Sofia Nyström

Transmissibility of systemic amyloidosis by a prion-like mechanism.

The generation of amyloid fibrils from an amyloidogenic polypeptide occurs by a nucleation-dependent process initiated in vitro by seeding the protein solution with preformed fibrils. This phenomenon is evidenced in vivo by the fact that amyloid protein A (AA) amyloidosis in mice is markedly accelerated when the animals are given, in addition to an inflammatory stimulus, an i.v. injection of protein extracted from AA amyloid-laden mouse tissue. Heretofore, the chemical nature of this “amyloid enhancing factor” (AEF) has not been definitively identified. Here we report that the active principle of AEF extracted from the spleen of mice with silver nitrate-induced AA amyloidosis was identified unequivocally as the AA fibril itself. Further, we demonstrated that this material was extremely potent, being active in doses <1 ng, and that it retained its biologic activity over a considerable length of time. Notably, the AEF was also effective when administered orally. Our studies have provided evidence that AA and perhaps other forms of amyloidosis are transmissible diseases, akin to the prion-associated disorders.

AA-Amyloidosis Can Be Transferred by Peripheral Blood Monocytes

Spongiform encephalopathies have been reported to be transmitted by blood transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows similarities with prion disease and amyloid-containing organ-extracts can prime a recipient for the disease. In this systemic form of amyloidosis N-terminal fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main amyloid protein. Initial amyloid deposits appear in the perifollicular region of the spleen, followed by deposits in the liver. We used the established murine model and induced AA-amyloidosis in NMRI mice by intravenous injections of purified amyloid fibrils (‘amyloid enhancing factor’) combined with inflammatory challenge (silver nitrate subcutaneously). Blood plasma and peripheral blood monocytes were isolated, sonicated and re-injected into new recipients followed by an inflammatory challenge during a three week period. When the animals were sacrificed presence of amyloid was analyzed in spleen sections after Congo red staining. Our result shows that some of the peripheral blood monocytes, isolated from animals with detectable amyloid, contained amyloid-seed that primed for AA-amyloid. The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes. Plasma recovered from mice with AA amyloidosis lacked seeding capacity. Amyloid enhancing activity can reside in monocytes recovered from mice with AA-amyloidosis and in a prion-like way trigger amyloid formation in conjunction with an inflammatory disorder. Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant. The monocyte-transfer mechanism should be eligible for the human disease and we point out blood transfusion as a putative route for transfer of amyloidosis.

A winding road – professional trajectories from higher education to working life: a case study of political science and psychology graduates

This qualitative and longitudinal study focuses on graduate employment and the development of graduate employment paths. The aim of this article is to explore the present professional trajectory from higher education to working life, with particular reference to graduates from two different study programmes at Linköping University in Sweden: Political Science and Psychology. More specifically, the article focuses on how graduates construe their professional trajectories in terms of their envisaged future work as senior students, and later as novice and early-career professionals with 18 and 34 months of work life experience. The results indicate that graduates’ professional identities and vision of their future work change over time. The set of categories, depicting the graduates’ vision and experiences of their professional trajectories, do not seem to follow a specific temporal and logical progression in their career. Rather, they appear in different order and at different points in time after graduation. The results, instead, endorse the discourse of lifelong learning and the need for flexibility and employability on the labour market.

AA-Amyloid is cleared by endogenous immunological mechanisms

Objective: AA amyloidosis is a complication to longstanding inflammatory diseases, but reduction of amyloid mass has been reported as the inflammation ceases. Not much is known about the endogenous factors that contribute to this amyloid resolution. Herein, we describe the dynamics of amyloid degradation and resolution in experimental murine AA-amyloidosis. Methods: AA-amyloidosis was induced in mice with injections of amyloid enhancing factor (AEF) and by inflammation induced with injections of silver nitrate. Resolution of amyloid deposits was monitored over time. Results: Virtually all amyloid was cleared within 34 weeks. Using the ELISA-technique, antibodies directed against protein AA were detected in animals during amyloid clearance phase and macrophages were shown to internalize amyloid. Also, passive immunization with an amyloid specific monoclonal antibody, produced by a B-cell clone recovered from an animal with advanced AA-amyloidosis, reduced amyloid development in murine AA-amyloidosis. Conclusion: Immunoglobulins co-localize with amyloid deposits and can contribute to amyloid degradation by Fc-receptor mediated phagocytosis, and should be considered key players in the degradation process.

Enacting simulation: A sociomaterial perspective on students' interprofessional collaboration.

ABSTRACT Full-scale simulation exercises are becoming more common as an educational feature of the undergraduate training of health professionals. This study explores how interprofessional collaboration is enacted by the participating students. Practice theory is used as the theoretical framework for a field study of two naturalistic educational settings, when medical and nursing students come together to practice in a simulated emergency situation, where a manikin is replacing the patient. Eighteen sessions of simulations were observed, and data were collected through standardised video recordings that were analysed collaboratively. To ensure transparency and scientific rigour, a stepwise constant comparative analysis was conducted, in which individual observations within and across single video recordings were compared, negotiated and eventually merged. The findings show that the student teams relate to the manikin as a technical, medical, and human body, and that interprofessional knowings and enactments emerge as a fluid movement between bodily positioning in synchrony and bodily positioning out of synchrony in relation to the sociomaterial arrangements. The findings are related to contemporary theorisations of practice comprising an integrated view of body and mind, and it is discussed how the findings can be used in simulation exercises to support participants’ learning in new ways.

Debriefing practices in interprofessional simulation with students: a sociomaterial perspective

BackgroundThe debriefing phase is an important feature of simulation activities for learning. This study applies a sociomaterial perspective on debriefing in interprofessional simulation with medical and nursing students. Sociomaterial perspectives are increasingly being used in order to understand professional practice and learning in new ways, conceptualising professional practice as being embodied, relational and situated in sociomaterial relations. The aim of the study is to explore how debriefing is carried out as a practice supporting students’ interprofessional learning.MethodsEighteen debriefing sessions following interprofessional full-scale manikin-based simulation with nursing and medical students from two different universities were video-recorded and analysed collaboratively by a team of researchers, applying a structured scheme for constant comparative analysis.ResultsThe findings show how debriefing is intertwined with, and shaped by social and material relationships. Two patterns of enacting debriefing emerged. Debriefing as algorithm was enacted as a protocol-based, closed inquiry approach. Debriefing as laissez-faire was enacted as a loosely structured collegial conversation with an open inquiry approach.ConclusionThe findings indicate that neither an imposed structure of the debriefing, nor the lack of structure assured interprofessional collaboration to emerge as a salient topic for reflection, even though that was an explicit learning objective for the simulation.

Impaired NK Cell Activation and Chemotaxis toward Dendritic Cells Exposed to Complement-Opsonized HIV-1

Mucosa resident dendritic cells (DCs) may represent one of the first immune cells that HIV-1 encounters during sexual transmission. The virions in body fluids can be opsonized with complement factors because of HIV-mediated triggering of the complement cascade, and this appears to influence numerous aspects of the immune defense targeting the virus. One key attribute of host defense is the ability to attract immune cells to the site of infection. In this study, we investigated whether the opsonization of HIV with complement (C-HIV) or a mixture of complement and Abs (CI-HIV) affected the cytokine and chemokine responses generated by DCs, as well as their ability to attract other immune cells. We found that the expression levels of CXCL8, CXCL10, CCL3, and CCL17 were lowered after exposure to either C-HIV or CI-HIV relative to free HIV (F-HIV). DCs exposed to F-HIV induced higher cell migration, consisting mainly of NK cells, compared with opsonized virus, and the chemotaxis of NK cells was dependent on CCL3 and CXCL10. NK cell exposure to supernatants derived from HIV-exposed DCs showed that F-HIV induced phenotypic activation (e.g., increased levels of TIM3, CD69, and CD25) and effector function (e.g., production of IFNγ and killing of target cells) in NK cells, whereas C-HIV and CI-HIV did not. The impairment of NK cell recruitment by DCs exposed to complement-opsonized HIV and the lack of NK activation may contribute to the failure of innate immune responses to control HIV at the site of initial mucosa infection.

Complement Opsonization Promotes Herpes Simplex Virus 2 Infection of Human Dendritic Cells

ABSTRACT Herpes simplex virus 2 (HSV-2) is one of the most common sexually transmitted infections globally, with a very high prevalence in many countries. During HSV-2 infection, viral particles become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of immune responses. In genital mucosa, the primary target cells for HSV-2 infection are epithelial cells, but resident immune cells, such as dendritic cells (DCs), are also infected. DCs are the activators of the ensuing immune responses directed against HSV-2, and the aim of this study was to examine the effects opsonization of HSV-2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV-2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV-2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV-1- or HSV-2-specific antibodies more or less abolished HSV-2 infection of DCs. Our results clearly demonstrate the importance of studying HSV-2 infection under conditions that ensue in vivo, i.e., conditions under which the virions are covered in complement fragments and complement fragments and antibodies, as these shape the infection and the subsequent immune response and need to be further elucidated. IMPORTANCE During HSV-2 infection, viral particles should become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of the immune responses. The dendritic cells are activators of the immune responses directed against HSV-2, and the aim of this study was to examine the effects of complement alone or complement and antibodies on HSV-2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses. Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV-2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV-2 pathogenesis.

The practice of supervision for professional learning: the example of future forensic specialists

Supervision intended to support learning is of great interest in professional knowledge development. No single definition governs the implementation and enactment of supervision because of different conditions, intentions, and pedagogical approaches. Uncertainty exists at a time when knowledge and methods are undergoing constant development. This situation affects professions with high demands on precision and safety, and thus supervision and learning. The aim of this article is to explore the practice of supervision for learning professional knowledge of forensic specialists. The context is the Swedish National Laboratory of Forensic Science internal training program, which focuses on learning in daily work when the forensic trainee is assigned a supervisor. Ethnographic studies of supervisors and trainees in different forensic specialties were conducted. Practice theory is used to understand how supervision is planned and implemented to support professional development. Findings show that supervision by seasoned professional forensic specialists is significant for trainee learning. However, supervision is arranged, and performed differently, indicating various conditions for learning. Furthermore, the material set-ups of the professional practice prefigure the practice of supervision. Supervision is an area of expertise that needs to be cultivated and learned to maintain highly specialized professional knowledge in current time of change and uncertainty.

Does gender matter? Differences between students at an interprofessional training ward.

Abstract Studies on graduates’ transitions from education into clinical work highlight inequalities concerning how women and men experience their professional learning and development. This study explores how female and male students from different programs within the health care education system (i.e. medicine, nursing, occupational therapy, and physiotherapy programmes) experience an interprofessional training ward (IPTW) as a part of their professional identity formation. Students from the medicine, nursing, physiotherapy, and occupational therapy programmes collaborate in teams during two weeks at one of three IPTWs at the medical school, Linköping University. They together take the responsibility for diagnosis, treatment, and rehabilitation of the patients, albeit with professional supervisors as support. During 2010 to 2011, 454 (93%) of the 488 students who practiced at the IPTWs answered a questionnaire on their experiences of the IPTW. The students stated that the IPTW had positively influenced their professional development. The female and male medical students were significantly less positive than other female and male students, respectively, concerning the value of IPTW. The male students from all programmes were slightly, but significantly, less positive than all the female students. These findings show that students “do gender” as an integral part of the educational practice. It is important to scrutinise the IPTW as an educational practice, influencing students’ preparation for future work. Gender should be discussed not only during the IPTW rotation but also in general during the curriculum for all healthcare programmes.