Classifying Polypharmacy According to Pharmacotherapeutic and Clinical Risks in Older Adults: A Latent Class Analysis in Quebec, Canada.

INTRODUCTION: The simplistic definition of polypharmacy, often designated as the concomitant use of five medications or more, does not distinguish appropriate from inappropriate polypharmacy. Classifying polypharmacy according to varying levels of health risk would help optimise medication use. OBJECTIVE: We aimed to characterise different types of polypharmacy among older adults and evaluate their association with mortality and institutionalisation. METHODS: Using healthcare databases from the Quebec Integrated Chronic Disease Surveillance System, we selected a community-based random sample of the population ≥ 66 years old covered by the public drug plan. Categorical indicators used to describe polypharmacy included number of medications, potentially inappropriate medications (PIMs), drug-drug interactions, enhanced surveillance medications, complex route of administration medications, anticholinergic cognitive burden (ACB) score and use of blister cards. We used a latent class analysis to subdivide participants into distinct groups of polypharmacy. Their association with 3-year mortality and institutionalisation was assessed with adjusted Cox models. RESULTS: In total, 93,516 individuals were included. A four-class model was selected with groups described as (1) no polypharmacy (46% of our sample), (2) high-medium number of medications, low risk (33%), (3) medium number of medications, PIM use with or without high ACB score (8%) and (4) hyperpolypharmacy, complex use, high risk (13%). Using the class without polypharmacy as the reference, all polypharmacy classes were associated with 3-year mortality and institutionalisation, with the most complex/inappropriate classes denoting the highest risk (hazard ratio [HR] [95% confidence interval]: class 3, 70-year-old point estimate for mortality 1.52 [1.30-1.78] and institutionalisation 1.86 [1.52-2.29]; class 4, 70-year-old point estimate for mortality 2.74 [2.44-3.08] and institutionalisation 3.11 [2.60-3.70]). CONCLUSIONS: We distinguished three types of polypharmacy with varying pharmacotherapeutic and clinical appropriateness. Our results highlight the value of looking beyond the number of medications to assess polypharmacy.

Development of optimised tissue-equivalent materials for proton therapy.

Objective. In proton therapy there is a need for proton optimised tissue-equivalent materials as existing phantom materials can produce large uncertainties in the determination of absorbed dose and range measurements. The aim of this work is to develop and characterise optimised tissue-equivalent materials for proton therapy.Approach. A mathematical model was developed to enable the formulation of epoxy-resin based tissue-equivalent materials that are optimised for all relevant interactions of protons with matter, as well as photon interactions, which play a role in the acquisition of CT numbers. This model developed formulations for vertebra bone- and skeletal muscle-equivalent plastic materials. The tissue equivalence of these new materials and commercial bone- and muscle-equivalent plastic materials were theoretical compared against biological tissue compositions. The new materials were manufactured and characterised by their mass density, relative stopping power (RSP) measurements, and CT scans to evaluate their tissue-equivalence.Main results. Results showed that existing tissue-equivalent materials can produce large uncertainties in proton therapy dosimetry. In particular commercial bone materials showed to have a relative difference up to 8% for range. On the contrary, the best optimised formulations were shown to mimic their target human tissues within 1%-2% for the mass density and RSP. Furthermore, their CT-predicted RSP agreed within 1%-2% of the experimental RSP, confirming their suitability as clinical phantom materials.Significance. We have developed a tool for the formulation of tissue-equivalent materials optimised for proton dosimetry. Our model has enabled the development of proton optimised tissue-equivalent materials which perform better than existing tissue-equivalent materials. These new materials will enable the advancement of clinical proton phantoms for accurate proton dosimetry.

Hydro-climatic changes of wetlandscapes across the world.

Assessments of ecosystem service and function losses of wetlandscapes (i.e., wetlands and their hydrological catchments) suffer from knowledge gaps regarding impacts of ongoing hydro-climatic change. This study investigates hydro-climatic changes during 1976-2015 in 25 wetlandscapes distributed across the world's tropical, arid, temperate and cold climate zones. Results show that the wetlandscapes were subject to precipitation (P) and temperature (T) changes consistent with mean changes over the world's land area. However, arid and cold wetlandscapes experienced higher T increases than their respective climate zone. Also, average P decreased in arid and cold wetlandscapes, contrarily to P of arid and cold climate zones, suggesting that these wetlandscapes are located in regions of elevated climate pressures. For most wetlandscapes with available runoff (R) data, the decreases were larger in R than in P, which was attributed to aggravation of climate change impacts by enhanced evapotranspiration losses, e.g. caused by land-use changes.

Towards a better understanding of the benefits and risks of country food consumption using the case of walruses in Nunavik (Northern Quebec, Canada).

Food insecurity affects Inuit communities. One solution is to consume locally harvested foods, named country foods. However, some country foods are not eaten as often as before, and pressures including contaminants and environmental changes threaten the health of Arctic fauna, thus its suitability for local consumption. By combining Inuit Knowledge with laboratory data, our study assessed the benefits and risks of walrus consumption by Inuit in Nunavik, Québec, Canada. It aimed to increase understanding of: 1) the hunt of healthy Atlantic walruses (Odobenus rosmarus rosmarus); 2) the safe preparation of walruses; 3) the nutritional benefits and risks of consuming walruses. To do so, we interviewed 34 hunters and Elders from Nunavik. Levels of mercury, omega-3 polyunsaturated fatty acids and selenium were evaluated from locally harvested walruses. Through the Nunavik Trichinellosis Prevention Program, a total of 755 Atlantic walrus samples, collected between 1994 and 2013, were tested for Trichinella nativa. Information on botulism was reviewed. While interviews informed on how to select healthy walruses and prepare them for consumption, laboratory analyses revealed that walruses had elevated levels of omega-3 fatty acids and selenium but low levels of mercury compared to some other wildlife. Only 3% of the 755 walruses were infected with T. nativa. Most walruses' infections were found within individuals from the South East Hudson Bay stock, where Inuit have thus decided to stop hunting since mid-2000s. Finally, although the number of outbreaks of trichinellosis related to the consumption of walruses has significantly reduced in Nunavik, botulism could continue to be an issue when igunaq (i.e. aged walrus) is not properly prepared. With the support of the Nunavik Trichinellosis Prevention Program and transmission of Inuit knowledge on igunaq preparation, the consumption of Atlantic walruses has the potential to help address issues related to food insecurity in Nunavik in the future.

Robust estimation of quantitative perfusion from multi-phase pseudo-continuous arterial spin labeling.

PURPOSE: Multi-phase PCASL has been proposed as a means to achieve accurate perfusion quantification that is robust to imperfect shim in the labeling plane. However, there exists a bias in the estimation process that is a function of noise in the data. In this work, this bias is characterized and then addressed in animal and human data. METHODS: The proposed algorithm to overcome bias uses the initial biased voxel-wise estimate of phase tracking error to cluster regions with different off-resonance phase shifts, from which a high-SNR estimate of regional phase offset is derived. Simulations were used to predict the bias expected at typical SNR. Multi-phase PCASL in 3 rat strains (n = 21) at 9.4 T was considered, along with 20 human subjects previously imaged using ASL at 3 T. The algorithm was extended to include estimation of arterial blood flow velocity. RESULTS: Based on simulations, a perfusion estimation bias of 6-8% was expected using 8-phase data at typical SNR. This bias was eliminated when a high-precision estimate of phase error was available. In the preclinical data, the bias-corrected measure of perfusion (107 ± 14 mL/100g/min) was lower than the standard analysis (116 ± 14 mL/100g/min), corresponding to a mean observed bias across strains of 8.0%. In the human data, bias correction resulted in a 15% decrease in the estimate of perfusion. CONCLUSIONS: Using a retrospective algorithmic approach, it was possible to exploit common information found in multiple voxels within a whole region of the brain, offering superior SNR and thus overcoming the bias in perfusion quantification from multi-phase PCASL.

Molecular surveillance of hepatitis C virus genotypes identifies the emergence of a genotype 4d lineage among men in Quebec, 2001-2017.

BACKGROUND: Molecular phylogenetics are generally used to confirm hepatitis C virus (HCV) transmission events. In addition, the Laboratoire de santé publique du Québec (LSPQ) has been using molecular phylogenetics for surveillance of HCV genotyping since November 2001. OBJECTIVES: To describe the emergence of a specific lineage of HCV genotype 4d (G4d) and its characteristics using molecular phylogenetics as a surveillance tool for identifying HCV strain clustering. METHODS: The LSPQ prospectively applied Sanger sequencing and phylogenetic analysis to determine the HCV genotype on samples collected from November 2001 to December 2017. When a major G4d cluster was identified, demographic information, HIV-infection status and syphilis test results were analyzed. RESULTS: Phylogenetic analyses performed on approximately 22,000 cases identified 122 G4d cases. One major G4d cluster composed of 37 cases was singled out. Two cases were identified in 2010, 10 from 2011-2014 and 25 from 2015-2017. Cases in the cluster were concentrated in two urban health regions. Compared to the other G4d cases, cluster cases were all male (p<0.001) and more likely to be HIV-positive (adjusted risk ratio: 4.4; 95% confidence interval: 2.5-7.9). A positive syphilis test result was observed for 27 (73%) of the cluster cases. The sequences in this cluster and of four outlier cases were located on the same monophyletic lineage as G4d sequences reported in HIV-positive men who have sex with men (MSM) in Europe. CONCLUSION: Molecular phylogenetics enabled the identification and surveillance of ongoing transmission of a specific HCV G4d lineage in HIV-positive and HIV-negative men in Quebec and its cross-continental spread. This information can orient intervention strategies to avoid transmission of HCV in MSM.

Modulation of mtDNA copy number ameliorates the pathological consequences of a heteroplasmic mtDNA mutation in the mouse.

Heteroplasmic mtDNA mutations typically act in a recessive way and cause mitochondrial disease only if present above a certain threshold level. We have experimentally investigated to what extent the absolute levels of wild-type (WT) mtDNA influence disease manifestations by manipulating TFAM levels in mice with a heteroplasmic mtDNA mutation in the tRNAAla gene. Increase of total mtDNA levels ameliorated pathology in multiple tissues, although the levels of heteroplasmy remained the same. A reduction in mtDNA levels worsened the phenotype in postmitotic tissues, such as heart, whereas there was an unexpected beneficial effect in rapidly proliferating tissues, such as colon, because of enhanced clonal expansion and selective elimination of mutated mtDNA. The absolute levels of WT mtDNA are thus an important determinant of the pathological manifestations, suggesting that pharmacological or gene therapy approaches to selectively increase mtDNA copy number provide a potential treatment strategy for human mtDNA mutation disease.

Reproductive plasticity of female white-tailed deer at high density and under harsh climatic conditions.

Life-history strategies of female ungulates usually depend on density-dependent and independent processes affecting body condition. Using a long-term data set on life-history traits of female white-tailed deer (2002-2014), we investigated the influence of population density and environmental factors on the reproductive effort of females. We also evaluated post-reproductive consequences on body condition using body mass, body fat, and body protein contents in the autumn following conception. We found that under high densities, females had a lower reproductive rate, which corresponds to a conservative reproduction strategy. However, females born at high density were more likely to reproduce and conceive larger litter size than females born at low density, a possible consequence of strong selective pressure in early life. Body condition was affected by reproduction; lactation had a large negative impact on body mass and body reserves, and conception, irrespectively of litter size, had a negative impact on body fat. Our long-term study demonstrates that plasticity in life-history strategies is a major determinant of reproductive potential for females living at high density and under harsh climates.

MicroRNA-19a enhances proliferation of bronchial epithelial cells by targeting TGFßR2 gene in severe asthma.

BACKGROUND: Allergic asthma is characterized by inflammation and airway remodeling. Bronchial epithelium is considered a key player in coordinating airway wall remodeling. In mild asthma, the epithelium is damaged and fails to proliferate and to repair, whereas in severe asthma, the epithelium is highly proliferative and thicker. This may be due to different regulatory mechanisms. The purpose of our study was to determine the role of miRNAs in regulating proliferation of bronchial epithelial cells obtained from severe asthmatic subjects in comparison with cells obtained from mild asthmatics and healthy controls. METHODS: Human bronchial epithelial cells (BEC) were isolated by bronchoscopy from bronchial biopsies of healthy donors and patients with mild and severe asthma. MiRNA expression was evaluated using the TaqMan low-density arrays and qRT-PCR. Transfection studies of bronchial epithelial cells were performed to determine the target genes. Cell proliferation was evaluated by BrdU incorporation test. RESULTS: MiR-19a was upregulated in epithelia of severe asthmatic subjects compared with cells from mild asthmatics and healthy controls. Functional studies based on luciferase reporter and Western blot assays suggest that miR-19a enhances cell proliferation of BEC in severe asthma through targeting TGF-ß receptor 2 mRNA. Moreover, repressed expression of miR-19a increased SMAD3 phosphorylation through TGF-ß receptor 2 signaling and abrogated BEC proliferation. CONCLUSION: Our study uncovers a new regulatory pathway involving miR-19a that is critical to the severe phenotype of asthma and indicates that downregulating miR-19a expression could be explored as a potential new therapy to modulate epithelium repair in asthma.

Quebec Integrated Chronic Disease Surveillance System (QICDSS), an innovative approach.

INTRODUCTION: With the growing burden of chronic diseases, surveillance will play an essential role in improving their prevention and control. The Institut national de santé publique du Québec has developed an innovative chronic disease surveillance system, the Quebec Integrated Chronic Disease Surveillance System (QICDSS). We discuss the primary features, strengths and limitations of this system in this report. METHODS: The QICDSS was created by linking five health administrative databases. Updated annually, it currently covers the period from January 1, 1996, to March 31, 2012. The operational model comprises three steps: (1) extraction and linkage of health administrative data according to specific selection criteria; (2) analysis (validation of case definitions essentially) and production of surveillance measures; and (3) data interpretation, submission and dissemination of information. The QICDSS allows the surveillance of the following chronic diseases: diabetes, cardiovascular diseases, respiratory diseases, osteoporosis, osteoarticular diseases, mental disorders, Alzheimer's disease and related disorders. The system also lends itself to the analysis of multimorbidity and polypharmacy. RESULTS: For 2011-2012, the QICDSS contained information on 7 995 963 Quebecers with an average age of 40.8 years. Of these, 95.3% met at least one selection criterion allowing the application of case definitions for chronic disease surveillance. The actual proportion varied with age, from 90.1% for those aged 19 years or less to 99.3% for those aged 65 years or over. CONCLUSION: The QICDSS provides a way of producing population-based data on the chronic disease burden, health services and prescription drug uses. The system facilitates the integrated study of several diseases in combination, an approach rarely implemented until now in the context of population surveillance. The QICDSS possesses all the essential features of a surveillance system and supports the dissemination of information to public health decision-makers for future actions.

TITRE: Le Système intégré de surveillance des maladies chroniques du Québec (SISMACQ), une approche novatrice. INTRODUCTION: Avec l'accroissement du fardeau des maladies chroniques, la surveillance est fondamentale pour améliorer la prévention et la prise en charge de ces dernières. L'Institut national de santé publique du Québec a donc développé un système novateur de surveillance des maladies chroniques, le Système intégré de surveillance des maladies chroniques du Québec (SISMACQ), dont les principales caractéristiques, les forces et les limites sont présentées ici. MÉTHODOLOGIE: Le SISMACQ est le résultat du jumelage de cinq fichiers médicoadministratifs. Mises à jour annuellement, ses données couvrent actuellement la période du 1er janvier 1996 au 31 mars 2012. Trois étapes en caractérisent le modèle opérationnel : 1) l'extraction et le jumelage des données médico-administratives grâce à divers critères de sélection; 2) les analyses (principalement la validation des définitions) et la production des mesures de surveillance et 3) l'interprétation, le dépôt et la diffusion de l'information. Le SISMACQ permet actuellement l'étude des maladies chroniques suivantes : diabète, maladies cardiovasculaires, maladies respiratoires, ostéoporose, maladies ostéoarticulaires, troubles mentaux et Alzheimer et maladies apparentées. Il permet également l'analyse de la multimorbidité et de la polypharmacie. RÉSULTATS: Pour 2011-2012, le SISMACQ contenait des données sur 7 995 963 Québécois, et leur moyenne d'âge était de 40,8 ans. Parmi eux, 95,3 % répondaient à au moins un critère de sélection permettant l'application de définitions de cas pour la surveillance des maladies chroniques. Cette proportion variait avec l'âge : de 90,1 % chez les Québécois de 19 ans et moins à 99,3 % chez ceux de 65 ans et plus. CONCLUSION: Le SISMACQ permet la production de données, à l'échelle de la population, sur le fardeau de plusieurs maladies chroniques, sur l'utilisation des services de santé et sur la consommation de médicaments. Il rend possible l'étude intégrée de la combinaison de plusieurs maladies, une approche jusqu'à présent rarement mise en oeuvre dans un contexte de surveillance populationnelle. Le SISMACQ répond aux attributs essentiels d'un système de surveillance et aide à la diffusion de l'information auprès des décideurs en vue d'actions en santé publique.

Pathological changes of stomach in ringed seal (Pusa hispida) from Arviat (North Canada) caused by anisakid nematodes.

This is a report of lesions associated with the nematodes (Anisakidae) from the stomach of ringed seals (Pusa hispida). On thirty one examined ringed seals from Arviat, thirteen were infected by 1 to 24 anisakids. Identification of nematodes from their stomachs showed two species; Contracaecum osculatum (sensu lato) (79 specimens) and Pseudoterranova decipiens (sensu lato) (11 specimens). In the gastric sections with parasites, larvae and adults of nematodes were present mainly in the fundic portion of the stomach. The anterior parts of the nematodes were embedded in mucosa and submucosa. Anisakids were associated with ulcerous gastric lesions and raised inflammatory areas in the stomachs. The histological examination of a sample taken from the tissue surrounding anisakids revealed the presence of more or less confluent focal necrotic areas. Most small petechial hemorrhages were located in the mucosal layer of the gastric wall and were surrounded by inflammatory mononuclear cells such as lymphocytes, histiocytes, eosinophils and fibroblasts. The Anisakidae larvae in the stomach caused atrophy of glands, hemorrhaging and eosinophilic infiltrations that consequently healed, creating fibrotic scars.

Two different corticosteroid-binding globulin variants that lack cortisol-binding activity in a greek woman.

BACKGROUND: Corticosteroid-binding globulin (CBG), encoded by SERPINA6, is the principal plasma binding protein for cortisol. Most nonsynonymous single-nucleotide polymorphisms that alter the production or function of CBG occur rarely, and their clinical significance remains obscure. METHODS: Serum and DNA were obtained from a Greek woman with low morning cortisol levels and from family members. SERPINA6 exons were sequenced, and serum CBG was measured by ELISA and cortisol-binding capacity assay. Recombinant CBG variants were produced for detailed functional studies. RESULTS: A novel heterozygous c.1282G>C transversion in exon 5 of SERPINA6, resulting in a p.Trp393Ser (W371S) substitution, was identified in the proband, who was also heterozygous for single-nucleotide polymorphisms encoding the CBG Lyon (D367N) and CBG A224S variants. The proband had no measurable plasma cortisol-binding activity despite a CBG level of 273 nm by ELISA. She inherited CBG W371S from her mother whose plasma cortisol-binding capacity was approximately 50% lower than the CBG measurements by ELISA (314 nm). The proband's father and four children were heterozygous for CBG D367N; their CBG levels by ELISA were normal, but corresponding cortisol-binding capacity measurements were 50% lower. Pedigree analysis revealed that W371S segregates with A224 and that D367N and W371S segregate separately. Recombinant CBG D367N and CBG W371S had no measureable cortisol-binding activity. CONCLUSION: A new CBG Athens (W371S) variant that lacks cortisol-binding activity has been identified in a carrier of the cortisol-binding deficient CBG Lyon (D367N) variant. Analyses of CBG levels in this pedigree illustrate how immunoassays fail to accurately reflect cortisol-binding activity.

Apoptosis-like programmed cell death induces antisense ribosomal RNA (rRNA) fragmentation and rRNA degradation in Leishmania.

Few natural antisense (as) RNAs have been reported as yet in the unicellular protozoan Leishmania. Here, we describe that Leishmania produces natural asRNAs complementary to all ribosomal RNA (rRNA) species. Interestingly, we show that drug-induced apoptosis-like programmed cell death triggers fragmentation of asRNA complementary to the large subunit gamma (LSU-γ) rRNA, one of the six 28S rRNA processed fragments in Leishmania. Heat and oxidative stress also induce fragmentation of asrRNA, but to a lesser extent. Extensive asrRNA cleavage correlates with rRNA breakdown and translation inhibition. Indeed, overexpression of asLSU-γ rRNA accelerates rRNA degradation upon induction of apoptosis. In addition, we provide mechanistic insight into the regulation of apoptosis-induced asrRNA fragmentation by a 67 kDa ATP-dependent RNA helicase of the DEAD-box subfamily. This helicase binds both sense (s)LSU-γ and asLSU-γ rRNAs, and appears to have a key role in protecting rRNA from degradation by preventing asrRNA cleavage and thus cell death. Remarkably, the asrRNA fragmentation process operates not only in trypanosomatid protozoa but also in mammals. Our findings uncover a novel mechanism of regulation involving asrRNA fragmentation and rRNA breakdown, that is triggered by apoptosis and conditions of reduced translation under stress, and seems to be evolutionary conserved.

Repression of cancer cell senescence by PKCι.

Senescence is an irreversible growth arrest phenotype adopted by cells that has a key role in protecting organisms from cancer. There is now considerable interest in therapeutic strategies that reactivate this process to control the growth of cancer cells. Protein kinase-Cι (PKCι) is a member of the atypical PKC family and an important downstream mediator in the phosphoinositide-3-kinase (PI-3-kinase) pathway. PKCι expression was found to be upregulated in a subset of breast cancers and breast cancer cell lines. Activation of the PI-3-kinase pathway by introduction of mutant, oncogenic PIK3CA into breast mammary epithelial cells increased both the expression and activation of PKCι. In breast cancer cells lines overexpressing PKCι, depletion of PKCι increased the number of senescent cells, as assessed by senescence-associated ß-galactosidase, morphology and bromodeoxyuridine incorporation. This phenomenon was not restricted to breast cancer cells, as it was also seen in glioblastoma cells in which PKCι is activated by loss of PTEN. Senescence occurred in the absence of a detectable DNA-damage response, was dependent on p21 and was enhanced by the aurora kinase inhibitor VX-680, suggesting that senescence is triggered by defects in mitosis. Depletion of PKCι had no effect on senescence in normal mammary epithelial cell lines. We conclude that PKCι is overexpressed in a subset of cancers where it functions to suppress premature senescence. This function appears to be restricted to cancer cells and inhibition of PKCι may therefore be an effective way to selectively activate premature senescence in cancer cells.

Spatio-temporal variations and age effect on Toxoplasma gondii seroprevalence in seals from the Canadian Arctic.

Toxoplasmosis is a significant public health threat for Inuit in the Canadian Arctic. This study aimed to investigate arctic seals as a possible food-borne source of infection. Blood samples collected from 828 seals in 7 Canadian Arctic communities from 1999 to 2006 were tested for Toxoplasma gondii antibodies using a direct agglutination test. Polymerase chain reaction (PCR) was used to detect T. gondii DNA in tissues of a subsample of seals. Associations between seal age, sex, species, diet, community and year of capture, and serological test results were investigated by logistic regression. Overall seroprevalence was 10·4% (86/828). All tissues tested were negative by PCR. In ringed seals, seroprevalence was significantly higher in juveniles than in adults (odds ratio=2·44). Overall, seroprevalence varied amongst communities (P=0·0119) and by capture year (P=0·0001). Our study supports the hypothesis that consumption of raw seal meat is a significant source of infection for Inuit. This work raises many questions about the mechanism of transfer of this terrestrial parasite to the marine environment, the preponderance of infection in younger animals and the natural course of infection in seals. Further studies to address these questions are essential to fully understand the health risks for Inuit communities.

Multiple work-related accidents: tracing the role of hearing status and noise exposure.

OBJECTIVES: Our main purpose was to investigate any relationship between noise exposure levels in the workplace, degree of hearing loss (HL), and the relative risk of accident (OR of single or multiple events). METHODS: We conducted a retrospective study of 52 982 male workers aged 16-64 years with long-standing exposures to occupational noise over a 5-year period, using "hearing status" and "noise exposure" from the registry held by the Quebec National Institute of Public Health. Information on work-related accidents was obtained from the Quebec Workers' Compensation Board. Hearing threshold level measurements and noise exposures were regressed on the numbers of accidents after adjusting for age. RESULTS: Exposure to extremely noisy environments (L(eq8h) (equivalent noise level for 8 h exposure) > or =90 dBA) is associated with a higher relative risk of accident. The severity of hearing impairment (average bilateral hearing threshold levels at 3, 4 and 6 kHz) increases the relative risk of single and multiple events when threshold levels exceed 15 dB of hearing loss. The relative risk of multiple events (four or more) is approximately three times higher among severely hearing-impaired workers who are exposed to L(eq8h) > or =90 dBA. CONCLUSION: Single and multiple events are associated with high noise exposure and hearing status. This suggests that reducing noise exposure contributes to increased safety in noisy industries and prevents hearing loss. Hearing-impaired workers assigned to noisy workstations should be provided with assistive listening devices and efficient communication strategies should be implemented.

Ultrastructural alterations in Fusarium sambucinum and Heterobasidion annosum treated with aluminum chloride and sodium metabisulfite.

Aluminum chloride (AlCl(3)) and sodium metabisulfite (Na(2)S(2)O(5)) have received increasing attention as antifungal agents for the control of plant diseases. In an effort to understand their toxic action on fungi, ultrastructural changes and membrane damage in Fusarium sambucinum (Ascomycota) and Heterobasidion annosum (Basidiomycota) in response to salt exposure was investigated using transmission electron microscopy. Conidial membrane damage was quantified using SYTOX Green stain, which only enters altered membranes. The results showed that mortality of the conidia was generally closely associated with SYTOX stain absorption in F. sambucinum treated with Na(2)S(2)O(5) and in H. annosum treated with AlCl(3) or Na(2)S(2)O(5), suggesting that these salts cause membrane alterations. For both fungi, ultrastructural alterations in conidia treated with AlCl(3) and Na(2)S(2)O(5) included membrane retraction, undulation, and invagination. At higher concentrations or exposure periods to the salts, loss of membrane integrity, cytoplasmic leakage, and cell rupture were observed. Ultrastructural alterations and increased SYTOX stain absorption in salt-treated conidia appear consistent with a mode of action where AlCl(3) and Na(2)S(2)O(5) alter membrane integrity and permeability.

Feedback effects of chronic browsing on life-history traits of a large herbivore.

1. Increasing ungulate populations are affecting vegetation negatively in many areas, but few studies have assessed the long-term effects of overbrowsing on individual life-history traits of ungulates. 2. Using an insular population of white-tailed deer (Odocoileus virginianus Zimmermann; Anticosti, Québec, Canada) introduced in 1896, and whose density has remained high since the first evidence of severe browsing in the 1930s, we investigated potential feedbacks of long-term and heavy browsing on deer life-history traits. 3. We assessed whether chronic browsing contributed to a decline of the quality of deer diet in early autumn during the last 25 years, and evaluated the impacts of reduced diet quality on deer body condition and reproduction. 4. Rumen nitrogen content declined 22% between two time periods, 1977-79 and 2002-04, indicating a reduction in diet quality. 5. After accounting for the effects of year within the time period, age and date of harvest in autumn, peak body mass of both sexes declined between the two time periods. At the end of November, males were on average 12% heavier and adult does 6% heavier in 1977-79 than in 2002-04. Hind foot length did not vary between time periods. 6. The probability of conception increased 15% between the two time periods, but litter size at ovulation declined 7%, resulting in a similar total number of ovulations in 2002-04 and in 1977-79. 7. Our results suggest that following a decline in diet quality, white-tailed deer females modified their life-history strategies to maintain reproduction at the expense of growth. 8. Deer appear to tolerate drastic reductions in diet quality by modifying their life history traits, such as body mass and reproduction, before a reduction in density is observed. Such modifications may contribute to maintain high population density of large herbivores following population irruption.

Do escaped transgenes persist in nature? The case of an herbicide resistance transgene in a weedy Brassica rapa population.

The existence of transgenic hybrids resulting from transgene escape from genetically modified (GM) crops to wild or weedy relatives is well documented but the fate of the transgene over time in recipient wild species populations is still relatively unknown. This is the first report of the persistence and apparent introgression, i.e. stable incorporation of genes from one differentiated gene pool into another, of an herbicide resistance transgene from Brassica napus into the gene pool of its weedy relative, Brassica rapa, monitored under natural commercial field conditions. Hybridization between glyphosate-resistant [herbicide resistance (HR)]B. napus and B. rapa was first observed at two Québec sites, Ste Agathe and St Henri, in 2001. B. rapa populations at these two locations were monitored in 2002, 2003 and 2005 for the presence of hybrids and transgene persistence. Hybrid numbers decreased over the 3-year period, from 85 out of approximately 200 plants surveyed in 2002 to only five out of 200 plants in 2005 (St Henri site). Most hybrids had the HR trait, reduced male fertility, intermediate genome structure, and presence of both species-specific amplified fragment length polymorphism markers. Both F(1) and backcross hybrid generations were detected. One introgressed individual, i.e. with the HR trait and diploid ploidy level of B. rapa, was observed in 2005. The latter had reduced pollen viability but produced approximately 480 seeds. Forty-eight of the 50 progeny grown from this plant were diploid with high pollen viability and 22 had the transgene (1:1 segregation). These observations confirm the persistence of the HR trait over time. Persistence occurred over a 6-year period, in the absence of herbicide selection pressure (with the exception of possible exposure to glyphosate in 2002), and in spite of the fitness cost associated with hybridization.