Search results for: Nour El Houda Bensiradj

Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

Abstract:

Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

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Authors: Carine Platat, Fatima Qshadi, Ghofran Kayed, Nour Hussein, Amjad Jarrar, Habiba Ali

Abstract:

Nowadays, smartphones are very popular. They are offering a variety of easy-to-use and free applications among which step counters and fitness tests. The number of users is huge making of such applications a potentially efficient new strategy to encourage people to become more active. Nonetheless, data on their reliability and validity are very scarce and when available, they are often negative and contradictory. Besides, weight status, which is likely to introduce a bias in the physical activity assessment, was not often considered. Hence, the use of these applications as motivational tool, assessment tool and in research is questionable. PACER is one of the free step counters application. Even though it is one of the best rated free application by users, it has never been tested for reliability and validity. Prior any use of PACER, this remains to be investigated. The objective of this work is to investigate the reliability and validity of the smartphone application PACER in measuring the number of steps and in assessing the cardiorespiratory fitness by the 6 minutes walking test. 20 overweight or obese students (10 male and 10 female) were recruited at the United Arab Emirate University, aged between 18 and 25 years old. Reliability and validity were tested in real life conditions and in controlled conditions by using a treadmill. Test-retest experiments were done with PACER on 2 days separated by a week in real life conditions (24 hours each time) and in controlled conditions (30 minutes on treadmill, 3km/h). Validity was tested against the pedometer OMRON in the same conditions. During treadmill test, video was recorded and steps numbers were compared between PACER, pedometer and video. The validity of PACER in estimating the cardiorespiratory fitness (VO2max) as part of the 6 minutes walking test (6MWT) was studied against the 20m shuttle running test. Reliability was studied by calculating intraclass correlation coefficients (ICC), 95% confidence interval (95%CI) and by Bland-Altman plots. Validity was studied by calculating Spearman correlation coefficient (rho) and Bland-Altman plots. PACER reliability was good in both male and female in real life conditions (p≤10-3) but only in female in controlled conditions (p=0.01). PACER was valid against OMRON pedometer in male and female in real life conditions (rho=0.94, p≤10-3 ; rho=0.64, p=0.01, in male and female respectively). In controlled conditions, PACER was not valid against pedometer. But, PACER was valid against video in female (rho=0.72, p≤10-3). PACER was valid against the shuttle run test in male and female (rho-=0.66, p=0.01 ; rho=0.51, p=0.04) to estimate VO2max. This study provides data on the reliability and viability of PACER in overweight or obese male and female young adults. Globally, PACER was shown as reliable and valid in real life conditions in overweight or obese male and female to count steps and assess fitness. This supports the use of PACER to assess and promote physical activity in clinical follow-up and community interventions.

Keywords: smartphone application, pacer, reliability, validity, steps, fitness, physical activity

Procedia PDF Downloads 416

Authors: Leen Al Kassab, Sarah Johns, Helen Noble, Nawal Nour, Elizabeth Janiak, Sarrah Shahawy

Abstract:

Introduction: Immigrant and refugee women experience disparities in sexual and reproductive health (SRH) outcomes, partially as a result of barriers to SRH literacy and to regular healthcare access and engagement. Despite the existing data highlighting growing needs for culturally relevant and structurally competent care, interventions are scarce and not well-documented. Methods: In this IRB-approved study, we used a community-based participatory research approach, with the assistance of a community advisory board, to conduct a qualitative needs assessment of SRH knowledge and service engagement with immigrant and refugee women from Africa or the Middle East and currently residing in Boston. We conducted a total of nine focus group discussions (FGDs) in partnership with medical, community, and religious centers, in six languages: Arabic, English, French, Somali, Pashtu, and Dari. A total of 44 individuals participated. We explored migrant and refugee women’s current and evolving SRH care needs and gaps, specifically related to the development of interventions and clinical best practices targeting SRH literacy, healthcare engagement, and informed decision-making. Recordings of the FGDs were transcribed verbatim and translated by interpreter services. We used open coding with multiple coders who resolved discrepancies through consensus and iteratively refined our codebook while coding data in batches using Dedoose software. Results: Participants reported immigrant adaptation experiences, discrimination, and feelings of trust, autonomy, privacy, and connectedness to family, community, and the healthcare system as factors surrounding SRH knowledge and needs. The context of previously learned SRH knowledge was commonly noted to be in schools, at menstruation, before marriage, from family members, partners, friends, and online search engines. Common themes included empowering strength drawn from religious and cultural communities, difficulties bridging educational gaps with their US- born daughters, and a desire for more SRH education from multiple sources, including family, health care providers, and religious experts & communities. Regarding further SRH education, participants’ preferences varied regarding ideal platform (virtual vs. in-person), location (in religious and community centers or not), smaller group sizes, and the involvement of men. Conclusions: Based on these results, empowering SRH initiatives should include both community and religious center-based, as well as clinic-based, interventions. Interventions should be composed of frequent educational workshops in small groups involving age-grouped women, daughters, and (sometimes) men, tailored SRH messaging, and the promotion of culturally, religiously, and linguistically competent care.

Keywords: community, immigrant, religion, sexual & reproductive health, women's health

Procedia PDF Downloads 99