| 1. |
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| 2. |
- Modvig, S, et al.
(författare)
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Value of Flow Cytometry for MRD-Based Relapse Prediction in B-Cell Precursor Acute Lymphoblastic Leukemia in a Multi-Center Setting
- 2019
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Ingår i: Blood. - 0006-4971 .- 1528-0020.
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Konferensbidrag (refereegranskat)abstract
- Background: PCR of rearranged antigen receptor genes is the method of choice for MRD quantification in ALL. Although FCM-MRD is faster and biologically more informative than PCR, the analysis requires a high level of training. The only larger published studies using FCM-MRD based stratification (Borowitz, Blood, 2008 and 2015) showed a clear association with clinical outcome in BCP-ALL. However, MRD analyses were centralized and these studies included only one MRD-based stratification (MRD levels at the end of induction). Patients and methods: We examined FCM-MRD as stratification tool in BCP-ALL at various timepoints in a large-scale multicenter (18 MRD centers) study. A total of 1487 patients with BCP-ALL (1298 children (younger than 18 years) and 189 adults (18-45 years) are included in the study and were treated according to the NOPHO ALL2008 protocol between July 2008 and February 2016. The median follow-up time for patients in first remission was 51 months (IQR 32-75). MRD was measured by FCM and/or real time quantitative PCR on days 15, 29 (end of induction) and 79 (for standard (SR) and intermediate risk (IR) patients) and prior to and after high risk blocks. A 6-colour FCM analysis including 3 standardized antibody combinations was used and performed in 18 laboratories. Patients were stratified by FCM-MRD, or by PCR-MRD if no FCM-MRD marker was available. End-of-induction MRD (cut-off 10-3) was used to stratify patients to standard risk (SR) vs intermediate risk (IR) or IR vs high risk consolidation therapy (in case of WBC > 100 x 109/L at diagnosis). Patients with MRD >=2.5x10-1 on day 15 were stratified to high risk block therapy. Patients with MRD >=5x10-2 on day 29 or day 79/post high risk-2 block MRD >=10-3 were stratified to HSCT. Primary outcomes were 5year event-free survival (5y EFS) and 5year cumulative incidence of relapse (5y CIR). Results: Only two patients (0.14% of total) had neither an informative FCM nor a PCR marker, and an informative FCM marker combination for MRD monitoring was identified in 96.2% of patients. There was a significant correlation between FCM- and PCR-MRD levels on day 15 (r=0.77, p<0.0001, n=153) and 29 (r=0.81, p<0.0001, n=140). Based on FCM-MRD only, the median MRD level on day 15, 29 and 79/post high risk-2 block was 5x10-3, 1.1x10-4, and below detection limit, respectively. Adults had significantly higher MRD levels at all time-points (p<0.0001 for day 15 and 29, p=0.0019 for day 79, Mann-Whitney). The 5y EFS was 86.1% (95% CI 84.1-88.1) with a 5y CIR of 9.5% (95% CI 7.8-11.3, n=1487). The day 29 FCM-MRD level was closely associated with clinical outcome and a higher hazard of relapse was seen independently for a FCM-MRD >=10-3 (hazard ratio (HR) 2.4, CI 1.6-3.7, p<0.0001), age>18 year (HR 3.0, CI 1.7-5.3, p<0.0001), WBC>=100 (HR 2.7, CI 1.6-4.6, p=0.0001), and B-other (HR 2.1, CI 1.2-3.5, p=0.0052) or high risk B-ALL cytogenetic aberration (rearranged KMT2A/iAMPchr21/hypodiploid) (HR 3.2, CI 1.6-6.1, p=0.0006) (multivariate cause-specific Cox regression, n=1328). Patients with a day 79 FCM-MRD >=10-4 and <10-3 had a significantly higher CIR (22.1%, CI 10.8-33.5%, n=68) compared to FCM-MRD <10-4 (7.5%, CI 2.1-12.8%, n=110) or undetectable (6.3%, CI 4.5-8.2%, n=999, p=0.0087 for FCM-MRD >=10-4 and <10-3vs <10-4 or undetectable). After adjusting for WBC, age, and the day 29 FCM-MRD level, a day 79 FCM-MRD >=10-4 and <10-3 was still significantly associated with a worse 5y CIR for non-transplanted patients (HR 2.3, CI 1.19-4.36, p=0.012 compared to undetectable FCM-MRD, n=1171). Patients with day 15 FCM-MRD <10-3 had a significantly better 5y EFS (92.0%, CI 89.2-95.0%) and CIR (3.9%, CI 1.7-6.1%, n=432) than patients with FCM-MRD >=10-3 and <2.5x10-1, who had a 5y EFS of 85.5% (CI 82.7-88.3%, p=0.0016, n=837) and a 3-fold higher 5y CIR (11.0%, CI 8.4-13.5%, p<0.0001, n=432). Among patients with day 15 FCM-MRD<10-3, the relapse incidence was comparable for patients with FCM-MRD 10-4 - <10-3 and below 10-4 (CIR 3.6, CI 0.5-6.7 vs. CIR 4.1, CI 1.0-7.2, p=0.83, n=432). Conclusion: FCM-MRD performed in a multi-center setting is a clinically useful method for disease monitoring and MRD-based treatment stratification in BCP-ALL. Moreover, FCM-MRD is a reliable indicator of outcome in BCP-ALL independently of other key risk factors. Residual disease >=10-4 and <10-3 at day 79 in SR/IR patients not allocated to HSCT further identifies patients with a high risk of relapse.
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| 3. |
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| 4. |
- Schjørring, O. L., et al.
(författare)
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Intensive care doctors’ preferences for arterial oxygen tension levels in mechanically ventilated patients
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:10, s. 1443-1451
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oxygen is liberally administered in intensive care units (ICUs). Nevertheless, ICU doctors’ preferences for supplementing oxygen are inadequately described. The aim was to identify ICU doctors’ preferences for arterial oxygenation levels in mechanically ventilated adult ICU patients. Methods: In April to August 2016, an online multiple-choice 17-part-questionnaire was distributed to 1080 ICU doctors in seven Northern European countries. Repeated reminder e-mails were sent. The study ended in October 2016. Results: The response rate was 63%. When evaluating oxygenation 52% of respondents rated arterial oxygen tension (PaO2) the most important parameter; 24% a combination of PaO2 and arterial oxygen saturation (SaO2); and 23% preferred SaO2. Increasing, decreasing or not changing a default fraction of inspired oxygen of 0.50 showed preferences for a PaO2 around 8 kPa in patients with chronic obstructive pulmonary disease, a PaO2 around 10 kPa in patients with healthy lungs, acute respiratory distress syndrome or sepsis, and a PaO2 around 12 kPa in patients with cardiac or cerebral ischaemia. Eighty per cent would accept a PaO2 of 8 kPa or lower and 77% would accept a PaO2 of 12 kPa or higher in a clinical trial of oxygenation targets. Conclusion: Intensive care unit doctors preferred PaO2 to SaO2 in monitoring oxygen treatment when peripheral oxygen saturation was not included in the question. The identification of PaO2 as the preferred target and the thorough clarification of preferences are important when ascertaining optimal oxygenation targets. In particular when designing future clinical trials of higher vs lower oxygenation targets in ICU patients.
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| 5. |
- Tulstrup, M., et al.
(författare)
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NT5C2 germline variants alter thiopurine metabolism and are associated with acquired NT5C2 relapse mutations in childhood acute lymphoblastic leukaemia
- 2018
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 32:12, s. 2527-2535
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Tidskriftsartikel (refereegranskat)abstract
- The antileukaemic drug 6-mercaptopurine is converted into thioguanine nucleotides (TGN) and incorporated into DNA (DNA-TG), the active end metabolite. In a series of genome-wide association studies, we analysed time-weighted means ((wm)) of erythrocyte concentrations of TGN (Ery-TGN) and DNA-TG in 1009 patients undergoing maintenance therapy for acute lymphoblastic leukaemia (ALL). In discovery analyses (454 patients), the propensity for DNA-TG incorporation ((wm)DNA-TG/(wm)Ery-TGN ratio) was significantly associated with three intronic SNPs in NT5C2 (top hit: rs72846714; P - 2.09 x 10(-10), minor allele frequency 15%). In validation analyses (555 patients), this association remained significant during both early and late maintenance therapy (P - 8.4 x 10(-6) and 1.3 x 10(-3), respectively). The association was mostly driven by differences in (wm)Ery-TGN, but in regression analyses adjusted for wmEry-TGN (P < 0.0001), rs72846714-A genotype was also associated with a higher (wm)DNA-TG (P - 0.029). Targeted sequencing of NT5C2 did not identify any missense variants associated with rs72846714 or (wm)Ery-TGN/(wm)DNA-TG. rs72846714 was not associated with relapse risk, but in a separate cohort of 180 children with relapsed ALL, rs72846714-A genotype was associated with increased occurrence of relapse-specific NT5C2 gain-of-function mutations that reduce cytosol TGN levels (P = 0.03). These observations highlight the impact of both germline and acquired mutations in drug metabolism and disease trajectory.
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| 6. |
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| 7. |
- Ding, Ming, et al.
(författare)
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Dairy consumption, systolic blood pressure, and risk of hypertension : Mendelian randomization study
- 2017
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.
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| 8. |
- Huang, Tao, et al.
(författare)
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Dairy Consumption and Body Mass Index Among Adults : Mendelian Randomization Analysis of 184802 Individuals from 25 Studies
- 2018
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 64:1, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27–0.92; P = 3.0 × 10−4).CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.
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| 9. |
- Landegren, Nils, et al.
(författare)
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Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis
- 2016
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Ingår i: Journal of the American Society of Nephrology: JASN. - 1533-3450 .- 1046-6673. ; 27:10, s. 3220-3228
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Tidskriftsartikel (refereegranskat)abstract
- Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.
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| 10. |
- Mikkelsen, L. H., et al.
(författare)
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Genomic and immunohistochemical characterisation of a lacrimal gland oncocytoma and review of literature
- 2017
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 14:4, s. 4176-4182
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to report the genetic and immunohistochemical profile of a rare case of lacrimal gland oncocytoma. A 20-year-old male underwent magnetic resonance imaging (MRI) due to viral encephalitis. Notably, the MRI revealed a multicystic tumor in the left lacrimal gland. A lateral orbitotomy was performed and the tumor was completely excised. Four months following surgery, the patient was free of symptoms. Histopathologically, the tumor was composed of large, eosinophilic and polyhedral cells with small round nuclei. The tumor cells stained strongly for antimitochondrial antibody MU213-UC, cytokeratin (CK) 5/6, CK 7, CK 17, CK 8/18 and CK 19. The final diagnosis was an oncocytoma of the lacrimal gland without any signs of malignancy. Array-based comparative genomic hybridisation demonstrated a gain of one copy of chromosome 8 and loss of one copy of chromosome 22 as the sole genomic imbalances. These chromosomal alterations have not previously been identified in oncocytoma and may be specific to lacrimal gland oncocytoma. Sequencing of the mitochondrial genome demonstrated multiple alterations of the NADH-ubiquinone oxidoreductase chain 5 (ND5) gene involved in mitochondrial oxidative phosphorylation. This may support the notion of a common genetic background of oncocytic lesions in the lacrimal gland and other anatomical sites. © 2017, Spandidos Publications. All rights reserved.
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| 11. |
- Modvig, S, et al.
(författare)
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Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia
- 2019
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Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 33:6, s. 1324-1336
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Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
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| 12. |
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| 13. |
- Rongve, Arvid, et al.
(författare)
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GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE ε4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 × 10 −8 ). One additional genetic locus previously linked to psychosis in Alzheimer’s disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 × 10 −6 . We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.
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| 14. |
- Anand-Ivell, Ravinder, et al.
(författare)
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Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias, and phthalate load : A large case-control study
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:APR
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Tidskriftsartikel (refereegranskat)abstract
- The period of the first to second trimester transition in human pregnancy represents a sensitive window for fetal organogenesis, particularly in regard to the development of the male reproductive system. This is a time of relative analytical inaccessibility. We have used a large national biobank of amniotic fluid samples collected at routine amniocentesis to determine the impacts of exogenous endocrine disruptor load on specific fetal biomarkers at this critical time. While adrenal and testicular steroids are highly correlated, they are also mostly positively influenced by increasing phthalate load, represented by the metabolites 7cx-MMeHP and 5cx-MEPP, by perfluorooctane sulfonate (PFOS) exposure, and by smoking, suggesting an adrenal stress response. In contrast, the testis specific biomarkers insulin-like peptide 3 (INSL3) and androstenedione are negatively impacted by the phthalate endocrine disruptors. Using a case-control design, we show that cryptorchidism and hypospadias are both significantly associated with increased amniotic concentration of INSL3 during gestational weeks 13-16, and some, though not all steroid biomarkers. Cases are also linked to a specifically increased variance in the Leydig cell biomarker INSL3 compared to controls, an effect exacerbated by maternal smoking. No influence of phthalate metabolites or PFOS was evident on the distribution of cases and controls. Considering that several animal and human studies have shown a negative impact of phthalate load on fetal and cord blood INSL3, respectively, the present results suggest that such endocrine disruptors may rather be altering the relative dynamics of testicular development and consequent hormone production, leading to a desynchronization of tissue organization during fetal development. Being born small for gestational age appears not to impact on the testicular biomarker INSL3 in second trimester amniotic fluid.
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| 15. |
- Babkevich, P., et al.
(författare)
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Dimensional Reduction in Quantum Dipolar Antiferromagnets
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 116:19
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Tidskriftsartikel (refereegranskat)abstract
- We report ac susceptibility, specific heat, and neutron scattering measurements on a dipolar-coupled antiferromagnet LiYbF4. For the thermal transition, the order-parameter critical exponent is found to be 0.20(1) and the specific-heat critical exponent -0.25(1). The exponents agree with the 2D XY/h(4) universality class despite the lack of apparent two-dimensionality in the structure. The order-parameter exponent for the quantum phase transitions is found to be 0.35(1) corresponding to (2 + 1)D. These results are in line with those found for LiErF4 which has the same crystal structure, but largely different T-N, crystal field environment and hyperfine interactions. Our results therefore experimentally establish that the dimensional reduction is universal to quantum dipolar antiferromagnets on a distorted diamond lattice.
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| 16. |
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| 17. |
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| 18. |
- Casey, Caitlin M., et al.
(författare)
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Physical Characterization of an Unlensed, Dusty Star-forming Galaxy at z = 5.85
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 887:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a physical characterization of MM J100026.36+021527.9 (a.k.a. "Mambo-9"), a dusty star-forming galaxy (DSFG) at z = 5.850 ± 0.001. This is the highest-redshift unlensed DSFG (and fourth most distant overall) found to date and is the first source identified in a new 2 mm blank-field map in the COSMOS field. Though identified in prior samples of DSFGs at 850 μm to 1.2 mm with unknown redshift, the detection at 2 mm prompted further follow-up as it indicated a much higher probability that the source was likely to sit at z > 4. Deep observations from the Atacama Large Millimeter and submillimeter Array (ALMA) presented here confirm the redshift through the secure detection of 12CO(J = 6→5) and p-H2O (21,1 → 20,2). Mambo-9 is composed of a pair of galaxies separated by 6 kpc with corresponding star formation rates of 590 M o˙ yr-1 and 220 M o˙ yr-1, total molecular hydrogen gas mass of (1.7 ± 0.4) × 1011 M o˙, dust mass of (1.3 ± 0.3) × 109 M o˙, and stellar mass of (3.2-1.5+1.0) × 109 M o˙. The total halo mass, (3.3 ± 0.8) × 1012 M o˙, is predicted to exceed 1015 M o˙ by z = 0. The system is undergoing a merger-driven starburst that will increase the stellar mass of the system tenfold in τ depl = 40-80 Myr, converting its large molecular gas reservoir (gas fraction of 96-2+1) into stars. Mambo-9 evaded firm spectroscopic identification for a decade, following a pattern that has emerged for some of the highest-redshift DSFGs found. And yet, the systematic identification of unlensed DSFGs like Mambo-9 is key to measuring the global contribution of obscured star formation to the star formation rate density at z ⪆ 4, the formation of the first massive galaxies, and the formation of interstellar dust at early times (≲1 Gyr).
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| 19. |
- Christensen, P S, et al.
(författare)
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Environmental cadmium and lead exposure and anti-Müllerian hormone in pregnant women
- 2016
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 61, s. 114-119
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anti-Müllerian Hormone (AMH) has been suggested as a marker for ovarian function. Cadmium and lead have been suggested to reduce female fecundity. In this study we aimed to investigate whether environmental exposure to cadmium and lead was associated with alterations in serum-AMH.MATERIALS AND METHOD: The associations between serum-AMH and whole blood cadmium or lead were investigated by general linear models in a population-based sample of 117 pregnant women.RESULTS: The mean concentrations of blood cadmium and lead were 0.71μg/L and 17.4μg/L, respectively. The mean serum-AMH was 17.3pmol/L. No association between lead and AMH was detected. In the cadmium analysis the adjusted mean AMH level (95% CI) in the highest exposure tertile was 12.4 (6.4;23.8) compared to 5.6 (2.7;11.4) in the lowest exposure tertile (p=0.06).CONCLUSION: The study provides suggestive evidence that environmental exposure to cadmium, but not lead, may alter the level of AMH.
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| 20. |
- Consales, Claudia, et al.
(författare)
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Exposure to persistent organic pollutants and sperm DNA methylation changes in Arctic and European populations.
- 2016
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 57:3, s. 200-209
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs), such as PCBs (polychlorinated biphenyls) and DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], are environmental contaminants with potential endocrine disrupting activity. DNA methylation levels in peripheral blood lymphocytes have been associated with serum concentrations of POPs in Greenland Inuit and Korean populations. Greenland Inuits are characterized by the highest worldwide POP levels. In this cross-sectional study we evaluated the relationship between serum POP concentrations and DNA methylation levels in sperm of non-occupationally exposed fertile men from Greenland, Warsaw (Poland), and Kharkiv (Ukraine). Serum levels of PCB-153 [1,2,4-trichloro-5-(2,4,5-trichlorophenyl)benzene], as a proxy of the total PCBs body burden, and of p,p'-DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene], the main metabolite of DDT were measured. Sperm DNA methylation level was assessed globally by flow cytometric (FCM) immunodetection of 5-methyl-cytosines and at specific repetitive DNA sequences (Alu, LINE-1, Satα) by PCR-pyrosequencing after bisulfite conversion. Multivariate linear regression analysis was applied to investigate correlations between serum POP concentrations and DNA methylation. No consistent associations between exposure to POPs and sperm DNA methylation at repetitive DNA sequences were detected. A statistically significant global decrease in methylation was associated with exposure to either POP by FCM analysis. This is the first study to investigate environmental exposure to POPs and DNA methylation levels considering sperm as the target cells. Although POP exposure appears to have a limited negative impact on sperm DNA methylation levels in adult males, the global hypomethylation detected by one of the methods applied suggests that further investigation is warranted. Environ. Mol. Mutagen., 2015. © 2015 Wiley Periodicals, Inc.
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| 21. |
- Góralczyk, Katarzyna, et al.
(författare)
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Is the fact of parenting couples cohabitation affecting the serum levels of persistent organohalogen pollutants?
- 2015
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Ingår i: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1618-131X .- 1438-4639. ; 218:4, s. 392-400
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Tidskriftsartikel (refereegranskat)abstract
- Organohalogen compounds constitute one of the important groups of persistent organic pollutants (POPs). Among them, due to their long-term health effects, one should pay attention on organochlorine pesticides, polychlorinated biphenyls (PCBs) and perfluoroalkylated substances (PFASs). This paper is an attempt to answer the question about relation between the fact of cohabitation by couples expecting a child and the level of the organohalogen compounds in the blood serum of both parents. The study was done on a population of parent couples from Greenland, Poland and Ukraine, from whom blood samples were collected in order to establish the levels of marker organohalogen compounds. We selected, as the representative of these compounds, the most persistent metabolite of DDT, i.e. p,p'-DDE, the most frequently detected PCB congener - CB-153, and PFOS and PFOA as the representatives of PFASs. The results show that in case of all compounds under study the highest concentrations were present always in men in relation to the levels detected in the blood serum of their female partners, regardless of the country of origin of the couple. A positive correlation was noted between the concentrations of the studied compounds in the blood serum of men and women in parenting couples. In some cases these correlations were statistically significant, e.g. for concentrations of p,p'-DDE in pairs from Greenland and Ukraine, of CB-153 in pairs from Poland and Ukraine, and of PFOS for parents from Greenland and Poland, while for PFOA - only for couples from Greenland. The concentrations of the compounds included in the study were similar to the levels found in general population in other countries. Our results show that the exposure to POPs resulting from cohabitation plays a role in the general exposure to these compounds.
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| 23. |
- Hermansson, Tomas, 1979, et al.
(författare)
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Identification of Material Parameters of Complex Cables from Scanned 3D Shapes
- 2016
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Ingår i: Procedia CIRP: 14th CIRP CAT 2016 - CIRP Conference on Computer Aided Tolerancing. - : Elsevier BV. - 2212-8271. ; 43, s. 280-285
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Konferensbidrag (refereegranskat)abstract
- Simulation of flexible components is becoming an integral part of virtual product design. However, for a simulation model to predict physically correct deformations, it is crucial that the material parameters are authentic. Conventional methods to acquire these parameters involve extensive force-displacement measurements, which may be unpractical or too expensive to perform. We propose an alternative method to identify the material parameters of a flexible one-dimensional component, such as a cable or a hose, from a scanned set of deformed reference shapes. The method finds the model parameters that give the best geometric fit between the model and the reference shapes.
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| 24. |
- Høyer, Birgit Bjerre, et al.
(författare)
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Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function : a Systematic Review of Human Evidence
- 2018
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Ingår i: Current Environmental Health Reports. - : Springer Science and Business Media LLC. - 2196-5412. ; 5:1, s. 20-33
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The purpose of this review is to systematically review the literature linking di-2-ethylhexyl phthalate (DEHP) exposure with effects on reproductive health in adult males. RECENT FINDINGS: Thirty-three papers were included of which 28 were cross-sectional. Twenty-one papers investigated semen samples, 18 investigated reproductive hormones, and three studies investigated time to pregnancy. Studies revealed some but inconsistent indications that higher urinary DEHP metabolite levels are associated with an increase in the proportion of spermatozoa with damaged DNA and to a decrease in sperm concentration and motility. A negative association between DEHP metabolites and testosterone levels was more consistent. DEHP metabolites do not seem to be associated with a delay in time to pregnancy, but data are sparse. The studies on DEHP exposure and reproductive biomarkers in men converge to support the hypothesis that DEHP exposure is related to impaired male reproductive function. Longitudinal studies are needed to establish if the observed associations are causal.
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