Patient-specific Bacteroides genome variants in pouchitis

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in mBio 7 (2016): e01713-16, doi:10.1128/mBio.01713-16.A 2-year longitudinal microbiome study of 22 patients who underwent colectomy with an ileal pouch anal anastomosis detected significant increases in distinct populations of Bacteroides during 9 of 11 patient visits that coincided with inflammation (pouchitis). Oligotyping and metagenomic short-read annotation identified Bacteroides populations that occurred in early samples, bloomed during inflammation, and reappeared after antibiotic treatment. Targeted cultivation of Bacteroides isolates from the same individual at multiple time points and from several patients detected subtle genomic changes, including the identification of rapidly evolving genomic elements that differentiate isogenic strains of Bacteroides fragilis from the mucosa versus lumen. Each patient harbored Bacteroides spp. that are closely related to commonly occurring clinical isolates, including Bacteroides ovatus, B. thetaiotaomicron, B. vulgatus, and B. fragilis, which contained unique loci in different patients for synthesis of capsular polysaccharides. The presence of unique Bacteroides capsular polysaccharide loci within different hosts and between the lumen and mucosa may represent adaptations to stimulate, suppress, and evade host-specific immune responses at different microsites of the ileal pouch.Leona M. and Harry B. Helmsley Charitable Trust; Bay and Paul Foundations; Frank R. Lillie Research Innovation Award; Gastrointestinal Research Foundation of Chicag

Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease

Severe amyloidosis and plaque-localized neuro-inflammation are key pathological features of Alzheimer’s disease (AD). In addition to astrocyte and microglial reactivity, emerging evidence suggests a role of gut microbiota in regulating innate immunity and influencing brain function. Here, we examine the role of the host microbiome in regulating amyloidosis in the APP(SWE)/PS1(ΔE9) mouse model of AD. We show that prolonged shifts in gut microbial composition and diversity induced by long-term broad-spectrum combinatorial antibiotic treatment regime decreases Aβ plaque deposition. We also show that levels of soluble Aβ are elevated and that levels of circulating cytokine and chemokine signatures are altered in this setting. Finally, we observe attenuated plaque-localised glial reactivity in these mice and significantly altered microglial morphology. These findings suggest the gut microbiota community diversity can regulate host innate immunity mechanisms that impact Aβ amyloidosis

Recalibrating Technology in Education using the Augmented Reality Mobile Application

Recalibration focuses on how teachers reevaluate and modify their teaching approach to provide quality education to the learners. Inquiry-based learning (IBL) allows the students to develop their investigatory skills and improve their critical thinking adeptness. The researchers adopted the Questioning, Investigation, Making, and Synthesizing (QIMS) model in teaching IBL. Integrating the Augmented Reality (AR) mobile application in IBL creates opportunities for student-centered learning. The AR app detects a marker and displays to the user the many facets of the Earth\u27s interior. This study aimed to investigate the students’ achievement and experiences in learning Earth Science using the Augmented Reality, as it was the first time that the teacher and the students utilized this technology in a classroom setting. The 30 Grade 8 Junior High School learners were purposively selected. The data needed were gathered using a researcher-made test. The test questionnaires focused on the different layers of the Earth, its composition, and the different types of the seismic waves. The researcher administered a pretest-posttest and integrated AR mobile application in teaching the lesson. The non-parametric Wilcoxon Signed Rank Test was used and yielded a result of p=0.000 significant difference at α≤0.05, which is strong proof that the observed data are very significant. Furthermore, students’ experiences show positive attitudes towards AR in the classroom and considered it as an effective tool in learning since distant learning in times of pandemic hinders students’ full capabilities to explore. This study found that using AR had a positive impact on student motivation, engagement, and achievement in a high school science class. This study is anchored on SDG No. 4- Quality education that aims to promote lifelong learning opportunities for all. Integrating technology in classroom teaching improves the quality of education and enhances the learning process of students

One assignment, two courses, multiple skills: A major engineering assignment with social, political and ethical dimensions

This paper discusses a major interdisciplinary assignment that spans two first year courses in the School of Sustainable Energy Engineering (SEE) at Simon Fraser University, Canada. The Persuasive Research Paper asks students to draw on ideas from multiple scholarly disciplines and fields of practice to argue a social, political, or ethical position in relation to a technical, engineering, or scientific topic. It is a combined assignment across two SEE courses, Energy, Society and Environment, and Process, Form and Convention in Professional Genres, and is intended to prepare students for future courses in the SEE program, their co-op placements, and their professional responsibilities as an engineer. Students are required to research and write a paper exploring opposing positions related to an area of controversy chosen from a list of topics supplied by the instructors. The assignment consists of four components, each of which involves a draft and final version, and peer reviews. Two preliminary assignments help students to plan their research, frame the position they will take on their topic, and conduct scholarly research. These prepare students for the other two components, a technical analysis and the final paper. For the peer review, students are grouped into threes and each person uses established criteria to review their group members’ papers using the ACE (Analytical, Constructive and Empowering) model of feedback. Students learn the skills of finding and using scholarly resources, and using persuasive arguments that draw on reliable sources and evidence. Also, throughout the assignment, students are practicing leadership skills, learning written and oral communication skills, and gaining a breadth of knowledge about energy, sustainability and society

Exuberant Endothelial C5b-9 Formation in Recurrent and De Novo Posttransplant Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation. It may present as a recurrence of atypical hemolytic uremic syndrome (aHUS) or may occur de novo. 1 Kidney graft outcome in patients with recurrent aHUS is poor and strongly dependent on the early initiation of anti-C5 therapy.1 However, diagnosing aHUS recurrence, as well as de novo TMA, is challenging because patients may present without hematological signs.1 A biopsy may not be feasible, particularly in patients with thrombocytopenia. Here, we evaluated whether an ex vivo assay of serum-induced terminal complement complex (C5b-9) formation on human microvascular endothelial cells (HMEC-1), which efficiently detects complement dysregulation in nontransplanted patients with aHUS,2 could also help diagnose posttransplant recurrent aHUS. We also evaluated whether de novo posttransplant TMA is associated with endothelial complement activation, which remains a widely discussed issue,3,4 and whether the C5b-9 formation assay could support diagnosis. Due to the high risk of recurrence, the incidence of TMA in kidney grafts exceeds 36 times in patients with a pretransplant history of aHUS, compared to those with other causes of end-stage renal disease. This underscores the importance of accurately diagnosing native kidney disease.1 Unfortunately, 20% to 30% of patients on transplant waiting lists have no diagnosis.5 To address this additional issue, we investigated whether the C5b-9 assay could help to identify aHUS cases among patients with end-stage renal disease

Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis

\ua9 2024 International Society of Nephrology. Introduction: Complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) have high risks for disease recurrence and allograft loss in transplant kidneys. Pegcetacoplan (targeted complement 3 [C3]/C3b inhibitor) may prevent excessive deposition of C3 and complement 5 [C5] breakdown products and associated renal damage. Methods: NOBLE (NCT04572854) is a prospective, phase 2, multicenter, open-label, randomized controlled trial evaluating the efficacy and safety of pegcetacoplan in posttransplant patients with recurrent C3G or IC-MPGN. The primary end point was reduction in C3c staining on renal biopsy at week 12 for patients who received either pegcetacoplan 1080 mg twice weekly by subcutaneous infusion plus standard-of-care (SOC) or SOC only. Results: Ten patients received pegcetacoplan and 3 received SOC only through week 12. At week 12, 5 of 10 pegcetacoplan-treated patients (50%) achieved ≥2 orders of magnitude (OOM) reduction in C3 staining (4 of these 5 had 0 staining and absent electron microscopy deposits) and 8 of 10 (80%) achieved ≥1 OOM reduction; 1 of 3 (33%) SOC-only patients showed staining reduction. Mean C3G histology activity score decreased by >54% in 8 of 10 pegcetacoplan-treated patients (80.0%). Pegcetacoplan-treated patients with baseline urine protein-to-creatinine ratio (uPCR) ≥1000 mg/g showed a median (interquartile range [IQR]) 54.4% (–56.33 to –53.95) reduction in proteinuria at week 12. In addition, pegcetacoplan-treated patients showed stable estimated glomerular filtration rate (eGFR), reduced plasma sC5b-9, and increased serum C3. Pegcetacoplan was well-tolerated and most adverse events were mild/moderate. No discontinuations, treatment withdrawals, or deaths were reported. Conclusion: NOBLE demonstrated efficacy, safety, and tolerability of pegcetacoplan for patients with posttransplant recurrent C3G and primary IC-MPGN

Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis.

Complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) have high risks for disease recurrence and allograft loss in transplant kidneys. Pegcetacoplan (targeted complement 3 [C3]/C3b inhibitor) may prevent excessive deposition of C3 and complement 5 [C5] breakdown products and associated renal damage. NOBLE (NCT04572854) is a prospective, phase 2, multicenter, open-label, randomized controlled trial evaluating the efficacy and safety of pegcetacoplan in posttransplant patients with recurrent C3G or IC-MPGN. The primary end point was reduction in C3c staining on renal biopsy at week 12 for patients who received either pegcetacoplan 1080 mg twice weekly by subcutaneous infusion plus standard-of-care (SOC) or SOC only. Ten patients received pegcetacoplan and 3 received SOC only through week 12. At week 12, 5 of 10 pegcetacoplan-treated patients (50%) achieved ≥2 orders of magnitude (OOM) reduction in C3 staining (4 of these 5 had 0 staining and absent electron microscopy deposits) and 8 of 10 (80%) achieved ≥1 OOM reduction; 1 of 3 (33%) SOC-only patients showed staining reduction. Mean C3G histology activity score decreased by >54% in 8 of 10 pegcetacoplan-treated patients (80.0%). Pegcetacoplan-treated patients with baseline urine protein-to-creatinine ratio (uPCR) ≥1000 mg/g showed a median (interquartile range [IQR]) 54.4% (-56.33 to -53.95) reduction in proteinuria at week 12. In addition, pegcetacoplan-treated patients showed stable estimated glomerular filtration rate (eGFR), reduced plasma sC5b-9, and increased serum C3. Pegcetacoplan was well-tolerated and most adverse events were mild/moderate. No discontinuations, treatment withdrawals, or deaths were reported. NOBLE demonstrated efficacy, safety, and tolerability of pegcetacoplan for patients with posttransplant recurrent C3G and primary IC-MPGN