Search

Objectives Since 2018, four establishments in Quebec have been instrumental in implementing the PAROLE-Onco program, which introduced accompanying patients (APs) in healthcare teams to improve cancer patients’ experience. APs are patient advisors who have acquired specific experiential knowledge related to living with cancer, using services, and interacting with healthcare professionals. They are therefore in a unique and reliable position to be able to provide emotional, informational, cognitive and navigational support to patients dealing with cancer. We aimed to explore APs’ perspectives regarding the limiting and facilitating factors in terms of how they are integrated into the clinical oncology teams. Methods A qualitative study based on semi-structured interviews and focus groups was conducted with 20 APs at the beginning of their intervention (T1) and two years afterwards (T2). Limiting and facilitating factors of APs’ integration into clinical teams were analyzed in terms of governance, culture, resources and tools. Results The most significant limiting factors raised by APs to be integrated into clinical teams were: governance involvement, organizational boundaries, team members' availabilities, and confusion about the specific roles played by APs. Communication challenges were also raised, leading to inadequate promotion of the program to patients. The lack of time, space and compensation were also mentioned as limiting factors. Creating opportunities for team members to meet APs, building trust and teaching team members how APs’ activities are complementary to theirs were enhancing factors. Other facilitators include APs being involved in decision-making committees, being leaders in the PAROLE-Onco program promotion to patients and clinical team members and creating opportunities to communicate with team members to help enhance their work and provide feedback to improve patient services. Awareness of APs’ added value for the team and patients is also a key facilitator. Regarding tools, offering accompanying services by telephone allows both patients and APs to benefit from the flexibility they need. Conclusion Over time, APs were able to identify the best factors for successful implementation. Recommendations include APs and professionals working in co-construction on organization, leadership, resources, and status factors. This could help catalyze a change in culture within health establishments and allow people dealing with cancer to benefit from the experiential knowledge of other patients within their clinical team.

Background Patient engagement in care is a priority and a key component of clinical practice. Different approaches to care have been introduced to foster patient engagement. There is a lack of a recent review on tools for assessing the main concepts and dimensions related to patient engagement in care. Objective Our scoping review sought to map and summarize recently validated tools for assessing various concepts and dimensions of patient engagement in care. Search strategy A scoping review of recent peer-reviewed articles describing tools that assess preferences in and experience with patient engagement in care was conducted in four databases (Ovid Medline, Ovid EMBASE, Cochrane Database of Systematic Reviews, CINAHL-EBSCO). We adopted a broad definition based on the main concepts of patient engagement in care: patient-centredness, empowerment, shared decision-making and partnership in care. Main results Of 2161 articles found, 16, each describing a different tool, were included and analysed. Shared decision-making and patient-centredness are the two main concepts evaluated, often simultaneously in most of the tools. Only four scales measure patient-centredness, empowerment and shared decision-making at the same time, but no tool measures the core dimensions of partnership in care. Most of the tools did not include patients in their development or validation or just consulted them during the validation phase. Discussion and conclusion There is no tool coconstructed with patients from development to validation, which can be used to assess the main concepts and dimensions of patient engagement in care at the same time. Patient and public contribution This manuscript was prepared with a patient expert who is one of the authors. Vincent Dumez, who is a patient expert and codirector of the Center of Excellence on Partnership with Patients and the Public, has contributed to the preparation of the manuscript.

Context Partnership between patients and health-care professionals (HCPs) is a concept that needs a valid, practical measure to facilitate its use by patients and HCPs. Objective To co-construct a tool for measuring the degree of partnership between patients and HCPs. Design The CADICEE tool was developed in four steps: (1) generate key dimensions of patient partnership in clinical care; (2) co-construct the tool; (3) assess face and content validity from patients' and HCPs' viewpoints; and (4) assess the usability of the tool and explore its measurement performance. Results The CADICEE tool comprises 24 items under 7 dimensions: 1) relationship of Confidence or trust between the patient and the HCPs; 2) patient Autonomy; 3) patient participation in Decisions related to care; 4) shared Information on patient health status or care; 5) patient personal Context; 6) Empathy; and 7) recognition of Expertise. Assessment of the tool's usability and measurement performance showed, in a convenience sample of 246 patients and relatives, high face validity, acceptability and relevance for both patients and HCPs, as well as good construct validity. Conclusions The CADICEE tool is developed in co-construction with patients to evaluate the degree of partnership in care desired by patients in their relationship with HCPs. The tool can be used in various clinical contexts and in different health-care settings. Patient or public contribution Patients were involved in determining the importance of constructing this questionnaire. They co-constructed it, pre-tested it and were part of the entire questionnaire development process. Three patients participated in the writing of the article.

Quebec is one of the Canadian provinces with the highest rates of cancer incidence and prevalence. A study by the Rossy Cancer Network (RCN) of McGill university assessed six aspects of the patient experience among cancer patients and found that emotional support is the aspect most lacking. To improve this support, trained patient advisors (PAs) can be included as full-fledged members of the healthcare team, given that PA can rely on their knowledge with experiencing the disease and from using health and social care services to accompany cancer patients, they could help to round out the health and social care services offer in oncology. However, the feasibility of integrating PAs in clinical oncology teams has not been studied. In this multisite study, we will explore how to integrate PAs in clinical oncology teams and, under what conditions this can be successfully done. We aim to better understand effects of this PA intervention on patients, on the PAs themselves, the health and social care team, the administrators, and on the organization of services and to identify associated ethical and legal issues. We will conduct six mixed methods longitudinal case studies. Qualitative data will be used to study the integration of the PAs into clinical oncology teams and to identify the factors that are facilitators and inhibitors of the process, the associated ethical and legal issues, and the challenges that the PAs experience. Quantitative data will be used to assess effects on patients, PAs and team members, if any, of the PA intervention. The results will be used to support oncology programs in the integration of PAs into their healthcare teams and to design a future randomized pragmatic trial to evaluate the impact of PAs as full-fledged members of clinical oncology teams on cancer patients’ experience of emotional support throughout their care trajectory. This study will be the first to integrate PAs as full-fledged members of the clinical oncology team and to assess possible clinical and organizational level effects. Given the unique role of PAs, this study will complement the body of research on peer support and patient navigation. An additional innovative aspect of this study will be consideration of the ethical and legal issues at stake and how to address them in the health care organizations.

The COVID-19 pandemic created an urgent need to act to reduce the spread of the virus and alleviate congestion in healthcare services, protect health professionals, and help them maintain satisfactory quality and safety of care. Remote monitoring platforms (RPM) emerged as potential solutions. In this study, we evaluate, from health professionals’ perspectives, the capacity and contribution of two different digital platforms to maintain quality, safety, and patient engagement in care. A cross-sectional study was conducted using a survey in which a total of 491 health professionals participated. The results show that, in general, user perceptions of the quality and safety of care provided through the platforms were positive. The ease of access to health professionals’ services in general and shorter waiting times for patients were the two main features that were highly appreciated by most participants. However, some problems were encountered during the use of these two platforms, such as a lack of training and/or direct support for users. To improve the two platforms and maximize their use, the areas for improvement and the issues identified should be addressed as part of a collaborative process involving health professionals and patients as well as health system leaders, decision-makers, and digital platform providers.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.toxlet.2019.05.020. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Cadmium (Cd), lead (Pb) and mercury (Hg) are known nephrotoxicants that have been associated with the risk of developing type-2 diabetes (T2D). The aim of this pilot study was to explore relations between biomarkers of Cd, Pb and Hg exposure, early urinary biomarkers of renal dysfunction (kidney-injured molecule-1 (KIM-1), N-acetylglucosaminidase and retinol-binding protein (RBP)) and plasma biomarkers deemed predictive of the risk of developing T2D (adiponectin, leptin, branched-chain and aromatic amino acids), among 70 participants (age range: (46-87 yrs)) from the Canadian Longitudinal Study on Aging (CLSA) with normal glycemic control (glycated haemoglobin ≤ 6.5%) in all but four of them. Significant (p 0.05) Spearman correlation coefficients were obtained between: plasma adiponectin and RBP (r = 0.42), urinary Cd (r = 0.32), blood Cd (r = 0.36); KIM-1 and CdU (r = 0.33) as well as HgU (r = 0.37); RBP and isoleucine (r = -0.28), leucine (r = -0.33), tyrosine (r = -0.3) and valine (r = -0.44); CdU and isoleucine and valine (r = -0.27 for both). Multiple linear regression analyses showed that some T2D-related biomarkers are confounders of associations between RBP and Hg or Cd biomarkers. Path analyses support a mediating effect of adiponectin on the relation between urinary Cd and RBP. Concluding, this pilot study originally investigated a comprehensive set of biomarkers on complex interactions between toxic metal exposure, renal function and T2D in a group of aging Canadians. Its findings warrant further investigation of longitudinal data in a greater number of participants.

54 Background: Since 2017, in Quebec (Canada), a research project is focusing on the feasibility, the processes, and the contribution of integrating patients who have already had cancer experiences (named patient advisors (PA)) in the oncology clinical team. In fact, the trained PA meet patients in health care settings in addition to the other health professionals in order to improve health care and partnership between professionals and patients. This presentation communicates the PA’s perception of their contribution and the factors influencing implementation of these programs in 4 establishments. Methods: Between April and May 2020, semi-structured virtual interviews lasting about 60 minutes were conducted on 12 patient advisors involved since 2017 in the elaboration of these support programs. The interviews were recorded and transcribed completely. The data analysis was done with content analysis using the QDA Miner 5.0 software, applying the qualitative analysis quality standards. Results: First of all, the 12 PAs have reported that the accompaniment of 67 patients have allowed them to share their experiential knowledge not only related to living with the illness but also about healthcare organization and the anticipation of treatments. They also highlighted their capacity to share situations that can be improved by healthcare professionals (example: wait times for exams; patients’ difficulty in understanding their illness, etc). However, they also highlighted 4 factors which limit the implementation: 1) organizational (the unclear and changing nature of the breast cancer consultation schedule, difficulty of access to consultation rooms and unsuitable schedules for the PA’s reality.; 2) leadership (lack of clinicians promoting the intervention; managers’ low involvement; lack of clarity of roles); 3) human (work overload and employee turnover); 4) PA’s status (lack of compensation and of recognition). Also, to optimize their integration, the PA’s suggest to work on a lasting bond of trust with the professionals, the creation of a status recognized by health establishments, the recognition of their role by the clinical team, to give them access to physical spaces, and an openness of the teams to their complementary knowledge. Conclusions: These first results suggest the importance during the implementation of such programs of working proactively with the PAs and the professionals on organization, leadership, resources, and status factors to allow the people dealing with cancer to benefit from experiential knowledge of other patients within their clinical team.

57 Background: Since 2018, three establishments in Quebec have introduced patient advisors (PA) in their healthcare team in order to improve cancer patients’ experience. These PA, who have had a cancer experience, meet patients undergoing radiotherapy treatments or in oncogenetics for breast cancer on the healthcare site. They conduct consultations to complete the offer of services by bringing emotional, informational, and educational support. Methods: A longitudinal study of multiple cases was completed from January to June 2020. After each accompaniment, the PA filled out a logbook to document the main themes covered and the accompanied patient fill out a survey to evaluate their experience one week after the intervention. A qualitative analysis of the logbook content and descriptive statistics were conducted. The REDCAP platform was used for monitoring the process of data collection and to administer the surveys online. Results: In total, 67 patients were accompanied by 4 PA. 71 logbooks were completed by the PA. The logbooks show that 70.3% of accompaniments took place right before radiotherapy and 63.6% following the results of the genetic test in oncogenetics. 50% of meetings took place in person in the establishment (in a space dedicated to the PA or not) and 45.8% were by phone. The meetings lasted approximately 37 minutes (min: 15 minutes and max: 90 minutes). The majority only met once (93.1 %). The most common themes discussed are: the role of the PA (94.1%), returning to day life (57.6%) and dealing with stress and anxiety (52.2%). 96% of PA felt that they did not encounter any difficulties during the accompaniment. For the accompanied women, the partnership was most beneficial for their experience with the illness (sharing experiences of side-effects, on the impact of the illness on every day life, with their social circle). 79% of patients found that the accompaniment met their needs. 90% of patients estimate that these meetings are complimentary to the healthcare professionals’ interventions. Finally, 89.5% of accompanied patients think that it would be very important to develop these types of meetings on a larger scale. Concerning the adaptation of spaces for the meetings, 26.3% are very satisfied and 26.3% are rather satisfied (probably an area for improvement). Conclusions: Overall, the partnerships seem to answer the needs of the accompanied patients and the PA can share their experience inside the clinical team.

Pesticide residues in food is a public health concern. This study aimed to evaluate health risk and benefit associated with chronic consumption of fruits and vegetables (F&V) containing residual pesticides in the province of Quebec, Canada. Based on a representative sample of Quebecers (n=4727, aged 1–79) enrolled in the Canadian nutrition survey, population's mean chronic dietary exposure through consumption of F&V was evaluated for 169 different pesticide active ingredients (PAI), including 135 for which toxicological reference values (TRV) were available in the literature. Total lifetime cancer risk was estimated to be 3.3×10−4 considering the 28 substances for which an oral slope factor was also available. Non-cancer risk quotients greater than 1 were obtained at the 95th percentile of children's exposure for 10 of the 135 PAIs, and considering the most severe pesticide-specific TRV. Dithiocarbamates and imazalil are the authorized PAI that contribute the most to cancer and non cancer risk; they are therefore identified as “priority” PAI. For each estimated case of cancer triggered by PAI exposure, at least 88 cases were deemed prevented by the consumed F&V, based on the population's etiological fraction of the cancer risk that F&V prevent. Concluding, chronic health risks investigated are low and health benefits of F&V consumption by far outweigh the PAI-related risk. However, risk estimates are not negligeable and uncertainties remain. Thus, reducing PAI exposure through F&V consumption with a particular focus on “priority” PAI mentionned above, while maintaining an abundant and varied F&V diet, is desirable. Keywords: Fruits, Risk assessment, Pesticide, Prioritization, Risk/benefits balance, Vegetables

Drinking water intake of arsenic (As) from private wells may represent a significant exposure pathway and induce oxidative DNA damage. We measured total As concentrations in hair and nails, and concentrations of the different species of As and its metabolites as well as 8-OHdG in urine of 110 non-smoking adults living in a rural region of the Province of Quebec, Canada. Significant differences in exposure biomarker levels were observed between individuals consuming drinking water with As levels of≤1.0,1.0 -≤10 and10 μg/l. Multivariate linear regression analysis also showed a significant relationship between estimated daily drinking water intakes of As and biomarker levels. Conversely, 8-OHdG levels were not significantly related to daily drinking water intakes of As or to hair, nail or urinary exposure biomarker levels, according to multivariate linear regression analysis. Even at the relatively low levels of As found in well water of our participants, water consumption significantly increases their body load of As, as confirmed by multiple matrix measurements, which reflected exposure over different time frames. However, this increased internal As dose was not associated with higher oxidative damage to DNA as reflected by urinary 8-OHdG levels.

Acrylamide (AA) is a probable human carcinogen found in several foods. Little information is available regarding exposure of adolescents, a subgroup potentially consuming more AA-rich foods. We investigated the relationship between dietary AA intake and levels of biomarkers of exposure (urinary metabolites and hemoglobin adducts) in 195 non-smoking teenagers of Montreal Island aged 10–17 years. Dietary habits and personal characteristics were documented by questionnaire. AA and its metabolites were quantified in 12-h urine collections by LC-MS/MS. Hemoglobin adducts from 165 blood samples were also analyzed by LC-MS/MS. Most prevalent urinary metabolites were NACP and NACP-S, with respective geometric mean concentrations of 31.2 and 14.2 μmol/mol creatinine. Geometric mean concentrations of AAVal and GAVal (hemoglobin adducts of AA and glycidamide (GA) with N-terminal valine residues) were 45.4 and 45.6 pmol/g globin, respectively. AA intake during the 2 days before urine collection was a significant predictor of NACP+NACP-S urinary concentrations (P

Chronic exposure to inorganic arsenic leads to an increased risk of cancer. A biological measurement was conducted in 153 private well owners and their families consuming water contaminated by inorganic arsenic at concentrations that straddle 10 μg/L. The relationship between the external dose indicators (concentration of inorganic arsenic in wells and daily well water inorganic arsenic intake) and the internal doses (urinary arsenic--sum of As(III), DMA, and MMA, adjusted for creatinine--and total arsenic in toenails) was evaluated using multiple linear regressions, controlling for age, gender, dietary sources of arsenic, and number of cigarettes smoked. It showed that urinary arsenic was associated with concentration of inorganic arsenic in wells (p.001) and daily well water inorganic arsenic intake (p.001) in adults, and with daily well water inorganic arsenic intake (p = .017) and rice consumption (p = .022) in children (n = 43). The authors' study reinforces the drinking-water quality guidelines for inorganic arsenic.

A longitudinal biomonitoring study was conducted to assess exposure to polycyclic aromatic hydrocarbons (PAH) in non-occupationally exposed nonsmoking adults living in the vicinity of an aluminum plant. Metabolites of several PAH (pyrene, naphthalene, chrysene, fluoranthene, benz[a]anthracene) were measured in the urine of the participants, including 1-hydroxypyrene (1-OHP) as a validated biomarker and pyrene diones as novel biomarkers. In total, 73 individuals living about 1 km away from the plant (taken as the exposed group) were compared repeatedly with 71 individuals living at least 11 km from the smelter (used as the control group). Complete first morning voids were collected twice, at a 2-wk interval, in the fall of 2005 and twice weekly for 2 consecutive weeks in the spring of 2006. Urinary biomarker concentrations were then measured by an ultra-performance liquid chromatography (UPLC) method with time-of-flight mass spectrometry detection (MS-TOF) (UPLC-MS-TOF). For most sampling days, individuals living near the plant showed significantly higher excretion values of both 1-OHP and pyrene diones (mean ratio up to 2- and 2.4-fold, respectively) than individuals living further from the plant. In the group living near the plant, geometric mean concentrations of 1-OHP varied from 0.047 to 0.058 micromol/mol creatinine, depending on the sampling day, as compared to 0.025 to 0.04 micromol/mol creatinine in the reference group. Corresponding mean values for pyrene diones were 0.017-0.056 micromol/mol creatinine and 0.014-0.039 micromol/mol creatinine, respectively. Urinary 1- and 2-naphthols were also measured as a reference and showed no significant differences between the two groups for most sampling days; metabolite concentrations of the other monitored PAH (chrysene, fluoranthene, benz[a]anthracene) were mostly below the analytical limit of detection of 0.005 to 0.01 microg/L, depending on the metabolite, with a detection rate varying from 0 to at most 21%. Individuals living near the aluminum plant thus appeared to be repeatedly exposed to higher pyrene levels than the control group, on the basis of both 1-OHP and pyrene dione excretions. However, 1-OHP concentrations observed in this first group were similar to those of other reference populations of nonsmokers studied in the past. Uptake of the other PAH associated with plant emissions was too small to significantly increase the excretion of their metabolites.

In Canada, Methylcyclopentadienyl manganese tricarbonyl (MMT) replaced tetraethyl lead in gasoline as an antiknock agent from 1976 until 2003. The combustion of MMT leads to increased manganese (Mn) concentrations in the atmosphere, and represents one of the main sources of human exposure to Mn. The nervous system is the major target of the toxicity of Mn and Mn compounds. The purpose of this study was to investigate exposure-response relationships for neuropathology and tremor, and the associated electromyogram (EMG), following subchronic inhalation exposure of rats to a mixture of Mn phosphate/sulfate particles. Rats were exposed 6 h per day, 5 days per week for 13 consecutive weeks at 30, 300 or 3000 microg m(-3) Mn phosphate/sulfate mixture and compared with controls. Half of the rats had EMG electrodes implanted in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Two days after the end of Mn exposure, rats were killed by exsanguination and Mn concentrations in the brain (caudate putamen, globus pallidus and frontal cortex) were determined by neutron activation analysis while neuropathology was assessed by counting neuronal cells in 2.5 mm x 2.5 mm grid areas. Increased Mn concentrations were observed in all brain sections at the highest level of exposure. The neuronal cell loss was significantly different in the globus pallidus and the caudate putamen at the highest level of exposure (3000 microg m(-3)). No sign of tremor was observed among the rats. In conclusion, exposure to a high level of Mn phosphate/sulfate mixture brought on neuropathological changes in a specific area of the brain; however, no sign of tremor was observed.

The central nervous system is an important target for manganese (Mn) intoxication in humans; it may cause neurological symptoms similar to Parkinson's disease. Manganese compounds emitted from the tailpipe of vehicles using methylcyclopentadienyl manganese tricarbonyl (MMT) are primarily Mn phosphate, Mn sulfate, and Mn phosphate/sulfate mixture. The purpose of this study is to compare the patterns of Mn distribution in various brain regions (olfactory bulb, frontal parietal cortex, globus pallidus, striatum and cerebellum) and other tissues (lung, liver, kidney, testis) and the neurobehavioral damage following inhalation exposure of rats to three Mn species. Rats (n=15 rats per Mn species) were exposed 6 h per day, 5 days per week for 13 consecutive weeks to metallic Mn, Mn phosphate or Mn phosphate/sulfate mixture at about 3000 microgm(-3) and compared to controls. At the end of the exposure period, spontaneous motor activity was measured for 36 h using a computerized autotrack system. Mn in tissues was determined by instrumental neutron activation analysis (INAA). The Mn concentrations in the brain were significantly higher in rats exposed to Mn phosphate and Mn phosphate/sulfate mixture than in control rats or rats exposed to metallic Mn. Exposure to Mn phosphate/sulfate mixture caused a decrease in the total ambulatory count related to locomotor activity. Our results confirm that Mn species and solubility have an influence on the brain distribution of Mn in rats.

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 microg/m(3). At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 microg/m(3), but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 microg/m(3) exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate.

Our research group previously established the time variation of atmospheric Mn in Montreal for the period 1981-1992. The results indicated stable Mn concentrations between 1981 and 1990 followed by a decrease of almost 50% attributed to the closing of a ferromanganese plant located approximately 25 km from Montreal. The aim of this study is to assess the atmospheric concentrations of Mn in Montreal between 1993 and 2000, to compare these data to those for the period 1981-1992, and to evaluate the presence of any trend. Three sampling stations belonging to the Montreal Urban Community (MUC) air quality surveillance network were selected. Filters from 1993 to 2000 were obtained from the MUC archives. The first sample of each month was selected and chemical analysis was performed by neutron activation analysis. The mean annual atmospheric Mn concentrations in Montreal from 1993 to 2000 were found to be very stable. The mean Mn concentration calculated for this time period was 0.01 microg/m(3) for station 99 (characterized by a low traffic density), which was significantly different (P0.05) from the mean of 0.03 microg/m(3) for stations 13 and 68 which had higher traffic densities. Even though Mn represented a small percentage of the TSP (varying between 0.02% and 0.14%), the comparison between Mn and TSP is interesting since the stable temporal profile of Mn since 1993 contrasts with the continuously decreasing atmospheric TSP concentrations. This observation suggests that the combustion of MMT used in gasoline could be contributing to maintaining stable atmospheric Mn levels.

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P < 0.05) while for the caudate/putamen, Mn concentrations were 1.06 vs 0.73 vs 0.62 vs 0.47 ppm (P < 0.05). The Mn concentrations in lung were also dose-dependent (10.30 vs 1.40 vs 0.42 vs 0.17 ppm; P < 0.05). No statistical difference was observed for loss of neurons in caudate/putamen and globus pallidus. Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic derivative of manganese (Mn) used in Canada as an antiknock agent and octane enhancer in gasoline. In a recent study, we measured the atmospheric concentrations of MMT at selected outdoor sites in Montreal. Results ranged from 0.18 to 25 ng m-3 (expressed as Mn) and do not reflect personal exposure levels. The highest values were obtained at a gas station (mean of 12 ng m-3). By extension, evaluation of the personal exposure of gas station attendants constitutes a promising area of research. In an earlier study, the sampling method used allowed the possibility that the samples could have included ultra-fine particles, which may have passed through the filters used, and the chemical analysis used (neutron activation) did not discriminate between MMT and other Mn compounds. The present study aims to validate an improved sampling method and to assess personal exposure of gas station attendants to MMT. The MMT recovery of the new sampling method was found to be 91.6%. The exposure of 13 gas station attendants was measured on 1 to 6 occasions each (n = 32). They were working in two busy gas stations located in Montreal and they were asked to wear a portable pump for 2 hr. The air was pumped through two tubes in series filled with the adsorbent Tenax TA™, with glass wool plugs at both ends. The tubes were wrapped in aluminum foil and samples were analyzed for MMT by gas chromatograph-atomic emission detector (GC-AED). Results vary between 0.3 and 11.4 ng m-3, with a mean of 3.9 ng m-3. The highest values obtained in the first study may be due to the analytical techniques used previously, where detection of different Mn compounds other than MMT was possible. Since GC-AED is specific to MMT in the samples, the MMT found in air raises doubt as to the time required for the photodegradation of MMT.

The central nervous system, and the basal ganglia in particular, is an important target in manganese neurotoxicity, a disorder producing neurological symptoms similar to that of Parkinson's disease. Increasing evidence suggests that astrocytes are a site of early dysfunction and damage; chronic exposure to manganese leads to selective dopaminergic dysfunction, neuronal loss, and gliosis in basal ganglia structures together with characteristic astrocytic changes known as Alzheimer type II astrocytosis. Astrocytes possess a high affinity, high capacity, specific transport system for manganese facilitating its uptake, and sequestration in mitochondria, leading to a disruption of oxidative phosphorylation. In addition, manganese causes a number of other functional changes in astrocytes including an impairment of glutamate transport, alterations of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, production of nitric oxide, and increased densities of binding sites for the "peripheral-type" benzodiazepine receptor (a class of receptor predominantly localized to mitochondria of astrocytes and involved in oxidative metabolism, mitochondrial proliferation, and neurosteroid synthesis). Such effects can lead to compromised energy metabolism, resulting in altered cellular morphology, production of reactive oxygen species, and increased extracellular glutamate concentration. These consequences may result in impaired astrocytic-neuronal interactions and play a major role in the pathophysiology of manganese neurotoxicity.

The use of the additive methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline has resulted in increased attention to the potential toxic effects of manganese (Mn). Hypothetically, people with chronic liver disease may be more sensitive to the adverse neurotoxic effects of Mn. In this work, bioaccumulation of Mn, as well as histopathology and neurobehavioral damage, in end-to-side portacaval anastomosis (PCA) rats exposed to Mn phosphate via inhalation was investigated. During the week before the PCA operation, 4 wk after the PCA operation, and at the end of exposure, the rats were subjected to a locomotor evaluation (day-night activities) using a computerized autotrack system. Then a group of 6 PCA rats (EXP) was exposed to 3050 microg m(-3) (Mn phosphate) for 8 h/day, 5 days/wk for 4 consecutive weeks and compared to a control group (CON), 7 PCA rats exposed to 0.03 microg m(-3). After exposure, the rats were euthanized and Mn content in tissues and organs was determined by neutron activation analysis. The manganese concentrations in blood (0.05 microg/g vs. 0.02 microg/g), lung (1.32 microg/g vs. 0.24 microg/g), cerebellum (0.85 microg/g vs. 0.64 microg/g), frontal cortex (0.87 microg/g vs. 0.61 microg/g), and globus pallidus (3.56 microg/g vs. 1.33 microg/g) were significantly higher in the exposed group compared to the control group (p.05). No difference was observed in liver, kidney, testes, and caudate putamen between the two groups. Neuronal cell loss was assessed by neuronal cell counts. The loss of cells in globus pallidus and caudate putamen as well as in frontal cortex was significantly higher (p.05) for the EXP group. Assessment of the locomotor activities did not reveal any significant difference. This study constitutes a first step toward our understanding of the potential adverse effects of Mn in sensitive populations.

The primary goal of this study is to determine the effects of Mn exposure via inhalation. The bioaccumulation of Mn in different organs and tissues, the alteration of biochemical parameters, and the locomotor activity were assessed. A group of 26 male Sprague-Dawley rats (E) were exposed to 3750 microg/m(3) of Mn dust for 6 h/day, 5 days/wk for 13 consecutive weeks and compared to a control group of 12 rats (C) exposed to 4 microg/m(3). After exposure, neurological evaluation was carried out for 36 h (a night-day-night cycle) using a computerized autotrack system. Rats were then sacrificed by exsanguination, and Mn content in organs and tissues was determined by neutron activation analysis. Mn concentrations in lung, putamen, and cerebellum were significantly higher in E than in C (0.30 vs. 0.17, 0.89 vs. 0.44, 0.63 vs. 0.48 ppm; p.01), as well as in the kidney, frontal cortex, and globus pallidus (1.15 vs. 0.96, 0.84 vs. 0.47, 1.28 vs. 0.55 ppm; p.05). Potassium concentration was significantly lower in E than in C (5.11 vs. 5.79 mmol/L; p.05), as was alkaline phosphatase (106.9 vs. 129.6 U/L; p.01). Locomotor activity indicated higher distance covered in the first 12-h period for E (45 383 vs. 36 098 cm; p.05) and lower resting time in the last 12-h period for E (36 326 vs. 37 393 s; p.05). This study is the first of several ongoing studies in our laboratory that address health concerns associated with inhalation exposure to different Mn species and to different levels of exposure.

Background & Aims: Manganese (Mn) deposition could be responsible for the T 1 -weighted magnetic resonance signal hyperintensities observed in cirrhotic patients. These experiments were designed to assess the regional specificity of the Mn increases as well as their relationship to portal-systemic shunting or hepatobiliary dysfunction. Methods: Mn concentrations were measured in (1) brain samples from basal ganglia structures (pallidum, putamen, caudate nucleus) and cerebral cortical structures (frontal, occipital cortex) obtained at autopsy from 12 cirrhotic patients who died in hepatic coma and from 12 matched controls; and from (2) brain samples (caudate/putamen, globus pallidus, frontal cortex) from groups (n = 8) of rats either with end-to-side portacaval anastomosis, with biliary cirrhosis, or with fulminant hepatic failure as well as from sham-operated and normal rats. Results: Mn content was significantly increased in frontal cortex (by 38%), occipital cortex (by 55%), pallidum (by 186%), putamen (by 66%), and caudate (by 54%) of cirrhotic patients compared with controls. Brain Mn content did not correlate with patient age, etiology of cirrhosis, or history of chronic hepatic encephalopathy. In cirrhotic and portacaval-shunted rats, Mn content was increased in pallidum (by 27% and 57%, respectively) and in caudate/putamen (by 57% and 67%, respectively) compared with control groups. Mn concentration in pallidum was significantly higher in portacaval-shunted rats than in cirrhotic rats. No significant changes in brain Mn concentrations were observed in rats with acute liver failure. Conclusions: These findings suggest that brain Mn deposition results both from portal-systemic shunting and from liver dysfunction. GASTROENTEROLOGY 1999;117:640-644

Amongst the potential neurotoxins implicated in the pathogenesis of hepatic encephalopathy, manganese emerges as a new candidate. In patients with chronic liver diseases, manganese accumulates in blood and brain leading to pallidal signal hyperintensity on T1-weighted Magnetic Resonance (MR) Imaging. Direct measurements in globus pallidus obtained at autopsy from cirrhotic patients who died in hepatic coma reveal 2 to 7-fold increases of manganese concentration. The intensity of pallidal MR images correlates with blood manganese and with the presence of extrapyramidal symptoms occurring in a majority of cirrhotic patients. Liver transplantation results in normalization of pallidal MR signals and disappearance of extrapyramidal symptoms whereas transjugular intrahepatic portosystemic shunting induces an increase in pallidal hyperintensity with a concomitant deterioration of neurological dysfunction. These findings suggest that the toxic effects of manganese contribute to extrapyramidal symptoms in patients with chronic liver disease. The mechanisms of manganese neurotoxicity are still speculative, but there is evidence to suggest that manganese deposition in the pallidum may lead to dopaminergic dysfunction. Future studies should be aimed at evaluating the effects of manganese chelation and/or of treatment of the dopaminergic deficit on neurological symptomatology in these patients.

The distribution of acrylamide in food items frequently consumed by Canadian adolescents was determined along with estimates of their contribution to the overall dietary intake of acrylamide. A total of 196 non-smoking adolescents (10-17 years old) were recruited in Montreal Island population, Canada. Participants were invited to fill out a 2-day food diary and a food frequency questionnaire over the last month. 146 samples of foods most frequently consumed by participants were analyzed for acrylamide contents. The highest acrylamide contents were measured in deep-fried french fries and potato chips (mean ± SD: 1053 ± 657 and 524 ± 276 ng/g respectively). On the basis of the 2-day food diary, median total daily intake of acrylamide was estimated at 0.29 μg/kg bw/d, as compared to 0.17 μg/kg bw/d on the basis of the food frequency questionnaire. These values are similar to those reported in comparable populations. Deep-fried french fries consumption contributed the most to daily acrylamide intake (50%) followed by potato chips (10%), oven-baked french fries (8%) and breakfast cereals (8%). Margins of exposure based on genotoxic benchmark dose limits were estimated to be low (≈

Exposure to manganese in an industrial or clinical setting can lead to manganism, a neurological disorder with similarities to Parkinson's disease. Although the pathogenetic basis of this disorder is unclear, studies indicate this metal is highly accumulated in astrocytes, suggesting an involvement of these glial cells. To investigate this issue, we have used a recently characterized, sub-acute model of manganese neurotoxicity. Treatment of rats with manganese (II) chloride (50 mg/kg body weight, i.p.) once daily for 1 or 4 days led to increases in manganese levels of up to 232, 523, and 427% in the cerebral cortex, globus pallidus, and cerebellum, respectively, by instrumental neutron activation analysis. These changes were accompanied by development of pathological changes in glial morphology identified as Alzheimer type II astrocytosis in both cortical and sub-cortical structures. Co-treatment with either the antioxidant N-acetylcysteine or the manganese chelator 1,2-cyclohexylenedinitrilotetraacetic acid completely blocked this pathology, indicating the cellular transformation may be mediated by oxidative stress associated with the presence of this metal. These findings represent, to our knowledge, the first report of early induction of this pathological hallmark of manganese neurotoxicity, an event previously considered a consequence of chronic exposure to manganese in primates and in human cases of manganism. Our results also indicate that use of this rodent model may provide a novel opportunity to examine the nature and role of the Alzheimer type II astrocyte in the pathophysiology of this disorder as well as in other disease processes in which cerebral accumulation of manganese occurs.

Methylcyclopentadienyl manganese tricarbonyl (MMT), is an additive in gasoline, and its combustion leads to the emission of Mn particles, which increase atmospheric metal concentrations. The objective of this study was to determine the level of outdoor and indoor respirable Mn (MnR) in Montreal, Canada, where MMT has been used since 1976. Ten women were involved in this study: five living in an urban area, near an expressway with high traffic density, and five residing in a rural area characterized by low traffic density. Outdoor and indoor air samples were collected each week (5 in total) during 3 consecutive days; blood samples were collected at the end of the air sampling period. The average concentration of outdoor MnR in the urban area was 0.025 microg/m3, which is significantly different from the average of 0.005 microg/m3 found in the rural area. The average indoor MnR concentration was also significantly different from teh average MnR indoor concentrations within both areas. The mean blood Mn concentrations were not significantly different between the urban area (0.017 microg/m3) and the rural area (0.007 microg/m3). The average outdoor MnR concentrations within both areas. The mean blood Mn concentrations were not significantly different between the two groups. Data suggest that a high outdoor atmospheric MnR leads to a high indoor MnR, but not to an increase in blood Mn levels.

Manganese neurotoxicity (MN) is a neurological disorder characterized by selective neuronal loss in the globus pallidus together with characteristic morphological changes known as Alzheimer type II astrocytosis. In order to understand the underlying mechanisms responsible for these processes, we studied early effects of this metal in a sub-acute rat model. Levels of manganese in the globus pallidus were increased by 81% after 1 day of treatment and elevated by 551% compared to controls after 4 days. In addition, manganese treatment led to a 60% increase in ptbr expression, and a 105% increase in levels of its product, the isoquinoline-carboxamide binding protein, a major constituent of the ‘peripheral-type’ benzodiazepine receptor (PTBR) that is localized to astrocytes, in this brain region after 4 days. These results indicate that PTBRs, and possibly neurosteroids, are an early response to manganese exposure and may play a major role in the pathophysiology of MN.

The central nervous system, and the basal ganglia in particular, is an important target in manganese neurotoxicity, a disorder producing neurological symptoms similar to that of Parkinson's disease. Increasing evidence suggests that astrocytes are a site of early dysfunction and damage; chronic exposure to manganese leads to selective dopaminergic dysfunction, neuronal loss, and gliosis in basal ganglia structures together with characteristic astrocytic changes known as Alzheimer type II astrocytosis. Astrocytes possess a high affinity, high capacity, specific transport system for manganese facilitating its uptake, and sequestration in mitochondria, leading to a disruption of oxidative phosphorylation. In addition, manganese causes a number of other functional changes in astrocytes including an impairment of glutamate transport, alterations of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, production of nitric oxide, and increased densities of binding sites for the "peripheral-type" benzodiazepine receptor (a class of receptor predominantly localized to mitochondria of astrocytes and involved in oxidative metabolism, mitochondrial proliferation, and neurosteroid synthesis). Such effects can lead to compromised energy metabolism, resulting in altered cellular morphology, production of reactive oxygen species, and increased extracellular glutamate concentration. These consequences may result in impaired astrocytic-neuronal interactions and play a major role in the pathophysiology of manganese neurotoxicity.

The human central nervous system is an important target for manganese intoxication, which causes neurological symptoms similar to those of Parkinson's disease. With the increasing use of methylcyclopentadienyl manganese tricarbonyl (MMT) as an octane-improving additive to unleaded gasoline, the prospect of worldwide manganese exposure is once again attracting attention as increases in environmental manganese concentrations have been recorded relative to traffic density. One crucial question is whether a small increase of manganese contamination resulting from the widespread use of MMT could have neurotoxic effects. In this review we concentrate on central nervous system abnormalities and neurobehavioral disturbances. Most experimental animal studies on manganese neurotoxicity have been conducted in nonhuman primates and rodents. Most studies performed in rodents used oral manganese administration and did not assess bioaccumulation or central nervous system changes. The major effect found was transient modification of spontaneous motor activity. Very few inhalation toxicological studies were carried out. As manganese intoxication in humans usually occurs via inhalation, more studies are required using the respiratory route of administration. Given the proven neurotoxic effects of manganese and the prospect of worldwide MMT usage, this metal should be considered a new environmental pollutant having potentially widespread public health consequences.

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound currently added to unleaded gasoline in Canada. It has been suggested that the combustion of MMT containing Mn could cause various deleterious health effects in animals and humans at very high concentrations. This study evaluates the potential of dandelions (Taraxacum officinale) as bioindicators of Mn environmental comtamination. Samples were picked at three different distances from a highway: a highly exposed site (E++), a lightly exposed site (E+) and a control site (E), located respectively at 10, 50 and 100 m. The total Mn, Mg, Ca, Al, Fe and Zn concentrations were measured in the soils and in the plants (flower, stem, leaves and root) by neutron activation analysis. Exchangeable Mn was measured in soils by atomic absorption spectrophotometry. Mn concentrations of the different parts of the plant and exchangeable Mn in soils were not correlated with distance from the roadway and, thus, do not seem to be a sensitive indicator of Mn contamination. Soil Mn concentrations were correlated with distance from the roadway. This suggests the hypothesis that the environmental fate of Mn from MMT sources could be associated with an increased total Mn in soil but does not lead to an increase in exchangeable Mn.