Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2017-05-10T20:18:04Z No. of bitstreams: 2 Tese - Heloisa de Sousa Gomes Rodrigues - 2016.pdf: 24514601 bytes, checksum: 5d8491e9be339376d5b3114ac0b8fd41 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-05-11T12:08:41Z (GMT) No. of bitstreams: 2 Tese - Heloisa de Sousa Gomes Rodrigues - 2016.pdf: 24514601 bytes, checksum: 5d8491e9be339376d5b3114ac0b8fd41 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-05-11T12:08:41Z (GMT). No. of bitstreams: 2 Tese - Heloisa de Sousa Gomes Rodrigues - 2016.pdf: 24514601 bytes, checksum: 5d8491e9be339376d5b3114ac0b8fd41 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-12-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Paediatric dental treatment may stress children and their parents influencing the child behaviour and the maternal dental anxiety. It is important to understand those behavioural and physiological alterations to aid using of adequate sedatives techniques during paediatric dental procedure. The aim of this study was to evaluate the stress of children and their mothers during the paediatric dental treatment using different sedation protocols. Also, the maternal dental anxiety, the child’s behaviour and age and its associations were evaluated. This observational study is a secondary analysis of two randomised controlled clinical trials. Children aged 2-6 years old received one tooth restoration under moderate sedation according to the groups: [A] 18 children received oral midazolam (1.0 mg/kg) and [B] 18 children received placebo in a crossover design [Clinical Trials database (NCT01795222)]; [C] 14 children received oral midazolam (0.5 mg/kg) and oral ketamine (3.0 mg/kg) plus sevoflurane inhalation (0.3% - 0.4%) and [D] 13 children had oral midazolam (0.5 mg/kg) and oral ketamine (3.0 mg/kg) plus oxygen inhalation in a parallel design (NCT02284204). The sessions were video recorded for evaluation of child behaviour using OSUBRS scale (Ohio State University Behavioural Rating Scale) and mothers answered the Brazilian version of Dental Anxiety Scale (DAS). The saliva samples were collected on children and on their mothers at 4 moments: waking up (T0), upon arrival at Dental School (T1), 25 minutes after the local anaesthesia injection on child (T2) and 25 minutes after the end of procedure (T3). Salivary cortisol was measured using an immunoassay kit (ELISA). As the data presented non normal distribution (Shapiro Wilk, p>0,05), Kruskal-Wallis and Mann-Whitney tests were used for non paired comparisons and Mann-Whitney for associations among the variables. For paired comparisons, Friedman and Wilcoxon tests were used (p<0,05). The increase of cortisol levels from T1 to T2 (reactivity to stressful stimulus – local anaesthesia) was higher in children of group [B] [median (interquartile)] – [0.53 (0.60)] following by groups [D] – [0.21 (0.35)], [C] – [0.11 (0.49)] and [A] – [0.02 (0.59)] (p=0.02). The decrease of cortisol levels from T2 to T3 (regulation to stress) was higher in children of group [B] – [0.08 (0.29)] following by groups [A] [-0.02 (0.40)], [C] – [-0.18 (0.41)] and [D] – [-0.19 (0.8)] (p=0.02). Majority of mothers were not stressed during their child’s local anaesthesia injection (67.9%) and presented low/moderate anxiety (69.6%), while 25.0% of them presented high/severe anxiety (DAS scale). Mothers who reacted to stress (increasing of cortisol at least 10% from T1 to T2) had higher cortisol levels at the moments T2 [0.15 (0.48)] and T3 [0.16 (0.50)] compared to T1 [0.09 (0.17)] (p<0.01 and p<0.006, respectively). On the other hand, mothers who did not react to stress had higher cortisol levels at the moments: T1 [0.36 (0.18)] compared to T2 [0.16 (0.18)] (p<0.01) and T3 [0.10 (0.12)] (p<0.01) and T2 compared to T3 (p=0.01). There was no statistically significant association between maternal stress (salivary cortisol levels) with child behaviour (p=0.56), child’s age (p=0.48) and maternal dental anxiety (DAS) (p=0.69). The findings of this study allow to conclude that sedation protocol using oral ketamine caused higher liberation of salivary cortisol at the moments of local anaesthesia and at the end of procedure (higher reactivity and lower regulation) indicating a prolonged response to physiological stress in children, which was not observed during the use of oral midazolam. Although, there was any maternal dental anxiety most of mothers were not stressed during the dental treatment under sedation of their children. Also, maternal dental anxiety, child’s age and child behaviour did not influence the maternal stress. / O tratamento odontopediátrico pode causar estresse em crianças e em seus acompanhantes prejudicando o comportamento infantil e a ansiedade odontológica materna. A compreensão dessas alterações fisiológicas e comportamentais é de suma importância a fim de auxiliar no uso de técnicas sedativas adequadas durante o atendimento odontológico infantil. O objetivo deste estudo foi avaliar o estresse de crianças e de suas respectivas mães durante o tratamento odontopediátrico sob diferentes protocolos de sedação. Além disso, objetivou-se avaliar a ansiedade odontológica materna e o comportamento infantil, bem como a associação destas características. Este estudo observacional é uma análise de dados de dois ensaios clínicos randomizados e controlados. Crianças de 2 a 6 anos de idade receberam tratamento odontológico restaurador padronizado sob sedação moderada de acordo com os grupos: [A] 18 crianças receberam midazolam oral 1,0 mg/kg e [B] 18 crianças receberam placebo, em um desenho cruzado [Clinical Trials database (NCT01795222)]; [C] 14 crianças receberam midazolam oral 0,5 mg/kg e cetamina oral 3,0 mg/kg mais inalação de sevoflurano (0,3% - 0,4%) e [D] 13 crianças tiveram midazolam oral 0,5 mg/kg e cetamina oral 3,0 mg/kg mais inalação de oxigênio, em um desenho paralelo (NCT02284204). As sessões foram filmadas para posterior avaliação do comportamento infantil usando a escala OSUBRS (Ohio State University Behavioural Rating Scale) e as mães responderam a versão Brasileira da Dental Anxiety Scale (DAS). As coletas de saliva foram realizadas concomitantemente nas crianças e mães em 4 momentos: ao acordar (T0), na chegada na clínica (T1), 25 minutos após a aplicação da anestesia local na criança (T2) e 25 minutos após o término do procedimento (T3). O cortisol salivar foi mensurado por meio de ensaio imunoenzimático (ELISA). Como os dados apresentaram distribuição não normal (Shapiro Wilk, p>0,05), o teste de KruskalWallis seguido de Mann-Whitney foram utilizados para comparações não pareadas e MannWhitney para associação entre as variáveis. Para análises pareadas, o teste de Friedman seguido de Wilcoxon foi utilizado adotando-se como nível de significância um valor de 5% (p<0,05). O aumento do cortisol de T1 para T2 (reatividade ao estímulo estressor – anestesia) foi maior em crianças do grupo [B] [mediana (interquartil)] – [0,53 (0,60)] seguido dos grupos [D] – [0,21 (0,35)], [C] – [0,11 (0,49)] e [A] – [0,02 (0,59)] (p=0,02). Já a redução do cortisol de T2 para T3 (regulação ao estresse) foi maior em crianças do grupo [B] – [0,08 (0,29)] seguido dos grupos [A] [-0,02 (0,40)], [C] – [-0,18 (0,41)] e [D] – [-0,19 (0,8)] (p=0,02). A maioria das mães não ficaram estressadas durante a aplicação da anestesia local em seus filhos (67,9%) e apresentaram ansiedade baixa/moderada (69,6%), enquanto 25,0% delas apresentaram alta/severa ansiedade (escala DAS). As mães que reagiram ao estresse (aumento de pelo menos 10% do nível de cortisol salivar do momento T1 ao T2) tiveram maiores níveis de cortisol nos momentos T2 [0,15 (0,48)] e T3 [0,16 (0,50)] comparado com T1 [0,09 (0,17)] (p<0,01 e p=0,006, respectivamente). Por outro lado, mães que não reagiram tiveram maior nível de cortisol nos momentos: T1 [0,36 (0,18)] comparado a T2 [0,16 (0,18)] (p<0,01) e T3 [0,10 (0,12)] (p<0,01); T2 comparado a T3 (p=0,01). Não houve associação estatisticamente significante entre o nível de cortisol salivar das mães com o comportamento infantil (p=0,56); idade das crianças (p=0,48) e ansiedade odontológica materna (DAS) (p=0,69). Os achados obtidos no presente estudo permitem concluir que o uso do protocolo de sedação com cetamina oral provocou aumento da liberação de cortisol salivar tanto no momento da anestesia quanto ao final do tratamento (maior reatividade e menor regulação) indicando uma resposta prolongada ao estresse fisiológico das crianças, o que não foi observado com o uso de midazolam oral. Embora algum grau de ansiedade odontológica materna tenha sido evidenciada, a maioria das mães não ficaram estressadas durante o tratamento odontológico sob sedação de seus filhos. Adicionalmente, a ansiedade odontológica das mães, bem como a idade e o comportamento infantil não influenciaram o estresse materno.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by preferential motor neuron death in the brain and spinal cord. The rapid disease progression results in death due to respiratory failure, typically within 3-5 years after disease onset. While ~90% of cases occur sporadically, remaining 10% of ALS cases show familial inheritance, and the number of genes linked to ALS has increased dramatically over the past decade. FUS/TLS (Fused in Sarcoma/ Translocated to liposarcoma) is a nucleic acid binding protein that may regulate several cellular functions, including RNA splicing, transcription, DNA damage repair and microRNA biogenesis. More than 50 mutations in the FUS gene are linked to 4% of familial ALS, and many of these may disrupt the nuclear localization signal, leading to variable amounts of FUS accumulation in the cytoplasm. However, the mechanism by which FUS mutants cause motor neuron death is still unknown. The studies presented in this dissertation focused on investigating the properties of FUS mutants in the absence and presence of stress conditions. We first examined how ALS-linked FUS mutants behaved in response to imposed stresses in both cell culture and zebrafish models of ALS. We found that FUS mutants were prone to accumulate in stress granules in proportion to their degree of cytoplasmic mislocalization under conditions of oxidative stress, ER stress, and heat shock. However, many FUS missense mutants are retained predominantly in the nucleus, and this suggested the possibility that these mutants might also perturb one or more nuclear functions. In a human cell line expressing FUS variants and in human fibroblasts from an ALS patient, mutant FUS expression was associated with enlarged promyelocytic leukemia nuclear bodies (PML-NBs) under basal condition. Upon oxidative insult with arsenic trioxide (ATO), PML-NBs in control cells increased acutely in size and were turned over within 12-24 h, as expected. However, PML-NBs in FUS mutant cells did not progress through the expected turnover but instead continued to enlarge over 24 h. We also observed a persistent accumulation of the transcriptional repressor Daxx and the 11S proteasome regulator in association with these enlarged PML-NBs. Furthermore, the peptidase activities of the 26S proteasome were decreased in FUS mutant cells without any changes in the expression of proteasome subunits. These results demonstrate that FUS mutant expression may alter cellular stress responses as manifested by (i) accumulation of mutant FUS into stress granules and (ii) inhibition of PML-NB dynamics. These findings suggest a novel nuclear pathology specific to mutant FUS expression that may perturb nuclear homeostasis and thereby contribute to ALS pathogenesis.

No description available.

No Brasil, o amplo escopo de responsabilidades e também a diversidade de situações que demandam ações da Polícia Rodoviária Federal contribuem para que agentes/eventos estressores façam parte da rotina diária de centenas de policiais. Contudo, ainda existem poucos estudos dedicados a identificar o estresse nesta população. Assim, o objetivo principal do presente estudo é identificar a prevalência do estresse neste grupo, além de identificar as prevalências de transtorno de estresse pós-traumático (TEPT), de estresse ocupacional e, finalmente, a prevalência dos sintomas de Síndrome de Burnout. Para tanto foi utilizado um desenho de estudo transversal com amostra probabilística (n = 202) de policiais rodoviários federais do Estado de São Paulo. Os instrumentos para obtenção dos dados da amostra foram: i) Questionário Geral (QG), para a caracterização da amostra e obtenção de dados sociodemográficos e profissionais; ii) Inventário de Sintomas de Stress para Adultos de Lipp (ISSL), para sintomas de estresse; iii) Escala de Impacto do Evento - Revisada (IES-R), para sintomas de TEPT; iv) Escala de Vulnerabilidade do Estresse no Trabalho (EVENT), para estresse ocupacional; v) Inventário de Burnout de Maslach, versão HSS (MBI-HSS), para identificação dos sintomas pertinentes à Síndrome de Burnout. Os dados foram armazenados em planilhas excel e analisados com a utilização dos softwares Stata 8.0 for Windows e R3.3.2. A medida de associação escolhida foi o Odds Ratio (OR) e o seu intervalo de confiança (IC). Para testar a significância estatística foram utilizados o teste de qui quadrado o teste Exato de Fisher, para as variáveis nominais e, o teste Mann-Whitney-Wilcoxon foi utilizado para as variáveis com distribuição não paramétrica: idade (faixa etária) e tempo de carreira. O nível de significância adotado foi de 5%. A prevalência de sintomas de estresse na amostra representou 43,1% (IC95% = 36,2-50,0) com a seguinte distribuição por fase: 2,3% (IC95% = 0,2-8,0) em \"Alerta\"; 82,7% (IC95% = 73,2-90,0) em \"Resistência\"; 11,5% (IC95% = 5,7-20,1) em \"Quase Exaustão\"; e 3,5% (IC95% = 0,7-9,7) em \"Exaustão\". Ainda, 60,9% da amostra apresentaram sintomas psicológicos de estresse, 33,3% sintomas físicos e 5,8% ambos. A prevalência de TEPT ocorreu em 25,4% (IC95% = 19,3-31,4) da amostra, sem a predominância entre as subescalas. A prevalência de sintomas de estresse ocupacional afetou 35,2% (IC95% = 28,5-41,8) dos policiais participantes do presente estudo. Não houve registro na amostra referente à Síndrome de Burnout. As prevalências de estresse encontradas neste estudo apresentaram valores compatíveis com os valores de pesquisas semelhantes - elaboradas em outras categorias de policiais -, tanto no contexto nacional como no internacional. Há indícios que o tempo para práticas de lazer pode exercer influência como fator de proteção contra os sintomas de estresse; por outro lado, há indícios que processos penais e o longo tempo de carreira podem exercer influência como fatores de risco. Em última análise, a combinação dos resultados aqui apresentados sugerem indícios do adoecimento - em curso - desta população em função dos elevados índices de prevalência dos sintomas de estresse, sintomas de TEPT e estresse ocupacional / In Brazil, the wide scope of responsibilities and also the diversity of situations that demand actions from the Federal Highway Police sharply contribute to stressor agents/events make part of the daily routine of hundreds police officers. However, there are still few studies dedicated to identify the stress symptoms in this population. Thus, this study aims to identify the prevalence of stress in this group as well as to identify also the prevalences of post-traumatic stress disorder (PTSD), occupational stress, and finally the prevalence of Burnout Syndrome symptoms. On this way, a cross-sectional design study was applied with probabilistic sample of (n=202) Federal Highway Police Officers on State of São Paulo. The tools to pick up the sample data were: i) General Questionnaire, picking up the sample features and getting socio-demographic and professional data; ii) Adult Stress Symptom Inventory by Lipp (pt.: ISSL), for stress symptoms; iii) Scale of Reviewed Event Impact (pt.: IES-R), for PTSD symptoms; iv) Stress Vulnerability Scale at Work (pt.: EVENT), for occupational stress; v) Maslach Burnout Inventory, HSS version (MBI-HSS), identifying the Burnout Syndrome symptoms. The database were stored in the excel spreadsheets and they were analyzed through by Stata 8.0 for Windows and R3.3.2 software. The association measure was Odds Ratio (OR) and its confidence interval (CI). In order to test the statistical significance the chi-square test and the Fisher Exact test were applied to the nominal variables. The Mann-Whitney-Wilcoxon test was applied to the variables with non-parametric distribution: age (age group) and professional career time. The significance level defined was 5%. The prevalence of stress symptoms appeared to 43,1% (CI95% = 36,2-50,0) of the sample and they were split in each phase as follow: 2,3% (CI95% = 0,2-8,0) in \"Alert\"; 82,7% (CI95% = 73,2-90,0) in \"Resistance\"; 11,5% (CI95% = 5,7-20,1) in \"Close Exhaustion\"; and 3,5% (CI95% = 0,7-9,7) in \"Exhaustion\". In addition, 60,9% of the sample presented stress psychological symptoms, 33,3% stress physical symptoms and 5,8% both ones. The prevalence of PTSD occurred in 25,4% (CI95% = 19,3-31,4) of the sample and there was no predominance among the subscales. The prevalence of occupational stress symptoms affects 35,2% (CI95% = 28,5-41,8) of the police officers who made part of this study. There was no record in the sample regarding Burnout Syndrome. The prevalence of stress found out in this study had compatible values as the same values found out in other similar researches - issued with other police categories - on the national as well as international context. It seems that booking time for leisure practices might be related as a protection factor against stress symptoms. In other hand, it seems criminal procedures and a long professional career time might be related as a risk factor. At last, the set of presented results suggests sickness signs - ongoing - in this population due to the high prevalence rates of stress symptoms, PTSD symptoms and occupational stress

OBJETIVO: avaliar a reprodutibilidade da curva tensional modificada e do teste de sobrecarga hídrica em portadores de glaucoma de ângulo aberto ou hipertensos oculares, sem uso de hipotensor ocular, em dois dias consecutivos. MÉTODOS: análise prospectiva de pacientes portadores de glaucoma de ângulo aberto ou hipertensos oculares, submetidos à curva tensional modificada (medida da pressão intraocular às 8h, 11h, 14h e 16h), seguida do teste de sobrecarga hídrica (três medidas com intervalo de 15 minutos, iniciando-se 15 minutos após a ingestão, em cinco minutos, de um litro de água em temperatura ambiente), realizados pelo mesmo examinador, em dois dias consecutivos. Foram avaliadas: a reprodutibilidade da pressão intraocular em cada horário de medida durante a curva tensional modificada; a reprodutibilidade da pressão intraocular média, flutuação e pico de pressão durante a curva tensional modificada; a reprodutibilidade da flutuação e do pico de pressão durante o teste de sobrecarga hídrica. Calculou-se o coeficiente de correlação intraclasse para cada parâmetro. RESULTADOS: oitenta e oito olhos de 88 pacientes foram estudados. Destes, 64 eram portadores de glaucoma de ângulo aberto. A média das idades dos participantes foi 68,7+10,8 (51-79) anos. 65% dos pacientes eram do sexo feminino. A curva tensional modificada apresentou coeficiente de correlação intraclasse igual a 0,80, 0,82, 0,83 e 0,86 para as medidas realizadas às 8h, 11h, 14h e 16h, respectivamente (p < 0,001). A flutuação da pressão durante a curva tensional modificada, calculada pela diferença entre as pressões máxima e mínima e pelo desvio-padrão da média das medidas diurnas de pressão, a pressão média e o pico pressórico apresentaram coeficientes 0,60, 0,62, 0,91 e 0,85, respectivamente (p < 0,001). Durante o teste de sobrecarga hídrica, a flutuação apresentou coeficiente de 0,37 e o pico pressórico, 0,79. (p < 0,001). CONCLUSÕES: neste estudo, as medidas de pressão intraocular realizadas durante a curva tensional modificada, a média e o pico apresentaram excelentes níveis de reprodutibilidade. O pico pressórico durante o teste de sobrecarga hídrica apresentou também excelente reprodutibilidade. A flutuação, tanto na curva tensional modificada, quanto no teste de sobrecarga hídrica, apresentou os menores índices de reprodutibilidade / OBJECTIVE: to evaluate the reproducibility of the modified daily tension curve and the water drinking test in patients with open-angle glaucoma or ocular hypertension, not under topical treatment, during two consecutive days. METHODS: prospective analysis of open-angle glaucoma or ocular hypertensive patients, submitted to a modified daily tension curve (intraocular pressure measurements at 8AM, 11AM, 2PM and 4PM), followed by the water drinking test (three intraocular pressure measurements with 15 minutes intervals, 15 minutes after ingestion of one liter of tap water), performed by the same examiner, within two consecutive days. The following parameters were evaluated for reproducibility: intraocular pressure obtained at each time-point during the modified daily tension curve; mean, peak and pressure fluctuation during the curve and peak and fluctuation during the water drinking test. Reproducibility was assessed using the intraclass correlation coefficient. RESULTS: eighty-eight eyes from 88 patients were studied. From these, 64 presented open-angle glaucoma. Mean age was 68.7+10.8 (51-79) years. 65% patients were female. Intraclass correlation coefficients were 0.80, 0.82, 0.83 and 0.86 for intraocular pressure measurements at 8AM, 11AM, 2PM and 4PM, respectively (p<0.001) Fluctuation calculated as the difference between maximum and minimum intraocular pressures, fluctuation calculated as the standard deviation of the four daily measurements, mean and peak pressures presented coefficients of 0.60, 0.62, 0.91 and 0.85, respectively (p<0.001). During the water drinking test, coefficient values for fluctuation and peak pressure were 0.37 and 0.79 (p<0.001). CONCLUSIONS: in this study, intraocular pressure measurements during a modified daily tension curve, mean intraocular pressure and pressure peaks presented excellent reproducibility levels; pressure peaks during the water drinking test also presented excellent reproducibility level, whereas fluctuation, both during the modified daily tension curve and during the water drinking test, was the least reproducible parameter

OBJETIVO: avaliar a reprodutibilidade da curva tensional modificada e do teste de sobrecarga hídrica em portadores de glaucoma de ângulo aberto ou hipertensos oculares, sem uso de hipotensor ocular, em dois dias consecutivos. MÉTODOS: análise prospectiva de pacientes portadores de glaucoma de ângulo aberto ou hipertensos oculares, submetidos à curva tensional modificada (medida da pressão intraocular às 8h, 11h, 14h e 16h), seguida do teste de sobrecarga hídrica (três medidas com intervalo de 15 minutos, iniciando-se 15 minutos após a ingestão, em cinco minutos, de um litro de água em temperatura ambiente), realizados pelo mesmo examinador, em dois dias consecutivos. Foram avaliadas: a reprodutibilidade da pressão intraocular em cada horário de medida durante a curva tensional modificada; a reprodutibilidade da pressão intraocular média, flutuação e pico de pressão durante a curva tensional modificada; a reprodutibilidade da flutuação e do pico de pressão durante o teste de sobrecarga hídrica. Calculou-se o coeficiente de correlação intraclasse para cada parâmetro. RESULTADOS: oitenta e oito olhos de 88 pacientes foram estudados. Destes, 64 eram portadores de glaucoma de ângulo aberto. A média das idades dos participantes foi 68,7+10,8 (51-79) anos. 65% dos pacientes eram do sexo feminino. A curva tensional modificada apresentou coeficiente de correlação intraclasse igual a 0,80, 0,82, 0,83 e 0,86 para as medidas realizadas às 8h, 11h, 14h e 16h, respectivamente (p < 0,001). A flutuação da pressão durante a curva tensional modificada, calculada pela diferença entre as pressões máxima e mínima e pelo desvio-padrão da média das medidas diurnas de pressão, a pressão média e o pico pressórico apresentaram coeficientes 0,60, 0,62, 0,91 e 0,85, respectivamente (p < 0,001). Durante o teste de sobrecarga hídrica, a flutuação apresentou coeficiente de 0,37 e o pico pressórico, 0,79. (p < 0,001). CONCLUSÕES: neste estudo, as medidas de pressão intraocular realizadas durante a curva tensional modificada, a média e o pico apresentaram excelentes níveis de reprodutibilidade. O pico pressórico durante o teste de sobrecarga hídrica apresentou também excelente reprodutibilidade. A flutuação, tanto na curva tensional modificada, quanto no teste de sobrecarga hídrica, apresentou os menores índices de reprodutibilidade / OBJECTIVE: to evaluate the reproducibility of the modified daily tension curve and the water drinking test in patients with open-angle glaucoma or ocular hypertension, not under topical treatment, during two consecutive days. METHODS: prospective analysis of open-angle glaucoma or ocular hypertensive patients, submitted to a modified daily tension curve (intraocular pressure measurements at 8AM, 11AM, 2PM and 4PM), followed by the water drinking test (three intraocular pressure measurements with 15 minutes intervals, 15 minutes after ingestion of one liter of tap water), performed by the same examiner, within two consecutive days. The following parameters were evaluated for reproducibility: intraocular pressure obtained at each time-point during the modified daily tension curve; mean, peak and pressure fluctuation during the curve and peak and fluctuation during the water drinking test. Reproducibility was assessed using the intraclass correlation coefficient. RESULTS: eighty-eight eyes from 88 patients were studied. From these, 64 presented open-angle glaucoma. Mean age was 68.7+10.8 (51-79) years. 65% patients were female. Intraclass correlation coefficients were 0.80, 0.82, 0.83 and 0.86 for intraocular pressure measurements at 8AM, 11AM, 2PM and 4PM, respectively (p<0.001) Fluctuation calculated as the difference between maximum and minimum intraocular pressures, fluctuation calculated as the standard deviation of the four daily measurements, mean and peak pressures presented coefficients of 0.60, 0.62, 0.91 and 0.85, respectively (p<0.001). During the water drinking test, coefficient values for fluctuation and peak pressure were 0.37 and 0.79 (p<0.001). CONCLUSIONS: in this study, intraocular pressure measurements during a modified daily tension curve, mean intraocular pressure and pressure peaks presented excellent reproducibility levels; pressure peaks during the water drinking test also presented excellent reproducibility level, whereas fluctuation, both during the modified daily tension curve and during the water drinking test, was the least reproducible parameter

No Brasil, o amplo escopo de responsabilidades e também a diversidade de situações que demandam ações da Polícia Rodoviária Federal contribuem para que agentes/eventos estressores façam parte da rotina diária de centenas de policiais. Contudo, ainda existem poucos estudos dedicados a identificar o estresse nesta população. Assim, o objetivo principal do presente estudo é identificar a prevalência do estresse neste grupo, além de identificar as prevalências de transtorno de estresse pós-traumático (TEPT), de estresse ocupacional e, finalmente, a prevalência dos sintomas de Síndrome de Burnout. Para tanto foi utilizado um desenho de estudo transversal com amostra probabilística (n = 202) de policiais rodoviários federais do Estado de São Paulo. Os instrumentos para obtenção dos dados da amostra foram: i) Questionário Geral (QG), para a caracterização da amostra e obtenção de dados sociodemográficos e profissionais; ii) Inventário de Sintomas de Stress para Adultos de Lipp (ISSL), para sintomas de estresse; iii) Escala de Impacto do Evento - Revisada (IES-R), para sintomas de TEPT; iv) Escala de Vulnerabilidade do Estresse no Trabalho (EVENT), para estresse ocupacional; v) Inventário de Burnout de Maslach, versão HSS (MBI-HSS), para identificação dos sintomas pertinentes à Síndrome de Burnout. Os dados foram armazenados em planilhas excel e analisados com a utilização dos softwares Stata 8.0 for Windows e R3.3.2. A medida de associação escolhida foi o Odds Ratio (OR) e o seu intervalo de confiança (IC). Para testar a significância estatística foram utilizados o teste de qui quadrado o teste Exato de Fisher, para as variáveis nominais e, o teste Mann-Whitney-Wilcoxon foi utilizado para as variáveis com distribuição não paramétrica: idade (faixa etária) e tempo de carreira. O nível de significância adotado foi de 5%. A prevalência de sintomas de estresse na amostra representou 43,1% (IC95% = 36,2-50,0) com a seguinte distribuição por fase: 2,3% (IC95% = 0,2-8,0) em \"Alerta\"; 82,7% (IC95% = 73,2-90,0) em \"Resistência\"; 11,5% (IC95% = 5,7-20,1) em \"Quase Exaustão\"; e 3,5% (IC95% = 0,7-9,7) em \"Exaustão\". Ainda, 60,9% da amostra apresentaram sintomas psicológicos de estresse, 33,3% sintomas físicos e 5,8% ambos. A prevalência de TEPT ocorreu em 25,4% (IC95% = 19,3-31,4) da amostra, sem a predominância entre as subescalas. A prevalência de sintomas de estresse ocupacional afetou 35,2% (IC95% = 28,5-41,8) dos policiais participantes do presente estudo. Não houve registro na amostra referente à Síndrome de Burnout. As prevalências de estresse encontradas neste estudo apresentaram valores compatíveis com os valores de pesquisas semelhantes - elaboradas em outras categorias de policiais -, tanto no contexto nacional como no internacional. Há indícios que o tempo para práticas de lazer pode exercer influência como fator de proteção contra os sintomas de estresse; por outro lado, há indícios que processos penais e o longo tempo de carreira podem exercer influência como fatores de risco. Em última análise, a combinação dos resultados aqui apresentados sugerem indícios do adoecimento - em curso - desta população em função dos elevados índices de prevalência dos sintomas de estresse, sintomas de TEPT e estresse ocupacional / In Brazil, the wide scope of responsibilities and also the diversity of situations that demand actions from the Federal Highway Police sharply contribute to stressor agents/events make part of the daily routine of hundreds police officers. However, there are still few studies dedicated to identify the stress symptoms in this population. Thus, this study aims to identify the prevalence of stress in this group as well as to identify also the prevalences of post-traumatic stress disorder (PTSD), occupational stress, and finally the prevalence of Burnout Syndrome symptoms. On this way, a cross-sectional design study was applied with probabilistic sample of (n=202) Federal Highway Police Officers on State of São Paulo. The tools to pick up the sample data were: i) General Questionnaire, picking up the sample features and getting socio-demographic and professional data; ii) Adult Stress Symptom Inventory by Lipp (pt.: ISSL), for stress symptoms; iii) Scale of Reviewed Event Impact (pt.: IES-R), for PTSD symptoms; iv) Stress Vulnerability Scale at Work (pt.: EVENT), for occupational stress; v) Maslach Burnout Inventory, HSS version (MBI-HSS), identifying the Burnout Syndrome symptoms. The database were stored in the excel spreadsheets and they were analyzed through by Stata 8.0 for Windows and R3.3.2 software. The association measure was Odds Ratio (OR) and its confidence interval (CI). In order to test the statistical significance the chi-square test and the Fisher Exact test were applied to the nominal variables. The Mann-Whitney-Wilcoxon test was applied to the variables with non-parametric distribution: age (age group) and professional career time. The significance level defined was 5%. The prevalence of stress symptoms appeared to 43,1% (CI95% = 36,2-50,0) of the sample and they were split in each phase as follow: 2,3% (CI95% = 0,2-8,0) in \"Alert\"; 82,7% (CI95% = 73,2-90,0) in \"Resistance\"; 11,5% (CI95% = 5,7-20,1) in \"Close Exhaustion\"; and 3,5% (CI95% = 0,7-9,7) in \"Exhaustion\". In addition, 60,9% of the sample presented stress psychological symptoms, 33,3% stress physical symptoms and 5,8% both ones. The prevalence of PTSD occurred in 25,4% (CI95% = 19,3-31,4) of the sample and there was no predominance among the subscales. The prevalence of occupational stress symptoms affects 35,2% (CI95% = 28,5-41,8) of the police officers who made part of this study. There was no record in the sample regarding Burnout Syndrome. The prevalence of stress found out in this study had compatible values as the same values found out in other similar researches - issued with other police categories - on the national as well as international context. It seems that booking time for leisure practices might be related as a protection factor against stress symptoms. In other hand, it seems criminal procedures and a long professional career time might be related as a risk factor. At last, the set of presented results suggests sickness signs - ongoing - in this population due to the high prevalence rates of stress symptoms, PTSD symptoms and occupational stress

Recent decades have seen an explosion of research centered on understanding the influential impact that job stressors have on employees' subjective well-being, and now more recently, on objective assessments of physical health. Utilizing baseline data from a larger study funded by the National Institute for Occupational Safety and Health (NIOSH), I conducted a field study on blue-collar employees from two organizations in the construction industry, with the goal of exploring the impact of job stressors on job satisfaction (subjective well-being) and body mass index (objective health), as well as the influence of organizational justice as a moderator and exercise as a mediator in those relationships. In support of previous research, results show that job stressors (job demands, low skill discretion, and low decision authority) all had significant direct effects on job satisfaction in the expected directions, signifying that the fewer demands and more control one has in their work role, the more satisfied one is. Results also indicate that distributive and procedural justice have significant main effects on job satisfaction, illustrating that higher perceptions of justice are related to higher levels of job satisfaction. With respect to objective health, the data provides empirical support for the relationship between job control (skill discretion and decision authority) and BMI; however, job demands did not have a significant main effect on BMI. More importantly, the rarely studied relationship between organizational justice and BMI was investigated (Robbins et al., 2012), with results indicating that procedural and distributive justice are important influences on one's BMI level. Post hoc analyses revealed that distributive and procedural justice are two relevant mediators to consider in the job stressor-job satisfaction relationship, illustrating the importance of considering employees' fairness perceptions with regards to their satisfaction levels. Moreover, exercise was found to be a significant moderator to the relationship between job demands and BMI, as well as the relationship between distributive justice and job satisfaction, shedding light on physical activity within the work and health contexts as a factor that interacts with employees' perceptions of justice and their workload demands to impact their psychological and physical health. Considering the cross-sectional nature of these data, all mediation and moderation results should be interpreted with caution. With empirical support found for the direct association between job stressors and organizational justice and the outcomes of job satisfaction and BMI, this study has significant implications for researchers and practitioners alike to further expand upon these findings and implement them into organizational practice in support of the Total Worker Health initiative, which aims to promote employee safety and health (Schill & Chosewood, 2013). Results suggest a healthy workforce is the result of the combination of employers transforming the work environment into a more just, transparent and trustworthy place to work, starting with the dynamics between supervisors and their employees, in conjunction with targeted interventions on employees' modifiable behaviors, such as engaging in physical activity and healthier eating habits.

During stress, eukaryotes regulate protein synthesis in part through formation of cytoplasmic, non-membrane-bound complexes called stress granules (SGs). SGs transiently store signaling proteins and stalled translational complexes in response to stress stimuli (e.g. oxidative insult, DNA damage, temperature shifts and ER dysfunction). The functional outcome of SGs is proper translational regulation and signaling, allowing cells to overcome stress. The fatal motor neuron disease Amyotrophic Lateral Sclerosis (ALS) develops in an age-related manner and is marked by progressive neuronal death, with cytoplasmic protein aggregation, excitotoxicity and increased oxidative stress as major hallmarks. Fused in Sarcoma/Translocated in Liposarcoma (FUS) is an RNA-binding protein mutated in ALS with roles in RNA and DNA processing. Most ALS-associated FUS mutations cause FUS to aberrantly localize in the cytoplasm due to a disruption in the nuclear localization sequence. Intriguingly, pathological inclusions in human FUSALS cases contain aggregated FUS as well as several SG-associated proteins. Further, cytoplasmic mutant FUS incorporates into SGs, which increases SG volume and number, delays SG assembly, accelerates SG disassembly, and alters SG dynamics. I posit that mutant FUS association with stress granules is a toxic gain-of-function in ALS that alters the function of SGs by interaction with SG components. Here, I show that mutant FUS incorporates in to SGs via its Cterminal RGG motifs, the methylation of which is not required for this localization. Further, I identify protein interactions specific to full-length mutant FUS under stress conditions that are potentially capable of interacting with FUS in SGs. Finally, I demonstrate a potential change in the protein composition of SGs upon incorporation of mutant FUS. These findings advance the field of ALS and SG biology, thereby providing groundwork for future investigation.

Indiana University-Purdue University Indianapolis (IUPUI) / Carbon nanomaterials are widely produced and used in industry, medicine and scientific research. To examine the impact of exposure to nanoparticles on human health, the human airway epithelial cell line, Calu-3, was used to evaluate changes in the cellular proteome that could account for alterations in cellular function of airway epithelia after 24 h exposure to 10 μg/mL and 100 ng/mL of two common carbon nanoparticles, singleand multi-wall carbon nanotubes (SWCNT, MWCNT). After exposure to the nanoparticles, label-free quantitative mass spectrometry (LFQMS) was used to study differential protein expression. Ingenuity Pathway Analysis (IPA) was used to conduct a bioinformatics analysis of proteins identified by LFQMS. Interestingly, after exposure to a high concentration (10 μg/mL; 0.4 μg/cm2) of MWCNT or SWCNT, only 8 and 13 proteins, respectively, exhibited changes in abundance. In contrast, the abundance of hundreds of proteins was altered in response to a low concentration (100 ng/mL; 4 ng/cm2) of either CNT. Of the 281 and 282 proteins that were significantly altered in response to MWCNT or SWCNT, respectively, 231 proteins were the same. Bioinformatic analyses found that the proteins common to both kinds of nanotubes are associated with the cellular functions of cell death and survival, cell-to-cell signaling and interaction, cellular assembly and organization, cellular growth and proliferation, infectious disease, molecular transport and protein synthesis. The decrease in expression of the majority proteins suggests a general stress response to protect cells. The STRING database was used to analyze the various functional protein networks. Interestingly, some proteins like cadherin 1 (CDH1), signal transducer and activator of transcription 1 (STAT1), junction plakoglobin (JUP), and apoptosis-associated speck-like protein containing a CARD (PYCARD), appear in several functional categories and tend to be in the center of the networks. This central positioning suggests they may play important roles in multiple cellular functions and activities that are altered in response to carbon nanotube exposure. To examine the effect of nanotubes on the plasma membrane, we investigated the interaction of short purified MWCNT with model lipid membranes using a planar bilayer workstation. Bilayer lipid membranes were synthesized using neutral 1, 2-diphytanoylsn-glycero-3-phosphocholine (DPhPC) in 1 M KCl. The ion channel model protein, Gramicidin A (gA), was incorporated into the bilayers and used to measure the effect of MWCNT on ion transport. The opening and closing of ion channels, amplitude of current, and open probability and lifetime of ion channels were measured and analyzed by Clampfit. The presence of an intermediate concentration of MWCNT (2 μg/ml) could be related to a statistically significant decrease of the open probability and lifetime of gA channels. The proteomic studies revealed changes in response to CNT exposure. An analysis of the changes using multiple databases revealed alterations in pathways, which were consistent with the physiological changes that were observed in cultured cells exposed to very low concentrations of CNT. The physiological changes included the break down of the barrier function and the inhibition of the mucocillary clearance, both of which could increase the risk of CNT’s toxicity to human health. The biophysical studies indicate MWCNTs have an effect on single channel kinetics of Gramicidin A model cation channel. These changes are consistent with the inhibitory effect of nanoparticles on hormone stimulated transepithelial ion flux, but additional experiments will be necessary to substantiate this correlation.