèse, fait jaillir de nouveaux thèmes et a posé de..