TRIF adaptor signaling is important in abdominal aortic aneurysm formation

Objective: Abdominal aortic aneurysm (AAA) is characterized by inflammation, loss of smooth muscle cells (SMCs), and degradation of the extracellular matrix in the vessel wall. Innate immune receptors such as Toll-like receptors (TLRs) were recently shown to regulate immunological processes leading to the formation and progression of atherosclerotic plaques as well as to other cardiovascular pathologies. Our aim was to investigate whether blockage of TLR signaling, under the control of TIR domain-containing adaptor protein including IFN-beta (TRIF), could inhibit the inflammatory response and AAA development in mice. Results: In human AAA, an increased TLR3 and TLR4 expression in association with macrophages and T lymphocytes was demonstrated with immunohistochemical analysis. Angiotensin (Ang) II-induced aneurysm formation was significantly reduced by 30% in ApoE(-/-)Trif(-/-) mice compared to ApoE(-/-) mice. Morphologically, AngII-infused ApoE(-/-)Trif(-/-) mice had a more intact cellular and extracellular matrix while ApoE(-/-) mice infused with AngII displayed an increased medial thickness associated with aortic dissection, thrombus formation, and a more disorganized vessel wall. Gene expression analysis of the abdominal aorta revealed a profound decrease of the inflammatory genes CD68 (P <0.05), CD11b (P <0.05), and TNF-alpha (P <0.05) and the protease gene MMP-12 (P <0.01) in ApoE(-/-)Trif(-/-) mice compared to ApoE(-/-) mice infused with AngII. Conclusion: Our results suggest that signaling through TRIF is important for the inflammatory response of AngII-induced AAA and that blockage of the TRIF pathway reduces vascular inflammation and protects against AAA formation. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.Peer reviewe

Expression of citrulline and homocitrulline residues in the lungs of non-smokers and smokers : implications for autoimmunity in rheumatoid arthritis

Introduction: Smoking is a well-established risk factor for rheumatoid arthritis (RA), and it has been proposed that smoking-induced citrullination renders autoantigens immunogenic. To investigate this mechanism, we examined human lung tissue from 40 subjects with defined smoking status, with or without chronic obstructive pulmonary disease (COPD), and control tissues from other organs for citrullinated proteins and the deiminating enzymes peptidylarginine deiminase type-2 (PAD2) and -4 (PAD4). Methods: Lung tissue samples, dissected from lobectomy specimens from 10 never smokers, 10 smokers without airflow limitation, 13 COPD smokers and eight COPD ex-smokers, and control tissue samples (spleen, skeletal muscle, liver, ovary, lymph node, kidney and heart), were analysed for citrullinated proteins, PAD2 and PAD4 by immunoblotting. Citrulline and homocitrulline residues in enolase and vimentin were analysed by partial purification by gel electrophoresis followed by mass spectrometry in 12 of the lung samples and one from each control tissues. Band intensities were scored semi-quantitatively and analysed by two-tailed Mann-Whitney T-test. Results: Within the lung tissue samples, citrullinated proteins, PAD2 and PAD4 were found in all samples, with an increase in citrullination in COPD (P = 0.039), but minimal difference between smokers and non-smokers (P = 0.77). Citrullination was also detected at lower levels in the tissues from other organs, principally in lymph node, kidney and skeletal muscle. Mass spectrometry of the lung samples showed that vimentin was citrullinated at positions 71, 304, 346, 410 and 450 in non-smokers and smokers both with and without COPD. A homocitrulline at position 104 was found in four out of six COPD samples and one out of six non-COPD. Citrulline-450 was also found in three of the control tissues. There were no citrulline or homocitrulline residues demonstrated in a-enolase. Conclusions: We have shown evidence of citrullination of vimentin, a major autoantigen in RA, in both non-smokers and smokers. The increase in citrullinated proteins in COPD suggests that citrullination in the lungs of smokers is mainly due to inflammation. The ubiquity of citrullination of vimentin in the lungs and other tissues suggests that the relationship between smoking and autoimmunity in RA may be more complex than previously thought

Survival trends in patients diagnosed with colon and rectal cancer in the nordic countries 1990-2016 : The NORDCAN survival studies

Background: Survival of patients with colon and rectal cancer has improved in all Nordic countries during the past decades. The aim of this study was to further assess survival trends in patients with colon and rectal cancer in the Nordic countries by age at diagnosis and to present additional survival measures. Methods: Data on colon and rectal cancer cases diagnosed in the Nordic countries between 1990 and 2016 were obtained from the NORDCAN database. Relative survival was estimated using flexible parametric models. Both age-standardized and age-specific measures for women and men were estimated from the models, as well as reference-adjusted crude probabilities of death and life-years lost. Results: The five-year age-standardized relative survival of colon and rectal cancer patients continued to improve for women and men in all Nordic countries, from around 50% in 1990 to about 70% at the end of the study period. In general, survival was similar across age and sex. The largest improvement was seen for Danish men and women with rectal cancer, from 41% to 69% and from 43% to 71%, respectively. The age-standardized and reference-adjusted five-year crude probability of death in colon cancer ranged from 30% to 36% across countries, and for rectal cancer from 20% to 33%. The average number of age-standardized and reference-adjusted life-years lost ranged between six and nine years. Conclusion: There were substantial improvements in colon and rectal cancer survival in all Nordic countries 1990-2016. Of special note is that the previously observed survival disadvantage in Denmark is no longer present. (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Trends in cancer survival in the Nordic countries 1990-2016 : the NORDCAN survival studies

Background Differences in cancer survival between the Nordic countries have previously been reported. The aim of this study was to examine whether these differences in outcome remain, based on updated information from five national cancer registers. Materials and methods The data used for the analysis was from the NORDCAN database focusing on nine common cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway and Sweden with maximum follow-up through 2017. Relative survival (RS) was estimated at 1 and 5 years using flexible parametric RS models, and percentage point differences between the earliest and latest years available were calculated. Results A consistent improvement in both 1- and 5-year RS was found for most studied sites across all countries. Previously observed differences between the countries have been attenuated. The improvements were particularly pronounced in Denmark that now has cancer survival similar to the other Nordic countries. Conclusion The reasons for the observed improvements in cancer survival are likely multifactorial, including earlier diagnosis, improved treatment options, implementation of national cancer plans, uniform national cancer care guidelines and standardized patient pathways. The previous survival disadvantage in Denmark is no longer present for most sites. Continuous monitoring of cancer survival is of importance to assess the impact of changes in policies and the effectiveness of health care systems.Peer reviewe

Age-specific survival trends and life-years lost in women with breast cancer 1990-2016 : the NORDCAN survival studies

BackgroundA recent overview of cancer survival trends 1990-2016 in the Nordic countries reported continued improvements in age-standardized breast cancer survival among women. The aim was to estimate age-specific survival trends over calendar time, including life-years lost, to evaluate if improvements have benefited patients across all ages in the Nordic countries.MethodsData on breast cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway, and Sweden were obtained from the NORDCAN database. Age-standardized and age-specific relative survival (RS) was estimated using flexible parametric models, as was reference-adjusted crude probabilities of death and life-years lost.ResultsAge-standardized period estimates of 5-year RS in women diagnosed with breast cancer ranged from 87% to 90% and 10-year RS from 74% to 85%. Ten-year RS increased with 15-18 percentage points from 1990 to 2016, except in Sweden (+9 percentage points) which had the highest survival in 1990. The largest improvements were observed in Denmark, where a previous survival disadvantage diminished. Most recent 5-year crude probabilities of cancer death ranged from 9% (Finland, Sweden) to 12% (Denmark, Iceland), and life-years lost from 3.3 years (Finland) to 4.6 years (Denmark). Although survival improvements were consistent across different ages, women aged >= 70 years had the lowest RS in all countries. Period estimates of 5-year RS were 94-95% in age 55 years and 84-89% in age 75 years, while 10-year RS were 88-91% in age 55 years and 69-84% in age 75 years. Women aged 40 years lost on average 11.0-13.8 years, while women lost 3.8-6.0 years if aged 55 and 1.9-3.5 years if aged 75 years.ConclusionsSurvival for Nordic women with breast cancer improved from 1990 to 2016 in all age groups, albeit with larger country variation among older women where survival was also lower. Women over 70 years of age have not had the same survival improvement as women of younger age.Peer reviewe

Large-scale long-term passive-acoustic monitoring reveals spatio-temporal activity patterns of boreal bats

The distribution ranges and spatio-temporal patterns in the occurrence and activity of boreal bats are yet largely unknown due to their cryptic lifestyle and lack of suitable and efficient study methods. We approached the issue by establishing a permanent passive-acoustic sampling setup spanning the area of Finland to gain an understanding on how latitude affects bat species composition and activity patterns in northern Europe. The recorded bat calls were semi-automatically identified for three target taxa; Myotis spp., Eptesicus nilssonii or Pipistrellus nathusii and the seasonal activity patterns were modeled for each taxa across the seven sampling years (2015-2021). We found an increase in activity since 2015 for E. nilssonii and Myotis spp. For E. nilssonii and Myotis spp. we found significant latitude -dependent seasonal activity patterns, where seasonal variation in patterns appeared stronger in the north. Over the years, activity of P. nathusii increased during activity peak in June and late season but decreased in mid season. We found the passive-acoustic monitoring network to be an effective and cost-efficient method for gathering bat activity data to analyze spatio-temporal patterns. Long-term data on the composition and dynamics of bat communities facilitates better estimates of abundances and population trend directions for conservation purposes and predicting the effects of climate change

Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice

Increasing evidence suggests that oxidative DNA damage accumulates in atherosclerosis. Recently, we showed that a genetic variant in the human DNA repair enzyme NEIL3 was associated with increased risk of myocardial infarction. Here, we explored the role of Neil3/NEIL3 in atherogenesis by both clinical and experimental approaches. Human carotid plaques revealed increased NEIL3 mRNA expression which significantly correlated with mRNA levels of the macrophage marker CD68. Apoe−/−Neil3−/− mice on high-fat diet showed accelerated plaque formation as compared to Apoe−/− mice, reflecting an atherogenic lipid profile, increased hepatic triglyceride levels and attenuated macrophage cholesterol efflux capacity. Apoe−/−Neil3−/− mice showed marked alterations in several pathways affecting hepatic lipid metabolism, but no genotypic alterations in genome integrity or genome-wide accumulation of oxidative DNA damage. These results suggest a novel role for the DNA glycosylase Neil3 in atherogenesis in balancing lipid metabolism and macrophage function, potentially independently of genome-wide canonical base excision repair of oxidative DNA damage

Changes in Community Mobility in Older Men and Women. A 13-Year Prospective Study

Community mobility, defined as “moving [ones] self in the community and using public or private transportation”, has a unique ability to promote older peoples’ wellbeing by enabling independence and access to activity arenas for interaction with others. Early predictors of decreased community mobility among older men and women are useful in developing health promoting strategies. However, long-term prediction is rare, especially when it comes to including both public and private transportation. The present study describes factors associated with community mobility and decreased community mobility over time among older men and women. In total, 119 men and 147 women responded to a questionnaire in 1994 and 2007. Respondents were between 82 and 96 years old at follow-up. After 13 years, 40% of men and 43% of women had decreased community mobility, but 47% of men and 45% of women still experienced some independent community mobility. Cross-sectional independent community mobility among men was associated with higher ratings of subjective health, reporting no depression and more involvement in sport activities. Among women, cross-sectional independent community mobility was associated with better subjective health and doing more instrumental activities of daily living outside the home. Lower subjective health predicted decreased community mobility for both men and women, whereas self-reported health conditions did not. Consequently, general policies and individual interventions aiming to improve community mobility should consider older persons’ subjective health

Family History of Schizophrenia and Bipolar Disorder as Risk Factors for Autism

The clinical and etiological relation between autism spectrum disorders (ASD) and schizophrenia is unclear. The degree to which these disorders share a basis in etiology has important implications for clinicians, researchers, and those affected. Our objective was to determine if a family history of schizophrenia and/or bipolar disorder was a risk factor for ASD. We conducted a case-control evaluation of histories of schizophrenia or bipolar disorder in first-degree relatives of probands in three samples, population registers in Sweden, Stockholm County, and Israel. Probands met criteria for ASD, and affection status of parents and siblings for schizophrenia and bipolar disorder were established