| 1. |
|
|
| 2. |
|
|
| 3. |
- Accordini, S., et al.
(författare)
-
Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach
- 2021
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:4
-
Tidskriftsartikel (refereegranskat)abstract
- Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited. We investigated multigeneration causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age 18-47 years; 52.0% female) and their 274 fathers, who had participated in the European Community Respiratory Health Survey (ECRHS)/Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multilevel mediation models were developed with: paternal grandmothers' smoking in pregnancy and fathers' smoking initiation in prepuberty as exposures; fathers' forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); and offspring's FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences (Delta) in expected z-scores related to fathers' and grandmothers' smoking history. Fathers' smoking initiation in prepuberty had a negative direct effect on both offspring's FEV1 (Delta z-score -0.36, 95% CI -0.63--0.10) and FVC (-0.50, 95% CI -0.80--0.20) compared with fathers' never smoking. Paternal grandmothers' smoking in pregnancy had a negative direct effect on fathers' FEV1/FVC -0.57, 95% CI -1.09--0.05) and a negative indirect effect on offspring's FEV1/FVC (-0.12, 95% CI -0.21--0.03) compared with grandmothers' not smoking before fathers' birth nor during fathers' childhood. Fathers' smoking in prepuberty and paternal grandmothers' smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations.
|
|
| 4. |
|
|
| 5. |
- White, S. A., et al.
(författare)
-
Natural attenuation of large anthropogenic nitrate loads in a subtropical stream revealed by delta N-15 and delta O-18
- 2021
-
Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694. ; 598
-
Tidskriftsartikel (refereegranskat)abstract
- Nitrogen pollution in subtropical waters is rapidly increasing due to land-use change, but specific sources, transformations, and attenuation rates remain understudied compared to cooler temperate catchments. Here, we quantify high-resolution nitrate (NO3--N) loads, sources and natural attenuation in a subtropical creek in Australia over contrasting hydrological conditions. We observed large creek NO3-N loads (ranging from 44 to 2938 mu mol m(-2) catchment d(-1)) exceeding the bottom-up estimates of nitrogen input to the catchment at the most upstream sites. Stable isotope natural abundances (delta N-15 and delta O-18 in NO3--N) and Bayesian analysis revealed that greywater was the dominant source accounting for similar to 55% of NO3--N in the upper creek, but fertilisers (similar to 29%) and rainfall (similar to 16%) were also relevant NO3--N sources. NO3--N loads at the most downstream site were only 0.2-9.7% of loads at the most upstream site. The resulting NO3--N attenuation efficiency (mainly via denitrification) was 52-84% of original upstream load per km of creek, depending on hydrological conditions. This large capacity to attenuate NO3--N during dry and first-flush events exceeds the attenuation found in temperate creeks subject to several decades of pollution in the northern hemisphere. During periods of high water flow and saturated soils, high NO3--N loads were exported downstream, turning the creek from a natural bioreactor to a system resembling a flow-through pipe. In spite of effective natural nitrogen attenuation providing a valuable ecosystem service, concentrations and loads remained well above expected for natural systems and water quality guidelines. Overall, our results highlight the need for modifying fertiliser use, capturing nitrogen on farms and reducing greywater nitrogen to prevent significant losses to subtropical waterways.
|
|
| 6. |
- Holloway, A., et al.
(författare)
-
EVALUATING GLOBAL PATTERNS IN TREATMENT AND PREVALENCE OF COMORBIDITIES IN SYSTEMIC LUPUS ERYTHEMATOSUS
- 2023
-
Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1456-1458
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Regional disparities in the management of systemic lupus erythematosus (SLE) are frequently described. Governance, funding, logistic barriers, and physician choice may be important determinants though scarce data from underrepresented regions limits our understanding.Objectives: To evaluate global patterns in treatment of SLE and identify the prevalence of comorbidities.Methods: We identified SLE patients from the COVAD 2 database, consisting of over 20,000 respondents worldwide. Healthy controls (HC) were included to assess population comorbidity levels. Demographics, treatment i.e., corticosteroids (CS), antimalarials, immunosuppressants (IS), cyclophosphamide and biologics plus comorbidity data was recorded. Country Human Development Index (HDI) classification, a composite index formulated by the United Nations to rank countries into tiers of development, was utilised.Results: 3323 HCs and 1167 SLE patients were included in analysis. Patients from low/medium HDI (lmHDI) countries were younger than those from high/very high HDI (hvhHDI) countries (median age 32, IQR 27-41 vs 41, IQR 32-52 years, p<0.0001). Disease duration was shorter in lmHDI countries (median 5, IQR 3-10 vs 10, IQR 5-19 years, p<0.0001).A higher proportion of SLE patients from lmHDI countries were on CS (73% vs 59%, p=0.0002), antimalarials (81% vs 68%, p=0.0002) and IS (66% vs 53%, p=0.0009) compared with patients from hvhHDI countries. Choice of IS varied with azathioprine prescribed more frequently in lmHDI countries (p=0.049). Biologics use was more common in hvhHDI countries (7% vs 2%, p=0.0055). Comorbidity prevalence was similar between groups, however when adjusted for age, patients with chronic kidney disease were significantly younger in lmHDI countries (36.67 vs 44.64 years, p=0.015), as were patients with coronary artery disease (35.7 vs. 44.6 years, p=0.015) and hypertension (41.5 vs 49.8 years, p=0.003). Results are detailed in Table 1.Conclusion: To our knowledge, this is the largest study evaluating treatment and comorbidity incidence in SLE populations based on country HDI. We identified striking differences in pharmacological management globally. Cardiovascular comorbidities were seen in younger patients and earlier in the disease course in lmHDI countries, suggestive of premature organ damage. This could be due to limited global access to high-cost medication and increasing access may improve outcomes. Our results call for review of cardiovascular risk guidelines and regional approaches to preventive action as well as pharmacological and non-pharmacological management of patients with established cardiovascular comorbidity.
|
|
| 7. |
|
|
| 8. |
- Kitaba, N. T., et al.
(författare)
-
Fathers' preconception smoking and offspring DNA methylation
- 2023
-
Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7075 .- 1868-7083. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are, however, limited. We aim to identify epigenetic marks in offspring associated with father's preconception smoking.Methods We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort (7-50 years) on father's any preconception smoking (n = 875 offspring) and father's pubertal onset smoking < 15 years (n = 304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, own smoking and maternal smoking. EWAS of maternal and offspring personal smoking were performed for comparison. Father's smoking-associated dmCpGs were checked in subpopulations of offspring who reported no personal smoking and no maternal smoking exposure.Results Father's smoking commencing preconception was associated with methylation of blood DNA in offspring at two cytosine-phosphate-guanine sites (CpGs) (false discovery rate (FDR) < 0.05) in PRR5 and CENPP. Father's pubertal onset smoking was associated with 19 CpGs (FDR < 0.05) mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (p < 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. Father's smoking-associated sites did not overlap with dmCpGs identified in EWAS of personal and maternal smoking (FDR < 0.05), and all sites remained significant (p < 0.05) in analyses of offspring with no personal smoking and no maternal smoking exposure.Conclusion Father's preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underlie epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity.
|
|
| 9. |
- Merid, Simon Kebede, et al.
(författare)
-
Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
-
Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
|
|
| 10. |
- Shorter, Gillian W., et al.
(författare)
-
The "Outcome Reporting in Brief Intervention Trials: Alcohol" (ORBITAL) Core Outcome Set : International Consensus on Outcomes to Measure in Efficacy and Effectiveness Trials of Alcohol Brief Interventions
- 2021
-
Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 82:5, s. 638-646
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this study was to report the "Outcome Reporting in Brief Intervention Trials: Alcohol" (ORBITAL) recommended core outcome set (COS) to improve efficacy and effectiveness trials/evaluations for alcohol brief interventions (ABIs).Method: A systematic review identified 2,641 outcomes in 401 ABI articles measured by 1,560 different approaches. These outcomes were classified into outcome categories, and 150 participants from 19 countries participated in a two-round e-Delphi outcome prioritization exercise. This process prioritized 15 of 93 outcome categories for discussion at a consensus meeting of key stakeholders to decide the COS. A psychometric evaluation determined how to measure the outcomes.Results: Ten outcomes were voted into the COS at the consensus meeting: (a) typical frequency, (b) typical quantity, (c) frequency of heavy episodic drinking, (d) combined consumption measure summarizing alcohol use, (e) hazardous or harmful drinking (average consumption), (1) standard drinks consumed in the past week (recent, current consumption), (g) alcohol-related consequences, (h) alcohol-related injury, (i) use of emergency health care services (impact of alcohol use), and (j) quality of life.Conclusions: The ORBITAL COS is an international consensus standard for future ABI trials and evaluations. It can improve the synthesis of new findings, reduce redundant/selective reporting (i.e., reporting only some, usually significant outcomes), improve between-study comparisons, and enhance the relevance of trial and evaluation findings to decision makers. The COS is the recommended minimum and does not exclude oilier. additional outcomes.
|
|
