Myelin Basic Protein-Induced Production of Tumor Necrosis Factor-α and Interleukin-6, and Presentation of the Immunodominant Peptide MBP85-99 by B Cells from Patients with Relapsing-Remitting Multiple Sclerosis

B cells are involved in driving relapsing-remitting multiple sclerosis (RRMS), as demonstrated by the positive effect of therapeutic B-cell depletion. Aside from producing antibodies, B cells are efficient antigen-presenting and cytokine-secreting cells. Diverse polyclonal stimuli have been used to study cytokine production by B cells, but here we used the physiologically relevant self-antigen myelin basic protein (MBP) to stimulate B cells from untreated patients with RRMS and healthy donors. Moreover, we took advantage of the unique ability of the monoclonal antibody MK16 to recognize the immunodominant peptide MBP85-99 presented on HLA-DR15, and used it as a probe to directly study B-cell presentation of self-antigenic peptide. The proportions of B cells producing TNF-α or IL-6 after stimulation with MBP were higher in RRMS patients than in healthy donors, indicating a pro-inflammatory profile for self-reactive patient B cells. In contrast, polyclonal stimulation with PMA + ionomycin and MBP revealed no difference in cytokine profile between B cells from RRMS patients and healthy donors. Expanded disability status scale (EDSS) as well as multiple sclerosis severity score (MSSS) correlated with reduced ability of B cells to produce IL-10 after stimulation with MBP, indicative of diminished B-cell immune regulatory function in patients with the most severe disease. Moreover, EDSS correlated positively with the frequencies of TNF-α, IL-6 and IL-10 producing B cells after polyclonal stimulation. Patient-derived, IL-10-producing B cells presented MBP85-99 poorly, as did IL-6-producing B cells, particulary in the healthy donor group. B cells from MS patients thus present antigen to T cells in a pro-inflammatory context. These findings contribute to understanding the therapeutic effects of B-cell depletion in human autoimmune diseases, including MS

The association between perceived stress and mortality among people with multimorbidity: a prospective population-based cohort study

Multimorbidity is common and is associated with poor mental health and high mortality. Nevertheless, no studies have evaluated whether mental health may affect the survival of people with multimorbidity. We investigated the association between perceived stress and mortality in people with multimorbidity by following a population-based cohort of 118,410 participants from the Danish National Health Survey 2010 for up to 4 years. Information on perceived stress and lifestyle was obtained from the survey. We assessed multimorbidity using nationwide register data on 39 conditions and identified 4,229 deaths for the 453,648 person-years at risk. Mortality rates rose with increasing levels of stress in a dose-response relationship (P-trend < 0.0001), independently of multimorbidity status. Mortality hazard ratios (highest stress quintile vs. lowest) were 1.51 (95% confidence interval (CI): 1.25, 1.84) among persons without multimorbidity, 1.39 (95% CI: 1.18, 1.64) among those with 2 or 3 conditions, and 1.43 (95% CI: 1.18, 1.73) among those with 4 or more conditions, when adjusted for disease severities, lifestyle, and socioeconomic status. The numbers of excess deaths associated with high stress were 69 among persons without multimorbidity, 128 among those with 2 or 3 conditions, and 255 among those with 4 or more conditions. Our findings suggested that perceived stress contributes significantly to higher mortality rates in a dose-response pattern, and more stress-associated deaths occurred in people with multimorbidity

Health promotion in primary and secondary schools in Denmark:time trends and associations with schools' and students' characteristics

BACKGROUND: Schools are important arenas for interventions among children as health promoting initiatives in childhood is expected to have substantial influence on health and well-being in adulthood. In countries with compulsory school attention, all children could potentially benefit from health promotion at the school level regardless of socioeconomic status or other background factors. The first aim was to elucidate time trends in the number and types of school health promoting activities by describing the number and type of health promoting activities in primary and secondary schools in Denmark. The second aim was to investigate which characteristics of schools and students that are associated with participation in many (≥3) versus few (0–2) health promoting activities during the preceding 2–3 years. METHODS: We used cross-sectional data from the 2006- and 2010-survey of the Health Behaviour in School-aged Children study. The headmasters answered questions about the school’s participation in health promoting activities and about school size, proportion of ethnic minorities, school facilities available for health promoting activities, competing problems and resources at the school and in the neighborhood. Students provided information about their health-related behavior and exposure to bullying which was aggregated to the school level. A total of 74 schools were available for analyses in 2006 and 69 in 2010. We used chi-square test, t-test, and binary logistic regression to analyze time trends and differences between schools engaging in many versus few health promoting activities. RESULTS: The percentage of schools participating in ≥3 health promoting activities was 63% in 2006 and 61% in 2010. Also the mean number of health promoting activities was similar (3.14 vs. 3.07). The activities most frequently targeted physical activity (73% and 85%) and bullying (78% and 67%). Schools’ participation in anti-smoking activities was significantly higher in 2006 compared with 2010 (46% vs. 29%). None of the investigated variables were associated with schools’ participation in health promoting activities. CONCLUSION: In a Danish context, schools’ participation in health promotion was rather stable from 2006 to 2010 and unrelated to the measured characteristics of the schools and their students

Demonstration of non-linear model predictive control for optimal flexible operation of a CO2 capture plant

Due to the penetration of renewable intermittent energy, there is a need for coal and natural gas power plants to operate flexibly with variable load. This has resulted in an increasing interest in flexible and operational issues in the capture plant as well. In the present paper a nonlinear model predictive control (NMPC) system was tested at the Tiller pilot plant in Norway. The most important part of the NMPC software is the dynamic model representing the absorber/desorber plant. A previous first principle (mechanistic) dynamic model of the plant using MEA was modified for a solvent of AMP and piperazine, and then successfully verified by step response tests. The NMPC, which was set up to minimize the deviation from the capture rate setpoint and minimize the specific reboiler duty was then tested in a closed loop with large changes in flue gas flow and CO2 composition. Even for gas rate variations of more than 300% (110–340 m3/h) and CO2 concentration changes of 30%, the dynamic response was satisfactory. A test with frequently occurring constraints on the reboiler duty revealed a need for an extension to include direct control of the lean loading. Test of setpoint changes in total CO2 recovery showed that the control system managed to rapidly change from one capture rate to another with a time constant of typically 10 min. This might be used in a second layer of optimization, a dynamic real-time optimizer, that minimizes the capture costs during a longer horizon considering varying energy prices.publishedVersio

Carcinogenesis in Prostate Cancer: The role of Long Non-Coding RNAs

LncRNAs appear to play a considerable role in tumourigenesis through regulating key processes in cancer cells such as proliferative signalling, replicative immortality, invasion and metastasis, evasion of growth suppressors, induction of angiogenesis and resistance to apoptosis. LncRNAs have been reported to play a role in prostate cancer, particularly in regulating the androgen receptor signalling pathway. In this review article, we summarise the role of 34 lncRNAs in prostate cancer with a particular focus on their role in the androgen receptor signalling pathway and the epithelial to mesenchymal transition pathway

Development of a High Throughput (HT) Raman Spectroscopy Method for Rapid Screening of Liquid Blood Plasma From Prostate Cancer Patients

Extensive research has been undertaken on the examination of tissue biopsies using vibrational spectroscopic techniques. However, fewer studies have focused on less invasive and commonly acquired blood samples. Recent studies have shown the ability of Raman and Fourier transform infrared (FTIR) spectroscopy to discriminate between non-cancer controls and cancer cases using blood serum or plasma. Even though many studies have proposed Raman spectroscopy as a potential diagnostic tool in various cancers, the Raman spectroscopic technique has not been introduced as a routine clinical technology. This is due to multiple drawbacks with the application of the technique, including sample preparation, the requirement for expensive substrates and long acquisition times. The current study aims to overcome these limitations and focuses on the translation of Raman spectroscopy into a high throughput clinical diagnostic tool for prostate cancer. In this study, the effect of different instrumental and sample preparation parameters were investigated, with the aim of identifying a combination that would reduce the overall acquisition time for spectra from peripheral blood plasma, reduce the complexity of sample preparation and retain the classification accuracy from Raman spectroscopic diagnostics. A high throughput (HT) system was developed and Raman spectroscopic measurements were performed on plasma samples from 10 prostate cancer patients and 10 healthy volunteers. The spectra were pre-processed and classified by principal component analysis – linear discriminant analysis (PCA-LDA) in the R environment. Statistically significant differences were observed between Raman spectra of prostate cancer patients and non-cancer controls. The (HT) classification resulted in a sensitivity and specificity of 96.5% and 95% respectively. Overall, this study has overcome some of the limitations associated with clinical translation of Raman spectroscopy. The HT-Raman spectroscopy method developed in this study can be used for rapid and accurate diagnosis of prostate cancer using liquid plasma samples

Development of a High Throughput (HT) Raman Spectroscopy Method for Rapid Screening of Liquid Blood Plasma From Prostate Cancer Patients

Extensive research has been undertaken on the examination of tissue biopsies using vibrational spectroscopic techniques. However, fewer studies have focused on less invasive and commonly acquired blood samples. Recent studies have shown the ability of Raman and Fourier transform infrared (FTIR) spectroscopy to discriminate between non-cancer controls and cancer cases using blood serum or plasma. Even though many studies have proposed Raman spectroscopy as a potential diagnostic tool in various cancers, the Raman spectroscopic technique has not been introduced as a routine clinical technology. This is due to multiple drawbacks with the application of the technique, including sample preparation, the requirement for expensive substrates and long acquisition times. The current study aims to overcome these limitations and focuses on the translation of Raman spectroscopy into a high throughput clinical diagnostic tool for prostate cancer. In this study, the effect of different instrumental and sample preparation parameters were investigated, with the aim of identifying a combination that would reduce the overall acquisition time for spectra from peripheral blood plasma, reduce the complexity of sample preparation and retain the classification accuracy from Raman spectroscopic diagnostics. A high throughput (HT) system was developed and Raman spectroscopic measurements were performed on plasma samples from 10 prostate cancer patients and 10 healthy volunteers. The spectra were pre-processed and classified by principal component analysis – linear discriminant analysis (PCA-LDA) in the R environment. Statistically significant differences were observed between Raman spectra of prostate cancer patients and non-cancer controls. The (HT) classification resulted in a sensitivity and specificity of 96.5% and 95% respectively. Overall, this study has overcome some of the limitations associated with clinical translation of Raman spectroscopy. The HT-Raman spectroscopy method developed in this study can be used for rapid and accurate diagnosis of prostate cancer using liquid plasma samples