ABSTRACT
The coproduction learning health system (CLHS) model extends the definition of a learning health system to explicitly bring together patients and care partners, health care teams, administrators, and scientists to share the work of optimizing health outcomes, improving care value, and generating new knowledge. The CLHS model highlights a partnership for coproduction that is supported by data that can be used to support individual patient care, quality improvement, and research. We provide a case study that describes the application of this model to transform care within an oncology program at an academic medical center.
Subject(s)
Learning Health System , Humans , Caregivers , Academic Medical Centers , Patient Care TeamABSTRACT
In this survey of 41 hospitals, 18 (72%) of 25 respondents reporting utilization of National Healthcare Safety Network resources demonstrated accurate central-line-associated bloodstream infection reporting compared to 6 (38%) of 16 without utilization (adjusted odds ratio, 5.37; 95% confidence interval, 1.16-24.8). Adherence to standard definitions is essential for consistent reporting across healthcare facilities.
Subject(s)
Catheter-Related Infections , Catheterization, Central Venous , Sepsis , Humans , Catheter-Related Infections/epidemiology , Surveys and Questionnaires , Delivery of Health CareABSTRACT
Topoisomerase IIα is an essential enzyme that resolves topological constraints in genomic DNA. It functions in disentangling intertwined chromosomes during anaphase leading to chromosome segregation thus preserving genomic stability. Here we describe a previously unrecognized mechanism regulating topoisomerase IIα activity that is dependent on the F-box protein Fbxo28. We find that Fbxo28, an evolutionarily conserved protein, is required for proper mitotic progression. Interfering with Fbxo28 function leads to a delay in metaphase-to-anaphase progression resulting in mitotic defects as lagging chromosomes, multipolar spindles and multinucleation. Furthermore, we find that Fbxo28 interacts and colocalizes with topoisomerase IIα throughout the cell cycle. Depletion of Fbxo28 results in an increase in topoisomerase IIα-dependent DNA decatenation activity. Interestingly, blocking the interaction between Fbxo28 and topoisomerase IIα also results in multinucleated cells. Our findings suggest that Fbxo28 regulates topoisomerase IIα decatenation activity and plays an important role in maintaining genomic stability.
Subject(s)
Antigens, Neoplasm/metabolism , DNA Topoisomerases, Type II/metabolism , DNA-Binding Proteins/metabolism , DNA/metabolism , Mitosis , SKP Cullin F-Box Protein Ligases/metabolism , Amino Acid Sequence , Chromosomes, Human/metabolism , Conserved Sequence , Down-Regulation , Evolution, Molecular , Gene Deletion , HEK293 Cells , HeLa Cells , Humans , Protein Binding , SKP Cullin F-Box Protein Ligases/chemistryABSTRACT
BACKGROUND: So far, there exists no golden standard for the treatment of arthrofibrosis (AF) following total knee arthroplasty (TKA). Although pain is a hallmark of AF, nociceptive nerve fibers have never been investigated in affected joint tissue. METHODS: A total of 24 patients with osteoarthritis (OA) of the knee (n = 12) and post-TKA AF of the knee (n = 12) were included. Along evaluation of typical clinical signs and symptoms by using the Knee Society Clinical Rating System (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC index), the innervation of joint tissue was studied by semiquantitative immunofluorescence of nerve fibers. RESULTS: Patients with AF compared to OA had a lower KSS and lower KOOS. In all compartments (anterior, medial, and lateral recesses), the density of synovial sympathetic nerve fibers was significantly higher in OA compared to AF, which was also true for the density of sensory nerve fibers in the medial and lateral recesses. In synovial tissue of the anterior recess of patients with AF compared to OA, the density of nociceptive sensory nerve fibers was significantly higher relative to sympathetic nerve fibers. This was similarly observed in the neighboring infrapatellar fat pad of the knee. CONCLUSIONS: Similar as in many painful musculoskeletal diseases, this study indicates that patients with arthrofibrosis of the knee after TKA demonstrate a preponderance of profibrotic sensory nerve fibers over antifibrotic sympathetic nerve fibers. This could serve as a starting point for AF therapy with specific antifibrotic pain medication or regional anesthetic techniques.
Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Nerve Fibers/pathology , Nociceptors/pathology , Osteoarthritis, Knee/pathology , Synovial Membrane/innervation , Aged , Aged, 80 and over , Female , Fibrosis , Humans , Knee Joint/metabolism , Knee Joint/pathology , Male , Middle Aged , Nerve Fibers/metabolism , Nociceptors/metabolism , Osteoarthritis, Knee/metabolism , Severity of Illness Index , Substance P/metabolismABSTRACT
Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle.