HIV Tat induces a prolonged MYC relocalization next to IGH in circulating B-cells.

With combined antiretroviral therapy (cART), the risk for HIV-infected individuals to develop a non-Hodgkin lymphoma is diminished. However, the incidence of Burkitt lymphoma (BL) remains strikingly elevated. Most BL present a t(8;14) chromosomal translocation which must take place at a time of spatial proximity between the translocation partners. The two partner genes, MYC and IGH, were found colocalized only very rarely in the nuclei of normal peripheral blood B-cells examined using 3D-FISH while circulating B-cells from HIV-infected individuals whose exhibited consistently elevated levels of MYC-IGH colocalization. In vitro, incubating normal B-cells from healthy donors with a transcriptionally active form of the HIV-encoded Tat protein rapidly activated transcription of the nuclease-encoding RAG1 gene. This created DNA damage, including in the MYC gene locus which then moved towards the center of the nucleus where it sustainably colocalized with IGH up to 10-fold more frequently than in controls. In vivo, this could be sufficient to account for the elevated risk of BL-specific chromosomal translocations which would occur following DNA double strand breaks triggered by AID in secondary lymph nodes at the final stage of immunoglobulin gene maturation. New therapeutic attitudes can be envisioned to prevent BL in this high risk group.

Genome- and Cell-Based Strategies in Therapy of Muscular Dystrophies.

Muscular dystrophies are a group of heterogeneous genetic disorders characterized by progressive loss of skeletal muscle mass. Depending on the muscular dystrophy, the muscle weakness varies in degree of severity. The majority of myopathies are due to genetic events leading to a loss of function of key genes involved in muscle function. Although there is until now no curative treatment to stop the progression of most myopathies, a significant number of experimental gene- and cell-based strategies and approaches have been and are being tested in vitro and in animal models, aiming to restore gene function. Genome editing using programmable endonucleases is a powerful tool for modifying target genome sequences and has been extensively used over the last decade to correct in vitro genetic defects of many single-gene diseases. By inducing double-strand breaks (DSBs), the engineered endonucleases specifically target chosen sequences. These DSBs are spontaneously repaired either by homologous recombination in the presence of a sequence template, or by nonhomologous-end joining error prone repair. In this review, we highlight recent developments and challenges for genome-editing based strategies that hold great promise for muscular dystrophies and regenerative medicine.

Participation restrictions in patients with psychiatric and/or cognitive disabilities: preliminary results for an ICF-derived assessment tool.

UNLABELLED: Participation in community life is a major challenge for most people with psychiatric and/or cognitive disabilities. Current assessments of participation lack a theoretical basis. However, the new International Classification of Functioning, Disability and Health (ICF) provides a relevant framework. AIMS: The present study used an ICF-derived assessment tool to activity limitations and participation restrictions in two groups of participants with disabilities linked to schizophrenia or traumatic brain injury respectively. METHODS: Twenty-six items (related to six ICF sections) were selected by reviewing the literature and gathering the clinician's opinions and representatives of patient associations. These items, yielded an ordinal rating of activity limitations, participation restrictions and contextual factors (social support, attitudes and, systems & politics). Special attention was paid to contextual and environmental factors. The final checklist (called the Grid for Measurements of Activity and Participation, G-MAP) was administered to 16 participants with traumatic brain injury (the TBI group) and 15 participants with schizophrenic disorders (the SD group). Psychometric assessments of cognition and, neurobehavioural, psychological and psychosocial functioning were also performed. RESULTS: The internal consistencies for activity limitations (Cronbach's alpha coefficient=0.89) and participation restriction (Cronbach's alpha coefficient=0.89) were satisfactory. We did not observe any significant differences between the two groups in terms of the psychometric test results. The G-MAP scores demonstrated that the two groups were confronted with the same limitations in self care, domestic life, leisure and community life (i.e., the intergroup differences were not statistically significant in Mann-Whitney tests). However, interpersonal relationships and economic and social productivity appeared to be more severely limited in the SD group than in the TBI group. Similarly, participation restrictions in domestic life, interpersonal relationships and economic and social productivity were more severe in the SD group than in the TBI group. CONCLUSION: G-MAP is a useful, feasible, relevant tool for performing a detailed, individualized assessment of participation restrictions in people with psychiatric and/or cognitive disabilities.

[Psychometric properties of the French adaptation of the Family Relationship Index (FRI)]. / Qualités psychométriques de l'adaptation française du Family Relationship Index (FRI).

OBJECTIVE: The aim of the present study was to investigate the psychometric properties of the French adaptation of the Family Relationship Index (FRI) from Moos and Moos. The FRI is a self-report inventory which consists of 27 items assessing family relations. It is composed of three dimensions: family cohesion, family expressiveness (of feelings and emotions) and family conflict. METHOD: The FRI was translated and adapted into French according to published recommendations. After appropriate cultural adaptations, the scale was administered to a sample of 976 students with a mean age of 21.9 years and 43.5% of men. The participants completed the FRI and three other questionnaires: the Family Adaptability and Cohesion Scale (FACES), the Satisfaction with Life Scale and the General Health Questionnaire. Confirmatory factor analyses were used to test different models with one and three factors. The psychometric properties of the short version of the FRI, proposed by Kissane and Bloch (2002) and composed of 12 items, were also studied. RESULTS: Confirmatory factor analyses showed that the three factors solution was more relevant that the one factor solution (for Khi(2)/ddl, Root mean square error of approximation [RMSEA], Root mean square residual [RMR], Goodness of fit index [GFI], Adjusted goodness of fit [AGFI] and Comparative fit index [CFI]). However, three items belonging to family expression explained a small variance. Therefore, a version consisting of 24 items seemed more appropriate than the 27 items version proposed by Moos and Moos. Cultural differences may explain these results. Internal consistency was satisfactory for cohesion (0.79) and conflict (0.71) but weak for expression (0.55 for 27 items version and 0.62 for 24 items version). One month test-retest reliability showed high correlations for the three dimensions (from 0.77 to 0.85). Correlation between the cohesion subscale of the FRI and the cohesion subscale of the FACES was high (0.77), showing a good convergent validity. The correlations between the three FRI dimensions and the Satisfaction with Life Scale and the General Health Questionnaire were quite low (from -0.31 to 0.41). High family cohesion and high family expression were associated with high life satisfaction and good mental health. Conversely, high family conflict was associated with low life satisfaction and weak mental health. These results support the criterion validity of the FRI. Concerning the 12 items version of the FRI, the factor analysis results showed very good psychometric qualities. However, this short version had lower internal consistency (which ranged between 0.50 and 0.71), test-retest reliability (which ranged 0.68 and 0.81), convergent (0.69 for cohesion) and criterion validity (from -0.21 to 0.37 for the Satisfaction with Life Scale and from -0.28 to 0.19 for the General Health Questionnaire) than the longer versions. CONCLUSION: The results of the present study show that the FRI's 24 items version seems to be the more relevant. Nevertheless, the 12 items version shows interesting qualities. Further studies should confirm these results on other samples. Given the lack of French-language surveys assessing family relations, the FRI will be a useful tool for research and clinical practice.