La vraie équation ? Les soins palliatifs = qualité de vie

Le Service de soins palliatifs de l'Université McGiIl est la réponse d'une équipe multidisciplinaire aux besoins de son milieu. Dans cet article, on trouve un résumé de la philosophie qui a servi de pierre d'assise à cette démarche et une brève description de chacun des cinq secteurs d'activités spécifiques et complémentaires ; l'unité de soins, le service de soins à domicile, la clinique externe, l'équipe de consultation et le service d'assistance au deuil. Enfin, les buts du service, les soins aux malades, la recherche et l'enseignement sont exposés.In this article the experience of the McGiIl Palliative Care Service is used as an illustration of the basic concepts of the palliative care philosophy in our community. A trained multidisciplinary team is oriented toward meeting the physical, psychosocial and spiritual needs of patients with advanced disease and their families through a home care service in the community, a consultation team throughout the hospital, an outpatient clinic, an inpatient unit and a bereavement follow-up program.The goals of the service are, in order of priority, patient care, research and teaching

Expression of the Hsp23 chaperone during Drosophila embryogenesis: association to distinct neural and glial lineages

BACKGROUND: In addition to their strong induction following stress, small heat shock proteins (Hsp) are also expressed during development in a wide variety of organisms. However, the precise identity of cell(s) expressing these proteins and the functional contribution of small heat shock proteins in such developmental context remain to be determined. The present study provides a detailed description of the Drosophila small heat shock protein Hsp23 expression pattern during embryogenesis and evaluates its functional contribution to central nervous system development. RESULTS: Throughout embryogenesis, Hsp23 is expressed in a stage-specific manner by a restricted number of neuronal and glial lineages of the central nervous system. Hsp23 is also detected in the amnioserosa and within a single lateral chordotonal organ. Its expression within the MP2 lineage does not require the presence of a functional midline nor the activity of the Notch signaling pathway. Transactivation assays demonstrate that transcription factors implicated in the differentiation of the midline also regulate hsp23 promoter activity. Phenotypic analysis of a transgenic line exhibiting loss of Hsp23 expression in the central nervous system suggests that Hsp23 is not required for development and function of this tissue. Likewise, its overexpression does not cause deleterious effects, as development remains unaffected. CONCLUSIONS: Based on the presented data, we suggest that the tightly regulated developmental expression of Hsp23 is not actively involved in cell differentiation and central nervous system development per se but rather reflects a putative role in preventive "pre-stress" neuroprotection or in non-vital process(es) common to the identified cell lineages

A minor alternative transcript of the fumarylacetoacetate hydrolase gene produces a protein despite being likely subjected to nonsense-mediated mRNA decay

BACKGROUND: Coupling of alternative splicing with nonsense-mediated mRNA decay (NMD) may regulate gene expression. We report here the identification of a nonsense alternative transcript of the fumarylacetoacetate hydrolase (fah) gene, which produces a protein despite the fact that it is subject to NMD. RESULTS: During the characterization of the effects of the W262X nonsense mutation on FAH mRNA metabolism, two alternative transcripts (del100 and del231) of the fah gene were identified. Del100 lacks exon 8 and as a consequence, the reading frame is shifted and a premature termination codon appears at the 3'end of exon 10. Exons 8 and 9 are skipped in del231, without any disruption of the reading frame. Specific amplification of these transcripts demonstrate that they are produced through minor alternative splicing pathways, and that they are not caused by the W262X mutation per se. As shown with an antiserum raised against the C-terminal part of the putative DEL100 protein, the del100 transcript produces a protein, expressed at different levels in various human tissues. Interestingly, the del100 transcript seems to be subjected to nonsense-mediated mRNA decay, as its level was stabilized following a cycloheximide treatment. CONCLUSIONS: The del100 and del231 transcripts arise due to minor alternative splicing pathways and del100 is likely subjected to nonsense-mediated mRNA decay. However the remaining amount of transcript seems sufficient to produce a protein in different human tissues. This suggests that NMD has a broader role than simply eliminating aberrant transcripts and when coupled to alternative splicing, may act to modulate gene expression, by allowing the production of low amounts of protein

Post Colonial Cosmopolitanism: Making Place for Nationalism

Rahul Rao, School of Oriental & African Studies, University of London, expresses a number of dissatisfactions with the debate between cosmopolitanism and communitarianism in international normative theory. Respondents: Robert Howse, New York University; Alice MacLachlan, York University, Philosophy

A Missense Mutation (Q279R) in the Fumarylacetoacetate Hydrolase Gene, Responsible for Hereditary Tyrosinemia, Acts as a Splicing Mutation

Background: Tyrosinemia type I, the most severe disease of the tyrosine catabolic pathway is caused by a deficiency in fumarylacetoacetate hydrolase (FAH). A patient showing few of the symptoms associated with the disease, was found to be a compound heterozygote for a splice mutation, IVS6-1g->t, and a putative missense mutation, Q279R. Analysis of FAH expression in liver sections obtained after resection for hepatocellular carcinoma revealed a mosaic pattern of expression. No FAH was found in tumor regions while a healthy region contained enzymeexpressing nodules. Results: Analysis of DNA from a FAH expressing region showed that the expression of the protein was due to correction of the Q279R mutation. RT-PCR was used to assess if Q279R RNA was produced in the liver cells and in fibroblasts from the patient. Normal mRNA was found in the liver region where the mutation had reverted while splicing intermediates were found in nonexpressing regions suggesting that the Q279R mutation acted as a splicing mutation in vivo. Sequence of transcripts showed skipping of exon 8 alone or together with exon 9. Using minigenes in transfection assays, the Q279R mutation was shown to induce skipping of exon 9 when placed in a constitutive splicing environment. Conclusion: These data suggest that the putative missense mutation Q279R in the FAH gene acts as a splicing mutation in vivo. Moreover FAH expression can be partially restored in certain liver cells as a result of a reversion of the Q279R mutation and expansion of the corrected cells

Comparative metal oxide nanoparticle toxicity using embryonic zebrafish

AbstractEngineered metal oxide nanoparticles (MO NPs) are finding increasing utility in the medical field as anticancer agents. Before validation of in vivo anticancer efficacy can occur, a better understanding of whole-animal toxicity is required. We compared the toxicity of seven widely used semiconductor MO NPs made from zinc oxide (ZnO), titanium dioxide, cerium dioxide and tin dioxide prepared in pure water and in synthetic seawater using a five-day embryonic zebrafish assay. We hypothesized that the toxicity of these engineered MO NPs would depend on physicochemical properties. Significant agglomeration of MO NPs in aqueous solutions is common making it challenging to associate NP characteristics such as size and charge with toxicity. However, data from our agglomerated MO NPs suggests that the elemental composition and dissolution potential are major drivers of toxicity. Only ZnO caused significant adverse effects of all MO particles tested, and only when prepared in pure water (point estimate median lethal concentration=3.5–9.1mg/L). This toxicity was life stage dependent. The 24h toxicity increased greatly (∼22.7 fold) when zebrafish exposures started at the larval life stage compared to the 24h toxicity following embryonic exposure. Investigation into whether dissolution could account for ZnO toxicity revealed high levels of zinc ion (40–89% of total sample) were generated. Exposure to zinc ion equivalents revealed dissolved Zn2+ may be a major contributor to ZnO toxicity

Development of a MSW gasification model for flexible integration into a MFA-LCA framework

This paper presents the development of a comprehensive gasification module designed to be integrated in a MFA-LCA framework. From existing gasification models present in the literature, the most appropriate modelling strategy is selected and implemented into the module. This module needs to be able to capture the influence of input parameters, such as gasification reactor type, oxidizing agent, feedstock composition and operating conditions on the process outputs, including syngas yield, its composition and LHV, as well as tar and char contents. A typical gasification process is usually modelled in four steps: drying, pyrolysis, oxidation and reduction. Models representing each of these steps are presented in this paper. Since the type of gasification reactor is taken into account in the module, models for downdraft moving bed and bubbling fluidized bed reactor are also reviewed. The gasification module will be integrated into a MFA framework (VMR-Sys), which enables calculation of relevant gasifier feedstock parameters, such as moisture content, composition, properties and particle size distribution. Outputs from the module will also include elemental compositions obtained from VMR-Sys calculations. Finally, all outputs from the module will be used to build LCA-inventory data