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| 3. |
- Caporale, N., et al.
(author)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Journal article (peer-reviewed)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 6. |
- Barregård, Lars, 1948, et al.
(author)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Journal article (peer-reviewed)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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| 7. |
- Hatschek, T, et al.
(author)
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Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial
- 2012
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In: Breast Cancer Research and Treatment. - New York, USA : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 131:3, s. 939-947
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Journal article (peer-reviewed)abstract
- Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(A (R))) and paclitaxel (Taxol(A (R))) alone (ET) or in combination with capecitabine (Xeloda(A (R)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.
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| 8. |
- Horne, B D, et al.
(author)
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Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy
- 2012
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In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 107:2, s. 232-240
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Journal article (peer-reviewed)abstract
- By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6-11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6-11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that "effective" dose constituted a treatment response index . Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R2 was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1-1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R2= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
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| 9. |
- Lenzini, P., et al.
(author)
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Integration of genetic, clinical, and INR data to refine warfarin dosing
- 2010
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In: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 87:5, s. 572-578
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Journal article (peer-reviewed)abstract
- Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.
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| 10. |
- BLOMGREN, J, et al.
(author)
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SEARCH FOR DOUBLE GAMOW-TELLER STRENGTH BY HEAVY-ION DOUBLE-CHARGE-EXCHANGE
- 1995
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In: PHYSICS LETTERS B. - 0370-2693. ; 362:1-4, s. 34-38
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Journal article (peer-reviewed)abstract
- We have carried out a search for double Gamow-Teller excitations, employing the Mg-24(O-18,Ne-18)Ne-24 reaction at 100 and 76 MeV/nucleon at NSCL-MSU and GANIL, respectively, The cross sections for low-lying excitations are typically a few nb/sr, providin
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| 12. |
- Gotfredsen, Klaus, et al.
(author)
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Implants and/or teeth: consensus statements and recommendations.
- 2008
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In: Journal of oral rehabilitation. - : Wiley. - 1365-2842 .- 0305-182X. ; 35:Suppl 1, s. 2-8
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Research review (peer-reviewed)abstract
- In August 23-25, 2007, the Scandinavian Society for Prosthetic Dentistry in collaboration with the Danish Society of Oral Implantology arranged a consensus conference on the topic 'Implants and/or teeth'. It was preceded by a workshop in which eight focused questions were raised and answered in eight review articles using a systematic approach. Twenty-eight academicians and clinicians discussed the eight review papers with the purpose to reach consensus on questions relevant for the topic. At the conference the consensus statements were presented as well as lectures based on the review articles. In this article the methods used at the consensus workshop are briefly described followed by the statements with comments.
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| 15. |
- Johnsson, A., et al.
(author)
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Anal cancer in Sweden 2015-2019. Implementation of guidelines, structural changes, national registry and early results
- 2022
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 61:5, s. 575-582
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Journal article (peer-reviewed)abstract
- Background Squamous cell cancer of the anus is an uncommon malignancy, usually caused by human papilloma virus (HPV). Chemoradiotherapy (CRT) is the recommended treatment in localized disease with cure rates of 60-80%. Local failures should be considered for salvage surgery. With the purpose of improving and equalizing the anal cancer care in Sweden, a number of actions were taken between 2015 and 2017. The aim of this study was to describe the implementation of guidelines and organizational changes and to present early results from the first 5 years of the Swedish anal cancer registry (SACR). Methods The following were implemented: (1) the first national care program with treatment guidelines, (2) standardized care process, (3) centralization of CRT to four centers and salvage surgery to two centers, (4) weekly national multidisciplinary team meetings where all new cases are discussed, (5) the Swedish anal cancer registry (SACR) was started in 2015. Results The SACR included 912 patients with a diagnosis of anal cancer from 2015 to 2019, reaching a national coverage of 95%. We could show that guidelines issued in 2017 regarding staging procedures and radiotherapy dose modifications were rapidly implemented. At baseline 52% of patients had lymph node metastases and 9% had distant metastases. Out of all patients in the SACR 89% were treated with curative intent, most of them with CRT, after which 92% achieved a local complete remission and the estimated overall 3-year survival was 85%. Conclusions This is the first report from the SACR, demonstrating rapid nation-wide implementation of guidelines and apparently good treatment outcome in patients with anal cancer in Sweden. The SACR will hopefully be a valuable source for future research.
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| 18. |
- Lindh, Jenny M., et al.
(author)
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Discovery of an oviposition attractant for gravid malaria vectors of the Anopheles gambiae species complex
- 2015
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In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 14:1
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Journal article (peer-reviewed)abstract
- Background: New strategies are needed to manage malaria vector populations that resist insecticides and bite outdoors. This study describes a breakthrough in developing 'attract and kill' strategies targeting gravid females by identifying and evaluating an oviposition attractant for Anopheles gambiae s.l. Methods: Previously, the authors found that gravid An. gambiae s.s. females were two times more likely to lay eggs in lake water infused for six days with soil from a natural oviposition site in western Kenya compared to lake water alone or to the same but autoclaved infusion. Here, the volatile chemicals released from these substrates were analysed with a gas-chromatograph coupled to a mass-spectrometer (GC-MS). Furthermore, the behavioural responses of gravid females to one of the compounds identified were evaluated in dual choice egg-count bioassays, in dual-choice semi-field experiments with odour-baited traps and in field bioassays. Results: One of the soil infusion volatiles was readily identified as the sesquiterpene alcohol cedrol. Its widespread presence in natural aquatic habitats in the study area was confirmed by analysing the chemical headspace of 116 water samples collected from different aquatic sites in the field and was therefore selected for evaluation in oviposition bioassays. Twice as many gravid females were attracted to cedrol-treated water than to water alone in two choice cage bioassays (odds ratio (OR) 1.84; 95% confidence interval (CI) 1.16-2.91) and in experiments conducted in large-screened cages with free-flying mosquitoes (OR 1.92; 95% CI 1.63-2.27). When tested in the field, wild malaria vector females were three times more likely to be collected in the traps baited with cedrol than in the traps containing water alone (OR 3.3; 95% CI 1.4-7.9). Conclusion: Cedrol is the first compound confirmed as an oviposition attractant for gravid An. gambiae s.l. This finding paves the way for developing new 'attract and kill strategies' for malaria vector control.
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| 20. |
- Nidens, N., et al.
(author)
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Associations of prenatal exposure to phthalates and one phthalate substitute with anthropometric measures in early life : Results from the German LIFE Child cohort study
- 2021
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In: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism. - : Bailliere Tindall Ltd. - 1521-690X .- 1532-1908. ; 35:5
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Journal article (peer-reviewed)abstract
- Exposure to phthalates is widespread and especially early life stages represent a critical window of exposure. In the present study, we investigated the effect of prenatal exposure to phthalates on birth outcomes and weight development in early life. In 130 mother–child pairs, we estimated the association of concentrations of 13 phthalates in spot-urine samples collected during pregnancy and birth outcomes and weight gain in the first two years of life using robust linear regression. High molecular weight phthalates were inversely associated with birth weight in girls but not in boys. Thus, prenatal exposure to phthalates may affect birth weight in a sex-specific manner.
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| 21. |
- Shin, J. H., et al.
(author)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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In: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Journal article (peer-reviewed)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 23. |
- Al-Okshi, Ayman, et al.
(author)
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Using GafChromic film to estimate the effective dose from dental cone beam CT and panoramic radiography
- 2013
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In: Dento-Maxillo-Facial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 42:7
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Journal article (peer-reviewed)abstract
- Objectives: To demonstrate the feasibility of GafChromic(®) XR-QA2 (ISP Corp., Wayne, NJ) as a dosemeter when performing measurements of the effective dose from three cone beam CT (CBCT) units and to compare the doses from examinations of three common dental clinical situations. A second aim was to compare the radiation doses for three digital panoramic units with the doses for the CBCT units. METHODS: The CBCT units used were Veraviewepocs 3De(®) (J Morita MFG Corp., Kyoto, Japan), ProMax(®) 3D (Planmeca, Helsinki, Finland) and NewTom VGi(®) (Quantitative Radiology, Verona, Italy). GafChromic XR-QA2 films were placed between the selected layers of the head and neck of a tissue-equivalent human skull (RANDO(®) phantom; The Phantom Laboratory, Salem, NY). The exposure parameters were set using the automatic exposure control function of the units. Depending on the availability, medium and smaller field of view (FOV) scanning modes were used. The effective dose was estimated using the 2007 International Commission on Radiological Protection formalism. RESULTS: The lowest effective dose of a CBCT unit was observed for ProMax 3D, FOV 4 × 5 cm (10 μSv), the highest for NewTom VGi, FOV 8 × 8 cm-high resolution (129 μSv). The range of effective doses for digital panoramic machines measured was 8-14 μSv. CONCLUSIONS: This study demonstrates the feasibility of using radiochromic films for dental CBCT and panoramic dosimetry.
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| 24. |
- Andaloussi, Mounir, et al.
(author)
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Design, Synthesis, and X-ray Crystallographic Studies of alpha-Aryl Substituted Fosmidomycin Analogues as Inhibitors of Mycobacterium tuberculosis 1-Deoxy-D-xylulose 5-Phosphate Reductoisomerase
- 2011
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54:14, s. 4964-4976
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Journal article (peer-reviewed)abstract
- The natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR), but it lacks antibacterial activity probably because of poor uptake. alpha-Aryl substituted fosmidomycin analogues have more favorable physicochemical properties and are also more active in inhibiting malaria parasite growth. We have solved crystal structures of MtDXR in complex with 3,4-dichlorophenyl substituted fosmidomycin analogues; these show important differences compared to our previously described forsmidomycin-DXR complex. Our best inhibitor has an IC(50) = 0.15 mu M on MtDXR but still lacked activity in a mycobacterial growth assay (MIC > 32 mu g/mL). The combined results, however, provide insights into how DXR accommodates the new inhibitors and serve as an excellent starting point for the design of other novel and more potent inhibitors, particularly against pathogens where uptake is less of a problem, such as the malaria parasite.
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| 25. |
- Ayukekbong, James A., et al.
(author)
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Monitoring of seasonality of norovirus and other enteric viruses in Cameroon by real-time PCR : an exploratory study
- 2014
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In: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 142:7, s. 1393-1402
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Journal article (peer-reviewed)abstract
- We studied the seasonal fluctuation of norovirus and other enteric viruses in Cameroon. Two hundred participants aged between 1 and 69 years were prospectively followed up. Each participant provided monthly faecal samples over a 12-month period. A total of 2484 samples were tested using multiplex real-time PCR assay for the detection of norovirus, rotavirus and enterovirus. The effect of weather variables and risk factors were analysed by Pearson correlation and bivariate analysis. Overall, enterovirus was the most commonly detected virus (216% of specimens), followed by norovirus (39%) and rotavirus (04%). Norovirus and enterovirus were detected throughout the year with a peak of norovirus detection at the beginning of the rainy season and a significant alternation of circulation of norovirus genogroups from one month to the next. Age <5 years and consumption of tap water were risk factors for norovirus infection. Better understanding of factors influencing transmission and seasonality may provide insights into the relationship between physical environment and risk of infection for these viruses.
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