Browsing by Subject "EXPOSURE"

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  • Halonen, Jaana I.; Erhola, Marina; Furman, Eeva; Haahtela, Tari; Jousilahti, Pekka; Barouki, Robert; Bergman, Åke; Billo, Nils E.; Fuller, Richard; Haines, Andrew; Kogevinas, Manolis; Kolossa-Gehring, Marike; Krauze, Kinga; Lanki, Timo; Vicente, Joana Lobo; Messerli, Peter; Nieuwenhuijsen, Mark; Paloniemi, Riikka; Peters, Annette; Posch, Karl-Heinz; Timonen, Pekka; Vermeulen, Roel; Virtanen, Suvi M.; Bousquet, Jean; Antó, Josep M. (2021)
    In 2015, the Rockefeller Foundation-Lancet Commission launched a report introducing a novel approach called Planetary Health and proposed a concept, a strategy and a course of action. To discuss the concept of Planetary Health in the context of Europe, a conference entitled: “Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health” was held in Helsinki in December 2019. The conference participants concluded with a need for action to support Planetary Health during the 2020s. The Helsinki Declaration emphasizes the urgency to act as scientific evidence shows that human activities are causing climate change, biodiversity loss, land degradation, overuse of natural resources and pollution. They threaten the health and safety of human kind. Global, regional, national, local and individual initiatives are called for and multidisciplinary and multisectorial actions and measures are needed. A framework for an action plan is suggested that can be modified for local needs. Accordingly, a shift from fragmented approaches to policy and practice towards systematic actions will promote human health and health of the planet. Systems thinking will feed into conserving nature and biodiversity, and into halting climate change. The Planetary Health paradigm ‒ the health of human civilization and the state of natural systems on which it depends ‒ must become the driver for all policies.
  • Odeh, Issam; Hussein, Tareq (2016)
    Knowledge of human activity patterns is needed in air pollution exposure and health risk assessment. However, human activity patterns have never been evaluated in the Eastern Mediterranean societies. Therefore, we investigated the activity pattern of 285 subjects (17-63 years) in Amman, Jordan during October to November, 2015. The subjects spent >80% of their time indoors during weekend days and >85% on workdays. They spent similar to 4.8% and similar to 5.7% in transportation during weekend days and workdays, respectively. Males had a different activity pattern than females on weekend days, but both genders had similar activity patterns on workdays. On workdays, males spent less time indoors than females. The activity pattern found in this study is a bit different than that for North Americans and Europeans, who spend more time indoors and in transit. The activity pattern found in this study was very different than that observed for Koreans, who spent about 59% and 67% indoors on workdays and weekend, respectively. The main outcomes of this survey can be utilized in human exposure studies. This study and the upcoming future studies have been encouraged and supported by the regional WHO office in Amman.
  • Maragkidou, Androniki; Jaghbeir, Omar; Hämeri, Kaarle; Hussein, Tareq (2018)
    In this study, we measured the concentrations of accumulation and coarse particles inside an educational workshop (March 31–April 6, 2015), calculated particle emission and losses rates, and estimated inhaled deposited dose. We used an Optical Particle Sizer (TSI OPS 3330) that measures the particle number size distribution (diameter 0.3–10 μm) and we converted that into particle mass size distribution (assuming spherical particles and unit density). We focused on two particle size fractions: 0.3–1 μm (referred as PN0.3−1 and PM0.3−1) and 1–10 μm (referred as PN1−10 and PM1−10). The occupants' activities included coffee brewing, lecturing, tobacco smoking, welding, scrubbing, and sorting/drilling iron. The highest concentrations were observed during welding with PN0.3−1 (PM0.3−1) was ∼1866 cm−3 (55 μg/m3) and PN1−10 (PM1−10) was ∼7 cm−3 (103 μg/m3). The lowest concentrations were observed during coffee brewing and metal turning with PN0.3−1 (PM0.3−1) was ∼22 cm−3 (0.7 μg/m3) and PN1−10 (PM1−10) was ∼0.5 cm−3 (4 μg/m3). The emissions rate of coarse particles was 85–1010 particles/hour × cm3 whereas that for submicron particle in the diameter range 0.3–1 μm was 5.7 × 104–9.3 × 104 particles/hour × cm3 depending on the activity and the ventilation rate. The coarse particles losses rate was 0.35–2.1 h−1 and the ventilation rate was 0.24–2.1 h−1. The alveolar received the majority and particles below 1 μm with a fraction of about 53% of the total inhaled deposited dose whereas the head/throat region received about 18%. This study is important for better understanding the health effects at educational workshops.
  • Malanchini, Margherita; Smith-Woolley, Emily; Ayorech, Ziada; Rimfeld, Kaili; Krapohl, Eva; Vuoksimaa, Eero; Korhonen, Tellervo; Bartels, Meike; van Beijsterveldt, Toos C. E. M.; Rose, Richard J.; Lundstrom, Sebastian; Anckarsater, Henrik; Kaprio, Jaakko; Lichtenstein, Paul; Boomsma, Dorret I.; Plomin, Robert (2019)
    Background Maternal smoking during pregnancy (MSDP) has been linked to offspring's externalizing problems. It has been argued that socio-demographic factors (e.g. maternal age and education), co-occurring environmental risk factors, or pleiotropic genetic effects may account for the association between MSDP and later outcomes. This study provides a comprehensive investigation of the association between MSDP and a single harmonized component of externalizing: aggressive behaviour, measured throughout childhood and adolescence. Methods Data came from four prospective twin cohorts - Twins Early Development Study, Netherlands Twin Register, Childhood and Adolescent Twin Study of Sweden, and FinnTwin12 study - who collaborate in the EU-ACTION consortium. Data from 30 708 unrelated individuals were analysed. Based on item level data, a harmonized measure of aggression was created at ages 9-10; 12; 14-15 and 16-18. Results MSDP predicted aggression in childhood and adolescence. A meta-analysis across the four samples found the independent effect of MSDP to be 0.4% (r = 0.066), this remained consistent when analyses were performed separately by sex. All other perinatal factors combined explained 1.1% of the variance in aggression across all ages and samples (r = 0.112). Paternal smoking and aggressive parenting strategies did not account for the MSDP-aggression association, consistent with the hypothesis of a small direct link between MSDP and aggression. Conclusions Perinatal factors, including MSDP, account for a small portion of the variance in aggression in childhood and adolescence. Later experiences may play a greater role in shaping adolescents' aggressive behaviour.
  • Korpela, Katri; Salonen, Anne; Saxen, Harri; Nikkonen, Anne; Peltola, Ville; Jaakkola, Tytti; de Vos, Willem; Kolho, Kaija-Leena (2020)
    BACKGROUND The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota. METHODS Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home. RESULTS One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions. CONCLUSIONS Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.
  • Weichert, I.; Romero-Ortuno, R.; Tolonen, J.; Soe, T.; Lebus, C.; Choudhury, S.; Nadarajah, C. V.; Nanayakkara, P.; Orru, M.; Di Somma, S. (2018)
    What is known and objectiveDrugs with anticholinergic properties increase the risk of falls, delirium, chronic cognitive impairment, and mortality and counteract procholinergic medications used in the treatment of dementia. Medication review and optimisation to reduce anticholinergic burden in patients at risk is recommended by specialist bodies. Little is known how effective this review is in patients who present acutely and how often drugs with anticholinergic properties are used temporarily during an admission. The aim of the study was to describe the changes in the anticholinergic cognitive burden (ACB) in patients admitted to hospital with a diagnosis of delirium, chronic cognitive impairment or falls and to look at the temporary use of anticholinergic medications during hospital stay. MethodsThis is a multi-centre observational study that was conducted in seven different hospitals in the UK, Finland, The Netherlands and Italy. Results and discussion21.1% of patients had their ACB score reduced by a mean of 1.7%, 19.7% had their ACB increased by a mean of 1.6%, 22.8% of DAP naive patients were discharged on anticholinergic medications. There was no change in the ACB scores in 59.2% of patients. 54.1% of patients on procholinergics were taking anticholinergics. Out of the 98 medications on the ACB scale, only 56 were seen. Medications with a low individual burden were accounting for 64.9% of the total burden. Anticholinergic drugs were used temporarily during the admission in 21.9% of all patients. A higher number of DAPs used temporarily during admission was associated with a higher risk of ACB score increase on discharge (OR=1.82, 95% CI for OR: 1.36-2.45, P What is new and conclusionThere was no reduction in anticholinergic cognitive burden during the acute admissions. This was the same for all diagnostic subgroups. The anticholinergic load was predominantly caused by medications with a low individual burden. More than 1 in 5 patients not taking anticholinergics on admission were discharged on them and similar numbers saw temporary use of these medications during their admission. More than half of patients on cholinesterase-inhibitors were taking anticholinergics at the same time on admission, potentially directly counteracting their effects.
  • Raju, Sajan C.; Viljakainen, Heli; Figueiredo, Rejane A. O.; Neuvonen, Pertti J.; Eriksson, Johan G.; Weiderpass, Elisabete; Rounge, Trine B. (2020)
    Background: The human microbiota contributes to health and well-being. Antimicrobials (AM) have an immediate effect on microbial diversity and composition in the gut, but next to nothing is known about their long-term contribution to saliva microbiota. Our objectives were to investigate the long-term impact of AM use on saliva microbiota diversity and composition in preadolescents. We compared the lifetime effects by gender and AMs. We used data from 808 randomly selected children in the Finnish Health In Teens (Fin-HIT) cohort with register-based data on AM purchases from the Social Insurance Institution of Finland. Saliva microbiota was assessed with 16S rRNA (V3-V4) sequencing. The sequences were aligned to the SILVA ribosomal RNA database and classified and counted using the mothur pipeline. Associations between AM use and alpha-diversity (Shannon index) were identified with linear regression, while associations between beta-diversity (Bray-Curtis dissimilarity) and low, medium or high AM use were identified with PERMANOVA. Results: Of the children, 53.6% were girls and their mean age was 11.7 (0.4) years. On average, the children had 7.4 (ranging from 0 to 41) AM prescriptions during their lifespan. The four most commonly used AMs were amoxicillin (n= 2622, 43.7%), azithromycin (n= 1495, 24.9%), amoxicillin-clavulanate (n= 1123, 18.7%) and phenoxymethylpenicillin (n= 408, 6.8%). A linear inverse association was observed between the use of azithromycin and Shannon index (b- 0.015,pvalue = 0.002) in all children, the effect was driven by girls (b- 0.032,pvalue = 0.001), while not present in boys. Dissimilarities were marked between high, medium and low users of all AMs combined, in azithromycin users specifically, and in boys with amoxicillin use. Amoxicillin and amoxicillin-clavulanate use was associated with the largest decrease in abundance ofRikenellaceae. AM use in general and phenoxymethylpenicillin specifically were associated with a decrease ofPaludibacterand pathways related to amino acid degradations differed in proportion between high and low AM users. Conclusions: A systematic approach utilising reliable registry data on lifetime use of AMs demonstrated long-term effects on saliva microbiota diversity and composition. These effects are gender- and AM-dependent. We found that frequent lifelong use of AMs shifts bacterial profiles years later, which might have unforeseen health impacts in the future. Our findings emphasise a concern for high azithromycin use, which substantially decreases bacterial diversity and affects composition as well. Further studies are needed to determine the clinical implications of our findings.
  • Leppilahti, Jussi; Majuri, Marja-Leena; Sorsa, Timo; Hirvonen, Ari; Piirilä, Päivi (2019)
    Introduction: Di-isocyanates TDI (toluene di-isocyanate), MDI (diphenylmethane di-isocyanate), and HDI (hexamethylene di-isocyanate) are the most common chemicals causing occupational asthma. Di-isocyanate inhalation has been reported to induce oxidative stress via reactive oxygen and nitrogen species leading to tissue injury. Glutathione transferases (GSTs) and N-acetyltransferases (NATs) are detoxifying enzymes whose general function is to inactivate electrophilic substances. The most important genes regulating these enzymes, i.e., GSTM1, GSTP1, GSTT1, NAT1, and NAT2 have polymorphic variants resulting in enhanced or lowered enzyme activities. Since inability to detoxify harmful oxidants can lead to inflammatory processes involving activation of bronchoconstrictive mechanisms, we studied whether the altered GST and NAT genotypes were associated with bronchial hyperreactivity (BHR) in patients with di-isocyanate exposure related occupational asthma, irrespective of cessation of di-isocyanate exposure, and adequacy of asthma treatment.Methods: Polymerase chain reaction (PCR) based methods were used to analyze nine common polymorphisms in GSTM1, GSTM3, GSTP1, GSTT1, NAT1, and NAT2 genes in 108 patients with diagnosed occupational di-isocyanate-induced asthma. The genotype data were compared with spirometric lung function and BHR status at diagnosis and in the follow-up examination on average 11 years (range 1–22 years) after the asthma diagnosis. Serum IgE and IL13 levels were also assessed in the follow-up phase.Results: An association between BHR and GSTP1 slow activity (Val105/Val105) genotype was demonstrated in the subjects at the follow-up phase but not at the diagnosis phase. Moreover, the patients with the GSTP1 slow activity genotype exhibited characteristics of Th-2 type immune response more often compared to those with the unaltered GSTP1 gene. Interestingly, all 10 patients with the GSTP1 slow activity genotype had both the GSTM3 slow activity genotype and the unaltered GSTT1 gene.Discussion: The results suggest associations of the low activity variants of the GSTP1 gene with BHR. The fact that these associations came up only at the follow-up phase when the subjects were not any more exposed to di-isocyanates, and used asthma medication, suggest that medication and environmental factors influence the presentation of these associations. However, due to the exploratory character of the study and relatively small study size, the findings remain to be confirmed in future studies with larger sample sizes.
  • Savelieva, Kateryna; Marttila, Tero; Lampi, Jussi; Ung-Lanki, Sari; Elovainio, Marko; Pekkanen, Juha (2019)
  • Vari, Heli; Roslund, Marja; Oikarinen, Sami; Nurminen, Noora; Puhakka, Riikka; Parajuli, Anirudra; Grönroos, Mira; Siter, Nathan; Laitinen, Olli; Hyöty, Heikki; Rajaniemi, Juho; Rantalainen, Anna-Lea; Sinkkonen, Aki; The ADELE Research Group (2021)
    There is evidence that polycyclic aromatic hydrocarbons (PAHs) and human gut microbiota are associated with the modulation of endocrine signaling pathways. Independently, studies have found associations between air pollution, land cover and commensal microbiota. We are the first to estimate the interaction between land cover categories associated with air pollution or purification, PAH levels and endocrine signaling predicted from gut metagenome among urban and rural populations. The study participants were elderly people (65-79 years); 30 lived in rural and 32 in urban areas. Semi-Permeable Membrane devices were utilized to measure air PAH concentrations as they simulate the process of bioconcentration in the fatty tissues. Land cover categories were estimated using CORINE database and geographic information system. Functional orthologues for peroxisome proliferator-activated receptor (PPAR) pathway in endocrine system were analyzed from gut bacterial metagenome with Kyoto Encyclopaedia of Genes and Genomes. High coverage of broad-leaved and mixed forests around the homes were associated with decreased PAH levels in ambient air, while gut functional orthologues for PPAR pathway increased along with these forest types. The difference between urban and rural PAH concentrations was not notable. However, some rural measurements were higher than the urban average, which was due to the use of heavy equipment on active farms. The provision of air purification by forests might be an important determining factor in the context of endocrine disruption potential of PAHs. Particularly broad-leaved forests around homes may reduce PAH levels in ambient air and balance pollution-induced disturbances within commensal gut microbiota. (C) 2020 The Author(s). Published by Elsevier Ltd.
  • Karvala, Kirsi; Uitti, Jukka; Taponen, Saara; Luukkonen, Ritva; Lehtimäki, Lauri (2018)
    Objective: To study the association between perceptions of various triggers of asthma and employment status. Methods: A questionnaire was administered to all those adults living in the city of Tampere, Finland, who were entitled to special reimbursement for asthma medication by the Social Insurance Institution (n = 2613). The response rate was 79%. The study population (n = 1657) consisted of individuals who worked full-time (n = 967), were unemployed (n = 197), had all-cause work disability (n = 334), or were retired due to old age (n = 159). Given a list of potential asthma triggers, the respondents were asked how often (never/sometimes/often) the trigger caused or worsened their asthma symptoms during leisure time. Results: After adjusting for background variables (age, sex, smoking, and professional status), frequency of asthma symptoms, and the use of asthma medication during the last year, any individual trigger identified as asthma-relevant was associated with having work disability (vs. working full-time). The highest odds ratio (OR) was found for vehicle exhaust (OR 5.0, CI 2.2-11.4). We found similar but less consistent associations between asthma trigger perceptions and unemployment. No elevated ORs were found regarding asthma trigger perceptions for old-age retirement. Conclusions: Perceptions of asthma triggers are associated with all-cause work disability. Our findings suggest that asthmatics have excess trigger perceptions that are not explained by asthma alone. Asthmatics need to be informed that inaccurate trigger perceptions may develop, and how they are induced, because unnecessary trigger avoidance may interfere with work life.
  • Twardziok, Monika; Schroder, Paul C.; Krusche, Johanna; Casaca, Vera I.; Illi, Sabina; Bock, Andreas; Loss, Georg J.; Kabesch, Michael; Toncheva, Antoaneta A.; Roduit, Caroline; Depner, Martin; Genuneit, Jon; Renz, Harald; Roponen, Marjut; Weber, Juliane; Braun-Fahrlander, Charlotte; Riedler, Josef; Lauener, Roger; Vuitton, Dominique Angele; Dalphin, Jean-Charles; Pekkanen, Juha; von Mutius, Erika; Schaub, Bianca; PASTURE Study Grp; Hyvarinen, Anne; Karvonen, Anne M.; Kirjavainen, Pirkka V.; Remes, Sami; Kaulek, Vincent; Dalphin, Marie-Laure; Ege, Markus; Pfefferle, Petra I.; Doekes, Gert (2017)
    Several studies report an important role of CD8(+) cytotoxic T-cells in atopy. Farm children show protection against atopy development, partly explained by CD4(+) T-cell subtypes. Additional effects of CD8(+) T-cells are unknown being investigated in this study within the PASTURE/EFRAIM birth cohort in PBMCs from farming and non-farming 6-year-old (N = 76) German children. CD3(+) CD8(+) CD25(+) T-cells were analyzed by flow cytometry. Genotyping of 17q21 locus-SNPs associated with childhood asthma was performed. No differences in CD8(+) T-cell subsets were seen between farmers and non-farmers regardless of asthma. Among farm children, asthmatics displayed increased CD3(+) CD8(low)(CD25(+)) T-cells compared to non-asthmatics. Asthmatic farm children exhibited a lower PI-induced stimulatory capacity of CD3(+) CD8(low)(CD25(+)) cells and a lower IFN-gamma secretion than non-asthmatic farm children. Among farm children with GSDMB and ORMDL3 risk alleles, asthmatics displayed higher CD3(+) CD8(low) cells than non-asthmatics. Our data indicates a specific role of CD8(low) T-cells in asthmatic farm children. (C) 2017 Elsevier Inc. All rights reserved.
  • Czamara, Darina; Dieckmann, Linda; Roeh, Simone; Kraemer, Sarah; Rancourt, Rebecca C.; Sammallahti, Sara; Kajantie, Eero; Laivuori, Hannele; Eriksson, Johan G.; Räikkönen, Katri; Henrich, Wolfgang; Plagemann, Andreas; Binder, Elisabeth B.; Braun, Thorsten; Entringer, Sonja (2021)
    Background Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. Results We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enhancer site was associated with higher expression of FKBP5 and a co-expressed gene module. This module is enriched for genes associated with preeclampsia and involved in inflammation and immune response. Conclusions Our findings suggest that BET exposure during pregnancy associates with few but lasting changes in placental DNAm and may promote a gene expression profile associated with placental dysfunction and increased inflammation. This may represent a pathway mediating GC-associated negative long-term consequences and health outcomes in offspring.
  • Philips, Elise M.; Santos, Susana; Trasande, Leonardo; Aurrekoetxea, Juan J.; Barros, Henrique; von Berg, Andrea; Bergstroem, Anna; Bird, Philippa K.; Brescianini, Sonia; Chaoimh, Carol Ni; Charles, Marie-Aline; Chatzi, Leda; Chevrier, Cecile; Chrousos, George P.; Costet, Nathalie; Criswell, Rachel; Crozier, Sarah; Eggesbo, Merete; Fantini, Maria Pia; Farchi, Sara; Forastiere, Francesco; van Gelder, Marleen M. H. J.; Georgiu, Vagelis; Godfrey, Keith M.; Gori, Davide; Hanke, Wojciech; Heude, Barbara; Hryhorczuk, Daniel; Iniguez, Carmen; Inskip, Hazel; Karvonen, Anne M.; Kenny, Louise C.; Kull, Inger; Lawlor, Debbie A.; Lehmann, Irina; Magnus, Per; Manios, Yannis; Melen, Erik; Mommers, Monique; Morgen, Camilla S.; Moschonis, George; Murray, Deirdre; Nohr, Ellen A.; Andersen, Anne-Marie Nybo; Oken, Emily; Oostvogels, Adriette J. J. M.; Papadopoulou, Eleni; Pekkanen, Juha; Pizzi, Costanza; Polanska, Kinga; Porta, Daniela; Richiardi, Lorenzo; Rifas-Shiman, Sheryl L.; Roeleveld, Nel; Rusconi, Franca; Santos, Ana C.; Sorensen, Thorkild I. A.; Standl, Marie; Stoltenberg, Camilla; Sunyer, Jordi; Thiering, Elisabeth; Thijs, Carel; Torrent, Maties; Vrijkotte, Tanja G. M.; Wright, John; Zvinchuk, Oleksandr; Gaillard, Romy; Jaddoe, Vincent W. V. (2020)
    Author summaryWhy was this study done? Maternal smoking during pregnancy is an important risk factor for various birth complications and childhood overweight. It is not clear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy. The associations of paternal smoking with birth and childhood outcomes also remain unknown. What did the researchers do and find? We conducted an individual participant data meta-analysis using data from 229,158 families from 28 pregnancy and birth cohorts from Europe and North America to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. We observed that smoking in the first trimester only did not increase the risk of preterm birth and small size for gestational age but was associated with a higher risk of childhood overweight, as compared to nonsmoking. Reducing the number of cigarettes during pregnancy, without quitting, was still associated with higher risks of these adverse outcomes. Paternal smoking seems to be associated, independently of maternal smoking, with the risks of childhood overweight. What do these findings mean? Population strategies should focus on parental smoking prevention before or at the start of, rather than during, pregnancy. Future studies are needed to assess the specific associations of smoking in the preconception and childhood periods with offspring outcomes. Background Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. Methods and findings We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35],Pvalue = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15],Pvalue = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23],Pvalue <0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48],Pvalue <0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to = 10 to 5-9 and
  • Vähänikkilä, N.; Pohjanvirta, T.; Haapala, V.; Simojoki, H.; Soveri, T.; Browning, G. F.; Pelkonen, S.; Wawegama, N. K.; Autio, T. (2019)
    Mycoplasma bovis causes bovine respiratory disease, mastitis, arthritis and otitis. The importance of M. bovis has escalated because of recent outbreaks and introductions into countries previously free of M. bovis. We characterized the course of M. bovis infection on 19 recently infected dairy farms over 24 months. Our objective was to identify diagnostic tools to assess the efficacy of control measures to assess low risk infection status on M. bovis infected farms. PCR assays and culture were used to detect M. bovis, and in-house and BioX ELISAs were used to follow antibody responses. Cows and young stock were sampled on four separate occasions, and clinical cases were sampled when they arose. On 17 farms, a few cases of clinical mastitis were detected, mostly within the first eight weeks after the index case. Antibodies detected by in-house ELISA persisted in the serum of cows at least for 1.5 years on all farms, regardless of the M. bovis infection status or signs of clinical disease or subclinical mastitis on the farm. Six out of 19 farms became low risk as the infection was resolved. Our results suggest that, for biosecurity purposes, regular monitoring should be conducted on herds by screening for M. bovis in samples from cows with clinical mastitis and calves with pneumonia, in conjunction with testing young stock by screening longitudinally collected nasal swabs for M. bovis and sequential serum samples for antibody against recombinant antigen.
  • Lamichhane, Santosh; Kemppainen, Esko; Trost, Kajetan; Siljander, Heli; Hyöty, Heikki; Ilonen, Jorma; Toppari, Jorma; Veijola, Riitta; Hyötyläinen, Tuulia; Knip, Mikael; Oresic, Matej (2019)
    Aims/hypothesis Metabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group. Methods We analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS. Results In early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids. Conclusions/interpretation Our findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.
  • Tharmalingam, Melissa D.; Matilionyte, Gabriele; Wallace, William H. B.; Stukenborg, Jan-Bernd; Jahnukainen, Kirsi; Oliver, Elizabeth; Goriely, Anne; Lane, Sheila; Guo, Jingtao; Cairns, Bradley; Jorgensen, Anne; Allen, Caroline M.; Lopes, Federica; Anderson, Richard A.; Spears, Norah; Mitchell, Rod T. (2020)
    Background Clinical studies indicate chemotherapy agents used in childhood cancer treatment regimens may impact future fertility. However, effects of individual agents on prepubertal human testis, necessary to identify later risk, have not been determined. The study aimed to investigate the impact of cisplatin, commonly used in childhood cancer, on immature (foetal and prepubertal) human testicular tissues. Comparison was made with carboplatin, which is used as an alternative to cisplatin in order to reduce toxicity in healthy tissues. Methods We developed an organotypic culture system combined with xenografting to determine the effect of clinically-relevant exposure to platinum-based chemotherapeutics on human testis. Human foetal and prepubertal testicular tissues were cultured and exposed to cisplatin, carboplatin or vehicle for 24 h, followed by 24-240 h in culture or long-term xenografting. Survival, proliferation and apoptosis of prepubertal germ stem cell populations (gonocytes and spermatogonia), critical for sperm production in adulthood, were quantified. Results Cisplatin exposure resulted in a significant reduction in the total number of germ cells (- 44%, p <0.0001) in human foetal testis, which involved an initial loss of gonocytes followed by a significant reduction in spermatogonia. This coincided with a reduction (- 70%, p <0.05) in germ cell proliferation. Cisplatin exposure resulted in similar effects on total germ cell number (including spermatogonial stem cells) in prepubertal human testicular tissues, demonstrating direct relevance to childhood cancer patients. Xenografting of cisplatin-exposed human foetal testicular tissue demonstrated that germ cell loss (- 42%, p <0.01) persisted at 12 weeks. Comparison between exposures to human-relevant concentrations of cisplatin and carboplatin revealed a very similar degree of germ cell loss at 240 h post-exposure. Conclusions This is the first demonstration of direct effects of chemotherapy exposure on germ cell populations in human foetal and prepubertal testis, demonstrating platinum-induced loss of all germ cell populations, and similar effects of cisplatin or carboplatin. Furthermore, these experimental approaches can be used to determine the effects of established and novel cancer therapies on the developing testis that will inform fertility counselling and development of strategies to preserve fertility in children with cancer.
  • Valtonen, Ville (2017)
    A great variety of non-specific symptoms may occur in patients living or working in moisture-damaged buildings. In the beginning, these symptoms are usually reversible, mild, and present irritation of mucosa and increased morbidity due to respiratory tract infections and asthma-like symptoms. Later, the disease may become chronic and a patient is referred to a doctor where the assessment of dampness and mold hypersensitivity syndrome (DMHS) often presents diagnostic challenges. Currently, unanimously accepted laboratory tests are not yet available. Therefore, the diagnosis of DMHS is clinical and is based on the patient's history and careful examination. In this publication, I reviewed contemporary knowledge on clinical presentations, laboratory methods, and clinical assessment of DMHS. From the literature, I have not found any proposed diagnostic clinical criteria. Therefore, I propose five clinical criteria to diagnose DMHS: (1) the history of mold exposure in water-damaged buildings, (2) increased morbidity to due infections, (3) sick building syndrome, (4) multiple chemical sensitivity, and (5) enhanced scent sensitivity. If all the five criteria are met, the patient has a very probable DMHS. To resolve the current problems in assigning correct DMHS diagnosis, we also need novel assays to estimate potential risks of developing DMHS.
  • Im, Ulas; Christensen, Jesper H.; Nielsen, Ole-Kenneth; Sand, Maria; Makkonen, Risto; Geels, Camilla; Anderson, Camilla; Kukkonen, Jaakko; Lopez-Aparicio, Susana; Brandt, Jørgen (2019)
    This modeling study presents the sectoral contributions of anthropogenic emissions in the four Nordic countries (Denmark, Finland, Norway and Sweden) on air pollution levels and the associated health impacts and costs over the Nordic and the Arctic regions for the year 2015. The Danish Eulerian Hemispheric Model (DEHM) has been used on a 50 km resolution over Europe in tagged mode in order to calculate the response of a 30 % reduction of each emission sector in each Nordic country individually. The emission sectors considered in the study were energy production, non-industrial/commercial heating, industry, traffic, off-road mobile sources and waste management/agriculture. In total, 28 simulations were carried out. Following the air pollution modeling, the Economic Valuation of Air Pollution (EVA) model has been used to calculate the associated premature mortality and their costs. Results showed that more than 80 % of the PM2.5 concentration was attributed to transport from outside these four countries, implying an effort outside the Nordic region in order to decrease the pollutant levels over the area. The leading emission sector in each country was found to be non-industrial combustion (contributing by more than 60 % to the total PM2.5 mass coming from the country itself), except for Sweden, where industry contributed to PM2.5 with a comparable amount to non-industrial combustion. In addition to non-industrial combustion, the next most important source categories were industry, agriculture and traffic. The main chemical constituent of PM2.5 concentrations that comes from the country itself is calculated to be organic carbon in all countries, which suggested that nonindustrial wood burning was the dominant national source of pollution in the Nordic countries. We have estimated the total number of premature mortality cases due to air pollution to be around 4000 in Denmark and Sweden and around 2000 in Finland and Norway. These premature mortality cases led to a total cost of EUR 7 billion in the selected Nordic countries. The assessment of the related premature mortality and associated cost estimates suggested that non-industrial combustion, together with industry and traffic, will be the main sectors to be targeted in emission mitigation strategies in the future.
  • Mocroft, Amanda; Lundgren, Jens D.; Ross, Michael; Law, Matthew; Reiss, Peter; Kirk, Ole; Smith, Colette; Wentworth, Deborah; Neuhaus, Jacqueline; Fux, Christoph A.; Moranne, Olivier; Morlat, Phillipe; Johnson, Margaret A.; Ryom, Lene; DAD Study Grp; Royal Free Hosp Clin Cohort; INSIGHT Study Grp; SMART Study Grp; ESPRIT Study Grp; Ristola, M. (2015)
    Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score <0, 33 events), rising to 1: 47 and 1: 6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score >= 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.