The association between urinary continence and quality of life in paediatric patients with spina bifida and tethered cord.

OBJECTIVE: To determine the association between urinary continence and quality of life (QoL) in a paediatric spina bifida population. METHODS: After appropriate ethics approval, a prospective study was initiated using multiple validated QoL instruments that were distributed to patients as they presented for their annual appointment at the Northern Alberta Spina Bifida Clinic (Edmonton, Alberta). General demographic information was collected and validated questionnaires were used. The survey package included two instruments to assess overall QoL: Global Pediatric QoL (PedsQL 4.0) and Health Specific QoL-Spina Bifida (HRQoL-SB). Two instruments were also included to quantify urinary symptoms and assess urinary specific QoL: the Urinary Incontinence Severity Index - Pediatric (ISI-P) and Urinary Specific QoL (PinQ). RESULTS: A total of 71 patients were enrolled in the study. The general QoL (PedsQL 4.0) and health-specific QoL (HRQoL-SB) scores for the population indicated an overall QoL of 66% (n=69) and 83% (n=67), respectively. Approximately 46% (33 of 71) reported >1 episode of urinary incontinence per week. Urinary continence was associated with a significantly higher urinary-specific QoL (PinQ; P<0.001), general QoL (PedsQL 4.0; P<0.05) and health-specific QoL (HRQoL-SB; P<0.05). Furthermore, urinary incontinence and its effect on QoL was not influenced by the presence of a shunt, level of the lesion or manner of dysraphism. CONCLUSION: These data suggest that QoL in patients with spina bifida is related to urinary continence. This effect appears to be independent of the type and level of the spinal dysraphism and the presence or absence of a shunt.

OBJECTIF: Déterminer l'association entre la continence urinaire et la qualité de vie (QdV) au sein de la population d'âge pédiatrique ayant un spina-bifida. MÉTHODOLOGIE: Après l'approbation déontologique pertinente, les chercheurs ont amorcé une étude prospective au moyen de multiples instruments validés relatifs à la QdV, qui ont été distribués aux patients lors de leur rendez-vous annuel à la clinique de spina-bifida du nord de l'Alberta située à Edmonton, en Alberta. Ils ont colligé les renseignements démographiques généraux et utilisé des questionnaires validés. Le dossier de l'étude se composait de deux instruments pour valider la QdV globale : la QdV pédiatrique globale (PedsQL 4.0) et la QdV propre à la santé (HRQoL-SB). Deux instruments ont également été utilisés pour quantifier les symptômes urinaires et évaluer la QdV propre aux symptômes urinaires : l'indice de gravité de l'incontinence urinaire ­ pédiatrique (ISI-P) et la QdV propre aux symptômes urinaires (PinQ). RÉSULTATS: Au total, 71 patients ont participé à l'étude. Les indices de QdV générale (PedsQL 4.0) et de QdV propre à la santé (HRQoL-SB) pour cette population ont indiqué une QdV globale de 66 % (n=69) et de 83 % (n=67), respectivement. Environ 46 % (33 sur 71) ont déclaré plus d'un épisode d'incontinence urinaire par semaine. La continence urinaire s'associait à une QdV propre aux symptômes urinaires, à une QdV générale et à une QdV propre à la santé nettement plus élevées (PinQ : P<0,001, PedsQL 4.0 : P<0,05 et HRQoL-SB : P<0,05, respectivement). Par ailleurs, la présence d'un shunt, le niveau de la lésion et la gravité de la dysraphie n'avaient pas d'influence sur l'incontinence urinaire et son effet sur la QdV. CONCLUSION: Selon ces données, la QdV des patients ayant un spina-bifida est liée à la continence urinaire. Cet effet semble indépendant du type et du niveau de dysraphie spinale et de la présence ou de l'absence d'un shunt.

14-3-3 mediated regulation of the tumor suppressor protein, RASSF1A.

Death receptor-dependent apoptosis is an important mechanism of growth control. It has been demonstrated that Ras association domain family protein 1A (RASSF1A) is a tumor suppressor protein involved in death receptor-dependent apoptosis. However, it is unclear how RASSF1A-mediated cell death is initiated. We have now detailed 14-3-3 dependent regulation of RASSF1A-mediated cell death. We demonstrate that basal association of RASSF1A with 14-3-3 was lost following stimulation with tumor necrosis factor alpha (TNFalpha) or TNFalpha related apoptosis inducing ligand (TRAIL). Subsequent to the loss of 14-3-3 association, RASSF1A associated with modulator of apoptosis (MOAP-1) followed by death receptor association with either TNFalpha receptor 1 (TNF-R1) or TRAIL receptor 1 (TRAIL-R1). 14-3-3 association required basal phosphorylation by the serine/threonine kinase, glycogen synthase kinase 3beta (GSK-3beta), on serine 175, 178, and 179. Mutation of these critical serines resulted in the loss of 14-3-3 association and earlier recruitment of RASSF1A to MOAP-1, TNF-R1, and TRAIL-R1. Furthermore, stable cells containing a triple serine mutant of RASSF1A [serine (S) 175 to alanine (A) [S175A], S178A, and S179A] resulted in increased basal cell death, enhanced Annexin V staining and enhanced cleavage of poly (ADP-ribose) polymerase (PARP) following TNFalpha stimulation when compared to stable cells containing wild type RASSF1A. RASSF1A-mediated cell death is, therefore, tightly controlled by 14-3-3 association.