Vulnerability and tolerance to nickel of periphytic biofilm harvested in summer and winter.

Metals are naturally present in freshwater ecosystems but anthropogenic activities like mining operations represent a long-standing concern. Metals released into aquatic environments may affect microbial communities such as periphytic biofilm, which plays a key role as a primary producer in stream ecosystems. Using two 28-day microcosm studies involving two different photoperiods (light/dark cycle of 16/8 vs 8/16), the present study assessed the effects of four increasing nickel (Ni) concentrations (0-6 µM) on two natural biofilm communities collected at different seasons (summer and winter). The two communities were characterized by different structural profiles and showed significant differences in Ni accumulated content for each treatment. For instance, the biofilm metal content was four times higher in the case of summer biofilm at the highest Ni treatment and after 28 days of exposure. Biomarkers examined targeted both heterotrophic and autotrophic organisms. For heterotrophs, the ß-glucosidase and ß-glucosaminidase showed no marked effects of Ni exposure and were globally similar between the two communities suggesting low toxicity. However, the photosynthetic yield confirmed the toxicity of Ni on autotrophs with maximum inhibition of 81 ± 7% and 60 ± 1% respectively for the summer and winter biofilms. Furthermore, biofilms previously exposed to the highest long-term Ni concentration ([Ni2+] = 6 µM) revealed no acute effects in subsequent toxicity based on the PSII yield, suggesting a tolerance acquisition by the phototrophic community. Taken together, the results suggest that the biofilm response to Ni exposure was dependent of the function considered and that descriptors such as biofilm metal content could be seasonally dependent, information of great importance in a context of biomonitoring.

New insights in copper handling strategies in the green alga Chlamydomonas reinhardtii under low-iron condition.

Copper (Cu) is a redox-active transition element critical to various metabolic processes. These functions are accomplished in tandem with Cu-binding ligands, mainly proteins. The main goal of this work was to understand the mechanisms that govern the intracellular fate of Cu in the freshwater green alga, Chlamydomonas reinhardtii, and more specifically to understand the mechanisms underlying Cu detoxification by algal cells in low-Fe conditions. We show that Cu accumulation was up to 51-fold greater for algae exposed to Cu in low-Fe medium as compared to the replete-Fe growth medium. Using the stable isotope 65Cu as a tracer, we studied the subcellular distribution of Cu within the various cell compartments of C. reinhardtii. These data were coupled with metallomic and proteomic approaches to identify potential Cu-binding ligands in the heat-stable proteins and peptides fraction of the cytosol. Cu was mostly found in the organelles (78%), and in the heat-stable proteins and peptides (21%) fractions. The organelle fraction appeared to also be the main target compartment of Cu accumulation in Fe-depleted cells. As Fe levels in the medium were shown to influence Cu homeostasis, we found that C. reinhardtii can cope with this additional stress by utilizing different Cu-binding ligands. Indeed, in addition to expected Cu-binding ligands such as glutathione and phytochelatins, 25 proteins were detected that may also play a role in the Cu-detoxification processes in C. reinhardtii. Our results shed new light on the coping mechanisms of C. reinhardtii when exposed to environmental conditions that induce high rates of Cu accumulation.

Role of iron in gene expression and in the modulation of copper uptake in a freshwater alga: Insights on Cu and Fe assimilation pathways.

Metal uptake and toxicity can generally be related to its aqueous speciation and to the presence of competitive ions as described by the biotic ligand model. Beyond these simple chemical interactions at the surface of aquatic organisms, several internal biological feedback mechanisms can also modulate metal uptake. This is particularly important for essential elements for which specific transport systems were developed over the course of evolution. Based on the results of short-term Cu2+ uptake experiments and on the analysis of the expression of certain genes involved in Cu and Fe homeostasis, we studied the effects of Fe3+ on Cu2+ uptake by the freshwater green alga Chlamydomonas reinhardtii. We observed a significant increase in Cu2+ uptake rate in algal cells acclimated to a low Fe3+ medium up to 4.7 times greater compared to non-acclimated algal cells. The overexpression of the ferroxidase FOX1 and permease FTR1 genes suggests an activation of the high affinity Fe3+ assimilation system, which could constitute a plausible explanation for the increase in Cu2+ uptake rate in acclimatized algae. We show that Fe availability can have a significant impact on Cu uptake. Our observations reinforce the importance of considering physiological factors to better predict metal bioavailability.

Temperature and Photoperiod Affect the Sensitivity of Biofilms to Nickel and its Accumulation.

Whereas metal impacts on fluvial communities have been extensively investigated, effects of abiotic parameters on community responses to contaminants are poorly documented. Variations in photoperiod and temperature commonly occur over the course of a season and could affect aquatic biofilm communities and their responses to contaminants. Our objective was to characterize the influence of environmental conditions (photoperiod and temperature) on nickel (Ni) bioaccumulation and toxicity using a laboratory-grown biofilm. Environmental parameters were chosen to represent variations that can occur over the summer season. Biofilms were exposed for 7 days to six dissolved Ni treatments (ranging from 6 to 115 µM) at two temperatures (14 and 20 °C) using two photoperiods (16:8 and 12:12-h light:dark cycle). Under these different scenarios, structural (dry weight biomass and chlorophyll-a) and functional biomarkers (photosynthetic yield and Ni content) were analyzed at four sampling dates, allowing us to evaluate Ni sensitivity of biofilms over time. The results highlight the effects of temperature on Ni accumulation and tolerance of biofilms. Indeed, biofilms exposed at 20 °C accumulated 1.6-4.2-fold higher concentrations of Ni and were characterized by a lower median effect concentration value using photosynthetic yield compared with those exposed at 14 °C. In terms of photoperiod, significantly greater rates of Ni accumulation were observed at the highest tested Ni concentration for biofilms exposed to a 12:12-h compared with a 16:8-h light:dark cycle. Our study demonstrates the influence of temperature on biofilm metabolism and illustrates that environmental factors may influence Ni accumulation response and thus Ni responses of phototrophic biofilms. Environ Toxicol Chem 2022;41:1649-1662. © 2022 SETAC.

Effects of thorium on bacterial, microalgal and micromeiofaunal community structures in a periphytic biofilm.

Few ecotoxicity studies are available on thorium (Th) which hinders the ability to evaluate its ecotoxicological risk. Its release in the environment is often associated with the extraction of rare earth elements and uranium, as well as the field applications of phosphate fertilizers. This study investigates the effects of Th on microbial communities of periphytic biofilms. Ceramic plates were left to colonize for one month in the laboratory with a biofilm sampled from Cap Rouge river (QC, Canada). Plates were randomly placed in channels containing culture media representing three different conditions: a control condition (C0; background Th concentrations of 0.004 ± 0.002 nM), a low Th concentration condition (C1; 0.18 ± 0.09 nM Th) and a moderately high Th condition (C10; 8.7 ± 3.4 nM) for up to 4 weeks. The presence of Th modified the diatom community by changing its taxonomic structure, reducing diversity and increasing cell density. The taxonomic structure of the bacterial community, followed by 16S metabarcoding analysis, was affected with a significant decrease in Pseudanabaena and Shingopyxis genera in the two Th exposed conditions. No direct toxic effect of Th was observed on counted micromeiofauna but the changes in diatom and bacterial communities could explain the higher number of individual diatoms and micromeiofauna observed in Th-exposed conditions. This work shows that low concentrations of Th can modify biofilm structure, which, in turn, could disturb its ecologically key functions.

Thorium Exposure Drives Fatty Acid and Metal Transfer from Biofilms to the Grazer Lymnaea sp.

Aquatic ecotoxicological risks associated with tetravalent metallic elements such as thorium (Th) are still poorly understood. Periphytic biofilm represents an important food source in aquatic environments; thus, such risks could severely affect nutrient and energy cycling in these ecosystems. The present study investigated the potential for Th to change the fatty acid composition of biofilm communities. Bioaccumulation of Th and fatty acids were measured after 4 wk to 2 exposure conditions: a control (C0) and Th exposure (C10). Some major fatty acids such as C16:1n-7 and docosahexaenoic acid C22:6n-3 differed significantly between control and C10 conditions. To determine if Th can be trophically transferred and to investigate the impacts of nutritional quality changes on primary consumers, common pond snails (Lymnaea sp.) were fed for 4 wk with control and Th-exposed biofilm. Thorium appeared to be trophically transferable to the grazers, although we cannot exclude that part of the Th accumulated by the snails may have been taken from the water through release from the biofilms. The composition of major fatty acids observed in the grazers was also significantly affected, notably by a decrease of total polyunsaturated fatty acids. These results indicate that very low Th concentrations can decrease the nutritional quality of organisms at the base of the food chain. Environ Toxicol Chem 2021;40:2220-2228. © 2021 SETAC.

Influence of Temperature and Nickel on Algal Biofilm Fatty Acid Composition.

Freshwater biofilms play an important role in aquatic ecosystems and are widely used to evaluate environmental conditions. Little is known about the effects of temperature and metals on biofilm fatty acid composition. In the present study, we exposed a natural biofilm cultured in mesocosms to a gradient of nickel (Ni) concentrations at 15 and 21 °C for 28 d. Metal bioaccumulation, algal taxonomic composition, and biofilm fatty acid profiles were determined. At both temperatures, bioaccumulated Ni increased with Ni exposure concentration and reached the highest values at 25 µM Ni, followed by a decrease at 55 and 105 µM Ni. In control biofilms, palmitic acid (16:0), palmitoleic acid (16:1n7), oleic acid (18:1n9), linoleic acid (18:2n6), and linolenic acid (18:3n3) were the dominant fatty acids at 15 and 21 °C. This composition suggests a dominance of cyanobacteria and green algae, which was subsequently confirmed by microscopic observations. The increase in temperature resulted in a decrease in the ratio of unsaturated to saturated fatty acids, which is considered to be an adaptive response to temperature variation. Polyunsaturated fatty acids (PUFAs) tended to decrease along the Ni gradient, as opposed to saturated fatty acids which increased with Ni concentrations. Temperature and Ni affected differently the estimated desaturase and elongase activities (product/precursor ratios). The increase in PUFAs at 15 °C was concomitant to an increase in Δ9-desaturase (D9D). The estimated activities of D9D, Δ12-desaturase, and Δ15-desaturase decreased along the Ni gradient and reflected a decline in PUFAs. The elevated estimated elongase activity reflected the observed increase in saturated fatty acids at the highest Ni exposure concentration (105 µM). Our results suggest that fatty acids could be used as an endpoint to evaluate environmental perturbations. Environ Toxicol Chem 2020;39:1566-1577. © 2020 SETAC.

Why Does Cysteine Enhance Metal Uptake by Phytoplankton in Seawater but Not in Freshwater?

Low-molecular-weight weak ligands such as cysteine have been shown to enhance metal uptake by marine phytoplankton in the presence of strong ligands, but the effect is not observed in freshwater. We hypothesized that these contrasting results might be caused by local cysteine degradation and a Ca effect on metal-ligand exchange kinetics in the boundary layer surrounding the algal cells; newly liberated free metal ions cannot be immediately complexed in seawater by Ca-bound strong ligands but can be rapidly complexed by free ligands at low-Ca levels. The present results consistently support this hypothesis. At constant bulk Cd2+ concentrations, buffered by strong ligands: (1) at 50 mM Ca, cysteine addition significantly enhanced Cd uptake in high-Ca preacclimated euryhaline Chlamydomonas reinhardtii (cultured with cysteine as a nitrogen source to enhance local Cd2+ liberation via cysteine degradation); (2) at 0.07 mM Ca, this enhancement was not observed in the algae; (3) at 50 mM Ca, the enhancement disappeared when C. reinhardtii were cultured with ammonium (to inhibit cysteine degradation and local Cd2+ liberation); (4) cysteine addition did not enhance Cd uptake by cysteine-cultured marine Thalassiosira weissflogii when the concentration of immediately reacting strong ligands was sufficient to complex local Cd2+ liberation.

Iron Modulation of Copper Uptake and Toxicity in a Green Alga ( Chlamydomonas reinhardtii).

Little attention has been paid to the role of essential trace elements on the toxicity of another element. In this work, we examined if low concentrations of essential elements (Co, Mn, Zn, and Fe) modified the response of a freshwater green alga ( Chlamydomonas reinhardtii) to copper. To do so, we followed cell growth over 72 h in exposure media where the essential element concentrations were manipulated. Among these elements, iron proved to have a strong impact on the cells' response to copper. The free Cu2+ concentrations required to inhibit cellular growth by 50% (EC50) over 72 h decreased from 2 nM in regular Fe medium (10-17.6 M Fe3+) to 4 pM in low iron medium (10-19.0 M Fe3+); a 500-fold increase in toxicity. Moreover, at low Cu2+ concentrations (10-13.0 to 10-10.5 M), Cu uptake increased under low iron conditions but remain relatively stable under regular iron conditions. These results show clearly that iron plays a protective role against copper uptake and toxicity to C. reinhardtii. In freshwaters, iron is always abundant but the expected free iron concentrations in surface waters can vary between 10-14.0 to 10-20.0 M, depending on pH (e.g., when pH increases from 6 to 8). We conclude that copper toxicity in natural waters can be modulated by iron and that, in some conditions, the Biotic Ligand Model may need to be further developed to account for the influence of iron.

Double lung transplantation in an HIV-positive patient with Mycobacterium kansasii infection.

Good outcomes with kidney and liver transplantation in HIV-positive patients have led clinicians to recommend lung transplantation in HIV-positive patients based on extrapolated data. Pre-transplant mycobacterial infection is associated with an increased risk of developing new infection or aggravating existing infection, though it does not contraindicate transplantation in non-HIV-infected patients. However, no data exists regarding the outcome of HIV-positive patients with pre-transplant mycobacterial infection. We report a case of double lung transplantation in a 50-year-old HIV-positive patient with alpha-1 antitrypsin deficiency. Prior to transplantation, Mycobacterium kansasii was isolated in one sputum culture and the patient was considered merely colonized as no clinical evidence of pulmonary or disseminated disease was present. The patient successfully underwent a double lung transplantation. Nontuberculous mycobacterial infection was diagnosed histologically on examination of native lungs. Surveillance and watchful waiting were chosen over treatment of the infection. HIV remained under control post-transplantation with no AIDS-defining illnesses throughout the follow-up. A minimal acute rejection that responded to increased corticosteroids was reported. At 12 months post-transplant, a bronchiolitis obliterans syndrome was diagnosed after a drop in FEV1. No evidence of isolation nor recurrence of nontuberculous mycobacteria was reported post-transplantation. At 15 months post-transplant, the patient remained stable with an FEV1 of 30%. The presence of pre-transplant nontuberculous mycobacterial infection did not translate into recurrence of nontuberculous mycobacterial infection post-transplant. Whether it contributed to bronchiolitis obliterans syndrome remains unknown.

Uptake and subcellular distribution of aluminum in a marine diatom.

Aluminum (Al) is widespread in the environment including the ocean. The effects of Al on marine organisms have attracted more and more attention in recent years. However, the mechanisms of uptake of Al by marine organisms and the subcellular distribution of Al once assimilated are unknown. Here we report the uptake and subcellular distribution of Al in a marine diatom Thalassiosira weissflogii. Short-term (< 120 min) uptake experiments showed that the Al uptake rate by the diatom was 0.033 ±â€¯0.013 fmol-1 cell-1 min-1 (internalization flux normalized to the exposure Al concentration of 2 µM = 0.034 ±â€¯0.013 nmol m-2 min-1 nM-1). Subcellular fractionation experiments showed that the internalized Al was partitioned to subcellular components in the following order: granules (69 ±â€¯5%) > debris (17 ±â€¯4%) > organelles (12 ±â€¯2%) > heat-stable peptides (HSP) (~2%) > heat-denaturable proteins (HDP) (< 1%), indicating that the majority of intracellular Al was detoxified and stored in inorganic forms. The subcellular distribution of Al in the diatom is different from that of Al in freshwater green algae, in which most of the internalized Al is partitioned to organelles. We also evaluated an artificial seawater-based EDTA rinse solution to remove Al adsorbed on the diatom cell surface. Overall, our study provides new information to understand the mechanisms of uptake of Al by marine diatoms, and the mechanisms responsible for the biological effects (both toxic and beneficial) of Al on the growth of marine phytoplankton, especially diatoms.

No. 164-Consensus Guidelines for the Management of Chronic Pelvic Pain.

OBJECTIVE: To improve the understanding of chronic pelvic pain (CPP) and to provide evidence-based guidelines of value to primary care health professionals, general obstetricians and gynaecologists, and those who specialize in chronic pain. BURDEN OF SUFFERING: CPP is a common, debilitating condition affecting women. It accounts for substantial personal suffering and health care expenditure for interventions, including multiple consultations and medical and surgical therapies. Because the underlying pathophysiology of this complex condition is poorly understood, these treatments have met with variable success rates. OUTCOMES: Effectiveness of diagnostic and therapeutic options, including assessment of myofascial dysfunction, multidisciplinary care, a rehabilitation model that emphasizes achieving higher function with some pain rather than a cure, and appropriate use of opiates for the chronic pain state. EVIDENCE: Medline and the Cochrane Database from 1982 to 2004 were searched for articles in English on subjects related to CPP, including acute care management, myofascial dysfunction, and medical and surgical therapeutic options. The committee reviewed the literature and available data from a needs assessment of subjects with CPP, using a consensus approach to develop recommendations. VALUES: The quality of the evidence was rated using the criteria described in the Report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice were ranked according to the method described in that report (Table 1). RECOMMENDATIONS: The recommendations are directed to the following areas: (a) an understanding of the needs of women with CPP; (b) general clinical assessment; (c) practical assessment of pain levels; (d) myofascial pain; (e) medications and surgical procedures; (d) principles of opiate management; (f) increased use of magnetic resonance imaging (MRI); (g) documentation of the surgically observed extent of disease; (h) alternative therapies; (i) access to multidisciplinary care models that have components of physical therapy (such as exercise and posture) and psychology (such as cognitive-behavioural therapy), along with other medical disciplines, such as gynaecology and anesthesia; G) increased attention to CPP in the training of health care professionals; and (k) increased attention to CPP in formal, high-calibre research. The committee recommends that provincial ministries of health pursue the creation of multidisciplinary teams to manage the condition.

No 164 - Directive clinique de consensus pour la prise en charge de la douleur pelvienne chronique.

OBJECTIF: Améliorer La compréhension de la douleur pelvienne chronique (DPC) et fournir des directives cliniques factuelles qui bénéficieront aux fournisseurs de soins de santé primaires, aux obstétriciens-gynécologues et aux spécialistes de la douleur chronique. FARDEAU DE LA SOUFFRANCE: La DPC est une pathologie débilitante courante qui affecte les femmes. Elle est à l'origine d'importantes souffrances personnelles et de dépenses de santé considérables associées aux interventions, dont de multiples consultations et un grand nombre de traitements médicaux et chirurgicaux. Puisque la pathophysiologie sous-jacente de cet état pathologique complexe est mal comprise, ces traitements n'ont obtenu que des taux de réussite variables. ISSUES: Efficacité des options diagnostiques et thérapeutiques (y compris l'évaluation du dysfonctionnement myofascial); soins multidisciplinaires; un modèle de réadaptation mettant l'accent sur l'obtention d'un fonctionnement supérieur malgré la présence d'une certaine douleur (plutôt que de chercher à obtenir une guérison totale); et utilisation appropriée des opiacés pour le soulagement de la douleur chronique. PREUVES: Des recherches ont été menées dans Medline et la base de données Cochrane en vue d'en tirer les articles de langue anglaise, publiés entre 1982 et 2004, portant sur des sujets liés à la DPC, dont la gestion des soins actifs, le dysfonctionnement myofascial et les options thérapeutiques médicales et chirurgicales. Les membres du comité ont analysé la littérature pertinente, ainsi que les données disponibles tirées d'une évaluation des besoins des personnes présentant une DPC; ils ont fait appel à une approche de consensus pour l'élaboration des recommandations. VALEURS: La qualité des résultats a été évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur l'examen médical périodique. Les recommandations visant la pratique ont été classées conformément à la méthode décrite dans ce rapport (Tableau 1). RECOMMANDATIONS: Les recommandations visent ce qui suit : (a) compréhension des besoins des femmes présentant une DPC ; (b) évaluation clinique générale ; (c) évaluation pratique des niveaux de douleur ; (d) douleur myofasciale ; (e) médicaments et interventions chirurgicales ; (f) principes de la gestion des opiacés; (g) utilisation accrue de l'imagerie par résonance magnétique (IRM) ; (h) documentation de l'étendue de La maladie constatée au moyen de la chirurgie ; (i) thérapies non conventionnelles; (j) accès à des modèles de soins multidisciplinaires faisant appel à des composantes de physiothérapie (comme l'exercice et la posture) et de psychologie (comme La thérapie cognitivo- comportementale), conjointement avec d'autres disciplines médicales, telles que La gynécologie et l'anesthésie ; (k) attention accrue portée à La DPC dans La formation des professionnels de La sante ; et (l) attention accrue portée à la DPC dans le domaine des recherches officielles et de haut calibre. Le comité recommande que les ministères provinciaux de La Sante prennent des mesures en faveur de la création d'équipes multidisciplinaires pouvant assurer La prise en charge de cette pathologie. Chapitre 2 : Portee et definition de La douleur pelvienne chronique Chapitre 3 : Anamnese, examen physique et évaluation psychologique Chapitre 4 : Explorations Chapitre 5 : Sources de douleur pelvienne chronique Chapitre 6 : Causes urologiques et gastro-intestinales de La douleur pelvienne chronique Chapitre 7 : Dysfonctionnement myofasclal Chapitre 8 : Therapie medicale - résultats en matiere d'efficacite Chapitre 9 : Chirurgie - résultats en matiere d'efficacite Chapitre 11 : Prise en charge multidisciplinaire de La douleur chronique Chapitre 14 : Orientations futures.

Improvement of reverse sequence algorithm for syphilis diagnosis using optimal treponemal screening assay signal-to-cutoff ratio.

BACKGROUND: Although reverse sequence algorithms (RSA) for syphilis screening are performing well, they still have to rely on treponemal confirmatory tests at least for sera reactive by enzyme immunoassay/chemiluminescence immunoassay (EIA/CIA) and unreactive by rapid plasma reagin (RPR). Quebec's laboratory network previously showed that 3.3% of EIA/CIA reactive and weakly-reactive RPR samples (RPR titer of 1 to 4) would have been misclassified as syphilis cases if a treponemal confirmatory test had not been performed. OBJECTIVES: To correlate the magnitude of signal-to-cutoff (S/CO) ratios of the 4 most used commercial first-line EIA/CIA kits in Quebec with syphilis confirmation results and establish a S/CO value above which treponemal confirmation would not be required. METHODS: Serum samples from previously undiagnosed individuals (n = 7 404) obtained between January 2014 and February 2017 that were reactive by EIA/CIA and either negative by RPR or reactive with a low titer (1 to 4) were included in the study. All samples were tested with Treponema pallidum particle agglutination (TP-PA) and, if negative or inconclusive, with a line immunoassay (LIA). Syphilis infection confirmation was defined by a reactive TP-PA or LIA. Logistic regression analysis was used to determine S/CO values (95% CI lower bound = 0.98) above which confirmation would not be required. The four kits studied were Architect TP, BioPlex IgG, Syphilis EIA II, and Trep-Sure. RESULTS: Of 2609 reactive EIA/CIA specimens tested for the determination of S/CO values, 1730 (66%) were confirmed as true syphilis cases. Confirmation rate was significantly higher in samples with low-titer positive RPR (92%) than with negative RPR samples (54%); p<0.01. A linear probability model (95% CI lower bound = 0.98) predicted the S/CO value above which a confirmation would no longer be needed for the Architect TP (16.4), Bioplex IgG (7.4) and Trep-Sure (24.6). No linearity was observed between the S/CO value of Syphilis EIA II and the confirmation rate. The validity of the predicted S/CO values was investigated using 4 795 specimens. The use of an S/CO value of 16.4 with the Architect TP kit and of 24.6 for the Trep-Sure kit would obviate the need for confirmation of 18.5% and 13.2% of sera from the all RPR subgroup, respectively. For the BioPlex IgG kit, 81.1% of sera would not require confirmation when using the S/CO value of 7.4 in the low titer RPR subgroup. CONCLUSION: Signal-to-cut-off values could be used to identify sera that do not require extra treponemal confirmation for 3 of the 4 most used first-line EIA/CIA kits in Quebec. Using these values in our current reverse screening algorithm (RSA) would avoid the need for confirmatory tests in 14 to 20% of sera, a proportion that could reach 75% among low-titer RPR.

Chemical Conditions in the Boundary Layer Surrounding Phytoplankton Cells Modify Cadmium Bioavailability.

In this study we tested the hypothesis that metal uptake by unicellular algae may be affected by changes in metal speciation in the boundary layer surrounding the algal cells. The freshwater alga Chlamydomonas reinhardtii was preacclimated to different N nutrition regimes; changes in N nutrition are known to change the nature of extracellular metabolites (e.g., reactive oxygen species "ROS", and OH-) and thus boundary layer chemical conditions. Specifically, at a constant bulk free Cd2+ concentration, Cd uptake by N-starved algae in cysteine-buffered solution was significantly higher than that in NTA-buffered solution. This enhancement was likely due to an increase of the free Cd2+ concentration in the boundary layer, resulting from localized cysteine oxidation by ROS released from these algae. On the other hand, Cd uptake was markedly lower when the free Cd2+ concentration near cell surface decreased as a result of an increase in the boundary layer pH of nitrate-acclimated algae or enhanced localized metal complexation. The results imply that redox, acid-base and metal complexation processes in the boundary layer differ from those in bulk water, even under chemically stable bulk conditions, and the boundary layer effect may well be of significance to phytoplankton acquisition of other trace metals.

Morphological, physiological and molecular responses of Nitzschia palea under cadmium stress.

The impact of cadmium on the diatom Nitzschia palea (Kützing) W. Smith 1856 was studied by examining the relation between valve deformities and response through biological processes and genetic expression. Cultures of N. palea were exposed to two Cd treatments (C1 = 2.4 ± 0.6 and C2 = 42.6 ± 4.2 µg Cd/L) along with a control (C0 = 0 µg Cd/L) for 28 days. Cadmium bioaccumulation, diatoms growth, photosynthetic efficiencies, valve deformities and genetic expression were investigated during the course of the experiment. Cadmium exposure had significant effects on bioaccumulation, growth, valve deformities and genetic expression. Maximal effects for all studied endpoints were recorded after 7 days of exposure for the C2 treatment, which corresponded to the sampling time and condition with maximum cadmium bioaccumulation. Abnormal raphe formations (deviation from its lateral position) were significantly more abundant in the C2 treatment compared to the control. Molecular responses were related to cadmium level based on the number of genes impacted, intensity of the response and the frequency of observations. The expression of genes involved in the regulation of mitochondrial metabolism, photosynthesis, oxidative stress and silica metabolism was affected by cadmium exposure.

A Randomized Controlled Multicenter US Food and Drug Administration Trial of the Safety and Efficacy of the Minerva Endometrial Ablation System: One-Year Follow-Up Results.

STUDY OBJECTIVE: To assess the safety and effectiveness of the Minerva Endometrial Ablation System for the treatment of heavy menstrual bleeding in premenopausal women. DESIGN: Multicenter, randomized, controlled, international study (Canadian Task Force classification I). SETTING: Thirteen academic and private medical centers. PATIENTS: Premenopausal women (n = 153) suffering from heavy menstrual bleeding (PALM-COEIN: E, O). INTERVENTION: Patients were treated using the Minerva Endometrial Ablation System or rollerball ablation. MEASUREMENTS AND MAIN RESULTS: At 1-year post-treatment, study success (alkaline hematin ≤80 mL) was observed in 93.1% of Minerva subjects and 80.4% of rollerball subjects with amenorrhea reported by 71.6% and 49% of subjects, respectively. The mean procedure times were 3.1 minutes for Minerva and 17.2 minutes for rollerball. There were no intraoperative adverse events and/or complications reported. CONCLUSION: The results of this multicenter randomized controlled trial demonstrate that at the 12-month follow-up, the Minerva procedure produces statistically significantly higher rates of success, amenorrhea, and patient satisfaction as well as a shorter procedure time when compared with the historic criterion standard of rollerball ablation. Safety results were excellent and similar for both procedures.

Canadian Contraception Consensus (Part 2 of 4).

OBJECTIVE: To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality. OUTCOMES: Guidance for Canadian practitioners on overall effectiveness, mechanism of action, indications, contraindications, non-contraceptive benefits, side effects and risks, and initiation of cited contraceptive methods; family planning in the context of sexual health and general well-being; contraceptive counselling methods; and access to, and availability of, cited contraceptive methods in Canada. EVIDENCE: Published literature was retrieved through searches of Medline and The Cochrane Database from January 1994 to January 2015 using appropriate controlled vocabulary (e.g., contraception, sexuality, sexual health) and key words (e.g., contraception, family planning, hormonal contraception, emergency contraception). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from January 1994 to January 2015. Searches were updated on a regular basis and incorporated in the guideline to June 2015. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of the evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). Chapter 1: Contraception in Canada Summary Statements 1. Canadian women spend a significant portion of their lives at risk of an unintended pregnancy. (II-2) 2. Effective contraceptive methods are underutilized in Canada, particularly among vulnerable populations. (II-2) 3. Long-acting reversible contraceptive methods, including contraceptive implants and intrauterine contraception (copper-releasing and levonorgestrel-releasing devices/systems), are the most effective reversible contraceptive methods and have the highest continuation rates. (II-1) 4. Canada currently does not collect reliable data to determine the use of contraceptive methods, abortion rates, and the prevalence of unintended pregnancy among reproductive-age women. (II-2) 5. A universal subsidy for contraceptive methods as provided by many of Canada's peer nations and a few Canadian provinces may produce health system cost-savings. (II-2) 6. Health Canada approval processes for contraceptives have been less efficient than those of other drug approval agencies and Health Canada processes for other classes of pharmaceuticals. (II-2) 7. It is feasible and safe for contraceptives and family planning services to be provided by appropriately trained allied health professionals such as midwives, registered nurses, nurse practitioners, and pharmacists. (II-2) Recommendations 1. Contraceptive counselling should include a discussion of typical use failure rates and the importance of using the contraceptive method consistently and correctly in order to avoid pregnancy. (II-2A) 2. Women seeking contraception should be counselled on the wide range of effective methods of contraception available, including long-acting reversible contraceptive methods (LARCs). LARCs are the most effective methods of reversible contraception, have high continuation rates, and should be considered when presenting contraceptive options to any woman of reproductive age. (II-2A) 3. Family planning counselling should include counselling on the decline of fertility associated with increasing female age. (III-A) 4. Health policy supporting a universal contraception subsidy and strategies to promote the uptake of highly effective methods as cost-saving measures that improve health and health equity should be considered by Canadian health decision makers. (III-B) 5. Canadian health jurisdictions should consider expanding the scope of practice of other trained professionals such as nurses, nurse practitioners, midwives, and pharmacists and promoting task-sharing in family planning. (II-2B) 6. The Canadian Community Health Survey should include adequate reproductive health indicators in order for health care providers and policy makers to make appropriate decisions regarding reproductive health policies and services in Canada. (III-B) 7. Health Canada processes and policies should be reviewed to ensure a wide range of modern contraceptive methods are available to Canadian women. (III-B) Chapter 2: Contraceptive Care and Access Summary Statements 8. Although there are many contraceptive options in Canada, only a narrow range of contraceptive methods are commonly used by those of reproductive age. (II-3) 9. Condom use decreases with longer relationship tenure and when the sexual partner is considered to be the main partner, likely due to a lower perceived risk of sexually transmitted infection in that relationship. Condom use may also decrease markedly as an unintended consequence when an effective non-barrier method, such as hormonal contraception or intrauterine contraception, is initiated. (II-3) 10. Family planning counselling provides a natural segue into screening for concerns about sexual function or intimate partner violence. (III) 11. Well-informed and well-motivated individuals who have developed skills to practise safer sex behaviours are more likely to use contraceptive and safer sex methods effectively and consistently. (II-2) Recommendations 8. Comprehensive family planning services, including abortion services, should be accessible to all Canadians regardless of geographic location. These services should be confidential, non-judgemental, and respectful of individuals' privacy and cultural contexts. (III-A) 9. A contraceptive visit should include history taking, screening for contraindications, dispensing or prescribing a method of contraception, and exploring contraceptive choice and adherence in the broader context of the individual's sexual behaviour, reproductive health risk, social circumstances, and relevant belief systems. (III-B) 10. Health care providers should provide practical information on the wide range of contraceptive options and their potential non-contraceptive benefits and assist women and their partners in determining the best user-method fit. (III-B) 11. Health care providers should assist women and men in developing the skills necessary to negotiate the use of contraception and the correct and consistent use of a chosen method. (III-B) 12. Contraceptive care should include discussion and management of the risk of sexually transmitted infection, including appropriate recommendations for condom use and dual protection, STI screening, post-exposure prophylaxis, and Hepatitis B and human papillomavirus vaccination. (III-B) 13. Health care providers should emphasize the use of condoms not only for protection against sexually transmitted infection, but also as a back-up method when adherence to a hormonal contraceptive may be suboptimal. (I-A) 14. Health care providers should be aware of current media controversies in reproductive health and acquire relevant evidence-based information that can be briefly and directly communicated to their patients. (III-B) 15. Referral resources for intimate partner violence, sexually transmitted infections, sexual dysfunction, induced abortion services, and child protection services should be available to help clinicians provide contraceptive care in the broader context of women's health. (III-B) Chapter 3: Emergency Contraception Summary Statements 12. The copper intrauterine device is the most effective method of emergency contraception. (II-2) 13. A copper intrauterine device can be used for emergency contraception up to 7 days after unprotected intercourse provided that pregnancy has been ruled out and there are no other contraindications to its insertion. (II-2) 14. Levonorgestrel emergency contraception is effective up to 5 days (120 hours) after intercourse; its effectiveness decreases as the time between unprotected intercourse and ingestion increases. (II-2) 15. Ulipristal acetate for emergency contraception is more effective than levonorgestrel emergency contraception up to 5 days after unprotected intercourse. This difference in effectiveness is more pronounced as the time from unprotected intercourse increases, especially after 72 hours. (I) 16. Hormonal emergency contraception (levonorgestrel emergency contraception and ulipristal acetate for emergency contraception) is not effective if taken on the day of ovulation or after ovulation. (II-2) 17. Levonorgestrel emergency contraception may be less effective in women with a body mass index > 25 kg/m2 and ulipristal acetate for emergency contraception may be less effective in women with a body mass index > 35 kg/m2. However, hormonal emergency contraception may still retain some effectiveness regardless of a woman's body weight or body mass index. (II-2) 18. Hormonal emergency contraception is associated with higher failure rates when women continue to have subsequent unprotected intercourse. (II-2) 19. Hormonal contraception can be initiated the day of or the day following the use of levonorgestrel emergency contraception, with back-up contraception used for the first 7 days. (III) 20. Hormonal contraception can be initiated 5 days following the use of ulipristal acetate for emergency contraception, with back-up contraception used for the first 14 days. (III) Recommendations 16. All emergency contraception should be initiated as soon as possible after unprotected intercourse. (II-2A) 17. Women should be informed that the copper intrauterine device (IUD) is the most effective method of emergency contraception and can be used by any woman with no contraindications to IUD use. (II-3A) 18.

Objectif : Fournir des lignes directrices aux fournisseurs de soins quant à l'utilisation de modes de contraception pour la prévention de la grossesse et quant à la promotion d'une sexualité saine. Issues : Orientation des praticiens canadiens en ce qui concerne l'efficacité globale, le mécanisme d'action, les indications, les contre-indications, les avantages n'étant pas liés à la contraception, les effets indésirables, les risques et le protocole de mise en œuvre des modes de contraception abordés; planification familiale dans le contexte de la santé sexuelle et du bien-être général; méthodes de counseling en matière de contraception; et accessibilité et disponibilité des modes de contraception abordés au Canada. Résultats : La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans MEDLINE et The Cochrane Library entre janvier 1994 et janvier 2015 au moyen d'un vocabulaire contrôlé (p. ex. contraception, sexuality, sexual health) et de mots clés (p. ex. contraception, family planning, hormonal contraception, emergency contraception) appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais entre janvier 1994 et janvier 2015. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en juin 2015. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats a été évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau). Chapitre 1 : Contraception au Canada Déclarations sommaires 1. Les Canadiennes sont exposées à des risques de grossesse non planifiée pendant une partie considérable de leur vie. (II-2) 2. Les modes efficaces de contraception sont sous-utilisés au Canada, particulièrement au sein des populations vulnérables. (II-2) 3. Les modes de contraception réversible à action prolongée, dont les implants contraceptifs et la contraception intra-utérine (dispositifs / systèmes à libération de cuivre ou de lévonorgestrel), sont les modes de contraception réversible les plus efficaces; de plus, ils comptent les taux les plus élevés de poursuite du traitement. (II-1) 4. Au Canada à l'heure actuelle, nous ne recueillons pas de données fiables qui permettraient d'établir le taux d'utilisation des modes de contraception, le taux d'avortement et la prévalence des grossesses non planifiées chez les femmes en âge de procréer. (II-2) 5. L'octroi d'une subvention universelle destinée aux modes de contraception, à l'instar de bon nombre d'autres pays et de quelques provinces canadiennes, pourrait générer des économies pour le système de santé. (II-2) 6. Dans le cas des contraceptifs, les processus d'homologation de Santé Canada ont été moins efficaces que ceux d'autres organismes d'homologation, en plus d'être moins efficaces que les processus qu'elle a elle-même mis en vigueur en ce qui concerne d'autres catégories de produits pharmaceutiques. (II-2) 7. L'offre de contraceptifs et de services de planification familiale par des professionnels paramédicaux (tels que les sages-femmes, les infirmières autorisées, les infirmières praticiennes et les pharmaciens) ayant bénéficié d'une formation adéquate est faisable et sûre. (II-2) Recommandations 1. Les services de counseling traitant de la contraception devraient comprendre une discussion au sujet des taux d'échec liés à l'utilisation typique et de l'importance d'utiliser régulièrement et correctement le mode de contraception choisi, de façon à éviter la grossesse. (II-2A) 2. Les services de counseling offerts aux femmes qui cherchent à se prévaloir d'un mode de contraception devraient porter sur la vaste gamme des modes efficaces disponibles, y compris sur les modes de contraception réversible à action prolongée. Ces derniers sont les modes les plus efficaces de contraception réversible, comptent des taux élevés de poursuite du traitement et devraient être pris en considération, pour toutes les femmes en âge de procréer, au moment d'aborder avec celles-ci les options de contraception qui s'offrent à elles. (II-2A) 3. Les services de counseling en matière de planification familiale devraient aborder la question du déclin de la fertilité qui est associé au vieillissement chez la femme. (III-A) 4. Les décideurs canadiens du domaine de la santé devraient envisager la mise en œuvre de politiques de santé soutenant l'offre universelle d'une subvention à la contraception et de stratégies visant à promouvoir l'adoption de modes de contraception grandement efficaces, et ce, à titre de mesures de réduction des coûts permettant l'amélioration de la santé et de l'équité en matière de santé. (III-B) 5. Les territoires de compétence canadiens en matière de santé devraient envisager d'élargir le champ de pratique d'autres professionnels formés (comme les infirmières, les infirmières praticiennes, les sages-femmes et les pharmaciens) et de promouvoir le partage des tâches en planification familiale. (II-2B) 6. L'Enquête sur la santé dans les collectivités canadiennes devrait englober des indicateurs adéquats en matière de santé génésique, de façon à pouvoir permettre aux fournisseurs de soins de santé et aux décideurs de prendre des décisions opportunes à l'égard des politiques et des services de santé génésique au Canada. (III-B) 7. Les processus et les politiques de Santé Canada devraient être passés en revue pour que l'on puisse s'assurer qu'ils ne nuisent pas indûment à l'offre d'une vaste gamme de modes de contraception modernes aux Canadiennes. (III-B) Chapitre 2 : Soins en matière de contraception et accès à la contraception Déclarations sommaires 8. Bien que le Canada compte de nombreuses options en matière de contraception, les modes de contraception couramment utilisés par les femmes en âge de procréer sont issus d'une gamme restreinte. (II-3) 9. L'utilisation du condom diminue au fur et à mesure que se poursuit une relation et lorsque le partenaire sexuel est considéré comme étant le partenaire principal, probablement en raison d'une baisse du risque perçu d'infections transmissibles sexuellement au sein de la relation en question. L'utilisation du condom pourrait, de façon fortuite, également connaître une baisse marquée à la suite de la mise en œuvre d'un mode de contraception efficace ne faisant pas partie des méthodes de barrière (comme la contraception hormonale ou intra-utérine). (II-3) 10. Le counseling en matière de planification familiale peut naturellement mener au dépistage de la violence conjugale et des problèmes liés à la fonction sexuelle. (III) 11. Les personnes bien renseignées et bien motivées qui ont acquis les compétences nécessaires à la pratique de comportements sexuels à risques réduits sont plus susceptibles d'utiliser des modes de contraception et des pratiques sexuelles à risques réduits de façon efficace et systématique. (II-2) Recommandations 8. Des services exhaustifs de planification familiale (y compris des services d'avortement) devraient être offerts à tous les Canadiens, peu importe leur emplacement géographique. Ces services devraient être confidentiels et assurer le respect de la vie privée et des contextes culturels des personnes qui les utilisent. (III-A) 9. Les consultations en matière de contraception devraient comprendre une anamnèse, un dépistage des contre-indications, l'offre ou la prescription d'un mode de contraception, ainsi que l'exploration des choix en matière de contraception et des facteurs associés à l'observance dans le cadre élargi du comportement sexuel, des risques liés à la santé génésique, du contexte social et des croyances de la femme en question. (III-B) 10. Les fournisseurs de soins devraient offrir des renseignements pratiques sur la vaste gamme des options en matière de contraception et sur leurs avantages potentiels n'étant pas liés à la contraception, en plus d'aider les femmes et leurs partenaires à choisir le mode de contraception étant le mieux adapté à leurs besoins. (III-B) 11. Les fournisseurs de soins devraient aider les femmes et les hommes à acquérir les compétences nécessaires à la négociation du recours à la contraception, ainsi qu'à l'utilisation correcte et systématique du moyen de contraception choisi. (III-B) 12. Les soins en matière de contraception devraient aborder les risques de contracter des infections transmissibles sexuellement et en assurer la prise en charge; ils devraient, à ce chapitre, être fondés sur la formulation de recommandations appropriées en ce qui concerne l'utilisation de condoms et d'une protection double, le dépistage des infections transmissibles sexuellement, la prophylaxie post-exposition et la vaccination contre l'hépatite B et le virus du papillome humain. (III-B) 13. Les fournisseurs de soins devraient souligner que l'utilisation de condoms n'a pas seulement pour but de conférer une protection contre les infections transmissibles sexuellement, mais qu'elle agit également à titre de méthode d'appoint lorsque l'observance envers un contraceptif hormonal pourrait être sous-optimale. (I-A) 14. Les fournisseurs de soins devraient se tenir au fait des controverses médiatiques qui font rage dans le domaine de la santé génésique et obtenir les données factuelles pertinentes qui pourront être communiquées (de façon brève et directe) à leurs patientes. (III-B) 15. Des ressources spécialisées en ce qui concerne la violence conjugale, les infections transmissibles sexuellement, le dysfonctionnement sexuel, lesservices d'avortement provoqué et les services de protection de l'enfance devraient être disponibles pour aider les cliniciens à offrir des soins en matière de contraception dans le contexte élargi de la santé des femmes. (III-B) Chapitre 3 : Contraception d'urgence Déclarations sommaires 12. Le dispositif intra-utérin au cuivre constitue la méthode de contraception d'urgence la plus efficace. (II-2) 13. Un dispositif intra-utérin au cuivre peut être utilisé à des fins de contraception d'urgence jusqu'à sept jours à la suite d'une relation sexuelle non protégée, pour autant que la présence d'une grossesse ait été écartée et qu'il n'existe aucune autre contre-indication à son insertion. (II-2) 14. La contraception d'urgence au lévonorgestrel est efficace jusqu'à cinq jours (120 heures) à la suite d'une relation sexuelle non protégée; son efficacité diminue au fur et à mesure que s'allonge le délai entre la relation sexuelle non protégée et son administration. (II-2) 15. La contraception d'urgence à l'acétate d'ulipristal est plus efficace que celle qui fait appel au lévonorgestrel, et ce, jusqu'à cinq jours à la suite d'une relation sexuelle non protégée. Cette différence en matière d'efficacité devient plus prononcée au fur et à mesure que s'allonge le délai entre la relation sexuelle non protégée et l'administration, particulièrement après 72 heures. (I) 16. La contraception d'urgence hormonale (au lévonorgestrel ou à l'acétate d'ulipristal) n'est pas efficace lorsqu'elle est administrée le jour de l'ovulation ou par la suite. (II-2) 17. La contraception d'urgence au lévonorgestrel pourrait être moins efficace chez les femmes dont l'indice de masse corporelle est supérieur à 25 kg/m2, tandis que la contraception d'urgence à l'acétate d'ulipristal pourrait être moins efficace chez les femmes dont l'indice de masse corporelle est de 35 kg/m2 ou plus. Quoi qu'il en soit, la contraception d'urgence hormonale pourrait tout de même conserver une certaine efficacité, peu importe le poids ou l'indice de masse corporelle de la femme qui en fait la demande. (II-2) 18. La contraception d'urgence hormonale est associée à des taux d'échec plus élevés lorsque les femmes qui l'utilisent continuent par la suite à connaître des relations sexuelles non protégées. (II-2) 19. Une contraception hormonale peut être entamée le jour de l'utilisation d'une contraception d'urgence au lévonorgestrel, ou le jour suivant celle-ci, en s'assurant de mettre en œuvre une contraception d'appoint pendant les sept premiers jours. (III) 20. Une contraception hormonale peut être entamée cinq jours à la suite de l'utilisation d'une contraception d'urgence à l'acétate d'ulipristal, en s'assurant de mettre en œuvre une contraception d'appoint pendant les quatorze premiers jours. (III) Recommandations 16. La contraception d'urgence, toutes méthodes confondues, devrait être mise en œuvre dès que possible à la suite d'une relation sexuelle non protégée. (II-2A) 17. Les femmes devraient être avisées que le dispositif intra-utérin au cuivre constitue la méthode de contraception d'urgence la plus efficace et que ce dispositif peut être utilisé par toute femme qui ne présente pas de contre-indications à son utilisation. (II-3A) 18. Les fournisseurs de soins ne devraient pas déconseiller l'utilisation de la contraception d'urgence hormonale en fonction de l'indice de masse corporelle de la femme qui en fait la demande. L'utilisation d'un dispositif intra-utérin au cuivre à des fins de contraception d'urgence devrait être recommandée pour les femmes présentant un indice de masse corporelle supérieur à 30 kg/m2 qui sollicitent une contraception d'urgence. En présence de conditions favorables en matière d'accessibilité et de coût, la contraception d'urgence faisant appel à l'acétate d'ulipristal devrait constituer l'option de première intention à offrir aux femmes présentant un indice de masse corporelle de 25 kg/m2 ou plus qui préfèrent avoir recours à une contraception d'urgence hormonale. (II-2B) 19. Les fournisseurs de soins devraient discuter d'un plan visant la mise en œuvre d'une contraception continue avec les femmes qui en viennent à utiliser des pilules de contraception d'urgence; ils devraient également offrir des modes adéquats de contraception continue à ces femmes, lorsque celles-ci s'y montrent intéressées. La contraception hormonale devrait être entamée dans les 24 heures suivant l'administration d'une contraception d'urgence faisant appel au lévonorgestrel; de plus, une contraception d'appoint (ou l'abstinence) devrait être mise en œuvre pendant les sept premiers jours suivant le début de l'utilisation d'une contraception hormonale. (III-B) Dans le cas de la contraception d'urgence faisant appel à l'acétate d'ulipristal, la contraception hormonale devrait être entamée cinq jours après l'administration de la contraception d'urgence. Une contraception d'appoint (ou l'abstinence) doit être mise en œuvre pendant les cinq premiers jours suivant l'administration d'une contraception d'urgence faisant appel à l'acétate d'ulipristal, puis pendant les 14 premiers jours suivant le début de l'utilisation d'une contraception hormonale. (III-B) 20. L'acétate d'ulipristal et le lévonorgestrel ne devraient pas être utilisés de façon concomitante à des fins de contraception d'urgence. (III-B) 21. Un test de grossesse devrait être mené en l'absence de menstruations dans les 21 jours suivant l'utilisation de pilules ou l'insertion d'un dispositif intra-utérin au cuivre à des fins de contraception d'urgence. (III-A) 22. Des services de santé devraient être élaborés pour permettre aux Canadiennes d'obtenir un accès en temps opportun à toutes les méthodes efficaces de contraception d'urgence. (III-B).