Porcine Circovirus Cap-Induced Apoptosis of Non-Infected PK15 Cells

Porcine Circovirus 2 (PCV2) is a pathogen of major importance for swine production around the world. Despite development of several vaccines and robust vaccination programs, PCV2 continues to persistently transmit within and between swine herds causing infections marked by immunosuppression via lymphocyte depletion. This study aims to improve understanding of porcine circovirus diseases (PCVD) pathogenesis caused by PCV capsid cytotoxicity which activates apoptosis in non-infected bystander cells. Putatively non-pathogenic Porcine Circovirus 1 (PCV1) was also included to help understand why there is a difference in pathogenicity between PCV1 and PCV2. Porcine Circovirus 3 (PCV3) has recently emerged worldwide as a possible etiological agent of clinical syndromes observed in swine that are similar to PCVD caused by PCV2. The capsid protein of PCV3 (PCV 3 Cap) was also included in this study to provide initial information regarding the cytotoxicity of this protein. Results were obtained through flow cytometric analysis of apoptosis using Annexin V-FITC and 7-AAD to measure apoptosis markers and cell death respectively. Flow cytometry results were reinforced by also utilizing a TUNEL assay in conjunction with confocal imaging to detect cells undergoing DNA fragmentation leading to apoptosis. Results show that monomeric PCV2 Cap, 1% formaldehyde inactivated and dialyzed PCV2, PCV1 virus-like particles (VLPs), PCV2 VLPs, and PCV3 VLPs are all able to activate apoptosis in porcine kidney (PK15) cells at a rate of ~%30 after a 24-hour exposure; this apoptotic similar to apoptosis caused by 50 µM etoposide, which is a strong chemical inducer of apoptosis. These results coupled with preliminary data obtained by pre-treating PK15 cells with caspase-8 or caspase-9 inhibitors suggest the involvement of caspase-8 and caspase-9 in PCV2 Cap induced apoptosis and lend weight to the idea of PCV2 Cap as a primary virulence factor during infections. In contrast, PCV1 Cap induced apoptosis does not appear to involve caspase-8 or caspase-9 indicating an alternate pathway to PK15 cell apoptosis, while PCV3 Cap appears to induce PK15 cell apoptosis with some involvement of caspase-9

Gentrification in Communities Across the Transatlantic

For our project, we decided to tackle the topic of gentrification. More specifically, we cover gentrification transatlantically by looking at Port Au Prince, and also look at gentrification in Miami and Indianapolis, our own backyard.https://digitalcommons.butler.edu/freedom-movement-spring-2022/1002/thumbnail.jp

Pure Award Final Report

Epstein-Barr virus (EBV) has infected more 90% of the world’s population, and is the cause of 2% of all neoplasms globally. In pigs, a closely related gammaherpes virus was identified called Porcine Lymphotrophic Herpesvirus 3 (PLHV3), that also causes lymphoproliferative disorders that resemble those caused by EBV. The purpose of this research is to generate a high titer viral stock of PLHV3 by shifting the viral life cycle from latency to lytic replication using baculovirus expression systems (BEVS) in latently infected cell lines. Infected lymphoblastic cell lines (LCL) will be infected with baculovirus vector carrying two PLHV3 immediate early genes that are crucial for lytic reactivation, BZLF1 and BRLF1. These immediate early genes will become expressed after the infection to produce recombinant proteins in high quantity, thus allowing viral reactivation. BZLF1, BRLF1 and an appropriate mammalian promoter will be cloned into the vector using PCR cloning. Acquiring a high titer viral stock will allow the generation of a chimeric PLHV3-EBV virus that could be used to establish a porcine model for studying EBV

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine