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1.	Aalto, Anne, et al. (författare) Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis 2007 Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 48:7, s. 755-762 Tidskriftsartikel (refereegranskat)abstract Background: Borrelia infections, especially chronic neuroborreliosis ( NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging ( MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well- characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- ( with and without gadolinium), T2-, and diffusion- weighted imaging plus fluid- attenuated inversion recovery ( FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls ( no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( rho=0.83, P < 0.01) and in controls ( rho=0.61, P < 0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2- weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.
2.	Abednazari, Hossein, 1959-, et al. (författare) Hepatocyte growth factor is a better indicator of therapeutic response than C-reactive protein within the first day of treatment in pneumonia 2006 Ingår i: Chemotherapy. - : S. Karger AG. - 0009-3157 .- 1421-9794. ; 52:5, s. 260-263 Tidskriftsartikel (refereegranskat)abstract Acute bacterial infectious diseases are mostly treated empirically at admission before the culture results are available. According to the risk for serious complications in the case of therapeutic failure, it is important to evaluate the therapy results and change to a more appropriate antibiotic regime as soon as possible. In the present study, 40 patients with X-ray-verified community-acquired pneumonia were examined and blood specimens were collected before and within 24 h of treatment. Body temperature, C-reactive protein (CRP) and hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an appropriate initial antibiotic therapy regarding clinical outcome, but in 8 patients the treatment was changed because of therapy failure. Changes of HGF levels after 18–24 h of treatment could predict the therapeutic results accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive likelihood ratio 16.0). HGF was significantly better to predict therapy outcome than CRP (p < 0.0001).
3.	Almgren, Matilda, et al. (författare) Fatigue after heart transplantation - a possible barrier to self-efficacy 2021 Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 35:4, s. 1301-1308 Tidskriftsartikel (refereegranskat)abstract Rationale Recovery after heart transplantation is challenging and many heart recipients struggle with various transplant-related symptoms, side-effects of immunosuppressive medications and mental challenges. Fatigue has been reported to be one of the most common and distressing symptoms after heart transplantation and might therefore constitute a barrier to self-efficacy, which acts as a moderator of self-management. Aim To explore the prevalence of fatigue and its relationship to self-efficacy among heart recipients 1-5 years after transplantation. Research method An explorative cross-sectional design, including 79 heart recipients due for follow-up 1-5 years after transplantation. Three different self-assessment instruments were employed; The Multidimensional Fatigue Inventory-19, Self-efficacy for managing chronic disease 6-Item Scale and The Postoperative Recovery Profile. Ethical approval The study was approved by the Regional Ethics Board of Lund (Dnr. 2014/670-14/10) with supplementary approval from the Swedish Ethical Review Authority (Dnr. 2019-02769). Results The reported levels of fatigue for the whole group were moderate in all dimensions of the Multidimensional Fatigue Inventory-19, with highest ratings in the General Fatigue sub-scale. Those most fatigued were the groups younger than 50 years; pretransplant treatment with Mechanical Circulatory Support; not recovered or had not returned to work. Self-efficacy was associated with the sub-dimensions Mental Fatigue (rho = -0 center dot.649) and Reduced Motivation (rho = -0 center dot 617), which explained 40 center dot 1% of the variance when controlled for age and gender. Study limitations The small sample size constitutes a limitation. Conclusions The moderate levels of fatigue reported indicate that it is not a widespread problem. However, for those suffering from severe fatigue it is a troublesome symptom that affects the recovery process and their ability to return to work. Efforts should be made to identify those troubled by fatigue to enable sufficient self-management support.
4.	Almgren, Matilda, et al. (författare) Self-efficacy, recovery and psychological wellbeing one to five years after heart transplantation: a Swedish cross-sectional study 2021 Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 20:1, s. 34-39 Tidskriftsartikel (refereegranskat)abstract Background Self-efficacy refers to a person ' s confidence in carrying out treatment-related activities and constitutes the foundation of self-management as well as long-term follow-up after heart transplantation. Exploring the heart recipients ' experiences by means of self-report instruments provides healthcare professionals with valuable information on how to supply self-management support after heart transplantation. Aims The aim was to explore self-efficacy in relation to the self-reported level of recovery and psychological wellbeing, among adult heart recipients, one to 5 years after transplantation. Methods This cross-sectional study includes 79 heart recipients, due for follow-up one to 5 years after transplantation. Three different self-assessment instruments were employed: the self-efficacy for managing chronic disease 6-item scale; the postoperative recovery profile; and the psychological general wellbeing instrument. Results The reported level of self-efficacy was high (median 8.3, maximum score 10). Significantly higher self-efficacy was seen among those who had returned to work (P = 0.003) and those without pre-transplant mechanical circulatory support (P = 0.033). In total, 65.5% (n = 52) reported being reasonably recovered, while 18.8% (n = 12) were not recovered. The median total psychological general wellbeing score was 108 (P-25 = 24,P-75 = 117), suggesting overall good psychological wellbeing in the whole group of heart recipients. Conclusion The heart transplant recipients in our study had an overall high level of self-efficacy. Low self-efficacy was found among those with a low self-reported level of recovery, pre-transplant treatment with mechanical circulatory support or who had not returned to work. This is important information for transplant professionals when helping heart recipients to balance their expectations about recovery.
5.	Antepohl, Wolfram, 1968-, et al. (författare) A follow-up of medical graduates of a problem-based learning curriculum 2003 Ingår i: Medical Education. - : Wiley. - 0308-0110 .- 1365-2923. ; 37:2, s. 155-162 Tidskriftsartikel (refereegranskat)abstract Introduction: There is little information available on the effects of problem-based undergraduate curricula on doctors and their performances after graduation. Therefore, we conducted a questionnaire study of all graduates of the new medical programme at the Faculty of Health Sciences, Link÷ping University. Methods: All 446 medical students who had graduated from the new programme were asked to fill in a questionnaire about selected activities during their studies and their careers after graduation. They were also asked to evaluate the quality of their undergraduate education retrospectively. Statistical analysis was performed using descriptive, multivariate and bivariate approaches. Results: A total of 77% of the graduates responded. They showed a high degree of overall contentment with their undergraduate education and felt well prepared for professional life during their preregistration period and specialist education (mean = 4.0 on a 6-point Likert scale ranging from 0 to 5). They felt especially well prepared in terms of skills for communication with patients, collaboration with other health professionals and development of critical thinking/scientific attitudes. The students' age at the beginning of their studies correlated positively with their contentment as graduates, especially in terms of preparation for patient communication and collaboration with other health professionals. No differences between students originally admitted via a local admission procedure and those admitted via a national procedure were detected concerning retrospective evaluation of undergraduate medical education. Conclusion: Graduates of the new curriculum showed a high degree of satisfaction with their undergraduate education and its preparation of them for medical practice. Specifically, they were very content with the particular emphases of the new curriculum.
6.	Asghar, Naveed, et al. (författare) Tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance. 2014 Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science (PLoS). - 1932-6203. ; 9:7 Tidskriftsartikel (refereegranskat)abstract The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A)3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A)3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the re-sequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.
7.	Bjuremark, Anna, 1950-, et al. (författare) En orientering i det akademiska riket 1998 Ingår i: Läkare, doktor, kvinna. - Lund : Studentlitteratur. - 9144009798 Bokkapitel (populärvet., debatt m.m.)
8.	Brodszki, Nicholas, et al. (författare) Swedish guidelines for the assessment, diagnosis and management of 6 primary immunodeficiency states : CVID, IgG subclass deficiency, IgA deficiency, XLA, SCID and CGD 2008 Ingår i: CLINICAL AND EXPERIMENTAL IMMUNOLOGY,ISSN 0009-9104. ; 154, s. 140-141 Konferensbidrag (refereegranskat)
9.	Carlströmer Berthén, Nellie, et al. (författare) The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finland 2023 Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 11:5 Tidskriftsartikel (refereegranskat)abstract The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finlandby Nellie Carlströmer Berthén 1,2,,† , Eszter Tompa 3,† , Susanne Olausson 1,2, Clara Nyberg 1, Dag Nyman 1,2, Malin Ringbom 1,4, Linda Perander 1,4, Joel Svärd 3, Per-Eric Lindgren 3,5, Pia Forsberg 3, Peter Wilhelmsson 3,5,‡, Johanna Sjöwall 3,6,‡ and Marika Nordberg 1,4,‡ 1Borrelia Research Group of the Aland Islands, 22100 Mariehamn, The Aland Islands, Finland2Bimelix AB, 22100 Mariehamn, The Aland Islands, Finland3Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linkoping University, 581 83 Linkoping, Sweden4The Aland Islands Healthcare Services, 22100 Mariehamn, The Aland Islands, Finland5Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, 551 85 Jonkoping, Sweden6Department of Infectious Diseases, Vrinnevi Hospital, 603 79 Norrkoping, SwedenAuthor to whom correspondence should be addressed.†These authors contributed equally to the study.‡These authors contributed equally to the study.Microorganisms 2023, 11(5), 1100; https://doi.org/10.3390/microorganisms11051100Received: 30 March 2023 / Revised: 17 April 2023 / Accepted: 19 April 2023 / Published: 22 April 2023(This article belongs to the Special Issue Research on Ticks and Tick-Borne Pathogens)Download Browse Figures Versions NotesArticle Views585 AbstractThe AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite.
10.	Cronhjort, Samuel, et al. (författare) The Tick-Borne Diseases STING study : Real-time PCR analysis of three emerging tick-borne pathogens in ticks that have bitten humans in different regions of Sweden and the Aland islands, Finland 2019 Ingår i: Infection Ecology & Epidemiology. - : Taylor & Francis. - 2000-8686. ; 9:1 Tidskriftsartikel (refereegranskat)abstract A milder climate has during the last decade contributed to an increased density and spreading of ixodid ticks, thus enhancing their role as emerging vectors for pathogenic microorganisms in northern Europe. It remains unclear if they contribute to the occurrence of infections caused by the bacteria Bartonella spp., Francisella tularensis subspecies holarctica and the parasite Toxoplasma gondii in Sweden and on the Åland islands, Finland. In this study, we want to improve understanding of the tick-borne transmission of these pathogens. Volunteers were recruited at primary healthcare centers. Ticks and blood samples were acquired from participants recruited in 2008 and 2009. Health questionnaires were completed, and medical records were acquired where applicable. Feeding time was estimated and screening of pathogens in the ticks was performed through real-time PCR. Ticks (n = 1849) were of mixed developmental stages: 76 larvae, 1295 nymphs, 426 adults and 52 undetermined. All analyzed ticks were considered negative for these pathogens since the CT-values were all below the detection limit for Bartonella spp. (1663 ticks), Francisella spp. (1849 ticks) and Toxoplasma gondii (1813 ticks). We assume that infections with these pathogens are caused by other transmission pathways within these regions of Sweden and the Åland islands, Finland.
11.	Dahle, L. O., et al. (författare) Problem-based medical education : development of a theoretical foundation and a science-based professional attitude 1997 Ingår i: Medical Education. - : Wiley. - 0308-0110 .- 1365-2923. ; 31:6, s. 416-424 Tidskriftsartikel (refereegranskat)abstract Problem-based learning, combined with early patient contact, integration between different subject areas, elements of multiprofessional education, and special emphasis on the development of communications skills has become the basis for the medical curriculum at the Faculty of Health Sciences in Linköping. Critics have questioned the depth of the scientific and theoretical aspects of the curriculum. Through a series of specific measures in the organization of the curriculum and examinations, and due to the pedagogical principles involved per se, our claim is that students graduating at Linköping do possess the required theoretical knowledge and a scientific attitude to the practice of medicine, at least equivalent to that obtained in a more conventional medical curriculum. One such specific measure is that all students perform one field study and two scientific studies during the course of the curriculum. An investigation of student opinions regarding the value of performing scientific projects of their own have shown that these projects have had a positive impact on the students' general scientific attitude and their willingness to engage in future scientific work. The specific skills acquired, as confirmed by oral examinations, were largely determined by the scientific nature of the chosen field of study. Our graduates have not yet progressed far enough in their careers for comparisons to be made on the basis of the Swedish Licensing Board Internship Examinations, but continuing evaluations of students, graduates and licensed doctors emerging from the curriculum will provide future evi-dence as to whether our present evaluation is correct.
12.	Dessau, Ram B, et al. (författare) Study of a Cohort of 1,886 Persons To Determine Changes in Antibody Reactivity to Borrelia burgdorferi 3 Months after a Tick Bite 2015 Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 22:7, s. 823-827 Tidskriftsartikel (refereegranskat)abstract Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi. The most frequent clinical manifestation is a rash called erythema migrans. Changes in antibody reactivity to B. burgdorferi 3 months after a tick bite are measured using enzyme-linked immunosorbent assays (ELISAs). One assay is based on native purified flagellum antigen (IgG), and the other assay is based on a recombinant antigen called C6 (IgG or IgM). Paired samples were taken at the time of a tick bite and 3 months later from 1,886 persons in Sweden and the Åland Islands, Finland. The seroconversion or relative change is defined by dividing the measurement units from the second sample by those from the first sample. The threshold for the minimum level of significant change was defined at the 2.5% level to represent the random error level. The thresholds were a 2.7-fold rise for the flagellar IgG assay and a 1.8-fold rise for the C6 assay. Of 1,886 persons, 102/101 (5.4%) had a significant rise in antibody reactivity in the flagellar assay or the C6 assay. Among 40 cases with a diagnosis of Lyme borreliosis, the sensitivities corresponding to a rise in antibodies were 33% and 50% for the flagellar antigen and the C6 antigen, respectively. Graphical methods to display the antibody response and to choose thresholds for a rise in relative antibody reactivity are shown and discussed. In conclusion, 5.4% of people with tick bites showed a rise in Borrelia-specific antibodies above the 2.5% threshold in either ELISA but only 40 (2.1%) developed clinical Lyme borreliosis.
13.	Ekerfelt, Christina, 1957-, et al. (författare) A symptomatic Borrelia-seropositive individuals display the same incidence of Borrelia-specific interferon-gamma (IFN-gamma)-secreting cells in blood as patients with clinical Borrelia infection. 1999 Ingår i: Clinical and Experimental Immunology. - 0009-9104 .- 1365-2249. ; 115, s. 498-502 Tidskriftsartikel (refereegranskat)
14.	Ekerfelt, Christina, 1957-, et al. (författare) Antibodies and T-cell reactivity to Borrelia burgdorferi in an asymptomatic population : A study of healthy blood donors in an Inland town district in the South-East of Sweden 2001 Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 33:11, s. 806-808 Tidskriftsartikel (refereegranskat)abstract To address the issue of whether Borrelia infection can be asymptomatic, blood donors with no history of borreliosis (n = 408) were screened for antibodies against Borrelia burgdorferi. Seropositive individuals (n = 17) were further investigated with respect to Borrelia-specific T-cell reactivity, using an interferon-? ELISPOT assay. Anti-Borrelia antibodies as well as Borrelia-specific T-cell responses were evident in 9 asymptomatic donors, strongly supporting a current or previous asymptomatic Borrelia infection.
15.	Ekerfelt, Christina, 1957-, et al. (författare) Lyme borreliosis in Sweden - Diagnostic performance of five commercial Borrelia serology kits using sera from well-defined patient groups 2004 Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 112:1, s. 74-78 Tidskriftsartikel (refereegranskat)abstract Five commercial Borrelia serology kits available in Sweden were evaluated and compared for their diagnostic performance in sera from clinically well-characterized patient groups. With the clinically defined groups as the gold standard, i.e. without knowledge of antibody status in serum and cerebrospinal fluid, the diagnostic performance of the kits was compared and important differences in diagnostic usefulness were found. The kits from Abbot and DAKO, that often predict clinically relevant Borrelia infection and do not detect antibodies in sera from patients without strong suspicion of Borrelia infection, were considered the most useful in the population studied. This kind of validation study is an important part of good laboratory practice and should be performed by laboratories serving patient populations with varying endemicity of Borrelia.
16.	Ekerfelt, Christina, 1957-, et al. (författare) Phenotypes indicating cytolytic properties of Borrelia-specific interferon-? secreting cells in chronic Lyme neuroborreliosis 2003 Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 145:1-2, s. 115-126 Tidskriftsartikel (refereegranskat)abstract The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-? (IFN-?), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-?. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-?-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCR?d, which both have cytolytic properties, were the main phenotypes of IFN-?-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.
17.	Esamai, Fabian, et al. (författare) A comparison of brain, core and skin temperature in children with complicated and uncomplicated malaria 2001 Ingår i: Journal of Tropical Pediatrics. - : Oxford University Press (OUP). - 0142-6338 .- 1465-3664. ; 47:3, s. 170-175 Tidskriftsartikel (refereegranskat)abstract A prospective study was carried out in which brain, core and skin temperatures were studied in children with cerebral malaria (n = 23), uncomplicated malaria (n = 12) and normal children (n = 9) using the zero heat flow method. Patients with cerebral or uncomplicated malaria were admitted to the paediatric wards (mean age, 6 years 8 months ± 2 years 8 months). Normal children, children of the investigators, of the same age group, served as controls. Parasitaemia levels were similar in the cerebral and uncomplicated malaria cases. Higher brain than core temperatures would have been expected in cerebral malaria but not in uncomplicated malaria but this was not the case in this study. There was no statistical difference in brain, core and skin temperature between cerebral and uncomplicated malaria patients. However, there was a highly significant difference between normal children and cerebral and uncomplicated malaria patients. Brain temperature was 0.02–0.2°C below core temperature in all the groups with larger differences during the febrile period. Mean differences of brain minus core, brain minus skin and core minus skin between the two groups of patients were not statistically significant. There was no correlation between temperature and the level of coma or parasitaemia for cerebral and uncomplicated malaria patients. There was a positive correlation between brain and core temperature in both groups of patients during the febrile phase. Brain temperature remained lower than core temperature in cerebral and uncomplicated malaria as in normal children. Normal thermoregulation appears to be maintained in cerebral malaria.
18.	Esamai, Fabian, et al. (författare) A comparison of core and skin temperature among normal and febrile children with cerebral malaria, uncomplicated malaria, and measles 1995 Ingår i: Pathophysiology. - 0928-4680. ; 2:1, s. 55-59 Tidskriftsartikel (refereegranskat)abstract Forty-four children were studied to compare the pathogenesis of fever in cerebral malaria, uncomplicated malaria and measles at the Eldoret District Hospital (EDH). A control group of normal children was used. The three patient groups were studied for three consecutive days measuring skin and core temperature three-times a day using the Liquid Crystal Device (LCD) thermometer. A statistical analysis of the results within and between the groups was carried out for core and skin temperature over the study period. No statistical differences were found between the groups for either the skin or the core temperature, but a significant statistical difference was demonstrated between the core and the skin temperature for all of the groups for each of the three days. No statistical difference was found when the differences between the core and skin temperature were compared between cerebral malaria and uncomplicated malaria. The possible roles of fever in morbidity and mortality are discussed, with special reference to cerebral malaria.
19.	Esamai, Fabian, et al. (författare) Cerebral malaria in children : Serum and cerebrospinal fluid TNF-α and TGF-ß levels and their relationship to clinical outcome 2003 Ingår i: Journal of Tropical Pediatrics. - : Oxford University Press (OUP). - 0142-6338 .- 1465-3664. ; 49:4, s. 216-223 Tidskriftsartikel (refereegranskat)abstract This was a prospective study conducted at the Moi Teaching and Referral Hospital, Eldoret, Kenya. Twenty‐three children admitted to the hospital with cerebral (CM) and 10 children with noncerebral malaria (NCM) were studied. The aim of the study was to establish and compare levels of tumour necrosis factor (TNF‐α) and transforming growth factor (TGF‐β1) in these children. Serum and cerebrospinal fluid (CSF) cytokine levels were assayed using ELISA kits. In serum, TGF‐β1 and TNF‐α decreased over 5 days after admission to the hospital in both groups of patients with CM and NCM. In the CSF of cerebral cases the levels of TNF‐α and TGF‐β1 were low and inversely related. Children in deeper coma had lower levels in serum of TGF‐β and higher levels of TNF‐α than those in lighter levels of coma. The serum TNF‐α levels in CM children were the same irrespective of the duration of illness before admission, but children with NCM who had been sick for a shorter duration before admission tended to have higher serum levels of TNF‐α and higher levels of TGF‐β than those with a longer duration of illness before admission. In conclusion, this study shows that TNF‐α and TGF‐β1 may not be useful in predicting the outcome for CM. They may, however, be useful in detecting children at risk of developing deep coma. TNF‐α and TGF‐β levels were inversely related both in serum and CSF.
20.	Esamai, Fabian, et al. (författare) Clinical presentation and diagnosis of cerebral malaria in children in the highlands of western Kenya 1999 Ingår i: East African Medical Journal. - 0012-835X. ; 76:2, s. 89-92 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:The clinical presentation of cerebral malaria in children in the highlands has not been documented.OBJECTIVE:To describe the presentation of cerebral malaria in the age group one to twelve years.DESIGN:Prospective study conducted from May to September 1997, the rainy season during which malaria occurs in epidemics in the highlands of Kenya.SETTING:Paediatric wards of the Moi Teaching and Referral Hospital, Eldoret which is the Teaching Hospital for Moi University and the referral centre for surrounding districts of Western Kenya, with an altitude of over 2000 metres above sea level.PATIENTS:Twenty three consecutive children aged one to twelve years with cerebral malaria as defined by the WHO were studied. All children were treated with the standard quinine regimen for cerebral malaria.RESULTS:Majority of the children were six to ten years of age with 95.7% having a normal weight for age. 91.3%, 89.5% and 72.2% had fever, headache and convulsions respectively. 68.1% had a short duration of illness (less than three days) with only 9.5% presenting with hypoglycaemia. Severe anaemia was not observed but 72% had mild to moderate anaemia. Hyperparasitaemia (parasite counts greater than 100,000 per microlitre) was found in majority of the cases.CONCLUSION:Cerebral malaria presentation in the highlands is similar to that among non-immune populations and is an acute fulminant illness presenting with coma, hyperparasitaemia, fever and convulsions in children with normal nutritional status.
21.	Forsberg, Eva, et al. (författare) Codification of present Swedish curriculum processes : linking educational activities over time and space 2015 Konferensbidrag (refereegranskat)
22.	Forsberg, Eva, 1955-, et al. (författare) Codification of Present Swedish Curriculum Processes : Linking Educational Activities over Time and Space 2017. - 1 Ingår i: Bridging Educational Leadership, Curriculum Theory and Didaktik. - Cham : Springer. - 9783319586489 - 9783319586502 ; , s. 363-393 Bokkapitel (refereegranskat)
23.	Forsberg, Eva, 1955-, et al. (författare) Codification of Present Swedish Curriculum Processes – Linking Educational Activities Over Time and Space : In session: Discursive Curriculum Leadership: Toward a Comparative, International Dialogue on Curriculum Theory and Leadership Research. Invited speaker. AERA Conference in Ontario, US. 2015 Konferensbidrag (refereegranskat)
24.	Forsberg, Eva, et al. (författare) Commodification of Present Swedish Processes : Linking Educational Experiences Over Time and Space 2017 Konferensbidrag (refereegranskat)abstract Objectives or purpose. In Sweden and other Nordic countries the formation of educational systems has primarily been an issue for the national state in a rather homogenous society. Today, governance of education is embedded in global movements and a multicultural society influencing the role and function of the state. We will use two empirical cases, based in three recently completed research projects, to illuminate how curriculum and leadership research have worked in tandem to explain and develop both policy and practice. The cases focus on the assessment culture of the Swedish schools and implications of changes in governance for local educational leadership.Perspectives or theoretical framework. In the Swedish curriculum theory tradition, the curriculum has been analyzed as a pedagogical, a political, a practical and research problem. In order to analyze data and develop curriculum and leadership research the central concept of curriculum code (Lundgren 1977) is further elaborated. We pay attention to different levels, actors and contexts in an era dominated by governance, new public management, accountability and international comparative tests. With mass education from preschool to higher education, marketization and an increasing number of stakeholders the complexity of education governance has also increased and curriculum processes have taken new forms. Lundgren elaborated the concepts of steering group, codes and contexts. Codes relate to the purpose, content and method of a curriculum. He raised questions on how the frames were constituted, and identified historically developed curriculum codes manifested in the selection and organization of school knowledge (e.g. Lundgren, 1977). Shifts in codes were related to changed relations between production and reproduction (Lundgren, 1983); neither the purposes of education nor the subject content were taken for granted.Methods. In a recent empirical study, we used questionnaires, interviews and policy texts with analyses grounded in both curriculum theory and leadership research. The empirical base is Sweden from the late 1980s up until today, a highly reform intense period. Findings are presented, focusing especially on governance, leadership and assessment cultures. We include comparative studies and studies covering all 290 Swedish municipalities using both surveys and case studies.Results and/or substantiated conclusions. By using empirical findings from projects relating curriculum activities taking place on different levels with a focus on interlinked curriculum processes, we discuss these processes and further develop contemporary curriculum theory. We address conceptual issues on curriculum making including educational leadership as practice and actors. By linking research on curriculum theory with leadership studies, it is possible to attend to these problems simultaneously.Scientific or scholarly significance. In conclusion, this paper is scanning new horizons for how to develop curriculum theory further as a relational practice appearing in various contexts. Specifically, we posit a new code to explain the contemporary situation for curriculum-leadership.
25.	Forsberg, Eva, 1955-, et al. (författare) Curriculum Code, Arena, and Context : Curriculum and Leadership Research in Sweden 2017 Ingår i: Leadership and Policy in Schools. - : Routledge. - 1570-0763 .- 1744-5043. ; 16:2, s. 357-382 Tidskriftsartikel (refereegranskat)abstract This article describes the development of the Swedish curriculum-theory tradition with a focus on different curriculum practices, educational message systems, arenas, and curriculum makers. Attention has been paid to different places, spaces, and times in relation to the selection, ordering, and manifestation of knowledge, norms, and values, as well as the management and organization of education. Curriculum and leadership research and changes in Swedish education are described and we introduce the comparative curriculum code as a codification of the contemporary changes in the education system and their consequences for the selection and ordering of knowledge and students.
26.	Forsberg, Maria, 1973-, et al. (författare) Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils 2003 Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 74:4, s. 611-619 Tidskriftsartikel (refereegranskat)abstract Phagocytosis is a complex process engaging a concerted action of signal-transduction cascades that leads to ingestion, subsequent phagolysosome fusion, and oxidative activation. We have previously shown that in human neutrophils, C3bi-mediated phagocytosis elicits a significant oxidative response, suggesting that activation of the small GTPase Rac is involved in this process. This is contradictory to macrophages, where only Fc receptor for immunoglobulin G (FcγR)-mediated activation is Rac-dependent. The present study shows that engagement of the complement receptor 3 (CR3) and FcγR and CR3- and FcγR-mediated phagocytosis activates Rac, as well as Cdc42. Furthermore, following receptor-engagement of the CR3 or FcγRs, a downstream target of these small GTPases, p21-activated kinase, becomes phosphorylated, and Rac2 is translocated to the membrane fraction. Using the methyltransferase inhibitors N-acetyl-S-farnesyl-L-cysteine and N-acetyl-S-geranylgeranyl-L-cysteine, we found that the phagocytic uptake of bacteria was not Rac2- or Cdc42-dependent, whereas the oxidative activation was decreased. In conclusion, our results indicate that in neutrophils, Rac2 and Cdc42 are involved in FcR- and CR3-induced activation and for properly functioning signal transduction involved in the generation of oxygen radicals.
27.	Forsberg, Pia, et al. (författare) Appraisal of the "Draft Programme for European Social Fund Objective 4, 1995-1999" submitted by the Kingdom of Sweden 1995 Rapport (övrigt vetenskapligt/konstnärligt)
28.	Forsberg, Pia, 1949- (författare) Fästingöverförda infektioner i Sverige 2004 Ingår i: Infektionsmedicin. - : Säve Förlag. - 9197268976 - 9789197268974 ; , s. 378-382 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract Denna klassiska lärobok kom 2011 ut i sin 5:e, omarbetade upplaga. Boken innehåller 28 kapitel, vilka täcker hela infektionspanoramat, från influensa till AIDS. Samtliga författare är läkare och flertalet universitetslärare. Den innehåller även 16 sidor färgplanscher med fotoillustrationer av olika sjukdomar. Boken är avsedd att användas i undervisningen av blivande läkare och som uppslagsbok i sjukvården.
29.	Forsberg, Per-Olof, et al. (författare) In vitro phosphorylation of human complement factor C3 by protein kinase A and protein kinase C : Effects on the classical and alternative pathways 1990 Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 265:5, s. 2941-2946 Tidskriftsartikel (refereegranskat)abstract Complement factor C3, recently found to contain covalently bound phosphate, was phosphorylated in vitro by cyclic AMP-dependent protein kinase (protein kinase A) and Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C). Both protein kinases phosphorylated the same serine residue(s) located in the C3a portion of the alpha-chain. In addition, protein kinase C phosphorylated the beta-chain to a lesser extent. Protein kinase A gave a maximal incorporation of 1 mol of phosphate/mol of C3 while that value with protein kinase C was 1.5 mol of phosphate/mol of C3. The velocity in pmol of [32P]phosphate/(min x unit kinase) was 20 times higher for protein kinase C than for protein kinase A although a 10 times lower ratio of protein kinase to C3 was used in the former case. The apparent Kmfor C3 was 2.6 µM when protein kinase C was used. The phosphorylated C3 was found to be more resistant to partial degradation by trypsin than unphosphorylated C3. It was also found that phosphorylation of C3 in the C3a portion of the alpha-chain inhibited both the classical and alternative complement activation pathways on an approximately stoichiometric basis.
30.	Forsberg, Pia, et al. (författare) Strategies and attitudes towards the older work-force among Swedish Firms. Some data from a 1995 survey on the employment patterns and policies towards the older work-force in 380 Swedish Firms 1996 Rapport (övrigt vetenskapligt/konstnärligt)
31.	Forsberg, Pia, et al. (författare) The controversy growth. A debate between economists and sociologists about the Swedish public sector 2007 Ingår i: Sociologisk Forskning. - 2002-066X. ; :3, s. 53-53 Tidskriftsartikel (refereegranskat)abstract Has the 'Swedish model' forced Sweden into stagnating economic growth? And has this caused Sweden to lag behind other comparable OECD-countries from the 1970s and onwards, i.e. since Sweden chose a welfare path different from many other countries? This has been the subject of a more than twenty year long controversy between Walter Korpi, professor of sociology and social policy, and leading Swedish mainstream economists. In a series of articles, especially during the years of economic crisis in the 1990s, Walter Korpi claimed that other reasons than the Swedish model has to be taken into account when comparing welfare states and their impact on economic growth, while the economists have persistently maintained the opposite view. These disputes over statistics and methodology have developed into what is here referred to as a science based controversy. This article analyzes the controversy between sociology and economy in accordance with controversy theory. In this way we can consider both the underlying social as well as political aspects of the debate, which leads to the conclusion that not every aspect of a science-based controversy is a by product of science itself
32.	Forsberg, Pia (författare) Tillväxt som kontrovers : Ekonomers och sociologers debatt om den svenska offentliga sektorn 2007 Ingår i: Sociologisk forskning. - : Sveriges sociologförbund. - 0038-0342 .- 2002-066X. ; 44:3, s. 52-74 Tidskriftsartikel (refereegranskat)abstract The controversy of growth: a debate between economists and sociologists about the Swedish public sectorHas the ‘Swedish model’ forced Sweden into stagnating economic growth? And has this caused Sweden to lag behind other comparable OECD-countries from the 1970s and onwards, i.e. since Sweden chose a welfare path different from many other countries? This has been the subject of a more than twenty year long controversy between Walter Korpi, professor of sociology and social policy, and leading Swedish mainstream economists. In a series of articles, especially during the years of economic crisis in the 1990s, Walter Korpi claimed that other reasons than the Swedish model has to be taken into account when comparing welfare states and their impact on economic growth, while the economists have persistently maintained the opposite view. These disputes over statistics and methodology have developed into what is here referred to as a science based controversy. This article analyzes the controversy between sociology and economy in accordance with controversy theory. In this way we can consider both the underlying social as well as political aspects of the debate, which leads to the conclusion that not every aspect of a science-based controversy is a byproduct of science itself.
33.	Forsberg, Pia (författare) Valfrihet och välfärd. En diskussion och analys av det liberala valfrihetsbegreppet 1993 Ingår i: Sociologisk forskning. - : Sveriges Sociologförbund. - 0038-0342 .- 2002-066X. ; 30:2, s. 59-78 Tidskriftsartikel (refereegranskat)abstract Freedom of choice and welfare. A discussion and analysis of the neo-liberal concept of freedom of choiceSweden is today witnessing large changes within its welfare sector which has been driven through by the present government. In this paper the ideological basis for the present politics is regarded as constituting two apparent contradictory demands. On the one hand there is the demand for “more family” and on the other, the demand for “more market". This paradox by the government can be solved by the use of the vague concept “freedom of choice”. This paper is an attempt to formulate and understand the concept, that is, to analyse its meaning and social consequences. The government’s key strategy is to make the “welfare-consumer” vote with his/her feet and to leave one service for another, so in this way they can express preferences on a market. By doing so they will not only become more satisfied themselves, but they can also exercise influence over the whole institution. Subsequently the “invisible hand” will automatically create efficency and quality. This paper argues that to properly understand the possibilities of and obstacles to a more substantial freedom of choice within social welfare, it is necessary to proceed from the characterstic distinguishing qualities of different services. This is illustrated by a comparison between the dental service and child care. It is less complicated to replace one dentist for another, than to break down the interwoven ties between a child, a parent and an institution because the choice in the second case is more socially embedded and restricted. It is the governments intention to reduce political influence over welfare production and increase the power of markets and economic steering, i.e . to encourage influence and steering by “exit” instead of “voice” (Hirschman 1972) which they believe will increase the individuals freedom of choice. This is a much more complicated matter than is generally agreed by the government, and implies social consequences which it has not taken into account.
34.	Fryland, Linda, et al. (författare) Biomarkers in blood a few days after a bite by a Borrelia burgdorferi infected tick: : Asymptomatic Borrelia burgdorferi-infected subjects show higher Th1-associated response compared with subjects who later develop Lyme borreliosis 2012 Annan publikation (övrigt vetenskapligt/konstnärligt)abstract The clinical outcome following infection with Borrelia (B.) burgdorferi sensu lato (s.l.) differs between individuals, ranging from asymptomatic infection to Lyme borreliosis (LB) with persistent symptoms post-treatment. Previous studies in mice and humans have generated the hypothesis that a successful outcome of B. burgdorferi s.l. infection is associated with an early strong pro-inflammatory T helper (Th)1-like immune response. The aim of this study was to assess the early course of events in B. burgdorferi s.l.-associated inflammation by screening for possible early immune biomarkers in peripheral blood from newly tick-bitten persons. The study subjects bitten by B. burgdorferi s.l.-infected ticks were divided into (1) those later developing clinical LB, (2) those who developed anti-B. burgdorferi s.l. antibodies but not clinical LB, (3) those who neither developed antibodies nor clinical LB. A fourth group consisted of bitten study subjects without development of antibodies or clinical LB. Two sets of samples, both comprising all four groups, were collected in order to repeat the analyses and confirm the data. Sera or plasma collected a few days after the tick bite were analysed for 18 biomarkers (IL-1β, IL-6, CXCL8/IL-8, IL-12p70, IL-17A, IL-27, TNF, CCL18, CCL20, CCL22, CXCL1, CXCL9, CXCL10, CXCL11, calprotectin, MMP-3, MMP-8, MMP-9) by multiplex bead assay and ELISA. In the first set of samples, the neutrophil activation marker calprotectin was increased in subjects who developed clinical LB compared with subjects who developed antibodies against B. burgdorferi s.l. but did not develop LB. However, the finding could not be confirmed in the second set of samples, thus the study failed to identify an early prognostic marker for development of clinical LB. Interestingly, both sets of samples showed increases in two different Th1-associated markers, CXCL10 and IL-12p70, respectively, in subjects who following a bite by a B. burgdorferi s.l.-infected tick developed antibodies against B. burgdorferi s.l. but did not develop LB compared with subjects who developed clinical LB, thus supporting the hypothesis of an early strong Th1-response being important for optimal resolution of B. burgdorferi s.l. infection.
35.	Fryland, Linda (författare) Immune mechanisms in Borrelia burgdorferi sensu lato infection in relation to clinical outcome 2013 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Lyme borreliosis (LB) is the most common tick-borne disease in the northern hemisphere. The infection is caused by spirochaetes from the Borrelia (B.) burgdorferi sensu lato (s.l.) group. The clinical outcome after B. burgdorferi s.l. infection differs between individuals from asymptomatic infection without history of LB to individuals who experience persistent symptoms post-treatment for more than six months after treatment. The difference in clinical outcome is not thought to be associated with persistent infection, but could instead be affected by the host’s ability to mount an optimal immune response to the spirochaete.The hypothesis of this thesis was that a strong inflammatory Th1-like immune response is required in the early stage of infection in order to achieve both an optimal eradication of the B. burgdorferi s.l. bacteria and a good clinical outcome. The inflammatory response must be down-regulated by an anti-inflammatory response in order to avoid excessive immune responses that will end in tissue injury. The proper down-regulation will also protect against development of a chronic Th1-like inflammatory response, with activated cytotoxic cells, which may lead to LB with persistent symptoms post-treatment.The thesis aimed to investigate the immunological mechanisms behind the optimal resolution of human B. burgdorferi s.l. infection and to define the aberrant mechanisms leading to development of persisting symptoms.prospective study on newly tick-bitten individuals showed that although 25% of the collected ticks were infected with B. burgdorferi s.l. very few individuals bitten by infected ticks developed LB (3.7%). In addition, 4.9% of the individuals bitten by infected ticks developed asymptomatic infection, i.e. B. burgdorferi s.l.-specific antibody seroconversion without LB. Approximately one third of all tick-bitten study subjects reported self-experienced symptoms possibly associated with LB. Individuals bitten by infected ticks were more likely to report experience of symptoms than those bitten by uninfected ticks. Thus, only 8.6% of the individuals bitten by B. burgdorferi s.l.-infected ticks were infected, verified by seroconversion, and out of them 57% were asymptomatic.A prospective study on EM patients showed that a good clinical outcome was associated with a strong early Th1 immune response since EM patients with persistent symptoms six months after treatment had reduced expression of Th1 cytokines in their EM lesions compared with EM patients without symptoms.The investigation of blood samples from newly tick-bitten individuals, for detection of possible early immune biomarkers indicating good clinical outcome of LB, showed that none of the investigated markers clearly discriminated between the individuals who developed LB, asymptomatic individuals, or non-infected individuals. However, tick-bitten individuals who developed asymptomatic infection showed an increase of early Th1-associated biomarkers in blood compared to individuals who developed clinical LB.In an experimental study, Th2-immune-deviated mice had more pronounced clinical signs of infection and could not eradicate the spirochaete as efficiently as non-deviated B. burgdorferi sensu stricto (s.s.)-infected mice. Non-deviated B. burgdorferi s.s.-infected mice showed a decrease of mRNA expression associated with Th2, anti-inflammatory and Treg/Th1 responses during the course of infection, which suggested a termination of the inflammatory response – something that was not seen in the immune-deviated mice. Trends for increased expression of pro-inflammatory GM-CSF and Treg marker Foxp3 in immune-deviated mice suggested on-going inflammation. Non-deviated B. burgdorferi s.s.-infected mice showed increased systemic expression of the Th1-associated CXCL9 and CXCL10 during the course of infection, while immune-deviated mice showed an initial decrease in both chemokines at day 15 p.i. compared with day 0 p.i.In conclusion, the risk of developing LB after a tick bite is low, and no infection or asymptomatic infection are the most common outcomes after a tick bite. The early immune response in humans and the immune response towards B. burgdorferi s.s. infection in mice support the hypothesis that a strong pro-inflammatory Th1 response is needed for an optimal clinical outcome and eradication of bacteria.
36.	Fryland, Linda, et al. (författare) Low risk of developing Borrelia burgdorferi infection in the south-east of Sweden after being bitten by a Borrelia burgdorferi-infected tick 2011 Ingår i: INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES. - : Elsevier Science B. V., Amsterdam. - 1201-9712. ; 15:3, s. E174-E181 Tidskriftsartikel (refereegranskat)abstract Objectives: The risk of developing Lyme borreliosis (LB) from Borrelia burgdorferi sensu lato (Bb)-infected ticks in Sweden is largely unknown. In the current study, we investigated the prevalence of Bb in ticks that had bitten humans and the risk of developing LB from Bb-infected ticks. Methods: Health questionnaires, blood samples, and ticks were collected from 394 tick-bitten study subjects in the County of Ostergotland, Sweden, at the time of the tick bite. Questionnaires and blood samples were also collected 3 months later. Ticks were screened for Bb DNA with PCR, while sera were analyzed for antibodies against Bb using two ELISA assays. Seroconversion, i.e., an at least two-fold increase in anti-Bb antibodies after 3 months, was confirmed using a Strip-Immunoassay. Results: Seventy-five of 397 ticks collected from the study subjects were determined to be Bb-positive. Sixty-four of the tick-bitten subjects had been bitten by Bb-infected ticks. Four of them showed seroconversion and were therefore considered to have an active Bb infection. None of these four subjects had sought health care due to symptoms, but one reported symptoms. Conclusions: Our data suggest that the risk of developing LB after being bitten by a Bb-infected tick is low, and asymptomatic Bb infections appear to be more frequent than symptomatic infections.
37.	Grankvist, Anna, et al. (författare) Infections with Candidatus Neoehrlichia mikurensis and Cytokine Responses in 2 Persons Bitten by Ticks, Sweden 2015 Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 21:8, s. 1462-1465 Tidskriftsartikel (refereegranskat)abstract The prevalence of Candidatus Neoehrlichia mikurensis infection was determined in 102 persons bitten by ticks in Sweden. Two infected women had erythematous rashes; 1 was co-infected with a Borrelia sp., and the other showed seroconversion for Anaplasma phagocytophilum. Both patients had increased levels of Neoehrlichia DNA and serum cytokines for several months.
38.	Gyllemark, Paula, et al. (författare) Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis : a large retrospective study. 2017 Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 14:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated.METHODS: We analysed a set of cytokines and chemokines associated with B cell and Th17 immunity in cerebrospinal fluid and serum from clinically well-characterized patients with definite Lyme neuroborreliosis (group 1, n = 49), defined by both cerebrospinal fluid pleocytosis and Borrelia-specific antibodies in cerebrospinal fluid and from two groups with possible Lyme neuroborreliosis, showing either pleocytosis (group 2, n = 14) or Borrelia-specific antibodies in cerebrospinal fluid (group 3, n = 14). A non-Lyme neuroborreliosis reference group consisted of 88 patients lacking pleocytosis and Borrelia-specific antibodies in serum and cerebrospinal fluid.RESULTS: Cerebrospinal fluid levels of B cell-associated markers (CXCL13, APRIL and BAFF) were significantly elevated in groups 1, 2 and 3 compared with the reference group, except for BAFF, which was not elevated in group 3. Regarding Th17-associated markers (IL-17A, CXCL1 and CCL20), CCL20 in cerebrospinal fluid was significantly elevated in groups 1, 2 and 3 compared with the reference group, while IL-17A and CXCL1 were elevated in group 1. Patients with time of recovery <3 months had lower cerebrospinal fluid levels of IL-17A, APRIL and BAFF compared to patients with recovery >3 months.CONCLUSIONS: By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment.
39.	Gyllemark, Paula, et al. (författare) Intrathecal Th17-driven inflammation is associated with prolonged post-treatment convalescence for patients with Lyme neuroborreliosis 2023 Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Lyme neuroborreliosis (LNB) is associated with increased levels of pro-inflammatory cytokines and chemokines in the cerebrospinal fluid (CSF). Residual symptoms after antibiotic treatment can have deleterious effects on patients and knowledge regarding the pathogenesis linked to prolonged recovery is lacking. In this prospective follow-up study, we investigated the B cell-associated and T helper (Th) cell-associated immune responses in well-characterized patients with LNB and controls. The aims were to assess the kinetics of selected cytokines and chemokines involved in the inflammatory response and to identify potential prognostic markers. We investigated 13 patients with LNB according to a standardized clinical protocol before antibiotic treatment and after 1, 6 and 12 months of follow-up. CSF and blood samples were obtained at baseline and after 1 month. As controls, we used CSF samples from 37 patients who received spinal anesthesia during orthopedic surgery. The CSF samples were analyzed for CXCL10 (Th1-related), CCL22 (Th2-related) and IL-17A, CXCL1 and CCL20 (Th17-related), as well as for the B cell-related cytokines of a proliferation-inducing ligand (APRIL), B cell-activating factor (BAFF) and CXCL13. The CSF levels of all the cytokines and chemokines, with the exception of APRIL, were significantly higher at baseline in patients with LNB compared with controls. All the cytokines and chemokines, except for IL-17A were significantly reduced at 1-month follow-up. Patients with quick recovery (< 1 month, n = 3) had significantly lower levels of CCL20 at baseline and lower levels of IL-17A at 1-month follow-up. Patients with time of recovery > 6 months (n = 7) had significantly higher levels of IL-17A at the one-month follow-up. No other cytokines or chemokines were associated with prolonged recovery. Dominating residual symptoms were fatigue, myalgia, radiculitis and/or arthralgia. In this prospective follow-up study of patients with LNB, we found significantly lower levels of CCL20 in those who recovered rapidly, and increased levels of IL-17A in patients with delayed recovery post-treatment. Our findings indicate persistent Th17-driven inflammation in the CSF, possibly contributing to a longer convalescence, and suggest IL-17A and CCL20 as potential biomarker candidates for patients with LNB.
40.	Gyllemark, Paula, 1975- (författare) Tick-borne diseases and the central nervous system : clinical and immunological aspects 2023 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Lyme neuroborreliosis (LNB) is the dominating form of disseminated infection by the tick-borne bacteria Borrelia (B.) burgdorferi in Sweden as well as in Europe. The diagnosis of the manifestation is based on typical symptoms, together with elevated mononuclear cell count in the cerebrospinal fluid (CSF) and elevated levels of Borrelia-specific antibodies in the CSF. The diagnostic arsenal has, in recent years, been complemented by analysis of the chemokine CXCL13 in the CSF, with increasing levels in the early phase of the disease, even before antibodies can be detected in the CSF. Most patients recover within a couple of months after antibiotic treatment, but a few can suffer from residual symptoms. The mechanisms behind this are still puzzling, but there are indications that the host´s immune response may play a role. Prognostic markers would be desirable and in-creased understanding of pathogenetic mechanisms may provide a basis for development of new treatment strategies. Other agents besides B. burgdorferi have, however, also been detected in ticks collected in Sweden, but the knowledge of their impact on human health and their ability to invade the central nervous system (CNS) is limited. The aims of this thesis were to investigate a set of cytokines and chemokines associated with Th1 (CXCL10), Th2 (CCL22), Th17 (IL-17A, CXCL1, CCL20) and B cell (APRIL, BAFF, CXCL13) -related im-munity and its association with recovery in patients with LNB included both retrospectively and prospectively. The chemokine CXCL13 was further analysed, comparing the performance of two different diagnostic methods. In a large cohort of patients investigated for LNB we investigated signs of other tick-borne diseases by analysing serum and CSF using both molecular and serological techniques. In the retrospective cytokine/chemokine study, all investigated cytokines and chemokines; namely, APRIL, BAFF, CXCL13, IL-17A, CXCL1, and CCL20 could be detected at elevated levels in patients with LNB compared to controls. Patients with recovery > 3 months had higher levels of APRIL, BAFF, and IL-17A. In the prospective study, patients with short recovery (< 1 month) had lower levels of CCL20 and patients with prolonged recovery (> 6 months) had higher levels of IL-17A. The analysis of the chemokine CXCL13 with both an enzyme-linked immunosorbent assay (ELISA) with a best-performanced cut-off of 56 pg/mL and bead-based (Luminex) method with a best-performance cut-off of 158 pg/mL (both assays with 100% sensitivity and specificity) displayed the im-portance of different cut-offs depending on which method that is used.In 600 patients, we analysed serum and CSF with PCR for the different tick-borne agents Ana-plasma phagocytophilum, B. burgdorfer spp. (including B. miyamotoi), Neoehrlichia (N.) mikurensis, Rickettsia spp., Babesia spp. and tick-borne encephalitis virus. N. mikurensis and B. burgdorferi could be detected by PCR in sera from two patients. Neither PCR, nor serological analysis could detect any potential co-infections.In conclusion, we can corroborate the Th17-related immunity in the pathogenesis of LNB where IL-17A and CCL20 are plausible prognostic markers. Other tick-borne pathogens with possible dissemination to the CNS seems to be uncommon in south-eastern Sweden.
41.	Hedin Skogman, Barbro, et al. (författare) Are There Undiagnosed TBE-, Herpes- or Enteroviral Infections among Children Being Evaluated for Lyme Neuroborreliosis? 2014 Ingår i: Open Journal of Clinical Diagnostics. - : Scientific Research Publishing. - 2162-5816 .- 2162-5824. ; 4:3, s. 123-129 Tidskriftsartikel (refereegranskat)abstract Lyme neuroborreliosis (LNB) in children is a challenging diagnosis based on clinical manifestations and laboratory findings. The aim of this study was to investigate whether herpes simplex virus (HSV) 1 or 2, varicella zoster virus (VZV), enterovirus or tick-borne encephalitis virus (TBEV) could be identified in cerebrospinal fluid (CSF) or serum from children being evaluated for LNB, in order to elucidate whether such infectious diseases may be missed by the clinician. Methods: Ninety-nine pediatric patients (n = 99) were retrospectively included from a previous study on LNB in southeast of Sweden. They had been diagnosed as “Possible LNB” or “Not determined” due to negative Borrelia antibody index in CSF. Routine polymerase chain reaction (PCR) methods were used for detection of herpes viral RNA or enteroviral DNA in CSF. An ELISA assay was used for detection of anti-TBEV antibodies (IgM and IgG) in serum. Results: One patient showed elevated anti-TBEV IgM and IgG antibodies in serum, indicating a current TBE infection. No positive PCR reactions for HSV 1 or 2, VZV or enterovirus were detected in CSF from any of the patients. In conclusion, our results suggest that undiagnosed herpes- or enteroviral infections are unlikely to explain CNS symptoms in children being evaluated for LNB, whereas missed TBE infections may occur. TBEV serology should be included when evaluating children for LNB in TBE endemic areas.
42.	Hedin-Skogman, Barbro, et al. (författare) Improved Laboratory Diagnostics of Lyme Neuroborreliosis in Children 2008 Ingår i: The Pediatric Infectious Disease Journal. - 0891-3668 .- 1532-0987. ; 27:7, s. 605-612 Tidskriftsartikel (refereegranskat)abstract Background: Laboratory diagnostics in Lyme neuroborreliosis need improvement. We hereby investigate 4 new recombinant or peptide Borrelia antigens in cerebrospinal fluid in children with neuroborreliosis to evaluate their performance as diagnostic antigens. Methods: An enzyme-linked immunosorbent assay was used to detect IgG antibodies to recombinant decorin binding protein A (DbpA), BBK32, outer surface protein C (OspC), and the invariable region 6 peptide (IR6). The recombinant antigens originated from 3 pathogenic subspecies; Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi sensu stricto. Cerebrospinal fluid and serum from children with clinical features indicative for neuroborreliosis (n = 57) were analyzed. Classification of patients was based on clinical symptoms and laboratory findings. Controls were children with other neurologic diseases (n = 20) and adult patients with no proven infection (n = 16). Results: Sensitivity for DbpA was 82%, for BBK32 70%, for OspC 58% and for IR6 70%. Specificities were 94%, 100%, 97%, and 97%, respectively. No single antigen was superior. When new antigens were combined in a panel, sensitivity was 80% and specificity 100%. The reference flagella antigen showed a sensitivity of 60% and a specificity of 100%. Over all, the B. garinii related antigens dominated. Conclusions: Recombinant DbpA and BBK32 as well as the peptide antigen IR6 perform well in laboratory diagnostics of neuroborreliosis in children. New antigens seem to improve diagnostic performance when compared with the routine flagella antigen. If different antigens are combined in a panel to cover the antigenic diversity, sensitivity improves further and a specificity of 100% can be achieve.
43.	Hedin-Skogman, Barbro, 1967-, et al. (författare) Kampanj för TBE vaccination av små barn oetisk och felaktig 2004 Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:37, s. 2832-2832 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
44.	Hedin-Skogman, Barbro, et al. (författare) Lyme Neuroborreliosis in Children - a Prospective Study of Clinical features, Prognosis, and Outcome 2008 Ingår i: The Pediatric Infectious Disease Journal. - 0891-3668 .- 1532-0987. ; 27:12, s. 1089-1094 Tidskriftsartikel (refereegranskat)abstract Background: Evaluation of children with clinically suspected neuroborreliosis (NB) is difficult. With a prospective study design we wanted to characterize children with signs and symptoms indicative for NB, investigate clinical outcome and, if possible, identify factors of importance for recovery. Material/Methods: Children being evaluated for NB (n = 177) in Southeast Sweden were categorized into 3 groups: "confirmed neuroborreliosis" (41%) with Borrelia antibodies in the cerebrospinal fluid, "possible neuroborreliosis" (26%) with pleocytosis but 110 Borrelia antibodies in the cerebrospinal fluid, and "not determined" (33%) with no pleocytosis and no Borrelia antibodies in the cerebrospinal fluid, Antibiotic treatment was given to 69% of children. Patients were followed during 6 months and compared with a matched control group (n = 174). Results: Clinical recovery at the 6-month follow-up (n = 177) was generally good and no patient was found to have recurrent or progressive neurologic symptoms. However, persistent facial nerve palsy caused dysfunctional and cosmetic problems in 11% of patients. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. Influence on daily life was reported to the same extent in patients and controls. Consequently, persistent headache and fatigue at follow-up should not be considered as attributable to NB. No prognostic factors could be identified. Conclusions: Clinical recovery was satisfactory in children being evaluated for NB although persistent symptoms from facial nerve palsy occurred. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls.
45.	Hedin Skogman, Barbro, 1967- (författare) Neuroborreliosis in childhood : Clinical, immunological and diagnostic aspects 2008 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Lyme Borreliosisis is a multi-organ infectious disease caused by the spirochete Borrelia burgdorferi. The spirochete is transmitted to humans by tick bites. Neuroborreliosis (NB) is a disseminated form of the disease, in which the spirochetes invade the nervous system. In children, subacute meningitis and facial nerve palsy are typical clinical manifestations of NB.The aim of this thesis was to study clinical, immunological and laboratory characteristics in children being evaluated for NB in a Lyme endemic area of Sweden, in order to identify factors of importance for prognosis and clinical recovery. A total of 250 patients and 220 controls were included during 1998-2005, with a prospective and a retrospective part.Less than half (41%) of children with signs and symptoms indicative of NB get the diagnosis confirmed by detection of Borrelia specific flagella antibodies in CSF (clinical routine method). Surprisingly few patients were diagnosed as having other infectious or neurologic diseases and consequently, many patients ended up with an uncertain diagnosis. However, four new Borrelia antigens (DbpA, BBK32, OspC, IR6) were evaluated and performed well in laboratory diagnostics. If they were combined in a panel, together with the flagella antigen, the sensitivity was 82% and the specificity 100%, leading to improved diagnostic accuracy in children with NB, as compared to using the routine flagella antibody test alone.Clinical recovery at the 6-month follow-up (n=177) was generally good and nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. No patient was found to have recurrent or progressive neurologic symptoms.However, permanent facial nerve palsy was found in 22% of patients at the 2-year follow-up, with consequences such as eye-closing problems, excessive tear secretion, pronunciation difficulties and cosmetic complaints.When cellular immune responses were investigated, the number of Borrelia-specific IL-4 and IFN-γ secreting cells in CSF was found to be more prominent in children with NB than in controls. Furthermore, a much stronger IL-4 response in CSF was seen in children as compared to adults with NB. This cytokine profile of children with NB is believed to represent an effective and balanced type1/type2 response in a relevant compartment, and could contribute to the less severe course of the disease seen in children as compared to adults with NB.No prognostic factors were found to influence the outcome in patients with “Confirmed NB” or facial nerve palsy. Nor was any specific cytokine profile, or antibody response to new Borrelia antigens in CSF, correlated to a less favorable clinical outcome.An NB prediction score test, based on clinical variables at admission, is suggested to help physicians to determine whether to start early antibiotic treatment, before results from Borrelia antibody tests are available.Results in this thesis support the notion that mononuclear pleocytosis in CSF, in patients being evaluated for NB, indicates that they are true NB cases despite the fact that an antibody response cannot yet be visualized. with the routine flagella test. Consequently, early antibiotic treatment in NB seems to be the correct course of action and over-treatment is not a substantial problem.
46.	Hedin-Skogman, Barbro, 1967-, et al. (författare) TBE-vaccinera barn över 7 år i endemiska områden, men låt de små barnen slippa. 2004 Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:43, s. 3367-3367 Tidskriftsartikel (populärvet., debatt m.m.)
47.	Henningsson, Anna, et al. (författare) Human tick-borne encephalitis and characterization of virus from biting tick 2016 Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 22:8, s. 1485-1487 Tidskriftsartikel (refereegranskat)abstract We report a case of human tick-borne encephalitis (TBE) in which the TBE virus was isolated from the biting tick. Viral growth and sequence were characterized and compared with those of a reference strain. Virus isolation from ticks from patients with TBE may offer a new approach for studies of epidemiology and pathogenicity. © 2016, Centers for Disease Control and Prevention (CDC). All rights reserved.
48.	Henningsson, Anna J, 1972- (författare) Clinical, epidemiological and immunological aspects of Lyme borreliosis with special focus on the role of the complement system 2011 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Lyme borreliosis (LB) is the most common vector-borne disease in the Northern Hemisphere. The infection is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex, and it is transmitted to humans by ticks. LB is associated with several clinical manifestations, of which erythema migrans (EM) and neuroborreliosis (NB) are the most common inEurope. The course of the disease is usually benign, but can vary between individuals. The underlying pathogenic mechanisms are not fully understood, but the prognosis is probably determined by a complex interplay between the bacteria and the host’s immune response. Previous studies have indicated that a strong initial T helper (Th) 1-response followed by a Th2 response is beneficial for the clinical outcome in LB.The aims of this thesis were to follow the incidence of NB inJönköping County,Sweden, over time, to search for clinical and laboratory markers associated with the risk of developing long-lasting post-treatment symptoms, and to explore the role of the complement system as well as the relative balance between Th-associated cytokine/chemokine responses in LB.The number of NB cases, diagnosed by cerebrospinal fluid (CSF) analysis, increased from 5 to 10/100,000 inhabitants/year in Jönköping County during 2000-2005. Post-treatment symptoms persisting more than 6 months occurred in 13 %, and were associated with higher age, longer-lasting symptoms prior to treatment, higher levels of Borrelia-specific IgG in CSF, and reported symptoms of radiculitis. Facial palsy, headache and fever were frequent manifestations in children, whereas unspecific muscle and joint pain were the most commonly reported symptoms in older patients.Complement activation occurred both locally in the skin in EM and in CSF of NB patients. However, no activation could be detected in blood in NB patients. Elevated levels of C1q, C4 and C3a in CSF, along with correlation between C1q and C3a levels, suggest complement activation via the classical pathway locally in the central nervous system in NB. In vitro experiments with two clinical Borrelia isolates revealed that B. garinii LU59 induced higher complement activation in human plasma compared to B. afzelii K78 that recruited more of complement regulator factor H. To elucidate the role of complement in the phagocytosis process, experiments were performed using whole blood from healthy donors incubated with fluorescence-labelled spirochetes and different complement inhibitors. The results illustrated a central role of complement for phagocytosis of Borrelia spirochetes.We also studied the relative contribution of different Th-associated cytokines/chemokine responses in NB. The results support the notion that early NB is dominated by a Th1 response, eventually accompanied by a Th2 response. IL-17A was increased in CSF in half of the patients with confirmed NB, suggesting a hitherto unknown role of Th17 in NB.In conclusion, the risk of developing long-lasting post-treatment symptoms tend to increase mainly with age and duration of symptoms prior to treatment in NB. The complement system seems to play an important role in host defence to recognize and kill Borrelia spirochetes. However, complement activation in inappropriate sites or to an excessive degree may cause tissue damage, and therefore, the role of complement in relation to disease course needs to be studied further. Likewise, the role of Th17 in LB pathogenesis and host defence should be further evaluated in prospective studies.
49.	Henningsson, Anna J., et al. (författare) Complement activation in Lyme neuroborreliosis : increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS 2007 Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 183:1-2, s. 200-207 Tidskriftsartikel (refereegranskat)abstract A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.
50.	Henningsson, Anna J, et al. (författare) Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis : a large retrospective study 2011 Ingår i: Journal of Neuroinflammation. - : BioMed Central. - 1742-2094. ; 8:36 Tidskriftsartikel (refereegranskat)abstract Background: Previous studies indicate that successful resolution of Lyme neuroborreliosis (NB) is associated with a strong T helper (Th) 1-type cytokine response in the cerebrospinal fluid (CSF) followed by a down-regulating Th2 response, whereas the role of the recently discovered Th17 cytokine response is unknown. Methods: To investigate the relative contribution of different Th associated cytokine/chemokine responses, we used a multiple bead array to measure the levels of CXCL10 (Th1 marker), CCL22 (Th2 marker), IL-17 (Th17 marker) and CXCL8 (general inflammation marker), in serum and in CSF from untreated patients with confirmed NB (n = 133), and non-NB patients (n = 96), and related the findings to clinical data. Samples from patients with possible early NB (n = 15) and possible late NB (n = 19) were also analysed, as well as samples from an additional control group with orthopaedic patients (n = 17), where CSF was obtained at spinal anaesthesia. Results: The most prominent differences across groups were found in the CSF. IL-17 was elevated in CSF in 49% of the patients with confirmed NB, but was not detectable in the other groups. Patients with confirmed NB and possible early NB had significantly higher CSF levels of CXCL10, CCL22 and CXCL8 compared to both the non-NB group and the control group (p andlt; 0.0001 for all comparisons). Patients in the early NB group, showing a short duration of symptoms, had lower CCL22 levels in CSF than did the confirmed NB group (p andlt; 0.0001). Furthermore, patients within the confirmed NB group showing a duration of symptoms andlt; 2 weeks, tended to have lower CCL22 levels in CSF than did those with longer symptom duration (p = 0.023). Cytokine/chemokine levels were not correlated with clinical parameters or to levels of anti-Borrelia-antibodies. Conclusion: Our results support the notion that early NB is dominated by a Th1-type response, eventually accompanied by a Th2 response. Interestingly, IL-17 was increased exclusively in CSF from patients with confirmed NB, suggesting a hitherto unknown role for Th17 in NB. However, for conclusive evidence, future prospective studies are needed.

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