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Objective: The aim of the study was to assess the potential association between serum 25-hydroxyvitamin D (25(OH)D) and whole-body bone mineral density (BMD) among 16-year-old adolescents and to study the prevalence of 25(OH)D insufficiency, defined as concentration under 50 nmol/l.Design: A cross-sectional study.Setting: Reykjavik, Iceland, latitude 64°08'N. Measurements took place in the Icelandic Heart Association's research lab during April-June 2015.Participants: In total, 411 students in Reykjavik, Iceland, were invited to participate, 315 accepted the invitation (76·6 %) and 289 had valid data (mainly Caucasian).Results: 25(OH)D < 50 nmol/l was observed in 70 % of girls and 66·7 % of boys. 25(OH)D ≥ 50 nmol/l was significantly associated with higher whole-body BMD after adjusting for the influence of sex, height, fat mass and lean mass. A linear relationship between 25(OH)D and whole-body BMD was significant for 25(OH)D < 50 nmol/l (n 199, P < 0·05) but NS for 25(OH)D ≥ 50 nmol/l (n 86, P = 0·48).Conclusions: Our results are in line with some but not all previous studies on the relationship between BMD and 25(OH)D in adolescents. The observed difference in BMD between those with above v. below a 25(OH)D concentration of 50 nmol/l was of about a fifth of one SD, which may have a clinical relevance as one SD decrease in volumetric BMD has been associated with a 89 % increase in 2 years risk of fracture. Icelandic adolescents should be encouraged to increase their vitamin D intake as it is possible that their current intake is insufficient to achieve optimal peak bone mass. [ABSTRACT FROM AUTHOR]

A disease outbreak in farmed Atlantic cod caused by Yersinia ruckeri is reported. Mortality started following vaccination of cod reared in two tanks (A and B). The accumulated mortality reached 1.9% in A and 4.8% in B in the following 30 days when treatment with oxytetracycline was applied. Biochemical and molecular analysis of Y. ruckeri isolates from the cod and other fish species from fresh and marine waters in Iceland revealed a high salinity-tolerant subgroup of Y. ruckeri serotype O1. Infected fish showed clinical signs comparable with those of Y. ruckeri -infected salmonids, with the exception of granuloma formations in infected cod tissues, which is a known response of cod to bacterial infections. Immunohistological examination showed Y. ruckeri antigens in the core of granulomas and the involvement of immune parameters that indicates a strong association between complement and lysozyme killing of bacteria. Experimental infection of cod with a cod isolate induced disease, and the calculated LD50 was 1.7 × 104 CFU per fish. The results suggest that yersiniosis can be spread between populations of freshwater and marine fish. Treatment of infected cod with antibiotic did not eliminate the infection, which can be explained by the immune response of cod producing prolonged granulomatous infection. [ABSTRACT FROM AUTHOR]

Background Age at menopause may affect women's subsequent morbidity and mortality. In contrast to numerous other health outcomes, little is known about the possible effects of physical activity on age at menopause. Objectives To assess the relationship between leisure-time physical activity and age at menopause. Methods Premenopausal women participating in a population-based health survey (HUNT 2) conducted in the county of Nord-Trøndelag, Norway reported their physical activity in the period of 1995--1997. Age at menopause was reported during 2006--2008 (HUNT 3). Cox proportional hazards models were used to estimate hazard ratios for menopause and logistic regression to estimate odds ratios for early menopause, with 95% confidence intervals, adjusting for age at menarche, parity, use of oral contraceptives prior to the 6 months preceding participation in HUNT 2, symptoms of depression, smoking status, and education. Results Women aged 40--49 years at baseline had lower hazard ratios for menopause when participating in any light leisure-time physical activity compared with no activity (p < 0.05) and similar results were observed in 19--39-year-olds. In 50--59-year-old women, the results varied greatly and did not reach statistical significance. Conclusions The effects of leisure-time physical activity on age at menopause may be age-dependent. We found indications of earlier menopause for the least active women aged 19--49 years at baseline. [ABSTRACT FROM AUTHOR]

BACKGROUND: Changes in the state of energy balance owing to changes in physical activity may affect the reproductive system. We evaluated the association between physical activity (PA) and fertility and parity in healthy women. [ABSTRACT FROM PUBLISHER]

A total of 1239 kidney samples from four species of salmonid fish, Atlantic salmon, Salmo salar L., brown trout, Salmo trutta L., Aretic charr. Salvelinus alpinus (L.), and rainbow trout, Oncorhynchus mykiss (Walbaum). were screened for Renibacterium salmoninarum using double-sandwich ELISA and bacterial isolation. For bacterial isolation, samples wore homogenized, washed, plated onto S-KDM and incubated for 12 weeks. Samples for ELISA were kept frozen until tested. After thawing, 25% homogenates in PBS were heated at KIOT for 15min in the presence (2 5% v/v) of HemoDe solvent (terpene and butylated hydroxyanisole) and then centrifuged. The supernatant was tested with polyclonal antibodies against whole bacterium in a double-sandwich ELISA. In seven out of 12 groups tested, all samples wore negative in both tests. Positive ELISA results occurred in five groups. Renibacterium salmoninarum was isolated on SKDM from samples in four out of these five groups. The ELISA test gave significantly higher numbers of positive samples in three out of the four groups showing positive results in both tests. [ABSTRACT FROM AUTHOR]

The article presents a study of the Acute Phase Response (APR) induced by Aeromonas salmonicida subspecies achromogenes (Asa), a common bacterial pathogen in cod and other fishes. Gene expression in cod's kidney and spleen and cortisol levels in serum were measured. Particular focus is also given to the role of cortisol in the suppression of the IL-1β gene expression.

Background: Signal transducer and activator of transcription 6 (STAT6) is central to type 2 (T2) inflammation, and common noncoding variants at the STAT6 locus associate with various T2 inflammatory traits, including diseases, and its pathway is widely targeted in asthma treatment., Objective: We sought to test the association of a rare missense variant in STAT6, p.L406P, with T2 inflammatory traits, including the risk of asthma and allergic diseases, and to characterize its functional consequences in cell culture., Methods: The association of p.L406P with plasma protein levels, white blood cell counts, and the risk of asthma and allergic phenotypes was tested. Significant associations in other cohorts were also tested using a burden test. The effects of p.L406P on STAT6 protein function were examined in cell lines and by comparing CD4 + T-cell responses from carriers and noncarriers of the variant., Results: p.L406P associated with reduced plasma levels of STAT6 and IgE as well as with lower eosinophil and basophil counts in blood. It also protected against asthma, mostly driven by severe T2-high asthma. p.L406P led to lower IL-4-induced activation in luciferase reporter assays and lower levels of STAT6 in CD4 + T cells. We identified multiple genes with expression that was affected by the p.L406P genotype on IL-4 treatment of CD4 + T cells; the effect was consistent with a weaker IL-4 response in carriers than in noncarriers of p.L406P., Conclusions: A partial loss-of-function variant in STAT6 resulted in dampened IL-4 responses and protection from T2-high asthma, implicating STAT6 as an attractive therapeutic target., Competing Interests: Disclosure statement Disclosure of potential conflict of interest: K. Kristjansdottir, G. L. Norddahl, E. V. Ivarsdottir, G. H. Halldorsson, G. Einarsson, K. Bjarnadóttir, G. Rutsdottir, A. O. Arnthorsson, S. Gudmundsdottir, K. Gunnarsdottir, B. V. Halldorsson, H. Holm, S. Saevarsdottir, A. S. Snaebjarnarson, G. Sveinbjornsson, G. E. Thorlacius, G. Thorleifsson, V. Tragante, P. Sulem, D. F. Gudbjartsson, P. Melsted, I. Jonsdottir, T. A. Olafsdottir, and K. Stefansson are employees of deCODE genetics, a subsidiary of Amgen., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and 4571 individuals under 18 years, we discover ten new and identify four known variants at five loci influencing IgG subclass levels. These variants also affect the risk of asthma, autoimmune diseases, and blood traits. Seven variants map to the IGH locus, three to the Fcγ receptor (FCGR) locus, and two to the human leukocyte antigen (HLA) region, affecting the levels of all IgG subclasses. The most significant associations are observed between the G1m (f), G2m(n) and G3m(b*) allotypes, and IgG1, IgG2 and IgG3, respectively. Additionally, we describe selective associations with IgG4 at 16p11.2 (ITGAX) and 17q21.1 (IKZF3, ZPBP2, GSDMB, ORMDL3). Interestingly, the latter coincides with a highly pleiotropic signal where the allele associated with lower IgG4 levels protects against childhood asthma but predisposes to inflammatory bowel disease. Our results provide insight into the regulation of antibody-mediated immunity that can potentially be useful in the development of antibody based therapeutics., (© 2024. The Author(s).)

Background: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear., Methods: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection., Results: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection., Conclusions: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection., (© 2023. The Author(s).)

Using a longitudinal field survey, we collected data on how implementing an activity-based work environment impacts employees across time [1]. The sample consisted of 100 employees in a government organization implementing an activity-based working environment, with each employee surveyed on three time-points. The sample included all employees affected by the implementation. At each time-point, the response rate was 87%, 75%, and 69%, respectively. The sample was approximately 75% female at each time-point. Data collection took place about two months before the activity-based environment was implemented (condition 1), again about four months after implementation (condition 2), and finally, about nine months after implementation (condition 3). All data were collected using an online survey. The survey included questions on privacy, psychological ownership, and attitude towards activity-based work, in addition to questions on productivity, job satisfaction, job strain, and satisfaction with the work environment., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2022 The Author(s). Published by Elsevier Inc.)

Background: Loss-of-function mutations in the LDL (low-density lipoprotein) receptor gene ( LDLR ) cause elevated levels of LDL cholesterol and premature cardiovascular disease. To date, a gain-of-function mutation in LDLR with a large effect on LDL cholesterol levels has not been described. Here, we searched for sequence variants in LDLR that have a large effect on LDL cholesterol levels., Methods: We analyzed whole-genome sequencing data from 43 202 Icelanders. Single-nucleotide polymorphisms and structural variants including deletions, insertions, and duplications were genotyped using whole-genome sequencing-based data. LDL cholesterol associations were carried out in a sample of >100 000 Icelanders with genetic information (imputed or whole-genome sequencing). Molecular analyses were performed using RNA sequencing and protein expression assays in Epstein-Barr virus-transformed lymphocytes., Results: We discovered a 2.5-kb deletion (del2.5) overlapping the 3' untranslated region of LDLR in 7 heterozygous carriers from a single family. Mean level of LDL cholesterol was 74% lower in del2.5 carriers than in 101 851 noncarriers, a difference of 2.48 mmol/L (96 mg/dL; P =8.4×10 - 8 ). Del2.5 results in production of an alternative mRNA isoform with a truncated 3' untranslated region. The truncation leads to a loss of target sites for microRNAs known to repress translation of LDLR . In Epstein-Barr virus-transformed lymphocytes derived from del2.5 carriers, expression of alternative mRNA isoform was 1.84-fold higher than the wild-type isoform ( P =0.0013), and there was 1.79-fold higher surface expression of the LDL receptor than in noncarriers ( P =0.0086). We did not find a highly penetrant detrimental impact of lifelong very low levels of LDL cholesterol due to del2.5 on health of the carriers., Conclusions: Del2.5 is the first reported gain-of-function mutation in LDLR causing a large reduction in LDL cholesterol. These data point to a role for alternative polyadenylation of LDLR mRNA as a potent regulator of LDL receptor expression in humans.

Background: Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed., Results: Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR., Conclusions: Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR., (Copyright © 2020 Massachusetts Medical Society.)

A novel 27 kDa ladder-lectin-like protein, showing a multimeric structure under non-reducing conditions, was isolated from halibut serum by binding to N-acetyl glucosamine. Mass-spectrometry analysis did not show significant homology with known proteins. Specific antibodies were produced and used in immunohistochemistry on tissue sections of early halibut ontogeny from 119 until 1050 °d post hatching. A strong positive response was detected in the mucosal cells of the skin, gills and gut, indicating a role in the mucosal immune defence at these sites. Further immunopositivity was detected in liver, myeloma of kidney and the brain at different developmental stages but predominant expression was found in mucosal surfaces at later stages of development tested (1050 °d). It is still uncertain whether this ladder-like lectin forms part of the complement pathway, as a lectin or ficolin, or if it belongs to galectins. A strong detection in mucosal surfaces on skin, gills and gut, show similar patterns of expression as both mucosal lectins and galectins in other fish. Detection in neuronal tissue may indicate putative roles in tissue remodelling of brain and in ongoing neurogenesis in the fish eye., (Copyright © 2018 Elsevier Ltd. All rights reserved.)