Project description:We used the ileal loop model to assess the effects of enteric bacteria organisms on host gene expression in intestinal tissue independent of and following early SIV infection. SIV infection in the gut causes rapid and severe immune dysfunction and damage to the intestinal structure, this may alter the intimate interaction with lumenal organisms. This study was performed to determine whether early SIV infection, prior to the depletion of CD4+ T cells, can alter interaction of the host with pathogenic Salmonella serovar Typhimurium (ST) or commensal Lactobacillus plantarum (LP), and to further understand the earliest changes to the intestinal mucosa following SIV infection. We used microarray analysis to detail the global program of gene expression underlying changes in the ileum following early SIV infection, and if these changes in any way alter the host interaction/ response to pathogenic and commensal enteric bacteria. A subset of animals were infected with SIVmac251 for 2.5 days, following which they underwent a loop surgery where the ileum was sectioned off with surgical ties and bacteria (ST or LP) or their respective media controls (LB or MRS) were injected intralumenally. Following 5 hours of incubation the loops were excised and frozen. Tissue sections were cut and RNA extracted for gene expression analysis. Rhesus Macaques infected with SIVmac251 for 2.5 days compared to uninfected controls. Comparisons are of ileum loop sections injected with Salmonella serovar Typhimurium, Lactobacillus Plantarum or respective media controls LB or MRS.
Project description:Surgical revision of infection can involve multiple procedures. Each revision activates a tissue injury response and disrupts the established bacterial biofilm. However, it is not well understood how the bacteria, immune system, and overall tissue environment coordinate their response to revision. Our results show that immunological niches already compromised by infection – such as the bone marrow, lymph nodes, and circulating blood – further upregulate pro-inflammatory programs in response to revision surgery. This enhanced inflammation at the incision site has no effect on reducing bacteria numbers. Instead, it leads to increased expression of virulence factors, enhanced tissue remodeling, and damage including bone osteolysis and muscle fibrosis. Whereas muscle fibrosis appears to resolve 14 days post-revision, osteolysis continues to progress. These findings show that revision surgery negatively impacts all tissues within the surgical site. It is therefore essential to question the risks and benefits of each revision on a case-by-case basis. Further, understanding the timing and tissue changes associated with revision of infected orthopedic sites will help inform the design of additional interventions to minimize tissue damage and maximize bactericidal effects.
Project description:Infective endocarditis is a severe disease caused by the infection of heart valves and endocardium by pathogenic germ. Antimicrobial therapy and surgery remain the basis of treatment, and up to 50% of the patients require surgical replacement of the affected valves to control the infectious source. The objective of this work is to identify the existence of endotypes in a prospective cohort of patients with infective endocarditis. We performed a bulk RNA-seq form peripheral blood to cluster patients according to their transcriptomic profiles at diagnosis and during their follow-up. Clinical data, outcomes and response to surgery were assessed in a cluster-specific manner, in order to identify differences in the pathogenesis that could help to find personalized treatments and improve the outcome.
Project description:Infective endocarditis is a severe disease caused by the infection of heart valves and endocardium by pathogenic germ. Antimicrobial therapy and surgery remain the basis of treatment, and up to 50% of the patients require surgical replacement of the affected valves to control the infectious source. The objective of this work is to identify the existence of endotypes in a prospective cohort of patients with infective endocarditis. We performed a bulk RNA-seq form peripheral blood to cluster patients according to their transcriptomic profiles at diagnosis and during their follow-up. Clinical data, outcomes and response to surgery were assessed in a cluster-specific manner, in order to identify differences in the pathogenesis that could help to find personalized treatments and improve the outcome.
Project description:This is a prospective randomized study to evaluate the difference in the rate of surgical site infection between the patients who used Sodium Picosulfate solution(PicosolutionⓇ) and tablet Oral Sulphate Solution(ORA·FANGⓇ) for bowel preparation before colorectal cancer surgery .
Project description:Gene expression was assessed with Nanostring in the surgical specimens obtained from a Window of Opportunity trial with MK-2206 in early stage breast cancer. Tumor biopsies and surgical specimens were compared for patients who received MK-2206 along with a prospective untreated control group of patients. Greater expression of interferon related genes was seen in surgical specimens following MK-2206 and compared to untreated controls.
Project description:Gene expression was assessed with Nanostring in the surgical specimens obtained from a Window of Opportunity trial with MK-2206 in early stage breast cancer. Tumor biopsies and surgical specimens were compared for patients who received MK-2206 along with a prospective untreated control group of patients. Greater expression of interferon related genes was seen in surgical specimens following MK-2206 and compared to untreated controls.
