Journal Staff

Background: Internet-based cognitive behavioral therapy (ICBT) is a form of guided self-help that has been found to be effective for addressing several problems. The target for this type of therapy is usually restricted to one specific disorder. Tailoring the treatment widens the scope of ICBT in that it can address comorbid conditions directly. Objectives: The working, or therapeutic, alliance has been found to predict outcome in studies of face-to-face therapy. The extent to which these findings apply to ICBT is largely unknown. We therefore decided to find out whether the working alliance could predict outcome in tailored ICBT for anxiety disorders. Methods: Data were obtained from the treatment group (n=27) in a randomized controlled trial aiming to test the effects of tailored ICBT for anxiety disorders. The forthcoming study was designed to test the hypothesis that the working alliance measured both pre-treatment and early in treatment (week 3) can predict treatment outcome as measured by the Clinical Outcomes in Routine Evaluation–Outcome Measure (CORE-OM) in a heterogeneous group of patients with anxiety disorders (n=27). Results: Working alliance measured at week 3 into the treatment correlated significantly with the residual gain scores on the primary outcome measure (r=-.47, P=.019, n=25), while expected working alliance pre-treatment did not (r=-.17, P=.42, n=27). Conclusions: These results raise questions about the importance of working alliance in ICBT treatments, and suggest that the working alliance could be important in ICBT.Funding Agencies|Swedish Council for Working Life and Social Research|2008-1145|</p

Locus specific DNA methylation in human immunological responses

All cells in the human body contains the same genome. Yet, there are hundreds of different cell types, with widely different phenotype, and function. The differential gene expression leading to this diversity is tightly regulated by epigenetics, i.e. modifications to the genome without interfering with the sequence. There are a number of epigenetic modifications. In this thesis, I have studied DNA methylation as a readout for lineage specificity or effector function in cells from the immune system, in clinical settings. In paper I we develop a method based on DNA methylation analysis to determine the lineage commitment of the CD4+ T helper cells. First, we establish a regulatory site in the promotor of the IL17A gene. Next, we use signature genes IFNG, IL13, IL17A and FOXP3, to determine lineage commitment towards corresponding T helper cell subsets Th1, Th2, Th17 and Tregs. We call this method EILA (Epigenetic immune lineage assay), and demonstrate that it is usable in clinical samples from rheumatoid arthritis and multiple sclerosis. In paper II, we take advantage of the same CD4+ T cell specific loci to investigate the adaptive immune response in and around the tumour microenvironment in specimens derived from patients with urinary bladder cancer (UBC). By sorting and examining CD4+ T cells from blood, tumour and regional lymph nodes, we conclude that patients with higher degree of lineage commitment have a better prognosis. Furthermore, we demonstrate that patients responding to neoadjuvant chemotherapy have a larger proportion of commitment cells, post treatment, compared with the non-responders. In paper III we further examine the same patient material from UBC patients, but instead focus on the cytotoxic features of CD8+ T lymphocytes. We establish a methylation pattern in the perforin gene PRF1 predictive for protein expression and deploy this locus as a readout for cytotoxic functionality. We demonstrate that the tumour infiltrating CD8+ T cells are pre- dispositioned to be cytotoxic through PRF1 demethylation, but that they lack corresponding protein expression, and show signs of exhaustion. The cells demonstrating a TRM phenotype, can still be woken anew, upon in vitro re-stimulation, demonstrating that they are not terminally exhausted. In paper IV we investigate whole blood leucocytes and the DNA methylation status of the glucocorticoid gene NR3C1. In contrast to literature studies on healthy volunteers, our cohort of surgical patients demonstrate a homogeneous pattern of demethylation in the previously described CpG island of NR3C1. As opposed to our hypothesis, we found no correlation between methylation and clinical outcome post-surgery in this patient cohort. Nevertheless, when employing multifactorial analysis to investigating the impact of genotype we found four single nucleotide polymorphisms that influenced the outcome. In conclusion, this thesis demonstrate multiple ways in which DNA methylation analysis can be used to read the immune system, but also that the loci selected for investigation has to be carefully chosen following thorough functional investigations. The results presented herein can contribute to further development of treatments to a variety of clinical conditions

Использование возможностей практико-ориентированного обучения в процессе развития интеллектуальных способностей слушателей факультета профориентации и довузовской подготовки

МЕДИЦИНСКИЕ УЧЕБНЫЕ ЗАВЕДЕНИЯОБРАЗОВАНИЕ МЕДИЦИНСКОЕСТУДЕНТЫ МЕДИЦИНСКИХ УЧЕБНЫХ ЗАВЕДЕНИЙПРАКТИКО-ОРИЕНТИРОВАННОЕ ОБУЧЕНИЕИНТЕЛЛЕКТУАЛЬНЫЕ СПОСОБНОСТИСЛУШАТЕЛИСЛУШАТЕЛИ ФПД

Work productivity in a population-based cohort of patients with spondyloarthritis.

Objective. To assess work productivity and associated factors in patients with SpA.Methods. This cross-sectional postal survey included 1773 patients with SpA identified in a regional health care register. Items on presenteeism (reduced productivity at work, 0-100%, 0 = no reduction) were answered by 1447 individuals. Absenteeism was defined as register-based sick leave using data from a national register. Disease duration, disease activity (BASDAI), physical function (BASFI), health-related quality of life (EQ-5D), anxiety (HAD-a), depression (HAD-d), self-efficacy [Arthritis Self-efficacy Scale (ASES) pain and symptom], physical activity and education were also measured.Results. Forty-five per cent reported reduced productivity at work with a mean reduction of 20% (95% CI 18, 21) and women reported a higher mean reduction than men (mean 23% vs 17%, P < 0.001). Worse quality of life, disease activity, physical function and anxiety all correlated with reduced productivity (r = 0.52-0.66, P < 0.001), while sick leave did not. Worse outcomes on the EQ-5D (β-est -9.6, P < 0.001), BASDAI (β-est 7.8, P < 0.001), BASFI (β-est 7.3, P < 0.001), ASES pain (β-est -0.5, P < 0.001) and HAD-d (β-est 3.4, P < 0.001) were associated with reduced productivity at work in patients with SpA regardless of age, gender and disease subgroup. ASES symptoms, HAD-a and education level <12 years were associated with reduced productivity but were not significant in all strata for age, gender and disease subgroup.Conclusion. Work productivity was reduced in patients with SpA and more so in women. Worse quality of life, disease activity, physical function, self-efficacy and depression were all associated with reduced productivity at work in patients with SpA

Correlation between cognitive assessment scores and circulating cerebral biomarkers in women with pre-eclampsia and eclampsia

OBJECTIVES: The cerebral injury biomarkers neurofilament light chain (NfL) and tau and the glial activation biomarker glial fibrillary acidic protein (GFAP) may reflect neurological injury in pre-eclampsia. We assessed if there was a correlation between cognitive function assessment scores and plasma concentrations of these biomarkers in pre-eclampsia. STUDY DESIGN: Women with eclampsia, pre-eclampsia and normotensive pregnancies from the South African PROVE biobank were included. Blood samples were taken at inclusion. The Montreal Cognitive Assessment was performed after delivery at the time of discharge. The correlation between cognitive assessment scores and plasma concentrations of cerebral biomarkers was analysed using Spearman correlation adjusted for time from eclamptic seizure. MAIN OUTCOME MEASURES: We included 49 women with eclampsia, 16 women with pre-eclampsia complicated by pulmonary oedema, 22 women with pre-eclampsia without pulmonary oedema, HELLP or neurological complications and 18 women with normotensive pregnancies. RESULTS: There was a correlation between impaired cognitive function and increased plasma concentrations of NfL in women with eclampsia and women with pre-eclampsia and pulmonary oedema (r = -0.37, p = 0.009 and r = -0.56, p = 0.025 respectively). No correlation between impaired cognitive function and NfL in pre-eclampsia cases without pulmonary oedema, HELLP or neurological complications or normotensive pregnancies was found. No correlation with cognitive impairment was found in any groups for tau or GFAP. CONCLUSIONS: We found a correlation between impaired cognitive function assessment and plasma NfL concentrations in women with eclampsia and pre-eclampsia complicated by pulmonary oedema. These findings suggest that acute neuroaxonal injury may cause or contribute to cognitive impairment in these women

Biologisk recipientkontroll vid Oskarshamns kärnkraftverk : årsrapport för 2022

Oskarshamns kärnkraftverk (OKG AB) påverkar den omgivande havsmiljön, främst genom användning av kylvatten. Den kylvattenpåverkade recipientens vattentemperatur var i medeltal 3,4 °C varmare än referensområdet Borholmsfjärden under 2022. Under 2022 pågick inga särskilda studier av fiskförluster i kylvattenhanteringen och det rapporterades inga avvikande händelser från kraftverkets silstation. Revisionsavställningen under våren, innebar en utebliven värmeökning i Hamnefjärden, vilket sannolikt påverkade resultatet i vårfisket med biologiska länkar till att en större andel av arterna var så kallade kallvattenarter som har högre förekomst i vatten med lägre temperaturer. Även ryssjefisket bör ha påverkats av detta och det kan vara en del i förklaringen till de låga ålfångsterna. I ryssjorna slogs däremot nytt fångstrekord av svartmunnad smörbult i år igen och storspigg fångades i ovanligt stort antal. I fisket med biologiska länkar, nätlänkar och nordiska kustöversiktsnät var fångsterna stora av abborre, mört, björkna och andra karpfiskar. De skillnader vi såg i fiskfångsterna mellan områdena kan förklaras av naturliga skillnader i temperatur, exponeringsgrad och geografisk lokalisering snarare än påverkan av varmvattenutsläppen från kärnkraftverket. I vårens fiske med kustöversiktsnät utanför Hamnefjärdens mynning registrerades låga fångster av de flesta för fisket vanligen förekommande arterna. Störning från säl noterades i nära 90 procent av fiskeansträngningarna. De varma somrarna 2018 och 2021 har resulterat i att en stor andel av de fångade abborrarna i provfiskena var fyra respektive ett år gamla. Konditionsvärdet för abborr- och mörthonor låg i samtliga områden omkring Simpevarp och Kvädöfjärden på eller över gränsvärdet för god kondition. Vid 2022 års provtagningar påträffades inga abborrhonor med missbildade gonader i något av ovan nämnda områden. Majoriteten av fiskar med sjukdomssymptom fångades i Simpevarp. Endast en sjuk fisk noterades i Kvädöfjärden. Antalet årsyngel av abborre och mört var lågt i Hamnefjärden 2022. Fångsterna i yrkesfisket efter vandrande ål, så kallad blankål, var återigen ett av de lägsta sedan journalföringen av detta fiske startades 1972.Under 2022 års undersökning av fauna på mjuka bottnar registrerades totalt 19 arter i Simpevarp och 21 arter i referensområdet Kvädöfjärden. Östersjömusslan var den vanligast förekommande arten på grunda bottnar och på djupa bottnar i Kvädöfjärden. På Simpevarps djupa bottnar var den rörbyggande havsborstmasken Pygospio elegans den mest förekommande arten. Vitmärla, en art som används som indikator för bland annat förändringar i halter av näringsämnen, sjönk ytterligare i antal på Kvädöfjärdens stationer. I år hittades den inte alls på grunda bottnar i Simpevarp. På djupa bottnar i samma område har den inte registrerats sedan 2013

Cerebral biomarkers in neurological complications of preeclampsia

BACKGROUND AND OBJECTIVES: There are no tools to accurately predict who is at risk of developing neurological complications of preeclampsia and no objective methods to determine disease severity. We assessed whether plasma levels of the cerebral biomarkers neurofilament light (NfL), tau and glial fibrillary acidic protein (GFAP) could reflect disease severity in various phenotypes of preeclampsia and compared them to the angiogenic biomarkers soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng) . STUDY DESIGN: In this observational study, we included women from the South African PROVE biobank. Plasma samples taken at diagnosis (preeclampsia cases) or at admission for delivery (normotensive controls) were analyzed for concentrations of NfL, tau, GFAP, PlGF, sFlt-1 and sEng. Cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age and parity. RESULTS: Compared to 28 normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of NfL (95% CI 1.64-2.88), 2.17-fold higher tau (1.49-3.16) and 2.77-fold higher GFAP (2.06-3.72). In total 72 women with neurological complications (eclampsia, cortical blindness and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher, 95% CI 1.92-4.65) and GFAP (3.22-fold higher, 95% CI 2.06-5.02) compared to women with preeclampsia without pulmonary edema, HELLP or neurological complications (n=31). Angiogenic markers were also higher but to a lesser extent. Women with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (n=20) demonstrated increased plasma concentrations of NfL (1.64-fold higher, 95% CI 1.06-2.55), tau (4.44-fold higher, 95% CI 1.85-10.66) and GFAP (1.82-fold higher, 95% CI 1.32-2.50) compared to women with preeclampsia without pulmonary edema, HELLP or neurological complications . No difference was shown in angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema, HELLP or neurological complications for any of the biomarkers. Plasma concentrations of tau and GFAP were increased in women with several neurological complications vs eclampsia only. CONCLUSIONS: Plasma NfL, GFAP and tau are candidate biomarkers for diagnosis and possibly prediction of cerebral complications of preeclampsia

Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age.

Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4+ T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (β-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein-Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination