Current Considerations in Emergency Airway Management.

Purpose of Review: Emergency airway management is populated by many new concepts, evolving equipment, and contemporary strategies for optimal procedural success. This review aims to discuss various topics within these realms and to continue the ongoing conversation regarding improvement of emergency airway management. Recent Findings: Various literature, opinion pieces, podcasts, and trials have prompted renewed interest in the field of emergency airway management. Though common threads can be found, there is significant debate on optimal practice. Accompanying these conversations is continuous production of new equipment which can be beneficial to providers. However, this ongoing accumulation of material, data, and pathways can create challenges in remaining up to date. Rather than a comprehensive review of current literature and discussion of research findings, this article aims to discuss selected and impactful concepts in real time context and provide potentially immediate additions to emergency airway manager practice. Summary: As emergency airway management evolves, it remains a significant task to maintain up to date on current trends, data, and new equipment. This article aims to discuss several of these items in a digestible fashion and provide immediate impact for emergency airway providers.

N-Heterocyclic Carbene Ligand Stability on Gold Nanoparticles in Biological Media.

The ability to functionalize gold nanoparticle surfaces with target ligands is integral to developing effective nanosystems for biomedical applications, ranging from point-of-care diagnostic devices to site-specific cancer therapies. By forming strong covalent bonds with gold, thiol functionalities can easily link molecules of interest to nanoparticle surfaces. Unfortunately, thiols are inherently prone to oxidative degradation in many biologically relevant conditions, which limits their broader use as surface ligands in commercial assays. Recently, N-heterocyclic carbene (NHC) ligands emerged as a promising alternative to thiols since initial reports demonstrated their remarkable stability against ligand displacement and stronger metal-ligand bonds. This work explores the long-term stability of NHC-functionalized gold nanoparticles suspended in five common biological media: phosphate-buffered saline, tris-glycine potassium buffer, tris-glycine potassium magnesium buffer, cell culture media, and human serum. The NHCs on gold nanoparticles were probed with surface-enhanced Raman spectroscopy (SERS) and X-ray photoelectron spectroscopy (XPS). SERS is useful for monitoring the degradation of surface-bound species because the resulting vibrational modes are highly sensitive to changes in ligand adsorption. Our measurements indicate that imidazole-based NHCs remain stable on gold nanoparticles over the 21 days of examination in all tested environments, with no observed change in the molecule's SERS signature, XPS response, or UV-vis plasmon band.

Foveated 3D range geometry compression via loss-tolerant variable precision depth encoding.

The capacity of three-dimensional (3D) range geometry acquisition methods to capture high-precision scans at high frame rates increases every year. These improvements have influenced a broadening range of disciplines to implement 3D range geometry capture systems, including telepresence, medicine, the visual arts, and many others. However, its increased popularity, precision, and capture rates have caused mounting pressure on the storage and transmission of 3D range geometry, thus straining their capacities. Compression techniques seek to alleviate this pressure by offering reduced file sizes, while maintaining the levels of precision needed for particular applications. Several such compression methods use sinusoidal modulation approaches to encode floating-point 3D data into conventional 2D red, green, and blue (RGB) images. In some applications, such as telepresence, high precision may only be required in a particular region within a depth scan, thus allowing less important data to be compressed more aggressively. This paper proposes a feature-driven compression method that provides a way to encode regions of interest at higher levels of precision while encoding the remaining data less precisely to reduce file sizes. This method supports both lossless and lossy compression, enabling even greater file-size savings. For example, in the case of a depth scan of a bust, an algorithmically extracted bounding box of the face was used to create a foveated encoding distribution so that the facial region was encoded at higher precisions. When using JPEG 80, the RMS reconstruction error of this novel, to the best of our knowledge, encoding was 0.56 mm in the region of interest, compared to a globally fixed higher precision encoding where the error was 0.54 mm in the same region. However, the proposed encoding achieved a 26% reduction in overall compressed file size compared to the fixed, higher-precision encoding.

Variable precision depth encoding for 3D range geometry compression.

State-of-the-art 3D range geometry compression algorithms that utilize principles of phase shifting perform encoding with a fixed frequency; therefore, it is not possible to encode individual points within a scene at various degrees of precision. This paper presents a novel, to the best of our knowledge, method for accurately encoding 3D range geometry within the color channels of a 2D RGB image that allows the encoding frequency-and therefore the encoding precision-to be uniquely determined for each coordinate. The proposed method can thus be used to balance between encoding precision and file size by encoding geometry along a statistical distribution. For example, a normal distribution allows for more precise encoding where the density of data is high and less precise encoding where the density of data is low. Alternative distributions may be followed to produce encodings optimized for specific applications. In general, the nature of the proposed encoding method enables the precision to be freely controlled at each point or centered around identified features of interest, ideally enabling this method to be used within a wide range of applications.

Two-channel depth encoding for 3D range geometry compression.

This paper presents a novel method for accurately encoding 3D range geometry within only two channels of a 2D RGB image using a two-frequency phase-shifting approach. Once encoded within a 2D image, 3D geometry can be further compressed with conventional lossless or lossy image compression methods. The nature of the proposed two-channel encoding is relatively smooth; thus, large compression ratios with high reconstruction accuracies can be achieved and are experimentally demonstrated. For example, a compression ratio of 2883:1 was achieved, compared with the STL format, with a reconstruction RMS error of 0.45 mm (99.8% accuracy) when JPEG 85 was used with the proposed method. This paper also demonstrates how a 24-bit color texture map can be encoded alongside 3D geometry within a single 2D image.

Intracellular signaling mechanisms associated with CD47 modified surfaces.

We have previously established that recombinant CD47 can ameliorate the inflammatory response to synthetic polymeric surfaces. Here, we begin to profile, at the transcriptional, translational and cell signaling level, the inflammatory cell response when blood interacts with CD47 modified polyvinyl chloride (PVC) (CD47-PVC). We used qPCR arrays to compare transcriptional changes between human whole blood exposed to CD47-PVC or PVC. Transcription of IL1F5, IL1F10, IL17F, CCL3, CCL8, CCL28, CXCL12, and CXCL13 was upregulated in blood exposed to PVC, compared to CD47-PVC. The increase in CCL3 and CCL8 transcription correlated with an increase in the chemokines' presence in the plasma. Exposure of blood to CD47-PVC resulted in an increase, compared to PVC, in transcription of CCL2, CCL4, CCL20, CXCL1, TGFß3, GDF3, GDF10, CD40LG, and TNFSF10. CD47-PVC exposure resulted in an increase of the following matrix metalloproteinase related genes: MMP1, MMP7, MMP13, and MMP16. Phosflow cytometry, and assays examining transcription factor binding, cell attachment, and genome-wide chromatin association indicated that members of the JAK-STAT signaling pathway, particularly JAK2 and STAT5, mediate inflammatory cell interactions with CD47-PVC. Our data demonstrate that differential molecular responses to CD47 involve downregulation of cytokines, upregulation of MMPs, and JAK/STAT signaling mechanisms.

Correlating macrophage morphology and cytokine production resulting from biomaterial contact.

The morphological and inflammatory responses of adherent macrophages are correlated to evaluate the biocompatibility of surfaces. Monocyte-derived macrophage (MDM), THP-1, and THP-1 cells expressing GFP-actin chimeric protein were seeded onto glass, polyurethane (PU), and glass surface modified with quaternary ammonium salt functionalized chitosan (CH-Q) and hyaluronic acid (HA). Using confocal microscopy, the surface area, volume and 3D shape factor of adherent macrophages was quantified. For comparison, functional consequences of cell-surface interactions that activate macrophages and thereby elicit secretion of a proinflammatory cytokine were evaluated. Using an enzyme linked immune sorbent assay, tumor necrosis factor-alpha (TNF-α) was measured. On glass, macrophages exhibited mainly an amoeboid shape, exhibited the largest surface area, volume, and 3D shape factor and produced the most TNF-α. On PU, macrophages displayed mainly a hemispherical shape, exhibited an intermediate volume, surface area and 3D shape factor, and produced moderate TNF-α. In contrast, on CH-Q and HA surfaces, macrophages were spherical, exhibited the smallest volume, surface area, and 3D shape factor, and produced the least TNF-α. These studies begin to validate the use of GFP-actin-modified MDM as a novel tool to correlate cell morphology with inflammatory cell response.

Diminished adhesion and activation of platelets and neutrophils with CD47 functionalized blood contacting surfaces.

CD47 is a ubiquitously expressed transmembrane protein that, through signaling mechanisms mediated by signal regulatory protein alpha (SIRPα1), functions as a biological marker of 'self-recognition'. We showed previously that inflammatory cell attachment to polymeric surfaces is inhibited by the attachment of biotinylated recombinant CD47 (CD47B). We test herein the hypothesis that CD47 modified blood conduits can reduce platelet and neutrophil activation under clinically relevant conditions. We appended a poly-lysine tag to the C-terminus of recombinant CD47 (CD47L) allowing for covalent linkage to the polymer. SIRPα1 expression was confirmed in isolated platelets. We then compared biocompatibility between CD47B and CD47L functionalized polyvinyl chloride (PVC) surfaces and unmodified control PVC surfaces. Quantitative and Qualitative analysis of blood cell attachment to CD47B and CD47L surfaces, via scanning electron microscopy, showed strikingly fewer platelets attached to CD47 modified surfaces compared to control. Flow cytometry analysis showed that activation markers for neutrophils (CD62L) and platelets (CD62P) exposed to CD47 modified PVC were equivalent to freshly acquired control blood, while significantly elevated in the unmodified PVC tubing. In addition, ethylene oxide gas sterilization did not inhibit the efficacy of the CD47 modification. In conclusion, CD47 modified PVC inhibits both the adhesion and activation of platelets and neutrophils.

The effect of CD47 modified polymer surfaces on inflammatory cell attachment and activation.

CD47 is a transmembrane protein that is a marker of "self". CD47 binding to its cognate receptor in leukocytes and macrophages, signal-regulatory protein alpha (SIRPα), causes inhibition of inflammatory cell attachment. We hypothesized that immobilization of recombinant CD47 on polymeric surfaces would reduce inflammation. Recombinant CD47 was appended to polyvinyl chloride (PVC) or polyurethane (PU) surfaces via photoactivation chemistry. Cell culture studies showed that CD47 immobilization significantly reduced human neutrophil (HL-60) and human monocyte derived macrophage (MDM) (THP-1) attachment to PVC and PU respectively. A neutralizing antibody, directed against SIRPα, inhibited THP-1 and HL-60 binding to PU and PVC surfaces respectively. This antibody also increased the level of SIRPα tyrosine phosphorylation, thereby indicating a direct role for SIRPα mediated signaling in preventing inflammatory cell attachment. Studies using human blood in an ex vivo flow-loop showed that CD47 modified PVC tubing significantly reduced cell binding and neutrophil activation compared to unmodified tubing or poly-2-methoxy-ethylacrylate (PMEA) coated tubing. In ten-week rat subdermal implants, CD47 functionalized PU films showed a significant reduction in markers of MDM mediated oxidative degradation compared to unmodified PU. In conclusion, CD47 functionalized surfaces can resist inflammatory cell interactions both in vitro and in vivo.

Transcriptional regulation of the major HIV-1 coreceptor, CXCR4, by the kappa opioid receptor.

Previous studies have demonstrated that KOR activation results in decreased susceptibility to infection by HIV-1 in human PBMCs. In the present studies, we have found this effect is, in part, a result of down-regulation of the major HIV-1 coreceptor, CXCR4. Using a combination of biochemical approaches, our results show that CXCR4 protein and mRNA levels were reduced significantly following KOR activation. We evaluated the nature of the signaling pathway(s), which were induced by KOR activation, using transcription factor-binding array analysis and comparing extracts from control and KOR-activated cells. We determined that the IRFs and STATs were induced following KOR activation, and these events were important for the inhibition of CXCR4 expression. Using chemical inhibitors and siRNA constructs, we determined that JAK2, STAT3, and IRF2 were critical members of this signal transduction pathway. Immediately following KOR activation, JAK2 was phosphorylated, and this was required for the phosphorylation/activation of STAT3. Moreover, IRF2 mRNA and protein expression were also up-regulated, and further studies using ChIP analysis showed that IRF2 was induced to bind in vivo to the CXCR4 promoter. This is the first report detailing the initiation of a KOR-induced JAK2/STAT3 and IRF2 signaling cascade, and these pathways result in substantial down-regulation of CXCR4 expression. The capacity of KOR to down-regulate CXCR4 expression may provide a strategy for the development of novel therapeutics for the inhibition of HIV replication.

Bi-directional heterologous desensitization between the major HIV-1 co-receptor CXCR4 and the kappa-opioid receptor.

We previously characterized multiple interactions between chemokine and opioid G protein-coupled receptors (GPCR), and we found both mu and delta-opioid receptors cross-desensitize CCR1, CCR2, CCR5, but not CXCR4. Here we report that the kappa-opioid receptor (KOR) is able to cross-desensitize CXCR4, and this phenomenon is bi-directional. Chemotactic responses by KOR activation are diminished with prior activation of CXCR4. Additionally, calcium mobilization assays show these cross-desensitization processes occur within seconds of receptor activation, and target receptor internalization is not responsible for desensitization between these receptors. These results have implications for several essential processes including neuronal and lymphocyte development, inflammatory responses, and pain/sensitivity.

Analysis of the RNASEL/HPC1, and macrophage scavenger receptor 1 in Asian-Indian advanced prostate cancer.

OBJECTIVES: Prostate cancer (PC) varies widely by geographic location and ethnicity. American men have a high PC risk but most have localized disease. In contrast, Asian Indians have a low PC risk but most are diagnosed with metastatic disease. Epidemiological and genetic data suggest an important role of genetic susceptibility in PC. Most studies were performed in whites. Substantially less is known about gene variation-associated PC in low-risk populations. The objective of this study was to investigate the role of RNASEL and MSR1 in Asian-Indian men with advanced PC. METHODS: We genotyped DNA samples obtained from 113 cases and 245 age-matched controls (Northern India). RESULTS: For RNASEL, we identified 8 variants (7 novel and 1 previously published, D541E), including 4 exonic, 3 intronic, and 1 change in the 3'-noncoding region. Of these, we detected a novel 4-bp truncation mutation (Val51ArgfsX2) in 2 controls. For MSR1, we identified 4 novel variants (2 intronic and 2 exonic) and 2 previously reported variants (P275A and promoter -4,637 A>G). We also genotyped 3 common MSR1 variations (promoter -14,742 A>G, IVS5-59 C>A, and IVS7 delinsTTA). We found no associations among any of the sequence variations and PC. Three major haplotypes account for most of all MSR1 haplotypes in Asian Indians. Haplotype frequencies were not significantly different between cases and controls. CONCLUSIONS: Our results do not support a role for RNASEL, or MSR1 mutations in advanced Asian-Indian PC. This study warrants additional investigations of these genes in etiology particularly among individuals from diverse ethnic and geographic groups.

DAMGO-induced expression of chemokines and chemokine receptors: the role of TGF-beta1.

Studies from a number of laboratories suggest that modulation of cytokine expression plays an integral role in the immunomodulatory activity of opioids. Previously, our laboratory reported that activation of the mu-opioid receptor induced the expression of CCL2, CCL5, and CXCL10, as well as CCR5 and CXCR4. Previous work has also suggested the possibility that TGF-beta may participate in the opioid-induced regulation of immune competence, and in the present study, we set out to determine the role of this cytokine in the control of chemokine and chemokine receptor expression. We found that D-ala(2),N-Me-Phe(4)-Gly-ol(5)enkephalin (DAMGO), a highly selective mu-opioid agonist, induced the expression of TGF-beta1 expression at the protein and mRNA levels. In turn, the addition of TGF-beta1 was found to induce CCL5 and CXCR4 expression but not CCL2, CXCL10, or CCR5. Further analysis showed that pretreatment with neutralizing anti-TGF-beta1 blocked the ability of DAMGO to induce CCL5 or CXCR4. Similarly, pretreatment with cycloheximide prevented CCL5 or CXCR4 mRNA expression, consistent with the observation that DAMGO induction of chemokine and chemokine receptor expression requires newly synthesized TGF-beta1 protein. These results describe a common molecular basis for the activation of chemokine and chemokine receptor expression and may permit the development of strategies to inhibit certain undesirable immunological properties of micro-opioid agonists such as morphine and heroin.

Association of susceptibility alleles in ELAC2/HPC2, RNASEL/HPC1, and MSR1 with prostate cancer severity in European American and African American men.

Reported associations of ELAC2/HPC2, RNASEL/HPC1, and MSR1 with prostate cancer have been inconsistent and understudied in African Americans. We evaluated the role of 16 sequence variants in these genes with prostate cancer using 888 European American and 131 African American cases, and 473 European American and 163 African American, controls. We observed significant differences in ELAC2, RNASEL, and MSR1 allele frequencies by race. However, we did not observe significant associations between prostate cancer and any variants examined for both races combined. Associations were observed when stratified by race, family history, or disease severity. European American men homozygous for MSR1 IVS7delTTA had an elevated risk for localized stage [odds ratio, (OR), 3.5; 95% confidence interval (95% CI), 1.4-6.9], low-grade (OR, 3.2; 95% CI, 1.4-7.3) disease overall, and with low-grade (OR, 2.9; 95% CI, 1.2-7.2) or late-stage disease (OR, 5.2; 95% CI, 1.1-25.7) in family history-negative African Americans. MSR1 Arg293X was associated with family history-negative high-grade disease (OR, 4.0; 95% CI, 1.1-14.1) in European Americans. RNASEL Arg462Gln was associated with low-grade (OR, 1.5; 95% CI, 1.04-2.2) and early-stage (OR, 1.5; 95% CI, 1.02-2.1) disease in family history-negative European Americans. In family history-positive individuals, Arg462Gln was inversely associated with low-grade (OR, 0.43; 95% CI, 0.21-0.88) and low-stage (OR, 0.46; 95% CI, 0.22-0.95) disease. In African Americans, Arg462Gln was associated with positive family history high-stage disease (OR, 14.8; 95% CI, 1.6-135.7). Meta-analyses revealed significant associations of prostate cancer with MSR1 IVS7delTTA, -14,742 A>G, and Arg293X in European Americans; Asp174Tyr in African Americans; RNASEL Arg462Gln in European American's overall and in family history-negative disease; and Glu265X in family history-positive European Americans. Therefore, MSR1 and RNASEL may play a role in prostate cancer progression and severity.