| 1. |
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| 2. |
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| 3. |
- Barregård, Lars, 1948, et al.
(författare)
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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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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Horne, B D, et al.
(författare)
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Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 107:2, s. 232-240
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Tidskriftsartikel (refereegranskat)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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| 5. |
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| 6. |
- Lenzini, P., et al.
(författare)
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Integration of genetic, clinical, and INR data to refine warfarin dosing
- 2010
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 87:5, s. 572-578
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Manni, Giovanni Li, et al.
(författare)
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The OpenMolcas Web : A Community-Driven Approach to Advancing Computational Chemistry
- 2023
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 19:20, s. 6933-6991
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Tidskriftsartikel (refereegranskat)abstract
- The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.
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| 8. |
- Bao, Jie J., et al.
(författare)
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Analytic gradients for compressed multistate pair-density functional theory
- 2022
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Ingår i: Molecular Physics. - : Taylor & Francis Group. - 0026-8976 .- 1362-3028. ; 120:19-20
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Tidskriftsartikel (refereegranskat)abstract
- Photochemical reactions often involve states that are closely coupled due to near degeneracies, for example by proximity to conical intersections. Therefore, a multistate method is used to accurately describe these states; for example, ordinary perturbation theory is replaced by quasidegenerate perturbation theory. Multiconfiguration pair-density functional theory (MC-PDFT) provides an efficient way to approximate the full dynamical correlation energy of strongly correlated systems, and we recently proposed compressed multistate pair-density functional theory (CMS-PDFT) to treat closely coupled states. In the present paper, we report the implementation of analytic gradients for CMS-PDFT in both OpenMolcas and PySCF, and we illustrate the use of these gradients by applying the method to the excited states of formaldehyde and phenol.
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| 9. |
- Bornehag, Carl-Gustaf, 1957-, et al.
(författare)
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Association of Prenatal Phthalate Exposure with Language Development in Early Childhood
- 2018
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Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 172:12, s. 1169-1176
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Prenatal exposure to phthalates has been associated with neurodevelopmental outcomes, but little is known about the association with language development. Objective: To examine the association of prenatal phthalate exposure with language development in children in 2 population-based pregnancy cohort studies. Design, Setting, and Participants: Data for this study were obtained from the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study conducted in prenatal clinics throughout Värmland county in Sweden and The Infant Development and the Environment Study (TIDES) conducted in 4 academic centers in the United States. Participants recruited into both studies were women in their first trimester of pregnancy who had literacy in Swedish (SELMA) or English or Spanish (TIDES). This study included mothers and their children from both the SELMA study (n = 963) and TIDES (n = 370) who had complete data on prenatal urinary phthalate metabolite levels, language delay, and modeled covariables. For SELMA, the data were collected from November 1, 2007, to June 30, 2013, and data analysis was conducted from November 1, 2016, to June 30, 2018. For TIDES, data collection began January 1, 2010, and ended March 29, 2016, and data analysis was performed from September 15, 2016, to June 30, 2018. Main Outcomes and Measures: Mothers completed a language development questionnaire that asked the number of words their children could understand or use at a median of 30 months of age (SELMA) and 37 months of age (TIDES). The responses were categorized as fewer than 25, 25 to 50, and more than 50 words, with 50 words or fewer classified as language delay. Results: In the SELMA study, 963 mothers, 455 (47.2%) girls, and 508 [52.8%] boys were included. In TIDES, 370 mothers, 185 (50.0%) girls, and 185 (50.0%) boys were included in this analysis. The prevalence of language delay was 10.0% in both SELMA (96 reported) and TIDES (37 reported), with higher rates of delay in boys than girls (SELMA: 69 [13.5%] vs 27 [6.0%]; TIDES: 12 [12.4%] vs 14 [7.6%]). In crude analyses, the metabolite levels of dibutyl phthalate and butyl benzyl phthalate were statistically significantly associated with language delay in both cohorts. In adjusted analyses, a doubling of prenatal exposure of dibutyl phthalate and butyl benzyl phthalate metabolites increased the odds ratio (OR) for language delay by approximately 25% to 40%, with statistically significant results in the SELMA study (dibutyl phthalate OR, 1.29 [95% CI, 1.03-1.63; P =.03]; butyl benzyl phthalate OR, 1.26 [95% CI, 1.07-1.49; P =.003]). A doubling of prenatal monoethyl phthalate exposure was associated with an approximately 15% increase in the OR for language delay in the SELMA study (OR, 1.14; 95% CI, 1.00-1.31; P =.05), but no such association was found in TIDES (OR, 0.98; 95% CI, 0.79-1.23). Conclusions and Relevance: In findings from this study, prenatal exposure to dibutyl phthalate and butyl benzyl phthalate was statistically significantly associated with language delay in children in both the SELMA study and TIDES. These findings, along with the prevalence of prenatal exposure to phthalates, the importance of language development, and the inconsistent results from a 2017 Danish study, suggest that the association of phthalates with language delay may warrant further examination.
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| 10. |
- Brown, J, et al.
(författare)
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Basic training requirements for the use of dental CBCT by dentists : a position paper prepared by the European Academy of DentoMaxilloFacial Radiology
- 2014
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Ingår i: Dento-Maxillo-Facial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 43:1
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Tidskriftsartikel (refereegranskat)abstract
- Cone beam CT (CBCT) is a relatively new imaging modality, which is now widely available to dentists for examining hard tissues in the dental and maxillofacial regions. CBCT gives a three-dimensional depiction of anatomy and pathology, which is similar to medical CT and uses doses generally higher than those used in conventional dental imaging. The European Academy of DentoMaxilloFacial Radiology recognizes that dentists receive training in two-dimensional dental imaging as undergraduates, but most of them have received little or no training in the application and interpretation of cross-sectional three-dimensional imaging. This document identifies the roles of dentists involved in the use of CBCT, examines the training requirements for the justification, acquisition and interpretation of CBCT imaging and makes recommendations for further training of dentists in Europe who intend to be involved in any aspect of CBCT imaging. Two levels of training are recognized. Level 1 is intended to train dentists who prescribe CBCT imaging, such that they may request appropriately and understand the resultant reported images. Level 2 is intended to train to a more advanced level and covers the understanding and skills needed to justify, carry out and interpret a CBCT examination. These recommendations are not intended to create specialists in CBCT imaging but to offer guidance on the training of all dentists to enable the safe use of CBCT in the dentoalveolar region.
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| 11. |
- Dias, Danilo R., et al.
(författare)
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The effect of marginal bone level changes on the stability of dental implants in a short-term evaluation
- 2015
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Ingår i: Clinical Oral Implants Research. - : John Wiley & Sons. - 0905-7161 .- 1600-0501. ; 26:10, s. 1185-1190
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo evaluate whether changes in marginal bone level (MBL) around implants, in sites with different bone types, affect the over time implant stability measured by resonance frequency analysis (RFA). Material and methodsSeventy-eight implants were inserted into jawbones of 32 patients using a two-stage surgical protocol, and implant bone sites were grouped according to the Lekholm and Zarb bone classification. The implant stability quotient (ISQ) was measured by RFA at four time points: implant placement, uncovering, rehabilitation, and at 1-year follow-up after loading. The MBL was measured on periapical radiographs at uncovering and at 1-year follow-up. Percent change in bone level was calculated based on the difference between the implant length and height from the crestal bone level to the implant apex. Descriptive statistics, Pearson's correlation, and repeated-measures ANOVA were used for data analysis. ResultsSignificant improvement of ISQ was found between implant insertion and uncovering surgery (P<0.001), while no significant changes were detected throughout the remaining follow-up period. The greatest improvement of ISQ was observed for bone type 4, compared with the other groups (P<0.001). Percent change in bone level had no effect on longitudinal measures of ISQ (P=0.337). The ISQ difference between uncovering and 1year after loading was not correlated with percent change in bone level (r=0.16; P=0.157). ConclusionThere was increased implant stability after implant placement, but it was not affected by changes in marginal bone level during the first year of loading.
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| 12. |
- Gising, Johan, et al.
(författare)
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Trisubstituted Imidazoles as Mycobacterium tuberculosis Glutamine Synthetase Inhibitors
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:6, s. 2894-2898
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium tuberculosis glutamine synthetase (MtGS) is a promising target for antituberculosis drug discovery. In a recent high-throughput screening study we identified several classes of MtGS inhibitors targeting the ATP-binding site. We now explore one of these classes, the 2-tert-butyl-4,5-diarylimidazoles, and present the design, synthesis, and X-ray crystallographic studies leading to the identification of MtGS inhibitors with submicromolar IC(50) values and promising antituberculosis MIC values.
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| 13. |
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| 14. |
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| 15. |
- Scott, Thais R., et al.
(författare)
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Analytic gradients for multiconfiguration pair-density functional theory with density fitting : Development and application to geometry optimization in the ground and excited states
- 2021
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Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 154:7
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Tidskriftsartikel (refereegranskat)abstract
- Density fitting reduces the computational cost of both energy and gradient calculations by avoiding the computation and manipulation of four-index electron repulsion integrals. With this algorithm, one can efficiently optimize the geometries of large systems with an accurate multireference treatment. Here, we present the derivation of multiconfiguration pair-density functional theory for energies and analytic gradients with density fitting. Six systems are studied, and the results are compared to those obtained with no approximation to the electron repulsion integrals and to the results obtained by complete active space second-order perturbation theory. With the new approach, there is an increase in the speed of computation with a negligible loss in accuracy. Smaller grid sizes have also been used to reduce the computational cost of multiconfiguration pair-density functional theory with little effect on the optimized geometries and gradient values.
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| 16. |
- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 17. |
- Sundberg, R., et al.
(författare)
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Dezincification (DA) and intergranular corrosion (IGA) of brass - influence of composition and heat treatment
- 2003
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Ingår i: Metall (Berlin. 1947). - 0026-0746. ; 57:11, s. 721-731
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Tidskriftsartikel (refereegranskat)abstract
- Dezincification of alpha-brass first became recognised as a problem when brass tubes were used in heat exchangers with seawater in the cooling system. In the early 1920s alloy additions of As were shown to inhibit DA. Later, P and Sb were both found to have a similar influence. Reports of Intergranular attack, IGA, appeared from time to time, however, in dezincification resistant brass.
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| 18. |
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| 19. |
- Weiland, O, et al.
(författare)
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Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection
- 1995
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 27:4, s. 319-24
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Tidskriftsartikel (refereegranskat)abstract
- A total of 42 Swedish patients with biopsy-proven chronic hepatitis C virus (HCV) infection were treated with a natural human leucocyte alpha-interferon (HuIFN-alpha-Le), Alfanative (BioNative AB, Umeå, Sweden) in an open uncontrolled study. Two patients were withdrawn from treatment within 2 weeks due to non-compliance and were omitted from further analysis, and 40 patients (17 females), mean age 39 years (range 24-71) completed the study. All patients were HCV RNA-positive in serum prior to treatment, with raised alanine aminotransferase (ALT) levels > 1.5 times the upper normal limit known for more than 6 months. Interferon was given at a dose of 3 MU t.i.w. for an intended 24 weeks and follow-up was a further 24 weeks after treatment. Biochemical non-responders were withdrawn from treatment within 12-16 weeks but continued follow-up. Overall 21/40 (52.5%) patients had a complete biochemical response with normal ALT levels at the end of treatment. Sustained response during follow-up was seen in 8 (20%) whereas 13 (32.5%) had a non-sustained response. At the end of treatment 23 (58%) patients had undetectable serum HCV RNA and 9 (23%) at follow-up. Patients with sustained, non-sustained and non-response had a mean pretreatment HCV RNA level of 3.2 x 10(5), 2.5 x 10(6) and 3.2 x 10(6) genomes/ml, respectively, differences that did not reach statistical significance. Of the patients 3, 9, 10 and 14 had genotype 1b, 3a, 1a, and 2b, respectively, and 4 had mixed genotypes. Of the 23 patients with genotype 2b or 3a, 7 had a sustained response vs. none of the 13 patients with genotype 1a or 1b (p = 0.03). No patients with cirrhosis had a sustained response whereas 4/18 with chronic persistent and 4/18 with chronic active hepatitis had such a response. It is concluded that some 50% of patients treated with HuIFN-alpha-Le responded with normalisation of ALT levels but that only 20% had a durable response 24 weeks post-treatment, and that patients with genotypes 3a or 2b seem to respond better than patients with other genotypes.
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| 20. |
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| 21. |
- Alajbeg, Ivan, et al.
(författare)
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Intraoralelectrostimulator for xerostomia relief : along-term, multicenter, open-label, uncontrolled, clinical trial
- 2012
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Ingår i: Oral surgery, oral medicine, oral pathology and oral radiology. - : Elsevier. - 2212-4403 .- 2212-4411. ; 113:6, s. 773-781
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. STUDY DESIGN: The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. RESULTS: Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected. CONCLUSIONS: The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period.
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| 22. |
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| 23. |
- Ali, Neserin, et al.
(författare)
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Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.
- 2016
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Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 10:2, s. 226-234
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Tidskriftsartikel (refereegranskat)abstract
- Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.
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| 24. |
- Andaloussi, Mounir, et al.
(författare)
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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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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54:14, s. 4964-4976
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Tidskriftsartikel (refereegranskat)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. |
- Andaloussi, Mounir, et al.
(författare)
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Microwave-promoted palladium(II)-catalyzed C-P bond formation by using arylboronic acids or aryltrifluoroborates.
- 2009
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Ingår i: Chemistry - A European Journal. - Weinheim : Wiley-VCH Verlag GmbH. - 0947-6539 .- 1521-3765. ; 15:47, s. 13069-13074
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Tidskriftsartikel (refereegranskat)abstract
- The first Pd-II-catalyzed P arylation has been performed by using palladium acetate, the rigid bidentate ligand dmphen (dmphen=2,9-dimethyl-1,10-phenanthroline), and without the addition of base or acid. Couplings of arylboronic acids or aryl trifluoroborates with H-phosphonate dialkyl esters were conducted in 30 min with controlled microwave (MW) heating under non-inert conditions. Aryl phosphites were also synthesized at room temperature with atmospheric air as the sole reoxidant. The arylated phosphonates were isolated in 44-90% yields. The excellent chemoselectivity of the method was illustrated in the synthesis of a Mycobacterium tuberculosis glutamine synthetase (MTB-GS) inhibitor. Online ESIMS was used to detect cationic palladium species in ongoing reactions directly, and a catalytic cycle has been proposed based on these results.
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| 26. |
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| 27. |
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| 28. |
- Borne, Kurtis D., et al.
(författare)
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Ultrafast electronic relaxation pathways of the molecular photoswitch quadricyclane
- 2024
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Ingår i: NATURE CHEMISTRY. - : Springer Nature. - 1755-4330 .- 1755-4349. ; 16, s. 499-505
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Tidskriftsartikel (refereegranskat)abstract
- The light-induced ultrafast switching between molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Prior work observed signatures of ultrafast molecular dynamics in both isomers upon ultraviolet excitation but could not follow the electronic relaxation all the way back to the ground state experimentally. Here we study the electronic relaxation of quadricyclane after exciting in the ultraviolet (201 nanometres) using time-resolved gas-phase extreme ultraviolet photoelectron spectroscopy combined with non-adiabatic molecular dynamics simulations. We identify two competing pathways by which electronically excited quadricyclane molecules relax to the electronic ground state. The fast pathway (<100 femtoseconds) is distinguished by effective coupling to valence electronic states, while the slow pathway involves initial motions across Rydberg states and takes several hundred femtoseconds. Both pathways facilitate interconversion between the two isomers, albeit on different timescales, and we predict that the branching ratio of norbornadiene/quadricyclane products immediately after returning to the electronic ground state is approximately 3:2.
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| 29. |
- Calio, Paul B., et al.
(författare)
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Minimum-Energy Conical Intersections by Compressed Multistate Pair-Density Functional Theory
- 2024
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 128:9, s. 1698-1706
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Tidskriftsartikel (refereegranskat)abstract
- Compressed multistate pair-density functional theory (CMS-PDFT) is a multistate version of multiconfiguration pair-density functional theory that can capture the correct topology of coupled potential energy surfaces (PESs) around conical intersections. In this work, we develop interstate coupling vectors (ISCs) for CMS-PDFT in the OpenMolcas and PySCF/mrh electronic structure packages. Yet, the main focus of this work is using ISCs to calculate minimum-energy conical intersections (MECIs) by CMS-PDFT. This is performed using the projected constrained optimization method in OpenMolcas, which uses ISCs to restrain the iterations to the conical intersection seam. We optimize the S1/S0 MECIs for ethylene, butadiene, and benzene and show that CMS-PDFT gives smooth PESs in the vicinities of the MECIs. Furthermore, the CMS-PDFT MECIs are in good agreement with the MECI calculated by the more expensive XMS-CASPT2 method.
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| 30. |
- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)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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| 31. |
- Cárdenas, Marité, et al.
(författare)
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Human Saliva Forms a Complex Film Structure on Alumina Surfaces
- 2007
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 8:1, s. 65-69
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Tidskriftsartikel (refereegranskat)abstract
- Films formed from saliva on surfaces are important for the maintenance of oral health and integrity by protection against chemical and/or biological agents. The aim of the present study was to investigate adsorbed amounts, thickness, and structure of films formed from human whole saliva on alumina surfaces by means of in situ ellipsometry, neutron reflectivity, and atomic force microscopy. Alumina (Al2O3, synthetic sapphire) is a relevant and interesting substrate for saliva adsorption studies as it has an isoelectric point close to that of tooth enamel. The results showed that saliva adsorbs rapidly on alumina. The film could be modeled in two layers: an inner and dense thin region that forms a uniform layer and an outer, more diffuse and thicker region that protrudes toward the bulk of the solution. The film morphology described a uniformly covering dense layer and a second outer layer containing polydisperse adsorbed macromolecules or aggregates.
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| 32. |
- Corrales Vargas, Andrea, et al.
(författare)
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Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 810
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development. Objectives: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). Methods: At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (μg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (μg/g) and blood (MnB) (μg/L), and blood lead (PbB) (μg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression. Results: About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: β = −0.79 (95%CI = −1.51, −0.08) and β = −0.29 (95%CI = −0.62, −0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (β = 0.04 (95%CI = 0.00, 0.07 per 1 μg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3. Discussion: Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action.
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| 33. |
- Dahlstrom, M., et al.
(författare)
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Affinity states of biocides determine bioavailability and release rates in marine paints
- 2015
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Ingår i: Biofouling. - : Informa UK Limited. - 0892-7014 .- 1029-2454. ; 31:2, s. 201-210
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Tidskriftsartikel (refereegranskat)abstract
- A challenge for the next generation marine antifouling (AF) paints is to deliver minimum amounts of biocides to the environment. The candidate AF compound medetomidine is here shown to be released at very low concentrations, ie ng ml(-1) day(-1). Moreover, the release rate of medetomidine differs substantially depending on the formulation of the paint, while inhibition of barnacle settlement is independent of release to the ambient water, ie the paint with the lowest release rate was the most effective in impeding barnacle colonisation. This highlights the critical role of chemical interactions between biocide, paint carrier and the solid/aqueous interface for release rate and AF performance. The results are discussed in the light of differential affinity states of the biocide, predicting AF activity in terms of a high surface affinity and preserved bioavailability. This may offer a general framework for the design of low-release paint systems using biocides for protection against biofouling on marine surfaces.
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| 34. |
- Delcey, Mickaël G., 1988-, et al.
(författare)
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Communication : Theoretical prediction of the structure and spectroscopic properties of the X∼ and A∼ states of hydroxymethyl peroxy (HOCH2OO) radical
- 2013
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 138:2, s. 021105-
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Tidskriftsartikel (refereegranskat)abstract
- The hydroxymethyl peroxy (HMOO) radical is a radical product from the oxidation of non-methane hydrocarbons. The present study provides theoretical prediction of critical spectroscopic features of this radical that should aid in its experimental characterization. Structure, rotational constants, and harmonic frequencies are presented for the ground and first excited electronic states of HMOO. The adiabatic transition energy for the A←X process is 7360 cm-1, suggesting that this transition, occurring in the mid to near infrared, is the most promising candidate for observing the radical spectroscopically. The band origin of the A←X transition of HMOO is calibrated and benchmarked with the corresponding state of the HOO radical, which is experimentally and theoretically well characterized.
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| 35. |
- Derakhshan, A., et al.
(författare)
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Association of phthalate exposure with thyroid function during pregnancy
- 2021
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 157
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Tidskriftsartikel (refereegranskat)abstract
- Background: The extent of thyroid disruptive effects of phthalates during pregnancy remains unclear. Aim: To investigate the association of maternal urinary phthalates with markers of the thyroid system during early pregnancy. Methods: Urinary concentrations of phthalate metabolites and serum concentrations of thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4) and free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (2007-ongoing), a population-based prospective cohort. Results: In the 1,996 included women, higher di-ethyl-hexyl phthalate (DEHP) metabolites were associated with a lower FT4 (β [SE] for the molar sum: −0.13 [0.06], P = 0.03) and a higher TSH/FT4 ratio (0.003 [0.001], P = 0.03). Higher concentrations of di-iso-nonyl phthalate (DINP) metabolites were associated with a lower TT4 (β [SE] for the molar sum: 0.93 [0.44], P = 0.03) as well as with lower TT4/FT4 and TT4/TT3 ratios. Higher metabolites of both dibutyl and butyl-benzyl phthalate (DBP and BBzP) were associated with lower T4/T3 ratio (free and total) and higher FT4/TT4 and FT3/TT3 ratios. A higher diisononyl cyclohexane dicarboxylate (DINCH) metabolite concentration was associated with a higher TT3. Conclusions: These results translate results from experimental studies suggesting that exposure to phthalates may interfere with the thyroid system during pregnancy. This is also true for compounds that have been introduced to replace known disruptive phthalates. Further experimental studies should take into account the human evidence to better investigate the potential underlying mechanisms of thyroid disruption by phthalates.
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| 36. |
- Derakhshan, A., et al.
(författare)
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Association of urinary bisphenols and triclosan with thyroid function during early pregnancy
- 2019
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 133
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bisphenols and triclosan are considered as potential thyroid disruptors. While mild alterations in maternal thyroid function can result in adverse pregnancy and child developmental outcomes, there is still uncertainty whether bisphenols or triclosan can interfere with thyroid function during pregnancy. Objectives: We aimed to investigate the association of urinary bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF) and triclosan with early pregnancy thyroid function. Methods: This study was embedded in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA), a population-based prospective pregnancy cohort. In total, 1996 participants were included in the current study. Maternal urinary concentrations of three bisphenols and triclosan, collected at median (95% range) 10 (6–14) weeks of pregnancy as well as serum concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were measured. Results: Higher BPA levels were associated with lower TT4 concentrations (non-monotonic, P = 0.03), a lower FT4/FT3 ratio (β [SE] -0.02 [0.01], P = 0.03) and a lower TT4/TT3 ratio (β [SE] -0.73 [0.27], P = 0.008). Higher BPF levels were associated with a higher FT3 (β [SE] 0.01 [0.007], P = 0.04). There were no associations between other bisphenols or triclosan and absolute TSH, (F)T4 or (F)T3 concentrations. The association of BPA with thyroid function differed with gestational age. The negative association of BPA with FT4/FT3 and TT4/TT3 ratios was only apparent in early but not late gestation (P for interaction: 0.003, 0.008, respectively). Conclusion: These human data during pregnancy substantiate experimental findings suggesting that BPA could potentially affect thyroid function and deiodinase activities in early gestation.
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| 37. |
- Dobritzsch, Doreen, 1972-, et al.
(författare)
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Crystal structure of an arthritogenic anticollagen immune complex
- 2011
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 63:12, s. 3740-3748
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In rheumatoid arthritis, joint inflammation and cartilage destruction are mediated by autoantibodies directed to various self antigens. Type II collagen (CII)-specific antibodies are likely to play a role in this process and have been shown to induce experimental arthritis in susceptible animals. The purpose of this study was to reveal how arthritogenic autoantibodies recognize native CII in its triple-helical conformation. METHODS: Site-directed mutagenesis and crystallographic studies were performed to reveal crucial contact points between the CII antibody and the triple-helical CII peptide. RESULTS: The crystal structure of a pathogenic autoantibody bound to a major triple-helical epitope present on CII was determined, allowing a first and detailed description of the interactions within an arthritogenic complex that is frequently occurring in both mice and humans with autoimmune arthritis. The crystal structure emphasizes the role of arginine residues located in a commonly recognized motif on CII and reveals that germline-encoded elements are involved in the interaction with the epitope. CONCLUSION: The crystal structure of an arthritogenic antibody binding a triple-helical epitope on CII indicates a crucial role of germline-encoded and arginine residues as the target structures.
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| 38. |
- Dugassa, Sisay, et al.
(författare)
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Development of a Gravid Trap for Collecting Live Malaria Vectors Anopheles gambiae s.l.
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:7, s. e68948-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Effective malaria vector control targeting indoor host-seeking mosquitoes has resulted in fewer vectors entering houses in many areas of sub-Saharan Africa, with the proportion of vectors outdoors becoming more important in the transmission of this disease. This study aimed to develop a gravid trap for the outdoor collection of the malaria vector Anopheles gambiae s.l. based on evaluation and modification of commercially available gravid traps. Methods: Experiments were implemented in an 80 m(2) semi-field system where 200 gravid Anopheles gambiae s.s. were released nightly. The efficacy of the Box, CDC and Frommer updraft gravid traps was compared. The Box gravid trap was tested to determine if the presence of the trap over water and the trap's sound affected catch size. Mosquitoes approaching the treatment were evaluated using electrocuting nets or detergents added to the water in the trap. Based on the results, a new gravid trap (OviART trap) that provided an open, unobstructed oviposition site was developed and evaluated. Results: Box and CDC gravid traps collected similar numbers (relative rate (RR) 0.8, 95% confidence interval (CI) 0.6-1.2; p = 0.284), whereas the Frommer trap caught 70% fewer mosquitoes (RR 0.3, 95% CI 0.2-0.5; p < 0.001). The number of mosquitoes approaching the Box trap was significantly reduced when the trap was positioned over a water-filled basin compared to an open pond (RR 0.7 95% CI 0.6-0.7; p < 0.001). This effect was not due to the sound of the trap. Catch size increased by 60% (RR 1.6, 1.2-2.2; p = 0.001) with the new OviART trap. Conclusion: Gravid An. Gambiae s.s. females were visually deterred by the presence of the trapping device directly over the oviposition medium. Based on these investigations, an effective gravid trap was developed that provides open landing space for egg-laying Anopheles.
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| 39. |
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| 40. |
- Fardost, Ashkan, et al.
(författare)
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Palladium(II)-Catalyzed Decarboxylative Heck Arylations of Acyclic Electron-Rich Olefins with Internal Selectivity
- 2014
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Ingår i: Advanced Synthesis and Catalysis. - : Wiley. - 1615-4150 .- 1615-4169. ; 356:4, s. 870-878
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Tidskriftsartikel (refereegranskat)abstract
- Despite the recent emergence of decarboxylative CC bond forming reactions, methodologies providing internally arylated electron-rich olefins are still lacking. We herein report on palladium(II)-catalyzed decarboxylative Heck arylations of linear electron-rich olefins with excellent selectivity for the internal position. The method allows a variety of electron-rich linear olefins to undergo arylation with ortho-functionalized aromatic carboxylic acids, including heterocycles. The reaction mechanism has been explored with ESI-MS studies to confirm previous findings, and to reveal the formation of a highly stable palladium complex as a result of the Heck product reacting with the catalyst.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Gonzales-Siles, Lucia, et al.
(författare)
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Identification and capsular serotype sequetyping of Streptococcus pneumoniae strains
- 2019
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Ingår i: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 68:8, s. 1173-1188
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Correct serotype identification of Streptococcus pneumoniae (pneumococcus) is important for monitoring disease epidemiology and assessing the impacts of pneumococcal vaccines. Furthermore, correct identification and differentiation of the pathogenic S. pneumoniae from closely related commensal species of the mitis group of the genus Streptococcus are essential for correct serotype identification. Methodology. A new protocol for determining the existing 98 serotypes of pneumococcus was developed, applying two PCR amplifications and amplicon sequencing, using newly designed internal primers. The new protocol was validated using S. pneumoniae genome sequences, reference strains with confirmed serotypes and clinical isolates, and comparing the results with those from the traditional Quellung reaction or antiserum panel gel precipitation, in addition to real-time PCR analysis. The taxonomic identifications of 422 publicly available (GenBank) genome sequences of S. pneumoniae, Streptococcus pseudopneumoniae and Streptococcus mitis were assessed by whole-genome sequence average nucleotide identity based on blast (ANIb) analysis. Results. The proposed sequetyping protocol generates a 1017 bp whole cpsB region sequence, increasing resolution for serotype identification in pneumococcus isolates. The identifications of all GenBank genome sequences of S. pneumoniae were confirmed, whereas most of the S. pseudopneumoniae and almost all of the S. mitis genome sequences did not fulfil the ANIb thresholds for species-level identification. The housekeeping biomarker gene, groEL, correctly identified S. pneumoniae but often misclassified S. pseudopneumoniae and S. mitis as S. pneumoniae. Conclusions. These studies affirm the importance of applying reliable identification protocols for S. pneumoniae before serotyping; our protocols provide reliable diagnostic tools, as well as an improved workflow, for serotype identification of pneumococcus and differentiation of serogroup 6 types.
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| 46. |
- Gotfredsen, Klaus, et al.
(författare)
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Implants and/or teeth: consensus statements and recommendations.
- 2008
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Ingår i: Journal of oral rehabilitation. - : Wiley. - 1365-2842 .- 0305-182X. ; 35:Suppl 1, s. 2-8
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Forskningsöversikt (refereegranskat)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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| 47. |
- Greenberg, R, et al.
(författare)
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Aggressive treatment of acute limb ischemia due to thrombosed popliteal aneurysms
- 1998
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Ingår i: European Journal of Radiology. - 1872-7727. ; 28:3, s. 211-218
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The absence of infra-popliteal runoff in patients with acute limb ischemia and thrombosed popliteal aneurysms carries a high risk of amputation. A combined treatment method involving thrombolysis and surgery is reported. MATERIAL AND METHODS: Information regarding six patients was reviewed. Ankle brachial indices and degree of ischemia were recorded. All patients underwent digital subtraction angiography. In five patients thrombus dissolution was achieved using a combination of mechanical and pharmacologic therapy. One patient was judged incapable of withstanding any delay in reperfusion and was treated with isolated limb perfusion using a thrombolytic agent. All patients underwent surgical revascularization. Follow-up (1-3 years) consisted of duplex examinations at 6 months and yearly thereafter. RESULTS: Five patients had no measurable ankle brachial index (ABI), while one patient had an ABI of 0.4. Initial angiography noted all patients to have no runoff in continuity to the pedal arch. Following thrombolytic therapy, an adequate bypass vessel was noted in all cases, with reconstitution of the plantar arch in five patients. Distal revascularizations included one peroneal, and five below knee popliteal arterial bypasses. Fasciotomies were performed in four of the six patients. There were no amputations. One patient developed a persistent foot drop. Two patients developed bypass grafts occlusions; one of which required therapy. CONCLUSION: The pre-operative use of thrombolytic therapy is a safe and effective method to achieve limb salvage in this patient population. Patients must be capable of withstanding an additional period of ischemia allowing for reconstitution of distal runoff. Isolated limb perfusion is of use when a delay to reperfusion cannot be tolerated.
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| 48. |
- Greenberg, R, et al.
(författare)
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Endovascular repair of descending thoracic aortic aneurysms: an early experience with intermediate-term follow-up
- 2000
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Ingår i: Journal of Vascular Surgery. - 1097-6809. ; 31:1 Pt 1, s. 147-156
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to report an initial experience with the endovascular repair of descending thoracic aortic aneurysm. Complications and intermediate-term morphologic changes were identified with the intent of altering patient selection and device design. METHODS: Endografts were placed into 25 patients at high-risk for conventional surgical repair over a 3(1/2)-year period. Devices were customized on the basis of preoperative imaging information. Follow-up computed tomography scans were obtained at 1, 3, 6, and 12 months and yearly thereafter. Additional interventions occurred in the setting of endoleaks, migration, and aneurysm growth. RESULTS: The overall 30-day mortality rate was 20% (12.5% for elective cases; 33% for emergent cases). There were 3 conversions to open repair. Neurologic deficits developed in 3 patients; 1 insult resulted in permanent paraplegia. Neurologic deficits were associated with longer endografts (P =.019). Three endoleaks required treatment, and 1 fatal rupture of the thoracic aneurysm treated occurred 6 months after the initial repair. Migrations were detected in 4 patients. The maximal aneurysm size decreased yearly by 9.15% (P =.01) or by 13.5% (P =.0005) if patients with endoleaks (n = 3 patients) were excluded. Both the proximal and distal neck dilated slightly over the course of follow-up (P =.019 and P =.001, respectively). The length of the proximal neck was a significant predictor of the risk for endoleakage (P =.02). CONCLUSION: The treatment of descending thoracic aortic aneurysms with an endovascular approach is feasible and may, in some patients, offer the best means of therapy. Early complications were primarily related to device design and patient selection. All aneurysms without endoleaks decreased in size after treatment. Late complications were associated with changing aneurysm morphologic features and device migration. The morphologic changes remain somewhat unpredictable; however, alterations in device design may result in improved fixation and more durable aneurysm exclusion.
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| 49. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 50. |
- Hamberg, Anna-Karin, et al.
(författare)
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A Pharmacometric Model Describing the Relationship Between Warfarin Dose and INR Response With Respect to Variations in CYP2C9, VKORC1, and Age
- 2010
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 87:6, s. 727-734
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to update a previous NONMEM model to describe the relationship between warfarin dose and international normalized ratio (INR) response, to decrease the dependence of the model on pharmacokinetic (PK) data, and to improve the characterization of rare genotype combinations. The effects of age and CYP2C9 genotype on S-warfarin clearance were estimated from high-quality PK data. Thereafter, a temporal dose-response (K-PD) model was developed from information on dose, INR, age, and CYP2C9 and VKORC1 genotype, with drug clearance as a covariate. Two transit compartment chains accounted for the delay between exposure and response. CYP2C9 genotype was identified as the single most important predictor of required dose, causing a difference of up to 4.2-fold in the maintenance dose. VKORC1 accounted for a difference of up to 2.1-fold in dose, and age reduced the dose requirement by ~6% per decade. This reformulated K-PD model decreases dependence on PK data and enables robust assessment of INR response and dose predictions, even in individuals with rare genotype combinations.
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