Sepse é um importante problema de saúde pública, uma vez que seu tratamento gera altos custos a um sistema de saúde já sobrecarregado. É uma síndrome de alta mortalidade e morbidade que afeta, em geral, pacientes jovens com plena capacidade produtiva. A identificação e o tratamento precoce desta síndrome reduzem a morbimortalidade, assim como o custo. A proteína C reativa (PCR) e a procalcitonina (PCT) são bem estudadas como ferramentas para diagnóstico de infecção bacteriana em imunocompetentes, mas seu uso como ferramenta diagnóstica ainda não está estabelecido em pacientes imunossuprimidos. Portanto, a proposta deste estudo é avaliar a acurácia diagnóstica destes biomarcadores, em pacientes críticos imunossuprimidos (vírus da imunodeficiência adquirida  HIV positivos, portadores de tuberculose (TBC), cirróticos e transplantados). Como o uso da proteína C ainda não está estabelecido, a primeira questão de pesquisa investigou seu potencial diagnóstico quando comparado ao teste padrão (cultural). O segundo artigo comparou a PCR com a PCT. Para isto foram realizados dois artigos de revisão sistemática com metanálise. O primeiro artigo comparou a acurácia em determinar infecção bacteriana em imunossuprimidos da PCR ao teste padrão-ouro (as culturas). A primeira revisão incluiu 1.418 pacientes e demonstrou uma boa acurácia da PCR como biomarcador no diagnóstico de infecção bacteriana, apresentando sensibilidade de 69% e especificidade de 76% com uma área sob a curva (AUC) de 0,77. Os resultados encontrados são similares aos da literatura para imunocompetentes,(3) sensibilidade de 75%, especificidade de 67% e Área Sob a Curva Receiver Operating Characteristic (AUROC) de 0,92. Quando a PCT foi comparada com a PCR, ambos os biomarcadores mostraram acurácia moderada na utilização como ferrramenta de diagnóstico de infecção bacteriana, com um diagnóstico da razão de chances (DOR) de 7,24 (95% CI (2,83-14,60) para PCT e de 5,56 (95% CI (5,21-10,30) para PCR. A PCT e a PCR apresentaram sensibilidade de 69% e 68% e uma especificidade de 75% e 71%, respectivamente. Ambas mostraram resultados semelhantes, podendo ser utilizadas no diagnóstico de sepse em imunossupressos. / Sepsis is a major public health problem, since its treatment generates high costs, a health system already overburdened. A high mortality and morbidity syndrome affects, in general, young patients with full production capacity. The identification and early treatment of this syndrome reduce morbidity and mortality as well as the cost. C-reactive protein (CRP) and procalcitonin (PCT) are well studied as tools for diagnosis of bacterial infection in immunocompetent patients, but its use as a diagnostic tool is not yet established in immunocompromised patients. Therefore, the purpose of this study is to evaluate the diagnostic accuracy of these biomarkers in immunosuppresses critical patients (human immunodeficiency virus, cirrhotic and transplant). As the use of the c protein is not yet established, the first research question investigated their diagnostic potential when compared to the pattern (cultural). The second article compared to CRP and PCT. For this, there were two articles of a systematic review and meta-analysis. The first article compared the accuracy in determining bacterial infection in immunosuppresses of CRP to the gold standard (cultures). Our first review included 1,418 patients and showed good accuracy of CRP as a biomarker for the diagnosis of bacterial infection presenting a sensibility of 69% and 76% specificity with an area under the curve (AUC) 0.77. The results are similar to those found in the literature for immunocompetent,(3) sensitivity 75%, specificity of 67% and Area Under the Receiver Operating Characteristic Curve (AUROC): 0.92. When the PCT was compared with PCR, both biomarkers showed a moderately accurate for use as tool diagnostic bacterial infection with a Odds ratio diagnostic (DOR) 7.24 (95% CI (2.83-14.60) and PCT to 5:56 (95% CI (5.21-10.30) for CRP. the PCT and CRP had a sensitivity of 69% and 68% and a specificity of 75% and 71%, respectively. Both showed similar results may be used in the diagnosis of sepsis in immunosuppression.

Sepse é um importante problema de saúde pública, uma vez que seu tratamento gera altos custos a um sistema de saúde já sobrecarregado. É uma síndrome de alta mortalidade e morbidade que afeta, em geral, pacientes jovens com plena capacidade produtiva. A identificação e o tratamento precoce desta síndrome reduzem a morbimortalidade, assim como o custo. A proteína C reativa (PCR) e a procalcitonina (PCT) são bem estudadas como ferramentas para diagnóstico de infecção bacteriana em imunocompetentes, mas seu uso como ferramenta diagnóstica ainda não está estabelecido em pacientes imunossuprimidos. Portanto, a proposta deste estudo é avaliar a acurácia diagnóstica destes biomarcadores, em pacientes críticos imunossuprimidos (vírus da imunodeficiência adquirida  HIV positivos, portadores de tuberculose (TBC), cirróticos e transplantados). Como o uso da proteína C ainda não está estabelecido, a primeira questão de pesquisa investigou seu potencial diagnóstico quando comparado ao teste padrão (cultural). O segundo artigo comparou a PCR com a PCT. Para isto foram realizados dois artigos de revisão sistemática com metanálise. O primeiro artigo comparou a acurácia em determinar infecção bacteriana em imunossuprimidos da PCR ao teste padrão-ouro (as culturas). A primeira revisão incluiu 1.418 pacientes e demonstrou uma boa acurácia da PCR como biomarcador no diagnóstico de infecção bacteriana, apresentando sensibilidade de 69% e especificidade de 76% com uma área sob a curva (AUC) de 0,77. Os resultados encontrados são similares aos da literatura para imunocompetentes,(3) sensibilidade de 75%, especificidade de 67% e Área Sob a Curva Receiver Operating Characteristic (AUROC) de 0,92. Quando a PCT foi comparada com a PCR, ambos os biomarcadores mostraram acurácia moderada na utilização como ferrramenta de diagnóstico de infecção bacteriana, com um diagnóstico da razão de chances (DOR) de 7,24 (95% CI (2,83-14,60) para PCT e de 5,56 (95% CI (5,21-10,30) para PCR. A PCT e a PCR apresentaram sensibilidade de 69% e 68% e uma especificidade de 75% e 71%, respectivamente. Ambas mostraram resultados semelhantes, podendo ser utilizadas no diagnóstico de sepse em imunossupressos. / Sepsis is a major public health problem, since its treatment generates high costs, a health system already overburdened. A high mortality and morbidity syndrome affects, in general, young patients with full production capacity. The identification and early treatment of this syndrome reduce morbidity and mortality as well as the cost. C-reactive protein (CRP) and procalcitonin (PCT) are well studied as tools for diagnosis of bacterial infection in immunocompetent patients, but its use as a diagnostic tool is not yet established in immunocompromised patients. Therefore, the purpose of this study is to evaluate the diagnostic accuracy of these biomarkers in immunosuppresses critical patients (human immunodeficiency virus, cirrhotic and transplant). As the use of the c protein is not yet established, the first research question investigated their diagnostic potential when compared to the pattern (cultural). The second article compared to CRP and PCT. For this, there were two articles of a systematic review and meta-analysis. The first article compared the accuracy in determining bacterial infection in immunosuppresses of CRP to the gold standard (cultures). Our first review included 1,418 patients and showed good accuracy of CRP as a biomarker for the diagnosis of bacterial infection presenting a sensibility of 69% and 76% specificity with an area under the curve (AUC) 0.77. The results are similar to those found in the literature for immunocompetent,(3) sensitivity 75%, specificity of 67% and Area Under the Receiver Operating Characteristic Curve (AUROC): 0.92. When the PCT was compared with PCR, both biomarkers showed a moderately accurate for use as tool diagnostic bacterial infection with a Odds ratio diagnostic (DOR) 7.24 (95% CI (2.83-14.60) and PCT to 5:56 (95% CI (5.21-10.30) for CRP. the PCT and CRP had a sensitivity of 69% and 68% and a specificity of 75% and 71%, respectively. Both showed similar results may be used in the diagnosis of sepsis in immunosuppression.

Introdução: A esquizofrenia é um transtorno mental grave e debilitante, que afeta o paciente tanto na sua saúde física como na diminuição de sua capacidade funcional, causando um grande comprometimento ao longo da vida. Apesar de ser possível que o prejuízo em motricidade e prejuízo cognitivo possam representar expressão de um mesmo processo inflamatório sistêmico, pouco se sabe sobre a relação entre motricidade e esquizofrenia. Objetivos: Avaliar a capacidade funcional motora em pacientes esquizofrênicos correlacionando com marcadores inflamatórios, gravidade de doença e tratamento medicamentoso. Métodos: Estudo transversal, por amostra de conveniência, aprovado pelo comitê de ética do Hospital de Clínicas de Porto Alegre (HCPA). Foram recrutados 40 indivíduos com esquizofrenia estabilizada, em tratamento no ambulatório do HCPA. Foi avaliada a capacidade funcional motora através do Teste de Caminhada de 6 Minutos. O nível de significância adotado foi de 5% para todas as variáveis e as análises foram realizadas no programa Statistical Package for the Social Sciences (SPSS, versão 21.0). Resultados: A amostra foi estratificada por anos de doença através do percentil 25, onde apresentou significância no estado civil apresentando uma maior frequência de solteiros e separados em pacientes com o maior tempo de doença (p=0.022). As médias das variáveis funcionais e clínicas laborais que comparadas com médias populacionais apresentaram significância foram: frequência cardíaca (p=0.004), pressão arterial diastólica e sistólica (p=0.001 e p<0.001), frequência respiratória (p<0.001), Proteína C reativa (p=0.015), borg (p<0.001) e Tc6m em homens e mulheres (p<0.001 e p=0.024). No desempenho funcional e dispneia houve uma correlação com a proteína C reativa (r=-0,369 e r= 0,535). Conclusão: O presente estudo mostrou a associação entre o prejuízo funcional com marcadores inflamatórios, principalmente com níveis elevados de PCR. Alterações clínicas foram associadas como reações adversas a utilização de antipsicóticos, apesar de não ser possível descartar também mecanismos inflamatórios antecedendo ambas as alterações. O prejuízo na capacidade funcional associado com aumento da PCR sugere um paciente com sinais de deterioração maior. Todos achados deste estudo apresentam uma contribuição para o entendimento do processo psicótico e abrem caminho para novas intervenções terapêuticas. / Introduction: Schizophrenia is a severe, debilitating mental disorder that affects both the physical health and the functional capacity of patients, causing great impairment throughout the life course. Although physical and cognitive impairments may represent different expressions of a single systemic inflammatory process, little is known about the relationship between motor function and schizophrenia. Objective: To evaluate physical functional capacity in patients with schizophrenia and ascertain whether it correlates with markers of inflammation, disease severity, and pharmacotherapy. Methods: Cross-sectional study using a convenience sampling strategy. Forty patients with stable schizophrenia, undergoing treatment, were recruited from the outpatient psychiatry clinic of Hospital de Clínicas de Porto Alegre (HCPA), a tertiary referral center in Southern Brazil. The 6-minute walk test (6MWT) was used to assess physical functional capacity. The significance level was set at 5% for all variables, and all statistical analyses were carried out in SPSS 21.0. The study was approved by the HCPA Research Ethics Committee. Results: The sample was homogeneous and normally distributed. Subjects were stratified by disease duration, which was significantly associated only with marital status (p=0.022). Comparison of mean functional and clinical variables to population averages showed significant differences in heart rate (p=0.004), diastolic (p=0.001) and systolic (p<0.001) blood pressure, respiratory rate (p<0.001), C-reactive protein levels (p=0.015), Borg Scale of Perceived Exertion scores (p<0.001), and 6MWT distances in men (p<0.001) and women (p=0.024). Conclusion: The present study detected an association between functional impairment and markers of inflammation, especially elevated CRP levels, in patients with schizophrenia. Clinical changes were associated with adverse reactions to antipsychotics, although underlying inflammatory mechanisms could not be ruled out. The loss of functional capacity associated with increased CRP suggests a patient with signs of deterioration increased. The findings of this study contribute to current understanding of the psychotic process and may pave the way for novel therapeutic interventions.

Introdução: A esquizofrenia é um transtorno mental grave e debilitante, que afeta o paciente tanto na sua saúde física como na diminuição de sua capacidade funcional, causando um grande comprometimento ao longo da vida. Apesar de ser possível que o prejuízo em motricidade e prejuízo cognitivo possam representar expressão de um mesmo processo inflamatório sistêmico, pouco se sabe sobre a relação entre motricidade e esquizofrenia. Objetivos: Avaliar a capacidade funcional motora em pacientes esquizofrênicos correlacionando com marcadores inflamatórios, gravidade de doença e tratamento medicamentoso. Métodos: Estudo transversal, por amostra de conveniência, aprovado pelo comitê de ética do Hospital de Clínicas de Porto Alegre (HCPA). Foram recrutados 40 indivíduos com esquizofrenia estabilizada, em tratamento no ambulatório do HCPA. Foi avaliada a capacidade funcional motora através do Teste de Caminhada de 6 Minutos. O nível de significância adotado foi de 5% para todas as variáveis e as análises foram realizadas no programa Statistical Package for the Social Sciences (SPSS, versão 21.0). Resultados: A amostra foi estratificada por anos de doença através do percentil 25, onde apresentou significância no estado civil apresentando uma maior frequência de solteiros e separados em pacientes com o maior tempo de doença (p=0.022). As médias das variáveis funcionais e clínicas laborais que comparadas com médias populacionais apresentaram significância foram: frequência cardíaca (p=0.004), pressão arterial diastólica e sistólica (p=0.001 e p<0.001), frequência respiratória (p<0.001), Proteína C reativa (p=0.015), borg (p<0.001) e Tc6m em homens e mulheres (p<0.001 e p=0.024). No desempenho funcional e dispneia houve uma correlação com a proteína C reativa (r=-0,369 e r= 0,535). Conclusão: O presente estudo mostrou a associação entre o prejuízo funcional com marcadores inflamatórios, principalmente com níveis elevados de PCR. Alterações clínicas foram associadas como reações adversas a utilização de antipsicóticos, apesar de não ser possível descartar também mecanismos inflamatórios antecedendo ambas as alterações. O prejuízo na capacidade funcional associado com aumento da PCR sugere um paciente com sinais de deterioração maior. Todos achados deste estudo apresentam uma contribuição para o entendimento do processo psicótico e abrem caminho para novas intervenções terapêuticas. / Introduction: Schizophrenia is a severe, debilitating mental disorder that affects both the physical health and the functional capacity of patients, causing great impairment throughout the life course. Although physical and cognitive impairments may represent different expressions of a single systemic inflammatory process, little is known about the relationship between motor function and schizophrenia. Objective: To evaluate physical functional capacity in patients with schizophrenia and ascertain whether it correlates with markers of inflammation, disease severity, and pharmacotherapy. Methods: Cross-sectional study using a convenience sampling strategy. Forty patients with stable schizophrenia, undergoing treatment, were recruited from the outpatient psychiatry clinic of Hospital de Clínicas de Porto Alegre (HCPA), a tertiary referral center in Southern Brazil. The 6-minute walk test (6MWT) was used to assess physical functional capacity. The significance level was set at 5% for all variables, and all statistical analyses were carried out in SPSS 21.0. The study was approved by the HCPA Research Ethics Committee. Results: The sample was homogeneous and normally distributed. Subjects were stratified by disease duration, which was significantly associated only with marital status (p=0.022). Comparison of mean functional and clinical variables to population averages showed significant differences in heart rate (p=0.004), diastolic (p=0.001) and systolic (p<0.001) blood pressure, respiratory rate (p<0.001), C-reactive protein levels (p=0.015), Borg Scale of Perceived Exertion scores (p<0.001), and 6MWT distances in men (p<0.001) and women (p=0.024). Conclusion: The present study detected an association between functional impairment and markers of inflammation, especially elevated CRP levels, in patients with schizophrenia. Clinical changes were associated with adverse reactions to antipsychotics, although underlying inflammatory mechanisms could not be ruled out. The loss of functional capacity associated with increased CRP suggests a patient with signs of deterioration increased. The findings of this study contribute to current understanding of the psychotic process and may pave the way for novel therapeutic interventions.

Introdução: A esquizofrenia é um transtorno mental grave e debilitante, que afeta o paciente tanto na sua saúde física como na diminuição de sua capacidade funcional, causando um grande comprometimento ao longo da vida. Apesar de ser possível que o prejuízo em motricidade e prejuízo cognitivo possam representar expressão de um mesmo processo inflamatório sistêmico, pouco se sabe sobre a relação entre motricidade e esquizofrenia. Objetivos: Avaliar a capacidade funcional motora em pacientes esquizofrênicos correlacionando com marcadores inflamatórios, gravidade de doença e tratamento medicamentoso. Métodos: Estudo transversal, por amostra de conveniência, aprovado pelo comitê de ética do Hospital de Clínicas de Porto Alegre (HCPA). Foram recrutados 40 indivíduos com esquizofrenia estabilizada, em tratamento no ambulatório do HCPA. Foi avaliada a capacidade funcional motora através do Teste de Caminhada de 6 Minutos. O nível de significância adotado foi de 5% para todas as variáveis e as análises foram realizadas no programa Statistical Package for the Social Sciences (SPSS, versão 21.0). Resultados: A amostra foi estratificada por anos de doença através do percentil 25, onde apresentou significância no estado civil apresentando uma maior frequência de solteiros e separados em pacientes com o maior tempo de doença (p=0.022). As médias das variáveis funcionais e clínicas laborais que comparadas com médias populacionais apresentaram significância foram: frequência cardíaca (p=0.004), pressão arterial diastólica e sistólica (p=0.001 e p<0.001), frequência respiratória (p<0.001), Proteína C reativa (p=0.015), borg (p<0.001) e Tc6m em homens e mulheres (p<0.001 e p=0.024). No desempenho funcional e dispneia houve uma correlação com a proteína C reativa (r=-0,369 e r= 0,535). Conclusão: O presente estudo mostrou a associação entre o prejuízo funcional com marcadores inflamatórios, principalmente com níveis elevados de PCR. Alterações clínicas foram associadas como reações adversas a utilização de antipsicóticos, apesar de não ser possível descartar também mecanismos inflamatórios antecedendo ambas as alterações. O prejuízo na capacidade funcional associado com aumento da PCR sugere um paciente com sinais de deterioração maior. Todos achados deste estudo apresentam uma contribuição para o entendimento do processo psicótico e abrem caminho para novas intervenções terapêuticas. / Introduction: Schizophrenia is a severe, debilitating mental disorder that affects both the physical health and the functional capacity of patients, causing great impairment throughout the life course. Although physical and cognitive impairments may represent different expressions of a single systemic inflammatory process, little is known about the relationship between motor function and schizophrenia. Objective: To evaluate physical functional capacity in patients with schizophrenia and ascertain whether it correlates with markers of inflammation, disease severity, and pharmacotherapy. Methods: Cross-sectional study using a convenience sampling strategy. Forty patients with stable schizophrenia, undergoing treatment, were recruited from the outpatient psychiatry clinic of Hospital de Clínicas de Porto Alegre (HCPA), a tertiary referral center in Southern Brazil. The 6-minute walk test (6MWT) was used to assess physical functional capacity. The significance level was set at 5% for all variables, and all statistical analyses were carried out in SPSS 21.0. The study was approved by the HCPA Research Ethics Committee. Results: The sample was homogeneous and normally distributed. Subjects were stratified by disease duration, which was significantly associated only with marital status (p=0.022). Comparison of mean functional and clinical variables to population averages showed significant differences in heart rate (p=0.004), diastolic (p=0.001) and systolic (p<0.001) blood pressure, respiratory rate (p<0.001), C-reactive protein levels (p=0.015), Borg Scale of Perceived Exertion scores (p<0.001), and 6MWT distances in men (p<0.001) and women (p=0.024). Conclusion: The present study detected an association between functional impairment and markers of inflammation, especially elevated CRP levels, in patients with schizophrenia. Clinical changes were associated with adverse reactions to antipsychotics, although underlying inflammatory mechanisms could not be ruled out. The loss of functional capacity associated with increased CRP suggests a patient with signs of deterioration increased. The findings of this study contribute to current understanding of the psychotic process and may pave the way for novel therapeutic interventions.

Inflammatory models of neurodegeneration suggest that higher circulating levels of inflammation can lead to cognitive decline. Despite established independent associations between greater body mass, increased inflammation, and cognitive decline, no prior research has explored whether markers of systemic inflammation might mediate the association between body mass and changes in cognitive functioning. To test such a model, we used two longitudinal subsamples (ns = 9066; 12,561) of aging adults from the English Longitudinal Study of Ageing (ELSA) study, which included two cognitive measures components of memory and executive functioning, as well as measurements of body mass and systemic inflammation, assessed via C-reactive protein (CRP). Greater body mass was indirectly associated with declines in memory and executive functioning over 6 years via relatively higher levels of CRP. Our results suggest that systemic inflammation is one biologically plausible mechanism through which differences in body mass might influence changes in cognitive functioning among aging adults.

Abstract To date, most epidemiological studies have shown a weak or moderate association between dental diseases such as periodontal infections, dental caries and tooth loss, and atherosclerotic vascular diseases. However, the nature of this association is not known; it may be due to the biological effect of oral infections on initiation or progress of atherosclerosis or it may be non-causal due to determinants in common, either biological or behavioural. Methodological shortcomings, inconsistent results and a lack of definite proof from intervention studies have led to the conclusion that causality between dental diseases and atherosclerotic vascular diseases has not been established. The aim of this study was to produce evidence on the nature of the association between dental diseases and atherosclerotic vascular diseases. The study uses data from the 1966 Birth Cohort of Northern Finland (N = 11,637). The data were collected in 1997–1998, when the cohort members had reached 31 years of age. The respondents were asked through a postal questionnaire about their oral health. In addition, respondents were asked about their general health and oral and general health habits. The response rate was 75.3%. Those who lived in Northern Finland or the capital city region were invited to clinical health examination (N = 8,463). Altogether 5,696 subjects supplied the data, representing 67.3% of those who were invited to the clinical examination. While the study showed an association of self-reported gingivitis, dental caries and tooth loss with the prevalent angina pectoris, it also showed that these self-reported dental diseases were not important determinants for elevated C-reactive protein levels. This suggests that the associations that were found between dental conditions and prevalent angina pectoris are mainly caused by factors other than biological mechanisms related to infection or inflammation. The lack of a biological explanation related to infections or inflammatory processes suggests that other biological mechanisms or biases, including confounding, should be considered as an alternative explanation. However, it must be noted that the possibility that oral infections also contribute to the development of atherosclerosis should not be rejected either.

Previous studies on the medical use of ozone therapies show a very diverse array of results, from ozone reducing the amount of HIV virus in the blood, to no effect, to causing the death of several patients due to pulmonary embolism and infections. However, ozone therapies are widely used in Europe and considered medically safe. In the U.S., doctors in 28 states use ozone therapies. The objectives of this study were to investigate the effects of medical grade ozone at varying concentrations used in ozone therapies. These were achieved by evaluating the C-reactive protein, erythrocyte sedimentation rate, total reduced and oxidized glutathione content of erythrocytes which were all markers used to determine ozone injury/inflammation. Despite the fact that ozone is a very strong oxidant, previous research indicates that depending on the dose and the health status of the biological system, sometimes ozone can act as an antioxidant. The medical exposure range for ozone is between 20-80 mg/ml with an average of 50 mg/ml. The concentrations used in this study were 20, 40, 80 and 160 mg/ml. Ozone was generated in the "Breath Lab" at USF from medical grade oxygen obtained through electrical corona arc discharge using an OL80C ozone generator. De-identified blood samples of 10 ml blood/sample containing EDTA as anticoagulant were obtained from the James A. Haley VA Hospital patients. Equal volumes of blood and ozone gas mixture were allowed to mix in ozone-resistant syringes prior to dividing each sample into three parts, one for each corresponding parameter to be studied. The C-reactive protein was analyzed through ELISA using the colorimetric method available from Helica Biosystems; erythrocyte sedimentation rate was measured in graduated sedimentation tubes; the total reduced glutathione (GSH) and oxidized glutathione (GSSG) content of erythrocytes was determined according to the colorimetric method developed by the Oxford Biomedical Research. Overall, the concentrations of ozone used did not have a statistically significant effect on the parameters investigated. However, a small percentage of the blood samples showed an improvement in the parameters studied, especially at the highest ozone concentration.

Receiving a breast cancer (BC) diagnosis generates significant physical and psychological stress that may persist months, years, or even decades beyond treatment completion. Such chronic stress can severely alter the biological systems of BC survivors (BCS). Yet, little is known about the impact and associated variables of these long-term physiological sequelae. Considering that the number of BCS continues to grow each year, it is imperative to assess the extent to which a BC experience impacts human physiological mechanisms by examining the secretion patterns of associated stress- and immune-related biomarkers and by exploring the behavioural, physical, and psychological variables implicated in these dysregulations. Such research is of particular importance in order to guide cancer survivorship care and develop interventions promoting optimal health outcomes in BCS. This research program sought to address this through three inter-related studies. Study One was a quasi-experimental design study examining both the diurnal and reactive concentration patterns of secretory immunoglobulin A (SIgA) in a sample of women with (n = 22) and without a prior history of BC (n = 26). SIgA concentration patterns were contrasted to concentration patterns of cortisol and salivary alpha-amylase (sAA) in the same individuals (complementary to two previously published studies). Participants supplied saliva samples at five time points on two consecutive typical days (for diurnal data) and at seven time points before, during, and after an acute laboratory stressor (for reactive data). Results reveled no evidence of uncharacteristic SIgA diurnal or reactive concentration patterns, suggesting a normal and well-functioning immunological SIgA system in BCS on average 4.6 years post-diagnosis. Study One acted as a summary article allowing readers to grasp the "big picture" of long-term physiological dysregulations in BCS as a whole. Building on this, Study Two, which used the same dataset as Study One, aimed to determine whether physical activity (PA) could mitigate the adverse physiological effects of a BC experience in BCS (n = 25), as indexed by their cortisol concentration patterns. Participants self-reported their PA frequency and engaged in the same cortisol assay protocol reported in Study One. Results indicated no statistically significant differences in diurnal and reactive cortisol patterns between low- and high-PA groups. A trend that PA might not have the same effect on women with and without a history of BC was noted. Important limitations to Study Two included the small sample size and the lack of sensitivity and objectivity of the PA measure. To address Study Two’s limitations and to consider a wider range of modifiable variables that could contribute to the physiological dysregulations observed in BCS, Study Three aimed to assess the predictive value of six behavioural, physical, and psychological variables on the physiological effects of a BC experience, as indexed by cortisol (n = 192) and C-reactive protein (CRP; n = 168) levels over the first 1.5 year post-treatment. CRP, a biomarker that had not been considered so far in this research program, allowed to assess systemic inflammation in BCS post-treatment. Study Three also aimed to describe naturally occurring changes in cortisol and CRP levels and assess whether they changed in tandem. Data were drawn from 201 BCS who provided capillary blood and saliva samples at approximately 3.5 months post-treatment and again 3, 6, 9, and 12 months later. At each time point, participants also completed self-report questionnaires and wore an accelerometer for seven consecutive days. Multilevel modeling analyses revealed no significant change over time for cortisol levels post-treatment and a non-linear trajectory of change for CRP levels which was not predicted by cortisol levels. Associations between cortisol and sedentary time as well as associations between CRP and PA, body mass index, and health- and cancer-related stress were found. Collectively, these three inter-related studies uniquely add to the literature by describing long-term physiological trajectories of stress- and immune-related biomarkers in BCS. This research program attempts to gain a better understanding of the underlying mechanisms that tie behavioural, physical, and psychological variables and biomarker secretion to a BC experience. It also offers opportunities to identify women at greater risk of physiological dysregulations following a BC experience. This represents an important step towards the development of tailored interventions targeting specific BCS that most warrant them. With the number of BCS climbing each year, cancer survivorship needs to be a priority in research and efforts to better understand, monitor, and mitigate the physiological consequences of a BC experience are critical.

Background: Elevation of C-reactive protein (CRP) levels in blood was recognized as one of the cardiac disease risk factors. Consumption of wine is shown to reduce the risk from heart disease and improve longevity. Objectives: In the present study, we evaluated the effect of various wine polyphenolic compounds and several active synthetic derivatives of resveratrol on the inflammatory cytokines (IL-1β+IL-6)-induced CRP expression in Hep3B cells. Results: Among the wine phenolics tested, quercetin and resveratrol, in a dose-dependent manner, suppressed cytokine-induced CRP expression. Two of the synthetic derivatives of resveratrol, R3 and 7b, elicited a fiftyfold higher suppressive effect compared with resveratrol. The inhibitory effects of resveratrol and its derivatives on CRP expression were at the level of mRNA production. Investigation of signaling pathways showed that the cytokines induced the phosphorylation of p38 and p44/42 MAP kinases. Inhibitors of p38 and p44/42 mitogen-activated protein kinase (MAPK) activation inhibited CRP expression, implicating the involvement of both pathways in cytokine-induced CRP expression. These data revealed a previously unrecognized role of the p44/42 MAPK signaling pathway in CRP expression. Wine polyphenolics or the synthetic compounds of resveratrol did not affect cytokine-activated phosphorylation of these MAPKs. Conclusions: Wine phenolics inhibit CRP expression; however, to do so, they do not utilize the MAPK pathways.