ABSTRACT
Aim: Graft-versus-host disease (GvHD) is a major complication arising in patients undergoing allogenic hematopoietic stem cell transplantation. Material & methods: We tested ruxolitinib (a selective JAK1/2 inhibitor) efficacy in three different preclinical models of GvHD. Results: Ruxolitinib, at doses that mimic clinically achievable human JAK/signal transducers and activators of transcription target inhibition, significantly reduced alloreactive T-cell activation and infiltration in the lung and skin, leading to improved outcomes in two experimental models of steroid-refractory acute and chronic GvHD. Additionally, we describe a novel humanized GvHD model in which immunodeficient NOG animals are engineered to produce human IL-15 to facilitate enhanced T- and NK cell engraftment, leading to severe GvHD. Conclusion: Ruxolitinib treatment ameliorated disease symptoms resulting from targeted immune modulation via JAK/signal transducers and activators of transcription signaling inhibition.
Subject(s)
Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation/adverse effects , Janus Kinase Inhibitors/pharmacology , Nitriles/pharmacology , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Animals , Disease Models, Animal , Heterografts , Humans , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 2/antagonists & inhibitors , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, TransgenicABSTRACT
Nurse practitioners are capable leaders in primary care design as practices nationwide move to consider and adopt the patient-centered medical home. The chronic care model provides a structure to enhance the care of chronic illness. Nurse practitioners are instrumental in many areas of this model as both leaders and caregivers. Safety and quality are basic medical home goals; nurse practitioners enhance both. The addition of a nurse practitioner to a practice is an effective "value add" in every way.
Subject(s)
Chronic Disease/nursing , Family Practice/organization & administration , Nurse Practitioners , Patient-Centered Care/organization & administration , Humans , Models, Organizational , Nurse Practitioners/education , Nurse's Role , Patient Care Team/organization & administration , Practice Management, Medical , United States , WorkforceABSTRACT
Salmonella enterica serovar Newport MDR-AmpC expressing TEM-1b and extended-spectrum beta-lactamase SHV-12 was isolated from affected animals during an outbreak of salmonellosis that led to a 3-month closure of one of the largest equine hospitals in the United States.
