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1.	Teede, Helena J, et al. (författare) Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. 2023 Ingår i: Fertility and sterility. - 1556-5653. ; 120:4, s. 767-793 Tidskriftsartikel (refereegranskat)abstract What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference?International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS.The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist.The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout.This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC).The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management.Overall, recommendations are strengthened and evidence is improved, but remain generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided.The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation programme supports the Guideline with an integrated evaluation program.This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and the Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the sponsoring organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.
2.	Unemo, Magnus, et al. (författare) Real-time PCR and subsequent pyrosequencing for screening of penA mosaic alleles and prediction of reduced susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae 2008 Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - Oxford : Blackwell. - 0903-4641 .- 1600-0463. ; 116:11, s. 1004-1008 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
3.	Pasupuleti, Mukesh, et al. (författare) Preservation of Antimicrobial Properties of Complement Peptide C3a, from Invertebrates to Humans 2007 Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:4, s. 2520-2528 Tidskriftsartikel (refereegranskat)abstract The human anaphylatoxin peptide C3a, generated during complement activation, exerts antimicrobial effects. Phylogenetic analysis, sequence analyses, and structural modeling studies paired with antimicrobial assays of peptides from known C3a sequences showed that, in particular in vertebrate C3a, crucial structural determinants governing antimicrobial activity have been conserved during the evolution of C3a. Thus, regions of the ancient C3a from Carcinoscorpius rotundicauda as well as corresponding parts of human C3a exhibited helical structures upon binding to bacterial lipopolysaccharide permeabilized liposomes and were antimicrobial against Gram-negative and Gram-positive bacteria. Human C3a and C4a (but not C5a) were antimicrobial, in concert with the separate evolutionary development of the chemotactic C5a. Thus, the results demonstrate that, notwithstanding a significant sequence variation, functional and structural constraints imposed on C3a during evolution have preserved critical properties governing antimicrobial activity.
4.	Gio-Batta, Monica, et al. (författare) Fecal short chain fatty acids in children living on farms and a link between valeric acid and protection from eczema. 2020 Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Children growing up on farms have low rates of allergy, but the mechanism for this protective effect has not been fully elucidated. Short chain fatty acids (SCFAs) produced by the gut microbiota may play a role in protection from allergy. We measured fecal SCFA levels in samples collected from 28 farming and 37 control children over the first 3years of life using gas chromatography. Data on diet and other host factors were recorded and allergy was diagnosed at 8years of age. Among all children, median propionic and butyric acid concentration increased over the first 3years, and longer SCFAs typically appeared by 1year of age. Farm children had higher levels of iso-butyric, iso-valeric and valeric acid at 3years of age than rural controls. In addition, children with elder siblings had higher levels of valeric acid at 3years of age, and dietary factors also affected SCFA pattern. High levels of valeric acid at 3years of age were associated with low rate of eczema at 8years of age. The fecal SCFA pattern in farm children suggests a more rapid maturation of the gut microbiota. Valeric acid or associated microbes may have protective potential against eczema.
5.	Dahl, Anna K., et al. (författare) Agreement between self-reported and measured height, weight and body mass index in old age : a longitudinal study with 20 years of follow-up 2010 Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 39:4, s. 445-451 Tidskriftsartikel (refereegranskat)abstract Background: self-reported body mass index (BMI) based on self-reported height and weight is a widely used measure of adiposity in epidemiological research. Knowledge about the accuracy of these measures in late life is scarce.Objective: the study aimed to evaluate the accuracy and changes in accuracy of self-reported height, weight and BMI calculated from self-reported height and weight in late life.Design: a longitudinal population-based study with five times of follow-up was conducted.Participants: seven hundred seventy-four community-living men and women, aged 40–88 at baseline (mean age 63.9), included in The Swedish Adoption/Twin Study of Aging.Methods: participants self-reported their height and weight in a questionnaire, and height and weight were measured by experienced research nurses at an in-person testing five times during a 20-year period. BMI was calculated as weight (kilogramme)/height (metre)2.Results: latent growth curve modelling showed an increase in the mean difference between self-reported and measured values over time for height (0.038 cm/year) and BMI (0.016 kg/m2/year), but not for weight.Conclusions: there is a very small increase in the mean difference between self-reported and measured BMI with ageing, which probably would not affect the results when self-reported BMI is used as a continuous variable in longitudinal studies.
6.	Svensson, Sara L, et al. (författare) Midkine and Pleiotrophin have bactericidal properties : preserved antibacterial activity in a family of Heparin-binding growth factors during evolution 2010 Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:21, s. 16105-16115 Tidskriftsartikel (refereegranskat)abstract Antibacterial peptides of the innate immune system combat pathogenic microbes, but often have additional roles in promoting inflammation and as growth factors during tissue repair. Midkine (MK) and pleiotrophin (PTN) are the only two members of a family of heparin-binding growth factors. They show restricted expression during embryogenesis and are up-regulated in neoplasia. In addition, MK shows constitutive and inflammation-dependent expression in some non-transformed tissues of the adult. In the present study, we show that both MK and PTN display strong antibacterial activity, present at physiological salt concentrations. Electron microscopy of bacteria and experiments using artificial lipid bilayers suggest that MK and PTN exert their antibacterial action via a membrane disruption mechanism. The predicted structure of PTN, employing the previously solved MK structure as a template, indicates that both molecules consist of two domains, each containing three antiparallel beta-sheets. The antibacterial activity was mapped to the unordered C-terminal tails of both molecules and the last beta-sheets of the N-terminals. Analysis of the highly conserved MK and PTN orthologues from the amphibian Xenopus laevis and the fish Danio rerio suggests that they also harbor antibacterial activity in the corresponding domains. In support of an evolutionary conserved function it was found that the more distant orthologue, insect Miple2 from Drosophila melanogaster, also displays strong antibacterial activity. Taken together, the findings suggest that MK and PTN, in addition to their earlier described activities, may have previously unrealized important roles as innate antibiotics.
7.	zenci, V., et al. (författare) Estimated burden of fungal infections in Sweden 2019 Ingår i: Mycoses. - : Wiley. - 0933-7407 .- 1439-0507. ; 62:11, s. 1043-1048 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to estimate the annual burden of fungal infections in Sweden using data mainly from 2016. Data on specific populations were obtained from Swedish national data registries. Annual incidence and prevalence of fungal disease was calculated based on epidemiological studies. Data on infections due to Cryptococcus sp., Mucorales, Histoplasma capsulatum, Coccidioides immitis and Pneumocystis jirovecii were retrieved from Karolinska University Laboratory and covers only 25% of Swedish population. In 2016, the population of Sweden was 9 995 153 (49.8% female). The overall burden of fungal infections was 1 713 385 (17 142/100 000). Superficial fungal infections affect 1 429 307 people (1429/100 000) based on Global Burden of Disease 14.3% prevalence. Total serious fungal infection burden was 284 174 (2843/100 000) in 2016. Recurrent Candida vulvovaginitis is common; assuming a 6% prevalence in women. Prevalence of allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation were estimated to be 20 095 and 26 387, respectively. Similarly, chronic pulmonary aspergillosis was estimated to affect 490 patients after tuberculosis, sarcoidosis and other conditions. Candidemia incidence was estimated to be 500 in 2016 (4.7/100 000) and invasive aspergillosis 295 (3.0/100 000). In Stockholm area, Mucorales were reported in three patients in 2015, while Cryptococcus spp. were reported in two patients. In 2016, there were 297 patients PCR positive for P jirovecii. The present study shows that the overall burden of fungal infections in Sweden is high and affects 17% of the population. The morbidity, mortality and the healthcare‐related costs due to fungal infections warrant further studies.
8.	Decker, Ralph, 1968, et al. (författare) Case report of a girl with secondary amenorrhea associated with aurantiasis cutis 2016 Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Introduction: --- Aurantiasis cutis is a condition of yellowish or golden skin discoloration that can result from eating excessive amounts of foods containing carotene leading to hypercarotenemia(1), described causing secondary amenorrhea(2). Objective & hypothesis: --- Hypercarotenemia can cause secondary amenorrhea without overconsumption of excessive quantities of carotene. Results: --- Laboratory tests showed a ß-Carotene level more than the 2-fold above the upper reference level. Hyperbilirubinemia could be excluded. Hypogonadotropic hypogonadism was not present. There was no evidence for adrenal dysfunction. Liver function tests were normal. Material/ Methods: --- A 16-year-old girl presented to our endocrine outpatient clinic with a 2-year history of varying yellow discoloration of her skin and secondary amenorrhea. The findings of the general physical examination were normal, but there was a marked yellow discoloration of the palms, soles, and nasolabial folds. A dietary history revealed a low carotene diet, but also a low carbohydrate diet. BMI was 19.9 kg/m² (-0.2 SDS) without signs of anorexia. Discussion: --- In this girl we observed hypercarotenemia associated with secondary nonhypothalamic amenorrhea in absence of excess external intake of carotenes. This suggests an intrinsic reason due to a polymorphism(3) in ß-carotene 15,15'-monooxygenase (BCO)(4), an enzyme breaking down carotenes to vitamin A(5). Phenotype-genotype association studies are needed to confirm this hypothesis. Conclusion: --- Secondary non-hypothalamic amenorrhea can be associated with hypercarotenemia. References: --- 1. Tanikawa K, Seta K, Machii A, Itoh S 1961 [Aurantiasis cutis due to overeating of dried laver (nori): a case report]. Jpn J Med Sci Biol 50:414-419 2. Kemmann E, Pasquale SA, Skaf R 1983 Amenorrhea associated with carotenemia. JAMA 249:926-929 3. Leung WC, Hessel S, Meplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G 2009 Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB j 23:1041-1053 4. Frumar AM, Meldrum DR, Judd HL 1979 Hypercarotenemia in hypothalamic amenorrhea. Fertil Steril 32:261-264 5. Lindqvist A, Andersson S 2002 Biochemical properties of purified recombinant human beta-carotene 15,15'-monooxygenase. J Biol Chem 277:23942-23948
9.	Papachristou, Panagiotis, et al. (författare) Evaluation of an artificial intelligence-based decision support for the detection of cutaneous melanoma in primary care: a prospective real-life clinical trial 2024 Ingår i: BRITISH JOURNAL OF DERMATOLOGY. - : OXFORD UNIV PRESS. - 0007-0963 .- 1365-2133. ; 191:1, s. 125-133 Tidskriftsartikel (refereegranskat)abstract Background Use of artificial intelligence (AI), or machine learning, to assess dermoscopic images of skin lesions to detect melanoma has, in several retrospective studies, shown high levels of diagnostic accuracy on par with - or even outperforming - experienced dermatologists. However, the enthusiasm around these algorithms has not yet been matched by prospective clinical trials performed in authentic clinical settings. In several European countries, including Sweden, the initial clinical assessment of suspected skin cancer is principally conducted in the primary healthcare setting by primary care physicians, with or without access to teledermoscopic support from dermatology clinics.Objectives To determine the diagnostic performance of an AI-based clinical decision support tool for cutaneous melanoma detection, operated by a smartphone application (app), when used prospectively by primary care physicians to assess skin lesions of concern due to some degree of melanoma suspicion.Methods This prospective multicentre clinical trial was conducted at 36 primary care centres in Sweden. Physicians used the smartphone app on skin lesions of concern by photographing them dermoscopically, which resulted in a dichotomous decision support text regarding evidence for melanoma. Regardless of the app outcome, all lesions underwent standard diagnostic procedures (surgical excision or referral to a dermatologist). After investigations were complete, lesion diagnoses were collected from the patients' medical records and compared with the app's outcome and other lesion data.Results In total, 253 lesions of concern in 228 patients were included, of which 21 proved to be melanomas, with 11 thin invasive melanomas and 10 melanomas in situ. The app's accuracy in identifying melanomas was reflected in an area under the receiver operating characteristic (AUROC) curve of 0.960 [95% confidence interval (CI) 0.928-0.980], corresponding to a maximum sensitivity and specificity of 95.2% and 84.5%, respectively. For invasive melanomas alone, the AUROC was 0.988 (95% CI 0.965-0.997), corresponding to a maximum sensitivity and specificity of 100% and 92.6%, respectively.Conclusions The clinical decision support tool evaluated in this investigation showed high diagnostic accuracy when used prospectively in primary care patients, which could add significant clinical value for primary care physicians assessing skin lesions for melanoma. We investigated the diagnostic performance of an AI-based decision support in the form of a mobile app to detect melanoma when used by primary care physicians. The app proved to have high levels of diagnostic accuracy in distinguishing melanomas from other skin lesions. We conclude that it appears to be a potentially valuable diagnostic aid for the primary care physician in the assessment of skin lesions of concern.
10.	Gio-Batta, Monica, et al. (författare) Low Concentration of Fecal Valeric Acid at 1 Year of Age Is Linked with Eczema and Food Allergy at 13 Years of Age : Findings from a Swedish Birth Cohort 2022 Ingår i: International Archives of Allergy and Immunology. - : S. Karger. - 1018-2438 .- 1423-0097. ; , s. 398-408 Tidskriftsartikel (refereegranskat)abstract Background: Short-chain fatty acids (SCFAs) are abundant bacterial metabolites in the gut, with immunomodulatory properties. Hence, they may influence allergy development. Previous studies have linked fecal SCFA pattern during infancy with allergy. However, the association of SCFAs to allergic outcomes in adolescence is not well established. Here, we examined how the fecal SCFA pattern at 1 year of age related to allergy at 13 years of age.Methods: Levels of 8 SCFAs in fecal samples collected at 1 year of age from 110 children were quantified using gas chromatography. The same individuals were evaluated at 13 years of age for allergic symptoms, allergy diagnosis and allergy medication by questionnaire, and for sensitization using skin prick test against egg, milk, fish, wheat and soy, cat, dog, horse, birch, and timothy grass.Results: The concentration of fecal valeric acid at 1 year of age was inversely associated with eczema at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.049) and showed a trend for inverse association with food allergy at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.057). In a sub-group analysis of children with eczema at 1 year of age, a higher concentration of fecal valeric acid was linked with reduced risk of their eczema remaining at 13 years of age (OR 0.2, 95% CI: 0.0-1.5), although this latter analysis did not reach statistical significance (p = 0.12).Conclusions: Our findings lend further support to the notion of early childhood as a critical period when allergy may be programmed via the gut microbiota. Higher levels of fecal valeric acid may be characteristic of a protective gut microbiota and/or actively contribute to protection from eczema and food allergy.
11.	Gunningberg, Lena, et al. (författare) Pressure ulcer knowledge of registered nurses, assistant nurses and student nurses : a descriptive, comparative multicentre study in Sweden 2015 Ingår i: International Wound Journal. - : Wiley. - 1742-4801 .- 1742-481X. ; 12:4, s. 462-468 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to describe and compare the knowledge of registered nurses (RNs), assistant nurses (ANs) and student nurses (SNs) about preventing pressure ulcers (PUs). PU prevention behaviours in the clinical practice of RNs and ANs were also explored. A descriptive, comparative multicentre study was performed. Hospital wards and universities from four Swedish county councils participated. In total, 415 participants (RN, AN and SN) completed the Pressure Ulcer Knowledge Assessment Tool. The mean knowledge score for the sample was 58·9%. The highest scores were found in the themes 'nutrition' (83·1%) and 'risk assessment' (75·7%). The lowest scores were found in the themes 'reduction in the amount of pressure and shear' (47·5%) and 'classification and observation' (55·5%). RNs and SNs had higher scores than ANs on 'aetiology and causes'. SNs had higher scores than RNs and ANs on 'nutrition'. It has been concluded that there is a knowledge deficit in PU prevention among nursing staff in Sweden. A major educational campaign needs to be undertaken both in hospital settings and in nursing education.
12.	Carré, Helena, 1979-, et al. (författare) Improved contact tracing for Chlamydia trachomatis with experienced tracers, tracing for one year back in time and interviewing by phone in remote areas 2008 Ingår i: Sexually Transmitted Infections. - : BMJ publishing. - 1368-4973 .- 1472-3263. ; 84:3, s. 239-242 Tidskriftsartikel (refereegranskat)abstract Objectives: To evaluate the Swedish model for contact tracing and especiallythe "Västerbotten model" with centralised, extended contactinterview periods, sometimes by telephone.Methods: Using questionnaires, the contact tracing and interview procedurewas evaluated during 2002, followed by an evaluation of contactinterviewing by phone in 2005–6.Results: Patients with diagnosed Chlamydia trachomatis infection reportedon average 2.5 sexual contacts, 3.0 contacts when contact interviewingwas performed at the clinic, and 2.3 contacts when performedby phone. 65% of the sexual contacts with a known test resultwere infected.Conclusion: Centralised contact tracing, exploring the sexual history forat least 12 months back in time, shows good results. Combinedwith screening of certain risk groups it is probably one effectiveway of preventing C trachomatis infections. Preventing C trachomatisby primary prevention such as information and counselling is,however, still of great importance.
13.	Barman, Malin, 1983, et al. (författare) Proportions of Polyunsaturated Fatty Acids in Umbilical Cord Blood at Birth Are Related to Atopic Eczema Development in the First Year of Life 2021 Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:11 Tidskriftsartikel (refereegranskat)abstract Atopic eczema, the most common atopic disease in infants, may pave the way for sensitization and allergy later in childhood. Fatty acids have immune-regulating properties and may regulate skin permeability. Here we examine whether the proportions of fatty acids among the infant and maternal plasma phospholipids at birth were associated with maternal dietary intake during pregnancy and development of atopic eczema during the first year of age in the Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) birth cohort. Dietary data were collected with a semi-quantitative food frequency questionnaire, fatty acids were measured with GC-MS and atopic eczema was diagnosed by a pediatric allergologist at 12 months of age. We found that higher proportions of n-6 PUFAs (including arachidonic acid) but lower proportions of n-3 PUFAs (including DPA) in the infant's phospholipids at birth were associated with an increased risk of atopic eczema at 12 months of age. The n-6 and n-3 PUFAs were related to maternal intake of meat and fish, respectively. Our results suggest that prenatal exposure to unsaturated fatty acids is associated with eczema development in the infant. Maternal diet during pregnancy may partly explain the fatty acid profiles in utero.
14.	Olsson, Jan, et al. (författare) Time trends in herpesvirus seroepidemiology among Swedish adults 2024 Ingår i: BMC Infectious Diseases. - : Springer Nature. - 1471-2334. ; 24:1 Tidskriftsartikel (refereegranskat)abstract Background: Human herpesviruses are widespread among the human population. The infections often occurunnoticed, but severe disease as well as long-term sequelae are part of the symptom spectrum. The prevalence variesamong subpopulations and with time. The aim of this study was to describe the seroprevalence of ImmunoglobulinG against Herpes simplex 1, Herpes simplex 2, Epstein-Barr virus and Cytomegalovirus in the adult Swedish populationover a time period of several decades.Methods: Serum samples (n = 892) from biobanks, originating from 30-year-old women, 50-year-old menand 50-year-old women sampled between 1975 and 2018, were analyzed for presence of anti-herpesvirus antibod-ies. Linear regression analysis was used to test for a correlation between birth year and seroprevalence. Multiple linearregression analysis was used to differentiate between other factors such as age and gender.Results: Birth year correlated negatively with the prevalence of immunoglobulin G against Herpes simplex 1and Epstein-Barr virus (p = 0.004 and 0.033), and positively with Immunoglobulin G against Cytomegalovirus(p = 0.039). When participant categories were analyzed separately, birth year correlated negatively with the preva-lence of Immunoglobulin G against Herpes simplex 1 and Herpes simplex 2 (p = 0.032 and 0.028) in 30-year-old women,and with the prevalence of Immunoglobulin G against Cytomegalovirus in 50-year-old men (p = 0.011).Conclusions: The prevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2 and Epstein-Barr virusdecreases in later birth cohorts. This indicates a trend of declining risk of getting infected with these viruses as a childand adolescen (9) (PDF) Time trends in herpesvirus seroepidemiology among Swedish adults.
15.	Mørk, Cato, et al. (författare) The Prostaglandin E1 Analog Misoprostol Reduces Symptoms and Microvascular Arteriovenous Shunting in Erythromelalgia : A Double-Blind, Crossover, Placebo-Compared Study 2004 Ingår i: Journal of Investigative Dermatology. - : Nature Publishing Group. - 0022-202X .- 1523-1747. ; 122:3, s. 587-593 Tidskriftsartikel (refereegranskat)abstract Based on previous experience with parenteral prostanoids, we studied the effect of misoprostol treatment, an orally administered prostaglandin E1 analog, in patients with erythromelalgia. Treatment with placebo was followed by treatment with misoprostol (0.4–0.8 mg per d), both for 6 wk. The patients (n=21) and a study nurse who administered the trial were blinded. The endpoints were change in pain and need for cooling and global assessment of the treatment. Following central body heat provocation, global skin perfusion, capillary morphology, and change in pain were also recorded before and after each treatment period. Results were compared with data from healthy control subjects (n=11) that did not undergo treatment. Clinical safety and tolerability evaluation included physical examinations, clinical laboratory tests, and monitoring of adverse events. All clinical outcome measures were significantly better after treatment with misoprostol (p<0.01) as compared with placebo treatment and after a 3-mo follow-up without treatment. The heat-induced increase in global perfusion after misoprostol treatment was similar to the control group and significantly lower when compared with baseline (p<0.01) and placebo treatment (p<0.05), respectively. This study demonstrates that misoprostol is clinically superior to placebo in patients with erythromelalgia. The results of the perfusion studies may imply that the mechanism of action of the beneficial effect of misoprostol is reduced microvascular arteriovenous shunting in affected skin.
16.	Jaenson, Thomas G. T., 1948-, et al. (författare) "Fågelloppor" kan ha varit fågelkvalster 2010 Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 107:29-31, s. 1791-1792 Tidskriftsartikel (populärvet., debatt m.m.)
17.	Berne, Berit, et al. (författare) Can the reporting of adverse skin reactions to cosmetics be improved? A prospective clinical study using a structured protocol. 2008 Ingår i: Contact dermatitis. - : Wiley. - 1600-0536 .- 0105-1873. ; 58:4, s. 223-7 Tidskriftsartikel (refereegranskat)abstract The use of cosmetics is rising, and adverse reactions to these products are increasing. In Sweden, the Medical Products Agency (MPA) keeps a voluntary reporting system for such adverse reactions. However, the reporting is sparse, consisting almost only of cases with test-proven allergic contact dermatitis, thus under-reporting the more common irritant reactions.
18.	Eldh, Maria, 1980, et al. (författare) MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma 2014 Ingår i: BMC Cancer. - London : Springer Science and Business Media LLC. - 1471-2407. ; 14 Tidskriftsartikel (refereegranskat)abstract Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.
19.	Ekbäck, Maria [Palmetun], et al. (författare) "It is always on my mind" : women's experiences of their bodies when living with hirsutism 2009 Ingår i: Health Care for Women International. - London : Taylor & Francis. - 0739-9332 .- 1096-4665. ; 30:5, s. 358-372 Tidskriftsartikel (refereegranskat)abstract Many women suffer from excessive hair growth, often in combination with polycystic ovarian syndrome (PCOS). It is unclear how hirsutism influences such women's experiences of their bodies. Our aim is to describe and interpret women's experiences of their bodies when living with hirsutism. Interviews were conducted with 10 women with hirsutism. We used a qualitative latent content analysis. Four closely intertwined themes were disclosed: the body was experienced as a yoke, a freak, a disgrace, and as a prison. Hirsutism deeply affects women's experiences of their bodies in a negative way.
20.	Arabpour, Mohammad, et al. (författare) ADP-ribosylating adjuvant reveals plasticity in cDC1 cells that drive mucosal Th17 cell development and protection against influenza virus infection 2022 Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 15:4, s. 745-761 Tidskriftsartikel (refereegranskat)abstract Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103(+) cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3-/- mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt(+) T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.
21.	Lan, P. T., et al. (författare) Reproductive tract infections including sexually transmitted infections : a population-based study of women of reproductive age in a rural district of Vietnam. 2008 Ingår i: Sexually Transmitted Infections. - London : BMJ Publishing Group. - 1368-4973 .- 1472-3263. ; 84:2, s. 126-132 Tidskriftsartikel (refereegranskat)abstract Objectives: To investigate the prevalences of reproductive tract infections (RTI)/sexually transmitted infections (STI) among married women in a rural district of Vietnam, and analyse the influence of socioeconomic, sociodemographic, and other determinants possibly related to RTI/STI. Methods: A community-based cross-sectional study. Married women aged 18–49 years (n = 1012) were interviewed and underwent a gynaecological examination. Specimens were collected for laboratory diagnosis of chlamydia, gonorrhoea, trichomonas, bacterial vaginosis (BV), candidiasis, hepatitis B, HIV, and syphilis. Results: In total, 37% of the women were clinically diagnosed with an RTI/STI. Aetiologically confirmed RTI/STI was identified in 39% of the women (including 6% with STI). Endogenous infections were most prevalent (candidiasis 26%, BV 11%) followed by hepatitis B 8.3%, Chlamydia trachomatis 4.3%, Trichomonas vaginalis 1%, Neisseria gonorrhoeae 0.7%, genital warts 0.2%, and HIV and syphilis 0%. Fifty per cent of the STI cases were asymptomatic. Younger age and intrauterine devices were significantly associated with an increased risk of BV. Determinants of candidiasis were vaginal douching, high education level and low economic status, whereas a determinant of chlamydia was high economic status. Outmigration of the husband was associated with an increased risk of hepatitis B surface antigen seroposivity among women. Conclusions: RTI/STI were prevalent among married women in a rural population of Vietnam. Syndromic algorithms should be consistently supplemented by risk assessment in order to reduce under and overtreatment. Microscopic diagnosis could be applied in primary care settings to achieve more accurate diagnoses. The promotion of health education aimed at reducing RTI/STI prevalences is an important tool in STI/HIV control programmes. Vaccination to prevent hepatitis B for migrants should be considered.
22.	Naeser, Ylva, et al. (författare) Survival in patients diagnosed with melanoma in situ compared to the general population. A Swedish population-based matched cohort study 2023 Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 65 Tidskriftsartikel (refereegranskat)abstract Background: The incidence of melanoma in situ (MIS) is increasing even more rapidly than the incidence of cutaneous malignant melanoma (CMM). No previous studies have in detail investigated the survival in individuals diagnosed with MIS compared to the general population.Methods: This population-based study included individuals with MIS diagnosed in Sweden between 2001 and 2010 and randomly selected MIS-free comparators matched on age, sex and county of residence. Exclusion criterion was a previous CMM. Data on socioeconomic status (SES) including educational level, income and marital status, comorbidity and cause of death were obtained from population-based registers. Overall survival (OS) was estimated by the Kaplan-Meier method. The mortality risk adjusted for SES and comorbidity was assessed by multivariable Cox regression analyses.Findings: The survival analyses included 7963 cases and 39,662 comparators. Median age at MIS diagnosis were 63 (IQR 50-75) and 67 (IQR 57-76) years in women and men respectively. Median follow-up time was 120 months (IQR 102-152 months). In individuals with MIS, the ten-year OS was 77% (95% CI 0.76-0.78) compared to 72% (95% CI 0.72-0.73) in comparators. The MIS patients had a higher SES and lower comorbidity burden than the comparators. In a fully adjusted multivariable analysis, including 7772 cases and 38,103 comparators, the mortality was significantly lower in women with MIS (HR 0.88, 95% CI 0.82-0.94) compared to the background population. The corresponding estimate in men was HR 0.94 (95% CI 0.88-1.0). The risk of melanoma-related deaths during the study period was ten-fold higher in MIS patients.Interpretation: Despite being at increased risk of developing CMM, MIS patients had a better OS compared to their matched comparators from the background population, findings which could not fully be explained by differences in SES and comorbidity. Our results are reassuring and should be communicated to patients who have been diagnosed with MIS.
23.	Malmberg, Per, 1974, et al. (författare) Imaging mass spectrometry for novel insights into contact allergy - a proof-of-concept study on nickel 2018 Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 78:2, s. 109-116 Tidskriftsartikel (refereegranskat)abstract Background. In spite of extensive regulation to limit exposure, nickel remains the main cause of contact allergy in the general population. More detailed knowledge on the skin uptake of haptens is required. So far, no method exists for the visualization of this clinically relevant hapten and its distribution in the skin. Objectives. To show, in terms of a proof of concept, that imaging mass spectrometry [time of flight secondary ion mass spectrometry (ToF-SIMS)] can be applied for investigation of the penetration and distribution of nickel in human skin. Method. Full-thickness human skin obtained from breast reduction surgery was exposed to nickel sulfate (5% in deionized water) for 24 h in Franz-type diffusion cells. Biopsies were obtained from nickel-treated samples and control (deionized water). The tissue was sliced, and analysed with ToF-SIMS, generating high-resolution images of ion distribution in the epidermis and upper dermis. Results. The skin layers could be discerned from the ToF-SIMS data, particularly on the basis of the collagen signal. Nickel ions were localized to the stratum corneum and upper epidermis. Conclusions. This is the first time that ToF-SIMS has been applied to trace the distribution of a hapten in human skin. Proof of principle was shown for nickel, and the technique can, in the future, be expanded for investigation of the skin distribution of clinically relevant sensitizers in general.
24.	Wallander, Mari-Ann, et al. (författare) Unspecified abdominal pain in primary care : the role of gastrointestinal morbidity 2007 Ingår i: International journal of clinical practice (Esher). - : Hindawi Limited. - 1368-5031 .- 1742-1241. ; 61:10, s. 1663-1670 Tidskriftsartikel (refereegranskat)abstract Background: Many patients with abdominal pain have no obvious cause for their symptoms and receive a diagnosis of unspecified abdominal pain. Aim: The objective of this study was to ascertain risk factors and consequences of a diagnosis of unspecified abdominal pain in primary care. Methods: A population-based, case-control study was conducted using the UK General Practice Research Database. We identified 29,299 patients with a new diagnosis of abdominal pain, and 30,000 age- and sex-matched controls. Only diagnostic codes that did not specify the type or location of abdominal pain were included. Results and discussion: The incidence of newly diagnosed unspecified abdominal pain was 22.3 per 1000 person-years. The incidence was higher in females than in males, and 29% of patients were below 20 years of age. Prior gastrointestinal morbidity was associated with abdominal pain, but high body mass index, smoking and alcohol intake were not. Patients newly diagnosed with abdominal pain were 16 to 27 times more likely than controls to receive a subsequent new diagnosis of gallbladder disease, diverticular disease, pancreatitis or appendicitis in the year after the diagnosis of abdominal pain. The likelihood of receiving other gastrointestinal diagnoses such as peptic ulcer disease, hiatus hernia, gastro-oesophageal reflux disease (GERD), irritable bowel syndrome (IBS) or dyspepsia was increased three- to 14-fold among patients consulting for abdominal pain. Conclusion: When managing abdominal pain in primary care, morbidities such as GERD and IBS should be considered as diagnoses once potentially life-threatening problems have been excluded.
25.	Ekbäck, Maria Palmetun, et al. (författare) Health-Related Quality of Life, Depression and Anxiety Correlate with the Degree of Hirsutism 2013 Ingår i: Dermatology. - : Karger. - 1018-8665 .- 1421-9832. ; 227:3, s. 278-284 Tidskriftsartikel (refereegranskat)abstract Background: Hirsutism has a negative impact on womens quality of life. The relation between quality of life, anxiety, depression and the level of hairiness has not been described. Aims: To investigate the correlations between the levels of hairiness, quality of life, anxiety and depression. Methods: 200 patients from Malmo, Orebro and Uppsala, who had been in contact with the clinics for problems with excessive hair growth, were invited to answer a self-administered questionnaire including sociodemographic questions, EQ-5D index score, Dermatology Life Quality Index (DLOI), Hospital Anxiety and Depression Scale (HADS) and Ferriman-Gallwey scale (F-G); of these, 127 women participated in the study. Results: The mean values were: EQ-5D index 0.73 (SD = 0.27), EQ visual analogue scale 61.0 (SD = 22.6), HADS-anxiety 9.5 +/- 5.3 and HADS-depression 6.5 +/- 4.6. The mean DLQI was 11.8 +/- 8.4, indicating a very large effect on patients lives. All were significantly correlated with the amount of hairiness. Conclusions: Higher levels of hair growth were significantly correlated with a lower level of quality of life and symptoms of both anxiety and depression.
26.	Törmä, Hans, et al. (författare) Skin barrier disruption by sodium lauryl sulfate-exposure alters the expressions of involucrin, transglutaminase 1, profilaggrin, and kallikreins during the repair phase in human skin in vivo 2008 Ingår i: Journal of Investigative Dermatology. - London : Nature publishing group. - 0022-202X .- 1523-1747. ; 128:5, s. 1212-1219 Tidskriftsartikel (refereegranskat)abstract Detergents are skin irritants affecting keratinocytes. In this study, healthy volunteers were exposed to water (vehicle) and 1% sodium lauryl sulfate (SLS) under occlusive patch tests for 24 hours. The messenger RNA (mRNA) expression of keratinocyte differentiation markers and of enzymes involved in corneodesmosome degradation was examined in skin biopsies (n=8) during the repair phase (6 hours to 7 days postexposure) using real-time reverse-transcription PCR. It was found that the expression of involucrin was increased at 6 hours, but then rapidly normalized. The expression of transglutaminase 1 exhibited a twofold increase after 24 hours in the SLS-exposed skin. Profilaggrin was decreased after 6 hours. Later (4–7 days), the expression in SLS-exposed areas was >50% above than in control areas. An increased and altered immunofluorescence pattern of involucrin, transglutaminase 1, and filaggrin was also found (n=4). At 6 hours post-SLS exposure, the mRNA expression of kallikrein-7 (KLK-7) and kallikrein-5 (KLK-5) was decreased by 50 and 75%, respectively, as compared with control and water-exposed areas. Thereafter, the expression pattern of KLK-7 and KLK-5 was normalized. Changes in protein expression of KLK-5 were also found. In conclusion, SLS-induced skin barrier defects induce altered mRNA expression of keratinocyte differentiation markers and enzymes degrading corneodesmosomes.
27.	Sato, Yuki, et al. (författare) Asthma and atopic diseases in adolescence and antidepressant medication in middle age 2018 Ingår i: Journal of Health Psychology. - London, United Kingdom : Sage Publications. - 1359-1053 .- 1461-7277. ; 23:6, s. 853-859 Tidskriftsartikel (refereegranskat)abstract This Swedish register-based cohort study examined whether asthma, hay fever and allergic dermatitis in late adolescence identified in the early 1970s are associated with antidepressant medication in middle age, between 2006 and 2009. After adjustment for childhood and adulthood sociodemographic characteristics, psychological, cognitive and physical function, and comorbidity, the magnitude of the associations diminished for asthma, while hay fever and atopic dermatitis retained associations. Hay fever and atopic dermatitis in adolescence have potentially important implications for future mental health, while asthma may already have influenced an individual's ability to cope with stress by late adolescence.
28.	Sveen, Josefin, 1976-, et al. (författare) Letter: Response to Letter to the Editor: Sleep quality implicates in life quality: An analysis about children who suffered burns. 2014 Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 40:4, s. 775-776 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract n/a
29.	Löfvendahl, Sofia, et al. (författare) Prevalence and incidence of generalized pustular psoriasis in Sweden : a population-based register study 2022 Ingår i: British Journal of Dermatology. - : John Wiley & Sons. - 0007-0963 .- 1365-2133. ; 186:6, s. 970-976 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Generalized pustular psoriasis (GPP) is a severe form of pustular psoriasis with generalized eruption of sterile pustules, often along with systemic symptoms. There is a scarcity of population-based estimates of GPP prevalence and incidence.OBJECTIVES: To estimate (i) the prevalence and incidence of GPP in the Swedish general population and (ii) the prevalence of psoriasis vulgaris within the GPP population.METHODS: We identified cases (2004-2015) with one ICD-10 diagnostic code (base case) for GPP within the Swedish National Patient Register, which covers inpatient and outpatient secondary care. Cases were linked to the Swedish Total Population Register, and point prevalence was estimated as on 31 December 2015. In two alternative analyses we changed case definitions to: (i) requiring two visits (strict case 1) and (ii) requiring two visits of which one was within dermatology/internal medicine (strict case 2).RESULTS: The base case point prevalence of GPP was estimated at 9.1 per 100 000 (women, 11.2; men, 7.0) and the annual prevalence in 2015 was estimated at 1.53 per 100 000. Among the GPP population, 43% also had a psoriasis vulgaris code. The incidence of GPP in 2015 was estimated at 0.82 per 100 000 (women, 0.93; men, 0.74). The criteria used had an impact on prevalence and incidence estimates: prevalence strict case 1 gave 3.8 per 100 000 and incidence strict case 1 gave 0.42 per 100 000.CONCLUSIONS: Results indicate that the estimated GPP population in Sweden is within the range of previous published estimates. However, estimates were sensitive to the GPP case criteria used. The findings enhance demands for studies using validated diagnostic algorithms.
30.	Kjölhede, P., et al. (författare) Individualized treatment for ovarian cancer may become possible 2015 Ingår i: Läkartidningen. - 0023-7205. ; 112 Tidskriftsartikel (refereegranskat)abstract Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in developed countries. Several promising steps toward individualized therapy have been taken recently due to increased knowledge of molecular biology. Multidisciplinary conferences for treatment planning and the centralization to tertiary surgical centers improve quality of surgery and survival. The primary treatment of EOC is radical surgery followed by adjuvant chemotherapy with carboplatin and paclitaxel. Bevacizumab added to the chemotherapy and used as maintenance treatment is standard in the primary treatment of patients with residual tumor or inoperable patients. The PARP inhibitor olaparib is recommended as maintenance treatment of women with platinum sensitive relapsed BRCA mutated high-grade serous EOC who have responded to platinum-based chemotherapy. BRCA testing should be offered to women with EOC. In platinum-resistant recurrence addition of bevacizumab to chemotherapy should be considered.
31.	Ljungman, Charlotta, 1977, et al. (författare) Treatment of Mild to Moderate Hypertension by Gender Perspective: A Systematic Review 2009 Ingår i: JOURNAL OF WOMENS HEALTH. - : Mary Ann Liebert Inc. - 1540-9996 .- 1931-843X. ; 18:7, s. 1049-1062 Forskningsöversikt (refereegranskat)
32.	Buraczewska, Izabela, et al. (författare) Long-term treatment with moisturizers affects the mRNA levels of genes involved in keratinocyte differentiation and desquamation 2009 Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 301:2, s. 175-181 Tidskriftsartikel (refereegranskat)abstract In a recent study, we showed that long-term treatment with two different moisturizers affected TEWL in opposite directions. Therefore, we decided to examine the effect of these moisturizers on the cellular and molecular level. In a randomized controlled study on 20 volunteers, epidermal mRNA expression of genes essential for keratinocyte differentiation and desquamation after a 7-week treatment with two moisturizers was analyzed. Treatment with one test moisturizer increased gene expression of involucrin, transglutaminase 1, kallikrein 5, and kallikrein 7, while the other moisturizer affected only expression of cyclin-dependent kinase inhibitor 1A. Thus, moisturizers are able to modify the skin barrier function and change the mRNA expression of certain epidermal genes. Since the type of influence depends on the composition of the moisturizer, these should be tailored in accordance with the requirement of the barrier of each individual patient, which merits further investigations.
33.	Bysell, Helena, et al. (författare) Effect of hydrophobicity on the interaction between antimicrobial peptides and poly(acrylic acid) microgels 2010 Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 114:3, s. 1307-1313 Tidskriftsartikel (refereegranskat)abstract The influence of peptide hydrophobicity on the interaction between antimicrobial peptides and poly(acrylic, acid) microgels wits studied by end-tagging the kininogen-derived antimicrobial peptide GKHKNKGKKNGKHNGWK (GKH17) and its truncated variant KNKGKKNGKH (KNK10) with oligotryptophan groups of different lengths. Microgel deswelling and reswelling in response to peptide binding and release was studied by micromanipulator-assisted light- and fluorescence microscopy, peptide uptake in microgels was determined from solution depletion measurements, and peptide oligomerization was monitored by fluorescence spectroscopy. Results showed that oligomerizition/aggregation of the hydrophobically end-tagged peptides is either absent or characterized by exposure of the tryptophan residues to the aqueous ambient, the latter suggesting small aggregation numbers. In addition, peptide uptake and affinity to the poly(acrylic acid) microgels increase with the number of trypthophan residues in the hydrophobic end tag, whereas peptide-induced microgel deswelling kinetics did not display this tag-length dependence to the same extent. Instead, long end tags resulted in anomalous shell formation, opposing further peptide-induced network deswelling. Theoretical modeling suggested that the deswelling kinetics in response to peptide binding is largely controlled by stagnant layer diffusion, but also that for peptides with Sufficiently long hydrophobic tags, the shell constitutes an additional diffusion barrier, thus resulting in slower microgel deswelling. In addition, GKH17 and KNK10 peptides lacking the tryptophan end tags were Substantially released on reducing peptide-microgel electrostatic interactions through addition of salt, an effect more pronounced for the shorter KNK10 peptide, whereas the hydrophobically end-tagged peptides remained bound to the microgels also at high ionic strength.
34.	Falk, Lars, 1954-, et al. (författare) Sampling for Chlamydia trachomatis infection : a comparison of vaginal, first-catch urine, combined vaginal and first-catch urine and endocervical sampling 2010 Ingår i: International Journal of STD and AIDS (London). - : SAGE Publications. - 0956-4624 .- 1758-1052. ; 21:4, s. 283-287 Tidskriftsartikel (refereegranskat)abstract The aim of the study was to evaluate the sensitivity of patients' self-sampled vaginal specimens, first-catch urine (FCU), combined vaginal/FCU specimens and endocervical specimens for detecting chlamydial infection in women. Women attending sexually transmitted disease clinics, youth clinics and a women's health clinic were enrolled. They self-collected a vaginal specimen with two swabs, which were placed into a sterile tube and into a tube containing a buffer medium, respectively. An FCU sample was collected and aliquoted into both an empty tube and the tube containing the vaginal swab. A clinician collected an endocervical swab. The samples were sent to laboratories for analysis using polymerase chain reaction testing and strand displacement amplification testing, respectively. The sensitivities calculated in all 171 Chlamydia trachomatis-infected women were equal for endocervical specimens (97.1%), vaginal specimens (96.5%) and combined vaginal/FCU specimens (95.3%), whereas the sensitivity for FCU was significantly lower (87.7%). The sensitivity of vaginal specimens for the detection of C. trachomatis is as high as that of combined vaginal/FCU specimens.
35.	Josefson, Anna, et al. (författare) Nickel allergy and hand eczema : a 20-year follow up 2006 Ingår i: Contact Dermatitis. - Oxford : Wiley. - 0105-1873 .- 1600-0536. ; 55:5, s. 286-290 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to investigate the occurrence of hand eczema after 20 years in women patch tested to nickel during childhood. In 1982-1983, 960 schoolgirls were patch tested for nickel allergy; its prevalence was found to be 9%. 20 years later, the same individuals received a questionnaire regarding hand eczema and factors of importance for the development of hand eczema. 735 of 908 women (80.9%) answered the questionnaire. In total, 17.6% of respondents reported hand eczema after the age of 15 years, and the 1-year prevalence was 12.8%. There was no statistically significant difference in the occurrence of hand eczema between the groups who had previously tested positive and negative for nickel allergy. 38.3% of the respondents considered themselves to be nickel sensitive at the time they answered the questionnaire; in this group, the reported prevalence of hand eczema after age 15 was 22.5%. 31.4% of those with a history of atopic dermatitis reported hand eczema after age 15, compared with 10.6% of those without (P < 0.001). In conclusion, contact allergy to nickel in childhood did not seem to increase the prevalence of hand eczema later in life.
36.	Josefson, Anna, et al. (författare) Nickel allergy as risk factor for hand eczema : a population-based study 2009 Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 160:4, s. 828-834 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: In population-based studies using self-reported nickel allergy, a hand eczema prevalence of 30-43% has been reported in individuals with nickel allergy. In a previous Swedish study, 958 schoolgirls were patch tested for nickel. In a questionnaire follow up 20 years later no association was found between nickel allergy and hand eczema. OBJECTIVES: To investigate further the relation between nickel allergy and hand eczema. METHODS: Three hundred and sixty-nine women, still living in the same geographical area, now aged 30-40 years, were patch tested and clinically investigated regarding hand eczema. RESULTS: Patch testing showed 30.1% nickel-positive individuals. The adjusted prevalence proportion ratio (PPR) for hand eczema after age 15 years in relation to nickel patch test results was 1.03 (95% confidence interval, CI 0.71-1.50). A history of childhood eczema was reported by 35.9%, and the PPR for hand eczema in relation to childhood eczema was 3.68 (95% CI 2.45-5.54). When analysing the relation separately in women with and without a history of childhood eczema a statistical interaction was found. The hand eczema risk was doubled in nickel-positive women without a history of childhood eczema, with a PPR of 2.23 (95% CI 1.10-4.49) for hand eczema after age 15 years. CONCLUSIONS: A doubled risk for hand eczema was found in nickel-positive women without a history of childhood eczema. When analysing all participants, there was no statistically significant difference between nickel-positive and nickel-negative women regarding occurrence of hand eczema. The most important risk factor for hand eczema was childhood eczema. The risk for hand eczema in nickel-positive women may previously have been overestimated.
37.	Josefson, Anna, et al. (författare) Validation of self-testing as a method to estimate the prevalence of nickel allergy 2011 Ingår i: Acta Dermato-Venereologica. - : Society for Publication of Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 91:5, s. 526-530 Tidskriftsartikel (refereegranskat)abstract Background: Valid epidemiological tools are required for surveillance of the prevalence of contact allergy. Population based studies including patch testing is the most reliable method, but implies heavy expenses and logistical problems. Clinical data are not representative for the general population and questionnaires concerning contact allergy have a low validity. Self-testing might be a useful method but it has to be validated and evaluated.Objectives: To investigate the validity of self-patch testing for nickel allergy. Methods: Patients from three dermatology clinics were included consecutively when referred to patch testing. In total, 191 patients participated and they were provided with a self-test package including written instructions. The self-test was applied on the arm by the patient, on the same day as the patch test was applied on the back, in the clinic. The patient evaluated the self-test before the patch test reading at the clinic.Results: Patch test at dermatology clinic (‘gold standard’) gave 46/191 (24%) nickel-positive individuals. The sensitivity of the self-test was 72% (95% CI 57–84), the specificity was 91% (95% CI 85–95) and the proportion of agreement was 86% (95% CI 81–91).Conclusions: The validity of self-testing for nickel allergy was adequate in the studied population. To determine whether self-testing is a useful tool for measuring the prevalence of nickel allergy in the general population further studies will be needed.
38.	Josefson, Anna, et al. (författare) Validity of self-reported nickel allergy 2010 Ingår i: Contact Dermatitis. - Oxford : Wiley. - 0105-1873 .- 1600-0536. ; 62:5, s. 289-293 Tidskriftsartikel (refereegranskat)abstract Background: To estimate the prevalence of nickel allergy, self-reports are sometimes used in epidemiological studies. Self-reports are practical and may facilitate estimation of prevalence provided that the questions are validated.Objectives: To investigate the validity of self-reported nickel allergy.Methods: Three hundred and sixty-nine women, aged 30–40 years, from the general population participated in the study. The participants answered a questionnaire before a clinical examination and patch testing. The two questions being validated were ‘Are you sensitive/hypersensitive/allergic to nickel?’ and ‘Do you get a rash from metal buttons, jewellery or other metal items that come in direct contact with your skin?’Results: Patch test showed nickel-positive reaction in 30% of the subjects. Self-reported prevalence of nickel allergy as indicated by the two respective questions was 40% and 35%. Positive predictive values for the two questions were 59% (95% CI 50–67) and 60% (95% CI 51–69). History of childhood eczema was over-represented among women with ‘false-positive’ self-reported nickel allergy (P = 0.008). Self-reported hand eczema or ‘high wet exposure’ did not influence the validity.Conclusions: The validity of self-reported nickel allergy is low. The questions regarding nickel allergy overestimate the true prevalence of nickel allergy.
39.	Kalle, Martina, et al. (författare) A Peptide of Heparin Cofactor II Inhibits Endotoxin-Mediated Shock and Invasive Pseudomonas aeruginosa Infection. 2014 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7 Tidskriftsartikel (refereegranskat)abstract Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.
40.	Papareddy, Praveen, et al. (författare) Antimicrobial Effects of Helix D-derived Peptides of Human Antithrombin III 2014 Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 289:43, s. 29790-29800 Tidskriftsartikel (refereegranskat)abstract Background: Antithrombin III (ATIII), an antiproteinase-inhibiting coagulation, was investigated for roles in host defense. Results: Extensive proteolysis of ATIII by endogenous and bacterial enzymes generated antimicrobial activity, mapped to helix D of the molecule. Conclusion: ATIII harbor cryptic host defense epitopes released during proteolysis. Significance: The results explain previously observed antimicrobial and anti-inflammatory effects of ATIII supplementation during infection. Antithrombin III (ATIII) is a key antiproteinase involved in blood coagulation. Previous investigations have shown that ATIII is degraded by Staphylococcus aureus V8 protease, leading to release of heparin binding fragments derived from its D helix. As heparin binding and antimicrobial activity of peptides frequently overlap, we here set out to explore possible antibacterial effects of intact and degraded ATIII. In contrast to intact ATIII, the results showed that extensive degradation of the molecule yielded fragments with antimicrobial activity. Correspondingly, the heparin-binding, helix d-derived, peptide FFFAKLNCRLYRKANKSSKLV (FFF21) of human ATIII, was found to be antimicrobial against particularly the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Fluorescence microscopy and electron microscopy studies demonstrated that FFF21 binds to and permeabilizes bacterial membranes. Analogously, FFF21 was found to induce membrane leakage of model anionic liposomes. In vivo, FFF21 significantly reduced P. aeruginosa infection in mice. Additionally, FFF21 displayed anti-endotoxic effects in vitro. Taken together, our results suggest novel roles for ATIII-derived peptide fragments in host defense.
41.	Pasupuleti, Mukesh, et al. (författare) Antimicrobial activity of a C-terminal peptide from human extracellular superoxide dismutase 2009 Ingår i: BMC research notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 2, s. 136- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Antimicrobial peptides (AMP) are important effectors of the innate immune system. Although there is increasing evidence that AMPs influence bacteria in a multitude of ways, bacterial wall rupture plays the pivotal role in the bactericidal action of AMPs. Structurally, AMPs share many similarities with endogenous heparin-binding peptides with respect to secondary structure, cationicity, and amphipathicity. FINDINGS: In this study, we show that RQA21 (RQAREHSERKKRRRESECKAA), a cationic and hydrophilic heparin-binding peptide corresponding to the C-terminal region of extracellular superoxide dismutase (SOD), exerts antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis and Candida albicans. The peptide was also found to induce membrane leakage of negatively charged liposomes. However, its antibacterial effects were abrogated in physiological salt conditions as well as in plasma. CONCLUSION: The results provide further evidence that heparin-binding peptide regions are multifunctional, but also illustrate that cationicity alone is not sufficient for AMP function at physiological conditions. However, our observation, apart from providing a link between heparin-binding peptides and AMPs, raises the hypothesis that proteolytically generated C-terminal SOD-derived peptides could interact with, and possibly counteract bacteria. Further studies are therefore merited to study a possible role of SOD in host defence.
42.	Pasupuleti, Mukesh, et al. (författare) Antimicrobial activity of human prion protein is mediated by its N-terminal region 2009 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10, s. e7358- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Cellular prion-related protein (PrP(c)) is a cell-surface protein that is ubiquitously expressed in the human body. The multifunctionality of PrP(c), and presence of an exposed cationic and heparin-binding N-terminus, a feature characterizing many antimicrobial peptides, made us hypothesize that PrP(c) could exert antimicrobial activity. METHODOLOGY AND PRINCIPAL FINDINGS: Intact recombinant PrP exerted antibacterial and antifungal effects at normal and low pH. Studies employing recombinant PrP and N- and C-terminally truncated variants, as well as overlapping peptide 20mers, demonstrated that the antimicrobial activity is mediated by the unstructured N-terminal part of the protein. Synthetic peptides of the N-terminus of PrP killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. In contrast to LL-37, however, no marked helix induction was detected for the PrP-derived peptides in presence of negatively charged (bacteria-mimicking) liposomes. PrP furthermore showed an inducible expression during wounding of human skin ex vivo and in vivo, as well as stimulation of keratinocytes with TGF-alpha in vitro. CONCLUSIONS: The demonstration of an antimicrobial activity of PrP, localisation of its activity to the N-terminal and heparin-binding region, combined with results showing an increased expression of PrP during wounding, indicate that PrPs could have a previously undisclosed role in host defense.
43.	Smirnova, Jevgenija, 1988-, et al. (författare) Associations of self-reported atopic dermatitis with comorbid conditions in adults : a population-based cross-sectional study 2020 Ingår i: BMC Dermatology. - : BioMed Central (BMC). - 1471-5945. ; 20:1 Tidskriftsartikel (refereegranskat)abstract Background: The objective of this study was to investigate the relationships between atopic dermatitis (AD) and other common chronic health conditions in adults.Methods: A cross-sectional survey was sent to a randomly selected population sample of 78,004 adults in Sweden. The questionnaires included measures of self-reported physical and mental health. Binary and multinomial logistic regression were used to examine the associations of AD with common chronic health conditions and psychological wellbeing.Results: AD was self-reported by 4,175 respondents, representing almost 14% of the study population of 34,313 adults. Our results showed positive associations between AD and chronic health disorders, including conditions of the oral cavity: chronic obstructive pulmonary disease (adjusted odds ratio [aOR] = 1.58, 95% confidence interval [CI]: 1.30 to 1.92), asthma (aOR = 2.13, 95% CI: 1.91 to 2.38), mild recurrent gastrointestinal symptoms (adjusted relative risk ratio [aRRR] = 1.78, 95% CI: 1.64 to 1.92), high blood pressure (aOR = 1.16, 95% CI: 1.06 to 1.26), obesity (aOR = 1.34, 95% CI: 1.23 to 1.47), mild joint pain (aRRR = 1.47, 95% CI: 1.35 to 1.61), mild headache or migraine (aRRR = 1.50, 95% CI: 1.38 to 1.64), caries (aOR = 1.25, 95% CI: 1.04 to 1.49), bleeding gums (aOR = 1.69, 95% CI: 1.38 to 2.08), periodontitis (aOR = 1.42, 95% CI: 1.13 to 1.77), sensitive teeth (aOR = 1.57, 95% CI: 1.35 to 1.82), and dry mouth (aOR = 1.52, 95% CI: 1.33 to 1.74). Adjustment for asthma and depression attenuated the magnitude of the associations between AD and the study outcomes. AD was also associated with poorer general psychological wellbeing.Conclusions: Adults reporting AD may be at increased risk of chronic disorders and decreased psychological wellbeing. Physicians should recognize that individuals with severe AD and those with comorbid asthma or depression may be especially vulnerable.
44.	Sonkoly, Enikö, et al. (författare) Protein kinase C-dependent upregulation of miR-203 induces the differentiation of human keratinocytes 2010 Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 130:1, s. 124-134 Tidskriftsartikel (refereegranskat)abstract Terminal differentiation of keratinocytes is a multistep process that requires a coordinated program of gene expression. We aimed to explore the possible involvement of a previously unreported class of non-coding RNA genes, microRNAs (miRNAs) in keratinocyte differentiation by using miRNA expression profiling. Out of 365 miRNAs tested, 7 showed significant change between keratinocytes cultured in low or high calcium concentration. The highest-ranked upregulated gene was miR-203, whose expression was significantly upregulated in response to calcium and other inducers of keratinocyte differentiation such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and vitamin D(3). Differentiation-induced upregulation of miR-203 expression was blocked by treatment with specific inhibitors of protein kinase C (PKC), GF109203X, and Ro31-8220. Moreover, our results showed that the activator protein-1 (AP-1) proteins c-Jun and JunB regulate miR-203 expression in keratinocytes. In contrast to inducers of keratinocyte differentiation, epidermal growth factor and keratinocyte growth factor suppressed miR-203 expression in keratinocytes below the basal level. Overexpression of miR-203 in keratinocytes resulted in enhanced differentiation, whereas inhibition of miR-203 suppressed calcium-induced terminal differentiation as judged by involucrin expression. These results suggest that upregulation of miR-203 in human keratinocytes is required for their differentiation and is dependent on the activation of the PKC/AP-1 pathway.
45.	Wallentin, Lars, et al. (författare) Swedish work with national guidelines can become an international model. With perspectives from cardiovascular diseases guidelines : Svenskt arbete med nationella riktlinjer kan bli internationellt föredöme. Med perspektiv från riktlinjerna vid hjärtsjukdom. 2008 Ingår i: Läkartidningen. - 0023-7205. ; 105:16, s. 1194-7 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
46.	Jin, Yuesheng, et al. (författare) Clonal chromosome abnormalities in premalignant lesions of the skin. 2002 Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 136:1, s. 48-52 Tidskriftsartikel (refereegranskat)abstract Two lesions, actinic keratosis (AK) and squamous cell carcinoma in situ (CIS), are believed to be precursors of squamous cell carcinoma (SCC) of the skin. These lesions can serve as an excellent model system for studying genetic changes associated with the inception of skin SCC. In the present study, five such lesions of the skin, three AKs and two AK+CIS, from three patients were short-term cultured and analyzed cytogenetically. One of the patients (case 3) had also an SCC in addition to three premalignant lesions. All lesions, but one, showed clonal karyotypic abnormalities. The recurrent changes identified were numerical, that is, +7 and +20. The structural rearrangements found in three AK were different, but it could be noted that the distal part of the long arm of chromosome 4 was involved in two AK and the SCC of case 3A. It was also interesting that chromosome 1 participated in structural rearrangements in three AK with band 1p31 being involved in two tumors. The karyotypic profile of these lesions is compared with that of skin SCC; it turns out that the general patterns are different in the sense that the SCC more often have complex karyotypes and display unbalanced aberrations involving the centromeric regions. Some karyotypic similarities between the SCC and their precursors are revealed. The fact that the structural rearrangements involving chromosomal band 3p13 and the centromeric region of chromosome 3 in AK are common features for many types of malignant tumors, including skin SCC, indicates that these changes are early genetic events associated with malignant transformation.
47.	Lyth, Johan, et al. (författare) Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark’s level of invasion : results of a population-based study from the Swedish Melanoma Register 2013 Ingår i: British Journal of Dermatology. - : Wiley-Blackwell. - 0007-0963 .- 1365-2133. ; 168:4, s. 779-786 Tidskriftsartikel (refereegranskat)abstract Background Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed.Objectives The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark’s level of invasion for risk stratification of T1 cutaneous melanoma.Methods From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13 026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11 165 patients with complete data.Results Ulceration, tumour thickness and Clark’s level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67·9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1·5% (1·2–1·9%); an intermediate-risk group (28·6% of T1 cases) with a 10-year mortality rate of 6·1% (5·0–7·3%); and a high-risk group (3·5% of T1 cases) with a 10-year mortality rate of 15·6% (11·2–21·4%). The high- and intermediate-risk groups accounted for 66% of melanoma deaths within T1.Conclusions Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark’s level of invasion, three distinct prognostic subgroups were identified.
48.	Muth, Andreas, 1974, et al. (författare) Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma 2019 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:2, s. 187-204 Tidskriftsartikel (refereegranskat)abstract Pheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first-degree relatives (and second-degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy-catecholamines and bi-annual rapid whole-body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre-symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow-up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.
49.	Shen, Yue, 1981- (författare) Plasminogen : a novel inflammatory regulator that promotes wound healing 2013 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The plasminogen activator (PA) system has been shown to be intimately involved in wound healing. However, the role of this system in the initiation and resolution of inflammation during healing process remained to be determined. The aims of this thesis were to investigate the molecular mechanism underlying the interaction between the PA system and the inflammatory system during wound healing and to explore the therapeutic potential of plasminogen in various wound-healing models.The role of plasminogen in the inflammatory phase of the healing process of acute and diabetic wounds was studied first. Our data showed that administration of additional plasminogen to wild-type mice accelerates the healing of acute wounds. After injury, both endogenous and exogenous plasminogen are bound to inflammatory cells and are transported to the wound site, which leads to activation of inflammatory cells. In diabetic db/db mice, wound-specific accumulation of plasminogen does not take place and the inflammatory response is impaired. However, when additional plasminogen is injected, plasminogen accumulates in the wound, the inflammatory response is enhanced, the signal transduction cascade is activated and the healing rate is significantly increased. These results indicate that administration of plasminogen may be a novel therapeutic strategy to treat different types of wounds, especially chronic wounds in diabetes.The role of plasminogen at the later stage of wound healing was also studied in plasminogen-deficient mice. Our data showed that even if re-epithelialization is achieved in these mice, a prolonged inflammatory phase with abundant neutrophil accumulation and persistent fibrin deposition is observed at the wound site. These results indicate that plasminogen is also essential for the later phases of wound healing by clearing fibrin and resolving inflammation.The functional role of two physiological PAs during wound healing was further studied in a tympanic membrane (TM) wound-healing model. Our data showed that the healing process was clearly delayed in urokinase-type PA (uPA)-deficient mice but not in tissue-type PA (tPA)-deficient mice. Less pronounced keratinocyte migration, abundant neutrophil accumulation and persistent fibrin deposition were observed in uPA-deficient mice. These results indicate that uPA plays a central role in the generation of plasmin during the healing of TM perforations.Finally the therapeutic potential of plasminogen in the TM wound-healing model was studied. Our data showed that local injection of plasminogen restores the ability to heal TM perforations in plasminogen-deficient mice in a dose-dependent manner. Plasminogen supplementation also potentiates healing of acute TM perforations in wild-type mice, independent of the administration method used. A single local injection of plasminogen in plasminogen-deficient mice can initiate healing of chronic TM perforations resulting in a closed TM with a continuous but rather thick outer keratinocyte layer. Three plasminogen injections lead to a completely healed TM with a thin keratinizing squamous epithelium covering a connective tissue layer that can start to reorganize and further mature to its normal appearance. In conclusion, our results suggest that plasminogen is a promising drug candidate for the treatment of chronic TM perforations in humans. Taken together, our data indicate that plasminogen is a novel inflammatory regulator that promotes wound healing.
50.	Walser, Marion, 1961, et al. (författare) Peripheral administration of bovine GH regulates the expression of cerebrocortical beta-globin, GABAB receptor 1, and the Lissencephaly-1 protein (LIS-1) in adult hypophysectomized rats. 2011 Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1532-2238. ; 21:1, s. 16-24 Tidskriftsartikel (refereegranskat)abstract Growth hormone (GH) therapy substantially improves several cognitive functions in hypopituitary experimental animals and in humans. Although a number of biochemical correlates to these effects have been characterized, there are no comprehensive analysis available examining effects of GH on the brain. Hypophysectomized female rats were given replacement therapy with cortisol and thyroxine (=hx). Subcutaneous infusions of bovine GH (bGH, henceforth designated GH) were supplied in osmotic minipumps for 6 days (=hx+GH). To evaluate whether GH normalized specific transcript expression levels in cerebral cortex, pituitary-intact rats were used as normal controls. DNA microarrays (Affymetrix) of cerebrocortical samples showed that 24 transcripts were changed by more than 1.5-fold by GH treatment in addition to being normalized by GH treatment. The expression of three selected highly regulated transcripts was confirmed by quantitative real-time polymerase chain reaction analysis. These were the GABAB receptor 1, Lissencephaly-1 protein (LIS-1), and hemoglobin b or beta-globin. A similar regulation was found for hemoglobin b also in the hippocampus. Both the GABAB receptor 1 and hemoglobin b may have importance for the previously described neuroprotective and perhaps cognitive potential of GH treatment. Altogether, these results show that short term GH treatment affects a number of transcripts in cerebral cortex with various biological functions. These transcripts represent potential novel mechanisms by which GH can interact with the brain.

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