Importance: Intestinal multidrug-resistant organism (MDRO) colonization is highly prevalent in long-term acute care hospital (LTACH) patients and is associated with MDRO infection and transmission. However, there are no therapies approved by the US Food and Drug Administration to reduce intestinal MDRO colonization.
Objective: To determine the safety and acceptability of fecal microbiota transplantation (FMT) in LTACH patients.
The enteric microbiota is an established reservoir for multidrug-resistant organisms that present urgent clinical and public health threats. Observational data and small interventional studies suggest that microbiome interventions, such as fecal microbiota products and characterized live biotherapeutic bacterial strains, could be an effective antibiotic-sparing prevention approach to address these threats. However, bacterial colonization is a complex ecological phenomenon that remains understudied in the context of the human gut.
View Article and Find Full Text PDFHospitals often seek to improve the effectiveness and experience of care through new building construction. However, the association between the built hospital environment, patient outcomes, and patient experience remains unclear. This retrospective matched cohort study leveraged natural experimental conditions to characterize major clinical outcomes and patient experience in medicine patients admitted to a new hospital building incorporating evidence-based design features compared with controls admitted to legacy buildings.
View Article and Find Full Text PDFThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape convalescent and vaccine-induced antibody responses has renewed focus on the development of broadly protective T-cell-based vaccines. Here, we apply structure-based network analysis and assessments of HLA class I peptide stability to define mutationally constrained CD8 T cell epitopes across the SARS-CoV-2 proteome. Highly networked residues are conserved temporally among circulating variants and sarbecoviruses and disproportionately impair spike pseudotyped lentivirus infectivity when mutated.
View Article and Find Full Text PDFDefining factors that govern CD8 T cell immunodominance is critical for the rational design of vaccines for viral pathogens. Here, we assess the contribution of human leukocyte antigen (HLA) class-I-peptide stability for 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with antigen processing (TAP)-deficient mono-allelic HLA-expressing cell lines. We find that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules in comparison to subdominant epitopes.
View Article and Find Full Text PDFCase-based conference preparation is a valuable skill rarely covered in medical school training. We implemented an innovative program to teach fourth-year medical students to prepare and facilitate a virtual case presentation conference with faculty mentorship. Feedback survey results indicated improved confidence in case presentation and in establishing a broad differential.
View Article and Find Full Text PDFHost proteins are essential for HIV entry and replication and can be important nonviral therapeutic targets. Large-scale RNA interference (RNAi)-based screens have identified nearly a thousand candidate host factors, but there is little agreement among studies and few factors have been validated. Here we demonstrate that a genome-wide CRISPR-based screen identifies host factors in a physiologically relevant cell system.
View Article and Find Full Text PDF