<p dir="ltr">High exposure to manganese (Mn) through the inhalation of welding fumes has been shown to have a toxic effect to the human brain, leading to parkinsonian-like symptoms such as changes in mood, cognition, and motor function. Oxidative stress and GABAergic dysfunction, two proposed mechanisms implicated in Mn neurotoxicity, can be measured by edited MR spectroscopy (MRS). Previous animal studies have found depleted levels of glutathione, the brain’s antioxidant, and GABA in response to exposure to Mn. Past welder studies have shown altered GABA levels in highly exposed welders. However, GSH has not yet been measured in welders. Recent advances in edited MRS allow for the simultaneous measurement of GABA and GSH, however, one sequence does not ‘fit all’. Thus, there is a need to ensure accurate and reproducible measurements of these metabolites in the study of neurological disorders, such as Mn neurotoxicity.</p><p dir="ltr">The overall goal of this dissertation is to establish a reproducible edited MRS protocol and ensure accurate measurement of metabolites in the context of Mn neurotoxicity. This work has been accomplished in three steps. First, we developed an optimized and reproducible HERMES sequence that allows for the consistently reliable measurement of GABA and GSH at 3T. Second, we investigated whether toenail concentrations of manganese (Mn) and iron (Fe) serve as biomarkers for levels of GABA, GSH, and Glx in the brains of welders exposed to these metals. This aim explores the potential for toenails to be used as a risk assessment tool by evaluating correlations between toenail metal levels and brain metals and metabolites. Lastly, we examined whether excessive accumulation of metals in the brain has an impact on the relaxation times of metabolites. Due to its paramagnetic properties, brain accumulation of two major components of welding fumes, Mn and iron (Fe), may be measured noninvasively through increased magnetic resonance imaging (MRI) relaxation rates, R1 and R2*, respectively. This aim delves into the potential effects of metal exposure on the physical properties of brain metabolites, which could shed light on the accuracy of quantification.</p><p dir="ltr">Overall, the dissertation is a successful step towards establishing reproducible edited MRS acquisitions, and the accurate quantification in the application of Mn neurotoxicity. This work focused on developing methodologies and assessing physical properties for accurate GABA and GSH measurements and investigating risk-assessment methods for metal-induced neurotoxicity.</p>

Aim. To assess associations between occupational air pollution and respiratory health, especially in miners. Background. Indications of associations between occupational exposure or social economic status and respiratory health have been found in several population-based studies. However, there have been few longitudinal studies of the putative correlations, the effects of environmental and genetic factors have seldom been simultaneously studied, and studies of miners have generated conflicting results. Material and methods. Population-based Obstructive Lung Disease in Northern Sweden (OLIN) cohorts surveyed in 1986, 1992 and 1996, and two industry-based materials, were used in cross-sectional and longitudinal studies. Inflammatory markers were compared in sputa from miners after a vacation of at least four weeks, after repeated occupational exposures for at least three months, and controls. The mortality from silicosis was studied in 7729 miners with at least 1 year of exposure. Multivariate analyses were used to adjust for confounders. Results. Up to about 30-40% (etiologic fraction) of incident symptoms in persons both with and without a family history of asthma (FHA) could be explained by exposure to occupational air pollution. Low socio-economic status (SES) was associated with impaired respiratory health. Population attributable risks for most examined disorders were about 10%. Current and ex-miners had increased prevalence of recurrent wheeze, longstanding cough, physician-diagnosed chronic bronchitis, and a trend for increased sputum production. For physician-diagnosed chronic bronchitis a multiplicative interaction was found between exposure and smoking habits. Ex-miners that had been exposed for on average 13 years and whose exposure had ceased 16 years before the study had an increased prevalence of physician-diagnosed chronic bronchitis and chronic productive cough and a trend to increased use of asthma medicines. Miners exposed underground for 18 years, on average, to diesel exhaust (with 0.28 mg/m3 nitrogen dioxide and 27 μg/m3 elemental carbon on average, EC) and particles (3.2 mg/m3 inhalable dust on average) had signs of higher inflammatory activity in their airways, i.e. significantly higher frequencies of macrophages, neutrophils, and total cells compared with referents. The activity in miners was similar after a vacation of at least four weeks and after repeated exposures for three months. There were 58 deaths from silicosis (underlying and contributing cause of death) and a clear dose-response relationship. The data indicated an increased risk of severe silicosis after long-term exposure to 0.1 mg/m3 respirable quartz, the current maximum allowable concentration (MAC) in Sweden and many other countries. Conclusion. Occupational exposure to dust, gases, and fumes impaired respiratory health, accounting for up to 30-40% of some respiratory symptoms in the general population. Low socio-economic status was associated with impaired respiratory health. The complex profiles of dust and diesel exhaust substances found in mines may cause inflammatory reactions in their lungs and persistent respiratory symptoms in occupationally exposed miners. Long-term exposure to quartz at the present MAC level may cause severe silicosis.

Introdução Os motoristas de ônibus urbano são submetidos às normas das empresas de forma peculiar, permanecendo a maior parte do tempo fora dos limites da contratante, submetidos a situações de trabalho com alto potencial estressante. Os distúrbios psíquicos são frequentes nesta população, gerando absenteísmo e impacto financeiro para profissionais, empresas e população usuária dos serviços. Objetivos Verificar o nível de sintomas ansiosos e depressivos referidos e traçar o perfil de uso de álcool nos motoristas de ônibus urbano da região metropolitana de São Paulo, que buscavam atendimento médico; Identificar fatores de risco psicossocial do trabalho associados a este perfil. Métodos Avaliada amostra de conveniência de 174 motoristas de ônibus urbano encaminhados ao Serviço de Saúde Ocupacional do ICHC-FMUSP. Realizadas entrevistas, preenchimento de prontuário médico ocupacional e aplicados questionários de avaliação da percepção de fatores psicossociais do trabalho, como variáveis independentes, e avaliação de condição de saúde quanto ao indicativo de transtornos depressivos, ansiosos e do padrão de consumo de álcool, como variáveis dependentes, sendo realizada análise estatística dos dados. Selecionados casos que ilustram as situações de trabalho a que estes profissionais estão expostos. Resultados 93,1 por cento consideram seu trabalho como de alta demanda psicológica e 87,4 por cento consideram ter baixo grau de controle sobre as atividades. 81,6 por cento posicionam-se na categoria de trabalho de alta exigência do Modelo Demanda-Controle e 57,5 por cento referem ter baixo suporte social. 61,5 por cento avaliam que há desequilíbrio na relação esforço-recompensa e 77,6 por cento consideram alto seu comprometimento pessoal com o trabalho. Pelo Modelo Desequilíbrio Esforço-Recompensa, 55,2 por cento dos casos estão expostos à situação considerada como de risco mais intenso de adoecimento. 60,9 por cento e 70,3 por cento dos casos apresentam sintomas sugestivos de diagnóstico de depressão e ansiedade, respectivamente. 13,8 por cento da amostra referem uso de álcool compatível com abuso/dependência. Ser mulher, ter menor idade, apresentar desequilíbrio esforço-recompensa e ter alto grau de comprometimento com o trabalho foram associados a sintomas indicativos de quadro depressivo. Apresentar desequilíbrio esforço-recompensa e ter alto comprometimento com o trabalho foram associados a sintomas indicativos de quadro de ansiedade. Ter baixo nível de apoio social foi associado a indicativo de abuso/dependência de álcool. Pela análise por regressão logística múltipla, desequilíbrio esforço-recompensa e comprometimento estão associados à depressão; controle e comprometimento à ansiedade e apoio social ao uso de álcool. Conclusão A população estudada mostrou-se exposta à situação de risco intenso de adoecimento psíquico relacionado ao trabalho. / Introduction Urban bus drivers are subjected to the companies regulations in a particular way as they work most of the time out of the physical limits of the companies, where they are subjected to working conditions that might lead to serious stress issues. Psychiatric disorders are typical in this community, causing absenteeism and financial impact for workers, companies and the population. Objectives To verify anxiety levels and depression symptoms and evaluate the pattern of alcohol usage on urban bus drivers from the metropolitan area of São Paulo (BR), who searched for medical aid; To identify psychosocial factors at work associated with this profile. Methodology The occupational and medical evaluation of the 174 urban bus drivers sample at Serviço de Saúde Ocupacional - ICHC-FMUSP consisted of interviews, use of medical protocols and questionnaires to evaluate how workers perceive psychosocial factors at work, as independent variables, and evaluate the health condition regarding depressive disorders, anxiety disorders and alcohol abuse/addiction, as dependent variables. Statistical methods were used to analyze the data. Cases were reported to illustrate their working conditions. Results 93.1 per cent consider their work as psychologically demanding and 87.4 per cent think they have a low degree of control over their activities. 81.6 per cent classify themselves at the category of high strain job of the Job Strain Model and 57.5 per cent consider themselves to have low social support. 61.5 per cent reckon there is an effort-reward imbalance and 77.6 per cent consider themselves to be highly commited to their Jobs. According to the Effort Reward Imbalance Model, 55.2 per cent of the cases are exposed to the situation of higher risk of developing disease. 60.9 per cent of the cases present symptons related to depression, 70.3 per cent present symptoms related to anxiety and 13,8 per cent refer symptoms that indicate alcohol abuse/addiction. Being a woman, younger, having an effort-reward imballance and a high degree of commitment with the job were associated with depression symptoms. Having an effort-reward imballance and a high degree of commitment with the job were associated with anxiety symptoms. Having a low social support was associated with the risk of presenting alcohol abuse/addiction. The variables effort-reward imballance and a high degree of commitment, for depression, control and high degree of commitment, and social support, for alcohol, are associated when the logistic regression analysis is used. Conclusion The group studied is exposed to a high risk of developing work related mental diseases.

Introdução - As ausências ao trabalho por doença são usadas como indicador da saúde dos trabalhadores e consideradas um significante problema de Saúde Pública. Diversos fatores são descritos como associados ao absenteísmo-doença, independentemente do agravo. A Previdência Social do Brasil regulamenta a concessão de benefício para trabalhadores que comprovarem incapacidade para o trabalho acima de quinze dias por adoecimento. Em 2010, transtornos mentais e comportamentais foram a terceira principal causa de concessão de auxílio-doença por incapacidade laborativa. Objetivo - Avaliar os fatores associados às longas ausências ao trabalho por transtornos mentais e comportamentais. Materiais e Método - Estudo de caso-controle composto por 385 participantes. Os casos foram requerentes de benefício previdenciário por transtorno mental incapacitante na cidade de São Paulo, Brasil. Foram realizadas entrevistas para preenchimento de questionários sociodemográfico e de hábitos/estilo de vida, ocupacional inclusive percepção de fatores psicossociais no trabalho, avaliação de condição de saúde e dados do laudo médico-pericial da Previdência Social. Foi realizada regressão logística múltipla hierarquizada para a avaliação da associação das variáveis independentes ao desfecho. Resultados - Os fatores associados foram: sexo feminino, alta escolaridade, cor da pele autorreferida como branca, alto grau de consumo de fumo e de ingesta de álcool, vínculo com empresa estatal, exposição à violência no trabalho, baixo apoio social, elevado comprometimento com o trabalho, atendimento médico por mais de dois diagnósticos no último ano. Na modelagem com interação entre as dimensões dos modelos de estresse ocupacional, a exposição à alta exigência com baixo apoio social, o desequilíbrio esforço-recompensa com elevado comprometimento e a interação entre essas quatro dimensões estão associadas ao desfecho de forma significativa. Considerações Finais - Aspectos sociodemográficos, hábitos e estilo de vida, característica e condição de trabalho, além do status de saúde, estão associados ao longo afastamento do trabalho por transtorno mental e comportamental. A exposição ocupacional a fatores desfavoráveis de natureza psicossocial é importante contribuidora no desfecho. Vê-se a necessidade de atenção para tais situações no intuito de ampliar as perspectivas de antecipação ao risco e implantação de ações intervencionistas que minimizem impactos negativos na saúde dos trabalhadores / Introduction - The absences from work due to illness are used as an indicator of the health of workers and are considered a significant public health problem. Several factors are described as associated with absenteeism and illness, regardless of condition. Brazilian Social Security regulates the payment of benefits to workers who prove work-disability longer than fifteen days due to illness. In 2010, mental and behavioral disorders were the third leading cause for granting disability benefits. Objective - To assess the factors associated with long-term sickness absences from work due to mental and behavioral disorders. Methods - A case-control study comprising 385 participants applicants for social security benefits due mental sickness was performed in the city of São Paulo, Brazil. Interviews were conducted and participants answered questionnaires about sociodemographic and habits/lifestyle, occupational characteristics (including perceptions of psychosocial factors at work), assessment of health status. Social Security medical expert data report were analyzed. It was performed hierarchical logistic regression to assess variables associated with the outcome. Results - The associated factors were: sex (female), college education, self-reported skin color as white, high consumption of tobacco and alcohol intake, working for a public company, exposure to violence at work, low social support, high overcommitment and more than two medical conditions diagnoses in the past year. There was observed interaction among the dimensions of occupational stress theorical models, exposure to high strain and low social support, effort-reward imbalance with high overcommitment. The interaction among those four dimensions were statistical significant to the outcome. Conclusions - Demographic aspects, habits and lifestyle, work features and condition of employment, and health status are associated with long-term sickness absence due mental and behavioral disorders. Occupational exposure to adverse psychosocial factors is an important contributor to the outcome. It´s necessary attention to negative psychosocial factor at work in order to detect risk factors and promote interventions to minimize negative impacts on workers health

Introdução Os motoristas de ônibus urbano são submetidos às normas das empresas de forma peculiar, permanecendo a maior parte do tempo fora dos limites da contratante, submetidos a situações de trabalho com alto potencial estressante. Os distúrbios psíquicos são frequentes nesta população, gerando absenteísmo e impacto financeiro para profissionais, empresas e população usuária dos serviços. Objetivos Verificar o nível de sintomas ansiosos e depressivos referidos e traçar o perfil de uso de álcool nos motoristas de ônibus urbano da região metropolitana de São Paulo, que buscavam atendimento médico; Identificar fatores de risco psicossocial do trabalho associados a este perfil. Métodos Avaliada amostra de conveniência de 174 motoristas de ônibus urbano encaminhados ao Serviço de Saúde Ocupacional do ICHC-FMUSP. Realizadas entrevistas, preenchimento de prontuário médico ocupacional e aplicados questionários de avaliação da percepção de fatores psicossociais do trabalho, como variáveis independentes, e avaliação de condição de saúde quanto ao indicativo de transtornos depressivos, ansiosos e do padrão de consumo de álcool, como variáveis dependentes, sendo realizada análise estatística dos dados. Selecionados casos que ilustram as situações de trabalho a que estes profissionais estão expostos. Resultados 93,1 por cento consideram seu trabalho como de alta demanda psicológica e 87,4 por cento consideram ter baixo grau de controle sobre as atividades. 81,6 por cento posicionam-se na categoria de trabalho de alta exigência do Modelo Demanda-Controle e 57,5 por cento referem ter baixo suporte social. 61,5 por cento avaliam que há desequilíbrio na relação esforço-recompensa e 77,6 por cento consideram alto seu comprometimento pessoal com o trabalho. Pelo Modelo Desequilíbrio Esforço-Recompensa, 55,2 por cento dos casos estão expostos à situação considerada como de risco mais intenso de adoecimento. 60,9 por cento e 70,3 por cento dos casos apresentam sintomas sugestivos de diagnóstico de depressão e ansiedade, respectivamente. 13,8 por cento da amostra referem uso de álcool compatível com abuso/dependência. Ser mulher, ter menor idade, apresentar desequilíbrio esforço-recompensa e ter alto grau de comprometimento com o trabalho foram associados a sintomas indicativos de quadro depressivo. Apresentar desequilíbrio esforço-recompensa e ter alto comprometimento com o trabalho foram associados a sintomas indicativos de quadro de ansiedade. Ter baixo nível de apoio social foi associado a indicativo de abuso/dependência de álcool. Pela análise por regressão logística múltipla, desequilíbrio esforço-recompensa e comprometimento estão associados à depressão; controle e comprometimento à ansiedade e apoio social ao uso de álcool. Conclusão A população estudada mostrou-se exposta à situação de risco intenso de adoecimento psíquico relacionado ao trabalho. / Introduction Urban bus drivers are subjected to the companies regulations in a particular way as they work most of the time out of the physical limits of the companies, where they are subjected to working conditions that might lead to serious stress issues. Psychiatric disorders are typical in this community, causing absenteeism and financial impact for workers, companies and the population. Objectives To verify anxiety levels and depression symptoms and evaluate the pattern of alcohol usage on urban bus drivers from the metropolitan area of São Paulo (BR), who searched for medical aid; To identify psychosocial factors at work associated with this profile. Methodology The occupational and medical evaluation of the 174 urban bus drivers sample at Serviço de Saúde Ocupacional - ICHC-FMUSP consisted of interviews, use of medical protocols and questionnaires to evaluate how workers perceive psychosocial factors at work, as independent variables, and evaluate the health condition regarding depressive disorders, anxiety disorders and alcohol abuse/addiction, as dependent variables. Statistical methods were used to analyze the data. Cases were reported to illustrate their working conditions. Results 93.1 per cent consider their work as psychologically demanding and 87.4 per cent think they have a low degree of control over their activities. 81.6 per cent classify themselves at the category of high strain job of the Job Strain Model and 57.5 per cent consider themselves to have low social support. 61.5 per cent reckon there is an effort-reward imbalance and 77.6 per cent consider themselves to be highly commited to their Jobs. According to the Effort Reward Imbalance Model, 55.2 per cent of the cases are exposed to the situation of higher risk of developing disease. 60.9 per cent of the cases present symptons related to depression, 70.3 per cent present symptoms related to anxiety and 13,8 per cent refer symptoms that indicate alcohol abuse/addiction. Being a woman, younger, having an effort-reward imballance and a high degree of commitment with the job were associated with depression symptoms. Having an effort-reward imballance and a high degree of commitment with the job were associated with anxiety symptoms. Having a low social support was associated with the risk of presenting alcohol abuse/addiction. The variables effort-reward imballance and a high degree of commitment, for depression, control and high degree of commitment, and social support, for alcohol, are associated when the logistic regression analysis is used. Conclusion The group studied is exposed to a high risk of developing work related mental diseases.

Introdução - As ausências ao trabalho por doença são usadas como indicador da saúde dos trabalhadores e consideradas um significante problema de Saúde Pública. Diversos fatores são descritos como associados ao absenteísmo-doença, independentemente do agravo. A Previdência Social do Brasil regulamenta a concessão de benefício para trabalhadores que comprovarem incapacidade para o trabalho acima de quinze dias por adoecimento. Em 2010, transtornos mentais e comportamentais foram a terceira principal causa de concessão de auxílio-doença por incapacidade laborativa. Objetivo - Avaliar os fatores associados às longas ausências ao trabalho por transtornos mentais e comportamentais. Materiais e Método - Estudo de caso-controle composto por 385 participantes. Os casos foram requerentes de benefício previdenciário por transtorno mental incapacitante na cidade de São Paulo, Brasil. Foram realizadas entrevistas para preenchimento de questionários sociodemográfico e de hábitos/estilo de vida, ocupacional inclusive percepção de fatores psicossociais no trabalho, avaliação de condição de saúde e dados do laudo médico-pericial da Previdência Social. Foi realizada regressão logística múltipla hierarquizada para a avaliação da associação das variáveis independentes ao desfecho. Resultados - Os fatores associados foram: sexo feminino, alta escolaridade, cor da pele autorreferida como branca, alto grau de consumo de fumo e de ingesta de álcool, vínculo com empresa estatal, exposição à violência no trabalho, baixo apoio social, elevado comprometimento com o trabalho, atendimento médico por mais de dois diagnósticos no último ano. Na modelagem com interação entre as dimensões dos modelos de estresse ocupacional, a exposição à alta exigência com baixo apoio social, o desequilíbrio esforço-recompensa com elevado comprometimento e a interação entre essas quatro dimensões estão associadas ao desfecho de forma significativa. Considerações Finais - Aspectos sociodemográficos, hábitos e estilo de vida, característica e condição de trabalho, além do status de saúde, estão associados ao longo afastamento do trabalho por transtorno mental e comportamental. A exposição ocupacional a fatores desfavoráveis de natureza psicossocial é importante contribuidora no desfecho. Vê-se a necessidade de atenção para tais situações no intuito de ampliar as perspectivas de antecipação ao risco e implantação de ações intervencionistas que minimizem impactos negativos na saúde dos trabalhadores / Introduction - The absences from work due to illness are used as an indicator of the health of workers and are considered a significant public health problem. Several factors are described as associated with absenteeism and illness, regardless of condition. Brazilian Social Security regulates the payment of benefits to workers who prove work-disability longer than fifteen days due to illness. In 2010, mental and behavioral disorders were the third leading cause for granting disability benefits. Objective - To assess the factors associated with long-term sickness absences from work due to mental and behavioral disorders. Methods - A case-control study comprising 385 participants applicants for social security benefits due mental sickness was performed in the city of São Paulo, Brazil. Interviews were conducted and participants answered questionnaires about sociodemographic and habits/lifestyle, occupational characteristics (including perceptions of psychosocial factors at work), assessment of health status. Social Security medical expert data report were analyzed. It was performed hierarchical logistic regression to assess variables associated with the outcome. Results - The associated factors were: sex (female), college education, self-reported skin color as white, high consumption of tobacco and alcohol intake, working for a public company, exposure to violence at work, low social support, high overcommitment and more than two medical conditions diagnoses in the past year. There was observed interaction among the dimensions of occupational stress theorical models, exposure to high strain and low social support, effort-reward imbalance with high overcommitment. The interaction among those four dimensions were statistical significant to the outcome. Conclusions - Demographic aspects, habits and lifestyle, work features and condition of employment, and health status are associated with long-term sickness absence due mental and behavioral disorders. Occupational exposure to adverse psychosocial factors is an important contributor to the outcome. It´s necessary attention to negative psychosocial factor at work in order to detect risk factors and promote interventions to minimize negative impacts on workers health

The occupational exposures of sewage workers are complex and variable, and include a great variety of biological and chemical agents. Previous research has focused mostly on infections and various symptoms among sewage workers, e.g. abdominal and respiratory symptoms. At several sewage plants in Sweden, concern arose about occupational cancer, specifically cancer of the stomach, the kidney, and the lung. The aim of this study was to study the cancer incidence among municipal sewage workers, some exposures that might be connected with cancer risk, and self reported abdominal and respiratory symptoms. In a cohort of municipal sewage workers there was no increase in the overall incidence of cancer when compared with the general population. However, there was a slight increase in the incidence of prostate cancer, but not in the sites of original concern among the workers. Infection by the gastric carcinogen Helicobacter pylori (determined from the presence of IgG antibodies in serum against H pylori) was no more prevalent in sewage workers than in comparable referents. Neither were sewage workers more exposed to genotoxic agents than comparable referents, as measured by the alkaline single cell gel electrophoresis (SCG) assay performed on peripheral lymphocytes. There was no increase in the three-month prevalence of abdominal symptoms when compared with other municipal workers. Specifically, there was no difference in prevalence of the common disorders dyspepsia and irritable bowel syndrome. Sewage workers reported adult bronchial asthma significantly more than the referents.