Chemotherapy for post-menopausal women with early breast cancer seems not to result in clinically significant changes in thyroid function.

OBJECTIVE: Adjuvant chemotherapy is often indicated in patients diagnosed with early breast cancer (EBC). Among others, weight gain is one of the observed side effects of both chemotherapy and other cancer treatments; however, the mechanism is not well-described. In this study, we aimed to assess thyroid function before and shortly after the course of chemotherapy for EBC. METHODS: This is a prospective cohort study of women diagnosed with EBC. The main outcome was the thyroid function and body weight before and after completing chemotherapy. Secondary outcomes were the presence of thyroid autoantibodies and treatment radiation dosage. We included 72 patients treated with adjuvant chemotherapy, whereas 59 patients also received supraclavicular locoregional radiotherapy. Triple-negative breast cancer (BC) patients receiving chemoimmunotherapy were excluded. RESULTS: After the chemotherapy, we observed an increase in thyroid-stimulating hormone (p = 0.03) and a decrease in free-thyroxine (p = 0.0006), with no significant weight change. The prevalence of autoimmune thyroiditis was low. On average 3 months post-chemo, we found no statistically significant difference in the thyroid function of women treated versus not treated with supraclavicular locoregional radiotherapy. CONCLUSIONS: Although statistically significant changes in thyroid hormones were observed, this study suggests no obvious clinically significant changes in thyroid function in women with early BC after the course of chemotherapy. The decrease in thyroid function was not related to autoimmunity, non-thyroidal illness, radiotherapy, or high-dose corticosteroids. Further studies with a longer follow-up of thyroid function after adjuvant chemotherapy and supraclavicular locoregional radiotherapy are needed.

Ambient polycyclic aromatic hydrocarbon exposure and breast cancer risk in a population-based Canadian case-control study.

PURPOSE: Polycyclic aromatic hydrocarbons (PAHs) represent a class of ubiquitous pollutants recognized as established human carcinogens and endocrine-disrupting chemicals. PAHs have seldom been modeled at the population-level in epidemiological studies. Fluoranthene is a prevalent PAH in urban settings and correlates with the occurrence of other PAHs. The purpose of this study was to evaluate associations between long-term residential exposure to ambient PAHs and breast cancer risk, both pre- and post-menopausal, in Canada. METHODS: Using the National Enhanced Cancer Surveillance System (NECSS), a national-scale Canadian population-based case-control study, annual fluoranthene exposures were estimated using the GEM-MACH-PAH chemical transport model on the basis of geocoded residential histories throughout a 20-year exposure window. Odds ratios (ORs) and 95% confidence intervals (CIs) controlling for potential confounders were estimated using logistic regression. Separate analyses were conducted for Ontario and national samples given a finer-resolution exposure surface and additional risk factor information available for Ontario. RESULTS: Positive associations were observed between fluoranthene exposure and premenopausal breast cancer, with inconsistent findings for postmenopausal breast cancer. For premenopausal breast cancer, adjusted ORs of 2.48 (95% CI: 1.29, 4.77) and 1.59 (95% CI: 1.11, 2.29) were observed when comparing the second highest category of exposure to the lowest, among the Ontario and national samples, respectively. For postmenopausal breast cancer, adjusted ORs were 1.10 (95% CI: 0.67, 1.80) and 1.33 (95% CI: 1.02, 1.73). Associations for the highest level of exposure, across both samples and menopausal strata, were non-significant. CONCLUSION: This study provides support for the hypothesis that ambient PAH exposures increase the risk of premenopausal breast cancer.

Postabsorptive and postprandial glucose and fat metabolism in postmenopausal women with breast cancer-Preliminary data after chemotherapy compared to healthy controls.

BACKGROUND: Breast cancer survivors are a growing population due to improved treatment. It is known that postmenopausal women treated for breast cancer may experience weight gain and increased insulin resistance, but detailed knowledge on how chemotherapy impact metabolic and endocrine mechanisms remain unknown. OBJECTIVES: We performed a thorough, preliminary study to elucidate the differing mechanisms of postprandial absorption and metabolism in postmenopausal early breast cancer (EBC) patients treated with adjuvant chemotherapy compared to healthy controls. We hypothesize that chemotherapy has a negative impact on metabolism in EBC patients. METHODS: We examined four postmenopausal women shortly after treatment with chemotherapy for EBC and four age-matched healthy women who served as controls using isotopic tracers during a mixed meal-test. Blood was sampled during the 240 min meal-test to examine postprandial absorption and endogenous synthesis of lipid and carbohydrate metabolites. RESULTS: We found that insulin concentrations were numerically higher before the meal-test in the EBC patients compared to controls (76.3 pmol/L vs 37.0 pmol/L; P = 0.06). Glucose kinetics was increased postprandial (most pronounced at 30 min, 9.46 mmol/L vs 7.33 mmol/L; P = 0.51), with no difference between the groups regarding liver glucose output. Fatty acid kinetics showed a numeric increase in oleic acid rate of appearance in BC patients, but only during the first hour after the mixed meal. There was no significant difference in VLDL-TAG synthesis between the two groups. CONCLUSIONS: This preliminary study is unique in using advanced tracer methods to investigate in vivo metabolism of EBC patients after chemotherapy although no statistical differences in glucose and fatty acid kinetics was seen compared to controls. However, during the first two postprandial hours, oral glucose and oleic acid appearance in the systematic circulation was elevated in the EBC patients. This could be due to changes in gastrointestinal uptake and further studies with altered set-up could provide valuable insights.

Peripheral blood mononuclear cells exhibit increased mitochondrial respiration after adjuvant chemo- and radiotherapy for early breast cancer.

BACKGROUND: Adjuvant chemo- and radiotherapy cause cellular damage to tumorous and healthy dividing cells. Chemotherapy has been shown to cause mitochondrial respiratory dysfunction in non-tumorous tissues, but the effects on human peripheral blood mononuclear cells (PBMCs) remain unknown. AIM: We aimed to investigate mitochondrial respiration of PBMCs before and after adjuvant chemo- and radiotherapy in postmenopausal patients with early breast cancer (EBC) and relate these to metabolic parameters of the patients. METHODS: Twenty-three postmenopausal women diagnosed with EBC were examined before and shortly after chemotherapy with (n = 18) or without (n = 5) radiotherapy. Respiration (O2 flux per million PBMCs) was assessed by high-resolution respirometry of intact and permeabilized PBMCs. Clinical metabolic characteristics and mitochondrial DNA (mtDNA) content of PBMCs (mtDN relative to nuclear DNA) were furthermore assessed. RESULTS: Respiration of intact and permeabilized PBMCs from EBC patients significantly increased with adjuvant chemo- and radiotherapy (p = 6 × 10-5 and p = 1 × 10-7 , respectively). The oxygen flux attributed to specific mitochondrial complexes and respiratory states increased by 17-43% compared to before therapy initiation. Similarly, PBMC mtDNA content increased by 40% (p = 0.002). Leukocytes (p = 0.0001), hemoglobin (p = 0.0003), and HDL cholesterol (p = 0.003) concentrations decreased whereas triglyceride (p = 0.01) and LDL (p = 0.02) concentrations increased after treatment suggesting a worsened metabolic state. None of the metabolic parameters or the mtDNA content of PBMCs correlated significantly with PBMC respiration. CONCLUSION: This study shows that mitochondrial respiration and mtDNA content in circulating PBMCs increase after adjuvant chemo- and radiotherapy in postmenopausal patients with EBC. Besides the increased mtDNA content, a shift in PBMC subpopulation proportions towards cells relying on oxidative phosphorylation, who may be less sensitive to chemotherapy, might influence the increased mitochondrial respiration observed iafter chemotherapy.

Inequalities in Environmental Cancer Risk and Carcinogen Exposures: A Scoping Review.

Background: Cancer is the leading cause of death in Canada and a major cause of death worldwide. Environmental exposure to carcinogens and environments that may relate to health behaviors are important to examine as they can be modified to lower cancer risks. Built environments include aspects such as transit infrastructure, greenspace, food and tobacco environments, or land use, which may impact how people move, exercise, eat, and live. While environments may play a role in overall cancer risk, exposure to carcinogens or healthier environments is not equitably spread across space. Exposures to carcinogens commonly concentrate among socially and/or economically disadvantaged populations. While many studies have examined inequalities in exposure or cancer risk, this has commonly been for one exposure. Methods: This scoping review collected and synthesized research that examines inequities in carcinogenic environments and exposures. Results: This scoping review found that neighborhoods with higher proportions of low-income residents, racialized people, or same-sex couples had higher exposures to carcinogens and environments that may influence cancer risk. There are currently four main themes in research studying inequitable exposures: air pollution and hazardous substances, tobacco access, food access, and other aspects of the built environment, with most research still focusing on air pollution. Conclusions: More work is needed to understand how exposures to these four areas intersect with other factors to reduce inequities in exposures to support longer-term goals toward cancer prevention.

Influence of the anti-oestrogens tamoxifen and letrozole on thyroid function in women with early and advanced breast cancer: A systematic review.

INTRODUCTION: Breast cancer (BC) is a common type of cancer in women. Advances in therapy options have resulted in higher overall survival rates but side effects of cancer treatment are increasingly in the spotlight. The beneficial effects of anti-oestrogen therapy with tamoxifen and letrozole in the prevention of BC recurrence are well documented. While the most common side-effects of this therapy are well-defined, less is known about its effects on thyroid function. In women treated for early BC, an average of 1-5 kg weight gain has been observed after treatment with chemotherapy/anti-oestrogens. We aim to evaluate the current knowledge on the side effects of tamoxifen and letrozole treatments on thyroid function, followed by its potential influence on the observed weight gain. METHODS: We searched PubMed and found 16 publications on thyroid function and tamoxifen treatment in pre- and post-menopausal women with early- and advanced BC, whereas five publications on letrozole treatment in post-menopausal women with advanced BC. RESULTS: According to the current literature, there is an overall tendency towards a mild and transient thyroid dysfunction, that is, subclinical hypothyroidism in tamoxifen-treated patients. Only one publication reported further significant changes in thyroid hormones beyond one year of tamoxifen treatment. No significant changes in thyroid function have been observed among letrozole-treated patients. CONCLUSION: Tamoxifen-treated patients can develop mild and transient thyroid dysfunction within the first 12 months, yet further significant changes in thyroid function beyond one year of tamoxifen treatment have been reported in a single study. There is no evidence of thyroid dysfunction in letrozole-treated patients. Current literature does not focus on subclinical hypothyroidism as a possible cause of weight gain in patients with BC. Subgrouping of BC patients and studies with a longer observation of thyroid hormones and weight changes during and after anti-oestrogen treatment are needed to further elucidate how anti-oestrogens affect thyroid function.

Potential Access to Emergency General Surgical Care in Ontario.

Limited access to timely emergency general surgery (EGS) care is a probable driver of increased mortality and morbidity. Our objective was to estimate the portion of the Ontario population with potential access to 24/7 EGS care. Geographic information system-based network-analysis was used to model 15-, 30-, 45-, 60-, and 90-min land transport catchment areas for hospitals providing EGS care, 24/7 emergency department (ED) access, and/or 24/7 operating room (OR) access. The capabilities of hospitals to provide each service were derived from a prior survey. Population counts were based on 2016 census blocks, and the 2019 road network for Ontario was used to determine speed limits and driving restrictions. Ninety-six percent of the Ontario population (n = 12,933,892) lived within 30-min's driving time to a hospital that provides any EGS care. The availability of 24/7 EDs was somewhat more limited, with 95% (n = 12,821,747) having potential access at 30-min. Potential access to all factors, including 24/7 ORs, was only possible for 93% (n = 12,471,908) of people at 30-min. Populations with potential access were tightly clustered around metropolitan centers. Supplementation of 24/7 OR capabilities, particularly in centers with existing 24/7 ED infrastructure, is most likely to improve access without the need for new hospitals.

Screening-level assessment of cancer risk associated with ambient air exposure in Aamjiwnaang First Nation.

The manuscript reports findings from a screening-level assessment of cancer risk from outdoor air in Aamjiwnaang First Nation. Ambient air pollution can contribute to cardiovascular/respiratory diseases, and certain types of cancer. Certain communities may be at higher risk to the negative health impacts due to their geographical proximity to pollution sources. Outdoor air concentrations were mapped and the Lifetime Excess Cancer Risks (LECR) associated with long-term exposure to known carcinogens were estimated. LECR results for both benzene and 1,3-butadiene were above one per million. The LECR for benzene was 6.4 per million when the Health Canada slope factor was applied and 12.0 when using the US EPA. For 1,3-butadiene the LECR estimate was 8.8 per million. This work provides a better understanding of environmental exposures and potential associated cancer risks for residents in the Aamjiwnaang community and highlights the need for further air monitoring and a more detailed risk assessment.

Weight Change in Post-Menopausal Women with Breast Cancer during Chemotherapy-Perspectives on Nutrition, Activity and Bone Metabolism: An Interim Analysis of a 5-Year Prospective Cohort.

Women with breast cancer are a growing population due to improved screening and treatment. It has been described that chemotherapy can negatively affect patients' metabolism. The aim of this study is to assess weight gain during chemotherapy treatment in an interim analysis on an ongoing prospective cohort of women with early breast cancer. To help untangle the many possible reasons for weight change, we examine blood tests, Patient-Reported Outcomes (PROs), and bone mineral density (BMD). We find that the 38 women that have measurements taken after chemotherapy have an average weight gain of 1.2 kg although not significant. Together with this, there is a significant drop in HDL cholesterol, an increase in triglycerides, and a non-significant tendency towards decreased insulin sensitivity. PROs show that although the women experience more pain and fatigue, they have higher activity levels. BMD is at an expected level according to age. All in all, we see an increased focus on physical activity and nutrition, leading to less severe metabolic changes as previously reported. However, even though more measures are taken, we still see an overall negative metabolic impact with unknown long-term implications.

Are Perceptions of Health Dependant on Social Class? Studying Soft Power and Symbolic Violence in a Health Promotion Program among Young Men at Vocational Schools.

Health behaviour among young people has a social gradient, and tends to be skewed in terms of gender as well. Young men in vocational educational settings are an example where the inequality in health is apparent. Addressing this problem requires an understanding of health behaviour and its determinants in the target group in order to be able to develop interventions that can address the problem. The aim of the paper is to investigate to what extent a multicomponent intervention based on the Whole School Approach, targeting the risk behaviours, smoking, eating and physical activity that have an impact on health behaviour among male students in a disadvantaged educational setting. The paper uses self-reported longitudinal data on risk behaviours from the "Gearing up the Body" 1-year intervention program that was implemented among students at a Danish vocational school. For the analysis, we created a score model to categorise students and behaviour. Analyses suggest that interventions had only a modest impact and what evidence there is shows that the interventions reduced the health behaviour scores by 0.03 points. More specifically, we find that symbolic violence reduces the health behaviour score of the healthy types by 0.20 points, whereas soft power increases the health behaviour of the unhealthy type by 0.05 points. An explanation for the disappointing results of the "Gearing up the Body" program is tension between different understanding of what is "right" and "wrong" health behaviour. We find that the ideas of soft power and symbolic violence can contribute to a better understanding of why health and health behaviour is understood differently among vocational students. Thus, the finding demonstrates that one needs to apply a participatory approach rather than a normative approach addressing the health behaviour of disadvantaged individuals.

Denosumab vs. zoledronic acid treatment in post-menopausal breast cancer: a 2-year prospective observational study.

Adjuvant treatment for post-menopausal women with early breast cancer (BC) includes aromatase inhibitors (AI), known to decrease bone mineral density (BMD). In this study, we investigate whether denosumab is a valid second option for patients unable to receive standard adjuvant i.v. zoledronic acid (ZA). In total, 212 patients have been evaluated after they did not receive ZA. Of those 194 were included. After evaluation by an endocrinologist, all patients were offered ZA as their first choice and 15% accepted (N = 29). The remaining 85% were offered denosumab (N = 165). All patients were followed prospectively with blood tests up to 24 months. DXA scans were performed at baseline and 24 months. No difference was observed between the two treatment groups at baseline, with regard to anthropometry and standard biochemistry. Markers of bone turnover (p-PINP, p-CTX, p-bone-specific alkaline phosphatase and p-osteocalcin) all showed significant suppression compared to baseline and remained suppressed throughout the 2 years. BMD showed small and significant increases at the spine (0.024 g/cm2) and total hip (0.019 g/cm2) in the denosumab group but no change at the femoral neck(-0.011g/cm2). In the ZA group, we observed no significant change at the spine (0.015 g/cm2) and total hip (-0.001g/cm2) and a small significant decrease at the femoral neck (-0.037 g/cm2). However, when we compared BMD change between the treatment groups, we found no significant difference.Conclusions: Our data indicate that for BC patients in AI treatment who refused or were not able to receive ZA treatment, denosumab might be recommended as a second choice. Regarding markers of bone turnover and BMD denosumab is equal to ZA.Summary: Women with early breast cancer receiving anti-estrogen treatment are at risk of developing osteoporosis.We followed 194 women receiving zoledronic acid (ZA) or denosumab for up to 2 years.We find that with regard to bone protection, denosumab is a viable alternative to ZA and might be recommended as a second choice.

Vibration Perception Threshold and Heart Rate Variability as methods to assess chemotherapy-induced neuropathy in women with breast cancer - a pilot study.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a recognized adverse effect of standard (neo)adjuvant chemotherapy in breast cancer (BC) treatment. However, there is no consensus on a validated method for assessing CIPN. Heart rate variability (HRV) and vibration perception threshold (VPT) could be used as objective measures to describe CIPN. The aim of this pilot study was to investigate whether subjectively reported CIPN was associated with altered HRV and VPT in BC patients. METHODS: We performed a cross-sectional pilot study evaluating 30 BCE patients previously treated with chemotherapy, 26 BCE patients who did not receive chemotherapy, and 22 controls without breast cancer. Self-reported CIPN was registered for the BC patients. All participants were subjected to multi-frequency vibration analyses to determine VPT along with short ECG measurements to determine HRV measures. RESULTS: Self-reported CIPN was registered in 14 (46.6%) BC patients treated with chemotherapy. The VPT at 64 Hz (P = 0.022) and mean HR (P = 0.022) were significantly higher and the HRV measures SDNN (P = 0.023), RMSSD (P = 0.007), LF (P = 0.050) and HF (P = 0.045) were significantly lower in BC patients reporting CIPN compared to controls when adjusted for age. VPT at 64 Hz and 125 Hz were significantly higher in BC patients not reporting CIPN compared to controls when adjusted for age. CONCLUSION: We found elevated VPT and mean HR along with decreased HRV parameters in 14 BCE patients reporting CIPN. These findings support the need for further investigation into whether HRV and vibration analysis could contribute to an objective assessment of CIPN.

Intensive Lifestyle Intervention Increases Plasma Midregional Proatrial Natriuretic Peptide Concentrations in Overweight Children.

Background Overweight adults have low circulating concentrations of ANP (atrial natriuretic peptide) and proANP fragments. We tested the hypothesis that an intensive lifestyle intervention with an intended weight loss would increase plasma concentrations of a proANP fragment in overweight children. Methods and Results We measured MR-proANP (midregional proANP) concentrations in plasma from overweight children who participated in the OOIS (Odense Overweight Intervention Study). OOIS randomized 115 overweight children (11-13 years, 55% girls) to an intensive day-camp intervention arm with increased physical activity and healthy diet or to a less intensive standard intervention arm for 6 weeks. We used linear mixed-effects modeling for repeated measures to estimate the difference in the mean change with 95% CIs in fasting plasma MR-proANP concentrations between the 2 arms, and we used partial least squares regression analysis to identify candidate mediators. Differences in weight, fitness, and metabolic factors were also analyzed. At baseline, fasting plasma MR-proANP concentrations were (median [interquartile range]) 35.0 pmol/L (26.8-42.0) in the day-camp intervention arm and 37.2 pmol/L (31.7-44.7) in standard intervention arm participants, respectively. After 6 weeks intervention, children in the day-camp intervention arm had increased their MR-proANP (5.4 pmol/L [0.8-10.0], P=0.022) and their fitness (2.33 mL O2/min per kg [0.52-4.14], P=0.012) and they had deceased their body mass index (-2.12 kg/m2 [-2.59 to -1.65], P<0.001) as compared with children in standard intervention arm. In the partial least squares analysis, decreases in fasting insulin and in estimated insulin resistance were associated with the observed increase in MR-proANP concentrations. Conclusions An intensive lifestyle intervention increases plasma MR-proANP among overweight children. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01574352.

Exercise-A Panacea of Metabolic Dysregulation in Cancer: Physiological and Molecular Insights.

Metabolic dysfunction is a comorbidity of many types of cancers. Disruption of glucose metabolism is of concern, as it is associated with higher cancer recurrence rates and reduced survival. Current evidence suggests many health benefits from exercise during and after cancer treatment, yet only a limited number of studies have addressed the effect of exercise on cancer-associated disruption of metabolism. In this review, we draw on studies in cells, rodents, and humans to describe the metabolic dysfunctions observed in cancer and the tissues involved. We discuss how the known effects of acute exercise and exercise training observed in healthy subjects could have a positive outcome on mechanisms in people with cancer, namely: insulin resistance, hyperlipidemia, mitochondrial dysfunction, inflammation, and cachexia. Finally, we compile the current limited knowledge of how exercise corrects metabolic control in cancer and identify unanswered questions for future research.

Heart rate variability and vibration perception threshold to assess chemotherapy-induced neuropathy in women with breast cancer - a systematic review.

BACKGROUND: It is well known that breast cancer (BC) patients often suffer from chemotherapy-induced peripheral neuropathy (CIPN). However, it is not always recognized that they have higher risk of falling, dizziness and other signs of dysfunctional autonomous nervous system. We performed a systematic review of the literature on vibration perception threshold (VPT) and heart rate variability (HRV) as methods to objectively assess (CIPN) in BC-patients. Could VPT and HRV describe coexisting sensory and autonomic nerve damage? MATERIALS AND METHODS: PubMed was searched in September 2019. The included studies had to address HRV and/or VPT in BC-patients who received chemotherapy. RESULTS: Seven studies assessed VPT and six studies assessed HRV in BC-patients. Studies showed lowered perception of vibrations after chemotherapy reflected in higher VPT and no changes in HRV after taxane-based chemotherapy. No studies evaluated VPT and HRV at the same time. CONCLUSION: The results were limited by short follow-up, small sample sizes, and different chemotherapy regimens which makes generalizability problematic. A standard assessment method of CIPN is still missing and further research is needed to evaluate if VPT and HRV could contribute to an objective assessment of CIPN. With higher survival rates for BC-patients autonomous and sensory nerve damage will be an increasing task. However, our literature review showed that no one have focused on the combination of autonomous and sensory affection measured by the simple methods VPT and HRV. Therefore, we encourage the development of international guidelines for the objective measure of nerve damage in BC-patients.

Estimating Exposure to Three Commonly Used, Potentially Carcinogenic Pesticides (Chlorolathonil, 2,4-D, and Glyphosate) Among Agricultural Workers in Canada.

OBJECTIVES: Certain pesticides have been associated with adverse health outcomes including cancer and reproductive harms. However, little is known about the prevalence of occupational pesticide exposure among agricultural workers in Canada. The purpose of this study was to estimate the prevalence and likelihood of occupational exposure to pesticides in Canada's agricultural industry, using three commonly used, potentially carcinogenic pesticides [chlorothalonil, 2,4-dichlorophenoxyacetic acid (2,4-D), and glyphosate] as an example. METHODS: Estimates were calculated using the Canadian Census of Population and the Census of Agriculture. The number of workers and the proportion of farms applying 'herbicides' or 'fungicides' by farm type was estimated using survey data from the Census of Agriculture. These values were multiplied to yield the potential number of workers at risk of exposure. Likelihood of exposure (i.e. exposed, probably exposed, and possibly exposed) was then qualitatively assigned using information on crop type, primary expected tasks, crop production practices, and residue transfer data. Additional agricultural workers who are at risk of exposure but not captured by the Census of Agriculture were identified using the 2016 Census of Population. RESULTS: An estimated range of 37 700-55 800 workers (11-13% of agricultural workers) were exposed to glyphosate in Canada while 30 800-43 600 workers (9-11%) and 9000-14 100 (2.9-3.2%) were exposed to 2,4-D and chlorothalonil, respectively. Approximately 70-75% of workers at risk of exposure were considered probably or possibly exposed to any of the pesticides. Glyphosate exposure was most common among workers in oilseed (29% of oilseed farm workers exposed) and dry pea/bean farms (28%), along with those providing support activities for farms (31%). 2,4-D exposure was most common in corn (28%), other grain (28%), and soybean farms (27%), while chlorothalonil exposure was more likely among greenhouse, nursery, and floriculture workers (42%), workers on farms (28%, for occupations not captured by the Census of Agriculture, specifically), and those providing support activities for farms (20%). Regional variations broadly reflected differences in farm types by province. CONCLUSIONS: This study estimated the prevalence of occupational exposure to three pesticides in Canada. Seasonal and temporary agricultural workers, which were captured by the Census of Agriculture, contributed to many additionally exposed workers. A large percent of the workers who were considered at risk of exposure were considered probably or possibly exposed, indicating a need for enhanced data collection and availability on pesticide use data in Canada. The study's methods can be applied to estimate workers' exposures to other pesticides within the agricultural industry.

Using geographic information systems to estimate potential pesticide exposure at the population level in Canada.

Residents in close proximity to agricultural land are at risk of higher pesticide exposures. The purpose of this study was to generate national population-level exposure estimates for Canada for three commonly applied pesticides that are suspected carcinogens (2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate and chlorothalonil). Using geographic information systems, pesticide exposure was estimated for every - census subdivision (CSD) in Canada (n = 5054) by combining raster-based surfaces for the distribution of crops with average crop-specific pesticide application rates data. Analyses examined all identified crops in combination with different pesticide application rates to obtain a cumulative potential total exposure. Specifically, the number of acres of particular crops were calculated for each CSD and then multiplied by the average pesticide application rates data, summed across crops, and combined with population data by CSD to provide a potential pesticide exposure estimate for each CSD. Results demonstrate that the population exposure varies greatly depending on agricultural production by CSD region. For example, in Ontario, the 2,4-D application rate was an average of 361 kg/km2, while in Saskatchewan, which primarily grows field/cereal crops, 2,4-D application rates were much higher (3810 kg/km2). The highest potential exposures to all three pesticides were in the prairie provinces (Alberta, Saskatchewan, Manitoba) along with Prince Edward Island, Southern Quebec and British Columbia. This work can be used in conjunction with other exposure assessment approaches to better understand overall pesticide exposure among Canada's general population.

Demographic, medical, social-cognitive, and environmental correlates of meeting independent and combined physical activity guidelines in kidney cancer survivors.

PURPOSE: Guidelines for cancer survivors recommend both aerobic physical activity (PA) and strength training (ST). Few kidney cancer survivors (KCS) are meeting single-activity or combined guidelines; therefore, examining factors influencing PA participation is warranted. The purpose of this study is to examine demographic, medical, social-cognitive, and environmental correlates of meeting independent (i.e., aerobic-only, strength training (ST)-only) and combined guidelines (i.e., aerobic and ST) in KCS. METHODS: KCS (N = 651) completed self-reported measures of PA and demographic, medical, social-cognitive, and perceived environmental factors. Built environment was assessed using the geographic information systems (GIS). Multinomial logistic regressions were conducted to determine the correlates of meeting the combined versus independent guidelines. RESULTS: Compared with meeting neither guideline, meeting aerobic-only guidelines was associated with higher intentions (p < .01) and planning (p < .01); meeting ST-only guidelines was associated with higher intentions (p = .02) and planning (p < .01), lower perceived behavioral control (PBC) (p = .03), healthy weight (p = .01), and older age (p < .01); and meeting the combined guidelines were associated with higher intentions (p < .01), planning (p = .02), higher instrumental attitudes (p < .01), higher education (p = .04), better health (p < .01), and localized cancer (p = .05). Additionally, compared with neither guideline, meeting aerobic-only (p < .01) and combined (p < .01) guidelines was significantly associated with access to workout attire. Compared with neither guideline, meeting aerobic-only guidelines was associated with proximity to retail (p = .02). CONCLUSION: PA participation correlates may vary based on the modality of interest. Interventions may differ depending on the modality promoted and whether KCS are already meeting single-modality guidelines.

Reaction kinetic studies for comparison of mutagenic potency between butadiene monoxide and glycidamide.

DNA adducts can be formed from covalent binding of electrophilic reactive compounds to the nucleophilic N- and O-atoms of the biomolecule. The O-sites on DNA, with nucleophilic strength (n) of ca. 2, is recognized as a critical site for mutagenicity. Characterization of the reactivity of electrophilic compounds at the O-sites can be used to predict their mutagenic potency in relative terms. In the present study, reaction kinetic experiments were performed for butadiene monoxide (BM) in accordance with the Swain-Scott relation using model nucleophiles representing N- and O-sites on DNA, and earlier for glycidamide (GA) using a similar approach. The epoxide from the kinetic experiments was trapped by cob(I)alamin, resulting in formation of an alkylcobalamin which was analyzed by liquid chromatography tandem mass spectrometry. The Swain-Scott relationship was used to determine selectivity constant (s) of BM and GA as 0.86 and 1.0, respectively. The rate constant for the reaction at n of 2 was extrapolated to 0.023 and 0.038 M-1 h-1 for BM and GA, respectively, implying a higher mutagenic potency per dose unit of GA compared to BM. The reaction kinetic parameters associated with mutagenic potency were also estimated by a density functional theory approach, which were in accordance to the experimental determined values. These types of reaction kinetic measures could be useful in development of a chemical reactivity based prediction tool that could aid in reduction of animal experiments in cancer risk assessment procedures for relative mutagenicity.