Phagocytosis is the central process by which macrophage cells internalize and eliminate infectious microbes as well as apoptotic cells. During maturation, phagosomes containing engulfed particles fuse with various endosomal compartments through the action of regulatory molecules on the phagosomal membrane. In this study, we performed a proteomic analysis of the membrane fraction from latex bead-containing (LBC) phagosomes isolated from macrophages. The profile, which comprised 546 proteins, suggests diverse functions of the phagosome and potential connections to secretory processes, toll-like receptor signaling, and autophagy. Many identified proteins were not previously known to reside in the phagosome. We characterized several proteins in LBC phagosomes that change in abundance on induction of autophagy, a process that has been previously implicated in the host defense against microbial pathogens. These observations suggest crosstalk between autophagy and phagocytosis that may be relevant to the innate immune response of macrophages.LC3 ͉ phagocytosis P hagosomes are specialized membrane-bound organelles generated in phagocytic cells such as macrophages, neutrophils, and dendritic cells. Their purpose is to internalize foreign particles, microorganisms, or apoptotic cells, to mount an immune response, or to maintain tissue homeostasis (1). The nascent phagosome undergoes a complex maturation process involving sequential fusion with endosomal compartments. Once mature, the phagosome degrades its constituents and facilitates antigen presentation in a highly controlled manner (2-4). Insight into the biogenesis and immunity-related functions of the phagosome has come from analysis of its protein contents. Previous studies have profiled the proteomes of latex bead-containing (LBC) phagosomes in cell lines from mice (5-7) and Drosophila sp. (8), as well as Dictyostelium discoideum (9) and Entamoeba histolytica (10). These elegant studies contribute to our understanding of phagosome maturation (6, 9) and modulation by cytokines (7); however, because the entire contents of the phagosomes were sampled, abundant proteins, such as soluble lysosomal hydrolases, might have obscured lower abundance membrane-bound regulatory proteins or signaling factors.To identify such lower abundance species, we enriched integral and peripheral membrane proteins from macrophage LBC phagosomes by organelle sub-fractionation, before carrying out a large-scale proteomic analysis. The 546 proteins identified in our study included 49 membrane receptors, 64 transporter proteins, 107 regulators of vesicle and protein trafficking (including GTPases), and many components from cellular machineries other than phagosomes. One of the new proteins exclusively found in our study, LC3-II, is considered a marker of autophagic activity. Its presence in phagosomes suggests an unexplored linkage between autophagy and phagocytosis. Apart from its housekeeping role in maintaining cellular homeostasis, autophagy has been implicated in cancer, neurodegerative di...
COVID-19 is an emerging viral illness that has rapidly transmitted throughout the world. Its impact on society and the health care system has compelled hospitals to quickly adapt and innovate as new information about the disease is uncovered. During this pandemic, essential medical and surgical services must be carried out while minimizing the risk of disease transmission to health care workers. There is an elevated risk of COVID-19 viral transmission to health care workers during surgical procedures of the head and neck due to potential aerosolization of viral particles from the oral cavity/naso-oropharynx mucosa. Thus, patients with facial fractures pose unique challenges to the variety of injuries and special considerations, including triaging injuries and protective measures against infection. The proximity to the oral cavity/naso-oropharyngeal mucosa, and potential for aerosolization of secretions containing viral particles during surgical procedures make most patients undergoing operative interventions for facial fractures high risk for COVID-19 transmission. Our proposed algorithm aims to balance patient care with patient/medical personnel protection as well as judicious health care utilization. It stratifies facial trauma procedures by urgency and assigns a recommended level of personal protective equipment, extreme or enhanced, incorporating current best practices and existing data on viral transmission. As this pandemic continues to evolve and more information is obtained, the protocol can be further refined and individualized to each institution.
The mycobacterial cell wall component lipoarabinomannan (LAM) has been described as one of the key virulence factors of Mycobacterium tuberculosis. Modification of the terminal arabinan residues of this lipoglycan with mannose caps in M. tuberculosis or with phosphoinositol caps in Mycobacterium smegmatis results in distinct host immune responses. Given that M. tuberculosis typically persists in the phagosomal vacuole after being phagocytosed by macrophages, we performed a proteomic analysis of that organelle after treatment of macrophages with LAMs purified from the two mycobacterial species. The quantitative changes in phagosomal proteins suggested a distinct role for mannose-capped LAM in modulating protein trafficking pathways that contribute to the arrest of phagosome maturation. Enlightened by our proteomic data, we performed further experiments to show that only the LAM from M. tuberculosis inhibits accumulation of autophagic vacuoles in the macrophage, suggesting a new function for this virulence-associated lipid.
This study shows that high-resolution, 3D-printed sinus and skull base models can be generated with anatomical and haptic accuracy. This technology has the potential to be useful in surgical training and preoperative planning and as a supplemental or alternative simulation or training platform to cadaveric dissection.
A PETG 3D printed temporal bone models performed the best for realistic appearance and HF as compared with PLA, ABS, PC, and nylon. The PLA and ABS were reliable alternatives that also performed well with both measures.
Studies reviewed demonstrated 3D printing applications in surgical planning including accurate anatomic biomodels, surgical cutting guides in reconstruction, and patient-specific implants fabrication. 3D printing technology also offers access to well tolerated, reproducible, and high-fidelity/patient-specific models for surgical training. Emerging research in 3D biomaterial printing have led to the development of biocompatible scaffolds with potential for tissue regeneration in reconstruction cases involving significant tissue absence or loss. Major limitations of utilizing 3D printing technology include time and cost, which may be offset by decreased operating times and collaboration between departments to diffuse in-house printing costs SUMMARY: The current state of the literature shows promising results, but has not yet been validated by large studies or randomized controlled trials. Ultimately, further research and advancements in 3D printing technology should be supported as there is potential to improve resident training, patient care, and surgical outcomes.
IMPORTANCEComplications that arise after treatment of mandible fractures can result in significant morbidity. Identifying modifiable risk factors associated with these complications is valuable in guiding clinical practice for improved patient outcomes.OBJECTIVE To describe the risk factors associated with complications in patients undergoing treatment for mandible fracture. DESIGN, SETTING, AND PARTICIPANTSA retrospective review was conducted of 137 patients presenting to a tertiary care, level 1 trauma center with mandible fractures between January 1, 2014, and January 1, 2017. Outcomes and demographic characteristics for patients with at least 3 weeks of follow-up were compared using multivariate logistic regression analysis. RESULTSOf the 137 patients meeting inclusion criteria, there were 113 males (82.5%) and 24 females (17.5%), with a mean (SD) age at presentation of 32.3 (15.7) years. Median follow-up was 71 days (range, 22-1189 days). Postoperative complications were identified in 29 patients (21.2%); complications included wound dehiscence or surgical site infection (n = 17), bony nonunion (n = 5), and hardware exposure (n = 13). Complications were managed surgically in 19 patients and nonsurgically in 10 patients. On univariate analysis, the initial surgery was completed later (mean [SD], 5.9 [6.6] days after injury) in patients who developed complications than in those who did not (mean [SD], 3.8 [4.0] days). On multivariate analysis, complications were associated with increased time from injury to treatment (odds ratio [OR], 1.60; 95% CI, 1.02-2.53; P = .04), tobacco use (OR, 8.10; 95% CI, 1.26-52.00; P = .03), and dental extraction (OR, 93.00; 95% CI, 1.19 to >999.00; P = .04). Residence in the same city as the medical center was associated with fewer complications (OR, 0.08; 95% CI, 0.01-0.69; P = .02). CONCLUSIONS AND RELEVANCEIn a 3-year review of mandible fractures managed at a single academic center, complications were associated with an increased time to treatment, tobacco use, dental extraction, and living farther from the treatment facility. On a systems level, the results of this study suggest that expediting intervention for mandible fractures may improve outcomes.LEVEL OF EVIDENCE 3.
As the face ages, there is thinning of the epidermis, volume loss and rearrangement of the soft tissues, and malabsorption of the skeletal framework. It is essential to have a thorough understanding of the aging process for successful facial augmentation and rejuvenation. Alloplastic implants can be used to provide a long-lasting solution for augmentation of skeletal deficiencies, restoration of facial irregularities, and rejuvenation of the face. In this study, we describe the ideal implant characteristics along with the advantages and disadvantages of various implant materials. We also present techniques in nasal and premaxillary augmentation, midface augmentation, mandibular augmentation, and lip augmentation. Additionally, computer-aided design and manufacturing as well as bioprinting are emerging technologies with growing applications in facial plastic and reconstructive surgery. We discuss their role in the creation of patient-specific custom implants. The overall goal of facial rejuvenation is to address multiple aspects of the facial aging process including deficiencies in the skin, soft tissues, and skeletal framework. The use of alloplastic implants alone or synergistically with additional surgical procedures can restore a wide range of anatomical deficits that occur with age.
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