Plant Biomarker Pattern, Screening Programme for Phytochemical Differences in Plants Exposed to Stress

A screening programme is developed to investigate phytochemical differences in plants xposed to stress compared with non-exposed plants. The screening programme, in its resent form or in a more simplified form, can be utilized in several different areas as a preliminary broad screening. The screening programme covers the most general groups of compounds found in plants. The following groups of phytochemical compounds are included in the programme: Unspecific compounds, organic acids, lipids, phenolic compounds, carbohydrates, terpenoids and N-, S- and P-containing compounds

Plant Biomarker Pattern, Apples grown with various availability of organic nitrogen and with or witout the use of pesticides

In the recent years there has been an increasing focus on the quality and health value of organic plant products compared with conventional products. The use of pesticides and concentrated fertilisers in conventional agriculture implies a risk of effects on plant composition, which may affect health of the consumer (Brandt & Mølgaard, 2001). To determine if organically grown plant food could provide more or less benefits to health than conventional food, a first step is to investigate the differences in the composition and relative concentration of natural compounds in the plant products. In this project apples were grown with two levels of nitrogen availability and with or without the use of pesticides. The apples were screened for changes in the phytochemical composition and concentration. The work is affiliated to the project "Organic food and health" supported by the Danish Research Centre for Organic Farming (DARCOF). Biomarkers and biomarker patterns were presented in plants cultivated with low and high N and with pesticides. One biomarker was related to: • the type of N with and without pesticides • pesticides at high N and type of N without pesticides • pesticides at low and high N One biomarker pattern was related to: • the type of N • the type of N without pesticides • pesticides at low N and type of N without pesticides • pesticides at high N and type of N with pesticide

Birth weight, cardiometabolic risk factors and effect modification of physical activity in children and adolescents : pooled data from 12 international studies

Objectives: Low and high birth weight is associated with higher levels of cardiometabolic risk factors and adiposity in children and adolescents, and increases the risk of cardiovascular diseases, obesity, and early mortality later in life. Moderate-to-vigorous physical activity (MVPA) is associated with lower cardiometabolic risk factors and may mitigate the detrimental consequences of high or low birth weight. Thus, we examined whether MVPA modified the associations between birth weight and cardiometabolic risk factors in children and adolescents. Methods: We used pooled individual data from 12 cohort- or cross-sectional studies including 9,100 children and adolescents. Birth weight was measured at birth or maternally reported retrospectively. Device-measured physical activity (PA) and cardiometabolic risk factors were measured in childhood or adolescence. We tested for associations between birth weight, MVPA, and cardiometabolic risk factors using multilevel linear regression, including study as a random factor. We tested for interaction between birth weight and MVPA by introducing the interaction term in the models (birth weight x MVPA). Results: Most of the associations between birth weight (kg) and cardiometabolic risk factors were not modified by MVPA (min/day), except between birth weight and waist circumference (cm) in children (p = 0.005) and HDL-cholesterol (mmol/l) in adolescents (p = 0.040). Sensitivity analyses suggested that some of the associations were modified by VPA, i.e., the associations between birth weight and diastolic blood pressure (mmHg) in children (p = 0.009) and LDL- cholesterol (mmol/l) (p = 0.009) and triglycerides (mmol/l) in adolescents (p = 0.028). Conclusion: MVPA appears not to consistently modify the associations between low birth weight and cardiometabolic risk. In contrast, MVPA may mitigate the association between higher birth weight and higher waist circumference in children. MVPA is consistently associated with a lower cardiometabolic risk across the birth weight spectrum. Optimal prenatal growth and subsequent PA are both important in relation to cardiometabolic health in children and adolescents.publishedVersio

A RT-qPCR system using a degenerate probe for specific identification and differentiation of SARS-CoV-2 Omicron (B.1.1.529) variants of concern

Fast surveillance strategies are needed to control the spread of new emerging SARS-CoV-2 variants and gain time for evaluation of their pathogenic potential. This was essential for the Omicron variant (B.1.1.529) that replaced the Delta variant (B.1.617.2) and is currently the dominant SARS-CoV-2 variant circulating worldwide. RT-qPCR strategies complement whole genome sequencing, especially in resource lean countries, but mutations in the targeting primer and probe sequences of new emerging variants can lead to a failure of the existing RT-qPCRs. Here, we introduced an RT-qPCR platform for detecting the Delta- and the Omicron variant simultaneously using a degenerate probe targeting the key ΔH69/V70 mutation in the spike protein. By inclusion of the L452R mutation into the RT-qPCR platform, we could detect not only the Delta and the Omicron variants, but also the Omicron sub-lineages BA.1, BA.2 and BA.4/BA.5. The RT-qPCR platform was validated in small- and large-scale. It can easily be incorporated for continued monitoring of Omicron sub-lineages, and offers a fast adaption strategy of existing RT-qPCRs to detect new emerging SARS-CoV-2 variants using degenerate probes.</p

Natural CD4+ T-Cell Responses against Indoleamine 2,3-Dioxygenase

The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides.In the present study, we show that CD4(+) helper T cells additionally spontaneously recognize IDO. Hence, we scrutinized the vicinity of the previously described HLA-A*0201-restricted IDO-epitope for CD4(+) T-cell epitopes. We demonstrated the presence of naturally occurring IDO-specific CD4(+) T cells in cancer patients and to a lesser extent in healthy donors by cytokine release ELISPOT. IDO-reactive CD4(+) T cells released IFN-γ, TNF-α, as well as IL-17. We confirm HLA class II-restriction by the addition of HLA class II specific blocking antibodies. In addition, we detected a trend between class I- and class II-restricted IDO responses and detected an association between IDO-specific CD4(+) T cells and CD8(+) CMV-responses. Finally, we could detect IL-10 releasing IDO-reactive CD4(+) T cells.IDO is spontaneously recognized by HLA class II-restricted, CD4(+) T cells in cancer patients and in healthy individuals. IDO-specific T cells may participate in immune-regulatory networks where the activation of pro-inflammatory IDO-specific CD4(+) responses may well overcome or delay the immune suppressive actions of the IDO-protein, which are otherwise a consequence of the early expression of IDO in maturing antigen presenting cells. In contrast, IDO-specific regulatory T cells may enhance IDO-mediated immune suppression

Birth weight, cardiometabolic risk factors and effect modification of physical activity in children and adolescents: pooled data from 12 international studies

Abstract: Objectives: Low and high birth weight is associated with higher levels of cardiometabolic risk factors and adiposity in children and adolescents, and increases the risk of cardiovascular diseases, obesity, and early mortality later in life. Moderate-to-vigorous physical activity (MVPA) is associated with lower cardiometabolic risk factors and may mitigate the detrimental consequences of high or low birth weight. Thus, we examined whether MVPA modified the associations between birth weight and cardiometabolic risk factors in children and adolescents. Methods: We used pooled individual data from 12 cohort- or cross-sectional studies including 9,100 children and adolescents. Birth weight was measured at birth or maternally reported retrospectively. Device-measured physical activity (PA) and cardiometabolic risk factors were measured in childhood or adolescence. We tested for associations between birth weight, MVPA, and cardiometabolic risk factors using multilevel linear regression, including study as a random factor. We tested for interaction between birth weight and MVPA by introducing the interaction term in the models (birth weight x MVPA). Results: Most of the associations between birth weight (kg) and cardiometabolic risk factors were not modified by MVPA (min/day), except between birth weight and waist circumference (cm) in children (p = 0.005) and HDL-cholesterol (mmol/l) in adolescents (p = 0.040). Sensitivity analyses suggested that some of the associations were modified by VPA, i.e., the associations between birth weight and diastolic blood pressure (mmHg) in children (p = 0.009) and LDL- cholesterol (mmol/l) (p = 0.009) and triglycerides (mmol/l) in adolescents (p = 0.028). Conclusion: MVPA appears not to consistently modify the associations between low birth weight and cardiometabolic risk. In contrast, MVPA may mitigate the association between higher birth weight and higher waist circumference in children. MVPA is consistently associated with a lower cardiometabolic risk across the birth weight spectrum. Optimal prenatal growth and subsequent PA are both important in relation to cardiometabolic health in children and adolescents

Targeted prevention in primary care aimed at lifestyle-related diseases:a study protocol for a non-randomised pilot study

Background: The consequences of lifestyle-related disease represent a major burden for the individual as well as for society at large. Individual preventive health checks to the general population have been suggested as a mean to reduce the burden of lifestyle-related diseases, though with mixed evidence on effectiveness. Several systematic reviews, on the other hand, suggest that health checks targeting people at high risk of chronic lifestyle-related diseases may be more effective. The evidence is however very limited. To effectively target people at high risk of lifestyle-related disease, there is a substantial need to advance and implement evidence-based health strategies and interventions that facilitate the identification and management of people at high risk. This paper reports on a non-randomized pilot study carried out to test the acceptability, feasibility and short-term effects of a healthcare intervention in primary care designed to systematically identify persons at risk of developing lifestyle-related disease or who engage in health-risk behavior, and provide targeted and coherent preventive services to these individuals. Methods: The intervention took place over a three-month period from September 2016 to December 2016. Taking a two-pronged approach, the design included both a joint and a targeted intervention. The former was directed at the entire population, while the latter specifically focused on patients at high risk of a lifestyle-related disease and/or who engage in health-risk behavior. The intervention was facilitated by a digital support system. The evaluation of the pilot will comprise both quantitative and qualitative research methods. All outcome measures are based on validated instruments and aim to provide results pertaining to intervention acceptability, feasibility, and short-term effects. Discussion: This pilot study will provide a solid empirical base from which to plan and implement a full-scale randomized study with the central aim of determining the efficacy of a preventive health intervention. Trial registration: Registered at Clinical Trial Gov (Unique Protocol ID: TOFpilot2016). Registered 29 April 2016. The study adheres to the SPIRIT guidelines

Use of cultivation-dependent and -independent techniques to assess contamination of central venous catheters: a pilot study

<p>Abstract</p> <p>Background</p> <p>Catheters are the most common cause of nosocomial infections and are associated with increased risk of mortality, length of hospital stay and cost. Prevention of infections and fast and correct diagnosis is highly important.</p> <p>Methods</p> <p>In this study traditional semiquantitative culture-dependent methods for diagnosis of bacteria involved in central venous catheter-related infections as described by Maki were compared with the following culture-independent molecular biological methods: Clone libraries, denaturant gradient gel electrophoresis, phylogeny and fluorescence in situ hybridization.</p> <p>Results</p> <p>In accordance with previous studies, the cultivation of central venous catheters from 18 patients revealed that <it>S. epidermidis </it>and other coagulase-negative staphylococci were most abundant and that a few other microorganisms such as <it>P. aeruginosa </it>and <it>K. pneumoniae </it>occasionally were found on the catheters. The molecular analysis using clone libraries and sequencing, denaturant gradient gel electrophoresis and sequencing provided several important results. The species found by cultivation were confirmed by molecular methods. However, many other bacteria belonging to the phyla <it>Proteobacteria, Firmicutes, Actinobacteria </it>and <it>Bacteroidetes </it>were also found, stressing that only a minor portion of the species present were found by cultivation. Some of these bacteria are known to be pathogens, some have not before been described in relation to human health, and some were not closely related to known pathogens and may represent new pathogenic species. Furthermore, there was a clear difference between the bacterial species found in biofilm on the external (exluminal) and internal (luminal) side of the central venous catheter, which can not be detected by Maki's method. Polymicrobial biofilms were observed on most of the catheters and were much more common than the cultivation-dependent methods indicated.</p> <p>Conclusion</p> <p>The results show that diagnosis based on molecular methods improves the detection of microorganisms involved in central catheter-related infections. The importance of these microorganisms needs to be investigated further, also in relation to contamination risk from improper catheter handling, as only in vivo contaminants are of interest. This information can be used for development of fast and more reliable diagnostic tools, which can be used in combination with traditional methods.</p

Expert consensus document:Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted