Foetal Microchimerism Correlates With Foetal-Maternal Histocompatibility Both During Pregnancy and Postpartum.

Foetal cells are detectable in women decades postpartum, a state termed foetal microchimerism. The interplay between these semi-allogeneic foetal cells and the mother could be affected by genetic mismatches in the HLA loci. Here, we relate HLA allele and molecular mismatch values to the presence and quantity of foetal microchimerism in the maternal circulation during pregnancy and postpartum.

Continuous infusion of resolvin D2 in combination with Angiotensin-II show contrary effects on blood pressure and intracardiac artery remodeling.

Specialized pro-resolving mediators (SPMs) are key effectors of resolution of inflammation. This is highly relevant for cardiac and vessel remodeling, where the net inflammatory response contributes to determine disease outcome. Herein, we used a mice model of angiotensin (Ang)-II-induced hypertension to study the effect of the SPM Resolvin D2 (RvD2), on hypertension and cardiac remodeling.

SLAMF1-derived peptide exhibits cardio protection after permanent left anterior descending artery ligation in mice.

Acute myocardial infarction (MI) results in tissue damage to affected areas of the myocardium. The initial inflammatory response is the most damaging for residual cardiac function, while at later stages inflammation is a prerequisite for proper healing and scar formation. Balancing the extent and duration of inflammation during various stages after MI is thus pivotal for preserving cardiac function.

T cells with increased responsiveness cause obesity in mice without diet intervention.

Obesity is a complex multicausal disease that can cause morbidity and mortality, and there is need for improved knowledge on the underlying mechanisms. Using a mouse model of increased T cell responsiveness, we show that development of obesity can be driven by immune cells. This was confirmed with bone marrow transplantation and adoptive T cell transfer to several recipient mouse models.

CD38 deficient mice are not protected from atherosclerosis.

CD38 is a multifunctional enzyme implicated in chemotaxis of myeloid cells and lymphocyte activation, but also expressed by resident cells such as endothelial and smooth muscle cells. CD38 is important for host defense against microbes. However, CD38's role in the pathogenesis of atherosclerosis is controversial with seemingly conflicting results reported so far.

Inhibition of the extracellular enzyme A disintegrin and metalloprotease with thrombospondin motif 4 prevents cardiac fibrosis and dysfunction.

Aims: Heart failure is a condition with high mortality rates, and there is a lack of therapies that directly target maladaptive changes in the extracellular matrix (ECM), such as fibrosis. We investigated whether the ECM enzyme known as A disintegrin and metalloprotease with thrombospondin motif (ADAMTS) 4 might serve as a therapeutic target in treatment of heart failure and cardiac fibrosis.

Methods And Results: The effects of pharmacological ADAMTS4 inhibition on cardiac function and fibrosis were examined in rats exposed to cardiac pressure overload.

"11 for Health" in the Faroe Islands: Popularity in schoolchildren aged 10-12 and the effect on well-being and health knowledge.

Background: We aimed to investigate the popularity of the "11 for Health program for Europe" for 10-12-year-old Faroese children and the effects on well-being and health knowledge.

Methods: We applied a cluster-randomized controlled trial, including a total of 19 school clusters, randomized into intervention schools (IG, n = 12) and control schools (CG, n = 7). A total of 261 children (137 boys and 124 girls) participated.

DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients.

Purpose: Reactive oxygen species (ROS) are an important part of the inflammatory response during infection but can also promote DNA damage. Due to the sustained inflammation in severe Covid-19, we hypothesized that hospitalized Covid-19 patients would be characterized by increased levels of oxidative DNA damage and dysregulation of the DNA repair machinery.

Patients And Methods: Levels of the oxidative DNA lesion 8-oxoG and levels of base excision repair (BER) proteins were measured in peripheral blood mononuclear cells (PBMC) from patients (8-oxoG, n = 22; BER, n = 17) and healthy controls (n = 10) (Cohort 1).

Mapping of pituitary stress-induced gene regulation connects Nrcam to negative emotions.

Environmental stressors such as repeated social defeat may initiate powerful activation of subconscious parts of the brain. Here, we examine the consequences of such stress (induced by resident-intruder paradigm) on the pituitary gland. In male stressed vs.

Targeting the Inflammasome in Cardiovascular Disease.

The pathogenesis of cardiovascular disease (CVD) is complex and multifactorial, and inflammation plays a central role. Inflammasomes are multimeric protein complexes that are activated in a 2-step manner in response to infection or tissue damage. Upon activation the proinflammatory cytokines, interleukins-1β and -18 are released.

NEIL3-deficient bone marrow displays decreased hematopoietic capacity and reduced telomere length.

Deficiency of NEIL3, a DNA repair enzyme, has significant impact on mouse physiology, including vascular biology and gut health, processes related to aging. Leukocyte telomere length (LTL) is suggested as a marker of biological aging, and shortened LTL is associated with increased risk of cardiovascular disease. NEIL3 has been shown to repair DNA damage in telomere regions .

Evaluating the prognostic performance of a polygenic risk score for breast cancer risk stratification.

Background: Polygenic risk scores (PRS) could potentially improve breast cancer screening recommendations. Before a PRS can be considered for implementation, it needs rigorous evaluation, using performance measures that can inform about its future clinical value.

Objectives: To evaluate the prognostic performance of a regression model with a previously developed, prevalence-based PRS and age as predictors for breast cancer incidence in women from the Estonian biobank (EstBB) cohort; to compare it to the performance of a model including age only.

NEIL3-deficiency increases gut permeability and contributes to a pro-atherogenic metabolic phenotype.

Atherosclerosis and its consequences cause considerable morbidity and mortality world-wide. We have previously shown that expression of the DNA glycosylase NEIL3 is regulated in human atherosclerotic plaques, and that NEIL3-deficiency enhances atherogenesis in Apoe mice. Herein, we identified a time point prior to quantifiable differences in atherosclerosis between ApoeNeil3 mice and Apoe mice.

Instability in NAD metabolism leads to impaired cardiac mitochondrial function and communication.

Poly(ADP-ribose) polymerase (PARP) enzymes initiate (mt)DNA repair mechanisms and use nicotinamide adenine dinucleotide (NAD) as energy source. Prolonged PARP activity can drain cellular NAD reserves, leading to de-regulation of important molecular processes. Here, we provide evidence of a pathophysiological mechanism that connects mtDNA damage to cardiac dysfunction via reduced NAD levels and loss of mitochondrial function and communication.

The diagnostic accuracy of human epididymis protein 4 (HE4) for discriminating between benign and malignant pelvic masses: a systematic review and meta-analysis.

Introduction: Many women with benign pelvic masses, suspected of ovarian cancer, are unnecessarily referred for treatment at specialized centers. There is an unmet clinical need to improve diagnostic assessment in these patients. Our objective was to obtain summary estimates of the accuracy of human epididymis protein (HE4) for diagnosing ovarian cancer and to compare the performance of HE4 with that of cancer antigen 125 (CA125).

Maximal Fat Oxidation Rate Is Higher in Fit Women and Unfit Women With Obesity, Compared to Normal-weight Unfit Women.

Context: The maximal fat oxidation rate (MFO) is higher in aerobically fit vs unfit young men, but this training-related increase in MFO is attenuated in middle-aged men. Further, it has also been found that unfit men with obesity may have an elevated MFO compared to unfit normal-weight men.

Objective: Based hereupon, we aimed to investigate whether a fitness-related higher MFO were attenuated in middle-aged women compared to young women.

Study designs for comparative diagnostic test accuracy: A methodological review and classification scheme.

Objectives: (1) To identify and classify comparative diagnostic test accuracy (DTA) study designs; (2) to describe study design labels used by authors of comparative DTA studies.

Methods: We performed a methodological review of 100 comparative DTA studies published between 2015 and 2017, randomly sampled from studies included in 238 comparative DTA systematic reviews indexed in MEDLINE in 2017. From each study report, we extracted six design elements characterizing participant flow and the labels used by authors.

DNA glycosylase Neil3 regulates vascular smooth muscle cell biology during atherosclerosis development.

Background And Aims: Atherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cell (VSMC) phenotype. The DNA glycosylase NEIL3 has previously been shown to have a role in atherogenesis, though whether this is due to its ability to repair DNA damage or to other non-canonical functions is not yet clear. Hereby, we investigate the role of NEIL3 in atherogenesis, specifically in VSMC phenotypic modulation, which is critical in plaque formation and stability.

Absence of NLRP3 Inflammasome in Hematopoietic Cells Reduces Adverse Remodeling After Experimental Myocardial Infarction.

An inflammatory response is required for tissue healing after a myocardial infarction (MI), but the process must be balanced to prevent maladaptive remodeling. This study shows that improved survival and cardiac function following MI, in mice deficient for the NLRP3 inflammasome, can be recapitulated in wild-type mice receiving bone marrow from mice. This suggests that NLRP3 activation in hematopoietic cells infiltrating in the myocardium increases mortality and late ventricular remodeling.

Reducing regional health inequality: a sub-national distributional cost-effectiveness analysis of community-based treatment of childhood pneumonia in Ethiopia.

Background: Increasing the coverage of community-based treatment of childhood pneumonia (CCM) is part of the strategy to improve child survival, increase life-expectancy at birth and promote equity in Ethiopia. However, full coverage of CCM has not been reached in any regions of the country. There are no sub-national cost-effectiveness analyses available to inform decision makers on the most equitable scale up strategy.

Reporting of test comparisons in diagnostic accuracy studies: A literature review.

Comparative accuracy studies evaluate the relative performance of two or more diagnostic tests. As any other form of research, such studies should be reported in an informative manner, to allow replication and to be useful for decision-making. In this study we aimed to assess whether and how components of test comparisons were reported in comparative accuracy studies.