Étude des déterminants génétiques et moléculaires de la scoliose idiopathique

La scoliose idiopathique (SI) est une maladie complexe de la colonne vertébrale. Elle survient principalement à l'adolescence et affecte ~ 1-4% de la population mondiale pédiatrique avec une prévalence plus élevée chez les femmes. Dans la plupart des cas, la cause sous-jacente de la SI est inconnue, bien qu'une composante génétique soit bien reconnue. Un certain nombre de gènes et de loci candidats ont été proposés, mais peu ont été répliqués avec succès dans de multiples études. Les études d'association génomique (GWAS) ont identifié plusieurs gènes candidats prédisposant à la SI. Parmi ceux-ci, le locus LBX1 est de loin celui qui a été répliqué avec le plus de succès dans différentes populations, bien que jusqu'à maintenant il n'ait pas été testé dans la population québécoise. L’objectif principal de cette thèse, a été l'étude des déterminants génétiques de la SI par des approches complémentaires. Dans la première étude, de nouveaux gènes enrichis de variants rares, pouvant contribuer à la maladie ont été identifiés par séquençage d’exomes entiers (WES) dans une cohorte de patients québécois atteints de SI, suivi d'une deuxième phase de séquençage ciblé des 24 meilleurs gènes candidats dans une seconde cohorte indépendante. Parallèlement, nous avons effectué une approche par WES dans une famille multiplex unique constituée de trois soeurs affectées avec des parents sains. Nos résultats impliquent un nouveau gène, FAT3, non précédemment associé à la SI, comme un gène candidat d’importance pour cette condition. Dans la deuxième étude, nous avons effectué un GWAS pour tester les marqueurs génétiques associés à la dans la population québécoise. Les résultats complets de l'analyse GWAS dépassent le cadre de cette thèse. L'objectif principal de l'analyse actuelle était de tester l'association du locus LBX1. Nos résultats appuient une association avec la région proche du gène LBX1 dans notre population. Dans la troisième étude, notre approche est une approche de gène candidat. Nous avons essayé d'élucider les corrélations génétiques et biochimiques des niveaux circulants en YKL-40 avec le risque de progression de la maladie. Une étude antérieure dans notre laboratoire a démontré que les patients atteints de SI ont un dysfonctionnement distinctif de la signalisation des récepteurs couplés aux protéines Gi inhibitrices (Gi), permettant leur classification en trois endophénotypes (FG1, FG2 et FG3). L'étude des profils d'expression de ces endophénotypes a montré une élévation significative de l'expression du gène CHI3L1, codant pour la glycoprotéine sécrétée YKL-40, chez les patients classés dans l’endophénotype FG1 par rapport à ceux classés dans les endophénotypes FG2 et FG3 qui sont plus enclins à développer une scoliose sévère. Nous avons démontré que les garçons du groupe FG1 présentent des niveaux plasmatiques significativement plus élevés en YKL-40 que les autres groupes tout comme les patients présentant une scoliose non-sévère. Les SNP dans le gène CH13L1 ont montré une association significative avec les niveaux plasmatiques d’YKL-40 dans des cas non-sévère. L'analyse fonctionnelle in vitro a révélé que la glycoprotéine YKL-40 pourrait jouer un rôle protecteur dans le contexte de la SI en bloquant le défaut de signalisation Gi induit par l'élévation de l'ostéopontine. En résumé, nous proposons une nouvelle association du gène FAT3 avec la SI, répliquons l'association du gène LBX1 dans une nouvelle cohorte et proposons un nouveau marqueur biochimique, YKL-40, associé à des formes non sévères de la SI.Idiopathic Scoliosis (IS) is a complex disorder of the spine. It mostly occurs between 10 and 15 years old and affects ~1-4% of the global pediatric population with a much higher prevalence in females. In most cases the underlying cause of IS is unknown, although a genetic component is well recognized. A number of candidate genes and loci have been suggested, but few have been successfully replicated in multiple studies. Genome wide association studies (GWAS) have identified several candidate genes for IS susceptibility. Among these the LBX1 locus is by far the most successfully replicated locus in different populations, although until now it has not been tested in the French-Canadian population. Few studies have attempted to detect rare causal variants in IS and this field of research is still in its infancy. The primary goal of this thesis was to investigate the genetic component of IS through complementary approaches. In the first study, we aimed to find new genes enriched with rare variants, which might contribute to the disease. Hence, we performed whole exome sequencing (WES) in a French-Canadian IS cohort, followed by a second phase of targeted sequencing of the 24 best candidate genes in a replication cohort. In parallel, we performed WES in a unique multiplex family of three affected sisters with healthy parents. Our results implicate a novel gene, FAT3, not previously associated with IS, as a strong candidate for this condition. In the second study we performed a GWAS to test for genetic markers associated with IS in our French-Canadian cohort. The complete results of the GWAS analysis are beyond the scope of this thesis. The main objective of the current analysis was to test association of the LBX1 locus. Our results support an association with the region near the LBX1 gene in our French-Canadian population. In the third study, our approach is a candidate gene approach. We attempted to elucidate the genetic and biochemical correlates of circulating YKL-40 levels with the risk of spinal deformity progression in the context of IS. Our prior works have demonstrated that IS patients exhibit a distinctive G inhibitory (Gi) proteincoupled receptor signaling dysfunction, which enabled their classification into three distinct biological endophenotypes (FG1, FG2 or FG3). Previous microarray analysis revealed a significant elevation in the expression of CHI3L1 gene, encoding for the secreted glycoprotein YKL-40, in IS patients classified in FG1 endophenotype when compared to FG2 and FG3 ones, which are more prone to develop a severe scoliosis. In this study, we demonstrated that IS males classified in FG1 endophenotype exhibit significant higher plasma YKL-40 levels than controls and other IS endophenotypes. Furthermore, the non-severe scoliosis group showed significant higher levels of YKL-40 than controls. SNPs in CHI3L1 gene showed significant association with YKL-40 plasma levels in non-severe cases. Functional in vitro analysis showed that YKL-40 could play a protective role in the context of IS by altering the Gi-signaling dysfunction induced by the elevation of osteopontin in IS. In sum, we propose a novel association of FAT3 gene with IS, replicated the association of LBX1 gene with IS in a new cohort, and propose a new biochemical marker, YKL-40, associated with non-severe forms of IS and has a plausible protective role in IS

VALIDATION OF THE ARABIC VERSION OF THE FOOD SAFETY AND HYGIENE QUESTIONNAIRE AMONG NUTRITION STUDENT

There is shortage of data on food safety knowledge and practices among Lebanese food handlers due to the lack of a reliable tool. The aim of the current study is to determine the reliability as well as the validity of an adopted Arabic version of the Osaili et al (2013) food safety questionnaire. Translation and back translation and testing equivalence were done using standard accepted procedures. A total of 110 undergraduate Nutrition and Dietetics students completed the questionnaire consisting of five subscales that covers major food safety concepts including personal hygiene, safe storage, cross contamination prevention, knowledge of health problems affecting food safety and symptoms of foodborne diseases. Construct validity was tested using knowledgeable group analysis; internal consistency was determined using Cronbach’s α and item-to-total correlation. Temporal stability was evaluated by test–retest reliability in a subgroup of 67 students. The results showed non-significant difference between scores of English and Arabic versions revealing equivalence. For the psychometric analysis, the significant statistical difference for most of food safety knowledge scores between lower and higher years of study indicates satisfactory construct validity. The test-retest reliability of the Arabic questionnaire showed a good temporal stability (ICC\u3e0.8), while the Cronbach’s α for the total scales ranged between 0.611 and 0.736 revealing an acceptable and satisfactory level of internal consistency for the items retained in the questionnaire. The translated Arabic version of the food safety questionnaire can be considered as a consistent and reliable tool, to be used as food safety knowledge assessment among food handlers

EVALUATION OF PHENOLIC CONTENT, ANTIRADICAL AND ANTIBACTERIAL ACTIVITIES OF ORANGE AND CARROT POMACE EXTRACTS

Orange and carrot pomace are considered as food wastes, despite their high content in beneficial health compounds. The comparison of phenolic extracts from orange and carrot pomace, showed higher values for Orange pomace, with a polyphenols concentration (130 mg/L), flavonoids (8.67 mg/L) and tannins (2.5 mg/L). A higher antiradical activity was also noted for orange pomace. However, carrot pomace presented a higher anti-bacterial activity. The beneficial activities of these extracts were owed to their high content in phenolic acids. Our study exhibited that orange and carrot pomace might be utilized as natural preservatives for many industrial applications

An Energy Efficient Sleep/Wake up Routing Protocol for Wireless Sensor Networks

In recent years, wireless sensor networks (WSNs) have a rapid development and they take a lot of research attention because of their wide-range applications. A WSN consists of a large number of distributed sensor nodes. These nodes are often deployed in remote or hostile areas to monitor physical or environmental conditions where they send this data to a main location. The most critical parameter in WSNs is network lifetime, so an efficient routing protocol is essential to reduce the energy consumption and to increase the network lifetime. This paper proposes an energy-efficient chain-based cooperative routing protocol based on node sleep/wake-up mechanism for WSNs. We compare this protocol with two efficient protocols; LEACH and CBCCP using MATLAB. Simulation results show that the proposed algorithm achieves better performance and conserves more energy than the other two protocols

Evaluasi Program Pendidikan Karakter di SMA Negeri 1 Pangkalan Koto Baru

Penelitian ini bertujuan untuk: (1) mengevaluasi ketercapaian program pendidikan karakter pada SMA Negeri 1 Pangkalan Koto Baru, (2) penelitian ini memberikan rekomendasi baik guru, sekolah, maupun pemerintah untuk perbaikan program pendidikan karakter. Jenis penelitian adalah evaluasi program (evaluasi formatif) dengan pendekatan kualitatif. Subjek penelitian adalah Sekolah Menengah Atas Negeri 1 Pangkalan Koto  Baru. Kesimpulan dari penelitian ini adalah: (1) kesiapan SMA Negeri 1 Pngkalan Koto Baru untuk mengimplementasikan pendidikan karakter baik, dinilai dari kurikulum yang telah terintegrasi pendidikan karakter, namun masih kurang dalam hal pengelolaan sarana prasarana pendukung dan banyak guru memerlukan lebih banyak pengetahuan dan keterampilan tentang pendidikan karakter; (2) implementasi pendidikan karakter belum tampak pada kegiatan pembelajaran; (3) dukungan dari pemerintah dalam sosialisasi atau pelatihan dirasa masih kurang oleh sekolah; (4) monitoring dan evaluasi pendidikan karakter masih terbatas pada kurikulum dan dilakukan melalui pembinaan pengawas di setiap sekolah; dan (5) kendala yang umum dihadapi sekolah adalah penilaian sikap siswa yang belum terdokumentasi, kurangnya pemahaman guru untuk mengimplementasikan pendidikan karakter, dan tidak adanya sinergi antara pendidikan di sekolah dengan pendidikan di rumah

Establishing an Institutional Framework for the Handicrafts Clusters in Egypt/ إنشاء إطار مؤسسي لتجمعات الحرف اليدوية في مصر

The Egyptian handicrafts sector, which employs more than a million Egyptians, and contributes to local economic growth and to the export market, has a lot of potentials but faces numerous challenges. Aware of the potential of the sector, the Egyptian government is currently focusing on the development of handicrafts, mostly organized as clusters. Nevertheless, artisans face numerous challenges, some of which are related to access to financial resources and raw materials, access to markets especially international ones, access to marketing opportunities, access to technical know-how, among others. Whilst handicrafts production is mostly cluster-based in Egypt, it is highly informal. One of the direst challenges facing handicrafts clusters is the lack of clarity on the roles and mandates of the various stakeholders working in the sector. To address this challenge, this policy memo recommends three different layers of multi-stakeholder cooperation. At the national level, a ministerial handicrafts clusters steering committee is to be established and led by the Prime Minister. Its administrative arm, the technical secretariat would be led by the Micro-, Small and Medium Enterprise Development Agency (MSMEDA). Also led by the MSMEDA is the operational arm of the national committee, and the executive committee, which would include members from the public and private sectors at the central level. At the local level, local handicrafts clusters platforms (HCPs) would be established and led by the governors in each governorate. These dialogue platforms would ensure coordination between the relevant stakeholders at the decentral level

The Effect of Waste Bagasse (Saccharum SP) Fertilizer Toward Growth of Peanuts (Arachis Hypogaea L.)

The process of sugar cane into sugar which is carried out in the sugar mill produces bagasse obtained from the milling process around 32% of the total cane processed. Sugarcane production in Indonesia in 2007 amounted to 21 million tons, the potential of bagasse produced about 6 million tons of bagasse per year. Up untill now almost every cane sugar mills uses bagasse as boiler fuel, animal feed mixes and the rest are burned or thrown away. One of alternative solid waste management is to turn solid waste into compost.The purpose of this research is to understand the effect of bagasse fertilizer on growth and progress of peanut plants (Arachis hypogaea L.). Bagasse fertilizer made using cow dung as bioactivator. Bagasse obtained from several places in Semarang mashed with finely enough size. Then, with a ratio of cow dung and bagasse 1: 3. Placed in a container then mix and sealed until there is no incoming air. Every 4 or 5 days in 4 weeks is being inverted. After 4 weeks it will get bagasse fertilizer with characteristic brown color, odorless and slightly moist. This research uses three treatments there are peanuts with mixed bagasse fertilizer on the soil medium, compost on the soil medium, and without fertilizer then measured the progress for 14 days. After 14 days, so it obtained an average of plants height and number of leaves. Respectively, are 2.10; 1.38; 2.24 while the number of leaves are 2.55; 2.66; 3.2

Physical activity, sedentary behaviors and dietary habits among Saudi adolescents relative to age, gender and region

<p>Abstract</p> <p>Background</p> <p>Few lifestyle factors have been simultaneously studied and reported for Saudi adolescents. Therefore, the purpose of the present study was to report on the prevalence of physical activity, sedentary behaviors and dietary habits among Saudi adolescents and to examine the interrelationships among these factors using representative samples drawn from three major cities in Saudi Arabia.</p> <p>Methods</p> <p>This school-based cross-sectional study was conducted during the years 2009-2010 in three cities: Al-Khobar, Jeddah and Riyadh. The participants were 2908 secondary-school males (1401) and females (1507) aged 14-19 years, randomly selected using a multistage stratified sampling technique. Measurements included weight, height, sedentary behaviors (TV viewing, playing video games and computer use), physical activity using a validated questionnaire and dietary habits.</p> <p>Results</p> <p>A very high proportion (84% for males and 91.2% for females) of Saudi adolescents spent more than 2 hours on screen time daily and almost half of the males and three-quarters of the females did not meet daily physical activity guidelines. The majority of adolescents did not have a daily intake of breakfast, fruit, vegetables and milk. Females were significantly (<it>p </it>< 0.05) more sedentary, much less physically active, especially with vigorous physical activity, and there were fewer days per week when they consumed breakfast, fruit, milk and diary products, sugar-sweetened drinks, fast foods and energy drinks than did males. However, the females' intake of French fries and potato chips, cakes and donuts, and candy and chocolate was significantly (<it>p </it>< 0.05) higher than the males'. Screen time was significantly (<it>p </it>< 0.05) correlated inversely with the intake of breakfast, vegetables and fruit. Physical activity had a significant (<it>p </it>< 0.05) positive relationship with fruit and vegetable intake but not with sedentary behaviors.</p> <p>Conclusions</p> <p>The high prevalence of sedentary behaviors, physical inactivity and unhealthy dietary habits among Saudi adolescents is a major public health concern. There is an urgent need for national policy promoting active living and healthy eating and reducing sedentary behaviors among children and adolescents in Saudi Arabia.</p