| 1. |
- Malm, Kerstin, 1960-, et al.
(författare)
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Analytical evaluation of nine serological assays for diagnosis of syphilis
- 2015
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley-Blackwell. - 0926-9959 .- 1468-3083. ; 29:12, s. 2369-2376
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Tidskriftsartikel (refereegranskat)abstract
- Background: The diagnosis of syphilis is most frequently dependent on antibody detection with serological assays. Assays for both treponemal and non-treponemal antibodies are needed to provide a sensitive and specific diagnosis. For decades, a first screening has been done with non-treponemal assays, followed by treponemal. However, in recent years, following laboratory automation, the reverse sequence screening algorithms have been developed, using a treponemal assay as the initial screening test.Objective: To evaluate serological assays for treponemal and non-treponemal antibodies, to use in reverse algorithm screening of syphilis.Material and methods: Six treponemal assays (one IgM-specific assay), two non-treponemal assays and one novel dual point-of-care (POC) assay for serological diagnosis of syphilis were evaluated. Serum samples from Guinea-Bissau and Sweden were examined, as well as two performance panels and samples from blood donors. Sensitivity and specificity were calculated for each assay, using different assays as gold standard test.Results: The Macro-Vue RPR Card test was the most sensitive non-treponemal test and the TrepSure Anti-Treponema EIA Screen and the SeroDia TP-PA were the most sensitive and specific treponemal assays. Among the automated assays, both the Liaison Treponema Screen and Architect Syphilis TP showed high sensitivity, however, the former had clearly higher specificity.Conclusions: In resourced settings, where the reverse sequence algorithm is preferred for screening, an automated treponemal immunoassay for initial screening subsequently followed by the TrepSure test or TP-PA assay as a second treponemal assay appear highly effective. Finally, a quantitative highly sensitive non-treponemal assay, e.g. the Macro-Vue RPR Card test, could then be used as a supplementary test to evaluate activity of the syphilis infection.
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| 2. |
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| 3. |
- Asplund, Sara, 1976, et al.
(författare)
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Extended analysis of the effect of learning with feedback on the detectability of pulmonary nodules in chest tomosynthesis
- 2011
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. ; 7966
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In chest tomosynthesis, low-dose projections collected over a limited angular range are used for reconstruction of section images of the chest, resulting in a reduction of disturbing anatomy at a moderate increase in radiation dose compared to chest radiography. In a previous study, we investigated the effects of learning with feedback on the detection of pulmonary nodules in chest tomosynthesis. Six observers with varying degrees of experience of chest tomosynthesis analyzed tomosynthesis cases for presence of pulmonary nodules. The cases were analyzed before and after learning with feedback. Multidetector computed tomography (MDCT) was used as reference. The differences in performance between the two readings were calculated using the jackknife alternative free-response receiver operating characteristics (JAFROC-2) as primary measure of detectability. Significant differences between the readings were found only for observers inexperienced in chest tomosynthesis. The purpose of the present study was to extend the statistical analysis of the results of the previous study, including JAFROC-1 analysis and FROC curves in the analysis. The results are consistent with the results of the previous study and, furthermore, JAFROC-1 gave lower p-values than JAFROC-2 for the observers who improved their performance after learning with feedback. © 2011 SPIE.
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| 4. |
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| 5. |
- Asplund, Sara, 1976, et al.
(författare)
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Learning aspects and potential pitfalls regarding detection of pulmonary nodules in chest tomosynthesis and proposed related quality criteria.
- 2011
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Ingår i: Acta radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 52:5, s. 503-512
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Tidskriftsartikel (refereegranskat)abstract
- Background In chest tomosynthesis, low-dose projections collected over a limited angular range are used for reconstruction of an arbitrary number of section images of the chest, resulting in a moderately increased radiation dose compared to chest radiography. Purpose To investigate the effects of learning with feedback on the detection of pulmonary nodules for observers with varying experience of chest tomosynthesis, to identify pitfalls regarding detection of pulmonary nodules, and present suggestions for how to avoid them, and to adapt the European quality criteria for chest radiography and computed tomography (CT) to chest tomosynthesis. Material and Methods Six observers analyzed tomosynthesis cases for presence of nodules in a jackknife alternative free-response receiver-operating characteristics (JAFROC) study. CT was used as reference. The same tomosynthesis cases were analyzed before and after learning with feedback, which included a collective learning session. The difference in performance between the two readings was calculated using the JAFROC figure of merit as principal measure of detectability. Results Significant improvement in performance after learning with feedback was found only for observers inexperienced in tomosynthesis. At the collective learning session, localization of pleural and subpleural nodules or structures was identified as the main difficulty in analyzing tomosynthesis images. Conclusion The results indicate that inexperienced observers can reach a high level of performance regarding nodule detection in tomosynthesis after learning with feedback and that the main problem with chest tomosynthesis is related to the limited depth resolution.
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| 6. |
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| 7. |
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| 8. |
- Biague, Antonio Jaime, et al.
(författare)
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High sexual risk taking and diverging trends of HIV-1 and HIV-2 in the military of Guinea Bissau
- 2011
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Ingår i: Journal of Infection in Developing Countries. ; 5:4, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HIV and other sexually transmitted infections are a growing problem in the military personnel of Africa, and information about this problem in Guinea-Bissau is lacking. The aims of this study were to determine the prevalence and trends of the HIV epidemics in the military forces of Guinea Bissau and to explore possible risk factors for HIV infection. METHODOLOGY: Repeated cross-sectional surveys of HIV-1 and HIV-2 were conducted between 1992 and 2005, and knowledge, sexual behaviour and risk factors for HIV-1 and HIV-2 in military personnel in Guinea-Bissau were assessed. RESULTS: The seroprevalence of HIV-1, HIV-2 and HIV-1+HIV-2 dual reactivity was 1.1%, 8.4% and 0.1% in 1992-95, and in 2005 7.7%, 5.1% and 1.9%, respectively. Both the increase of HIV-1 and the decline of HIV-2 between 1992-95 and 2005 were significant when adjusted for age (p < 0.001 for both changes). Only a minority did not know how HIV transmits, but sexual risk taking was high. Several significant risk factors were found in univariate analyses for HIV-1 and HIV-2, but the only risk factor that remained significant after multivariate regression analysis was previous contact with a prostitute among HIV-1-positive subjects (single and dually reactive) (p < 0.01). CONCLUSION: The increasing trend of HIV-1 and the high risky sexual behavior illustrate the need for improvement in HIV/AIDS prevention efforts among military personnel in Guinea Bissau.
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| 9. |
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| 10. |
- Esbjörnsson, Joakim, et al.
(författare)
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Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease - indication of an evolving epidemic in West Africa
- 2010
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Ingår i: Retrovirology. - : Springer Science and Business Media LLC. - 1742-4690. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: HIV-1 is one of the fastest evolving pathogens, and is distinguished by geographic and genetic variants that have been classified into different subtypes and circulating recombinant forms (CRFs). Early in infection the primary coreceptor is CCR5, but during disease course CXCR4-using HIV-1 populations may emerge. This has been correlated with accelerated disease progression in HIV-1 subtype B. Basic knowledge of HIV-1 coreceptor tropism is important due to the recent introduction of coreceptor antagonists in antiretroviral therapy, and subtype-specific differences regarding how frequently HIV-1 CXCR4-using populations appear in late-stage disease need to be further investigated. To study how frequently CXCR4-using populations appear in late-stage disease among HIV-1 subtype A and CRF02_AG, we evaluated the accuracy of a recombinant virus phenotypic assay for these subtypes, and used it to determine the HIV-1 coreceptor tropism of plasma samples collected during late-stage disease in Guinea-Bissau. We also performed a genotypic analysis and investigated subtype-specific differences in the appearance of CXCR4 tropism late in disease. Results: We found that the recombinant virus phenotypic assay accurately predicted HIV-1 coreceptor tropism of subtype A and CRF02_AG. Over the study period (1997-2007), we found an increasing and generally high frequency of CXCR4 tropism (86%) in CRF02_AG. By sequence analysis of the V3 region of our samples we developed a novel genotypic rule for predicting CXCR4 tropism in CRF02_AG, based on the combined criteria of the total number of charged amino acids and net charge. This rule had higher sensitivity than previously described genotypic rules and may be useful for development of future genotypic tools for this CRF. Finally, we conducted a literature analysis, combining data of 498 individuals in late-stage disease, and found high amounts of CXCR4 tropism for all major HIV-1 subtypes (60-77%), except for subtype C (15%). Conclusions: The increase in CXCR4 tropism over time suggests an evolving epidemic of CRF02_AG. The results of the literature analysis demonstrate the need for further studies investigating subtype-specific emergence for CXCR4-tropism; this may be particularly important due to the introduction of CCR5-antagonists in HIV treatment regimens.
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| 11. |
- Esbjörnsson, Joakim, et al.
(författare)
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HIV-1 Molecular Epidemiology in Guinea-Bissau, West Africa: Origin, Demography and Migrations
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- The HIV-1 epidemic in West Africa has been dominated by subtype A and the recombinant form CRF02_AG. Little is known about the origins and the evolutionary history of HIV-1 in this region. We employed Maximum likelihood and Bayesian methods in combination with temporal and spatial information to reconstruct the HIV-1 subtype distribution, demographic history and migration patterns over time in Guinea-Bissau, West Africa. We found that CRF02_AG and subsubtype A3 were the dominant forms of HIV-1 in Guinea-Bissau and that they were introduced into the country on at least six different occasions between 1976 and 1981. These estimates also corresponded well with the first reported HIV-1 cases in Guinea-Bissau. Migration analyses suggested that (1) the HIV-1 epidemic started in the capital Bissau and then dispersed into more rural areas, and (2) the epidemic in Guinea-Bissau was connected to both Cameroon and Mali. This is the first study that describes the HIV-1 molecular epidemiology in a West African country by combining the results of subtype distribution with analyses of epidemic origin and epidemiological linkage between locations. The multiple introductions of HIV-1 into Guinea-Bissau, during a short time-period of five years, coincided with and were likely influenced by the major immigration wave into the country that followed the end of the independence war (1963-1974).
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| 12. |
- 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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| 13. |
- Esbjörnsson, Joakim, et al.
(författare)
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Increased survival among HIV-1 and HIV-2 dual-infected individuals compared to HIV-1 single-infected individuals
- 2014
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Ingår i: AIDS. - 1473-5571. ; 28:7, s. 949-957
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare survival times of HIV-1 single and HIV-1 and HIV-2 dual-infected individuals. Design: Prospective open cohort study. Methods: We analysed data from 259 HIV-1-seroincident cases (either HIV-1 single or HIV-1 and HIV-2 dual-infected) from a cohort with long follow-up (similar to 20 years) in order to study the influence of type of infection and infection order on mortality. Sex and age at HIV-1 infection date was controlled for in a Cox proportional-hazards model. Results: Dual-infected individuals had a 42% longer time from HIV-1 infection to death compared with single-infected individuals, adjusting for age asymmetries between groups. Dual-infected individuals with an HIV-2 infection preceding the HIV-1 infection had a more than two-fold lower mortality risk during follow-up than HIV-1 single-infected individuals. Conclusion: Survival time is longer and the risk of progression to death is lower among HIV-1 and HIV-2 dual-infected individuals compared to HIV-1 single-infected individuals. This natural inhibition could have implications for the development of future HIV-1 vaccines and therapeutics.
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| 14. |
- Esbjörnsson, Joakim, et al.
(författare)
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Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection.
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:3, s. 224-232
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood. METHODS: We analyzed data from 223 participants who were infected with HIV-1 after enrollment (with either HIV-1 infection alone or HIV-1 and HIV-2 infection) in a cohort with a long follow-up duration (approximately 20 years), according to whether HIV-2 infection occurred first, the time to the development of AIDS (time to AIDS), CD4+ and CD8+ T-cell counts, and measures of viral evolution. RESULTS: The median time to AIDS was 104 months (95% confidence interval [CI], 75 to 133) in participants with dual infection and 68 months (95% CI, 60 to 76) in participants infected with HIV-1 only (P=0.003). CD4+ T-cell levels were higher and CD8+ T-cell levels increased at a lower rate among participants with dual infection, reflecting slower disease progression. Participants with dual infection with HIV-2 infection preceding HIV-1 infection had the longest time to AIDS and highest levels of CD4+ T-cell counts. HIV-1 genetic diversity was significantly lower in participants with dual infections than in those with HIV-1 infection alone at similar time points after infection. CONCLUSIONS: Our results suggest that HIV-1 disease progression is inhibited by concomitant HIV-2 infection and that dual infection is associated with slower disease progression. The slower rate of disease progression was most evident in participants with dual infection in whom HIV-2 infection preceded HIV-1 infection. These findings could have implications for the development of HIV-1 vaccines and therapeutics. (Funded by the Swedish International Development Cooperation Agency-Swedish Agency for Research Cooperation with Developing Countries and others.).
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| 15. |
- 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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| 16. |
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| 17. |
- Frånlund, Maria, et al.
(författare)
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Prostate cancer risk assessment in men with an initial P.S.A. below 3 ng/mL : results from the Göteborg randomized population-based prostate cancer screening trial
- 2018
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:4, s. 256-262
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective: To evaluate the long-term outcome of men with an initial prostate-specific antigen (PSA) level below 3 ng/mL and whether the free-to-total (F/T PSA) ratio is a useful prognostic marker in this range. Materials and methods: This study is based on 5,174 men aged 50–66 years, who in 1995–1996 participated in the first round of the Göteborg randomized screening trial (initial T-PSA level <3 ng/mL). These men were subsequently invited biennially for PSA and F/T PSA screening until they reached the upper age limit (on average 69 years). Biopsy was recommended if PSA ≥ 3 ng/mL. Results: After a median follow-up of 18.9 years, 754 men (14.6%) were diagnosed with prostate cancer (PC). The overall cumulative PC incidence was 17.2%. It increased from 7.9% among men with T-PSA of ≤0.99 ng/mL to 26.0% in men with T-PSA levels of 1–1.99 ng/mL and 40.3% in men between 2–2.99 ng/mL (p < 0.001). The initial PSA was also related to the incidence of Gleason ≥7 PC (3.7% vs 9.7% vs 10.9%) and PC death (0.3% vs 1.1% vs 1.5%). Adding F/T PSA did not improve PC prediction in terms of Harrell concordance index (base model 0.76 vs 0.76) nor improvement of the likelihood of the model (p = 0.371). Conclusions: Some men with initial PSA < 3 ng/mL will be diagnosed too late, despite participating in an organized screening program, indicating that prompt diagnosis is justified in these men. PC incidence and risk of PC death was associated with PSA., but F/T PSA had no predictive value.
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| 18. |
- Giordanetto, Fabrizio, et al.
(författare)
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Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1 H-indol-1-yl]pyridine-2-yl}propanoic Acid
- 2018
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society. - 1948-5875. ; 9:7, s. 600-605
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Tidskriftsartikel (refereegranskat)abstract
- A lead generation campaign identified indole-based sPLA2-X inhibitors with a promising selectivity profile against other sPLA2 isoforms. Further optimization of sPLA2 selectivity and metabolic stability resulted in the design of (-)-17, a novel, potent, and selective sPLA2-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (-)-17 was tested in an ApoE-/- murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA2-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (-)-17 did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis.
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| 19. |
- Glantz, Maria, et al.
(författare)
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Effect of polymorphisms in the leptin, leptin receptor and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) genes and genetic polymorphism of milk proteins on bovine milk composition.
- 2012
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Ingår i: Journal of Dairy Research. - 0022-0299. ; 79:1, s. 110-118
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Tidskriftsartikel (refereegranskat)abstract
- The relations between cow genetics and milk composition have gained a lot of attention during the past years, however, generally only a few compositional traits have been examined. The aim of this study was to determine if polymorphisms in the leptin (LEP), leptin receptor (LEPR) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) genes as well as genetic polymorphism of β-casein (β-CN), κ-CN and β-lactoglobulin (β-LG) impact several bovine milk composition traits. Individual milk samples from the Swedish Red and Swedish Holstein breeds were analyzed for components in the protein, lipid, carbohydrate and mineral profiles. Cow alleles were determined on the following SNP: A1457G, A252T, A59V and C963T on the LEP gene, T945M on the LEPR gene and Nt984+8(A-G) on the DGAT1 gene. Additionally, genetic variants of β-CN, κ-CN and β-LG were determined. For both the breeds, the same tendency of minor allele frequency was found for all SNPs and protein genes, except on LEPA1457G and LEPC963T. This study indicated significant (P<0·05) associations between the studied SNPs and several compositional parameters. Protein content was influenced by LEPA1457G (G>A) and LEPC963T (T>C), whereas total Ca, ionic Ca concentration and milk pH were affected by LEPA1457G, LEPA59V, LEPC963T and LEPRT945M. However, yields of milk, protein, CN, lactose, total Ca and P were mainly affected by β-CN (A2>A1) and κ-CN (A>B>E). β-LG was mainly associated with whey protein yield and ionic Ca concentration (A>B). Thus, this study shows possibilities of using these polymorphisms as markers within genetic selection programs to improve and adjust several compositional parameters.
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| 20. |
- Glantz, Maria, et al.
(författare)
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Genomic selection in relation to bovine milk composition and processability.
- 2012
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Ingår i: Journal of Dairy Research. - 0022-0299. ; 79:1, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- Genomic selection is a new technology in which selection decisions are based on direct genomic values (DGVs) or genomic enhanced breeding values (GEBVs). The objective of this study was to evaluate the relations between DGVs and several milk traits important for both the nutritional value and processability of milk. This is a new approach and can be used to increase the knowledge on how genomic selection can be used in practice. Morning milk samples from Swedish Holstein cows were analyzed for milk composition and technological properties. DGVs were received for each cow for milk, protein and fat yield, milk index, udder health, Nordic total merit and a quota was calculated between fat and milk yield as well as protein and milk yield. The results show that linear correlations exist (P<0·10) between the studied DGVs and contents and yields of parameters in the protein (P=0·002-0·097), fat (P=0·024-0·055) and mineral profiles (P=0·001-0·099) as well as for cheese characteristics (P=0·004-0·065), thus making it possible to obtain detailed information on milk traits that are not registered in the milk recording scheme. Hence, genomic selection will be an efficient tool for breeding and dairy industry to select cows early in life for targeted milk production.
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| 21. |
- Gudjonsson, Sigurdur, et al.
(författare)
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The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)
- 2012
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 110:2B, s. E41-E45
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. PATIENTS AND METHODS Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. RESULTS The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (greater than= 2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively. CONCLUSION Traditional cold-cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.
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| 22. |
- Harfeldt, Kristin, et al.
(författare)
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Spectroscopic differences in posterior insula in patients with chronic temporomandibular pain
- 2018
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Ingår i: Scandinavian Journal of Pain. - : De Gruyter Open. - 1877-8860 .- 1877-8879. ; 18:3, s. 351-361
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Chronic pain including temporomandibular disorder (TMD) pain involves a complex interplay between peripheral and central sensitization, endogenous modulatory pathways, cortical processing and integration and numerous psychological, behavioral and social factors. The aim of this study was to compare spectroscopic patterns of N-Acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (MI), glutamate (Glu), and the combination of Glu and glutamine in the posterior insula in patients with chronic generalized or regional chronic TMD pain (gTMD and rTMD, respectively) compared to healthy individuals (HI) in relation to clinical findings of TMD pain. Methods: Thirty-six female patients with chronic rTMD or gTMD with at least 3 months duration were included in the study. Ten healthy women were included as controls. All participants completed a questionnaire that comprised assessment of degrees of depression, anxiety, stress, catastrophizing, pain intensity, disability and locations. A clinical Diagnostic Criteria for Temporomandibular Disorders examination that comprised assessment of pain locations, headache, mouth opening capacity, pain on mandibular movement, pain on palpation and temporomandibular joint noises was performed. Pressure-pain threshold (PPT) over the masseter muscle and temporal summation to pressure stimuli were assessed with an algometer. Within a week all participants underwent non-contrast enhanced MRI on a 3T MR scanner assessing T1-w and T2-w fluid attenuation inversion recovery. A single-voxel H-1-MRS examination using point-resolved spectroscopy was performed. The metabolite concentrations of NAA, tCr, Cho, MI, Glu and Glx were analyzed with the LC model. Metabolite levels were calculated as absolute concentrations, normalized to the water signal. Metabolite concentrations were used for statistical analysis from the LC model if the Cramer-Rao bounds were less than 20%. In addition, the ratios NAA/tCr, Cho/tCr, Glu/tCr and MI/tCr were calculated. Results: The results showed significantly higher tCr levels within the posterior insula in patients with rTMD or gTMD pain than in HI (p = 0.029). Cho was negatively correlated to maximum mouth opening capacity with or without pain (r(s) = -0.42, n = 28, p = 0.031 and r(s) = -0.48, n = 28, p = 0.034, respectively) as well as pressure-pain threshold on the hand (r(s) = -0.41, n = 28, p = 0.031). Glu was positively correlated to temporal summation to painful mechanical stimuli (r(s) = 0.42, n = 26, p = 0.034). Conclusions: The present study found that increased concentrations of Cho and Glu in the posterior insular cortex is related to clinical characteristics of chronic TMD pain, including generalized pain. These findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. Implications: The findings in this study have indirect implications for the diagnosis and management of TMD patients. That said, the findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. It is also a further step towards understanding and accepting chronic pain as a disorder in itself.
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| 23. |
- Hugosson, Jonas, 1955, et al.
(författare)
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A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 76:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality. Objective: To determine whether PSA screening decreases PCa mortality for up to 16 yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended. Design, setting, and participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55-69 yr), selected from population registry. Outcome measurements and statistical analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended. Results and limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p < 0.001) at 16 yr. The difference in absolute PCa mortality increased from 0.14% at 13 yr to 0.18% at 16 yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16 yr compared with 742 at 13 yr. The number needed to diagnose was reduced to 18 from 26 at 13 yr. Men with PCa detected during the first round had a higher prevalence of PSA >20 ng/ml (9.9% compared with 4.1% in the second round, p < 0.001) and higher PCa mortality (hazard ratio = 1.86, p < 0.001) than those detected subsequently. Conclusions: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level. Patient summary: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology.
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| 24. |
- Jahnson, Staffan, et al.
(författare)
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Urinary diversion after cystectomy for bladder cancer: A population-based study in Sweden
- 2010
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Ingår i: SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 44:2, s. 69-75
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the type of urinary diversion performed after cystectomy in patients with muscle-invasive bladder cancer in Sweden, using data from a population-based national register. Material and methods. Since 1997, the Swedish Bladder Cancer Register has included more than 90% of all patients with newly diagnosed bladder cancer. The different types of urinary diversion performed in 1997-2003 were analysed, comparing non-continent diversion (ileal conduit) with continent reconstruction (bladder substitution or continent cutaneous diversion). Results. During the study period, 3463 patients were registered with clinical T2-T4 non-metastatic bladder cancer. Cystectomy was performed in 1141 patients with ileal conduit in 732 (64%) and continent reconstruction in 409 (36%). Ileal conduit was used more frequently in females than males (p = 0.019), in patients older than 75 years (p andlt; 0.00001), and in those with less favourable TNM classification. Continent reconstruction was done more often at university hospitals than at county hospitals (p andlt; 0.00001), but rarely in the northern and western healthcare regions compared with other regions (p andlt; 0.00001). Nationwide, the proportion of registered continent reconstructions decreased, although the absolute number was relatively stable (50-60 per year). Conclusions. Continent reconstruction after cystectomy for muscle-invasive bladder cancer is performed more often in some healthcare regions and in patients at university hospitals than in county hospitals, indicating a substantial provider influence on the choice of urinary diversion. Over time, the proportion of these procedures has decreased, while the absolute number has remained low and stable; therefore, concentration in high-volume hospitals specialized in bladder cancer and continent reconstruction seems appropriate.
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| 25. |
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| 26. |
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| 27. |
- Liedberg, Fredrik, et al.
(författare)
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Long-term follow-up after radical cystectomy with emphasis on complications and reoperations: A Swedish population-based survey
- 2012
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 46:1, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate outcome after radical cystectomy for primary bladder cancer in a large population-based material. Material and methods. Between 1997 and 2002 all patients treated with radical cystectomy within 3 months after diagnosis of primary bladder cancer without distant metastasis were retrieved through the Swedish Bladder Cancer Registry. A follow-up questionnaire was distributed to all units where the primary registration of patients was performed. Follow-up data on recurrence date were retrieved from the patient charts and causes of death were obtained from the Swedish Cause of Death Registry until 2003. Results. During the study period radical cystectomy was performed in 39 units in Sweden, of which only five units were considered high-volume hospitals performing 10 or more procedures annually. Mean blood loss was 2300 ml (median 2000 ml) and the 90-day mortality rate was 5.7%. Blood loss was higher in high-volume units than in hospitals with lower hospital volumes, but the 90-day mortality rates were similar. During a median follow-up of 3.5 years, 24% of the patients were submitted to a reoperation. Reoperation rates were significantly higher in patients who received a continent urinary diversion (29%) compared with an ileal conduit (22%, p andlt; 0.015). Conclusions. Radical cystectomy was associated with a reoperation rate of 24% in Sweden during the study period. The reoperation rates were higher in patients receiving a continent cutaneous diversion or bladder substitution. Blood loss was higher in high-volume units; otherwise, surgical volume did not affect mortality rates, cancer-specific survival or reoperation rates.
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| 28. |
- Linderholm, Linda, et al.
(författare)
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Human exposure to persistent organic pollutants in West Africa - A temporal trend study from Guinea-Bissau
- 2010
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 36:7, s. 675-682
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Tidskriftsartikel (refereegranskat)abstract
- Background Humans, independent on where they live, are exposed to complex and various mixtures of chemicals, including persistent organic pollutants (POPs). The variability of the exposure depends on sources of the chemicals and is influenced by e.g. geography, social and cultural heritage. While exposures to POPs are frequently studied in populations from developed industrial countries, very little is known on levels and trends of POPs in developing countries, especially in Africa. Objectives The aim of the present study was to investigate levels and temporal trends of POPs in adults from Guinea-Bissau. Methods Serum samples were obtained from an open cohort of police officers in Guinea-Bissau. Repeated samples from 33 individuals were obtained at five time points between 1990 and 2007, in all 147 samples. Pooled serum samples were extracted and cleaned-up prior to analysis by gas chromatography and mass spectrometry. The concentration of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (4,4′-DDT) and its metabolites, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and hexachlorocyclohexanes (HCHs) were determined. Results The major POP found in all samples was 1,1-dichloro-2,2-bis(4-chlorophenyl)ethene (4,4′-DDE) followed by 4,4′-DDT. 4,4′-DDE, 4,4′-DDT, PCBs and β- and γ-HCH were significantly decreasing over time. The PBDEs were found at low concentrations, with an increasing temporal trend for BDE-153. Conclusion National and international management may be behind the observed decreased organohalogen compound concentrations in humans from Guinea-Bissau from the early 1990's and onwards, similarly to the development of these compounds in humans from industrial countries. In contrast, PBDEs follow a trend of increasing concentrations even though at low levels
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| 29. |
- Lindman, Jacob, et al.
(författare)
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Performance of Bio-Rad HIV-1/2 Confirmatory Assay in HIV-1, HIV-2 and HIV-1/2 dually reactive patients - comparison with INNO-LIA and immunocomb discriminatory assays
- 2019
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Ingår i: Journal of Virological Methods. - : Elsevier BV. - 0166-0934. ; 268, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- Background: Being able to discriminate between HIV-1, HIV-2 and HIV-1/2 dual infection is imperative for the appropriate selection of antiretroviral therapy (ART) in regions with high HIV-2 endemicity. Objectives: To evaluate Bio-Rad Geenius HIV-1/2 Confirmatory Assay against INNO-LIA HIV 1/2 Score and ImmunoComb HIV 1/2 BiSpot with an emphasis towards ability to discriminate between HIV-1, HIV-2 and HIV-1/2 dual infection. Material and Methods: 131 samples from ART naïve HIV infected patients in Guinea-Bissau were selected retrospectively and tested with Geenius, INNO-LIA and Immunocomb. HIV-1/2 RNA were measured in all samples and HIV-1/2 DNA in 59 samples. Results: The Geenius reader typed 62 samples as HIV-1 reactive, 37 samples as HIV-2 reactive and 32 samples as HIV-1/2 dually reactive. Geenius manual reading classified 10% more samples as HIV-1/2 dually reactive (n = 35). INNO-LIA typed 63 samples as HIV-1 reactive, 36 samples as HIV-2 reactive and 32 samples as HIV-1/2 dually reactive while Immunocomb classified a large proportion of samples as HIV-1/2 dually reactive (n = 45). The measurement of agreement of the Geenius reader compared with INNO-LIA and Immunocomb was 92.4% and 84.0% respectively while the measurement of agreement of Geenius manual reading compared with INNO-LIA and Immuncomb was 93.1% and 89.3% respectively. Conclusions: Geenius has similar performance characteristics as INNO-LIA, and performs considerably better than Immunocomb, for differentiating between HIV types. This is especially true when using the Geenius reader while manual reading of the Geenius assay seemed to overestimate the numbers of HIV-1/2 dually reactive samples.
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| 30. |
- Lopatko Lindman, Jacob, et al.
(författare)
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Declining prevalence rates of syphilis among police officers in Guinea-bissau, west Africa, 1990-2010.
- 2013
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Ingår i: Sexually Transmitted Diseases. - 1537-4521. ; 40:10, s. 794-796
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed prevalence rates of syphilis (positive Treponema pallidum hemagglutinin antigen/T. pallidum particle antigen and venereal disease research laboratory test) among police officers in Guinea-Bissau from 1990 to 2010 and found a significant decline from 4.5% to 0.4% (P = 0.0065). Our results are in line with other recent reports from West Africa. More research is needed to identify the reasons for this decline.
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| 31. |
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| 32. |
- Månsson, Fredrik, et al.
(författare)
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High prevalence of HIV-1, HIV-2 and other sexually transmitted infections among women attending two sexual health clinics in Bissau, Guinea-Bissau, West Africa.
- 2010
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Ingår i: International journal of STD & AIDS. - : SAGE Publications. - 1758-1052 .- 0956-4624. ; 21:9, s. 631-635
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to examine the prevalence of HIV-1, HIV-2 and 10 other sexually transmitted infections (STIs), and to explore the relationship between HIV and those STIs in women attending two sexual health clinics in Bissau, Guinea-Bissau. In all, 711 women with urogenital problems were included. Clinical examination was performed and HIV-1, HIV-2, human T-cell lymphotropic virus (HTLV)-1, HTLV-2 and syphilis were diagnosed by serology. Trichomonas vaginalis was examined using wet mount microscopy. Cervical samples (and swabs from visible ulcers, if present) were used for polymerase chain reaction (PCR) diagnosis of Chlamydia trachomatis, Mycoplasma genitalium, Haemophilus ducreyi, herpes simplex virus (HSV)-1 and HSV-2, and culture diagnosis of Neisseria gonorrhoeae. The prevalence of HIV-1, HIV-2, and HIV-1 and HIV-2 (dual infection) was 9.5%, 1.8% and 1.1%, respectively. The prevalence of HTLV-1 was 2.8%, HTLV-2 0%, HSV-1 1.4%, HSV-2 7.7%, T. vaginalis 20.4%, syphilis 1.0%, N. gonorrhoeae 1.3%, H. ducreyi 2.7%, M. genitalium 7.7% and C. trachomatis 12.6%. HIV-1 and/or HIV-2 infection was significantly associated with active HSV-2 and HIV-1 was significantly associated with M. genitalium infection. In conclusion, HIV-1 and HIV-2 prevalence was higher compared with previous studies of pregnant women in Guinea-Bissau. The prevalence of co-infection of HIV and other STIs is high. National evidence-based guidelines for the management of STIs in Guinea-Bissau are essential.
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| 33. |
- Nilsson, Kajsa, et al.
(författare)
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Characterisation of non-coagulating milk and effects of milk composition and physical properties on rennet-induced coagulation in Swedish Red Dairy Cattle
- 2019
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Ingår i: International Dairy Journal. - : Elsevier BV. - 0958-6946 .- 1879-0143. ; 95, s. 50-57
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Tidskriftsartikel (refereegranskat)abstract
- Non-coagulating milk is a serious problem in the cheese industry, since it decreases cheese yield, resulting in decreased economic output. This study evaluated rennet-induced coagulation properties and composition of milk from individual Swedish Red Dairy Cattle. Milk samples from 679 individual cows were rheologically evaluated, of which 18.1% of the cows produced non-coagulating milk and 18.9% produced poor-coagulating milk. This resulted in 37% of the milk samples being non-optimal in cheese production, which is an alarmingly high figure. A comparison between non-coagulating and coagulating milk showed a significantly lower calcium content and less free Ca 2+ in non-coagulating milk. The results provide more information about non- and poor-coagulating milk and will be further used to understand the genetic background of non-coagulating milk and breed against this undesired milk property.
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| 34. |
- Nowroozalizadeh, Salma, et al.
(författare)
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Microbial Translocation Correlates with the Severity of Both HIV-1 and HIV-2 Infections
- 2010
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 201:8, s. 1150-1154
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Tidskriftsartikel (refereegranskat)abstract
- Microbial translocation has been linked to systemic immune activation during human immunodeficiency virus (HIV) type 1 infection. Here, we show that an elevated level of microbial translocation, measured as plasma lipopolysaccharide (LPS) concentration, correlates with AIDS in both individuals infected with HIV type 1 and individuals infected with HIV type 2. LPS concentration also correlates with CD4(+) T cell count and viral load independently of HIV type. Furthermore, elevated plasma LPS concentration was found to be concomitant with defective innate and mitogen responsiveness. We suggest that microbial translocation may contribute to loss of CD4(+) T cells, increase in viral load, and defective immune stimuli responsiveness during both HIV type 1 and HIV type 2 infections.
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| 35. |
- Nowroozalizadeh, Salma, et al.
(författare)
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Reply to Redd et al
- 2011
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 203:5, s. 746-746
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 36. |
- Olsen, Birgitta, 1952-, et al.
(författare)
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Phenotypic and genetic characterisation of bacterial sexually transmitted infections in Bissau, Guinea-Bissau, West Africa : a prospective cohort study
- 2012
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Ingår i: BMJ Open. - London, United Kingdom : BMJ Publishing Group Ltd. - 2044-6055. ; 20:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowledge regarding characteristics and transmission of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium and antibiotic resistance in N gonorrhoeae in Guinea-Bissau, West Africa, is entirely lacking.Objectives: To characterise N gonorrhoeae, C trachomatis and M genitalium samples from Guinea-Bissau and to define bacterial populations, possible transmission chains and for N gonorrhoeae spread of antibiotic-resistant isolates.Design: Prospective cohort study.Setting: Two sexual health and family planning clinics, Bissau, Guinea-Bissau.Participants: Positive samples from 711 women and 27 men.Material and methods: Positive samples for N gonorrhoeae (n=31), C trachomatis (n=60) and M genitalium (n=30) were examined. The gonococcal isolates were characterised with antibiograms, serovar determination and N gonorrhoeae multiantigen sequence typing (NG-MAST). The C trachomatis ompA gene and the M genitalium mgpB gene were sequenced, and phylogenetic analyses were performed.Results: For N gonorrhoeae, the levels of resistance (intermediate susceptibility) to ciprofloxacin, erythromycin, rifampicin, ampicillin, tetracycline, penicillin G and cefuroxime were 10% (0%), 6% (10%), 13% (10%), 68% (0%), 74% (0%), 68% (16%) and 0% (84%), respectively. All isolates were susceptible to cefixime, ceftriaxone, spectinomycin and azithromycin, and the minimum inhibitory concentrations of kanamycin (range: 8-32 mg/l) and gentamicin (range: 0.75-6 mg/l) were low (no resistance breakpoints exist for these antimicrobials). 19 NG-MAST sequence types (STs) (84% novel STs) were identified. Phylogenetic analysis of the C trachomatis ompA gene revealed genovar G as most prevalent (37%), followed by genovar D (19%). 23 mgpB STs were found among the M genitalium isolates, and 67% of isolates had unique STs.Conclusions: The diversity among the sexually transmitted infection (STI) pathogens may be associated with suboptimal diagnostics, contact tracing, case reporting and epidemiological surveillance. In Guinea-Bissau, additional STI studies are vital to estimate the STI burden and form the basis for a national sexual health strategy for prevention, diagnosis and surveillance of STIs.
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| 37. |
- Palm, Angelica A., et al.
(författare)
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Low Postseroconversion CD4+ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection
- 2019
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Ingår i: mBio. - 2161-2129. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- A positive correlation between virus evolutionary rate and disease progression has been shown for human immunodeficiency virus type 1 (HIV-1) infection. Much less is known about HIV-2, the second causative agent of AIDS. We analyzed 528 HIV-2 env V1-C3 sequences generated from longitudinal plasma samples that were collected from 16 study participants during a median observation time of 7.9 years (interquartile range [IQR], 5.2 to 14.0 years). Study participants were classified as faster or slower disease progressors based on longitudinal CD4+ T-cell data. The HIV-2 evolutionary rate was significantly associated with CD4+ T-cell levels and was almost twice as high among the faster progressors as among the slower progressors. Higher evolutionary rates were accounted for by both synonymous and nonsynonymous nucleotide substitutions. Moreover, slow disease progression was associated with stronger positive selection on HIV-2/SIVsm (simian immunodeficiency virus infecting sooty mangabey) surface-exposed conserved residues. This study demonstrated a number of previously unknown characteristics linking HIV-2 disease progression with virus evolution. Some of these findings distinguish HIV-2 from HIV-1 and may contribute to the understanding of differences in pathogenesis.IMPORTANCE The relationship between HIV evolution and disease progression is fundamental to our understanding of HIV immune control and vaccine design. There are no clear definitions for faster and slower HIV-2 disease progression and for the relationship of the rate of progression with HIV-2 evolution. To address the hypothesis that viral evolution is correlated with disease progression in HIV-2 infection, we determined faster and slower disease progression based on follow-up data from a prospective cohort of police officers in Guinea-Bissau. The analysis showed that although the CD4+ T-cell level and the decline in the level were independently associated with progression to AIDS, only the CD4+ T-cell level or a combined CD4+ T-cell level/decline stratification was associated with the rate of HIV-2 evolution. The HIV-2 evolutionary rate was almost twice as high among the faster progressors as among the slower progressors. Importantly, this report defines previously unknown characteristics linking HIV-2 disease progression with virus evolution.
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| 38. |
- Palm, Angelica, et al.
(författare)
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Co-circulation of several similar but unique HIV-1 recombinant forms in Guinea-Bissau revealed by near full-length genomic sequencing.
- 2015
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Ingår i: AIDS Research and Human Retroviruses. - 1931-8405. ; 31:9, s. 938-945
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Tidskriftsartikel (refereegranskat)abstract
- The dynamic HIV-1 epidemic has resulted in the emergence of several different subtypes and recombinant forms that may differ in biological properties. A recombinant form of CRF02_AG and sub-subtype A3 (A3/02) was recently described based on env sequencing and associated with faster disease progression rates compared with its parental strains. Here, we performed near full-length sequencing of the A3/02 variant to characterize the recombination patterns of a potential novel and more pathogenic circulating recombinant form of HIV-1 in Guinea-Bissau.
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| 39. |
- Palm, Angelica, et al.
(författare)
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Faster progression to AIDS and AIDS-related death among seroincident individuals infected with recombinant HIV-1 A3/CRF02_AG compared to sub subtype A3.
- 2014
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 209:5, s. 721-728
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 is divided into different subtypes and circulating recombinant forms (CRFs) but the impact of HIV-1 subtype/CRF on disease progression is not fully understood. We determined the HIV-1 subtype/CRF of 152 seroincident individuals from Guinea-Bissau, based on the C2-V3 region of env. Rate of disease progression was measured as time from estimated seroconversion to AIDS and AIDS-related death. Hazard ratios (HRs) were calculated using a Cox proportional hazard model, adjusting for gender and age at seroconversion. The major subtypes/CRFs identified were CRF02_AG (53%), A3 (29%) and A3/02 (a recombinant of A3 and CRF02_AG) (13%). Infection with A3/02 was associated with a close to 3-fold increased risk of AIDS and AIDS-related death compared to A3 (HR=2.6 [P=0.011] and 2.9 [P=0.032], respectively). The median estimated time from seroconversion to AIDS and AIDS-related death was 5.0 and 8.0 years for A3/02, 6.2 and 9.0 years for CRF02_AG and 7.2 and 11.3 years for A3. Our results show that there are significant differences in disease progression between HIV-1 A-like subtypes/CRFs. Individuals infected with the A3/02 recombinant have among the fastest progression rates to AIDS reported to date. Determining the HIV-1 subtype of infected individuals could be of importance in the management of HIV-1 infections.
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| 40. |
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| 41. |
- Sabir, Emad F., et al.
(författare)
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Impact of hospital volume on local recurrence and distant metastasis in bladder cancer patients treated with radical cystectomy in Sweden
- 2013
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1813 .- 2168-1805. ; 47:6, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- Objective. This study evaluated the impact of hospital volume on local recurrence and distant metastasis in a population-based series of radical cystectomy patients in Sweden. Material and methods. All patients who underwent cystectomy for bladder cancer in 1997-2002 in Sweden and were reported to the National Bladder Cancer Registry were included. A high-volume hospital (HVH) was defined as one with >= 10 cystectomies/year and a low-volume hospital (LVH) as one with <10 cystectomies/year. Information on preoperative tumour, node, metastasis (TNM) classification, operative procedure, postoperative course and follow-up was obtained from medical records. Results. Of the 1126 patients, 827 (74%) were males. The mean age was 66 years and median follow-up 47 months. Of the 610 (54%) HVH patients, 68 (11%) were pT0, 123 (20%) pT2 and 69 (11%) were microscopic non-radical. Corresponding figures for the 516 (46%) LVH patients were 35 (7%), 68 (13%), 191 (37%), 222 (43%) and 96 (19%). Local recurrence was observed in 245 patients (22%): 113 (19%) at HVHs and 132 (26%) at LVHs. Distant metastasis was found in 363 (32%): 203 (33%) at HVHs and 160 (31%) at LVHs. Perioperative chemotherapy was given to 193 (17%). Multivariate Cox proportional hazards analysis showed that local recurrence was associated with LVHs and non-organ-confined disease, whereas distant metastasis was correlated with non-organ-confined disease and lymph-node metastases. Conclusions. In this retrospective analysis, local tumour recurrence after cystectomy was common, particularly in patients with non-organ-confined disease. Furthermore, local recurrence was more frequent at LVHs than HVHs, and overall survival was better at HVHs. These findings suggest that concentrating cystectomies in HVHs may improve outcomes such as local recurrence and overall survival.
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| 42. |
- Söderberg, Christopher A.G., et al.
(författare)
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Structural modelling of the DNAJB6 oligomeric chaperone shows a peptide-binding cleft lined with conserved S/T-residues at the dimer interface
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- = The remarkably efficient suppression of amyloid fibril formation by the DNAJB6 chaperone is dependent on a set of conserved S/T-residues and an oligomeric structure, features unusual among DNAJ chaperones. We explored the structure of DNAJB6 using a combination of structural methods. Lysine-specific crosslinking mass spectrometry provided distance constraints to select a homology model of the DNAJB6 monomer, which was subsequently used in crosslink-assisted docking to generate a dimer model. A peptide-binding cleft lined with S/T-residues is formed at the monomer-monomer interface. Mixed isotope crosslinking showed that the oligomers are dynamic entities that exchange subunits. The purified protein is well folded, soluble and composed of oligomers with a varying number of subunits according to small-angle X-ray scattering (SAXS). Elongated particles (160 x 120 angstrom) were detected by electron microscopy and single particle reconstruction resulted in a density map of 20 angstrom resolution into which the DNAJB6 dimers fit. The structure of the oligomer and the S/T-rich region is of great importance for the understanding of the function of DNAJB6 and how it can bind aggregation-prone peptides and prevent amyloid diseases.
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| 43. |
- Wilhelmson, Sten, et al.
(författare)
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Prevalence of HIV-1 pretreatment drug resistance among treatment naïve pregnant women in Bissau, Guinea Bissau
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:10, s. 0206406-0206406
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: With increased access to antiretroviral treatment (ART) in sub-Saharan Africa emergence of HIV-1 pretreatment drug resistance constitutes a serious risk. This may lead to rapid virological failure in subjects initiating ART, and mother-to-child transmission despite prophylaxis.METHODS: Treatment-naïve pregnant women from four antenatal care clinics in Bissau, Guinea-Bissau, were enrolled from October 2016 to November 2017. Genotypic resistance testing and phylogenetic subtype analysis was performed on 48 specimens.RESULTS: Forty eight women met the survey inclusion criteria. All specimens were successfully amplified and genotyped. Specimens from five women were associated with HIV-1 drug resistance mutations. Four carried mutations exclusively linked to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (K103N, K103N/S) and one carried mutations to both NNRTIs (G190S, K101E) and nucleoside reverse transcriptase inhibitors (NRTIs) (M184V). These results corresponded to 10.4% (95% CI: 4.5-22.2%), 2.1% (95% CI: 0.4-10.9%) and 0% (95% CI: 0.0-7.4%) drug resistance mutations to NNRTIs, NRTIs and protease inhibitors, respectively. HIV-1 circulating recombinant form 02AG was most commonly found, followed by HIV-1 sub-subtype A3. Subtype/CRF was not associated with drug resistance mutations.CONCLUSION: Our study reports a 10.4% prevalence of pretreatment drug resistance to NNRTIs in HIV-1-infected pregnant women in the capital Bissau, Guinea Bissau. Since NNRTIs are part of first-line ART in the country, baseline resistance screenings or adjustment of national treatment guidelines should be considered as antiretroviral treatment programs are scaled up.
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| 44. |
- Özkaya Sahin, Gülsen, et al.
(författare)
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Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent
- 2013
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Ingår i: Journal of Virology. - 1098-5514. ; 87:1, s. 273-281
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus type-2 (HIV-2) infected individuals develop immunodeficiency with a considerable delay and transmit the virus at a lower rate as compared to HIV-1 infected. Conceivably, comparative studies on immune responsiveness of the HIV-1 and HIV-2 infected hosts may help to explain differences in pathogenesis and transmission between the two types of infection. Previous studies have shown that the neutralizing antibody response is more potent and broader in HIV-2 than HIV-1 infection. In the present study we have further examined the function of the humoral immune response and studied the potentiating effect of complement (C') on antiviral activity of plasma from singly HIV-1 or HIV-2 infected, as well as HIV-1/HIV-2 dually infected individuals. Neutralization and antibody-dependent complement-mediated inactivation of HIV-1 and HIV-2 isolates were tested in a plaque reduction assay using U87.CD4-CCR5 cells. Results showed that addition of C' increased intra-type antiviral activity of both HIV-1 and HIV-2 plasma, although the C' effect was more pronounced with HIV-2 than HIV-1 plasma. Using the area-under-curve (AUC)-based readout, multivariate statistical analysis confirmed that type of HIV infection was independently associated with the magnitude of the C' effect. Analysis carried out with purified IgG indicated that the C' effect was largely exerted through the classical C' pathway involving IgG in both HIV-1 and HIV-2 infections. In summary, these findings suggest that antibody binding to HIV-2 structures facilitates efficient use of C', and may thereby be one factor contributing to a strong antiviral activity present in HIV-2 infection.
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| 45. |
- Özkaya Sahin, Gülsen, et al.
(författare)
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Frequent intratype neutralization by plasma immunoglobulin A identified in HIV-2 infection.
- 2013
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Ingår i: AIDS Research and Human Retroviruses. - 1931-8405. ; 29:3, s. 470-478
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus type 2 (HIV-2) is less transmissible and less pathogenic compared to HIV-1 and, when matched for CD4+ T cell count, the plasma viral load in HIV-2 infected individuals is approximately one log lower than in HIV-1 infected individuals. The explanation for these observations is elusive, but differences in virus controlling immunity generated in the two infections may be contributing factors. In the present study, we investigated neutralization by immunoglobulin A (IgA), in parallel with IgG, purified from plasma of HIV-1, HIV-2 and HIV-1/HIV-2 dually (HIV-D)-infected individuals. Neutralization was analyzed against HIV-1 and HIV-2 isolates using a plaque reduction assay. In HIV-2 infection, intratype-specific neutralization by IgA was frequently detected, although at a lesser magnitude then the corresponding IgG neutralizing titers. In contrast, neutralization by IgA could rarely be demonstrated in HIV-1 infection despite similar plasma IgA levels in both infections. In addition, IgA and IgG of HIV-D plasma neutralized the HIV-2 isolate more potently than the HIV-1 isolate, suggesting that the difference between neutralizing activity of plasma IgA and IgG depends on the virus itself. Taken together, these findings suggest that both IgA and IgG adds to the potent intratype neutralizing activity detected in HIV-2 plasma, which may contribute to virus control in HIV-2 infection.
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- Özkaya Sahin, Gülsen, et al.
(författare)
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Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1
- 2012
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Ingår i: Journal of Virology. - 1098-5514. ; 86:2, s. 961-971
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1, 20 HIV-2 and 11 dually HIV-1/2 (HIV-D) seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2, were tested in a plaque reduction assay using U87.CD4-CCR5 cells as targets. Intratype NAc in HIV-2 plasma was found to be considerably more potent, and also broader, than intratype NAc in HIV-1 plasma. This indicates that HIV-2 infected individuals display potent type-specific neutralizing antibodies, whereas such a strong type-specific antibodies are absent in HIV-1 infection. Furthermore, potency of intratype NAc was positively associated with viral load of HIV-1, but not HIV-2, suggesting that NAc in HIV-1 infection is more antigen stimulation-dependent than in HIV-2 infection where plasma viral loads typically are at least tenfold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infected was instead of low potency. HIV-D subjects had NAc to HIV-2 with similar high potency as singly HIV-2 infected individuals, whereas neutralization of HIV-1 remained poor, indicating that the difference in NAc between HIV-1 and HIV-2 infections depends on the virus itself. We suggest that immunogenicity and/or antigenicity, meaning the neutralization phenotype, of HIV-2 is distinct from HIV-1, and that HIV-2 may display structures that favour triggering of potent neutralizing antibody responses.
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