Faculty Bibliography

SIGNIFICANCE/CONCLUSIONS:Skin wounds and disorders compromise the protective functions of skin and patient quality of life. Though accessible on the surface, they are challenging to address due to paucity of effective therapies. Exogenous extracellular vesicles (EVs), cell-free derivatives of adult multipotent stromal cells (MSCs), are developing as a treatment modality. Knowledge of origin MSCs, EV processing and mode of action is necessary for directed use of EVs in preclinical studies and methodical translation. Recent advances: Nano to microscale EVs, though from non-skin cells, induce functional responses in cutaneous wound cellular milieu. EVs allow a shift from cell-based to cell-free/derived modalities by carrying the MSC beneficial factors but eliminating risks associated with MSC transplantation. EVs have demonstrated striking efficacy in resolution of preclinical wound models, specifically within the complexity of skin structure and wound pathology. CRITICAL ISSUES/RESULTS:To facilitate comparison across studies, tissue sources and processing of MSCs, culture conditions, isolation and preparations of EVs, and vesicle sizes require standardization as these criteria influence EV types and contents, and potentially determine the induced biological responses. Procedural parameters for all steps preceding the actual therapeutic administration may be the key to generating EVs that demonstrate consistent efficacy through known mechanisms. We provide a comprehensive review of such parameters and the subsequent tissue, cellular and molecular impact of the derived EVs in different skin wounds/disorders. FUTURE DIRECTIONS/CONCLUSIONS:We will gain more complete knowledge of EV-induced effects in skin, and specificity for different wounds/conditions. The safety and efficacy of current preclinical xenogenic applications will favor translation into allogenic clinical applications of EVs as a biologic.

Pre- and postoperative imaging is increasingly used in plastic and reconstructive surgery for the evaluation of bony and soft tissue anatomy. Imaging plays an important role in preoperative planning. In the postoperative setting, imaging is used for the assessment of surgical positioning, bone healing and fusion, and for the assessment of early or delayed surgical complications. This article will focus on imaging performed for surgical reconstruction of the face, including orthognathic surgery, facial feminization procedures for gender dysphoria, and face transplantation.

Skeletal conditions represent a considerable challenge to health systems globally. Barriers to effective therapeutic development include a lack of accurate preclinical tissue and disease models. Most recently, work was attempted to present a novel whole organ approach to modeling human bone and cartilage tissues. These self-assembling skeletal organoids mimic the cellular milieu and extracellular organization present in native tissues. Bone organoids demonstrated osteogenesis and micro vessel formation, and cartilage organoids showed evidence of cartilage development and maturation. Skeletal organoids derived from both bone and cartilage tissues yielded spontaneous polarization of their cartilaginous and bone components. Using these hybrid skeletal organoids, we successfully generated "mini joint" cultures, which we used to model inflammatory disease and test Adenosine (A_2A ) receptor agonists as a therapeutic agent. The work and respective results indicated that skeletal organoids can be an effective biological model for tissue development and disease as well as to test therapeutic agents.

Movement disorder emergencies of the aerodigestive tract are dramatic and often life threatening. With appropriate timely evaluation and intervention, most patients can be effectively managed and major morbidity avoided. This chapter provides a comprehensive review of both the causes and appropriate treatment of breathing disturbances secondary to primary disorders and iatrogenic causes, as well as swallowing emergencies. Additionally, basic physiology, anatomy, and various methods for assessment of the upper aerodigestive tract are reviewed. Specific disorders that are addressed include the following: spasmodic dysphonia, adductor laryngeal breathing dystonia, Shy-Drager abductor weakness, drug-induced tardive dystonia, oromandibulolingual dystonia, multiple system atrophy, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and palatal myoclonus.
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HYPOTHESIS/OBJECTIVE:Injuries requiring resection of tissue followed by autogenous bone transfer may be prone to infection by Staphylococcus aureus, impeding recovery and increasing medical costs. For critical sized defects, the common approach to reconstruction is a tissue transfer procedure but is subject to limitations (e.g., donor site morbidity, cost, operating time). Utilizing beta tricalcium phosphate (β-TCP) as bone grafting material augmented with silver (Ag), a custom graft may be 3D printed to overcome limitations and minimize potential infections. EXPERIMENTS/METHODS:) groups followed by electron microscopy, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to gather information of chemical and physical properties. Preliminary biocompatibility and bactericidal capacity of the scaffolds were tested using human osteoprogenitor (hOP) cells and methicillin-sensitive S. aureus strain, respectively. RESULTS:groups, whereas electron microscopy showed a decrease in Ca and an increase in Ag ions, decreasing Ca/P ratio with increasing surfactant concentrations. PrestoBlue assays yielded an increase in fluorescence cell counts among experimental groups with lower concentrations of Ag characterized by their characteristic trapezoidal shape whereas cytotoxicity was observed at higher concentrations. Similar observations were made with alkaline phosphatase assays. Antimicrobial evaluation showed reduced colony-forming units (CFU) among all experimental groups when compared to 100% β-TCP. β-TCP scaffolds augmented with Ag ions facilitate antibacterial effects while promoting osteoblast adhesion and proliferation.

BACKGROUND: From both a medical and surgical perspective, obese breast cancer patients are considered to possess higher risk when undergoing autologous breast reconstruction relative to nonobese patients. However, few studies have evaluated the continuum of risk across the full range of obesity. This study sought to compare surgical risk between the three World Health Organization (WHO) classes of obesity in patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: A retrospective review of 219 obese patients receiving 306 individual DIEP flaps was performed. Subjects were stratified into WHO obesity classes I (body mass index [BMI]: 30-34), II (BMI: 35-39), and III (BMI: ≥ 40) and assessed for risk factors and postoperative donor and recipient site complications. RESULTS: = 0.03) complications. CONCLUSION/CONCLUSIONS: DIEP breast reconstruction in the obese patient is more complex for both the patient and the surgeon. Although not a contraindication to undergoing surgery, obese patients should be diligently counseled regarding potential complications and undergo preoperative optimization of health parameters. Morbidly obese (class III) patients should be approached with additional caution, and perhaps even delay major reconstruction until specific BMI goals are met.

OBJECTIVE:The effectiveness of µ-opioid receptor (MOPr) agonists for treatment of visceral pain is compromised by constipation, respiratory depression, sedation and addiction. We investigated whether a fentanyl analogue, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), which preferentially activates MOPr in acidified diseased tissues, would inhibit pain in a preclinical model of inflammatory bowel disease (IBD) without side effects in healthy tissues. DESIGN/METHODS:Antinociceptive actions of NFEPP and fentanyl were compared in control mice and mice with dextran sodium sulfate colitis by measuring visceromotor responses to colorectal distension. Patch clamp and extracellular recordings were used to assess nociceptor activation. Defecation, respiration and locomotion were assessed. Colonic migrating motor complexes were assessed by spatiotemporal mapping of isolated tissue. NFEPP-induced MOPr signalling and trafficking were studied in human embryonic kidney 293 cells. RESULTS:NFEPP inhibited visceromotor responses to colorectal distension in mice with colitis but not in control mice, consistent with acidification of the inflamed colon. Fentanyl inhibited responses in both groups. NFEPP inhibited the excitability of dorsal root ganglion neurons and suppressed mechanical sensitivity of colonic afferent fibres in acidified but not physiological conditions. Whereas fentanyl decreased defecation and caused respiratory depression and hyperactivity in mice with colitis, NFEPP was devoid of these effects. NFEPP did not affect colonic migrating motor complexes at physiological pH. NFEPP preferentially activated MOPr in acidified extracellular conditions to inhibit cAMP formation, recruit β-arrestins and evoke MOPr endocytosis. CONCLUSION/CONCLUSIONS:In a preclinical IBD model, NFEPP preferentially activates MOPr in acidified microenvironments of inflamed tissues to induce antinociception without causing respiratory depression, constipation and hyperactivity.

STATEMENT OF PROBLEM/BACKGROUND:Understanding how maxillofacial prosthodontists are perceiving changes in head and neck care and the impact of advanced digital technologies on maxillofacial prosthodontics is important. However, no studies could be identified that specifically addressed these subjects. PURPOSE/OBJECTIVE:The purpose of this review of selected literature was to identify issues that guided the development of maxillofacial prosthodontics and the concerns that persist. The review also considered contemporary influences that will affect the future of maxillofacial prosthodontics. The conclusions of the review were used to interpret the results of the exploratory survey reported in Part II. MATERIAL AND METHODS/METHODS:The review of selected literature was related to the development of maxillofacial prosthodontics in North America between 1950 and 2018. Literature that was considered relevant to the purpose of the review was included. RESULTS:The review yielded 37 references of interest: 34 peer-reviewed publications, 1 guideline, 1 historical publication, and 1 website. Periods in the development of maxillofacial prosthodontics in North America were identified as formation, consolidation, and innovation. CONCLUSIONS:It was concluded that concerns in subspecialty programs and clinical practice had origins in the formation and consolidation periods. These persisting concerns extended into the innovation period. Contemporary influences in head and neck surgery will continue to affect the future of maxillofacial prosthodontics. Advanced digital technologies appeared to be central to driving change. Understanding the evolution of maxillofacial prosthodontics was an important first step in providing context when interpreting the results of a survey of maxillofacial prosthodontists reported as Part II of this work.

STATEMENT OF PROBLEM/BACKGROUND:Head and neck care has been transformed by the introduction of advanced digital technologies that will continue to be important change drivers for maxillofacial prosthodontics. Insight into these changes is important in answering the question of whether maxillofacial prosthodontics is appropriately prepared to contribute effectively to future multidisciplinary care of the head and neck. PURPOSE/OBJECTIVE:The purpose of this survey was to gain insight into the perception of changes experienced by maxillofacial prosthodontists in relation to clinical practice. The findings of this survey may assist the future development of the subspecialty. MATERIAL AND METHODS/METHODS:An exploratory cross-sectional survey was conducted by using a convenience sample of members of the American Academy of Maxillofacial Prosthetics. The survey considered 10 domains and 31 questions. Fully completed surveys (164) provided a 59% response. Descriptive statistics used percentage responses to reduce and characterize perceptions across respondents. RESULTS:Eighty-four percent of the respondents were from the United States. Results should be interpreted based on this cohort. Respondents reported a change in care delivered over the past 10 years (72%), with the most important causes of change attributed to surgery (60%) and advanced digital technologies (56%). Respondents perceived advanced digital technologies as being central to the future of maxillofacial prosthodontics (89%) and important in attracting younger colleagues (88%). Sixty-three percent believed training programs were not providing adequate education and training in the use of advanced digital technology. CONCLUSIONS:The perception of maxillofacial prosthodontists regarding changes taking place in care delivery was that the most important changes in the past 10 years were attributed to surgery and advanced digital technologies, that persisting pressures related to few institutional positions, that the subspecialty was poorly visible, that remuneration for care was inadequate and referring disciplines did not understand the subspecialty, that advanced digital technologies were considered central to the future of maxillofacial prosthodontics and important to attract younger colleagues to the subspecialty, that barriers to advanced digital technology use included funding for equipment acquisition, institutional funding support, and remuneration for their use in care delivery, and that maxillofacial prosthodontic programs were not providing adequate education and training in advanced digital technologies.