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- Alitalo, Antti, et al.
(author)
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Expression of complement factor H binding immunoevasion proteins in Borrelia garinii isolated from patients with neuroborreliosis.
- 2005
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In: Eur J Immunol. - 0014-2980. ; 35:10, s. 3043-3053
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Journal article (peer-reviewed)abstract
- The Lyme disease-pathogen Borrelia burgdorferi binds the complement inhibitor factor H (FH) to its outer surface protein E- (OspE) and BbA68-families of lipoproteins. In earlier studies, only serum-resistant strains of the genospecies B. burgdorferi sensu stricto or B. afzelii, but not serum-sensitive B. garinii strains, have been shown to bind FH. Since B. garinii often causes neuroborreliosis in man, we have readdressed the interactions of B. garinii with FH. B. garinii 50/97 strain did not express FH-binding proteins. By transforming the B. garinii 50/97 strain with an OspE-encoding gene from complement-resistant B. burgdorferi (ospE-297), its resistance to serum killing could be increased. OspE genes were detected and cloned from the B. garinii BITS, Pistoia and 40/97 strains by PCR and sequencing. The deduced amino acid sequences differed in an N-terminal lysine-rich FH-binding region from OspE sequences of resistant strains. Recombinant B. garinii BITS OspE protein was found to have a considerably lower FH-binding activity than the B. burgdorferi sensu stricto 297 OspE protein P21 (P21-297). Unlike bacteria that had been kept in culture for a long time, neurovirulent B. garinii strains from neuroborreliosis patients were found to express approximately 27-kDa FH-binding proteins. These were not recognized by polyclonal anti-OspE or anti-BbA68 antibodies. We conclude that B. garinii strains carry ospE genes but have a decreased expression of OspE proteins and a reduced ability to bind FH, especially when grown for prolonged periods in vitro. Recently isolated neuroinvasive B. garinii strains, however, can express FH-binding proteins, which may contribute to the virulence of neuroborreliosis-causing B. garinii strains.
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- Duffy, Stephen W., et al.
(author)
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Mammography screening reduces rates of advanced and fatal breast cancers : Results in 549,091 women
- 2020
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In: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 126:13, s. 2971-2979
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Journal article (peer-reviewed)abstract
- Background: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.Methods: Among 549,091 women, covering approximately 30% of the Swedish screening‐eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.Results: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51‐0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66‐0.84 [P < .001]).Conclusions: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.
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- Forsberg, Anna, et al.
(author)
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Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial
- 2022
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In: The Lancet Gastroenterology & Hepatology. - : ELSEVIER INC. - 2468-1253. ; 7:6, s. 513-521
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Journal article (peer-reviewed)abstract
- Background Screening for colorectal cancer is done with lower gastrointestinal endoscopy or stool-based tests. There is little evidence from randomised trials to show primary colonoscopy reduces mortality in colorectal cancer We aimed to investigate the effect of screening with once-only colonoscopy or two rounds of faecal immunochemical test screening on colorectal cancer mortality and incidence. Methods We did a randomised controlled trial in Sweden (SCREESCO). Residents in 18 of 21 regions who were age 60 years in the year of randomisation were identified from a population register maintained by the Swedish Tax Agency. A statistician with no further involvement in the trial used a randomised block method to assign individuals to once-only colonoscopy, two rounds of faecal immunochemical testing (OC-Sensor; 2 years apart), or a control group (no intervention; standard diagnostic pathways), in a ratio of 1:6 for colonoscopy versus control and 1:2 for faecal immunochemical testing versus control. Masking was not possible due to the nature of the trial. The primary endpoints of the trial are colorectal cancer mortality and colorectal cancer incidence. Here, we report preliminary participation rates, baseline findings, and adverse events from March, 2014, to December, 2020, in the two intervention groups after completion of recruitment and screening, up to the completion of the second faecal immunochemical testing round. Analyses were done in the intention-to-screen population, defined as all individuals who were randomly assigned to the respective study group. This study is registered with Clinical Trials.gov, NCT02078804. Findings Between March 1, 2014, and Dec 31, 2020, 278 280 people were induded in the study; 31 140 were assigned to the colonoscopy group, 60 300 to the faecal immunochemical test group, and 186 840 to the control group. 10 679 (35.1%) of 30 400 people who received an invitation for colonoscopy participated. 33 383 (55.5%) of 60 137 people who received a postal faecal immunochemical test participated. In the intention-to-screen analysis, colorectal cancer was detected in 49 (0.16%) of 31140 people in the colonoscopy group versus 121 (0. 20%) of 60 300 in the faecal immunochemical test group (relative risk [RR] 0.78, 95% CI 0.56-1.09). Advanced adenomas were detected in 637 (2.05%) people in the colonoscopy group and 968 (1.61%) in the faecal immunochemical test group (RR 1.27, 95% CI 1.15-1.41). Colonoscopy detected more right-sided advanced adenomas than faecal immunochemical testing. There were two perforations and 15 major bleeds in 16 555 colonoscopies. No intervention-related deaths occurred. Interpretation The diagnostic yield and the low number of adverse events indicate that the design from this trial, both for once-only colonoscopy and faecal immunochemical test screening, could be transferred to a population-based screening service if a benefit in disease-specific mortality is subsequently shown. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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- Melin, Anna K., Assistant Professor, 1965-, et al.
(author)
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Impact of Menstrual Function on Hormonal Response to Repeated Bouts of Intense Exercise
- 2019
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In: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 10, s. 1-8
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Journal article (peer-reviewed)abstract
- Background: Strenous exercise stimulates the hypothalamic-pituitary (HP) axis in order to ensure homeostasis and promote anabolism. Furthermore, exercise stimulates a transient increase in the neurotrophin brain-derived neurotrophic factor (BDNF) suggested to mediate the anxiolytic effects of exercise. Athletes with secondary functional hypothalamic amenorrhea (FHA) have been reported to have lower BDNF, and a blunted HP axis response to exercise as athletes with overtraining syndrome. Aim: The aim of the study was to investigate the hormonal and BDNF responses to a two-bout maximal exercise protocol with four hours of recovery in between in FHA and eumenorrheic (EUM) athletes. Methods: Eumenorrheic (n = 16) and FHA (n = 14) endurance athletes were recruited from national teams and competitive clubs. Protocols included gynecological examination; body composition (DXA); 7-day assessment of energy availability; blood sampling pre and post the two exercises tests. Results: There were no differences between groups in hormonal responses to the first exercise bout. After the second exercise bout IGFBP-3 increased more in FHA compared with EUM athletes (2.1 +/- 0.5 vs. 0.6 +/- 0.6 mu g/L, p = 0.048). There were non-significant trends toward higher increase in IGF-1 (39.3 +/- 4.3 vs. 28.0 +/- 4.6 mu g/L, p = 0.074), BDNF (96.5 +/- 22.9 vs. 34.4 +/- 23.5 mu g/L, p = 0.058), GH to cortisol ratio (0.329 +/- 0.010 vs. 0.058 +/- 0.010, p = 0.082), and decrease in IGF-1 to IGFBP-3 ratio (-2.04 +/- 1.2 vs. 0.92 +/- 1.22, p = 0.081) in athletes with FHA compared with EUM athletes. Furthermore, there was a non-significant trend toward a higher increase in prolactin to cortisol ratio in EUM athletes compared with athletes with FHA (0.60 +/- 0.15 vs. 0.23 +/- 0.15, p = 0.071). No differences in the hormonal or BDNF responses between the two exercise bouts as a result of menstrual function were found. Conclusion: No major differences in the hormonal or BDNF responses between the two exercise bouts as a result of menstrual function could be detected.
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- Melin, Anna K., 1965-, et al.
(author)
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The LEAF questionnaire : a screening tool for the identification of female athletes at risk for the female athlete triad
- 2014
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In: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 48, s. 540-545
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Journal article (peer-reviewed)abstract
- Background Low energy availability (EA) in female athletes with or without an eating disorder (ED) increases the risk of oligomenorrhoea/functional hypothalamic amenorrhoea and impaired bone health, a syndrome called the female athlete triad (Triad). There are validated psychometric instruments developed to detect disordered eating behaviour (DE), but no validated screening tool to detect persistent low EA and Triad conditions, with or without DE/ED, is available.Aim The aim of this observational study was to develop and test a screening tool designed to identify female athletes at risk for the Triad.Methods Female athletes (n=84) with 18–39 years of age and training≥5 times/week filled out the Low Energy Availability in Females Questionnaire (LEAF-Q), which comprised questions regarding injuries and gastrointestinal and reproductive function. Reliability and internal consistency were evaluated in a subsample of female dancers and endurance athletes (n=37). Discriminant as well as concurrent validity was evaluated by testing self-reported data against measured current EA, menstrual function and bone health in endurance athletes from sports such as long distance running and triathlon (n=45).Results The 25-item LEAF-Q produced an acceptable sensitivity (78%) and specificity (90%) in order to correctly classify current EA and/or reproductive function and/or bone health.Conclusions The LEAF-Q is brief and easy to administer, and relevant as a complement to existing validated DE screening instruments, when screening female athletes at risk for the Triad, in order to enable early detection and intervention.
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- Naucler, Pontus, et al.
(author)
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Human papillomavirus and Papanicolaou tests to screen for cervical cancer.
- 2007
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In: New England Journal of Medicine. - Boston, Massachusetts : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 357:16, s. 1589-97
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Journal article (peer-reviewed)abstract
- Background Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown. Methods In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated. Results At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy. Conclusions The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.
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- Silfverdal, Lena, 1955-, et al.
(author)
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Risk of invasive cervical cancer in relation to management of abnormal Pap smear results
- 2009
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In: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 201:2
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Journal article (peer-reviewed)abstract
- OBJECTIVE: We sought to evaluate the management of women with abnormal cytology in terms of subsequent risk of invasive cervical cancer. STUDY DESIGN: The screening histories of all invasive cervical cancer cases diagnosed in Sweden 1999-2001 and of 5 population-based controls per case were reviewed. In all, 159 patients and 258 control subjects aged < 67 years had an abnormal smear result 0.5-6.5 years prior to cancer diagnosis. The cervical cancer risk was estimated in relation to management by calculating odds ratios. RESULTS: Histologic assessment of low-grade squamous abnormalities strongly reduced the risk compared to repeated cytology (odds ratio, 0.46; 95% confidence interval, 0.24-0.89). Delaying histologic assessment was also associated with a higher risk ( odds ratio, 5.65; 95% confidence interval, 1.39-23.05). After high-grade squamous atypia, absence of any cytologic or histologic specimen was a major determinant of cancer risk (odds ratio, 12.52; 95% confidence interval, 1.42-infinitive). CONCLUSION: For adequate protection against invasive cervical cancer, further assessment with histology must be recommended also for women with low-grade squamous abnormalities.
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- Tishelman, Carol, et al.
(author)
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Research on Risk and Risk in Research : Theoretical and Practical Experiences From a Multidisciplinary Study on Cervix Cancer Screening in Urban Sweden
- 1999
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In: Qualitative Health Research. - : SAGE Publications. - 1049-7323 .- 1552-7557. ; 9:1, s. 45-60
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Journal article (peer-reviewed)abstract
- This article describes a qualitative research project on secondary cancer prevention that was conducted using a multidisciplinary team and that was inspired by perspectives from feminist research and fourth-generation evaluation. A screening program for cervical cancer was investigated from the perspective of different stakeholders through a series of substudies using a variety of qualitative approaches, in order to have a broad basis for consideration and negotiation of improvements. The first sections of this article describe the theoretical and methodological basis for the project, which triangulates a variety of qualitative and quantitative research strategies, whereas the latter sections describe some of our experiences, positive and negative, as a research team (and thus also as stakeholders) in actually conducting the studies.
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- Tornberg, Åsa B.B., et al.
(author)
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Reduced Neuromuscular Performance in Amenorrheic Elite Endurance Athletes
- 2017
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In: Medicine & Science in Sports & Exercise. - : Lippincott Williams & Wilkins. - 0195-9131 .- 1530-0315. ; 49:12, s. 2478-2485
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Journal article (peer-reviewed)abstract
- Introduction Secondary functional hypothalamic amenorrhea (SFHA) is common among female athletes, especially in weight-sensitive sports. The aim of this study was to investigate the link between SFHA and neuromuscular performance in elite endurance athletes. Methods Sixteen eumenorrheic (EUM) and 14 SFHA athletes from national teams and competitive clubs participated. Methods included gynecological examination, body composition (dual-energy x-ray absorptiometry), resting metabolic rate and work efficiency, exercise capacity, knee muscular strength (KMS) and knee muscular endurance (KME), reaction time (RT), blood sampling performed on the third to fifth days of the menstrual cycle, and 7-d assessment of energy availability. Results SFHA athletes had lower estrogen (0.12 0.03 vs 0.17 +/- 0.09 nmolL(-1), P < 0.05), triiodothyronine (T-3) (1.4 +/- 0.2 vs 1.7 +/- 0.3 nmolL(-1), P < 0.01), and blood glucose (3.8 +/- 0.3 vs 4.4 +/- 0.3 mmolL(-1), P < 0.001) but higher cortisol levels (564 +/- 111 vs 400 +/- 140 nmolL(-1), P < 0.05) compared with EUM athletes. SFHA had a lower body weight (55.0 +/- 5.8 vs 60.6 +/- 7.1 kg, P < 0.05), but no difference in exercise capacity between groups was found (56.4 +/- 5.8 vs 54.0 +/- 6.3 mL O(2)min(-1)kg(-1)). RT was 7% longer, and KMS and KME were 11% and 20% lower compared with EUM athletes. RT was negatively associated with glucose (r = -0.40, P < 0.05), T-3 (r = -0.37, P < 0.05), and estrogen (r = -0.43, P < 0.05), but positively associated with cortisol (r = 0.38, P < 0.05). KMS and KME correlated with fat-free mass in the tested leg (FFMleg; r = 0.52, P < 0.001; r = 0.58, P < 0.001) but were negatively associated with cortisol (r = -0.42, P < 0.05; r = -0.59, P < 0.001). FFMleg explained the differences in KMS, while reproductive function and FFMleg independently explained the variability in KME. Conclusions We found lower neuromuscular performance among SFHA compared with EUM athletes linked to a lower FFMleg, glucose, estrogen, T-3, and elevated cortisol levels.
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- Varga, Tibor V, et al.
(author)
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Lipidomic profiles, lipid trajectories and clinical biomarkers in female elite endurance athletes
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10, s. 1-9
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Journal article (peer-reviewed)abstract
- We assessed whether blood lipid metabolites and their changes associate with various cardiometabolic, endocrine, bone- and energy-related comorbidities of Relative Energy Deficiency in Sport (RED-S) in female elite endurance athletes. Thirty-eight Scandinavian female elite athletes underwent a day-long exercise test. Five blood samples were obtained during the day - at fasting state and before and after two standardized exercise tests. Clinical biomarkers were assessed at fasting state, while untargeted lipidomics was undertaken using all blood samples. Linear and logistic regression was used to assess associations between lipidomic features and clinical biomarkers. Overrepresentations of findings with P < 0.05 from these association tests were assessed using Fisher's exact tests. Self-organizing maps and a trajectory clustering algorithm were utilized to identify informative clusters in the population. Twenty associations PFDR < 0.05 were detected between lipidomic features and clinical biomarkers. Notably, cortisol demonstrated an overrepresentation of associations with P < 0.05 compared to other traits (PFisher = 1.9×10-14). Mean lipid trajectories were created for 201 named features for the cohort and subsequently by stratifying participants by their energy availability and menstrual dysfunction status. This exploratory analysis of lipid trajectories indicates that participants with menstrual dysfunction might have decreased adaptive response to exercise interventions.
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