Landspítali University Hospital Research Archive
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Higher Alkylresorcinol Concentrations, a Consequence of Whole-Grain Intake, are Inversely Associated with Gestational Diabetes Mellitus in Iceland.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: A diet rich in whole grains may provide benefits for pregnant women due to whole grains' high nutritional value and dietary fiber content.
Objectives: To study the associations of whole-grain consumption, as well as the plasma alkylresorcinol concentration, a whole-grain consumption biomarker, in early pregnancy with gestational diabetes mellitus (GDM) diagnoses.
Methods: Subjects were women from the prospective study Pregnant Women in Iceland II (PREWICE II; n = 853) who attended their ultrasound appointment in gestational weeks 11-14 during the period from October 2017 to March 2018. During that visit, whole-grain consumption was estimated using a diet screening questionnaire, and blood samples were collected for analysis of plasma alkylresorcinols (ARs). Information on GDM diagnoses was later extracted from medical records. Multivariate log-binomial regression was used to evaluate the association of dietary whole-grain and AR concentrations with GDM.
Results: In total, 14.9% of the women adhered to the national food-based dietary guidelines (n = 127), which recommend 2 portions of whole grains daily. GDM was diagnosed in 127 women (14.9%). The frequency of whole-grain consumption was lower in women who were later diagnosed with GDM compared to the women without GDM (median, 5 times/week vs. 6 times/week, respectively; P = 0.02). This difference was reflected in the lower median concentration of total AR in women diagnosed with GDM (163 nmol/L vs. 209 nmol/L, respectively; P < 0.01). The quartile with the highest concentrations of AR had a RR of 0.50 (95% CI: 0.27-0.90) of being diagnosed with GDM, in comparison to the lowest quartile. There was a significant dose response in the GDM risk with higher AR levels.
Conclusions: We found that a higher consumption of whole grains, reflected both by reported consumption according to the FFQ and AR biomarkers, was associated with a decreased risk of receiving a GDM diagnosis.University of Iceland Research Fund
Science Fund of The National University Hospital in Icelan
Evaluation of mechanism of change in transdiagnostic cognitive behaviour therapy using single case experimental design.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground and objectives: Transdiagnostic mechanisms of change (txMOC) specific to cognitive behaviour therapy are poorly understood. Salkovskis (1996) proposed one such mechanism in terms of the shift towards an alternative, less negative view of their problems or cognitive flexibility. This hypothesis has been described as involving a shift in beliefs, from "theory A″ to "theory B". The objective of this research was to evaluate this hypothesis.
Methods: Effectiveness of a novel txCBT and temporal changes in process and symptom measures were evaluated using a non-concurrent multiple baseline design and Tau-U calculations with thirteen participants (five with obsessive-compulsive disorder, two with panic disorder with agoraphobia and six with major depressive disorder). As a secondary analysis authors calculated Kendall's - Tau correlation between process and symptom measures, performed the Wilcoxon signed-rank test to assess treatment modules effect on negative thought and calculated Reliable change index (RCI).
Results: The txCBT was clearly effective for eight participants. The results varied dependent on the stimuli evaluated as negative or threatening. Level and trend of the ratings of belief in theory A followed the level and trend of symptom measures to a greater extent than the (inverse) level and trend of belief in theory B.
Limitations: Only thirteen participants were recruited and evaluated.
Conclusions: The results are consistent with the view that effective treatment may involve a txMOC characterized by the ability to shift from a relatively fixed negative view of their experience to a less negative psychologically focused alternative.
Keywords: Anxiety; Depression; Mechanism of change; Single case experimental design; Transdiagnostic cognitive behavior therapy
Leveraging the Mendelian disorders of the epigenetic machinery to systematically map functional epigenetic variation.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAlthough each Mendelian Disorder of the Epigenetic Machinery (MDEM) has a different causative gene, there are shared disease manifestations. We hypothesize that this phenotypic convergence is a consequence of shared epigenetic alterations. To identify such shared alterations, we interrogate chromatin (ATAC-seq) and expression (RNA-seq) states in B cells from three MDEM mouse models (Kabuki [KS] type 1 and 2 and Rubinstein-Taybi type 1 [RT1] syndromes). We develop a new approach for the overlap analysis and find extensive overlap primarily localized in gene promoters. We show that disruption of chromatin accessibility at promoters often disrupts downstream gene expression, and identify 587 loci and 264 genes with shared disruption across all three MDEMs. Subtle expression alterations of multiple, IgA-relevant genes, collectively contribute to IgA deficiency in KS1 and RT1, but not in KS2. We propose that the joint study of MDEMs offers a principled approach for systematically mapping functional epigenetic variation in mammals.
Keywords: IgA deficiency; Mendelian; chromatin; computational biology; computational methods; epigenetics; genetics; genomics; histone machinery; mouse; systems biology.Louma G Foundation
Icelandic Research Fund
Icelandic Technology Development Fund
Johns Hopkins University
Maryland Genetics, Epidemiology and Medicine (MD-GEM) training program - Burroughs-Wellcome Fund
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of General Medical Sciences (NIGMS
Can ultrasound on admission in active labor predict labor duration and a spontaneous delivery?
No full textTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Identifying predictive factors for a normal outcome at admission in the labor ward would be of value for planning labor care, timing interventions, and preventing labor dystocia. Clinical assessments of fetal head station and position at the start of labor have some predictive value, but the value of ultrasound methods for this purpose has not been investigated. Studies using transperineal ultrasound before labor onset show possibilities of using these methods to predict outcomes.
Objective: This study aimed to investigate whether ultrasound measurements during the first examination in the active phase of labor were associated with the duration of labor phases and the need for operative delivery.
Study design: This was a secondary analysis of a prospective cohort study at Landspitali University Hospital, Reykjavík, Iceland. Nulliparous women at ≥37 weeks' gestation with a single fetus in cephalic presentation and in active spontaneous labor were eligible for the study. The recruitment period was from January 2016 to April 2018. Women were examined by a midwife on admission and included in the study if they were in active labor, which was defined as regular contractions with a fully effaced cervix, dilatation of ≥4 cm. An ultrasound examination was performed by a separate examiner within 15 minutes; both examiners were blinded to the other's results. Transabdominal and transperineal ultrasound examinations were used to assess fetal head position, cervical dilatation, and fetal head station, expressed as head-perineum distance and angle of progression. Duration of labor was estimated as the hazard ratio for spontaneous delivery using Kaplan-Meier curves and Cox regression analysis. The hazard ratios were adjusted for maternal age and body mass index. The associations between study parameters and mode of delivery were evaluated using receiver operating characteristic curves.
Results: Median times to spontaneous delivery were 490 minutes for a head-perineum distance of ≤45 mm and 682 minutes for a head-perineum distance of >45 mm (log-rank test, P=.009; adjusted hazard ratio for a shorter head-perineum distance, 1.47 [95% confidence interval, 0.83-2.60]). The median durations were 506 minutes for an angle of progression of ≥93° and 732 minutes for an angle of progression of <93° (log-rank test, P=.008; adjusted hazard ratio, 2.07 [95% confidence interval, 1.15-3.72]). The median times to delivery were 506 minutes for nonocciput posterior positions and 677 minutes for occiput posterior positions (log-rank test, P=.07; adjusted hazard ratio, 1.52 [95% confidence interval, 0.96-2.38]) Median times to delivery were 429 minutes for a dilatation of ≥6 cm and 704 minutes for a dilatation of 4 to 5 cm (log-rank test, P=.002; adjusted hazard ratio, 3.11 [95% confidence interval, 1.68-5.77]). Overall, there were 75 spontaneous deliveries; among those deliveries, 16 were instrumental vaginal deliveries (1 forceps delivery and 15 ventouse deliveries), and 8 were cesarean deliveries. Head-perineum distance and angle of progression were associated with a spontaneous delivery with area under the receiver operating characteristic curves of 0.68 (95% confidence interval, 0.55-0.80) and 0.67 (95% confidence interval, 0.55-0.80), respectively. Ultrasound measurement of cervical dilatation or position at inclusion was not significantly associated with spontaneous delivery.
Conclusion: Ultrasound examinations showed that fetal head station and cervical dilatation were associated with the duration of labor; however, measurements of fetal head station were the variables best associated with operative deliveries.
Keywords: angle of progression; delivery time; fetal head station; head-perineum distance; labor; transperineal ultrasound.Icelandic Centre for Researc
Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort.
No full textTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadOne thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy.Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.
Keywords: Asia; Europe; International Severe Asthma Registry; Middle East; North America.Optimum Patient Care Global
AstraZenec
Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus: data from an international inception cohort.
No full textTo access publisher's full text version of this article click on the hyperlink belowObjectives: Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance.
Methods: The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10-36 nmol/l), T2 (37-60 nmol/l) and T3 (61-174 nmol/l). MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the HOMA-IR model. Linear and logistic regressions were used to assess the association of variables with vitamin D levels.
Results: Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased high-density lipoprotein (HDL) were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance.
Conclusions: MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.
Keywords: cardiovascular disease; epidemiology; systemic lupus erythematosus; vitamin D.Canadian Institutes of Health Research (CIHR)
Versus Arthritis (Versus Arthritis Research UK Epidemiology Unit Core Support Programme Grant)
National Institute for Health Research (NIHR
Keratinocytes secrete multiple inflammatory and immune biomarkers, which are regulated by LL‐37, in a psoriasis mimicking microenvironment
No full textTo access publisher's full text version of this article click on the hyperlink belowPsoriasis is an autoimmune disease driven by a Th17 response linked to the antimicrobial peptide (AMP) LL-37 that has been connected to the induction and chronicity of psoriasis. We show that keratinocytes secrete various immune biomarkers with a direct link to psoriasis immunopathogenesis. Under pro-inflammatory microenvironmental conditions, LL-37 was found to regulate keratinocyte secretion of various immune biomarkers (eg C-X-C motif chemokine ligand (CXCL)8 and interleukin (IL)-1 beta) and alter extracellular signal-regulated kinase (ERK)1/2 signalling. However, during neutral conditions LL-37 induced a different pattern of keratinocyte immune biomarker secretion (eg vascular endothelial growth factor, CXCL8 and IL-6). Thus, an interesting pattern emerged regarding the immunomodulatory effects of LL-37 on keratinocytes; in general, expression of immune biomarkers that were upregulated in a Th1-like microenvironment was downregulated in the presence of LL-37. In contrast, LL-37 reinforced the Th17 response. In active psoriatic skin lesions, LL-37 expression was found to be significantly upregulated, which was also evident from the unique diffuse epidermic expression pattern not found in healthy skin. Finally, successful phototherapy of psoriasis patients converted this LL-37 inflammatory psoriatic skin pattern into a more localized basal layer expression as found in healthy controls. Thus, these findings demonstrate that LL-37 has a significant role in skin immune homeostasis and that its interplay with keratinocytes may have a more direct role in the immunopathogenesis of psoriasis than previously thought.Icelandic Research Fund
Landspitali University Hospital Research Fun
Genomic and Transcriptomic Analyses of Breast Cancer Primaries and Matched Metastases in AURORA, the Breast International Group (BIG) Molecular Screening Initiative.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 targeted gene sequencing, 152 RNA sequencing, 67 single nucleotide polymorphism arrays), we found a driver role for GATA1 and MEN1 somatic mutations. Metastases were enriched in ESR1, PTEN, CDH1, PIK3CA, and RB1 mutations; MDM4 and MYC amplifications; and ARID1A deletions. An increase in clonality was observed in driver genes such as ERBB2 and RB1. Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-enriched switching was associated with TP53 and/or PIK3CA mutations. Metastases had lower immune score and increased immune-permissive cells. High tumor mutational burden correlated to shorter time to relapse in HR+/HER2- cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could affect treatment strategies in MBC. SIGNIFICANCE: The AURORA program, through the genomic and transcriptomic analyses of matched primary and metastatic samples from 381 patients with breast cancer, coupled with prospectively collected clinical data, identified genomic alterations enriched in metastases and prognostic biomarkers. ESCAT tier I/II alterations were detected in more than half of the patients.This article is highlighted in the In This Issue feature, p. 2659.Breast Cancer Research Foundation (BCRF)
Fondation Cancer (Luxembourg)
National Lottery (Belgium)
Think Pink Belgium (SMART Fund)
Fund Friends of BIG
Foundation NIF
Fondation contre le Cancer (Belgium
The Benefit of a Couple-Based Intervention Among Women in Active Cancer Treatment on Sexual Concerns: A Quasi-Experimental Study.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Sexuality-related problems are common in women with cancer, threatening their sexual well-being and intimate relationships. Evidence-based interventions addressing the full range of sexual concerns among women in active cancer treatment are scarce.
Objective: The aim of this study was to evaluate the benefits of a novel couple-based intervention focusing on sexual concerns among women undergoing cancer treatment, including a subgroup of women with breast cancer. A secondary aim was to assess changes in illness intrusiveness in daily life.
Methods: A quasi-experimental single-group pre-post follow-up design was used. The study was initially planned as a randomized controlled trial with waitlist control group receiving delayed intervention. However, substantial differences were observed in clinical and demographic variables between the treatment group and control group, resulting in using a single-group pre-post follow-up design. The intervention consists of 3 advanced nurse-led, face-to-face couple-based sessions supported by access to web-based information.
Results: Women in active cancer treatment participated in the study (n = 60) together with their partners (n = 60). The main results showed significant differences between time points in the outcome measures for concerns related to the sexual adverse effects of cancer treatment (T1 vs T2, and T2 vs T3), sexual concerns related to the women's partners (T1 vs T2), and for concerns related to communication with healthcare providers about sexuality-related issues (T1 vs T2). No significant changes were found over time with respect to illness interference on the intimacy or instrumental subscales.
Conclusions: The results demonstrated that the approach of 3 couple-based therapeutic conversations is beneficial in reducing sexual concerns among women in active cancer treatment.
Implications for practice: Advanced nurse practitioners can develop and offer brief psychoeducational support that is helpful in reducing sexual concerns among women in active cancer treatment.Icelandic Nurses' Association Scientific Fund
LandspitaliUniversityHospital Scientific Fund
Scientific Fund of the Icelandic Cancer Society
Research Fund of Ingibjorg R. Magnusdotti
Underrepresentation of older adults in clinical trials on COVID-19 vaccines: A systematic review.
No full textTo access publisher's full text version of this article click on the hyperlink belowDuring the COVID-19 pandemic older subjects have been disproportionately affected by the disease. Vaccination is a fundamental intervention to prevent the negative consequences of COVID-19, but it is not known if the needs and vulnerabilities of older people are adequately addressed by their inclusion in randomized clinical trials (RCTs) evaluating the efficacy of vaccines for COVID-19. Given this background, we aimed to evaluate if current and ongoing phase II-III RCTs evaluating the efficacy of COVID-19 vaccines included a representative sample of older people. A systematic literature search in PubMed and Clinicaltrials.gov was performed until May 01st, 2021. Among 474 abstracts initially retrieved, 20 RCTs (ten already published, ten ongoing) were included. In the ten studies already published, the mean age of participants was 45.2 ± 11.9 years and only 9.83% of the participants were more than 65 years, 1.66% more than 75 years and less than 1% (0.55%) more than 85 years. In the ten ongoing RCTs, many of the studies aimed at including participants older than 18 years, with one study including participants between 18 and 84 years, and two between 21 and 100 years. In conclusion, our systematic review demonstrates that in published and ongoing phase II-III randomized clinical trials evaluating the efficacy of COVID-19 vaccines only a tiny fraction of the most vulnerable group of older people was included, although they clearly were the first population that had to be vaccinated.
Keywords: COVID-19; Older adults; Vaccination