Immunohistochemical expression of epithelial and stromal immunomodulatory signalling molecules is a prognostic indicator in breast cancer

<p>Abstract</p> <p>Background</p> <p>The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells.</p> <p>Methods</p> <p>On immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity.</p> <p>Results</p> <p>The expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both <it>P </it>< 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (<it>P </it>= 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both <it>P </it>< 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (<it>P </it>< 0.001), whereas in the metastases the expression was highest in tumor cell areas (<it>P </it>< 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (<it>P </it>< 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality.</p> <p>Conclusions</p> <p>Stromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer.</p

Trends in prevalence of ultrasound-assessed carotid atherosclerosis in a general population over time. The Tromsø Study 1994-2016

Background: During the past decades, there has been a shift in risk factor levels in many high-income countries, with decrease in smoking, blood pressure and cholesterol levels, while body mass index, obesity and diabetes increase. The diverging trends may have opposite effects on prevalence of atherosclerosis. We aimed to assess carotid plaque prevalence and the association with risk factor levels in a general population over a period of 22 years. Methods: Prevalence of plaque, number of plaques and total plaque area in the carotid arteries were assessed in three repeated cross-sectional surveys of the population-based Tromsø Study from 1994 through 2016. The number of participants from the first to the last survey was 6362, 7069 and 3021. All surveys included physical examinations, questionnaires, and blood samples. Multivariable logistic regression analysis models were fitted to assess the relationship between risk factors and carotid plaque. Results: We found no significant change in plaque burden over a period of 22 years, neither when measured as plaque presence, plaque number or total plaque area. Plaques were more frequent in men (70%) than in women (59.4%) and increased by age. Systolic blood pressure and smoking increased, while BMI and diabetes decreased over time both in participants with and without plaque. Most risk factors remained higher in participants with plaque than in plaque- free participants while cholesterol levels decreased and reached similar levels in both groups. Age, male sex, systolic blood pressure, smoking, diabetes and HDL cholesterol (inverse) were associated with plaque prevalence. Conclusions: Plaque prevalence remained stable in the observation period. Favorable reductions in systolic blood pressure, cholesterol and smoking may have been partly counteracted by increased diabetes prevalence. Risk factor levels remained higher in participants with plaque than in plaque-free participants, indicating a potential for further improvement in primary prevention of carotid atherosclerosis

Evaluation of error production in animal fluency and its relationship to frontal tracts in normal aging and mild Alzheimer's disease: A combined LDA and time-course analysis investigation

Semantic verbal fluency (VF), assessed by animal category, is a task widely used for early detection of dementia. A feature not regularly assessed is the occurrence of errors such as perseverations and intrusions. So far, no investigation has analyzed the how and when of error occurrence during semantic VF in aging populations, together with their possible neural correlates. The present study aims to address the issue using a combined methodology based on latent Dirichlet allocation (LDA) analysis for word classification together with a time-course analysis identifying exact time of errors’ occurrence. LDA is a modeling technique that discloses hidden semantic structures based on a given corpus of documents. We evaluated a sample of 66 participants divided into a healthy young group (n = 24), healthy older adult group (n = 23), and group of patients with mild Alzheimer’s disease (AD) (n = 19). We performed DTI analyses to evaluate the white matter integrity of three frontal tracts purportedly underlying error commission: anterior thalamic radiation, frontal aslant tract, and uncinate fasciculus. Contrasts of DTI metrics were performed on the older groups who were further classified into high-error rate and low-error rate subgroups. Results demonstrated a unique deployment of error commission in the patient group characterized by high incidence of intrusions in the first 15 s and higher rate of perseverations toward the end of the trial. Healthy groups predominantly showed very low incidence of perseverations. The DTI analyses revealed that the patients with AD committing high-error rate presented significantly more degenerated frontal tracts in the left hemisphere. Thus, our findings demonstrated that the appearance of intrusions, together with left hemisphere degeneration of frontal tracts, is a pathognomic trait of mild AD. Furthermore, our data suggest that the error commission of patients with AD arises from executive and working memory impairments related partly to deteriorated left frontal tracts

Healthcare professionals' knowledge of modifiable stroke risk factors: A cross-sectional questionnaire survey in greater Gaborone, Botswana

Background - Stroke remains the second leading cause of deaths and disability globally, with highest mortality in Africa (low- and middle-income countries). It is crucial for healthcare professionals to have sufficient stroke risk factors' knowledge in order to reduce the stroke burden. Aims - We investigated healthcare professionals' knowledge of modifiable stroke risk factors, and identified demographic factors influencing this knowledge. Methods - In this cross-sectional survey study from Botswana (upper middle-income country), structured questionnaires reflecting recent stroke guidelines were administered to a representative selection of healthcare workers in greater Gaborone. The response rate was 61.4%, comprising 84 doctors, 227 nurses and 33 paramedics. Categorical data were described using percentages and Chi-square tests. Associations between stroke risk factors' knowledge and demographic factors were analyzed with one-way ANOVA using SPSS 25 statistical software. Results - Awareness rate of individual stroke risk factors was highest for hypertension (96.5%), followed by obesity (93.3%), smoking (91.9%), elevated total cholesterol (91.0%), physical inactivity (83.4%), elevated low-density lipoprotein (LDL) cholesterol (81.1%), excessive alcohol drinking (77.0%), and lowest for diabetes (73.3%). For all-8 risk factors, doctors had the highest knowledge, followed by nurses and paramedics lowest (7.11 vs 6.85 vs 6.06, P < 0.05)

The association between anthropometric measures of adiposity and the progression of carotid atherosclerosis.

BACKGROUND: Few reports are available on the contribution of general and abdominal obesity to the progression of carotid atherosclerosis in late adulthood. This study investigated the impact of four simple anthropometric measures of general and abdominal obesity on the progression of carotid atherosclerosis and the extent to which the association between adiposity and the progression of plaque burden is mediated by cardiometabolic markers. METHODS: Four thousand three hundred forty-five adults (median age 60) from the population-based Tromsø Study were followed over 7 years from the first carotid ultrasound screening to the next. The progression of carotid atherosclerosis was measured in three ways: incidence of plaques in previously plaque-free participants; change in the number of plaques; and total plaque area (TPA). We used generalised linear models to investigate the association between each adiposity measure - body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) - and each outcome. Models were adjusted for potential confounders (age, sex, smoking, education, physical activity). The pathways through which any associations observed might operate were investigated by further adjusting for cardiometabolic mediators (systolic blood pressure, cholesterol, and HbA1c). RESULTS: There was little evidence that adiposity was related to the formation of new plaques during follow-up. However, abdominal adiposity was associated with TPA progression. WHtR showed the largest effect size (mean change in TPA per one standard deviation (SD) increase in WHtR of 0.665 mm2, 95% confidence interval 0.198, 1.133) while BMI showed the smallest. Effect sizes were substantially reduced after the adjustment for potential mediators. CONCLUSIONS: Abdominal obesity indirectly measured with WC seems more strongly associated with the progression of TPA than general obesity. These associations appear to be largely mediated by known cardiometabolic markers

The contribution of obesity to carotid atherosclerotic plaque burden in a general population sample in Norway: The Tromsø Study.

BACKGROUND AND AIMS: Few studies have investigated the association of different measures of adiposity with carotid plaque. We aimed to investigate and compare the associations of four measures of adiposity: body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) with the presence of carotid plaque and total plaque area (TPA) in the right carotid artery. METHODS: We included 4906 individuals aged 31-88 years who participated in a population-based study with ultrasonography of the right carotid artery. Adiposity measures were converted to sex-specific SD units to allow comparison of effect sizes. TPA was log transformed due to its skewed distribution. Logistic and linear regression models were used respectively to investigate the association of each adiposity measure with the presence of plaque and with log-transformed TPA. Estimates were adjusted for potential confounders and mediators such as blood pressure and lipids. RESULTS: After adjustment for age, sex, smoking, and education level, there was strong evidence of an association between all adiposity measures and log-transformed TPA, whereas only WHR was weakly associated with presence of plaque. WHR showed the largest adjusted effect size for both log-transformed TPA (beta 0.055, 95%CI 0.028-0.081) and the presence of plaque (OR 1.07, 95%CI 1.01-1.15). Adjustment for mediators led to appreciable attenuation of observed effects. CONCLUSIONS: Adiposity is more consistently associated with extent of plaque burden than with whether an individual does or does not have any plaque. There was evidence that established biomarkers mediate much of this association. Abdominal adiposity appears to show the strongest effect

The contribution of obesity to carotid atherosclerotic plaque burden in a general population sample in Norway: The Tromsø Study.

BACKGROUND AND AIMS: Few studies have investigated the association of different measures of adiposity with carotid plaque. We aimed to investigate and compare the associations of four measures of adiposity: body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) with the presence of carotid plaque and total plaque area (TPA) in the right carotid artery. METHODS: We included 4906 individuals aged 31-88 years who participated in a population-based study with ultrasonography of the right carotid artery. Adiposity measures were converted to sex-specific SD units to allow comparison of effect sizes. TPA was log transformed due to its skewed distribution. Logistic and linear regression models were used respectively to investigate the association of each adiposity measure with the presence of plaque and with log-transformed TPA. Estimates were adjusted for potential confounders and mediators such as blood pressure and lipids. RESULTS: After adjustment for age, sex, smoking, and education level, there was strong evidence of an association between all adiposity measures and log-transformed TPA, whereas only WHR was weakly associated with presence of plaque. WHR showed the largest adjusted effect size for both log-transformed TPA (beta 0.055, 95%CI 0.028-0.081) and the presence of plaque (OR 1.07, 95%CI 1.01-1.15). Adjustment for mediators led to appreciable attenuation of observed effects. CONCLUSIONS: Adiposity is more consistently associated with extent of plaque burden than with whether an individual does or does not have any plaque. There was evidence that established biomarkers mediate much of this association. Abdominal adiposity appears to show the strongest effect