Le savoir expérientiel des enfants aux prises avec des allergies alimentaires

Les familles d’enfants aux prises avec des allergies alimentaires font souvent face à des besoins éducationnels non comblés. La reconnaissance du savoir expérientiel émanant du vécu d’une maladie chronique ainsi que l’attribution de plus amples responsabilités aux patients pourraient être bénéfiques au système de santé et répondre davantage aux besoins des familles. À ce jour, le savoir expérientiel des enfants aux prises avec des maladies chroniques n’est cependant pas documenté. L’objectif de ce projet est alors d’explorer qualitativement le savoir expérientiel des enfants de moins de 13 ans vivant avec des allergies alimentaires afin de pouvoir inclure leur perspective dans notre pratique clinique. Ainsi, 33 participants ont témoigné de leur expérience par entrevue. Parmi ceux-ci se trouvaient 14 enfants âgés de 8 et 12 ans ainsi que 19 parents. Les entrevues ont été analysées en utilisant une approche inductive générale. Notre étude démontre que le développement du savoir expérientiel dans cette population débute tôt dans l’enfance. Ce savoir est surtout acquis par la mise en pratique des enseignements parentaux ainsi que par l’expérimentation de réactions allergiques. Les perspectives distinctes de la maladie entre l’enfant et ses parents mènent à des différences sur le plan de leur savoir expérientiel respectif. Chez ces enfants, le savoir expérientiel promeut la gestion autonome de la maladie ainsi qu’un degré de normalité ainsi que d’équilibre ce qui contribue a une amélioration de leur qualité de vie. En conclusion, le savoir expérientiel des enfants aux prises avec des allergies alimentaires existe et doit être reconnu. Ce savoir est distinct de celui des parents et influence positivement les habiletés de gestion autonome de l’enfant ainsi que leur perspective de la maladie. Les professionnels de la santé ainsi que les parents bénéficieraient d’accompagnement afin de comprendre et mobiliser ce savoir expérientiel chez l’enfant.Families with a food-allergic child often mention unmet education needs. Recognizing the experiential knowledge from living with the illness and entrusting the patient with greater responsibilities could better the health care and respond to the families’ needs. However, experiential knowledge is not well documented in children with chronic health conditions. Therefore, the objective in our study was to explore the experiential knowledge of children under 13 years old living with food allergies as recounted by them and their families to include their views in clinical practice. Thirty-three participants were interviewed including 14 children between eight and twelve years old and 19 parents. Interviews were analyzed using a general inductive approach. Our study shows that the development of experiential knowledge in food-allergic children starts in childhood. Children’ experiential knowledge is mostly acquired by applying teachings and experiencing reactions. The different illness perspectives between the child and his parents explain the distinctive properties of the children’s experiential knowledge. In food-allergic children, experiential knowledge promotes self-management skills and also senses of normality and balance thus contributing to better quality of life. In conclusion, experiential knowledge of food-allergic children exists and should be recognized. This knowledge is distinctive from their parent’s and impacts positively the children’s self-management skills and their own illness perspective. Clinicians and parents would benefit of support and methods to understand and mobilize the food-allergic child’s experiential knowledge

Synthèse cinématique d'un octopode parallèle sans surcontrainte avec conditions de singularité simples

Ce mémoire présente l'étude du lieu des singularités de type II pour un mécanisme parallèle cinématiquement redondant à (6+2) degrés de liberté dont l'architecture est préalablement donnée. Cette étude se concentre sur les conditions mathématiques telles que le déterminant de la matrice jacobienne s'annule pour toutes configurations dues à la mobilité interne du mécanisme permise par la redondance cinématique. Pour ce faire, la construction d'une matrice partageant les mêmes conditions de singularité que la matrice jacobienne du mécanisme est présentée. La réécriture du déterminant de cette matrice par une sommation de quatre sous-déterminants pondérée par les paramètres de mobilité interne du mécanisme mène à un système d'équations non linéaires à résoudre pour obtenir le lieu des singularités. Une méthode d'élimination de variables, le résultant des polynômes, est ensuite appliquée de manière récursive à ce système d'équations afin d'en extraire les conditions pouvant le résoudre. Les lieux de singularité sont ensuite analysés suivant deux cas de figure. Le premier se penche sur les configurations spécifiques du mécanisme où l'angle de torsion de la plateforme est nul, et le second se concentre sur le cas général, où cet angle de torsion n'est pas nécessairement nul. Dans le premier cas d'analyse, il est montré que les lieux de singularité se situent à l'extérieur de l'espace atteignable du mécanisme cinématiquement redondant. Dans le second cas d'analyse, il est montré que l'espace en orientation demeure quelque peu affecté par la présence de singularités, bien que leur localisation par des équations mathématiques analytiques simples soit possible. Finalement, une comparaison graphique des espaces atteignables en orientation entre le mécanisme cinématiquement redondant et le mécanisme non redondant standard est effectuée afin de visualiser l'impact de l'ajout de la redondance cinématique sur l'agrandissement de l'espace en orientation.This thesis presents the study of the type II singularity locus of a kinematically redundant(6+2) degree-of-freedom parallel mechanism whose architecture is prescribed. This studyfocuses on the mathematical conditions for which the determinant of the Jacobian matrixvanishes for all configurations of the internal mobility in the mechanism due to its kinematicredundancy. To do so, a matrix that captures the same conditions of singularity as the Jacobian matrix is presented. The expansion of the determinant of the aforementioned matrixinto a weighted sum of four sub-determinants whose weighting factors correspond to theinternal mobility parameters leads to a nonlinear system of equations whose solution yieldsthe locus of singularity. A method of elimination theory, the resultant of polynomials, isapplied afterwards on the system of equations in a recursive manner to extract the mathematical conditions corresponding to the solution. The loci of singularity are then analyzedfollowing two cases. The first case focuses on the specific configurations of the mechanismwhere the torsion angle of the platform is zero, whereas the second case takes into accountthe general configurations, i.e. the configurations in which the torsion angle is not necessarily zero. In the former case of analysis, it is shown that the loci of singularity lie outsideof the reachable orientational workspace of the kinematically redundant mechanism. In thelatter case of analysis, it is presented that the orientational workspace is still somewhat restrained by singularities, yet their localization by simple analytical mathematical equationsis possible. Finally, a graphical comparison of the orientational reachable workspace of thekinematically redundant mechanism and that of the standard non-redundant mechanism isperformed to visualize the impact of the kinematic redundancy on the enhancement of theorientational workspace

DYRK1A-Related Trabecular Defects in Male Ts65Dn Mice Emerge During a Critical Developmental Window

Indiana University-Purdue University Indianapolis (IUPUI)Down syndrome (DS) is a complex genetic disorder caused by the triplication of human chromosome 21 (Hsa21). The presence of an extra copy of an entire chromosome greatly disrupts the copy number and expression of over 350 protein coding genes. This gene dosage imbalance has far-reaching effects on normal development and aging, leading to cognitive and skeletal defects that emerge earlier in life than the general population. The present study begins by characterizing skeletal development in young male Ts65Dn mice to test the hypothesis that skeletal defects in male Ts65Dn mice are developmental in nature.Femurs from young mice ranging from postnatal day 12- to 42-days of age (P12-42) were measured and analyzed by microcomputed tomography (μCT). Cortical defects were present generally throughout development, but trabecular defects emerged at P30 and persisted until P42. The gene Dual-specificity tyrosine-regulated kinase 1a (Dyrk1a) is triplicated in both DS and in Ts65Dn mice and has been implicated as a putative cause of both cognitive and skeletal defects. To test the hypothesis that trisomic Dyrk1a is related to the emergence of trabecular defects at P30, expression of Dyrk1a in the femurs of male Ts65Dn mice was quantified by qPCR. Expression was shown to fluctuate throughout development and overexpression generally aligned with the emergence of trabecular defects at P30. The growth rate in trabecular measures between male Ts65Dn and euploid littermates was similar between P30 and P42, suggesting a closer look into cellular mechanisms at P42. Assessment of proliferation of BMSCs, differentiation and activity of osteoblasts showed no significant differences between Ts65Dn and euploid cellular activity, suggesting that the cellular microenvironment has a greater influence on cellular activity than genetic background. These data led to the hypothesis that reduction of Dyrk1a gene expression and pharmacological inhibition of DYRK1A could be executed during a critical period to prevent the emergence of trabecular defects at P30. To tests this hypothesis, doxycycline-induced cre-lox recombination to reduce Dyrk1a gene copy number or the DYRK1A inhibitor CX-4945 began at P21. The results of both genetic and pharmacological interventions suggest that trisomic Dyrk1a does not influence the emergence of trabecular defects up to P30. Instead, data suggest that the critical window for the rescue of trabecular defects lies between P30 and P42

Using Amino Acid Derivatives to Inhibit Pseudomonas aeruginosa Biofilm Formation on Cystic Fibrosis Bronchial Epithelia Cells

poster abstractCystic Fibrosis is a genetic disease caused by a mutation which inhibits the proper transport of sodium and chloride ions across epithelium. Improper ion transport results in the accumulation of thick mucus in critical organs such as the lungs, pancreas, liver, and intestines. The genetic mutation is incurable, but treating the symptoms can vastly increase life expectancy. CF patients are often afflicted with bacterial infections which colonize the excess mucus within the lungs. The most prevalent pathogen associated with CF lung infection is Pseudomonas aeruginosa, a Gram-negative bacterium found in soil and water. Pseudomonas aeruginosa exists in two forms: planktonic (free-swimming) and sessile (immobile within a biofilm community). The planktonic form is about 1,000x more susceptible to antibiotics and immune cells than the sessile form. Biofilm communities of sessile bacteria are protected by an exopolysaccharide layer outside of the cell wall. Small molecules which inhibit biofilm formation or initiate biofilm disassembly can dramatically increase the effectiveness of drugs and the immune system. In order to identify novel biofilm-inhibitory molecules, we assessed the activity of a library of small molecules in biofilm assays. Active compounds were then screened for activity on living Cystic Fibrosis bronchial epithelial cells infected with Pseudomonas aeruginosa. Compounds which successfully inhibit biofilm formation without affecting the Cystic Fibrosis bronchial epithelium cells can potentially be a new drug for treating Cystic Fibrosis infections

Skeletal Dynamics of Down Syndrome: A Developing Perspective

Individuals with Down syndrome (DS) display distinctive skeletal morphology compared to the general population, but disparate descriptions, methodologies, analyses, and populations sampled have led to diverging conclusions about this unique skeletal phenotype. As individuals with DS are living longer, they may be at a higher risk of aging disorders such as osteoporosis and increased fracture risk. Sexual dimorphism has been suggested between males and females with DS in which males, not females, experience an earlier decline in bone mineral density (BMD). Unfortunately, studies focusing on skeletal health related to Trisomy 21 (T21) are few in number and often too underpowered to answer questions about skeletal development, resultant osteoporosis, and sexual dimorphism, especially in stages of bone accrual. Further confounding the field are the varied methods of bone imaging, analysis, and data interpretation. This review takes a critical look at the current knowledge of DS skeletal phenotypes, both from human and mouse studies, and presents knowledge gaps that need to be addressed, differences in research methodologies and analyses that affect the interpretation of results, and proposes guidelines for overcoming obstacles to understand skeletal traits associated with DS. By examining our current knowledge of bone in individuals with T21, a trajectory for future studies may be established to provide meaningful solutions for understanding the development of and improving skeletal structures in individuals with and without DS

Genetic and Functional Modularity of Hox Activities in the Specification of Limb-Innervating Motor Neurons

A critical step in the assembly of the neural circuits that control tetrapod locomotion is the specification of the lateral motor column (LMC), a diverse motor neuron population targeting limb musculature. Hox6 paralog group genes have been implicated as key determinants of LMC fate at forelimb levels of the spinal cord, through their ability to promote expression of the LMC-restricted genes Foxp1 and Raldh2 and to suppress thoracic fates through exclusion of Hoxc9. The specific roles and mechanisms of Hox6 gene function in LMC neurons, however, are not known. We show that Hox6 genes are critical for diverse facets of LMC identity and define motifs required for their in vivo specificities. Although Hox6 genes are necessary for generating the appropriate number of LMC neurons, they are not absolutely required for the induction of forelimb LMC molecular determinants. In the absence of Hox6 activity, LMC identity appears to be preserved through a diverse array of Hox5–Hox8 paralogs, which are sufficient to reprogram thoracic motor neurons to an LMC fate. In contrast to the apparently permissive Hox inputs to early LMC gene programs, individual Hox genes, such as Hoxc6, have specific roles in promoting motor neuron pool diversity within the LMC. Dissection of motifs required for Hox in vivo specificities reveals that either cross-repressive interactions or cooperativity with Pbx cofactors are sufficient to induce LMC identity, with the N-terminus capable of promoting columnar, but not pool, identity when transferred to a heterologous homeodomain. These results indicate that Hox proteins orchestrate diverse aspects of cell fate specification through both the convergent regulation of gene programs regulated by many paralogs and also more restricted actions encoded through specificity determinants in the N-terminus

Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes

Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~ 50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~ 10 mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~ 20 mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2–3 mg per day (~ 40–60 mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4 mg/mL] or a water control, with treatments yielding average daily intakes of ~ 50 mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)—which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking—and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis in the cerebellum. The lack of beneficial therapeutic behavioral effects and potentially detrimental skeletal effects of EGCG found in Ts65Dn mice emphasize the importance of identifying dosages of EGCG that reliably improve DS phenotypes and linking those effects to actions of EGCG (or EGCG-containing supplements) in specific targets in brain and bone

Evaluation of the therapeutic potential of Epigallocatechin-3-gallate (EGCG) via oral gavage in young adult Down syndrome mice

Epigallocatechin-3-gallate (EGCG) is a candidate therapeutic for Down syndrome (DS) phenotypes based on in vitro inhibition of DYRK1A, a triplicated gene product of Trisomy 21 (Ts21). Consumption of green tea extracts containing EGCG improved some cognitive and behavioral outcomes in DS mouse models and in humans with Ts21. In contrast, treatment with pure EGCG in DS mouse models did not improve neurobehavioral phenotypes. This study tested the hypothesis that 200 mg/kg/day of pure EGCG, given via oral gavage, would improve neurobehavioral and skeletal phenotypes in the Ts65Dn DS mouse model. Serum EGCG levels post-gavage were significantly higher in trisomic mice than in euploid mice. Daily EGCG gavage treatments over three weeks resulted in growth deficits in both euploid and trisomic mice. Compared to vehicle treatment, EGCG did not significantly improve behavioral performance of Ts65Dn mice in the multivariate concentric square field, balance beam, or Morris water maze tasks, but reduced swimming speed. Furthermore, EGCG resulted in reduced cortical bone structure and strength in Ts65Dn mice. These outcomes failed to support the therapeutic potential of EGCG, and the deleterious effects on growth and skeletal phenotypes underscore the need for caution in high-dose EGCG supplements as an intervention in DS

Crossover Scaling in Dendritic Evolution at Low Undercooling

We examine scaling in two-dimensional simulations of dendritic growth at low undercooling, as well as in three-dimensional pivalic acid dendrites grown on NASA's USMP-4 Isothermal Dendritic Growth Experiment. We report new results on self-similar evolution in both the experiments and simulations. We find that the time dependent scaling of our low undercooling simulations displays a cross-over scaling from a regime different than that characterizing Laplacian growth to steady-state growth