Faculty Bibliography

Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.

Distraction osteogenesis is a bone-regenerative process in which an osteotomy is followed by distraction of the surrounding vascularized bone segments, with formation of new bone within the distraction gap. Distraction osteogenesis is efficacious for reconstructing critical sized bony defects in the appendicular and craniofacial skeleton. To provide opportunity to expand applications of distraction osteogenesis, it is important to have a thorough understanding of the underlying molecular biology and physiology of bone development and fracture healing. To accomplish these objectives a review of the literature was performed using search terms "endochondral ossification, intramembranous ossification, craniofacial skeleton, appendicular skeleton, fracture healing, bone development, and distraction osteogenesis." Bones of the craniofacial and appendicular skeleton have distinct mechanisms of embryonic development. The former develops from growth centers of mesenchymal precursors through intramembranous ossification. The latter forms though endochondral ossification in growth plates. However, both endochondral and intramembranous bone share similar master regulatory transcription factors and downstream growth factors. Fracture healing mirrors the pathway by which these bones developed embryonically. In contrast, bone formed by distraction osteogenesis does so by intramembranous ossification, regardless of whether it occurs within the appendicular or craniofacial skeleton. Understanding molecular pathway differences between bone formation by these mechanisms may allow for optimization and expansion of skeletal reconstruction by distraction osteogenesis.

BACKGROUND:Fifteen million U.S. patients each year seek medical care abroad; however, there are no data on outcomes and follow-up of these procedures. This study aims to identify, evaluate, and survey patients presenting with complications from aesthetic procedures abroad and estimate their cost to the U.S. health care system. METHODS:A single-center retrospective review was conducted. A cohort of patients presenting with complications from aesthetic procedures performed abroad was generated. Demographic, complication, and cost data were compiled. Patients were surveyed to assess their overall experience. RESULTS:Over a 36-month period, 42 patients met inclusion criteria (one man and 41 women), with an average age of 35 ± 11.4 years (range, 20 to 60 years). Comorbidities included four active smokers, two patients with hypertension, and one patient with diabetes. Average body mass index was 29 ± 4.4 kg/m (range, 22 to 38 kg/m). Procedures performed abroad included abdominoplasty (n = 28), liposuction (n = 20), buttock augmentation (n = 10), and breast augmentation (n = 7), with several patients undergoing combined procedures. Eleven patients presented with abscesses and eight presented with wound dehiscence. Eight of the 18 patients who were surveyed were not pleased with their results and 11 would not go abroad again for subsequent procedures. Average cost of treating the complications was $18,211, with an estimated cost to the U.S. health care system of $1.33 billion. The main payer group was Medicaid. CONCLUSIONS:Complications from patients seeking aesthetic procedures abroad will continues to increase. Patients should be encouraged to undergo cosmetic surgery in the United States to improve patient outcomes and satisfaction and because it is economically advantageous. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, IV.

Dental caries and gingival and periodontal diseases are commonly occurring, preventable chronic conditions in children. These diseases are more common in disadvantaged communities and marginalized populations. Thus, public health approaches that stress prevention are key to improving oral health equity. There is currently limited evidence on which community-based, population-level interventions are most effective and equitable in promoting children's oral health. More rigorous measurement and reporting of study findings are needed to improve the quality of available evidence. Improved understanding of the multilevel influences of children's oral health may lead to the design of more effective and equitable social interventions.

BACKGROUND: Despite a body of evidence on racial/ethnic minority enrollment and retention in research, literature specifically focused on recruiting racially/ethnically diverse older adults for social science studies is limited. There is a need for more rigorous research on methodological issues and the efficacy of recruitment methods. Cultural obstacles to recruitment of racial/ethnic minority older adults include language barriers, lack of cultural sensitivity of target communities on the part of researchers, and culturally inappropriate assessment tools. METHODS: Guided by the Consolidated Framework for Implementation Research (CFIR), this study critically appraised the recruitment of racial/ethnic minority older adults for focus groups. The initial approach involved using the physical and social infrastructure of the ElderSmile network, a community-based initiative to promote oral and general health and conduct health screenings in places where older adults gather, to recruit racial/ethnic minority adults for a social science component of an interdisciplinary initiative. The process involved planning a recruitment strategy, engaging the individuals involved in its implementation (opinion leaders in senior centers, program staff as implementation leaders, senior community-based colleagues as champions, and motivated center directors as change agents), executing the recruitment plan, and reflecting on the process of implementation. RESULTS: While the recruitment phase of the study was delayed by 6 months to allow for ongoing recruitment and filling of focus group slots, the flexibility of the recruitment plan, the expertise of the research team members, the perseverance of the recruitment staff, and the cultivation of change agents ultimately resulted in meeting the study targets for enrollment in terms of both numbers of focus group discussions (n = 24) and numbers of participants (n = 194). CONCLUSIONS: This study adds to the literature in two important ways. First, we leveraged the social and physical infrastructure of an existing program to recruit participants through community sites where older adults gather. Second, we used the CFIR to guide the appraisal of the recruitment process, which underscored important considerations for both reaching and engaging this underserved population. This was especially true in terms of understanding the disparate roles of the individuals involved in implementing and facilitating the recruitment plan.

Background/UNASSIGNED:Liposuction is among the most commonly performed aesthetic procedures, and is being performed increasingly as an adjunct to other procedures. Objectives/UNASSIGNED:To report the incidence and risk factors of significant complications after liposuction, and to determine whether adding liposuction to other cosmetic surgical procedures impacts the complication risk. Methods/UNASSIGNED:A prospective cohort of patients who underwent liposuction between 2008 and 2013 was identified from the CosmetAssure database. Primary outcome was occurrence of major complications requiring emergency room visit, hospital admission, or reoperation within 30 days of the operation. Univariate and multivariate analysis evaluated risk factors including age, gender, body mass index (BMI), smoking, diabetes, type of surgical facility, and combined procedures. Results/UNASSIGNED:Of the 31,010 liposuction procedures, only 11,490 (37.1%) were performed as a solitary procedure. Liposuction alone had a major complication rate of 0.7% with hematoma (0.15%), pulmonary complications (0.1%), infection (0.1%), and confirmed venous thromboembolism (VTE) (0.06%) being the most common. Independent predictors of major complications included combined procedures (Relative Risk (RR) 4.81), age (RR 1.01), BMI (RR 1.05), and procedures performed in hospitals (RR 1.36). When examining specifically other aesthetic procedures performed alone or with liposuction, combined procedures had a higher risk of confirmed VTE (RR 5.65), pulmonary complications (RR 2.72), and infection (RR 2.41), but paradoxically lower hematoma risk (RR 0.77) than solitary procedures. Conclusions/UNASSIGNED:Liposuction performed alone is a safe procedure with a low risk of major complications. Combined procedures, especially on obese or older individuals, can significantly increase complication rates. The impact of liposuction on the risk of hematoma in combined procedures needs further investigation. Level of Evidence 2/UNASSIGNED/: