Tripartite motif containing-21 (TRIM21) is a cytosolic ubiquitin ligase and antibody receptor that provides a last line of defense against invading viruses. It does so by acting as a sensor that intercepts antibody-coated viruses that have evaded extracellular neutralization and breached the cell membrane. Upon engagement of the Fc of antibodies bound to viruses, TRIM21 triggers a coordinated effector and signaling response that prevents viral replication while at the same time inducing an anti-viral cellular state. This dual effector function is tightly regulated by auto-ubiquitination and phosphorylation. Therapeutically, TRIM21 has been shown to be detrimental in adenovirus based gene therapy, while it may be favorably utilized to prevent tau aggregation in neurodegenerative disorders. In addition, TRIM21 may synergize with the complement system to block viral replication as well as transgene expression. TRIM21 can also be utilized as a research tool to deplete specific proteins in cells and zebrafish embryos. Here, we review our current biological understanding of TRIM21 in light of its versatile functions.

Humans have four IgG antibody subclasses that selectively or differentially engage immune effector molecules to protect against infections. Although IgG1 has been studied in detail and is the subclass of most approved antibody therapeutics, increasing evidence indicates that IgG3 is associated with enhanced protection against pathogens. Here, we report that IgG3 has superior capacity to mediate intracellular antiviral immunity compared with the other subclasses due to its uniquely extended and flexible hinge region, which facilitates improved recruitment of the cytosolic Fc receptor TRIM21, independently of Fc binding affinity. TRIM21 may also synergize with complement C1/C4-mediated lysosomal degradation via capsid inactivation. We demonstrate that this process is potentiated by IgG3 in a hinge-dependent manner. Our findings reveal differences in how the four IgG subclasses mediate intracellular immunity, knowledge that may guide IgG subclass selection and engineering of antiviral antibodies for prophylaxis and therapy.

Med udgangspunkt i tre cases fra et feltarbejde blandt mennesker med multisygdom beskriver forfatterne en række temaer i informanternes hverdagsliv - social identitet, nære relationer og sygdomsforståelse - som vigtige for forståelse af multisyges oplevelse af kompleksitet i sygdomsforløb. I artiklen præsenteres data, der peger i retning af, at hverdagsliv har væsentlig indflydelse på patienternes prioriteringer af behandling og egenomsorg. Der argumenteres for, at særligt multisyge patienter har brug for at blive inddraget i beslutninger om behandling og pleje, fordi kompleksiteten af deres sygdomsforløb påvirker hverdagen i betydelig grad.

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IntroductionThe number of people living with visual impairment is increasing. Visual impairment causes loss in quality of life and reduce self-care abilities. The burden of disease is heavy for people experiencing visual impairment and their relatives. The severity and progression of age-related eye diseases are dependent on the time of detection and treatment options, making timely access to healthcare critical in reducing visual impairment. General practice plays a key role in public health by managing preventive healthcare, diagnostics and treatment of chronic conditions. General practitioners (GPs) coordinate services from other healthcare professionals. More involvement of the primary sector could potentially be valuable in detecting visual impairment.MethodsWe apply the Medical Research Council framework for complex interventions to develop a primary care intervention with the GP as a key actor, aimed at identifying and coordinating care for patients with low vision. The development process will engage patients, relatives and relevant health professional stakeholders. We will pilot test the feasibility of the intervention in a real-world general practice setting. The intervention model will be developed through a participatory approach using qualitative and creative methods such as graphical facilitation. We aim to explore the potentials and limitations of general practice in relation to detection of preventable vision loss.Ethics and disseminationEthics approval is obtained from local authority and the study meets the requirements from the Declaration of Helsinki. Dissemination is undertaken through research papers and to the broader public through podcasts and patient organisations.

Resume Antallet af børn og unge som diagnosticeres med en psykisk sygdom er stigende. Det betyder dog ikke, at alle de diagnosticerede børn har en sygdom, fordi denne stigning også delvist kan være et udtryk for overdiagnostik. I denne oversigtsartikel redegør vi for, med baggrund i nyeste viden og publicerede artikler, hvad psykiske diagnoser hos børn er, og hvorfor der kan forekomme overdiagnostik. Vi viser desuden, at opfattelser af det ’normale’ ændres, både fordi symptomer kan blive så udbredte, at det ikke længere giver mening at tale om symptomer, men om normal-tilstande, og fordi der er en øget tendens til at medikalisere og diagnosticere adfærd, der er en reaktion på specifikke begivenheder. Vi argumenterer for, at det er en væsentlig baggrundsviden at have for dem, som er beskæftiget inden for det pædagogiske område, særligt i folkeskolen, hvor børnene har den alder, de oftest diagnosticeres i. Vi slutter derfor med en diskussion af overdiagnostik i et pædagogisk perspektiv. Den pædagogiske faglighed kan være nøglen til at være mere præcis over for, hvordan en given adfærd skal tolkes – og kan derved medvirke til, at færre børn bliver overdiagnosticerede med en diagnose, de aldrig får gavn af. Abstract Leaving Normal? How overdiagnosis enter and form the field of pedagogic practiceThe number of children and adolescents diagnosed with mental diseases is rising. It does, however, not mean that all these children necessarily have a mental disease; overdiagnosis is a well-known problem among medical researchers, but the pedagogical researchers and staff also need this insight. In this paper, we provide an overview of mental diagnoses among children and adolescents, the diagnostic procedures that may lead to overdiagnosis and how the concept of normal are constantly changing. This is relevant for the pedagogical staff that will evidently meet children with severe and invalidating mental illnesses, but also children, whose illness and symptoms are potentially overdiagnosed. The professional insights from pedagogy and pedagogical research are much needed if we are to improve the diagnostic process by input to better distinguish between the children who will need medical attention – and thus a diagnosis – and children who may have challenges, but not related to any medical conditions.

Participation in medical screening programs is presented as a voluntary decision that should be based on an informed choice. An informed choice is often emphasized to rely on three assumptions: (1) the decision-maker has available information about the benefits and harms, (2) the decision-maker can understand and interpret this information, and (3) the decision-maker can relate this information to personal values and preferences. In this article, we empirically challenge the concept of informed choice in the context of medical screening. We use document analysis to analyze and build upon findings and interpretations from previously published articles on participation in screening. We find that citizens do not receive neutral or balanced information about benefits and harms, yet are exposed to manipulative framing effects. The citizens have high expectations about the benefits of screening, and therefore experience cognitive strains when informed about the harm. We demonstrate that decisions about screening participation are informed by neoliberal arguments of personal responsibility and cultural healthism, and thus cannot be regarded as decisions based on individual values and preferences independently of context. We argue that the concept of informed choice serves as a power technology for people to govern themselves and can be considered an implicit verification of biopower.