Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway

Circulating levels of chylomicron remnants (CMRs) increase postprandially and their composition directly reflects dietary lipid intake. These TG-rich lipoproteins likely contribute to the development of endothelial dysfunction, albeit via unknown mechanisms. Here, we investigated how the FA composition of CMRs influences their actions on human aortic endothelial cells (HAECs) by comparing the effects of model CMRs—artificial TG-rich CMR-like particles (A-CRLPs)—containing TGs extracted from fish, DHA-rich algal, corn, or palm oils. HAECs responded with distinct transcriptional programs according to A-CRLP TG content and oxidation status, with genes involved in antioxidant defense and cytoprotection most prominently affected by n-3 PUFA-containing A-CRLPs. These particles were significantly more efficacious inducers of heme oxygenase-1 (HO-1) than n-6 PUFA corn or saturated FA-rich palm CRLPs. Mechanistically, HO-1 induction by all CRLPs requires NADPH oxidase 4, with PUFA-containing particles additionally dependent upon mitochondrial reactive oxygen species. Activation of both p38 MAPK and PPARβ/δ culminates in increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression/nuclear translocation and HO-1 induction. These studies define new molecular pathways coupling endothelial cell activation by model CMRs with adaptive regulation of Nrf2-dependent HO-1 expression and may represent key mechanisms through which dietary FAs differentially impact progression of endothelial dysfunction

Primary Arthrodesis for Diabetic Ankle Fractures

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: Treatment of ankle fractures in patients with diabetes is associated with increased complication rates. Ankle arthrodesis is considered a salvage procedure after failed ankle fracture fixation, yet primary ankle arthrodesis has been proposed as a treatment option for patients with significant diabetes-related complications. To date, the characteristics of patients who undergo primary ankle arthrodesis and the associated outcomes have not been described. Methods: A retrospective review was performed of 13 patients with diabetes who underwent primary arthrodesis for traumatic ankle fracture. Patient demographics were characterized in addition to their diabetes complications, Adelaide Fracture in the Diabetic Ankle (AFDA) score, and fracture type. Outcomes assessed included reoperation rates, infection rates, wound complications, nonunion/malunion, amputation, and development of Charcot arthropathy postoperatively. Results: Patients who underwent primary arthrodesis had high rates of diabetes complications, average AFDA scores of 6.4, and high rates of severe injuries, including 38.5% open fractures and 69.2% fracture dislocations. The overall complication rate for primary arthrodesis of ankle fractures in diabetes patients was more than 75% in this cohort. Complications included a 38.5% reoperation rate, 38.5% infection rate, 53.8% wound complication rate, and 23.1% amputation rate. Despite a high nonunion rate at the attempted fusion sites, 89.9% of fractures healed and patients had a stable extremity. Conclusion: This review is the first to characterize the epidemiology and complications of diabetes patients undergoing primary ankle arthrodesis for ankle fractures. In this cohort, patients with multiple diabetic complications and severe injuries underwent primary arthrodesis, which led to an overall high complication rate. Further research is needed to determine the appropriate treatment option for these high-risk patients, and tibiotalocalcaneal stabilization without arthrodesis may be beneficial

Artificial decellularized extracellular matrix improves the regenerative capacity of adipose tissue derived stem cells on 3D printed polycaprolactone scaffolds

Ideal tissue engineering frameworks should be both an optimal biological microenvironment and a shape and stability providing framework. In this study we tried to combine the advantages of cell-derived artificial extracellular matrix (ECM) with those of 3D printed polycaprolactone (PCL) scaffolds. In Part A, both chondrogenic and osteogenic ECMs were produced by human adipose derived stem cells (hASCs) on 3D-printed PCL scaffolds and then decellularized to create cell free functionalized PCL scaffolds, named acPCL and aoPCL respectively. The decellularization resulted in a significant reduction of the DNA content as well as the removal of nuclei while the ECM was largely preserved. In Part B the bioactivation and the effect of the ac/aoPCL scaffolds on the proliferation, differentiation, and gene expression of hASCs was investigated. The ac/aoPCL scaffolds were found to be non-toxic and allow good adhesion, but do not affect proliferation. In the in vitro investigation of cartilage regeneration, biochemical analysis showed that acPCL scaffolds have an additional effect on chondrogenic differentiation as gene expression analysis showed markers of cartilage hypertrophy. The aoPCL showed a large influence on the differentiation of hASCs. In control medium they were able to stimulate hASCs to produce calcium alone and all genes relevant investigated for osteogenesis were significantly higher expressed on aoPCL than on unmodified PCL. Therefore, we believe that ac/aoPCL scaffolds have a high potential to improve regenerative capacity of unmodified PCL scaffolds and should be further investigated

Lack of evidence for the efficacy of enhanced surveillance compared to other specific interventions to control neonatal healthcare-associated infection outbreaks.

BACKGROUND: Despite current prevention efforts, outbreaks of healthcare-associated infections in neonatal units remain high globally, with a considerable burden of mortality and morbidity. METHODS: We searched Medline, Cochrane Library and Outbreak database to identify studies of neonatal healthcare-associated outbreaks between 2005 and 2015 that described interventions to control outbreaks. All studies were evaluated using the ORION guidance. RESULTS: Thirty studies were identified including 17 102 infants of whom 664 (3.9%) became infected. No single intervention was identified that reduced duration or mortality. Studies that introduced multiple interventions had significantly reduced case fatality ratio and outbreak duration compared to those that used basic surveillance only. Low and low-middle income countries reported the fewest interventions to control outbreaks and these studies were also associated with higher mortality than that found in middle and high income countries. CONCLUSIONS: Systematic reporting and formal evaluation of interventions used to reduce healthcare-associated neonatal infection outbreaks is key to identifying containment strategies worldwide

The consequences of perceived age discrimination amongst older police officers : is social support a buffer ?

This paper considers the possible psychological consequences of perceived agediscrimination, and the possible buffering effect of social support. Findings, based on a studyof perceived age discrimination amongst police officers in the North of England, suggest thatage discrimination acts as a stressor, with officers experiencing negative effects of perceivedage discrimination on job and life satisfaction, perceived power and prestige of the job, andaffective and normative commitment, along with positive effects on withdrawal cognitionsand continuance commitment. For work-based social support, there were positive maineffects on job and satisfaction, power and prestige of the job, and affective and normativecommitment, and a negative main effect on withdrawal cognitions. However, there were nosignificant moderating effects for work-based social support, and we found the anticipatedbuffering effect for non-work-based social support only for life satisfaction, with reversebuffering for job satisfaction and normative commitment. The limitations and implications ofthe study are discussed

Varicella-zoster virus induces apoptosis in cell culture

peer reviewedaudience: researcherApoptosis is an active mechanism of cell death which can be initiated in response to various stimuli including virus infections. In this work, we demonstrate that lytic infection by varicella-zoster virus (VZV), a human herpesvirus, is characterized by nuclear fragmentation of DNA into oligonucleosomal fragments and by chromatin condensation. In vitro, VZV-induced cell death is actually mediated by apoptosis. The mechanisms developed by cells to protect themselves against apoptosis could be one of the parameters allowing the establishment of virus latency. In the case of VZV, which can remain latent in sensory ganglia, we have not yet identified a cellular or viral protein which could play this protective role, since the observed apoptosis mechanism seems to be independent from Bcl-2, the most frequently described inhibitor of apoptosis