| 1. |
- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 2. |
- Bondesson, Eva, et al.
(författare)
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Planar gamma scintigraphy - points to consider when quantifying pulmonary dry powder aerosol deposition
- 2003
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Ingår i: International Journal of Pharmaceutics. - 1873-3476. ; 251:1-2, s. 33-47
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Tidskriftsartikel (refereegranskat)abstract
- Methodological aspects of planar gamma scintigraphy used to quantify pulmonary aerosol deposition were investigated using an experimental dry powder formulation. Particles of micronized salbutamol sulphate were labelled with technetium-99m and admixed to an ordered mixture of unlabelled micronized salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was administered to 24 healthy subjects, 12 in each of two consecutive, similarly designed studies. Pulmonary deposition was determined using two methods: repeated planar imaging, and pharmacokinetic assessments following charcoal co-administration to prevent gastrointestinal salbutamol absorption. After due consideration had been taken to ensure appropriate radiolabelling, image acquisition and processing procedures, a scintigraphic estimate of 26.2% (24.2-28.4%) was obtained, which did not significantly differ from the pharmacokinetic estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the radiolabelling technique, quality control of radioaerosols produced during the study, correction for re-distribution of radiolabel from the lungs, selection of regions of interest, assessment of lung contours, correction for tissue attenuation of gamma rays and establishment of the actual recovery of radioactivity in the scintigraphic measurements could potentially affect the accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should be carefully considered in the design or evaluation of any such study.
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| 3. |
- Esbjörnsson, Joakim, et al.
(författare)
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HIV-2 as a model to identify a functional HIV cure
- 2019
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Ingår i: AIDS Research and Therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 16:1
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Forskningsöversikt (refereegranskat)abstract
- Two HIV virus types exist: HIV-1 is pandemic and aggressive, whereas HIV-2 is confined mainly to West Africa and less pathogenic. Despite the fact that it has been almost 40 years since the discovery of AIDS, there is still no cure or vaccine against HIV. Consequently, the concepts of functional vaccines and cures that aim to limit HIV disease progression and spread by persistent control of viral replication without life-long treatment have been suggested as more feasible options to control the HIV pandemic. To identify virus-host mechanisms that could be targeted for functional cure development, researchers have focused on a small fraction of HIV-1 infected individuals that control their infection spontaneously, so-called elite controllers. However, these efforts have not been able to unravel the key mechanisms of the infection control. This is partly due to lack in statistical power since only 0.15% of HIV-1 infected individuals are natural elite controllers. The proportion of long-Term viral control is larger in HIV-2 infection compared with HIV-1 infection. We therefore present the idea of using HIV-2 as a model for finding a functional cure against HIV. Understanding the key differences between HIV-1 and HIV-2 infections, and the cross-reactive effects in HIV-1/HIV-2 dual-infection could provide novel insights in developing functional HIV cures and vaccines.
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| 4. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets
- 2017
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 18:4, s. 305-307
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV-1-infected population in Sweden. Methods: The Swedish InfCare HIV Cohort Study collects viral loads, CD4 counts, and viral sequences, along with demographic and clinical data, through an electronic clinical decision support system. Almost 100% of those diagnosed with HIV infection are included in the database, corresponding to 6946 diagnosed subjects living with HIV-1 in Sweden by 31 December 2015. Results: Using HIV surveillance data reported to the Public Health Agency of Sweden, it was estimated that 10% of all HIV-infected subjects in Sweden remain undiagnosed. Among all diagnosed patients, 99.8% were linked to care and 97.1% of those remained in care. On 31 December 2015, 6605 of 6946 patients (95.1%) were on ART. A total of 6395 had been on treatment for at least 6 months and 6053 of those (94.7%) had a viral load < 50 HIV-1 RNA copies/mL. Conclusions: The 2014 UNAIDS/WHO 90-90-90 goals for HIV care means that > 73% of all patients living with HIV should be virologically suppressed by 2020. Sweden has already achieved this target, with 78% suppression, and is the first country reported to meet all the UNAIDS/WHO 90-90-90 goals.
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| 5. |
- Håkansson, H., et al.
(författare)
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In vivo and in vitro toxicity of fractionated fish lipids, with particular regard to their content of chlorinated organic compounds
- 1991
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 69:6, s. 459-471
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Tidskriftsartikel (refereegranskat)abstract
- Six different lipid matrices (the intact lipid (IL), four lipid fractions with different polarity, and the free fatty acids (FFAs) obtained by hydrolysis of the triacylglycerol (TAG) containing fraction) were obtained from salmon (Salmo salar) and eel (Anguilla anguilla), each collected at a contaminated and a comparatively uncontaminated catch site along the coast of Scandinavia. The lipid matrices were studied in toxicological test systems representing various biological functions of different organ systems from several species and trophic levels. The results were evaluated with particular respect to the concentrations of extractable organically bound chlorine (EOCl) in the matrices tested. In some test systems, the specimens with a higher EOCl concentration appeared to be more toxic. For example, the TAG containing fraction (F2) from Idefjord eel, having a higher EOCl content than F2 from Oslofjord eel, reduced the number and hatchability of eggs laid by zebrafish. Both IL and F2 of Idefjord eel increased mortality and reduced the oxygen/nitrogen-ratio in blue mussels. Non-polar compounds (F1) from Bothnian Sea salmon induced 7-ethoxyresurofin O-deethylase (EROD) activity in rainbow trout hepatocytes, whereas F1 from Senja salmon did not. F1 from Bothnian Sea salmon also reduced the number of T-cells in foetal mouse thymus anlagen in vitro compared with the cell number in anlagen exposed to F1 from Senja salmon. A positive correlation between EOCl concentration and test response was found for EROD activity in rainbow trout hepatocytes and for ATP-leakage in Erlich ascites tumour cells when testing the phospolipid containing fraction (F4). However, in most test systems the fish oils, irrespective of EOCl content, were of low toxicity, and the observed effects need to be verified in future studies.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Åkerblom, N, et al.
(författare)
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Impact of Polychlorinated Naphthalenes (PCNs) in Juvenile Baltic Salmon, Salmo salar: Evaluation of Estrogenic Effects, Development, and CYP1A Induction
- 2000
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Ingår i: Archives of Environmental Contamination and Toxicology. - : Springer Science and Business Media LLC. - 0090-4341 .- 1432-0703. ; 38:2, s. 225-33
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Tidskriftsartikel (refereegranskat)abstract
- Juvenile Baltic salmon, Salmo salar, were fed commercial salmon food contaminated with different concentrations of polychlorinated naphthalenes (PCNs; 0.1, 1, 2, or 10 μg PCN/g food). Among other effects, possible estrogenic impact caused by PCNs were evaluated. Fish were therefore fed a diet contaminated with 17β-estradiol (E2; 0.94 or 9.4 μg E2/g food), as a positive control. After 8, 13, 17, and 41 weeks, sampling took place. Growth, liver somatic index (LSI), EROD activity, and vitellogenin content in blood plasma were measured along with morphological studies of gonads and chemical analyses to determine the effects caused by PCNs. Exposure to PCNs did not seem to have any effects on body weight gain, since the group fed the high dose followed the growth in the control group during the entirely experimental period. After 41 weeks of exposure the groups fed 2 and 10 μg PCN/g food had significantly lower LSIs compared with the control, indicating liver toxic effects of PCNs. Furthermore, a dose-dependent induction of EROD activity was found. At week 41, the control group had an activity of 4.9 ± 4.8 pmol/mg prot/min, whereas it was between 69 ± 21 and 720 ± 370 pmol/mg prot/min in the exposed groups, respectively. Examination of gonadal morphology showed that PCNs also had negative effects on ovaries in Baltic salmon, including delayed development. The distribution between females and males, gonadal morphology, and vitellogenin content in blood plasma did, however, indicate that PCNs are not capable of causing effects similar to E2 or xenoestrogens. Exposure to both of the concentrations of E2 resulted in decreased body weight gain, increased LSI, and feminization of the gonads. E2 did, however, not induce any EROD activity.
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| 10. |
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| 11. |
- Adler, Niclas, et al.
(författare)
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Integrationdriven Development
- 1997
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Ingår i: Proceedings : the creation of prosperity, business and work opportunities through technology management. - Stockholm : Swedish Society of Mechanical Engineers, Naval Architects and Aeronautical Engineers. - 9163056119
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 12. |
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| 13. |
- Ahmed, R K S, et al.
(författare)
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Antigen-specific beta-chemokine production and CD8(+) T-cell noncytotoxic antiviral activity in HIV-2-infected individuals
- 2005
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 61:1, s. 63-71
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus-2 (HIV-2) is less pathogenic than HIV-1, and the disease progression in HIV-2-infected individuals seems to be similar to that seen in HIV-1-infected long-term nonprogressors. Cell-mediated immune responses and the production of noncytotoxic CD8(+) T-cell antiviral factors (CAF) and beta-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-induced beta-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also compared in vitro CD8(+) T-cell-mediated noncytotoxic antiviral activity against beta-chemokine-sensitive R5 virus (HIV-1(Bal)) and beta-chemokine-insensitive X4 virus (HIV-1(IIIB)) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specific beta-chemokine production was demonstrated in a majority of the HIV-2-infected subjects. CD8(+) T cells of both HIV-1 and HIV-2-infected individuals suppressed R5 virus replication in vitro in a similar manner, while the inhibition of X4 virus replication seemed to be more frequent and of a higher magnitude among HIV-2-infected patients compared to HIV-1-infected subjects. Taken together, our results indicate that the production of CD8(+) T-cell noncytotoxic antiviral factors may contribute to the low transmission of the virus and slower disease progression in HIV-2-infected patients.
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| 14. |
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| 15. |
- Amcoff, P., et al.
(författare)
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Alterations of dopaminergic and serotonergic activity in the brain of sea-run Baltic salmon suffering a thiamine deficiency-related disorder
- 2002
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Ingår i: Journal of Fish Biology. - : Elsevier. - 0022-1112 .- 1095-8649. ; 60:6, s. 1407-1416
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Tidskriftsartikel (refereegranskat)abstract
- Baltic salmon Salmo salar females displaying wiggling behaviour had significantly lower (P<0.05) hepatic and ovarian thiamine (vitamin B1) concentrations than the normal females, confirming that they suffered from a thiamine deficiency. A significantly (P<0.05) increased monoaminergic activity was found in the telencephalon and the hypothalamus of the wiggling individuals as indicated by [5-hydroxyindoleacetic acid (5-HIAA)]: [5-hydroxytryptamine (5-HT)] and [3,4-dihydroxyphenylacetic acid (DOPAC)]: [dopamine (DA)] ratios. The 5-HIAA concentrations of wiggling individuals were significantly (P<0.05) higher in the telencephalon and the hypothalamus compared to normal fish. Wiggling fish showed significantly (P<0.05) higher concentrations of the DA metabolite DOPAC in the hypothalamus and the brain stem compared to normal fish. Furthermore, the brain stem in wiggling fish contained significantly (P<0.05) less 5-HT than in normal individuals, which was also reflected in a significant (P<0.05) increase in the (5-HIAA): (5-HT) ratio. These results demonstrate an increased serotonergic and dopaminergic activity in wiggling compared to normal fish. The altered monoaminergic activity may be directly related to altered brain thiamine metabolism, but a general stress caused by thiamine deficiency and an inability to regulate swim bladder inflation may contribute. Furthermore, a changed brain monoaminergic activity may contribute to the behaviour characterizing wiggling fish.
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| 16. |
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| 17. |
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| 18. |
- Boswell, M. T., et al.
(författare)
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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| 19. |
- Carlander, C., et al.
(författare)
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Cohort profile: InfCareHIV, a prospective registry-based cohort study of people with diagnosed HIV in Sweden
- 2023
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The Swedish InfCareHIV cohort was established in 2003 to ensure equal and effective care of people living with HIV (PLHIV) and enable long-term follow-up. InfCareHIV functions equally as a decision support system as a quality registry, ensuring up-to-date data reported in real time. Participants InfCareHIV includes data on >99% of all people with diagnosed HIV in Sweden and up to now 13029 have been included in the cohort. InfCareHIV includes data on HIV-related biomarkers and antiretroviral therapies (ART) and also on demographics, patient-reported outcome measures and patient-reported experience measures. Findings to date Sweden was in 2015 the first country to reach the UNAIDS (United Nations Programme on HIV/AIDS)/WHO's 90-90-90 goals. Late diagnosis of HIV infection was identified as a key problem in the Swedish HIV-epidemic, and low-level HIV viraemia while on ART associated with all-cause mortality. Increased HIV RNA load in the cerebrospinal fluid (CSF) despite suppression of the plasma viral load was found in 5% of PLHIV, a phenomenon referred to as 'CSF viral escape'. Dolutegravir-based treatment in PLHIV with pre-existing nucleoside reverse transcriptase inhibitor-mutations was non-inferior to protease inhibitor-based regimens. An increase of transmitted drug resistance was observed in the InfCareHIV cohort. Lower efficacy for protease inhibitors was not due to lower adherence to treatment. Incidence of type 2 diabetes and insulin resistance was high in the ageing HIV population. Despite ART, the risk of infection-related cancer as well as lung cancer was increased in PLHIV compared with HIV-negative. PLHIV were less likely successfully treated for cervical precancer and more likely to have human papillomavirus types not included in current HPV vaccines. Self-reported sexual satisfaction in PLHIV is improving and is higher in women than men. Future plans InfCareHIV provides a unique base to study and further improve long-term treatment outcomes, comorbidity management and health-related quality of life in people with HIV in Sweden.
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| 20. |
- Esbjörnsson, Joakim, et al.
(författare)
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Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau : a prospective open cohort study
- 2019
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Ingår i: The Lancet HIV. - : The Lancet Publishing Group. - 2405-4704 .- 2352-3018. ; 6:1, s. E25-E31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HIV type 2 (HIV-2) is considered more benign and has fewer pathogenic consequences than HIV type 1 (HIV-1) for most infected individuals. However, reliable estimates of time to AIDS and mortality among those with HIV-2 infection are absent. We therefore aimed to compare the time to AIDS and mortality, and the CD4 T-cell dynamics between those infected with HIV-1 and HIV-2.METHODS: We did a prospective open cohort study. We included all police officers with regular employment from police stations in both urban and rural areas of Guinea-Bissau since Feb 6, 1990. We continued to include participants until Sept 28, 2009, and follow-up of HIV-1-positive and HIV-2-positive individuals continued until Sept 28, 2013. We collected blood samples at enrolment and at scheduled annual follow-up visits at police stations. We analysed longitudinal data from individuals infected with HIV-1 and HIV-2 according to time to AIDS, time to death, and T-cell dynamics. Time of HIV infection was estimated as the mid-timepoint between last HIV-seronegative and first HIV-seropositive sample. Data from an additional 2984 HIV-uninfected individuals from the same population were analysed to assess the effect of natural mortality on HIV-related mortality.FINDINGS: 872 participants tested HIV positive during the 23-year study period: 408 were infected with HIV-1 (183 infected before and 225 infected after enrolment) and 464 were infected with HIV-2 (377 before and 87 after enrolment). The median time from HIV infection to development of AIDS was 6·2 years (95% CI 5·4-7·1) for HIV-1 infection and 14·3 years (10·7-18·0) for HIV-2 infection (p<0·0001). The median survival time after HIV infection was 8·2 years (95% CI 7·5-8·9) for HIV-1 infection and 15·6 years (12·0-19·2) for HIV-2 infection (p<0·0001). Individuals who were infected with HIV-1 or HIV-2 before enrolment showed similar results. Comparison with uninfected individuals indicated limited confounding contribution from natural mortality. Mean CD4 percentages were higher in individuals with HIV-2 than in those with HIV-1 during early infection (28·0% [SE 1·3] vs 22·3% [1·7]; p=0·00094) and declined at a slower rate (0·4% [0·2] vs 0·9% [0·2] per year; p=0·028). HIV-2-infected individuals developed clinical AIDS at higher mean CD4 percentages (18·2%, IQR 7·2-25·4) than HIV-1-infected individuals (8·2%, 3·0-13·8; p<0·0001).INTERPRETATION: Our results show that both HIV-1-infected and HIV-2-infected individuals have a high probability of developing and dying from AIDS without antiretroviral treatment.
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| 21. |
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| 22. |
- Holbech, Henrik, et al.
(författare)
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Comparison of zebrafish (Danio rerio) and fathead minnow (Pimephales promelas) as test species in the Fish Sexual Development Test (FSDT).
- 2012
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Ingår i: Comparative Biochemistry and Physiology - Part C. - : Elsevier BV. - 1532-0456 .- 1878-1659. ; 155:2, s. 407-15
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Tidskriftsartikel (refereegranskat)abstract
- Results are presented from a validation (with 5 laboratories) of the Fish Sexual Development Test (FSDT) developed to detect endocrine disrupters (EDs) and included in the OECD (Organisation for Economic Co-operation and Development) working program. The aromatase-inhibiting fungicide prochloraz was tested in zebrafish (Danio rerio) and fathead minnow (Pimephales promelas). The fish were exposed during sexual differentiation and development from 0 to 60 days post hatch (dph). After exposure, the vitellogenin (VTG) concentrations were quantified in head/tail homogenate and the sex ratio was determined (defined as female, male, intersex or undifferentiated). NOEC/LOEC and EC(x) designs were compared to optimize the test approach. Results show that both species are highly sensitive to prochloraz during sexual development. They respond by skewing of the sex ratio towards male phenotype and by a VTG decline in females. The NOEC/LOEC approach is preferred because sex ratio is difficult to analyze with a regression model. The mean NOEC/LOEC for prochloraz on the sex ratio was 43.3/134 μg/L and 101/293 μg/L for zebrafish and fathead minnow, respectively. The mean NOEC/LOEC on the decline in female VTG concentration was 65/110 μg/L and ~30/68 μg/L respectively. In conclusion, zebrafish and fathead minnow are suitable species in the FSDT and their sexual differentiation is equally labile to EDs.
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| 23. |
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| 24. |
- Kling, Peter, 1968, et al.
(författare)
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Gender-specific proteomic responses in zebrafish liver following exposure to a selected mixture of brominated flame retardants
- 2008
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Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier Inc. - 1090-2414 .- 0147-6513. ; 71:2, s. 319-27
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Tidskriftsartikel (refereegranskat)abstract
- Proteomic effect screening in zebrafish liver was performed to generate hypotheses following exposure (21 days) to a structurally diverse mixture of brominated flame retardants (BFRs). Fish were exposed to two doses (10 and 100 nmol/g feed). Two-dimensional gel-electrophoresis, image analysis and MALDI-TOF mass-spectrometry revealed 13 and 19 significant responses in males and females, respectively. Effects on proteins related to cellular maintenance and stress were observed in both genders. Regulated proteins were gender-specific, but functionally indicated common protective responses (peroxiredoxin 6 and Zgc:92891 in males and transketolase in females) suggesting oxidative stress. Betaine homocysteine methyltransferase (BHMT) was induced in both genders. In addition a female-specific downregulation of ironhomeostatic proteins (iron-regulatory protein 1 and transferrin) were observed. Our proteomic approach revealed novel responses that suggest important gender-specific sensitivity to BFRs that should be considered when interpreting adverse effects of BFRs.
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| 25. |
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