Virus infection drives IL-2 antibody complexes into pro-inflammatory agonists in mice

The use of IL-2/JES6-1 Ab complex (IL-2 Ab Cx) has been considered as a potential therapeutic for inflammatory diseases due to its selective expansion of regulatory T cells (Tregs) in mice. Here, IL-2 Ab Cx was explored as a therapeutic agent to reduce joint inflammation induced by chikungunya virus, an alphavirus causing debilitating joint disease globally. Virus-infected mice treated with IL-2 Ab Cx exhibited exacerbated joint inflammation due to infiltration of highly activated CD4(+) effector T cells (Teffs). Virus infection led to upregulation of CD25 on the Teffs, rendering them sensitive towards IL2 Ab Cx. Ready responsiveness of Teffs to IL-2 was further demonstrated in healthy human donors, suggesting that the use of IL-2 Ab Cx in humans is not suitable. Changes in IL-2 sensitivity during active virus infection could change the responsive pattern towards the IL-2 Ab Cx, resulting in the expansion of pro-inflammatory rather than anti-inflammatory responses

Co-infection with Chikungunya virus alters trafficking of pathogenic CD8(+) T cells into the brain and prevents Plasmodium-induced neuropathology

Arboviral diseases have risen significantly over the last 40 years, increasing the risk of co‐infection with other endemic disease such as malaria. However, nothing is known about the impact arboviruses have on the host response toward heterologous pathogens during co‐infection. Here, we investigate the effects of Chikungunya virus (CHIKV ) co‐infection on the susceptibility and severity of malaria infection. Using the Plasmodium berghei ANKA (PbA) experimental cerebral malaria (ECM ) model, we show that concurrent co‐infection induced the most prominent changes in ECM manifestation. Concurrent co‐infection protected mice from ECM mortality without affecting parasite development in the blood. This protection was mediated by the alteration of parasite‐specific CD8+ T‐cell trafficking through an IFN γ‐mediated mechanism. Co‐infection with CHIKV induced higher splenic IFN γ levels that lead to high local levels of CXCL 9 and CXCL 10. This induced retention of CXCR 3‐expressing pathogenic CD8+ T cells in the spleen and prevented their migration to the brain. This then averts all downstream pathogenic events such as parasite sequestration in the brain and disruption of blood–brain barrier that prevents ECM ‐induced mortality in co‐infected mice

Enhancing Mentoring in Palliative Care: An Evidence Based Mentoring Framework

Background: Growing concerns over ethical issues in mentoring in medicine and surgery have hindered efforts to reinitiate mentoring for Palliative Care (PC) physicians following the easing of COVID-19 restrictions. Ranging from the misappropriation of mentee’s work to bullying, ethical issues in mentoring are attributed to poor understanding and structuring of mentoring programs, underlining the need for a consistent approach to mentoring practices. Methods: Given diverse practices across different settings and the employ of various methodologies, a novel approach to narrative reviews (NR)s is proposed to summarize, interpret, and critique prevailing data on novice mentoring. To overcome prevailing concerns surrounding the reproducibility and transparency of narrative reviews, the Systematic Evidenced Based Approach (SEBA) adopts a structured approach to searching and summarizing the included articles and employed concurrent content and thematic analysis that was overseen by a team of experts. Results: A total of 18 915 abstracts were reviewed, 62 full text articles evaluated and 41 articles included. Ten themes/categories were ascertained identified including Nature; Stakeholders; Relationship; Approach; Environment; Benefits; Barriers; Assessments; Theories and Definitions. Conclusion: By compiling and scrutinizing prevailing practice it is possible to appreciate the notion of the mentoring ecosystem which sees each mentee, mentor, and host organization brings with them their own microenvironment that contains their respective goals, abilities, and contextual considerations. Built around competency based mentoring stages, it is possible to advance a flexible yet consistent novice mentoring framework. </jats:sec

Short-term comparative outcomes between reverse shoulder arthroplasty for shoulder trauma and shoulder arthritis: a Southeast Asian experience

Background Reverse shoulder arthroplasty (RSA), first introduced as a management option for cuff tear arthropathy, is now an accepted treatment for complex proximal humeral fractures. Few studies have identified whether the outcomes of RSA for shoulder trauma are comparable to those of RSA for shoulder arthritis. Methods This is a retrospective, single-institution cohort study of all patients who underwent RSA at our institution between January 2013 and December 2019. In total, 49 patients met the inclusion criteria. As outcomes, we evaluated the 1-year American Shoulder and Elbow Surgeons (ASES) and Constant shoulder scores, postoperative shoulder range of motion, intra- and postoperative complications, and cumulative revision rate. The patients were grouped based on preoperative diagnosis to compare postoperative outcomes across two broad groups. Results The median follow-up period was 32.8 months (interquartile range, 12.6–66.6 months). The 1-year visual analog scale, range of motion, and Constant and ASES functional scores were comparable between RSAs performed to treat shoulder trauma and that performed for arthritis. The overall complication rate was 20.4%, with patients with a preoperative diagnosis of arthritis having significantly more complications than those with a preoperative diagnosis of trauma (34.8% vs. 7.7%). Conclusions Patients who underwent RSA due to a proximal humeral fracture or dislocation did not fare worse than those who underwent RSA for arthritis at 1 year, in terms of both functional and radiological outcomes

Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections

10.1172/jci.insight.92428JCI insight2

Mentoring in palliative medicine in the time of covid-19: a systematic scoping review : Mentoring programs during COVID-19.

IntroductionThe redeployment of mentors and restrictions on in-person face-to-face mentoring meetings during the COVID-19 pandemic has compromised mentoring efforts in Palliative Medicine (PM). Seeking to address these gaps, we evaluate the notion of a combined novice, peer-, near-peer and e-mentoring (CNEP) and interprofessional team-based mentoring (IPT) program.MethodsA Systematic Evidence Based Approach (SEBA) guided systematic scoping review was carried out to study accounts of CNEP and IPT from articles published between 1st January 2000 and 28th February 2021. To enhance trustworthiness, concurrent thematic and content analysis of articles identified from structured database search using terms relating to interprofessional, virtual and peer or near-peer mentoring in medical education were employed to bring together the key elements within included articles.ResultsFifteen thousand one hundred twenty one abstracts were reviewed, 557 full text articles were evaluated, and 92 articles were included. Four themes and categories were identified and combined using the SEBA's Jigsaw and Funnelling Process to reveal 4 domains - characteristics, mentoring stages, assessment methods, and host organizations. These domains suggest that CNEP's structured virtual and near-peer mentoring process complement IPT's accessible and non-hierarchical approach under the oversight of the host organizations to create a robust mentoring program.ConclusionThis systematic scoping review forwards an evidence-based framework to guide a CNEP-IPT program. At the same time, more research into the training and assessment methods of mentors, near peers and mentees, the dynamics of mentoring interactions and the longitudinal support of the mentoring relationships and programs should be carried out

HOST IMMUNE MODULATION DURING MALARIA PARASITES AND CHIKUNGUNYA VIRUS COINFECTION IN EXPERIMENTAL MODELS

Ph.DDOCTOR OF PHILOSOPH

Vancomycin-loaded bone cement bullet for treatment of chronic septic arthritis post ACL reconstruction surgery

The consequence of post-operative infection can be devastating despite its rare incidence. Common organisms causing post-operative infection are normal flora of the skin: Staphylococcus aureus and Staphylococcus epidermidis. Early diagnosis followed by arthroscopic debridement and antibiotic therapy with graft retention remains the main aim of treatment. However, there are certain cases where the infection persists despite early intervention. Vancomycin-loaded bone cement bullet inserted into bone tunnel can provide a high local concentration of vancomycin with bactericidal effect and low systemic complications to treat deep-seated infection. © 2019 UPM Press. All rights reserved

Impaired Th1 responses in patients with acute exacerbations of COPD are improved with PD-1 blockade

Poor T-cell function is implicated in susceptibility to infections in COPD patients. Proportion of circulating PD-1+ CD4+ T-cells is elevated in AECOPD patients. Systemic inflammation is associated with elevated proportion of PD-1+ CD4+ T-cells. PD-1 blockade increased the production of IFNγ, TNF, IL-6 and IL-10 by anti-CD3-induced PBMC