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The use of arrays in genomics has led to a fast and reliable way to screen the transcriptome of an organism. It can be automated and analysis tools have become available and hence the technique has become widely used within the past few years. Signal-transduction routes rely mainly on the phosphorylation status of already available proteins; therefore kinases are central players in signal-transduction routes. The array technology can now also be used for the analysis of the kinome. To enable array analysis, consensus peptides for kinases are spot on a solid support. After incubation with cell lysates and in the presence of radioactive ATP, radioactive peptides can be visualized and the kinases that are active in the cells can be determined. The present paper reviews comprehensively the different kinome array platforms available and results obtained hitherto using such platforms. It will appear that this technology does not disappoint its high expectations and is especially powerful because of its species independence. Nevertheless, improvements are still possible and I shall also sketch future possible directions. [ABSTRACT FROM AUTHOR]

Background: Migraine is a disabling neurological disorder whose diagnosis is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the underlying neurobiological factors and sex-specific complications in migraine such as cardio- and cerebrovascular disease. Biomarker research can help to improve disease characterization and identify pathophysiological mechanism underlying these comorbidities. Objective: In this narrative review we searched for sex-specific metabolomics research to identify markers that may explain the migraine-cardiovascular disease (CVD) relationship. Discussion: Large-scale plasma metabolome analyses revealed alterations in migraine. Sex-specific findings showed a less CVD-protective HDL metabolism as well as the ApoA1 lipoprotein, especially for women with migraine. To explore other possible pathophysiological pathways, we expanded our review to include inflammatory markers, endothelial and vascular markers and sex hormones. Biological sex differences may affect the pathophysiology of migraine and its complications. Conclusions: There is no general large dyslipidemia profile in migraine patients, in line with findings that the increased risk of CVD in migraine patients seems not to be due to (large artery) atherosclerosis. Sex-specific associations are indicative towards a less CVD-protective lipoprotein profile in women with migraine. Future studies into the pathophysiology of CVD and migraine need to take sex specific factors into account. By establishing the overlapping pathophysiological mechanism of migraine and CVD, and unraveling the associated effects these diseases exert on each other, better preventative measures can be identified. Key points : • There is no general large dyslipidemia profile in migraine patients, in line with findings that the increased risk of CVD in migraine patients seems not to be due to (large artery) atherosclerosis. • Sex-specific associations are indicative towards a less CVD-protective lipoprotein profile in women with migraine. • Future studies into the pathophysiology of CVD and migraine need to take sex specific factors into account. [ABSTRACT FROM AUTHOR]

Objectives The presence of melanoma differentiation-associated protein 5 (MDA5) antibodies in patients with DM is associated with the development of a rapidly progressive interstitial lung disease (RPILD), unresponsive to conventional treatment. We characterize patients and provide more insight into potential biomarkers to identify patients with RPILD. Methods Patients diagnosed with anti-MDA5 positive DM between December 2015 and November 2017 were included in this study. Clinical data were retrospectively retrieved from medical records. A total of 180 immune-related markers were measured in sera of 16 patients and 15 healthy controls using proximity extension assay-based technology. Results Twenty patients were included, with a median time from symptoms till diagnosis of 4 months. All patients had clinically amyopathic DM. Interstitial lung disease (ILD) was present at diagnosis in 94% of the patients, 45% presented with RPILD. The mortality rate was 35% within 4 months after diagnosis and respiratory failure was the main cause of death in these patients. Furthermore, unsupervised analysis revealed that patients with RPILD show clearly different inflammatory serum profiles than healthy controls. In addition, in comparison to healthy controls, the IFN, IL1, IL10 and IL18 signalling pathways are different regulated in anti-MDA5 positive patients. Conclusion In this Dutch anti-MDA5 positive clinically amyopathic DM (CADM) cohort, one-third of the patients died due to RPILD soon after diagnosis, which underlines the severity of this disease. In addition, we have found several possible pathways that are differentially regulated in RPILD vs no RPILD DM and healthy controls. These markers await further validation before clinical use. [ABSTRACT FROM AUTHOR]

Purpose: The association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+ breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+ breast cancer etiology. Methods: The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55–69 years. At baseline, a random subcohort of 2589 women was sampled from the total cohort for a case–cohort analysis approach. Dietary acrylamide intake of subcohort members (n = 1449) and ER+ breast cancer cases (n = 844) was assessed with a food frequency questionnaire. We genotyped single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis, based on 20.3 years of follow-up. Results: Unexpectedly, there was a statistically non-significant inverse association between acrylamide and ER+ breast cancer risk among all women but with no clear dose–response relationship, and no association among never smokers. Among the results for 57 SNPs and 2 gene deletions, rs1056827 in CYP1B1, rs2959008 and rs7173655 in CYP11A1, the GSTT1 gene deletion, and rs1052133 in hOGG1 showed a statistically significant interaction with acrylamide intake for ER+ breast cancer risk. Conclusions: This study did not provide evidence for a positive association between acrylamide intake and ER+ breast cancer risk. If anything, acrylamide was associated with a decreased ER+ breast cancer risk. The interaction with SNPs in CYP1B1 and CYP11A1 suggests that acrylamide may influence ER+ breast cancer risk through sex hormone pathways. [ABSTRACT FROM AUTHOR]

Background: Chronic fatigue syndrome (CFS) is a medically unexplained syndrome for which no somatic or pharmacological treatment has been proven effective. Dysfunction of the cytokine network has been suspected to play a role in the pathophysiology of CFS. The disturbances of the cytokine network detected in CFS patients are highly variable, in part due to the lack of adequate controls in many studies. Furthermore, all studies have been performed on peripheral venous blood of patients. As cytokines mainly act in tissues, for example, the brain, the information that can be derived from peripheral blood cells is limited. The information regarding the possible role of cytokines in the pathophysiology could come from intervention studies in which the activities of relevant cytokines are reduced, for example, reducing interleukin-1, interleukin-6 or tumor necrosis factor. In this study, the clinical usefulness of anakinra, an IL-1 antagonist, will be assessed in patients with CFS.Methods/design: A randomized placebo-controlled, double-blind trial will be conducted. Fifty adult female patients meeting the Centers for Disease Control (CDC) criteria for CFS and without psychiatric co-morbidity will be included. After inclusion, patients will be randomized between treatment with anakinra (recombinant human interleukin-1 receptor antagonist) or placebo. Each group will be treated for 4 weeks. Outcome measures will be assessed at baseline, after 4 weeks of intervention, and 6 months after baseline assessment. The primary outcome measure will be fatigue severity at 4 weeks, measured with the validated Checklist of Individual Strength (CIS). Secondary outcome measures are functional impairment, physical and social functioning, psychological distress, pain severity, presence of accompanying symptoms, and cytokine and cortisol concentrations.Discussion: This is the first randomized placebo-controlled trial that will evaluate the effect of interference with IL-1 on the experience of fatigue in patients with CFS. The results of this study may expand treatment options for patients with CFS, for whom graded exercise therapy and cognitive behavioral therapy are the only evidence-based interventions that exist at this moment.Trial Registration: Clinicaltrials.gov: NCT02108210 . Clinicaltrials.gov registration date: 8 April 2014. EudraCT: 2013-005466-19. [ABSTRACT FROM AUTHOR]