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This article explores how current legislation addresses adolescents’ need for support in upper secondary school through school–home collaboration and introduces the framework of collaborative autonomy–support as the pivotal approach for analyses. Self-determination theory is used to describe adolescents’ need for competence, relatedness and autonomy. The study involved a document analysis in which Norwegian legislation was deconstructed through the lens of pedagogy in order to consider how legislative enactment challenges professional educational practices. The study uncovered three tensions in the legislation: the adolescents’ self-determination versus parental obligations, parents’ lack of formal representation in upper secondary school, and different directions in language used about parents in school. The article illuminates how legislation promotes adolescents’ autonomy, intrinsic motivation and volitional functioning.

Purpose of ReviewTo improve our clinical understanding of facial onset sensory and motor neuronopathy (FOSMN).Recent FindingsWe identified 29 new cases and 71 literature cases, resulting in a cohort of 100 patients with FOSMN. During follow-up, cognitive and behavioral changes became apparent in 8 patients, suggesting that changes within the spectrum of frontotemporal dementia (FTD) are a part of the natural history of FOSMN. Another new finding was chorea, seen in 6 cases. Despite reports of autoantibodies, there is no consistent evidence to suggest an autoimmune pathogenesis. Four of 6 autopsies had TAR DNA-binding protein (TDP) 43 pathology. Seven cases had genetic mutations associated with neurodegenerative diseases.SummaryFOSMN is a rare disease with a highly characteristic onset and pattern of disease progression involving initial sensory disturbances, followed by bulbar weakness with a cranial to caudal spread of pathology. Although not conclusive, the balance of evidence suggests that FOSMN is most likely to be a TDP-43 proteinopathy within the amyotrophic lateral sclerosis–FTD spectrum.

Among the disabled workforce, many are engaged in part-time work. However, research regarding the relationship between disability and part-time work has only partially elucidated how people with disabilities who are in receipt of partial or graded disability pensions perceive and handle the combination of part-time work with their pension payments. This article addresses the narrated strategies employed by people with disabilities in managing part-time employment, drawing on interview data from 10 Norwegian citizens who worked part-time in addition to receiving a graded disability pension. The findings illustrate that flexibility and visibility are specific strategies that our informants implement when health issues and reduced working hours result in weakened connections to the workplace. The article demonstrates how the discourses around paid employment facilitate these strategies. By providing insight into people's narrated experiences of engaging in part-time work with disabilities, the article offers significant recommendations into the conditions necessary for people with disabilities to remain employed while also in receipt of graded disability pensions.

Background Cuprizone administration in mice leads to oligodendrocyte death and demyelination. The effect is thought to reflect copper-chelation that leads to inhibition of complex IV of the mitochondrial respiratory chain. The effects this drug has on neurons are less well known. Objective To investigate the toxic effects of cuprizone on mitochondria in neurons. Methods Male c57Bl/6 mice were fed 0.2% cuprizone for up to 5 weeks. Cuprizone-fed and control mice were examined at week 1, 3, 5 and 4 weeks after cessation of cuprizone exposure. The brain was examined for myelin, complex I, complex IV and for COX/SDH activities. Mitochondrial-DNA was investigated for deletions and copy number variation. Results We found decreased levels of complex IV in the cerebellar Purkinje neurons of mice exposed to cuprizone. This decrease was not related to a general decrease in mitochondrial volume or mass, as there were no differences in the levels of complex I or TOMM20. Conclusion Neurons are affected by cuprizone-treatment. Whether this mitochondrial dysfunction acts as a subclinical trigger for demyelination and the long-term axonal degeneration that proceeds after cuprizone treatment stops remains unclear.

Improved understanding of the mechanisms involved in neurodegenerative disease has been hampered by the lack of robust cellular models that faithfully replicate in vivo features. Here, we present a refined protocol for generating age-dependent, well-developed and synaptically active rat Purkinje neurons in a 3D cell network culture which are responsive to a disease inducer. Using our model, we found that the application of autoantibody Yo, a paraneoplastic cerebellar degeneration (PCD) inducer, alters the structure of the dendritic arbour of cultured Purkinje neurons. The numbers of dendrites per branch-order, the branch-order in itself and the dendritic length were reduced by anti-Yo, proving a functional role for anti-Yo in the pathogenesis of PCD. Our new ex-vivo model is flexible and can be used to investigate disease mechanisms that disturb Purkinje neuron function and communication in 3D. Since it is possible to use the approach in a multi-well format, this method also has high-throughput screening potential.

BackgroundThe predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear.ObjectiveInvestigate the relation between sNfL levels over a 2-year period in patients with relapsing-remitting MS, and clinical disability and grey matter (GM) atrophy after 10 years.Methods85 patients, originally enrolled in a multicentre, randomised trial of ω−3 fatty acids, participated in a 10-year follow-up visit. sNfL levels were measured by Simoa quarterly until month 12, and then at month 24. The appearance of new gadolinium-enhancing (Gd+) lesions was assessed monthly between baseline and month 9, and then at months 12 and 24. At the 10-year follow-up visit, brain atrophy measures were obtained using FreeSurfer.ResultsHigher mean sNfL levels during early periods of active inflammation (Gd+ lesions present or recently present) predicted lower total (β=−0.399, p=0.040) and deep (β=−0.556, p=0.010) GM volume, lower mean cortical thickness (β=−0.581, p=0.010) and higher T2 lesion count (β=0.498, p=0.018). Of the clinical outcomes, higher inflammatory sNfL levels were associated with higher disability measured by the dominant hand Nine-Hole Peg Test (β=0.593, p=0.004). Mean sNfL levels during periods of remission (no Gd+ lesions present or recently present) did not predict GM atrophy or disability progression.ConclusionHigher sNfL levels during periods of active inflammation predicted more GM atrophy and specific aspects of clinical disability 10 years later. The findings suggest that subsequent long-term GM atrophy is mainly due to neuroaxonal degradation within new lesions.

I anledning Lars Grues 75-års dag, gir NOVA ut notatet Homo sapiens, homo ludens. I alt 17 bidragsytere dekker hans faglige virksomhet om forskning om funksjonshemming og hyller Grue som det lekende menneske han er. Med sine brede kompetanse på flere forskningsfelt, har Grue i mange år vært en viktig medarbeider på NOVA. I festskriftet hylles han av tidligere kolleger, samarbeidspartnere, venner og familie.

Existing research has found adverse short-term effects of the COVID-19 pandemic on mental health, but longer-term effects have been less documented. Using newly released register data on all general practitioner consultations in Norway through 2020 (about 14 million consultations in total), we find that during the spring and early summer 2020, the number of psychological cases initially increased relative to prior years, but then fell back towards the level of prior years during the summer 2020. In early September 2020, the number of cases accelerated, a pattern that held up through December 2020, so that the gap between 2020 and prior years became largest end-of-year. Our findings suggest that the accumulated adverse effects of the COVID-19 pandemic on mental health far exceeds the short-term effects. The effects are particularly strong for females and for residents in urban areas. Supplementary Information The online version contains supplementary material available at 10.1007/s10654-021-00836-3.

NOVA har gjennomført en litteraturgjennomgang og en nettbasert spørreundersøkelse om levekår og livskvalitet blant voksne med ADHD. Hovedtemaene er helse, utdanning og arbeid. Spørreundersøkelsen ble gjennomført våren 2022 og fikk 3145 svar. Resultatene gir et bilde av at voksne med ADHD er mindre tilfredse med livet og har det vanskeligere enn befolkningen som helhet på en rekke områder som har stor betydning for den enkeltes levekår og livskvalitet.

The expression and localization of the oncoprotein c-Myc is highly regulated at the level of transcription, mRNA transport, translation, as well as stability of the protein. We previously showed that Annexin A2 (AnxA2) binds to a specific localization element in the 3ʹuntranslated region (UTR) of c-myc mRNA and is involved in its localization to the perinuclear region. In the present study, we demonstrate that AnxA2 binds in a Ca2+-dependent manner to the internal ribosomal entry site (IRES) containing two pseudo-knots in the 5´UTR of the c-myc mRNA. Here, we employ an in vitro rabbit reticulocyte lysate system with chimeric c-myc reporter mRNAs to demonstrate that binding of AnxA2 to the c-myc IRES modulates the expression of c-Myc. Notably, we show that low levels of AnxA2 appear to increase, while high levels of AnxA2 inhibits translation of the chimeric mRNA. However, when both the AnxA2-binding site and the ribosomal docking site in the c-myc IRES are deleted, AnxA2 has no effect on the translation of the reporter mRNA. Forskolin-treatment of PC12 cells results in upregulation of Ser25 phosphorylated AnxA2 expression while c-Myc expression is down-regulated. The effect of forskolin on c-Myc expression and the level of Ser25 phosphorylated AnxA2 was abolished in the presence of EGTA. These findings indicate that AnxA2 regulates both the transport and subsequent translation of the c-myc mRNA, possibly by silencing the mRNA during its transport. They also suggest that AnxA2 act as a switch to turn off the c-myc IRES activity in the presence of calcium. Abbreviations: AnxA2, Annexin A2; β2--µglob, β2-microglobulin; cpm, counts per minute; hnRNP, heterogenous nuclear ribonucleoprotein; IRES, internal ribosomal entry site; ITAF, IRES trans-acting factor; MM, multiple myeloma; PABP, poly(A)-binding protein; PCBP, poly(rC) binding protein; PSF, PTB-associated splicing factor; PTB, polypyrimidine tract binding protein; RRL, rabbit reticulocyte lysate; UTR, untranslated region; YB, Y-box binding protein.

The expression and localization of the oncoprotein c-Myc is highly regulated at the level of transcription, mRNA transport, translation, as well as stability of the protein. We previously showed that Annexin A2 (AnxA2) binds to a specific localization element in the 3ʹuntranslated region (UTR) of c-myc mRNA and is involved in its localization to the perinuclear region. In the present study, we demonstrate that AnxA2 binds in a Ca2+-dependent manner to the internal ribosomal entry site (IRES) containing two pseudo-knots in the 5´UTR of the c-myc mRNA. Here, we employ an in vitro rabbit reticulocyte lysate system with chimeric c-myc reporter mRNAs to demonstrate that binding of AnxA2 to the c-myc IRES modulates the expression of c-Myc. Notably, we show that low levels of AnxA2 appear to increase, while high levels of AnxA2 inhibits translation of the chimeric mRNA. However, when both the AnxA2-binding site and the ribosomal docking site in the c-myc IRES are deleted, AnxA2 has no effect on the translation of the reporter mRNA. Forskolin-treatment of PC12 cells results in upregulation of Ser25 phosphorylated AnxA2 expression while c-Myc expression is down-regulated. The effect of forskolin on c-Myc expression and the level of Ser25 phosphorylated AnxA2 was abolished in the presence of EGTA. These findings indicate that AnxA2 regulates both the transport and subsequent translation of the c-myc mRNA, possibly by silencing the mRNA during its transport. They also suggest that AnxA2 act as a switch to turn off the c-myc IRES activity in the presence of calcium. Abbreviations: AnxA2, Annexin A2; β2--µglob, β2-microglobulin; cpm, counts per minute; hnRNP, heterogenous nuclear ribonucleoprotein; IRES, internal ribosomal entry site; ITAF, IRES trans-acting factor; MM, multiple myeloma; PABP, poly(A)-binding protein; PCBP, poly(rC) binding protein; PSF, PTB-associated splicing factor; PTB, polypyrimidine tract binding protein; RRL, rabbit reticulocyte lysate; UTR, untranslated region; YB, Y-box binding protein., Graphical abstract

Background\ud When Europe was hit by the COVID-19 pandemic, changes were made in maternity care to reduce infections. In Norway, hospital maternity wards, postnatal wards, and neonatal units’ companions and visitors were restricted. We aimed to explore the experiences of being pregnant, giving birth and becoming a parent in Norway during the COVID-19 pandemic.\ud \ud Methods\ud The study is based on the responses from women who provided in-depth qualitative accounts to the ongoing Babies Born Better survey version 3 during the first year of the COVID-19 pandemic. The responses were analysed with inductive thematic analysis.\ud \ud Results\ud In all, 806 women were included, regardless of parity and mode of birth. They gave birth in 42 of 45 available birthing units across Norway. The analysis resulted in four themes: 1) Pregnancy as a stressful waiting period; 2) Feeling lonely, isolated, and disempowered without their partner; 3) Sharing experiences and becoming a family; and 4) Busy postnatal care without compassion.\ud \ud Conclusion\ud The COVID-19 pandemic seems to have affected women's experiences of giving birth and becoming a parent in Norway. The restrictions placed on companionship by the healthcare facilities varied between hospitals. However, the restrictions seem to have affected a range of aspects related to women's experiences of late pregnancy, early labour and birth and the early postpartum period. Postnatal care was already poor, and the pandemic has highlighted the shortcomings, especially where companionship was banned.

We analyse the economic effects of nationwide Norwegian reforms on the state benefit programme targeting single mothers. Our results show that for each reduction of 100 Norwegian kroner (NOK) in benefit payments from the programme, single mothers replaced 65 NOK through benefit substitution. Their labour supply and disposable income also increased in the short term. However, the reforms doubled the poverty rate among single mothers in the long term. The reforms led to a total net gain to public expenditure of 3.6 billion NOK (449 million euros) during the 1998–2008 period, corresponding to a 14 percent decrease in total benefit payments to single mothers. acceptedVersion

Besides altering its own expression during cell transformation, Annexin A2 is upregulated during the progression of many cancer types and also plays key roles during viral infection and multiplication. Consequently, there has been great interest in Annexin A2 as a potential drug target. The successful design of efficient in vivo delivery systems constitutes an obstacle in full exploitation of antisense and RNA-cleaving technologies for the knock-down of specific targets. Efficiency is dependent on the method of delivery and accessibility of the target. Here, hairpin ribozymes and an antisense RNA against rat annexin A2 mRNA were tested for their efficiencies in a T7-driven coupled transcription/translation system. The most efficient ribozyme and antisense RNA were subsequently inserted into a retroviral vector under the control of a tRNA promoter, in a cassette inserted between retroviral Long Terminal Repeats for stable insertion into host DNA. The Phoenix package system based on defective retroviruses was used for virus-mediated gene transfer into PC12 cells. Cells infected with the ribozyme-containing particles died shortly after infection. However, the same ribozyme showed a very high catalytic effect in vitro in cell lysates, explained by its loose hinge helix 2 region. This principle can be transferred to other ribozymes, such as those designed to cleave the guide RNA in the CRISPR/Cas9 technology, as well as to target specific viral RNAs. Interestingly, efficient down-regulation of the expression of Annexin A2 by the antisense RNA resulted in up-regulation of Annexin A7 as a compensatory effect after several cell passages. Indeed, compensatory effects have previously been observed during gene knock-out, but not during knock-down of protein expression. This highlights the problems in interpreting the phenotypic effects of knocking down the expression of a protein. In addition, these data are highly relevant when considering the effects of the CRISPR/Cas9 approach. publishedVersion

This article presents findings from a survey on hate speech reported by disabled people in Norway. Previous British and American research shows that disabled people are more likely than their non-d...

Receptor occupancy, the ratio between amount of drug bound and amount of total receptor on single cells, is a biomarker for treatment response to therapeutic monoclonal antibodies. Receptor occupancy is traditionally measured by flow cytometry. However, spectral overlap in flow cytometry limits the number of markers that can be measured simultaneously. This restricts receptor occupancy assays to the analysis of major cell types, although rare cell populations are of potential therapeutic relevance. We therefore developed a receptor occupancy assay suitable for mass cytometry. Measuring more markers than currently available in flow cytometry allows simultaneous receptor occupancy assessment and high‐parameter immune phenotyping in whole blood, which should yield new insights into disease activity and therapeutic effects. However, varying sensitivity across the mass cytometer detection range may lead to misinterpretation of the receptor occupancy when drug and receptor are detected in different channels. In this report, we describe a method for optimization of mass cytometry receptor occupancy measurements by using antibody‐binding quantum simply cellular (QSC) beads for standardization across channels with different sensitivities. We evaluated the method in a mass cytometry‐based receptor occupancy assay for natalizumab, a therapeutic antibody used in multiple sclerosis treatment that binds to α4‐integrin, which is expressed on leukocyte cell surfaces. Peripheral blood leukocytes from a treated patient were stained with a panel containing metal‐conjugated antibodies for detection of natalizumab and α4‐integrin. QSC beads with known antibody binding capacity were stained with the same metal‐conjugated antibodies and were used to standardize the signal intensity in the leukocyte sample before calculating receptor occupancy. We found that QSC bead standardization across channels corrected for sensitivity differences for detection of drug and receptor and generated more accurate results than observed without standardization. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

Background: When Europe was hit by the COVID-19 pandemic, changes were made in maternal care to reduce infections. In hospital maternity wards, postnatal wards, and neonatal units’ companions and visitors were restricted. There is emerging evidence that changes in maternity care delivery and restrictions due to social distancing have been distressing for many childbearing women. We aimed to explore the experiences of giving birth and becoming a parent in Norway during the COVID-19 pandemic. Methods: The study is based on the responses from women who provided in-depth qualitative comments to Babies Born Better survey version 3, December 2020. The responses were analysed with inductive thematic analysis.Results: In all, 827 women who gave birth in 42 of 45 available birthing units across Norway, regardless of parity and mode of birth, were included. The qualitative analysis resulted in four themes: 1) Waiting period filled with stress and worries; 2) Feeling lonely, isolated and disempowered without the partner; 3) Sharing experiences and becoming a family; and 4) Busy postnatal care without compassion.Conclusion: The COVID-19 pandemic has had an impact on women’s experiences of giving birth and becoming a parent in Norway. The denial of companionship and postnatal visiting varied between hospitals, which suggests that some of the restrictions were related to organisational protectionism than the protection of women and babies. Early postnatal care is the area of care that seems to have been most negatively affected and clearly requires more attention. The balance between humanised healthcare and protection from infection has not been well maintained through this current pandemic.

To explore and describe what women who have given birth in Norway emphasise as important aspects of care during childbirth.The study is based on data from the Babies Born Better online survey, version 2.The maternity care system in Norway.Women who gave birth in Norway between 2013 and 2018.Descriptive statistics were used to describe sample characteristics and to compare data from the B3 survey with national data from the Medical Birth Registry of Norway. The open-ended questions were analysed with an inductive thematic analysis.Themes developed from two open-ended questions.The final sample included 8401 women. There were no obvious differences between the sample population and the national population with respect to maternal age, marital status, parity, mode of birth and place of birth, except for the proportion of planned home births. Four themes and one overarching theme were identified; Compassionate and Respectful Care, A Family Focus, Sense of Continuity and Consistency, and Sense of Security. Overarching theme: Coherence in Childbearing.Norwegian women across all birth settings emphasise maternity care that authentically focuses on both socio-cultural and psychological aspects of care, and physical and clinical factors. If the positive aspects of care identified in this study are adopted at all levels of the maternity care system and from all care providers, there is a high chance that most women will have a safe outcome, and a strong sense of coherence related to a positive birth and motherhood experience.Having a baby is a pivotal life changing experience and not just a clinical event, according to a survey of 8400 women in Norway. Positive birth and motherhood experiences depend on maternity staff who are both skilled and kind.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder causing inflammatory demyelination of peripheral nerves and consecutive disability. Diagnostic criteria and treatments are well established, but it is unknown how clinical practice may differ in different geographical regions. In this multicentre study, clinical management of CIDP was compared in 44 patients from Germany, India and Norway regarding diagnostic and therapeutic procedures. All centres used EFNS/PNS diagnostic criteria for CIDP but diagnostic workup varied regarding screening for infectious diseases, genetic testing and nerve biopsy. Intravenous immunoglobulin and prednisolone were the most common therapies in all centres with differences in indication and dosage. Patients from the Indian cohort were the most severely affected with less diverse therapeutic approaches, whereas psychological strain did not differ significantly from the two other cohorts. Our exploratory study discloses an unaddressed issue in management of CIDP that should be further investigated to optimise standard of care for CIDP worldwide.

Neurosarcoidosis is a rare form of sarcoidosis that affects the nervous system. The aim of the study was to survey clinical manifestations, findings from assessments and treatment strategies for patients with neurosarcoidosis.The study performed a retrospective assessment of 17 patients with definitive, probable and possible neurosarcoidosis diagnosed in the period 2008-2019 at the Department of Neurology, Haukeland University Hospital.The average prevalence of definitive, probable or possible neurosarcoidosis in Norway's Vestland county was 2.7 per 100 000 inhabitants in the period in question. Onset took the form of central nervous affection (8 of 17), hydrocephalus (5 of 17) and cranial neuropathy (5 of 17). Sarcoidosis-like findings were made in 14 of 17 patients by means of contrast-enhanced magnetic resonance tomography (MRT) of the central nervous system, in 7 of 8 patients by positron emission tomography (PET), and in 12 of 16 patients by computed tomography (CT) of the thorax. There were cerebrospinal fluid abnormalities in 15 of 15 patients, with biopsy verification for 13 of 15. The symptoms of 16 of 17 patients improved or stabilised with prednisolone and/or other immunotherapy.Neurosarcoidosis affects both the central and the peripheral nervous system. Cerebrospinal fluid analysis and contrast-enhanced MRT are important means of detecting inflammation. A biopsy is necessary for making a definitive diagnosis, but is not always feasible. PET can be used as a supplement to other examinations to assess various organ manifestations and to pinpoint biopsy sites. Corticosteroid therapy, and in some cases other immunotherapy, elicits a good response.

Patients with ovarian cancer and paraneoplastic cerebellar degeneration, a cancer-related immune disorder, often have anti-Yo antibody. Here we studied the distributions of anti-Yo antigens CDR2L and CDR2 in rat and human brain using immunohistochemistry and western blot. CDR2L localized mainly to the Purkinje cells and large neurons scattered in the brain stem. CDR2 was detected in vascular smooth muscle cells of rat and human and in cells lining the ventricle system in rats. The observed distribution of CDR2L is compatible with the hypothesis that this antigen is the major target of anti-Yo. CDR2 and CDR2L are expressed by different cell subtypes.