Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Primary vertebral osteosarcoma: Five cases

Primary vertebral osteosarcoma is a rare type of osteosarcoma, differing from the appendicular forms by an incidence peak occurring at a higher age and a poorer prognosis, due to the difficulties of the surgical treatment. We present five cases of histologically proven primary vertebral osteosarcomas followed in our institution between 2004 and 2012. They allow to illustrate some essential radiologic features, useful to evoke this rare entity.     

Analytical validation of anti-toxoplasma IgG immunoassays

There are often discrepancies when using different methods to measure anti-Toxoplasma gondii IgG levels in patient samples. The diagnostic performance of a chemiluminescent immunoassay (CLIA) and an enzyme-linked fluorescent assay (ELFA) used as confirmatory tests for samples identified as positive or equivocal by an electrochemiluminescent immunoassay (ECLIA) were examined. Cut-off values were those stated by the manufacturer, and Western blot was used to confirm the results of all methods. All samples identified as positive by ECLIA (n = 93) were confirmed as positive by Western blot, as were 14 of the 28 samples identified as equivocal. When these 121 samples were retested, the sensitivities of CLIA and ELFA were 64.4% and 73.8%, respectively. Both methods exhibited a specificity of 100%. This study confirms that the results obtained from the different immunoassays are not comparable, and neither CLIA nor ELFA should be used to confirm ECLIA results, which should instead be confirmed by methods such as Western blot or Sabin-Feldman dye test.     

Symposium on obesity and asthma �CNovember 2, 2006

Asthma and obesity are frequently associated, and obesity has been considered a factor contributing to both an increase in severity of asthma and to its development. The present document summarizes the proceedings of a symposium held in Montreal, Quebec, on November 2, 2006, under the auspices of the Réseau en santé respiratoire du Fonds de la recherche en santé du Québec in collaboration with the McGill University – Strauss Severe Asthma Program, Université Laval (Quebec City) and Université de Montréal. It includes an overview of the various aspects of the relationships between asthma and obesity with regard to animal models; genetic, hormonal and physiological determinants; influence of comorbidities (eg, sleep apnea syndrome); epidemiology; clinical and psychological features; and management of asthma in the obese population.     

Is the volume-outcome relation still an issue in the era of PCI with systematic stenting? Results of the greater Paris area PCI registry.

AIMS: In acute myocardial infarction (AMI), primary percutaneous transluminal angioplasty (PTCA) is the preferred option when it can be performed rapidly. Because of the limited access to high PTCA volume centres in some areas, it has been suggested that PTCA could be performed in low-volume centres on AMI patients. Little data exist on the validity of this strategy in modern era PTCA. METHODS AND RESULTS: The Greater Paris area comprises 11 million inhabitants and accounts for 18% of the French population. In 2001, the hospital agency of the Greater Paris area set up a registry of all PTCAs performed in this region. Data from 2001 and 2002 was analysed. Hospitals performing <400 PTCAs per year were classified as low-volume. A case-control analysis (propensity score) compared in-hospital mortality in low- and high-volume centres. A total of 37 848 angioplasty procedures were performed in 44 centres during the study period; 24.7% were performed in low-volume centres. A non-statistically significant trend towards reduced in-hospital mortality was noted in high-volume centres as opposed to low-volume centres: 2.01 vs. 2.42%, P = 0.057. In-hospital mortality rates were significantly different in the sub-group of emergency procedures: 6.75% in high- vs. 8.54% in low-volume centres, P = 0.028. No difference was noted between low- and high-volume centres in non-emergency procedures (0.62 vs. 0.62%, P = 0.99). CONCLUSION: In the era of modern stenting, a clear inverse relationship exists between hospital PTCA volume and in-hospital mortality after emergency procedures. Tolerance of low-volume thresholds for angioplasty centres with the purpose of providing primary PTCA in AMI should not be recommended, even in underserved areas.     

Creation and testing of the Geriatric Self-Efficacy Index for Urinary Incontinence

OBJECTIVES: To report on the content development, construct validity, and reliability testing of the Geriatric Self-Efficacy Index for Urinary Incontinence (GSE-UI).
DESIGN: Prospective cohort study.
SETTING: Six UI outpatient clinics in Quebec, Canada.
PARTICIPANTS: Community-dwelling incontinent men and women aged 65 and older.
MEASUREMENTS: Thirty-eight items were generated using a literature search and interdisciplinary panel of experts. Item reduction was achieved through field-testing with 75 older men and women with UI attending an information session. The final 20-item draft, measuring older adults' level of confidence in preventing urine loss, was administered to a new group of consecutive patients 1 week before and at the time of their first visit to the UI clinic to enable evaluation of test–retest reliability. A 3-day voiding diary, quantifying the frequency of UI, and the Incontinence Quality of Life questionnaire were used to test construct validity.
RESULTS: One hundred sixteen of 300 eligible patients (39%) participated (mean age±standard deviation 74±6, range 65–87). The GSE-UI items showed normal distributions and no ceiling effects. Self-efficacy scores ranged from 16 to 193 (mean 104±41, possible range 0–200) and correlated positively with quality of life scores ( r =0.7, P <.001) and negatively with UI severity ( r =−0.4, P <.001). Internal consistency for the GSE-UI was 0.94 (Cronbach alpha). Initial test–retest reliability of the 20 items using intraclass correlations ranged from 0.50 to 0.86.
CONCLUSION: The GSE-UI will enable measurement of whether a person's confidence in their ability to prevent urine loss is an important mechanism contributing to improvements in UI.     

POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project

Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients’ literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.