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Title. Nurses' moral strength: a hermeneutic inquiry in nursing practice.Aim. This paper is a report of a study to interpret nurses' experiences of moral strength in practice.Background. Moral strength is said to be beneficial in providing nursing care for patients, thereby contributing to high qualitative care. However, few studies focus on the meaning of nurses' moral strength.Methods. This study included eight Registered Nurses working in different aspects of health care in southern Sweden. Individual interviews were conducted in 2006 and 2007. We recorded, transcribed verbatim, and interpreted the interviews by a method grounded in hermeneutics.Findings. Three themes were interpreted on three different levels: the action level as 'having courage to act on one's convictions', the relational level as 'being attentive and recognizing vulnerability', and the existential level as 'facing the unpredictable' . Overall, moral strength was understood as a driving force to be someone special in the care of patients, i.e. someone who makes a difference.Conclusion. The value of nurses' moral strength in patient care should be recognized. Attention must be given to aspects outside the individual, e.g. professional and institutional processes that influence the work environment. Clinical team supervision can help make such processes visible and supportive. [ABSTRACT FROM AUTHOR]

Background: In many countries, persons seeking medical abortion with mifepristone followed by misoprostol can self-administer the second drug, misoprostol, at home, but self-administration of the first drug, mifepristone, is not allowed to the same extent., Objectives: This systematic review aims to evaluate whether the efficacy, safety and women's satisfaction with abortion treatment are affected when mifepristone is self-administered at home instead of in a clinic., Search Strategy: A literature search covered CINAHL, Cochrane Library, Embase, Ovid MEDLINE and APA PsycInfo in October 2022., Selection Criteria: Eligible studies focused on persons undergoing medical abortion comparing home and in-clinic mifepristone intake. Outcomes included abortion effectiveness, compliance, acceptability, and practical consequences for women., Data Collection and Analysis: Two reviewers independently assessed eligibility and risk of bias. Meta-analysis included similar studies while those differing in design were synthesised without meta-analysis., Results: Six studies (54 233 women) of medical abortions up to 10 weeks were included. One randomised controlled trial and one retrospective register study had moderate risk of bias, and four non-randomised clinical trials where women could choose the place for intake of mifepristone had serious risk of bias. There was no difference in abortion effectiveness (high confidence) or compliance (moderate confidence) between mifepristone administered at home or in-clinic. No differences in complications were detected between groups and most women who chose home administration of mifepristone expressed a preference for this approach., Conclusions: Our systematic review demonstrates that the effectiveness of medical abortion is comparable regardless of mifepristone administration and intake, at home or in the clinic., Competing Interests: Competing interests: KGD has received honorarium for lectures or advice on abortion and contraception on ad hoc basis for Organon, Bayer, Gedeon Richter, Exelgyn, Mithra, Exeltis, Medincell, HRA Pharma, Cirqle, Natural cycles, Obseva, Norgene, and Ferring. IL has received compensation from Gedeon Richter and Exeltis for lectures in hormonal contraception and participation in an Advisory Board. JB has received honorariums for giving lectures in hormonal contraception for Organon, Campus Pharma, Exeltis and Gedeon Richter. SJ, AC, KM and EW have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Low birth weight is a known risk factor for adult coronary heart disease (CHD), but the additional effect of weight development during childhood and early adult life has not been studied., Methods: We included 35 659 men born 1945 to 1961 from the population-based BMI Epidemiology Study Gothenburg, with data available on birthweight, BMI in childhood (8 years), and BMI in young adulthood (20 years). Information on CHD diagnoses was retrieved from national registers. We used Cox proportional hazards regression to estimate hazard ratios and 95% CIs for the risk of early and late CHD (before and after 58.4 years of age, respectively)., Results: During follow-up, a total of 3380 cases of CHD (fatal and nonfatal) were registered. Birth weight was inversely associated with the risk of both early (hazard ratio, 0.88 per SD increase [95% CI, 0.84-0.92]) and late (hazard ratio, 0.94 per SD increase [95% CI, 0.90-0.98]) CHD, independently of BMI at 8 years and BMI change during puberty. In a model including birth weight (below or above the median) together with overweight at 8 and 20 years, only birth weight and young adult overweight, but not overweight in childhood, were significantly associated with the risk of CHD. A birth weight below the median, followed by overweight at 20 years of age was associated with a more than doubled risk of early CHD (hazard ratio, 2.29 [95% CI, 1.86-2.81]), compared with the reference (birth weight above the median and normal weight at 20 years of age). This excess risk was even more pronounced for a birthweight below 2.5 kg., Conclusions: We demonstrate that low birth weight and young adult overweight are important developmental markers of risk for adult CHD. These findings motivate a life course perspective for prevention and risk assessment of adult CHD., Competing Interests: Disclosures I. Lindh has received compensation from Gedeon Richter and Exeltis for lectures and participation in Advisory Board during the previous 3 years. The other authors report no conflicts.

Background: Birth weight is an indicator of intra-uterine conditions but also a determinant for future health. The importance of preconception health for a healthy birth weight has been emphasized, but evidence is lacking on how modifiable factors in adolescence, such as body mass index (BMI) and smoking, affect future pregnancy outcome. We evaluated associations between BMI and smoking in adolescence and at the start of pregnancy and birth weight of the first-born child., Methods: This longitudinal study included 1256 mothers, born 1962-1992, and their first-born children, born between 1982-2016. Self-reported questionnaire information on weight, height and smoking at age 19 was cross-linked with national register data obtained at the start of pregnancy and with the birth weights of the children. Univariable and multivariable linear regressions were performed to determine the impact of maternal factors at 19 years of age and at the start of the pregnancy respectively, and the importance of BMI status at these points of time for the birth weight of the first child., Results: BMI and smoking at the start of the pregnancy displayed strong associations with birth weight in a multivariable analysis, BMI with a positive association of 14.9 g per BMI unit (95% CI 6.0; 23.8 p = 0.001) and smoking with a negative association of 180.5 g (95% CI -275.7; -85.4) p = 0.0002). Smoking and BMI at 19 years of age did not show this association. Maternal birth weight showed significant associations in models at both time-points. Becoming overweight between age 19 and the start of the pregnancy was associated with a significantly higher birth weight (144.6 (95% CI 70.7;218.5) p = 0.0002) compared to mothers with normal weight at both time points., Conclusions: Our findings indicate that the time period between adolescence and first pregnancy could be a window of opportunity for targeted health promotion to prevent intergenerational transmission of obesity., (© 2023. The Author(s).)

Introduction: The aim was to describe and compare changes in the reproductive pattern of women in their 40s observed over a decade in Scandinavia., Material and Methods: Cross-sectional study using the total population of women aged 40-49 years between 2008-2018 in Denmark, Norway and Sweden (on average n = 1.5 million). Aggregated data concerning birth and induced abortion rate were collected and analyzed from national health registers. National data on redeemed prescriptions of hormonal contraceptives in the three countries were collected from prescription registers. Births after spontaneous and assisted conceptions were identified by using cross-linked data on deliveries from the Medical Birth Registers and National Registers of Assisted Reproduction in the three countries., Results: Use of hormonal contraception increased among women aged 40-44 years in Denmark from 24% to 31%, in Sweden from 27% to 30%, and in Norway from 22% to 24%. The levonorgestrel-releasing intrauterine device was the most frequently used method in all countries. Birth rates among women 40-44 years increased continuously from 9.5 to 12/1000 women in Denmark and from 11.7 to 14.3/1000 in Sweden, but remained stable in Norway at ~11/1000 women. There was a doubling of assisted conceptions in Denmark from 0.71 to 1.71/1000 women, Sweden from 0.43 to 0.81/1000 and Norway from 0.25 to 0.53/1000 women 40-49 years of age. Sweden had the highest induced abortion rate (7.7 to 8.1/1000 women) in women aged 40-49 years during the study period., Conclusions: From 2008 to 2018, birth rates continuously increased among women aged 40-49 years in Denmark and Sweden and births resulting from assisted reproductive technology doubled in all three countries., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: Our primary objective was to evaluate whether new types of single-size diaphragms or cervical caps differ in prevention of pregnancy compared with older types of diaphragms, and whether different types of gels differ in their ability to prevent pregnancy. A secondary aim was to evaluate method discontinuation and complications., Methods: A comprehensive search was conducted in PubMed, Embase and the Cochrane Library. The certainty of evidence was assessed according to the GRADE system., Results: Four randomised controlled studies were included in the assessment. When comparing the new and old types of female barrier contraceptives the 6-month pregnancy rate varied between 11%-15% and 8%-12%, respectively. More women reported inability to insert or remove the FemCap device (1.1%) compared with the Ortho All-Flex diaphragm (0%) (p<0.0306). Urinary tract infections were lower when using the single-size Caya, a difference of -6.4% (95% CI -8.9 to -4.09) compared with the Ortho All-Flex diaphragm. The 6-month pregnancy rate for acid-buffering gel and spermicidal nonoxynol-9 gel varied between 10% and 12%. The discontinuation rate was lower in women who used acid-buffering gel compared with nonoxynol-9 gel (risk ratio (RR) 0.77, 95% CI 0.68 to 0.97)., Conclusions: Pregnancy rates were generally high in women using female barrier contraceptives. There was no difference in the efficacy for pregnancy prevention between the new types of diaphragms and cervical caps and the older diaphragms. The new types of diaphragms and cervical caps resulted in fewer urinary tract infections. Acid-buffering gels did not differ from spermicidal nonoxynol-9 gels regarding pregnancies but seemed to be better tolerated., Competing Interests: Competing interests: AS has nothing to disclose, IL has received compensation from Exeltis and Campus Pharma for lectures during the previous 3 years, and JO has received compensation from Astellas for lectures;, (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Compare hormonal contraceptive use, birth and abortion rates among teenagers in the Nordic countries. A secondary aim was to explore plausible explanations for possible differences between countries., Design: Ecological study using national registry data concerning births and abortions among all women aged 15-19 years residing in Denmark, Finland, Iceland, Norway and Sweden 2008-2015. Age-specific data on prescriptions for hormonal contraceptives for the period 2008-2015 were obtained from national databases in Denmark, Norway and Sweden., Setting: Denmark, Finland, Iceland, Norway and Sweden., Participants: Women 15-19 years old in all Nordic countries (749 709) and 13-19 years old in Denmark, Norway and Sweden (815 044)., Results: Both annual birth rates and abortion rates fell in all the Nordic countries during the study period. The highest user rate of hormonal contraceptives among 15-19-year-olds was observed in Denmark (from 51% to 47%) followed by Sweden (from 39% to 42%) and Norway (from 37% to 41%). Combined oral contraceptives were the most commonly used methods in all countries. The use of long-acting reversible contraceptives (LARC), implants and the levonorgestrel-releasing intrauterine systems, were increasing, especially in Sweden and Norway. In the subgroup of 18-19-year-old teenagers, the user rates of hormonal contraceptives varied between 63% and 61% in Denmark, 56% and 61% in Norway and 54% and 56% in Sweden. In the same subgroup, the steepest increase of LARC was seen, from 2% to 6% in Denmark, 2% to 9% in Norway and 7% to 17% in Sweden., Conclusions: Birth and abortion rates continuously declined in the Nordic countries among teenagers. There was a high user rate of hormonal contraceptives, with an increase in the use of LARC especially among the oldest teenagers., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi.disclosure.pdf (available on request from the corresponding author) and declare that IL has received compensation from Bayer AG, MSD and Actavis for lectures and participation in an Advisory Board during the previous 3 years; FES has over the past 3 years nothing to disclose; KGD has served ad hoc on advisory boards or as invited speaker for Bayer AG, Merck/MSD, Actavis, HRA-Pharma, Exelgyn, Mithra, NaturalCycles and Gedeon Richter; OH has served ad hoc on advisory boards or as invited speaker for Bayer AG, MSD, Actavis, Exelgyn, Sandoz and Gedeon Richter; HH has had no relationships with any company in the previous 3 years; IM has served ad hoc on advisory boards or as invited speaker for Bayer AG, Gedeon Richter and Actavis during the previous 3 years; ØL has within the last 3 years received honoraria for presentation/lectures in pharmacoepidemiological issues. For all authors, their spouses, partners or children have no financial interests that may be relevant to the submitted work., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The effect of combined oral contraceptives (COC) on female sexuality has long been a matter of discussion, but placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate if an estradiol-containing COC influences sexual function., Design: Investigator-initiated, randomised, double-blinded, placebo-controlled clinical trial where 202 healthy women were randomized to a combined oral contraceptive (1.5 mg estradiol and 2.5 mg nomegestrol acetate) or placebo for three treatment cycles., Methods: Sexual function at baseline and during the last week of the final treatment cycle was evaluated by the McCoy Female Sexuality Questionnaire. Serum and hair testosterone levels were assessed at the same time points., Results: Compared to placebo, COC use was associated with a small decrease in sexual interest (COC median change score: -2.0; interquartile range (IQR): -5.0-0.5 vs. placebo: -1.0; IQR: -3.0-2.0, p = 0.019), which remained following adjustment for change in self-rated depressive symptoms B = -0.80 ± 0.30, Wald = 7.08, p = 0.008. However, the proportion of women who reported a clinically relevant deterioration in sexual interest did not differ between COC or placebo users (COC 18 (22.2%) vs. placebo 16 (17.8%), p = 0.47). Change in other measured aspects of sexual function as well as total score of sexual function did not differ between the two treatments., Conclusions: This study suggests that use of estradiol-based combined oral contraceptives is associated with reduced sexual interest. However, the changes are minute, and probably not of clinical relevance.

Purpose: Previous studies have emphasised that women with pre-existing mood disorders are more inclined to discontinue hormonal contraceptive use. However, few studies have examined the effects of combined oral contraceptives (COC) on mood in women with previous or ongoing mental disorders., Materials and Methods: This is a supplementary analysis of an investigator-initiated, double-blinded, randomised clinical trial during which 202 women were treated with either a COC (1.5 mg estradiol and 2.5 mg nomegestrolacetate) or placebo during three treatment cycles. The Mini International Neuropsychiatric Interview was used to collect information on previous or ongoing mental disorders. The primary outcome measure was the total change score in five mood symptoms on the Daily Record of Severity of Problems (DRSP) scale in the intermenstrual phase of the treatment cycle., Results: Women with ongoing or previous mood, anxiety or eating disorders allocated to COC had higher total DRSP Δ-scores during the intermenstrual phase of the treatment cycle in comparison with corresponding women randomised to placebo, mean difference 1.3 (95% CI 0.3-2.3). In contrast, among women without mental health problems, no difference in total DRSP Δ-scores between COC- and placebo users was noted. Women with a risk use of alcohol who were randomised to the COC had higher total DRSP Δ-scores than women randomised to placebo, mean difference 2.1 (CI 95% 1.0-3.2)., Conclusions: Women with ongoing or previous mental disorders or risk use of alcohol have greater risk of COC-induced mood symptoms. This may be worth noting during family planning and contraceptive counselling.

Introduction: The aim of this study was to describe and compare contraceptive use, fertility, birth, and abortion rates in the Nordic countries., Material and Methods: National data on births, abortions, fertility rate (1975-2013), redeemed prescriptions of hormonal contraceptives and sales figures of copper intrauterine devices (2008-2013) among women 15-49 years of age in the Nordic countries were collected and analyzed., Results: Use of hormonal contraceptives and copper intrauterine devices varied between 31 and 44%. The highest use was in Denmark (39-44%) and Sweden (40-42%). Combined hormonal contraception followed by the levonorgestrel-releasing intrauterine system were the most common methods. During 1975-2013 abortion rates decreased in Denmark (from 27/1000 women to 15/1000 women aged 15-44/1000 women) and Finland (from 20 to 10/1000 women), remained stable in Norway (≈16) and Sweden (≈20) and increased in Iceland (from 6 to 15/1000 women). Birth rates remained stable around 60/1000 women aged 15-44 in all countries except for Iceland where the birth rate decreased from 95 to 65/1000 women. Abortion rates were highest in the age group 20-24 years. In the same age group, Sweden had a lower contraceptive use (51%) compared with Denmark (59%) and Norway (56%) and a higher abortion rate 33/1000 compared with Denmark (25/1000) and Norway (27/1000)., Conclusions: In contrast to the declining average fertility and birth rates in Europe, rates in the Nordic countries remain high and stable despite high contraceptive use and liberal access to abortion on women's request., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: Ever since the introduction of combined oral contraception (COC), one of the major reasons for discontinuing the pill use has been mood-related side effects. Moreover, women who discontinue the pill turn to less effective methods whereby the probability of an unintended conception increases. Approximately 4-10% of COC users complain of depressed mood, irritability or increased anxiety, but drug-related causality has been difficult to prove. Given the lack of randomized controlled trials in this area, we aimed to prospectively estimate the severity of adverse mood in COC users that would be as representative of general users as possible., Methods: This investigator-initiated, multi-center, randomized, double-blinded, placebo-controlled study included 202 healthy women. Women were randomized to a COC (1.5mg estradiol and 2.5mg nomegestrolacetate) or placebo for three treatment cycles. Main outcome measure was the Daily Record of Severity of Problems (DRSP), which was filled out daily during one baseline cycle and the final treatment cycle., Results: Results from 84 women in the COC group and 94 women in the placebo group were analysed. COC use was associated with small, but statistically significant, increases in mean anxiety (0.22; 95% CI: 0.07-0.37, p=0.003), irritability (0.23; 95% CI: 0.07-0.38, p=0.012), and mood swings scores (0.15; 95% CI: 0.00-0.31, p=0.047) during the intermenstrual phase, but a significant premenstrual improvement in depression (-0.33; 95% CI: -0.62 to -0.05, p=0.049). Secondary analyses showed that women with previous adverse hormonal contraceptive experience reported significantly greater mood worsening in the intermenstrual phase in comparison with healthy women, p<0.05. The proportion of women who reported a clinically relevant mood deterioration did not differ between those allocated to COC (24.1%) or placebo (17.0%), p=0.262., Conclusion: COC use is associated with small but statistically significant mood side effects in the intermenstrual phase. These findings are driven by a subgroup of women who clearly suffer from COC-related side effects. However, positive mood effects are noted in the premenstrual phase and the proportion of women with clinically relevant mood worsening did not differ between treatment groups., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: The aim was to compare contraceptive use in the Nordic countries and to assess compliance with recommendations from the European Medicines Agency regarding the use of combined oral contraception containing low-dose estrogen and levonorgestrel, norethisterone or norgestimate., Material and Methods: Data on hormonal contraceptive prescriptions and sales figures for copper intrauterine devices were obtained from national databases and manufacturers in Denmark, Finland, Iceland, Norway and Sweden in 2010-2013., Results: Contraceptive use was highest in Denmark (42%) and Sweden (41%), followed by Finland (40%). Combined oral contraception was the most used method in all countries, with the highest use in Denmark (26%). The second most used method was the levonorgestrel-releasing intrauterine system, with the highest use in Finland (15%) and ≈10% in the other countries. Copper intrauterine devices (7%) and the progestin-only pill (7%) were most often used in Sweden. Combined oral contraception use decreased with increasing age and levonorgestrel-releasing intrauterine system and progestin-only pills use increased. The use of long-acting reversible methods of contraception (=levonorgestrel-releasing intrauterine system, copper intrauterine devices, and implants) increased with time and was highest in Sweden (20%) and Finland (18%). The highest use of European Medicines Agency recommended combined oral contraception was in Denmark, increasing from 13 to 50% between 2010 and 2013. In Finland, recommended combined oral contraception remained below 1%., Conclusions: Contraceptive use was highest in Denmark and Sweden, levonorgestrel-releasing intrauterine system use was highest in Finland and all long-acting methods were most common in Sweden. The use of combined oral contraception recommended by the European Medicines Agency was highest in Denmark., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Study Question: Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion?, Summary Answer: A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion., What Is Already Known: The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known., Study Design Size, Duration: This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat., Participants/materials, Setting, Methods: Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland., Main Results and the Role of Chance: Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the ±5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018., Limitations, Reasons for Caution: For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis., Wider Implications of the Findings: Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days., Study Funding/competing Interests: This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare., Trial Registration Number: ClinicalTrials number NCT01920022., Trial Registration Date: 06 August 2013., Date of First Patient's Enrolment: 13 October 2013., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: The aim of this study was to describe contraceptive use and pregnancies and their relationship to socio-economic status (SES) in four generations of young Swedish women., Material and Methods: Questionnaires regarding contraceptive use and pregnancies were sent to random samples of 19-year-old women in 1981, 1991, 2001 and 2011 (n = 4732)., Results: Current contraceptive use was higher in 2001 (78%) (p < 0.01) and 2011 (69%) (p < 0.05) compared with 1981 (60%) and 1991 (62%). Combined hormonal contraception (CHC) was the most common form of contraception throughout (p < 0.0001). The use of long-acting reversible contraception (LARC = implants, intrauterine contraception) and progestogen-only pills increased over time (p < 0.01). Mental side effects as a reason for CHC cessation increased over time and was the most common reason for cessation of CHC in 2011 (p < 0.001). Contraceptive use was lower in women from low SES areas (p < 0.05) in 2011. The percentage of young women who had been pregnant at ≤19 years of age was lower (p < 0.05) in the assessment from 2001 (7%) than in that in 1991 (13%) and 2011 (12%). The proportion of teenage mothers decreased from 4.4% (1981) to 1.6% (2011) (p < 0.01). More women had been pregnant at ≤19 years of age in low SES areas than in middle and high SES areas (p < 0.05)., Conclusions: The lowest pregnancy rate was in the cohort with the highest contraceptive use. Term pregnancies declined over time. A greater number of pregnancies in low SES areas and a change towards lower contraceptive use in low SES areas was recorded in 2011., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Antibodies towards type II collagen (CII) are detected in patients with rheumatoid arthritis (RA) and in non-human primates and rodents with collagen induced arthritis (CIA). We have previously shown that antibodies specific for several CII-epitopes are pathogenic using monoclonal antibodies from arthritic mice, although the role of different anti-CII epitopes has not been investigated in detail in other species. We therefore performed an inter-species comparative study of the autoantibody response to CII in patients with RA versus monkeys and mice with CIA., Methods: Analysis of the full epitope repertoire along the disease course of CIA was performed using a library of CII triple-helical peptides. The antibody responses to the major CII epitopes were analyzed in sera and synovial fluid from RA patients, and in sera from rhesus monkeys (Macaca mulatta), common marmosets (Callithrix jacchus) and mice., Results: Many CII epitopes including the major C1, U1, and J1 were associated with established CIA and arginine residues played an important role in the anti-CII antibody interactions. The major epitopes were also recognized in RA patients, both in sera and even more pronounced in synovial fluid: 77% of the patients had antibodies to the U1 epitope. The anti-CII immune response was not restricted to the anti-citrulline protein antibodies (ACPA) positive RA group., Conclusion: CII conformational dependent antibody responses are common in RA and are likely to originate from rheumatoid joints but did not show a correlation with ACPA response. Importantly, the fine specificity of the anti-CII response is similar with CIA in monkeys and rodents where the recognized epitopes are conserved and have a major pathogenic role. Thus, anti-CII antibodies may both contribute to, as well as be the consequence of, local joint inflammation.

During early infection with human immunodeficiency virus type 1 (HIV-1), there is a rapid depletion of CD4(+) T-cells in the gut-associated lymphoid tissue (GALT) in the gastrointestinal tract. Therefore, immediate protection at these surfaces is of high priority for the development of an HIV-1 vaccine. Thus, transgenic plants expressing HIV-1 antigens, which are exposed to immune competent cells in the GALT during oral administration, can be interesting as potential vaccine candidates. In the present study, we used two HIV-1 p24 antigen-expressing transgenic plant systems, Arabidopsis thaliana and Daucus carota, in oral immunization experiments. Both transgenic plant systems showed a priming effect in mice and induced humoral immune responses, which could be detected as anti-p24-specific IgG in sera after an intramuscular p24 protein boost. Dose-dependent antigen analyses using transgenic A. thaliana indicated that low p24 antigen doses were superior to high p24 antigen doses., (Copyright © 2014. Published by Elsevier Ltd.)

Autoantibody formation is essential for the development of certain autoimmune diseases like rheumatoid arthritis (RA). Anti-type II collagen (CII) antibodies are found in RA patients; they interact with cartilage in vivo and are often highly pathogenic in the mouse. Autoreactivity to CII is directed to multiple epitopes and conserved between mice and humans. We have previously mapped the antibody response to CII in a heterogeneous stock cohort of mice, with a strong association with the IgH locus. We positioned the genetic polymorphisms and determined the structural requirements controlling antibody recognition of one of the major CII epitopes. Polymorphisms at positions S31R and W33T of the associated variable heavy chain (VH) allele were identified and confirmed by gene sequencing. The Fab fragment binding the J1 epitope was crystallized, and site-directed mutagenesis confirmed the importance of those two variants for antigen recognition. Back mutation to germline sequence provided evidence for a preexisting recognition of the J1 epitope. These data demonstrate a genetic association of epitope-specific antibody responses with specific VH alleles, and it highlights the importance of germline-encoded antibodies in the pathogenesis of antibody-mediated autoimmune diseases.

Introduction: Immune responses against collagen type II (CII) are crucial for the development of collagen-induced arthritis (CIA). The aim of the present study was to evaluate and compare the CII-directed T cell and antibody specificity at different time points in the course of CIA using two mouse strains on the B10 genetic background - B10.Q, expressing Aq MHC class II molecules, and B10.DR4.Ncf1*/*, expressing human rheumatoid arthritis-associated MHC II DR4 molecules (DRA*0101/DRB*0401)., Methods: B10.Q and B10.DR4.Ncf1*/* mice were immunized with CII emulsified in adjuvant and development of CIA was assessed. T cells from draining lymph nodes were restimulated in vitro with CII peptides and interferon-gamma (IFN-γ) levels in culture supernatants were evaluated by ELISA. CII-specific antibody levels in serum samples were measured by ELISA., Results: At four different CIA time points we analyzed T cell specificity to the immunodominant CII epitope 259-273 (CII259-273) and several posttranslationally modified forms of CII259-273 as well as antibody responses to three B cell immunodominant epitopes on CII (C1, U1, J1). Our data show that CII-specific T and B cell responses increase dramatically after disease onset in both strains and are sustained during the disease course. Concerning anti-CII antibody fine specificity, during all investigated stages of CIA the B10.Q mice responded predominantly to the C1 epitope, whereas the B10.DR4.Ncf1*/* mice also recognized the U1 epitope. In the established disease phase, T cell reactivity toward the galactosylated CII259-273 peptide was similar between the DR4- and the Aq-expressing strains whereas the response to the non-modified CII peptide was dramatically enhanced in the DR4 mice compared with the B10.Q. In addition, we show that the difference in the transgenic DR4-restricted T cell specificity to CII259-273 is not dependent on the degree of glycosylation of the collagen used for immunization., Conclusions: The present study provides important evaluation of CII-specific immune responses at different phases during CIA development as well as a comparative analysis between two CIA mouse models. We indicate significant differences in CII T cell and antibody specificities between the two strains and highlight a need for improved humanized B10.DR4 mouse model for rheumatoid arthritis.

Objective: In rheumatoid arthritis, joint inflammation and cartilage destruction are mediated by autoantibodies directed to various self antigens. Type II collagen (CII)-specific antibodies are likely to play a role in this process and have been shown to induce experimental arthritis in susceptible animals. The purpose of this study was to reveal how arthritogenic autoantibodies recognize native CII in its triple-helical conformation., Methods: Site-directed mutagenesis and crystallographic studies were performed to reveal crucial contact points between the CII antibody and the triple-helical CII peptide., Results: The crystal structure of a pathogenic autoantibody bound to a major triple-helical epitope present on CII was determined, allowing a first and detailed description of the interactions within an arthritogenic complex that is frequently occurring in both mice and humans with autoimmune arthritis. The crystal structure emphasizes the role of arginine residues located in a commonly recognized motif on CII and reveals that germline-encoded elements are involved in the interaction with the epitope., Conclusion: The crystal structure of an arthritogenic antibody binding a triple-helical epitope on CII indicates a crucial role of germline-encoded and arginine residues as the target structures., (Copyright © 2011 by the American College of Rheumatology.)

The major outer membrane protein (MOMP) of Chlamydia trachomatis is a highly antigenic and hydrophobic transmembrane protein. Our attempts to express the full-length protein in a soluble form in Escherichia coli and in transgenic plants failed. A chimeric gene construct of C. trachomatis serovar E MOMP was designed in order to increase solubility of the MOMP protein but with retained antigenicity. The designed construct was successfully expressed in E. coli, in Arabidopsis thaliana, and in Daucus carota. The chimeric MOMP expressed in and purified from E. coli was used as antigen for production of antibodies in rabbits. The anti-chimeric MOMP antibodies recognized the corresponding protein in both E. coli and in transgenic plants, as well as in inactivated C. trachomatis elementary bodies. Transgenic Arabidopsis and carrots were characterized for the number of MOMP chimeric genetic inserts and for protein expression. Stable integration of the transgene and the corresponding protein expression were demonstrated in Arabidopsis plants over at least six generations. Transgenic carrots showed a high level of expression of the chimeric MOMP - up to 3% of TSP., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The calcium-dependent enzyme tissue transglutaminase (tTG) is associated with diverse biological functions, such as induction of apoptosis, modeling of the extracellular matrix, receptor-mediated endocytosis, cell growth and differentiation, cell adhesion and signal transduction. Also, it may deamidate glutamine residues to glutamic acid and catalyze cross-linking of proteins. In this study, we have investigated the impact of tTG for posttranslational modifications and cross-linking of the immunodominant T-cell epitope CII260-270 and their effects on the collagen-induced arthritis, an animal model for rheumatoid arthritis. By using mass spectrometry analysis and hybridoma assays, we have demonstrated that tTG could perform both types of modifications (deamidation and cross-link formation) on the immunodominant T-cell epitope CII259-273. Replacement of the glutamine at position 267 with glutamic acid leads to a decreased binding affinity to MHC II. T cells recognized both non-modfied (Q(267)) and modified (E(267)) CII259-273-peptides. We also show that administration of tTG leads to increased incidence, severity and histopathological manifestations of collagen-induced arthritis in mice. Moreover, we conclude that both processes, deamidation and cross-linking, are involved in the tTG-catalyzed reactions, and in vivo administration of tTG enhances arthritis severity and joint destruction in mice.

Background: The primary objective of the study was to describe contraceptive use, reasons for discontinuation of contraception and pregnancy outcome in three generations of female teenagers over a period of 20 years. The secondary objective was to describe the relationship between contraception, smoking, body mass index (BMI) and socioeconomic status (SES)., Study Design: A cross-sectional comparison of 19-year-old women born in 1962, 1972 and 1982 and living in the city of Gothenburg, Sweden, in 1981, 1991 and 2001 was conducted. Contraceptive use, pregnancy outcome, smoking and weight/height were assessed by a postal questionnaire., Results: Current contraceptive use was unchanged between the 62 (60%) and 72 cohorts (62%) but had increased (p<.01) in the 82 cohort (78%); there was no difference in contraceptive use between SES groups at any time. Condom use alone increased over time (p<.01), and the use of oral contraception and a condom together had increased in the 72 and 82 cohorts compared to the 62 cohort (p<.01). Reasons given for using and discontinuing oral contraceptives in three generations of teenagers were studied over 20 years. In addition to contraception, oral contraception was used to reduce dysmenorrhea and heavy bleeding. Discontinuation due to bleeding disturbances decreased (p<.01) over time, whereas discontinuation due to mental side effects increased (p<.01). The percentage of women who had been pregnant at < or =19 years of age in the 82 cohort (7%) was lower (p<.01) than in the 1962 (11%) and 1972 (13%) cohorts. However, there was a successive increase (p<.001) in the percentage of women who had been pregnant more than once at < or =19 years of age (1962/1972/1982: pregnant more than once, 8%/21%/31%). Smoking decreased over time (p<.01) and was no longer related to SES in the 82 cohort. BMI increased (p<.01) over time. There was no difference in BMI between SES groups in the 62 and 72 cohorts but was higher in the low-SES group in the 82 cohort compared to the middle (p<.01) and high (p<.05) SES groups., Conclusions: Contraceptive use was higher in the 82 cohort where there was a corresponding reduction in the percentage of women who had been pregnant at < or =19 years of age compared with the 62 and 72 cohorts. Discontinuation of oral contraception due to mental side effects increased over time. The prevalence of smoking decreased and BMI increased, and there were changes in smoking prevalence and BMI in the different SES groups over time.

An optimized gene expression construct was designed in order to increase the accumulation of the HIV-1 subtype C p24 protein in Arabidopsis thaliana and carrot (Daucus carota) plants. An ER retention signal was introduced into the genetic construct generating a p24 protein containing a SEKDEL amino acid sequence at its C-terminus. Mature A. thaliana plants and carrot cells were transformed using Agrobacterium tumefaciens carrying the improved pGreen0229/p24&#95;SEKDEL vector. Several transgenic plant lines were obtained from both plant species by growth on selective medium and confirmed by PCR. Transformed lines were analyzed for p24 protein content by western blotting using anti-p24-specific antibodies and by Southern blotting to establish the number of copies of the insert in the plant nuclear genome. To estimate the accumulation levels of p24 protein in the plants, ELISA was run using soluble plant extracts. By comparing these results with our previous findings, the ER retention signal increased the level of p24 protein fivefold in the A. thaliana plants. In carrot taproot, the content of p24&#95;SEKDEL protein was approximately half of that in Arabidopsis on a fresh weight basis and was stable in planta for several months. However, on a total soluble protein basis, carrots produced considerable higher levels of the p24&#95;SEKDEL protein than Arabidopsis.

Development of transgenic edible plants, to be used as production, storage and delivery systems for recombinant vaccine antigens, is a promising strategy to obtain cost effective vaccines against infectious diseases, not least for use in developing countries. Therefore, we used Agrobacterium tumefaciens-mediated gene transfer to introduce the p24 gag gene encoding the nucleocapsid protein from HIV-1 subtype C into the Arabidopsis thaliana plant genome. Eighteen plant lines were confirmed positive for the p24 gene by PCR; four of these lines showed an apparent homozygous phenotype when grown on selective medium and these lines also showed transcription of the p24 gene into its corresponding mRNA. The mRNA in all four cases generated the p24 protein in plants, as verified by Western blot analysis. The plants were shown to contain between 0.2 mug and 0.5 mug p24 protein per g of fresh tissue. Analysis of the localisation of the p24 protein showed that stem tissue contained the largest amount of protein, more than twice as much as leaf tissue, whereas no p24 protein was detected in roots. By using Southern blotting, we found that 4, 2-3, 2 and 1 T-DNA insertion events took place in the four lines 1, 2, 7, and 10, respectively. The genetic insertions of line 1 were stable from the T(2) to the T(5) generation and gave rise to the p24 protein in all cases, as verified by Western blotting. In mice fed with fresh transgenic A. thaliana (line 10), anti-gag IgG was obtained in serum after a booster injection with recombinant p37Gag. No immune response was observed after equal booster injection of untreated mice or mice fed with A. thaliana WT plants.

Background: The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone., Methods: A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles., Results: Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences., Conclusion: NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.

Of methods for dissociation of multiply charged peptide and protein ions, electron capture dissociation (ECD) has the advantages of cleaving between a high proportion of amino acids, without loss of such posttranslational modifications as glycosylation and carboxylation. Here this capability is successfully extended to phosphorylation, for which collisionally activated dissociation (CAD) can cause extensive loss of H3PO4 and HPO3. As shown here, these losses are minimal in ECD spectra, an advantage for measuring the degree of phosphorylation. For phosphorylated peptides, ECD and CAD spectra give complementary backbone cleavages for identifying modification sites. For a 24-kDa heterogeneous phosphoprotein, bovine beta-casein, activated ion ECD cleaved 87 of 208 backbone bonds that identified a phosphorylation site at Ser-15, and localized three more among Ser-17,-18, -19, and -22 and Thr-24, and the last among four other sites. This is the first direct site-specific characterization of this key post-translational modification on a protein without its prior degradation, such as proteolysis.