The experience of healthcare professionals treating adolescents with eating disorders in psychiatric and pediatric inpatient units for adolescents: A qualitative study.

OBJECTIVES: The recommended treatment for Eating Disorders (EDs) is multidisciplinary and multimodal. Nonetheless, the complex linkage of the different disciplines involved is not necessarily simple. We analyzed the experience of healthcare professionals faced with psychiatric and psychological symptoms in adolescents with EDs in two "multidisciplinary" inpatient units embedded predominantly in different paradigms - one pediatric and one psychiatric. METHODS: Qualitative analysis of 20 healthcare staff members' interviews from different professional backgrounds working in inpatient units for EDs in Montreal (Canada) and Paris (France). RESULTS: The "Complex patients" theme discusses the need for a global approach to the multiplicity of symptoms presented by these patients. "Management and its limits" describes the daily management of psychiatric symptoms in both units. "Psychiatry and Adolescent medicine: from opposition to collaboration" describes the different levels at which these disciplines work together and how this cooperation may be evolving. CONCLUSIONS: The complex entanglement intrinsic in EDs of the patients' somatic, psychosocial, psychiatric, and adolescent problems requires collaboration between disciplines, but the modalities of this collaboration are multiple and evolve non-linearly in specialized treatment units. A multilevel approach must be offered, with the degree of collaboration (multidisciplinary, interdisciplinary and transdisciplinary) appropriate to the complexity of each adolescent's issues.

Ecological Assessment Battery for Numbers (EABN) for brain-damaged patients: standardization and validity study.

OBJECTIVES: Number-processing may be altered following brain injury and might affect the everyday life of patients. We developed the first ecological tool to assess number-processing disorders in brain-injured patients, the Ecological Assessment Battery for Numbers (EABN; in French, the BENQ). The aim of the present study was to standardize and validate this new tool. MATERIAL AND METHODS: Standardization included 126 healthy controls equally distributed by age, sex and sociocultural level. First, 17 patients were evaluated by the EABN; then scores for a subgroup of 10 were compared with those from a French analytical calculation test, the Évaluation Clinique des Aptitudes Numériques (ECAN). The concordance between the EABN and the ECAN was analyzed to determine construct validity. Discrimination indexes were calculated to assess the sensitivity of the subtests. RESULTS: Standardization highlighted a major effect of sociocultural level. In total, 9 of 17 patients had a pathological EABN score, with difficulties in telling time, making appointments and reading numerical data. The results of both the EABN and ECAN tests were concordant (Kendall's w=0.97). Finally, the discriminatory power was good, particularly for going to the movies, cheque-writing and following a recipe: scores were>0.4. CONCLUSION: The EABN is a new tool to assess number-processing disorders in adults. This tool has been standardized and has good psychometric properties for patients with brain injury.

[Pulmonary diffusion test to NO and CO time course during thoracic radiotherapy for lung cancer: the CONORT prospective study protocol]. / Évolution de la double diffusion au CO et au NO au cours de la radiothérapie pulmonaire pour cancer bronchique : présentation du protocole de l'étude prospective Conort.

Thoracic radiotherapy is a usual treatment for lung cancer. Early-stages may be treated in stereotactic mode while locally advanced stages are usually treated with conventional radiotherapy mode. Pulmonary function tests show that thoracic irradiation has no impact on lung volume such as forced expiratory volume in one second (FEV1) or forced vital capacity (FCV). However, some studies found that CO (carbon monoxide) diffusing capacity (TLCO) may be altered under thoracic radiotherapy. DLCO alteration is usually symptomatic of either a lesion in the alveolar membrane or a pulmonary capillary alteration. Pulmonary diffusion may be also appreciated by the NO (azote monoxide) diffusion capacity. Moreover, using a double measurement of NO and CO diffusing capacities permit to assess which lung compartment (capillary or membrane) is affected. CONORT is an observational prospective monocentric study, aiming to assess the CO and NO diffusing capacity (as well as other pulmonary function tests) during thoracic radiotherapy. Inclusion criteria are patients with lung cancer, treated by thoracic radiotherapy (conformational or stereotactic), who signed consent. Pulmonary function tests are performed before, during, at the end and six weeks and six months after thoracic irradiation. To estimate a difference of 15% in diffusing capacity test, we have to include 112 patients with a 90% power and a 5% alpha risk. Four months after beginning, 36 patients were included. Preliminary data will be presented at the SFRO meeting.

Assessing the containment efficiency of a microbiological safety cabinet during the simultaneous generation of a nanoaerosol and a tracer gas.

The intention of this article is to compare the containment performance of a Type II microbiological safety cabinet (MSC) confronted with the simultaneous generation of a saline nanoparticle aerosol and a tracer gas (SF(6)). The back dissemination coefficient, defined as the ratio of the pollutant concentration measured outside the enclosure to the pollutant flow rate emitted inside the enclosure, is calculated in order to quantify the level of protection of each airborne contaminant tested for three enclosure operating configurations: an initial configuration (without perturbations), a configuration exposing a dummy in front of the enclosure (simulation of an operator), and a configuration employing the movement of a plate in front of the enclosure (simulation of human movement). Based on the results of this study, we observed that nanoparticulate and gaseous behaviours are strongly correlated, thus showing the predominance of air-driven transport over particle-specific behaviour. The average level of protection afforded by the MSC was found systematically slightly higher for the nanoaerosol than for the gas in the studied configurations (emission properties of the source, operating conditions, and measurement protocols). This improved protection efficiency, however, cannot be considered as a warrant of protection for operators since operating condition and ventilation parameters are still more influential on the containment than the pollutant nature (i.e. nanoaerosol or gas).

Diversity of ARSACS mutations in French-Canadians.

BACKGROUND: The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability. METHODS: Search for SACS mutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause. Western blot on lymphoblast protein from cases with different genotypes was probed to establish if they still expressed sacsin. RESULTS: A total of 12 mutations, including 7 novels, were uncovered in Quebec ARSACS cases. The screening of 104 spastic ataxia cases of unknown cause for 98 SACS mutations did not uncover carriers of two mutations. Compounds heterozygotes for one missense SACS mutation were found to minimally express sacsin. CONCLUSIONS: The large number of SACS mutations present even in Quebec suggests that the size of the gene alone may explain the great genotypic diversity. This study does not support an expanding ARSACS phenotype in the French-Canadian population. Most mutations lead to loss of function, though phenotypic variability in other populations may reflect partial loss of function with preservation of some sacsin expression. Our results also highlight the challenge of SACS mutation screening and the necessity to develop new generation sequencing methods to ensure low cost complete gene sequencing.

Evaluation of the overall haemostatic effect of recombinant factor VIIa by measuring thrombin generation and stability of fibrin clots.

It has been reported that thrombin generation test (TGT) may be a useful tool to monitor recombinant factor VIIa (rFVIIa). However, TGT does not reflect the stability of fibrin clot and its resistance to fibrinolysis which are crucial. Using whole-blood thromboelastography (TEG) and tissue plasminogen activator (tPA), we developed an in-vitro model to assess fibrin clot stability. Fibrin fibres were thicker in haemophiliacs compared with controls (P < 0.0001). After addition of rFVIIa 90 µg kg(-1), the diameter of fibrin fibres was dramatically decreased (P = 0.006). TEG-tPA assay showed a dose-dependent improvement of clot stability in the presence of rFVIIa. These data demonstrate a significant correlation between fibrin clot structure and its stability (P = 0.001). We also showed a correlation between thrombin generating capacity and clot resistance to fibrinolysis. Despite this overall correlation, a relatively large spreading around a general trend was observed, suggesting that the two assays bring complementary information on the haemostatic effect of rFVIIa.

Clinical and genetic knowledge and attitudes of patients with myotonic dystrophy type 1.

AIMS: The goal was to assess clinical and genetic knowledge and attitudes in patients affected by myotonic dystrophy type 1 (DM1). METHODS: Two hundred patients with molecular confirmation of the diagnosis of DM1 completed a multi-choice questionnaire. DM1 patients' knowledge and views were compared to clinically normal DM1 noncarriers (n = 264) and controls (n = 1,474). RESULTS: Knowledge of the DM1 mode of inheritance was better in noncarriers than in patients (p < 0.001). Noncarriers were more aware than DM1 patients of the common clinical characteristics of DM1 such as limitations in physical activities and problems related to employment, schooling, activities of daily living, parenthood, peer relationships, and personality (p < 0.001). Compared to controls, DM1 patients felt less informed about the availability of clinical genetic services (p < 0.05) and new genetic technologies (p < 0.001). Among patients, logistic regression revealed that each additional year of education (p < 0.05) and each additional 100 CTG repeats (p < 0.01), respectively, increased and decreased the odds of knowing the DM1 mode of inheritance by about 23% and 18% respectively, independently of age, age at onset of symptoms, gender, severity of muscular impairment, and intellectual quotient. CONCLUSIONS: DM1 patients' genetic knowledge is significantly dependent of the level of education and the number of CTG repeats. Healthcare providers should be aware of this situation in order to adjust counselling and education accordingly.

Src kinase activation is mandatory for MDA-9/syntenin-mediated activation of nuclear factor-kappaB.

The scaffolding postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domain-containing protein melanoma differentiation associated gene-9 (MDA-9)/syntenin is a tandem PDZ protein overexpressed in human melanoma, and breast and gastric cancer cells. MDA-9/syntenin affects cancer cell motility and invasion through distinct biochemical and signaling pathways, including focal adhesion kinase and p38 mitogen-activated protein kinase (MAPK), resulting in activation of the nuclear factor (NF)-kappaB pathway. MDA-9/syntenin also promotes melanoma metastasis by activating c-Src, but how c-Src regulates NF-kappaB activation is unclear. Using a human melanoma model, we document that MDA-9/syntenin-c-Src interactions are positive regulators of NF-kappaB activation. Inhibition of c-Src by PP2 treatment, by blocking c-Src or mda-9/syntenin expression with small interfering RNA, or in c-Src (-/-) knockout cell lines, reduces NF-kappaB activation following overexpression of mda-9/syntenin or c-Src. Deletion or point mutations of the PDZ binding motif preventing MDA-9/syntenin association with c-Src reveals that both PDZ domains, with PDZ2 being the dominant module, are required for activating downstream signaling pathways, including p38 MAPK and NF-kappaB. We also document that MDA-9/syntenin-c-Src complexes functionally cooperate with NF-kappaB to promote anchorage-independent growth, motility and invasion of melanoma cells. These findings underscore PDZ domains of MDA-9/syntenin as promising potential therapeutic targets for intervening in a decisive component of cancer progression, namely, metastatic tumor spread.

Liver fibrosis staging with contrast-enhanced ultrasonography: prospective multicenter study compared with METAVIR scoring.

We prospectively assessed contrast-enhanced sonography for evaluating the degree of liver fibrosis as diagnosed via biopsy in 99 patients. The transit time of microbubbles between the portal and hepatic veins was calculated from the difference between the arrival time of the microbubbles in each vein. Liver biopsy was obtained for each patient within 6 months of the contrast-enhanced sonography. Histological fibrosis was categorized into two classes: (1) no or moderate fibrosis (F0, F1, and F2 according to the METAVIR staging) or (2) severe fibrosis (F3 and F4). At a cutoff of 13 s for the transit time, the diagnosis of severe fibrosis was made with a specificity of 78.57%, a sensitivity of 78.95%, a positive predictive value of 78.33%, a negative predictive value of 83.33%, and a performance accuracy of 78.79%. Therefore, contrast-enhanced ultrasound can help with differentiation between moderate and severe fibrosis.

Insights on protein-DNA recognition by coarse grain modelling.

Coarse grain modelling of macromolecules is a new approach, potentially well adapted to answer numerous issues, ranging from physics to biology. We propose here an original DNA coarse grain model specifically dedicated to protein-DNA docking, a crucial, but still largely unresolved, question in molecular biology. Using a representative set of protein-DNA complexes, we first show that our model is able to predict the interaction surface between the macromolecular partners taken in their bound form. In a second part, the impact of the DNA sequence and electrostatics, together with the DNA and protein conformations on docking is investigated. Our results strongly suggest that the overall DNA structure mainly contributes in discriminating the interaction site on cognate proteins. Direct electrostatic interactions between phosphate groups and amino acid side chains strengthen the binding. Overall, this work demonstrates that coarse grain modeling can reveal itself a precious auxiliary for a general and complete description and understanding of protein-DNA association mechanisms.

Compliance and immunogenicity of two hepatitis B vaccination schedules in sex workers in Belgium.

OBJECTIVES: To compare the coverage for the third dose and the compliance to two hepatitis B vaccination schedules: 0,1,4 versus 0,1,6 months, in commercial sex workers (CSW) in Belgium; to compare the immunogenicity of the actually administered schedules. METHODS: In seven health centres in Belgium, hepatitis B vaccination was offered free of charge to CSW. In a randomised, prospective study a commercialised hepatitis B vaccine (Engerix-B 20mcgr) was offered according to one of both schedules. After complete vaccination, bleeding was performed to assess immunogenicity. RESULTS: Between June 2003 and September 2004, 615 non-immune CSW were enrolled, of whom 52% in the 0,1,4 month schedule (n=322). Coverage of the third dose was 57% overall, 59% (0,1,4) and 54% (0,1,6), respectively. Age, the health centre and drug use significantly influenced the compliance and the coverage of dose 3, whereas the planned vaccination did not. When comparing the immunogenicity results as a function of the actually administered vaccination schedule, immune responses did not significantly differ between CSW receiving the third dose 4-6 months and those receiving it at least 6 months after the first dose. In total, 19 persons (8%) were not protected after a full vaccination course (anti-HBs <10IU/L). Two health centres measured markedly lower anti-HBs levels. CONCLUSIONS: In this highly mobile at-risk population, a 0,1,4 month schedule is more easy to offer and confers equal protection within a shorter period of time. We therefore propose this 0,1,4 month schedule to vaccinate CSW in the future.

Clinical characteristics of myotonic dystrophy type 1 patients with small CTG expansions.

The authors report a genotype-phenotype correlation study in 102 patients with myotonic dystrophy type 1 carrying small CTG repeat expansions. Most patients carrying 50 to 99 CTG repeats were asymptomatic, except for cataracts. Myotonia, weakness, excessive daytime sleepiness, and myotonic discharges at EMG were significantly more present in the patients with 100 to 200 CTG repeats. These findings highlight different outcomes related to the expansion size, even among small CTG expansions.

Sibship stability of genotype and phenotype in myotonic dystrophy.

Myotonic dystrophy (DM1) is caused by an unstable CTG repeat expansion. Despite the evidence of birth order effect in congenital DM1, the expansion's dynamics among sibships is still unknown. The objective of this study was to determine phenotype and CTG repeat size variability in DM1 sibships, and to investigate their predictive values. We compared 86 sib pairs for CTG repeat, 61 for age at onset and 89 for DM1 phenotype. CTG repeats remained stable for 66 of the 86 sib pairs, including 25 of 27 maternal transmissions and 30 of 42 paternal transmissions. Variations of less than 10 years in the age at onset were observed in 44 of 61 sib pairs, including 16 of 18 maternal transmissions and 19 of 28 paternal transmissions. The same phenotypic severity or a variation of only one class was observed among 86 of the 89 sib pairs, including all of the 35 maternal transmissions and 30 of the 33 paternal transmissions. Birth order, intergenesic interval, oldest sib's CTG repeat or parental age and CTG repeat did not exert any significant influence. These results suggest that genotype and phenotype remained stable among sibs, although the paternal origin of the mutation seemed to reduce the predictability of the severity.

Rapid detection of the sacsin mutations causing autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS; MIM SACS 270550) is frequent in northeastern Québec. Two causal mutations have been identified in the 11.7-kb single exon sacsin gene by sequence-based analyses. Mutation g.6594delT (DeltaT) was reported in 96% of the patients whereas a g.5254C --> T nonsense mutation has been observed only in 2 families. Here we report a reliable and inexpensive method to detect more than 95% of the ARSACS disease alleles from northeastern Québec using allele-specific oligonucleotide (ASO) hybridization. This procedure is being incorporated into the diagnosis of ARSACS, as well as being used for carrier detection in at-risk families from northeastern Québec.

A Mechanism for RecA-Promoted Sequence Homology Recognition and Strand Exchange Between Single-Stranded DNA and Duplex DNA, via Triple-Helical Intermediates.

Abstract A central function of RecA protein during homologous recombination is to promote sequence recognition and strand exchange between a stretched and unwound single-stranded DNA, to which it is complexed, and a duplex DNA. By studying the properties of DNA under the conditions of deformation imposed by RecA, we propose a model for recognition and strand exchange at the atomic level, via unusual triple-helical intermediates. In this model, association takes place within a stretched and unwound triple helix of a new type, where the invading single strand occupies the minor groove of the duplex in a parallel orientation. Our calculations indicate that strand exchange within this structure is exothermic and results in a triple helix where the third strand interacts in the major groove, the so-called R-DNA triple helix. Preliminary calculations suggest that sequence homology recognition within the triplex of association is partial and that it is completed during strand exchange and product formation.

A molecular model for RecA-promoted strand exchange via parallel triple-stranded helices.

A number of studies have concluded that strand exchange between a RecA-complexed DNA single strand and a homologous DNA duplex occurs via a single-strand invasion of the minor groove of the duplex. Using molecular modeling, we have previously demonstrated the possibility of forming a parallel triple helix in which the single strand interacts with the intact duplex in the minor groove, via novel base interactions (Bertucat et al., J. Biomol. Struct. Dynam. 16:535-546). This triplex is stabilized by the stretching and unwinding imposed by RecA. In the present study, we show that the bases within this triplex are appropriately placed to undergo strand exchange. Strand exchange is found to be exothermic and to result in a triple helix in which the new single strand occupies the major groove. This structure, which can be equated to so-called R-form DNA, can be further stabilized by compression and rewinding. We are consequently able to propose a detailed, atomic-scale model of RecA-promoted strand exchange. This model, which is supported by a variety of experimental data, suggests that the role of RecA is principally to prepare the single strand for its future interactions, to guide a minor groove attack on duplex DNA, and to stabilize the resulting, stretched triplex, which intrinsically favors strand exchange. We also discuss how this mechanism can incorporate homologous recognition.

A 10-year study of mortality in a cohort of patients with myotonic dystrophy.

OBJECTIVE: To determine the age and causes of death as well as the predictors of survival in patients with myotonic dystrophy (DM). METHODS: In a longitudinal study, a cohort of 367 patients with definite DM was followed for 10 years. RESULTS: During the 10-year period, 75 of the 367 DM patients (20%) died. The mean age at death (53.2 years, range 24 to 81) was similar for men and women. Among these 75 patients, 32 (43%) died of a respiratory problem, 15 (20%) of cardiovascular disease, 8 (11%) of a neoplasia, and 8 (11%) died suddenly. The ratio of observed to expected deaths was significantly increased to 56.6 (95% confidence interval [CI] 38.7 to 78.0) for respiratory diseases, 4.9 (95% CI 2.7 to 7.7) for cardiovascular diseases, and 2.5 (95% CI 1.1 to 4.6) for neoplasms. The mean age at death was 44.7 years for the childhood phenotype of DM, 47.8 years for the early-adult, 55.4 years for the adult, and 63.5 years for the mild phenotype (F = 4.8, p = 0.005). The age-adjusted risk of dying was 3.9 (95% CI 1.3 to 11.0) times greater for a patient with a distal weakness and 5.6 (95% CI 2.2 to 14.4) times greater for a patient with proximal weakness as compared with a person without limb weakness. CONCLUSIONS: Life expectancy is greatly reduced in DM patients, particularly in those with early onset of the disease and proximal muscular involvement. The high mortality reflects an increase in death rates from respiratory diseases, cardiovascular diseases, neoplasms, and sudden deaths presumably from cardiac arrhythmias.

A model for parallel triple helix formation by RecA: single-single association with a homologous duplex via the minor groove.

The nucleoproteic filaments of RecA polymerized on single stranded DNA are able to integrate double stranded DNA in a coaxial arrangement (with DNA stretched by a factor 1.5), to recognize homologous sequences in the duplex and to perform strand exchange between the single stranded and double stranded molecules. While experimental results favor the hypothesis of an invasion of the minor groove of the duplex by the single strand, parallel minor groove triple helices have never been isolated or even modeled, the minor groove offering little space for a third strand to interact. Based on an internal coordinate modeling study, we show here that such a structure is perfectly conceivable when the two interacting oligomers are stretched by a factor 1.5, in order to open the minor groove of the duplex. The model helix presents characteristics that coincide with known experimental data on unwinding, base pair inclination and inter-proton distances. Moreover, we show that extension and unwinding stabilize the triple helix. New patterns of triplet interaction via the minor groove are presented.

Familial intracranial aneurysms: recurrence risk and accidental aggregation study.

BACKGROUND: The Saguenay-Lac-Saint-Jean (SLSJ) region is a geographically isolated area (population 285,955) located in the Northeastern part of the Province of Quebec, Canada. Using a population-based register, the genealogical reconstruction of 502 individuals with ruptured intracranial aneurysm (RIA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 144 (28.7%) of them; this proportion is much higher than reported elsewhere. OBJECTIVE: In order to assess the genetic predisposition to RIA in the SLSJ population, the objective of the present study is to compare familial and non-familial cases and to provide an estimate of the recurrence risk ratio for siblings. RESULTS: The age at the time of rupture, the number of intracranial aneurysms for each patient and the location of RIAs were not statistically different in the familial versus the non-familial group. Of the 3449 siblings, 20 (0.58%) had suffered a RIA. The recurrence risk ratio calculated for siblings (defined as the risk of disease among siblings divided by the estimated population prevalence) is 1.6 (CI 95% 1.0-2.4). In other respects, we observed very large kinships in the SLSJ population, with an average number of siblings of 7.2 (SD +/- 3.4), ranging from 0 to 17 individuals. With such large families and on the basis of chance alone, we expected 31.3% of the patients to have at least one first- to third-degree relative with RIA. CONCLUSION: These data show that siblings of patients with RIA in the SLSJ population have a greater risk of RIA than the general population. Nevertheless, the largest part of the familial occurrence observed in the SLSJ region can be explained by accidental aggregation, due to large kinships. We propose that, in this population, an underlying genetic predisposition must be suspected only when three or more cases of RIA are identified among first- to third-degree relatives.