ObjectiveThe aim of this study was to investigate the feasibility of using augmented reality (AR) glasses in central line simulation by novice operators and compare its efficacy to standard central line simulation/teaching.DesignThis was a prospective randomized controlled study enrolling 32 novice operators. Subjects were randomized on a 1:1 basis to either simulation using the augmented virtual reality glasses or simulation using conventional instruction.SettingThe study was conducted in tertiary-care urban teaching hospital.SubjectsA total of 32 adult novice central line operators with no visual or auditory impairments were enrolled. Medical doctors, respiratory therapists, and sleep technicians were recruited from the medical field.Measurements and main resultsThe mean time for AR placement in the AR group was 71±43 s, and the time to internal jugular (IJ) cannulation was 316±112 s. There was no significant difference in median (minimum, maximum) time (seconds) to IJ cannulation for those who were in the AR group and those who were not (339 [130, 550] vs 287 [35, 475], p=0.09), respectively. There was also no significant difference between the two groups in median total procedure time (524 [329, 792] vs 469 [198, 781], p=0.29), respectively. There was a significant difference in the adherence level between the two groups favoring the AR group (p=0.003).ConclusionAR simulation of central venous catheters in manikins is feasible and efficacious in novice operators as an educational tool. Future studies are recommended in this area as it is a promising area of medical education.

Sepsis survivors suffer from a myriad of physiologic, physical and psychological challenges. Survivors overall reveal dissatisfaction with sepsis-related care, suggesting areas for improvement both in-hospital and post-discharge.

BackgroundThe wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, thus safe designs of MOx with reduced hazard potential are desired. Currently, there is a lack of a simple yet effective safe design approach for the toxic MOx. In this study, we determined the key physicochemical properties of MOx that lead to cytotoxicity and explored a safe design approach for toxic MOx by modifying their hazard properties.ResultsTHP-1 and BEAS-2B cells were exposed to 0–200 μg/mL MOx for 24 h, we found some toxic MOx including CoO, CuO, Ni2O3 and Co3O4, could induce reactive oxygen species (ROS) generation and cell death due to the toxic ion shedding and/or oxidative stress generation from the active surface of MOx internalized into lysosomes. We thus hypothesized that surface passivation could reduce or eliminate the toxicity of MOx. We experimented with a series of surface coating molecules and discovered that ethylenediamine tetra (methylene phosphonic acid) (EDTMP) could form stable hexadentate coordination with MOx. The coating layer can effectively reduce the surface activity of MOx with 85-99% decrease of oxidative potential, and 65-98% decrease of ion shedding. The EDTMP coated MOx show negligible ROS generation and cell death in THP-1 and BEAS-2B cells. The protective effect of EDTMP coating was further validated in mouse lungs exposed to 2 mg/kg MOx by oropharyngeal aspiration. After 40 h exposure, EDTMP coated MOx show significant decreases of neutrophil counts, lactate dehydrogenase (LDH) release, MCP-1, LIX and IL-6 in bronchoalveolar lavage fluid (BALF), compared to uncoated particles. The haematoxylin and eosin (H&E) staining results of lung tissue also show EDTMP coating could significantly reduce the pulmonary inflammation of MOx.ConclusionsThe surface reactivity of MOx including ion shedding and oxidative potential is the dominated physicochemical property that is responsible for the cytotoxicity induced by MOx. EDTMP coating could passivate the surface of MOx, reduce their cytotoxicity and pulmonary hazard effects. This coating would be an effective safe design approach for a broad spectrum of toxic MOx, which will facilitate the safe use of MOx in commercial nanoproducts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-017-0193-5) contains supplementary material, which is available to authorized users.

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 µg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm3, respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

Hepatic ischemia and reperfusion injury (IRI), an exogenous antigen-independent local inflammation response, occurs in multiple clinical settings including liver transplantation, hepatic resection, trauma, and shock. The immune system and the nervous system maintain extensive communication, and mount a variety of integrated responses to danger signals through intricate chemical messengers. This study examined the function and potential therapeutic potential of neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) in a murine model of partial liver “warm” ischemia (90min) followed by reperfusion. Liver IR readily triggered the expression of intrinsic PACAP and its receptors, whereas the hepatocellular damage was exacerbated in PACAP-deficient mice. Conversely, PACAP27, or PACAP38 peptide monotherapy, which elevates intracellular cyclic adenosine monophosphate - protein kinase A (cAMP-PKA) signaling, protected livers from IRI, as evidenced by diminished serum alanine aminotransferase (sALT) levels and well-preserved tissue architecture. The liver protection rendered by PACAP peptides was accompanied by diminished neutrophil/macrophage infiltration and activation, reduced hepatocyte necrosis/apoptosis, and selectively augmented hepatic IL-10 expression. Strikingly, PKA inhibition readily restored liver damage in otherwise IR-resistant PACAP-conditioned mice. In vitro, PACAP treatment not only diminished macrophage TNF-α/IL-6/IL-12 levels in an PKA-dependent manner, but also prevented necrosis and apoptosis in primary mouse hepatocyte cultures. Conclusion Our novel findings document the importance of PACAP mediated cAMP-PKA signaling in hepatic homeostasis and cytoprotection in vivo. As the enhancement of neural modulation differentially regulates local inflammation and prevents hepatocyte death, these results provide the rationale for novel approaches to manage liver inflammation and IRI in transplant patients.

Hepatic ischemia and reperfusion injury (IRI) occurs in multiple clinical settings including liver transplantation. Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway inhibits hepatocellular apoptosis and regulates TLR4-triggered inflammation responses in vitro. Here, we examined the function and therapeutic potential of cAMP-PKA activation in a murine (C57/BL6) model of liver warm ischemia (90 min) followed by reperfusion. Liver IRI triggered cAMP-PKA activation, whereas administration of its specific inhibitor, H-89, exacerbated hepatocellular damage. Conversely, Forskolin therapy, which activates PKA by elevating cAMP levels, protected livers from IRI, evidenced by diminished serum ALT and well-preserved tissue architecture. Liver protection rendered by cAMP-PKA stimulation was accompanied by diminished neutrophil and macrophage infiltration/activation, reduced hepatocyte necrosis/apoptosis, yet increased cAMP response element-binding protein (CREB) and augmented IL-10 expression. Neutralization of IL-10 restored liver damage in otherwise IR-resistant Forskolin-treated mice. In vitro, cAMP-PKA activation diminished macrophage TNF-α/IL-6/IL-12 in an IL-10-dependent manner, and prevented necrosis/apoptosis in primary mouse hepatocyte cultures. Our novel findings in a mouse model of liver IRI document the importance of cAMP-PKA signaling in hepatic homeostasis and cytoprotection in vivo. Activation of cAMP-PKA signaling differentially regulates local inflammation and prevents hepatocyte death, providing the rationale for novel therapeutic approaches to combat liver IRI in transplant recipients.

After mastectomy for pT1 N0 breast cancer, there is a small subgroup of patients with grade 3 disease and a close or positive margin (≤ 3 mm) who have an increased risk of LRR. These patients may benefit from the administration of PMRT.

In this study, we used extracellular matrix (ECM) gels and human bone allograft as matrix vehicles to deliver the sphingolipid growth factor FTY720 to rodent models of tibial fracture and a critical-sized cranial defect. We show that FTY720 released from injectable ECM gels may accelerate callous formation and resolution and bone volume in a mouse tibial fracture model. We then show that FTY720 binds directly to human trabecular allograft bone and releases over 1 week in vitro. Rat critical-sized cranial defects treated with FTY720-coated grafts show increases in vascularization and bone deposition, with histological and micro-computed topography (microCT) evidence of enhanced bone formation within the graft and defect void. Immunohistochemical analysis suggests that osteogenesis within FTY720-coated grafts is associated with reduced CD68+ macrophage infiltration and recruitment of CD29+ bone progenitor cells. Matrix binding of FTY720 thus represents a promising and robust bone regeneration strategy with potential clinical translatability.