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Acute coronary syndrome (ACS) is a major cause of mortality worldwide. We have previously shown that increased interleukin-10 (IL-10) levels are associated with poor outcome in ACS patients. We performed a genome-wide association study in 2864 ACS patients and 408 healthy controls, to identify genetic variants associated with IL-10 levels. Then haplotype analyses of the identified loci were done and comparisons to levels of IL-10 and other known ACS related biomarkers. Genetic variants at the ABO blood group locus associated with IL-10 levels (top SNP: rs676457, P = 4.4 × 10-10) were identified in the ACS patients. Haplotype analysis, using SNPs tagging the four main ABO antigens (A1, A2, B and O), showed that O and A2 homozygous individuals, or O/A2 heterozygotes have much higher levels of IL-10 compared to individuals with other antigen combinations. In the ACS patients, associations between ABO antigens and von Willebrand factor (VWF, P = 9.2 × 10-13), and soluble tissue factor (sTF, P = 8.6 × 10-4) were also found. In the healthy control cohort, the associations with VWF and sTF were similar to those in ACS patients (P = 1.2 × 10-15 and P = 1.0 × 10-5 respectively), but the healthy cohort showed no association with IL-10 levels (P>0.05). In the ACS patients, the O antigen was also associated with an increased risk of cardiovascular death, all causes of death, and recurrent myocardial infarction (odds ratio [OR] = 1.24-1.29, P = 0.029-0.00067). Our results suggest that the ABO antigens play important roles, not only for the immunological response in ACS patients, but also for the outcome of the disease.

There are several documented events of changes in subnuclear localization during gene activation. However, there are conflicting data on whether the nuclear periphery is a compartment for gene repression or activation and whether genes are moved to the pores at the nuclear membrane (NM) or not during gene activation. Nitrogen starvation of fission yeast serves as a good model system for studying gene induction, as it causes fast regulation of hundreds of genes. In this study, the subnuclear localization of two gene clusters repressed by nitrogen was investigated. During normal growth conditions, the gene clusters localized to the nuclear periphery at the opposite side of the nucleus as compared to the spindle pole body. This constrained localization was dependent on the histone deacetylase Clr3, known to transcriptionally repress genes in these clusters. Already 20 min after nitrogen depletion, drastic changes in subnuclear localization of the two loci were observed, away from the NM toward the nuclear interior. At least for one of the clusters, the movement was clearly transcription dependent. Data presented in this paper illustrates how interconnected events of gene activation and nuclear reorganization are as well as provides a suggestion of how nuclear organization might be maintained.

Cardiovascular diseases (CVDs) are a common cause of death, and a search for biomarkers for risk stratification is warranted. Elevated levels of cell-derived microparticles (MPs) are found in patients with CVD and in groups with risk factors for CVD. Subpopulations of MPs are promising biomarkers for improving risk prediction, as well as monitoring treatment. However, the field has been hampered by technical difficulties, and the ongoing development of sensitive standardized techniques is crucial for implementing MP analyses in the clinic. Large prospective studies are required to establish which MPs are of prognostic value in different patient groups. In this review, we discuss methodological challenges and progress in the field, as well as MP populations that are of interest for further clinical evaluation.

Introduction Acute coronary syndrome (ACS) is a major cause of mortality worldwide. We have previously shown that increased interleukin-10 (IL-10) levels are associated with poor outcome in ACS patients. Method We performed a genome-wide association study in 2864 ACS patients and 408 healthy controls, to identify genetic variants associated with IL-10 levels. Then haplotype analyses of the identified loci were done and comparisons to levels of IL-10 and other known ACS related biomarkers. Results Genetic variants at the ABO blood group locus associated with IL-10 levels (top SNP: rs676457, P = 4.4 10-10) were identified in the ACS patients. Haplotype analysis, using SNPs tagging the four main ABO antigens (A1, A2, B and O), showed that O and A2 homozygous individuals, or O/A2 heterozygotes have much higher levels of IL-10 compared to individuals with other antigen combinations. In the ACS patients, associations between ABO antigens and von Willebrand factor (VWF, P = 9.2 10-13), and soluble tissue factor (sTF, P = 8.6 10-4) were also found. In the healthy control cohort, the associations with VWF and sTF were similar to those in ACS patients (P = 1.2 10-15 and P = 1.0 10-5 respectively), but the healthy cohort showed no association with IL-10 levels (P>0.05). In the ACS patients, the O antigen was also associated with an increased risk of cardiovascular death, all causes of death, and recurrent myocardial infarction (odds ratio [OR] = 1.24-1.29, P = 0.029-0.00067). Conclusion Our results suggest that the ABO antigens play important roles, not only for the immunological response in ACS patients, but also for the outcome of the disease.

Background The estimated prognos of a patient might influence the expected benefit/risk ratio of different interventions. The main purpose of this study was to investigate the Clinical Frailty Scale (CFS) score as an independent predictor of short-, mid- and long-term mortality in critically ill older adults (aged ≥ 70) admitted to the emergency department (ED). Methods This is a retrospective, single-center, observational study, involving critically ill older adults, recruited consecutively in an ED. All patients were followed for 6.5–7.5 years. The effect of CFS score on mortality was adjusted for the following confounders: age, sex, Charlson’s Comorbidity Index, individual comorbidities and vital parameters. All patients ( n  = 402) were included in the short- and mid-term analyses, while patients discharged alive ( n  = 302) were included in the long-term analysis. Short-term mortality was analysed with logistic regression, mid- and long-term mortality with log rank test and Cox proportional hazard models. The CFS was treated as a continuous variable in the primary analyses, and as a categorical variable in completing analyses. Results There was a significant association between mortality at 30 days after ED admission and CFS score, adjusted OR (95% CI) 2.07 (1.64–2.62), p  < 0.0001. There was a significant association between mortality at one year after ED admission and CFS score, adjusted HR (95% CI) 1.75 (1.53–2.01), p  < 0.0001. There was a significant association between mortality 6.5–7.5 years after discharge and CFS score, adjusted HR (95% CI) 1.66 (1.46–1.89), p  < 0.0001. Adjusted HRs are also reported for long-term mortality, when the CFS was treated as a categorical variable: CFS-score 5 versus 1–4: HR (95% CI) 1.98 (1.27–3.08); 6 versus 1–4: HR (95% CI) 3.60 (2.39–5.44); 7 versus 1–4: HR (95% CI) 3.95 (2.38–6.55); 8–9 versus 1–4: HR (95% CI) 20.08 (9.30–43.38). The completing analyses for short- and mid-term mortality indicated a similar risk-predictive value of the CFS. Conclusions Clinical frailty scale score was independently associated with all-cause short-, mid- and long-term mortality. A nearly doubled risk of death was observed in frail patients. This information is clinically relevant, since individualised treatment and care planning for older adults should consider risk of death in different time perspectives.

ObjectiveTo examine the relation between long working hours and change in body mass index (BMI).MethodsWe performed random effects meta-analyses using individual-participant data from 19 cohort studies from Europe, US and Australia (n = 122,078), with a mean of 4.4-year follow-up. Working hours were measured at baseline and categorised as part time (<35 h/week), standard weekly hours (35–40 h, reference), 41–48 h, 49–54 h and ≥55 h/week (long working hours). There were four outcomes at follow-up: (1) overweight/obesity (BMI ≥ 25 kg/m2) or (2) overweight (BMI 25–29.9 kg/m2) among participants without overweight/obesity at baseline; (3) obesity (BMI ≥ 30 kg/m2) among participants with overweight at baseline, and (4) weight loss among participants with obesity at baseline.ResultsOf the 61,143 participants without overweight/obesity at baseline, 20.2% had overweight/obesity at follow-up. Compared with standard weekly working hours, the age-, sex- and socioeconomic status-adjusted relative risk (RR) of overweight/obesity was 0.95 (95% CI 0.90–1.00) for part-time work, 1.07 (1.02–1.12) for 41–48 weekly working hours, 1.09 (1.03–1.16) for 49–54 h and 1.17 (1.08–1.27) for long working hours (P for trend <0.0001). The findings were similar after multivariable adjustment and in subgroup analyses. Long working hours were associated with an excess risk of shift from normal weight to overweight rather than from overweight to obesity. Long working hours were not associated with weight loss among participants with obesity.ConclusionsThis analysis of large individual-participant data suggests a small excess risk of overweight among the healthy-weight people who work long hours.

IntroductionAn increasing number of women now work in previously male dominated occupations with high exposure to chemicals and particles, but high-quality epidemiological studies on effects of occupational exposure to chemicals and particles during pregnancy are lacking.Material and MethodsThis cohort study covers full-time employed women in Sweden, giving birth between 1994 and 2014, providing a sample of 719,330 pregnancies. Data were extracted from the Medical Birth Register, which contains information from prenatal care facilities and hospitals regarding the pregnancy (including diagnoses), background characteristics (maternal age, parity, smoking status, BMI, nationality), and occupation in gestational week 10.Occupational exposure to chemicals and particles were obtained by linking occupational codes to the Swedish Job Exposure Matrix (SWEJEM), partly based on FINJEM. Exposure levels derives from measurements and for each occupation, the proportion of workers exposed, and the mean intensity level are estimated. The JEM contains estimates for 41 different types of dust, gases, fumes, and particles in three-year intervals. Additional JEMs in SWEJEM were used to adjust for other occupational exposures.Results and ConclusionsPreliminary results indicate that exposure to several agents during pregnancy were positively associated with adverse pregnancy outcomes, in particular asphyxiants (carbon monoxide), combustion compounds (gasoline and diesel exhaust) for gestational hypertension and preeclampsia, and to an extent also exposure to paper or pulp for preeclampsia. For gestational diabetes, mainly metals (lead), were found associated with the specific outcome.To conclude, increased risks were found in association with several of the chemicals and particles under study. Many of these previously male dominated occupations, do not have guideline or exposure limit values in place to protect pregnant workers. This study has an explorative approach and further studies are therefore needed to verify the results.

IntroductionThe COVID-19 pandemic has profoundly challenged occupational safety and health. We assessed risk for hospitalization for COVID-19 in relation to potential routes and degree of occupational exposure.Material and MethodsThe study includes 1 105 042 subjects in the county of Stockholm of age 18–64 years, with an occupational code, followed regarding hospitalization from 1 March 2020 until 15 September 2022. We used two different job-exposure matrices (JEMs), based on survey data (Office for National Statistics 2020) and expert assessment (Oude Hengel et al 2022, module for Denmark), respectively. Hazard ratios (HRs) and 95% confidence intervals (CI) were obtained with Cox´s proportional hazards models. Fully adjusted models included age, sex, vaccination (time-dependent), household size, living space per person, income quintile, proportion of smokers in the occupation, and country of birth.ResultsWe observed 6523 hospitalizations with COVID-19 as the main diagnosis. HRs increased incrementally with the exposure dimensions in both JEMs and were increased already from the low-exposed categories.The fully adjusted HRs (95% CI) for the highest exposure category were for the survey-based JEM: Closeness to other people (very close, almost touching): 1.51 (1.42–1.59); Exposure to other people´s diseases (daily): 1.41 (1.33–1.50). Similarly, we found for the expert-based JEM: Number of co-workers in close vicinity (>30/day): 1.47 (1.39–1.57); Nature of contact with other people (regular contact with COVID-19 patients): 1.51 (1.40–1.63); Location of work (>4h/day indoors): 1.25 (1.19–1.31); Inability to keep social distancing (can never maintain >1m): 1.42 (1.33–1.51).ConclusionsDimensions of potential occupational exposure in both the survey- and expert-based JEMs were consistently associated with hospitalization for COVID-19 and may thus guide risk assessment. Increased risks observed already in the lower exposure categories indicate a need for enhanced preventive measures also in those settings.

Basalts are recognized as one of the major habitats on Earth, harboring diverse and active microbial populations. Inconsistently, this living component is rarely considered in engineering operations carried out in these environments. This includes carbon capture and storage (CCS) technologies that seek to offset anthropogenic CO 2 emissions into the atmosphere by burying this greenhouse gas in the subsurface. Here, we show that deep ecosystems respond quickly to field operations associated with CO 2 injections based on a microbiological survey of a basaltic CCS site. Acidic CO 2 -charged groundwater results in a marked decrease (by ~ 2.5–4) in microbial richness despite observable blooms of lithoautotrophic iron-oxidizing Betaproteobacteria and degraders of aromatic compounds, which hence impact the aquifer redox state and the carbon fate. Host-basalt dissolution releases nutrients and energy sources, which sustain the growth of autotrophic and heterotrophic species whose activities may have consequences on mineral storage. The impacts of carbon capture and storage (CCS) on subsurface microorganisms are poorly understood. Here, the authors show that deep ecosystems respond quickly to CO2 injections and that the environmental consequences of their metabolic activities need to be properly assessed for sustainable CCS in basalt.

JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006), and controls (OR = 2.69, p = 1×10(-5)). The German dataset confirmed these findings (OR = 0.54, p = 1×10(-4) and OR = 1.58, p = 0.03 respectively for these haplotypes). HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and lays the ground for risk stratification for PML and development of therapy and prevention.