How context affects transdisciplinary research: insights from Asia, Africa and Latin America

Transdisciplinary research (TDR) has been developed to generate knowledge that effectively fosters the capabilities of various societal actors to realize sustainability transformations. The development of TDR theories, principles, and methods has been largely governed by researchers from the global North and has reflected their contextual conditions. To enable more contextsensitive TDR framing, we sought to identify which contextual characteristics affect the design and implementation of TDR in six case studies in Asia, Latin America, and Africa, and what this means for TDR as a scientific approach. To this end, we distinguished four TDR process elements and identified several associated context dimensions that appeared to influence them. Our analysis showed that contextual characteristics prevalent in many Southern research sites—such as highly volatile socio-political situations and relatively weak support infrastructure—can make TDR a challenging endeavour. However, we also observed a high degree of variation in the contextual characteristics of our sites in the global South, including regarding group deliberation, research freedom, and dominant perceptions of the appropriate relationship between science, society, and policy. We argue that TDR in these contexts requires pragmatic adaptations as well as more fundamental reflection on underlying epistemological concepts around what it means to conduct “good science”, as certain contextual characteristics may influence core epistemological values of TDR

The astrocyte-produced growth factor HB-EGF limits autoimmune CNS pathology

Central nervous system (CNS)-resident cells such as microglia, oligodendrocytes and astrocytes are gaining increasing attention in respect to their contribution to CNS pathologies including multiple sclerosis (MS). Several studies have demonstrated the involvement of pro-inflammatory glial subsets in the pathogenesis and propagation of inflammatory events in MS and its animal models. However, it has only recently become clear that the underlying heterogeneity of astrocytes and microglia can not only drive inflammation, but also lead to its resolution through direct and indirect mechanisms. Failure of these tissue-protective mechanisms may potentiate disease and increase the risk of conversion to progressive stages of MS, for which currently available therapies are limited. Using proteomic analyses of cerebrospinal fluid specimens from patients with MS in combination with experimental studies, we here identify Heparin-binding EGF-like growth factor (HB-EGF) as a central mediator of tissue-protective and anti-inflammatory effects important for the recovery from acute inflammatory lesions in CNS autoimmunity. Hypoxic conditions drive the rapid upregulation of HB-EGF by astrocytes during early CNS inflammation, while pro-inflammatory conditions suppress trophic HB-EGF signaling through epigenetic modifications. Finally, we demonstrate both anti-inflammatory and tissue-protective effects of HB-EGF in a broad variety of cell types in vitro and use intranasal administration of HB-EGF in acute and post-acute stages of autoimmune neuroinflammation to attenuate disease in a preclinical mouse model of MS. Altogether, we identify astrocyte-derived HB-EGF and its epigenetic regulation as a modulator of autoimmune CNS inflammation and potential therapeutic target in MS. Linnerbauer and colleagues find that HB-EGF produced by reactive astrocytes is protective during autoimmune neuroinflammation, but epigenetically suppressed during late stages

Activation of Human Monocytes by Live Borrelia burgdorferi Generates TLR2-Dependent and -Independent Responses Which Include Induction of IFN-β

It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs) elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-β and a number of interferon-stimulated genes (ISGs), which are not known to result from TLR2 signaling. Using isolated monocytes, we demonstrated that cell activation signals elicited by live Bb result from cell surface interactions and uptake and degradation of organisms within phagosomes. As with PBCMs, live Bb induced markedly greater transcription and secretion of TNF-α, IL-6, IL-10 and IL-1β in monocytes than did lysates. Secreted IL-18, which, like IL-1β, also requires cleavage by activated caspase-1, was generated only in response to live Bb. Pro-inflammatory cytokine production by TLR2-deficient murine macrophages was only moderately diminished in response to live Bb but was drastically impaired against lysates; TLR2 deficiency had no significant effect on uptake and degradation of spirochetes. As with PBMCs, live Bb was a much more potent inducer of IFN-β and ISGs in isolated monocytes than were lysates or a synthetic TLR2 agonist. Collectively, our results indicate that the enhanced innate immune responses of monocytes following phagocytosis of live Bb have both TLR2-dependent and -independent components and that the latter induce transcription of type I IFNs and ISGs

ETIOLOGIES DES HYPERCALCITONINEMIES DANS LES PATHOLOGIES ENDOCRINIENNES CHIRURGICALES

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Improving a Process to Obtain Hepatitis B Serology Among Patients Treated with Infliximab at a Large Urban Children\u27s Hospital

Background: Hepatitis B infection is a significant public health challenge despite improvements in vaccination efforts. Patients such as those on chronic immunosuppressive therapy for inflammatory bowel disease (IBD) or rheumatic disease may incur greater risk. The risk of reactivation of hepatitis B while on immunosuppressive therapy may have mortality rates up to 25%. These patients should be screened for acute or chronic infection and vaccinated if necessary. Our aim was to reliably complete hepatitis B screenings in patients receiving infliximab at Cincinnati Children\u27s Hospital Medical Center (CCHMC). Methods: Eligible patients included all patients with gastroenterology (GI) IBD and rheumatology receiving infliximab between October 2015 and March 2016. Using quality improvement methodology and the \u27plan-do-study-act\u27 (PDSA) approach, interventions centred around education of clinical providers, previsit planning and the development of \u27talking points\u27 for patients. Results: An initial screen of the IBD population revealed that 48% of the IBD patient population had been screened for anti-HBs alone, but no patients from GI or rheumatology divisions had a complete set of hepatitis B serology prior to the intervention including anti-Hep B Core and Hep B Surface Antigen. Seven PDSA cycles were performed during the 32-week intervention period, resulting in an increase in patients screened from 0% to ~85%. By March 2016, a total of 251 patients (201 GI, 50 rheumatology) had up-to-date hepatitis B serology screening. Automated ordering of the hepatitis B serology and \u27talking points\u27 for the provider had the greatest impact on successful screening. Conclusions: We developed a method to obtain hepatitis B serology on at-risk patients on infliximab within two subspecialty divisions within a large children\u27s hospital. Next steps will be to develop a process to reliably provide vaccines for patients who are seronegative, expand this process to all patients who are identified as immunocompromised within GI and rheumatology and then expand this process to other divisions at the CCHMC

Improving a Process to Obtain Hepatitis B Serology Among Patients Treated with Infliximab at a Large Urban Children\u27s Hospital

Background: Hepatitis B infection is a significant public health challenge despite improvements in vaccination efforts. Patients such as those on chronic immunosuppressive therapy for inflammatory bowel disease (IBD) or rheumatic disease may incur greater risk. The risk of reactivation of hepatitis B while on immunosuppressive therapy may have mortality rates up to 25%. These patients should be screened for acute or chronic infection and vaccinated if necessary. Our aim was to reliably complete hepatitis B screenings in patients receiving infliximab at Cincinnati Children\u27s Hospital Medical Center (CCHMC). Methods: Eligible patients included all patients with gastroenterology (GI) IBD and rheumatology receiving infliximab between October 2015 and March 2016. Using quality improvement methodology and the \u27plan-do-study-act\u27 (PDSA) approach, interventions centred around education of clinical providers, previsit planning and the development of \u27talking points\u27 for patients. Results: An initial screen of the IBD population revealed that 48% of the IBD patient population had been screened for anti-HBs alone, but no patients from GI or rheumatology divisions had a complete set of hepatitis B serology prior to the intervention including anti-Hep B Core and Hep B Surface Antigen. Seven PDSA cycles were performed during the 32-week intervention period, resulting in an increase in patients screened from 0% to ~85%. By March 2016, a total of 251 patients (201 GI, 50 rheumatology) had up-to-date hepatitis B serology screening. Automated ordering of the hepatitis B serology and \u27talking points\u27 for the provider had the greatest impact on successful screening. Conclusions: We developed a method to obtain hepatitis B serology on at-risk patients on infliximab within two subspecialty divisions within a large children\u27s hospital. Next steps will be to develop a process to reliably provide vaccines for patients who are seronegative, expand this process to all patients who are identified as immunocompromised within GI and rheumatology and then expand this process to other divisions at the CCHMC