IntroductionWomen with a history of gestational diabetes mellitus (GDM) are at increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Recommendations for postpartum ...follow-up include targeted lifestyle advice to lower the risk.The aim of this study was to compare postpartum lifestyle behaviours and perceptions among women with and without a history of GDM. In addition, we examined whether lifestyle behaviours of women with a history of GDM participating in a lifestyle intervention study differed from lifestyle behaviours of women with a history of GDM in the general population.Research design and methodsWe linked data from the fourth survey of the population-based Trøndelag Health Study (HUNT4) to information from the Medical Birth Registry of Norway for women with registered births between 2000 and 2019. Using logistic regression, we compared lifestyle behaviours in women with and without GDM. In secondary analyses, lifestyle behaviours in women with GDM participating in a postpartum lifestyle intervention study were compared with HUNT participants with GDM using Fisher’s exact tests/t-tests.ResultsA high proportion of the women in our population, regardless of GDM history, reported several unhealthy lifestyle behaviours. We found no significant association between history of GDM and lifestyle behaviours. The lifestyle intervention study for women with a history of GDM appeared to recruit women with more favourable lifestyle behaviours.ConclusionsWomen, regardless of GDM history, could potentially benefit from further support for lifestyle improvement, but it may be especially important in women with a history of GDM given their increased risk of T2DM and CVD. Interventions targeting women with GDM might not reach the women with the unhealthiest lifestyle behaviours, and measures to reach out to all women should be further investigated.
Chronic inflammation contributes to prostate cancer and the transcription factor Nuclear Factor-kappa B (NF-κB) is constitutively active in most such cancers. We examine the effects of coffee on ...NF-κB and on the regulation of selected genes in human-derived prostate cancer cells (PC3) and in PC3 xenografts in athymic nude mice. PC3 cells stably transduced with an NF-κB-luciferase reporter were used both in vitro and for xenografts. NF-κB activity was measured by reporter assays, DNA binding and in vivo imaging. Gene expression was measured in PC3 cells, xenografts and tumor microenvironment by low-density arrays. Western blotting of activated caspases was used to quantify apoptosis.
Coffee inhibited TNFα-induced NF-κB activity and DNA-binding in PC3 cells. Furthermore, coffee increased apoptosis and modulated expression of a number of inflammation- and cancer-related genes in TNFα-treated PC3 cells. In vivo imaging revealed a 31% lower NF-κB-luciferase activation in the xenografts of the mice receiving 5% coffee compared to control mice. Interestingly, we observed major changes in gene expression in the PC3 cells in xenografts as compared to PC3 cells in vitro. In PC3 xenografts, genes related to inflammation, apoptosis and cytoprotection were down-regulated in mice receiving coffee, and coffee also affected the gene expression in the xenograft microenvironment. Our data demonstrate that coffee inhibits NF-κB activity in PC3 cells in vitro and in xenografts. Furthermore, coffee modulates transcription of genes related to prostate cancer and inflammation. Our results are the first to suggest mechanistic links between coffee consumption and prostate cancer in an experimental mouse model.
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Purpose
We hypothesized that biomarkers and dietary factors related to cardiovascular disease risk were associated with serum retinol and evaluated these potential associations in patients with ...suspected coronary artery disease (CAD).
Methods
We used cross-sectional data from 4116 patients hospitalised for suspected CAD. Dietary data were obtained from a subgroup of 1962 patients using a food frequency questionnaire. Potential biomarkers and dietary factors were explored using linear regression modelling adjusted for age and sex. Regression coefficients and corresponding confidence intervals (CI) are given as % change in serum retinol per unit change in the predictors. Analyses were performed in the total population and in strata of serum retinol tertiles.
Results
In age- and sex-adjusted models, serum creatinine (standardized β: 0.38, 95% CI 0.35, 0.42), plasma total cysteine (0.26, 0.23, 0.29), serum uric acid (0.30, 0.26, 0.33) and plasma neopterin (0.22, 0.18, 0.25) were positively associated, whereas plasma serine (− 0.15, − 0.18, − 0.12) and serum C-reactive protein (− 0.15, − 0.18, − 0.12) were inversely associated with serum retinol. When we included the significant biomarkers in a multivariate model, the model explained 33% of the variability (
R
2
= 0.33) in serum retinol. The results were similar in the lower and upper tertiles of serum retinol. Weak or no associations were observed for dietary factors.
Conclusions
In patients with suspected CAD, concentrations of creatinine, cysteine and uric acid were positively associated with serum retinol. Future studies should assess whether retinol concentrations are influenced by metabolic alterations in patients at risk of cardiovascular disease.
Qualified systematic reviews (SRs) will form the main basis for evaluating causal effects of nutrients or food groups on health outcomes in the sixth edition of Nordic Nutrition Recommendations to be ...published in 2022 (NNR2022).
To describe rationale and structure of SRs used in NNR2022.
The SR methodologies of the previous edition of NNR were used as a starting point. Methodologies of recent SRs commissioned by leading national food and health authorities or international food and health organizations were examined and scrutinized. Methodologies for developing SRs were agreed by the NNR2022 Committee in a consensus-driven process.
Qualified SRs will be developed by a cross-disciplinary group of experts and reported according to the requirements of the EQUATOR network. A number of additional requirements must also be fulfilled, including 1) a clearly stated set of objectives and research questions with pre-defined eligibility criteria for the studies, 2) an explicit, reproducible methodology, 3) a systematic search that attempts to identify all studies that would meet the eligibility criteria, 4) an assessment of the validity of the findings of the included studies through an assessment of 'risk of bias' of the studies, 5) a systematic presentation and synthesis of the characteristics and findings of the included studies, and 6) a grading of the overall evidence. The complete definition and requirements of a qualified SR are described.
Most SRs published in scientific journals do not fulfill all criteria of the qualified SRs in the NNR2022 project. This article discusses the structure and rationale for requirements of qualified SRs in NNR2022. National food and health authorities have only recently begun to use qualified SRs as a basis for nutrition recommendations.
Qualified SRs will be used to inform dietary reference values (DRVs) and food-based dietary guidelines (FBDGs) in the NNR2022 project.
All-trans retinoic acid (atRA), an active derivative of vitamin A, regulates cell differentiation, proliferation and cardiac morphogenesis via transcriptional activation of retinoic acid receptors ...(RARs) acting on retinoic acid response elements (RARE). We hypothesized that the retinoic acid (RA) signalling pathway is activated in myocardial ischemia and postischemic remodelling.
Myocardial infarction was induced through ligating the left coronary artery in mice. In vivo cardiac activation of the RARs was measured by imaging RARE-luciferase reporter mice, and analysing expression of RAR target genes and proteins by real time RT-PCR and western blot. Endogenous retinoids in postinfarcted hearts were analysed by triple-stage liquid chromatography/tandem mass spectrometry. Cardiomyocytes (CM) and cardiofibroblasts (CF) were isolated from infarcted and sham operated RARE luciferase reporter hearts and monitored for RAR activity and expression of target genes. The effect of atRA on CF proliferation was evaluated by EdU incorporation. Myocardial infarction increased thoracic RAR activity in vivo (p<0.001), which was ascribed to the heart through ex vivo imaging (p = 0.002) with the largest signal 1 week postinfarct. This was accompanied by increased cardiac gene and protein expression of the RAR target genes retinol binding protein 1 (p = 0.01 for RNA, p = 0,006 for protein) and aldehyde dehydrogenase 1A2 (p = 0.04 for RNA, p = 0,014 for protein), while gene expression of cytochrome P450 26B1 was downregulated (p = 0.007). Concomitantly, retinol accumulated in the infarcted zone (p = 0.02). CM and CF isolated from infarcted hearts had higher luminescence than those from sham operated hearts (p = 0.02 and p = 0.008). AtRA inhibited CF proliferation in vitro (p = 0.02).
The RA signalling pathway is activated in postischemic hearts and may play a role in regulation of damage and repair during remodelling.
To determine the plasma and urine levels of antioxidants and oxidative stress biomarkers in subjects with spinal cord injury (SCI) the first year after injury.
Descriptive 1-year follow-up study.
...Rehabilitation and research center.
SCI subjects (n=37; age range, 18-70 y) consecutively enrolled within the first month after injury. A healthy, able-bodied control group (n=346) was also included.
Not applicable.
Blood and urine levels of antioxidants and oxidative stress biomarkers were measured at inclusion and after 3 and 12 months postinjury.
One month after injury, the plasma antioxidants (total and oxidized glutathione and 6 different carotenoids and α-tocopherol) were reduced by 19% to 71% among the SCI subjects compared with the controls. The redox potential was reduced by 7% among the SCI subjects. The oxidative stress biomarker urinary 8-epi prostagladin F2α (PGF2α) increased to 161% in the SCI subjects compared with the controls. After 3 and 12 months, most of the antioxidant biomarkers were still significantly reduced compared with the controls, while urinary 8-epi PGF2α had increased to 208% compared with the controls.
The levels of antioxidants were significantly lower, while the marker of oxidative stress was higher in the SCI subjects compared with the controls. This observation demonstrates that SCI patients experience increased oxidative stress and reduced antioxidant defense the first year after injury. Our findings warrant intervention studies where SCI patients receive dietary antioxidant support as part of their rehabilitation.
Scope: Cytoprotective gene products, e.g. phase II - and antioxidant enzymes, are important in cellular redox homeostasis. A common feature of these genes is binding sites for transcription factor ...nuclear factor erythroid-2-related factor 2 (Nrf2), named electrophile response elements (EpREs) within their promoters. Methods and results: To identify dietary bioactive compounds and foods with Nrf2/EpRE inducing properties in an intact organism, we utilized transgenic mice encoding luciferase under control of EpRE from the thioredoxin promoter. We found that 18 of 31 phytochemicals and 10 of 14 dietary plant extracts induced EpRE activity in liver HepG2 cells. Surprisingly, some dietary plant extracts showed profound inducing capability as compared to pure compounds indicating combinatorial effects of compounds found in whole foods. Furthermore, intraperitoneal injections of carnosol, curcumin and tert benzohydroquinine induced EpRE-dependent promoter activity in transgenic mice. In further experiments with curcumin, we found highly induced EpRE activity in intestine, liver, kidney and spleen. Finally, a combination extract made of coffee, thyme, broccoli, rosemary, turmeric and red onion fed orally, induced EpRE mediated luciferase in lung and adipose tissue. Conclusion: These results show that plant-based foods contain compounds that can be absorbed and induce the antioxidant defence in a living organism in an organ-specific manner.
Background
In-person dietary counseling and interventions have shown promising results in changing habits toward healthier lifestyles, but they are costly to implement in large populations. ...Developing digital tools to assess individual dietary intake and lifestyle with integrated personalized feedback systems may help overcome this challenge. We developed a short digital food frequency questionnaire, known as the DIGIKOST-FFQ, to assess diet and other lifestyle factors based on the Norwegian Food-Based Dietary Guidelines. The DIGIKOST-FFQ includes a personalized feedback system, the DIGIKOST report, that benchmarks diet and lifestyle habits. We used qualitative focus group interviews and usability tests to test the feasibility and usability of the DIGIKOST application.
Objective
We aimed to explore attitudes, perceptions, and challenges in completing the DIGIKOST-FFQ. We also investigated perceptions and understanding of the personalized feedback in the DIGIKOST report and the technical flow and usability of the DIGIKOST-FFQ and the DIGIKOST report.
Methods
Healthy individuals and cancer survivors were invited to participate in the focus group interviews. The transcripts were analyzed using thematic analysis. Another group of healthy individuals completed the usability testing, which was administered individually by a moderator and 2 observers. The results were analyzed based on predefined assignments and discussion with the participants about the interpretation of the DIGIKOST report and technical flow of the DIGIKOST-FFQ.
Results
A total of 20 individuals participated in the focus group interviews, divided into 3 groups of healthy individuals and 3 groups of cancer survivors. Each group consisted of 3 to 4 individuals. Five main themes were investigated: (1) completion time (on average 19.1, SD 8.3, minutes, an acceptable duration), (2) layout (participants reported the DIGIKOST-FFQ was easy to navigate and had clear questions but presented challenges in reporting dietary intake, sedentary time, and physical activity in the last year), (3) questions (the introductory questions on habitual intake worked well), (4) pictures (the pictures were very helpful, but some portion sizes were difficult to differentiate and adding weight in grams would have been helpful), and (5) motivation (users were motivated to obtain personalized feedback). Four individuals participated in the usability testing. The results showed that the users could seamlessly log in, give consent, fill in the DIGIKOST-FFQ, and receive, print, and read the DIGIKOST report. However, parts of the report were perceived as difficult to interpret.
Conclusions
The DIGIKOST-FFQ was overall well received by participants, who found it feasible to use; however, some adjustments with regard to reporting dietary intake and lifestyle habits were suggested. The DIGIKOST report with personalized feedback was the main motivation to complete the questionnaire. The results from the usability testing revealed a need for adjustments and updates to make the report easier to read.
Multiple myeloma is an incurable disease requiring the development of effective therapies which can be used clinically. We have elucidated the potential for manipulating the cAMP signaling pathway as ...a target for inhibiting the growth of multiple myeloma cells.
As a model system, we primarily used the murine multiple myeloma cell line MOPC315 which can be grown both in vivo and in vitro. Human multiple myeloma cell lines U266, INA-6 and the B-cell precursor acute lymphoblastic leukemia cell line Reh were used only for in vitro studies. Cell death was assessed by flow cytometry and western blot analysis after treatment with cAMP elevating agents (forskolin, prostaglandin E2 and rolipram) and cAMP analogs. We followed tumor growth in vivo after forskolin treatment by imaging DsRed-labelled MOPC315 cells transplanted subcutaneously in BALB/c nude mice.
In contrast to the effect on Reh cells, 50 μM forskolin more than tripled the death of MOPC315 cells after 24 h in vitro. Forskolin induced cell death to a similar extent in the human myeloma cell lines U266 and INA-6. cAMP-mediated cell death had all the typical hallmarks of apoptosis, including changes in the mitochondrial membrane potential and cleavage of caspase 3, caspase 9 and PARP. Forskolin also inhibited the growth of multiple myeloma cells in a mouse model in vivo.
Elevation of intracellular levels of cAMP kills multiple myeloma cells in vitro and inhibits development of multiple myeloma in vivo. This strongly suggests that compounds activating the cAMP signaling pathway may be useful in the field of multiple myeloma.
Background
While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal ...carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients.
Methods
Adherence to the seven‐point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self‐administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen‐detected lesions.
Results
Of 1486 screening participants, 548 were free from adenomas, 524 had non‐advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively.
Conclusions
Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen‐detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions.
While several studies have documented an association between adherence to cancer prevention recommendations and CRC, data are sparse when it comes to the precancerous lesions. In this study, including participants representing the entire spectrum of colorectal carcinogenesis, strong inverse associations were observed between adherence and advanced precancerous lesions, highlighting the importance of adopting a healthy lifestyle early on to prevent the development of CRC. The separate assessment among CRC patients reveals a potential for improving adherence to the recommendations, especially when it comes to limiting alcohol intake and red and processed meat.
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