Cerium oxide nanoparticle conjugation to microRNA-146a mechanism of correction for impaired diabetic wound healing.

Diabetic wounds represent a significant healthcare burden and are characterized by impaired wound healing due to increased oxidative stress and persistent inflammation. We have shown that CNP-miR146a synthesized by the conjugation of cerium oxide nanoparticles (CNP) to microRNA (miR)-146a improves diabetic wound healing. CNP are divalent metal oxides that act as free radical scavenger, while miR146a inhibits the pro-inflammatory NFκB pathway, so CNP-miR146a has a synergistic role in modulating both oxidative stress and inflammation. In this study, we define the mechanism(s) by which CNP-miR146a improves diabetic wound healing by examining immunohistochemical and gene expression analysis of markers of inflammation, oxidative stress, fibrosis, and angiogenesis. We have found that intradermal injection of CNP-miR146a increases wound collagen, enhances angiogenesis, and lowers inflammation and oxidative stress, ultimately promoting faster closure of diabetic wounds.

Cerium oxide nanoparticle delivery of microRNA-146a for local treatment of acute lung injury.

Acute respiratory distress syndrome (ARDS) is a devastating pulmonary disease with significant in-hospital mortality and is the leading cause of death in COVID-19 patients. Excessive leukocyte recruitment, unregulated inflammation, and resultant fibrosis contribute to poor ARDS outcomes. Nanoparticle technology with cerium oxide nanoparticles (CNP) offers a mechanism by which unstable therapeutics such as the anti-inflammatory microRNA-146a can be locally delivered to the injured lung without systemic uptake. In this study, we evaluated the potential of the radical scavenging CNP conjugated to microRNA-146a (termed CNP-miR146a) in preventing acute lung injury (ALI) following exposure to bleomycin. We have found that intratracheal delivery of CNP-miR146a increases pulmonary levels of miR146a without systemic increases, and prevents ALI by altering leukocyte recruitment, reducing inflammation and oxidative stress, and decreasing collagen deposition, ultimately improving pulmonary biomechanics.

Outcomes of Bariatric Surgery in Older Versus Younger Adolescents.

OBJECTIVES: In this report, we compare weight loss, comorbidity resolution, nutritional abnormalities, and quality of life between younger and older adolescents after metabolic and bariatric surgery. METHODS: From March 2007 to December 2011, 242 adolescents (≤19 years of age) who underwent bariatric surgery at 5 clinical centers in the United States were enrolled in the prospective, multicenter, long-term outcome study Teen-Longitudinal Assessment of Bariatric Surgery. Outcome data from younger (13-15 years; n = 66) and older (16-19 years; n = 162) study participants were compared. Outcomes included percent BMI change, comorbidity outcomes (hypertension, dyslipidemia, and type 2 diabetes mellitus), nutritional abnormalities, and quality of life over 5 years post surgery. RESULTS: Baseline characteristics, except for age, between the 2 cohorts were similar. No significant differences in frequency of remission of hypertension (P = .84) or dyslipidemia (P = .74) were observed between age groups. Remission of type 2 diabetes mellitus was high in both groups, although statistically higher in older adolescents (relative risk 0.86; P = .046). Weight loss and quality of life were similar in the 2 age groups. Younger adolescents were less likely to develop elevated transferrin (prevalence ratio 0.52; P = .048) and low vitamin D levels (prevalence ratio 0.8; P = .034). CONCLUSIONS: The differences in outcome of metabolic and bariatric surgery between younger and older adolescents were few. These data suggest that younger adolescents with severe obesity should not be denied consideration for surgical therapy on the basis of age alone and that providers should consider adolescents of all ages for surgical therapy for obesity when clinically indicated.

Nanosilk Increases the Strength of Diabetic Skin and Delivers CNP-miR146a to Improve Wound Healing.

Diabetes mellitus is a metabolic disorder associated with properties and an increased risk of chronic wounds due to sustained pro-inflammatory response. We have previously of radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA (miR)-146a, termed CNP-miR146a, improves diabetic wound healing by synergistically lowering oxidative stress and inflammation, and we sought to evaluate this treatment in a topical application. Silk fibroin is a biocompatible polymer that can be fabricated into nanostructures, termed nanosilk. Nanosilk is characterized by a high strength-to-density ratio and an ability to exhibit strain hardening. We therefore hypothesized that nanosilk would strengthen the biomechanical properties of diabetic skin and that nanosilk solution could effectively deliver CNP-miR146a to improve diabetic wound healing. The ability of nanosilk to deliver CNP-miR146a to murine diabetic wounds and improve healing was assessed by the rate of wound closure and inflammatory gene expression, as well as histologic analysis. The effect of nanosilk on the properties of human diabetic skin was evaluated by testing the biomechanical properties following topical application of a 7% nanosilk solution. Diabetic murine wounds treated with topical nanosilk and CNP-miR146a healed by day 14.5 compared to day 16.8 in controls (p = 0.0321). Wounds treated with CNP-miR146a had higher collagen levels than controls (p = 0.0126) with higher pro-fibrotic gene expression of TGFß-1 (p = 0.0092), Col3α1 (p = 0.0369), and Col1α2 (p = 0.0454). Treatment with CNP-miR146a lowered pro-inflammatory gene expression of IL-6 (p = 0.0488) and IL-8 (p = 0.0009). Treatment of human diabetic skin with 7% nanosilk solution resulted in significant improvement in maximum load and modulus (p < 0.05). Nanosilk solution is able to strengthen the biomechanical properties of diabetic skin and can successfully deliver CNP-miR146a to improve diabetic wound healing through inhibition of pro-inflammatory gene signaling and promotion of pro-fibrotic processes.

Excess skin problems among adolescents after bariatric surgery.

BACKGROUND: Bariatric surgery results in significant and durable weight loss and improved health in severely obese adolescents. An important adverse consequence of the massive weight loss after bariatric surgery is excess skin and soft tissue. The prevalence and clinical characteristics of excess skin-related symptoms have been described in adults undergoing bariatric surgery but not in adolescents. Although the higher skin elasticity of adolescents may result in fewer excess skin problems compared with adults, this hypothesis remains untested. OBJECTIVES: The purpose of the present study was to describe the natural history of excess skin and its associated complications among severely obese adolescents undergoing bariatric surgery. SETTING: University Hospitals, United States. METHODS: We evaluated data from the Teen-Longitudinal Assessment of Bariatric Surgery cohort, a prospective, multiinstitutional study of adolescents (13-19 yr) undergoing bariatric surgery. Abdominal pannus severity (graded 0-5) and excess skin symptoms were evaluated preoperatively and for the first 5 years after bariatric surgery. RESULTS: Among the 217 study participants, 198 (90%) had an abdominal pannus and 16 (7%) reported pannus-related symptoms at the time of bariatric surgery. Preoperative symptoms included intertriginous infections (n = 12, 75%), recurrent cellulitis (n = 5, 31%), and superficial cutaneous ulcerations (n = 1, 6%). Participants with a higher pannus grade preoperatively experienced both a greater reduction in pannus severity (P < .0001) and a higher incidence of pannus-related symptoms (P = .002) postoperatively. Changes in pannus severity occurred during the first 24 months after bariatric surgery; mean pannus severity remained unchanged beyond 24 months. CONCLUSIONS: Severely obese adolescents who undergo bariatric surgery often present with an abdominal pannus at the time of surgery with associated symptoms. Higher preoperative pannus grade is associated with more pannus related symptoms after surgery. Counseling about need for body contouring surgery should be considered in this group.

Weight Loss and Health Status 5 Years After Adjustable Gastric Banding in Adolescents.

OBJECTIVE: This prospective cohort analysis describes changes in weight, cardiometabolic health, and weight-related quality of life (WRQOL) following adolescent LAGB. METHODS: Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) collected demographic, anthropometric, micronutrient, cardiometabolic risk, and WRQOL data for 242 adolescents. Data through 5 years were analyzed for 14 participants who underwent LAGB with 2 patients lost to follow-up. RESULTS: Participants (mean age 18.2 ± 0.4 years) were mostly female (86%) and white (71%) with a median body mass index (BMI) of 48.7 kg/m2 (45.5-54.1). Preoperatively, 100%(13/13), 62%(8/13), 57%(8/14), and 7%(1/14) had elevated high sensitivity C-reactive protein (hs-CRP), dyslipidemia, elevated blood pressure (EBP), and type 2 diabetes (T2D), respectively. At 5 years, mean BMI decreased by 3.3% (51.0 vs. 49.3 kg/m2, p = 0.6), 43%(6/14) had BMI values exceeding baseline and 21% (3/14) underwent band removal. Postoperative prevalence of hs-CRP, dyslipidemia, EBP, and T2D was 45% (4/11), 36% (5/11), 33% (4/12), and 0% (0/11), respectively. CONCLUSION: Adolescents undergoing LAGB experienced modest initial weight loss and improvements in cardiovascular risk factors with later weight regain and frequent need for band removal. Despite the small sample size, this prospective study highlights long-term outcomes with high rates of participant retention over time. CLINICAL TRIAL REGISTRATION: NCT00465829.

Determining maternal risk factors for gastroschisis using colorado's birth registry database.

AIM OF STUDY: Gastroschisis is a congenital abdominal wall defect which results in herniation of abdominal contents. The objective of this study was to determine the maternal risk factors for gastroschisis in Colorado. METHODS: A case-control study was performed using the Birth Registry database from 2007 to 2016. The outcome was gastroschisis, and the main variable was maternal age which was divided into <21, 21-30, and >30 years of age. Descriptive analysis, bivariate analysis, and logistic regression was performed. RESULTS: There were 236 cases of gastroschisis compared to 944 controls. Maternal age did vary significantly between groups (23.4 ±â€¯5 years (cases) vs. 28.7 ±â€¯5.9 years (controls); p < 0.0001). Unadjusted analysis demonstrated that those with young maternal age (<21 years of age) had a 14.14 (95% CI 8.44-23.67) higher odds of gastroschisis compared to those >30 years of age. Independent risk factors for gastroschisis were exposure to prenatal and first trimester cigarettes, prenatal and first trimester alcohol, and chlamydia infection. The odds (4.41, 95% CI 1.36-14.26) of gastroschisis were highest in those with first trimester cigarette exposure and young maternal age (p = 0.03). CONCLUSIONS: Young maternal age, cigarette exposure, alcohol exposure, and chlamydia infection increase the odds of gastroschisis. The interaction between young maternal age and first trimester cigarette exposure significantly increases the odds of gastroschisis. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level III.

A congenital cystic pulmonary airway malformation occurring together with both an extralobar pulmonary sequestration and an esophageal duplication cyst.

A foregut duplication cyst occurring together with both a congenital cystic pulmonary airway malformation and extralobar pulmonary sequestration is an unusual combination. Prenatal ultrasound, MRI, and postnatal CT are helpful for operative planning. Surgical resection is the definitive management for all three anomalies.

Is Tapering Enteroplasty an Alternative to Resection of Dilated Bowel in Small Intestinal Atresia?

BACKGROUND: Intestinal atresia is a congenital defect resulting in intestinal discontinuity and can be associated with significant morbidity related to intestinal failure. The bowel proximal to the atresia is often significantly dilated and dysfunctional. The treatment approaches of this dilated bowel include resection with primary anastomosis versus tapering enteroplasty with preservation of bowel length. The purpose of this study was to compare these two approaches in regard to bowel function as characterized by the time to full enteral feeding. METHODS: A retrospective review was performed of intestinal atresia repair performed at a tertiary referral pediatric hospital from 2007 to 2017. Length of stay, time to full enteral feeds, and complications were assessed in patients who underwent repair with tapering enteroplasty (n = 8) and compared with those who underwent resection and anastomosis (n = 39). RESULTS: The median age at surgery, gender distribution, weeks gestational age (WGA), location of the atresia, and comorbidities were similar between the two groups. Overall, there was no statistically significant difference in length of stay and time to full enteral feeds between groups. Three of eight (38%) patients in the tapered group and five of 39 patients (13%; P = 0.12) in the nontapered group underwent further surgical exploration because of bowel dysmotility. Factors associated with longer length of hospital stay were abdominal reoperation and WGA, and factors associated with longer time to full enteral feeds were WGA, abdominal reoperation, and gastroschisis. CONCLUSIONS: Tapering enteroplasty at initial operation for intestinal atresias preserves bowel length and has statistically equivalent outcomes to resection and anastomosis in regard to the length of stay and time to full enteral feeds.

Examination of Prenatal Sonographic Findings: Intra-Abdominal Bowel Dilation Predicts Poor Gastroschisis Outcomes.

BACKGROUND: Gastroschisis is an anterior abdominal wall defect with variable outcomes. There are conflicting data regarding the prognostic value of sonographic findings. OBJECTIVES: The aim of this study was to identify prenatal ultrasonographic features associated with poor neonatal outcomes. METHOD: A retrospective review of 55 patients with gastroschisis from 2007 to 2017 was completed. Ultrasounds were reviewed for extra-abdominal intestinal diameter (EAID) and intra-abdominal intestinal diameter (IAID), echogenicity, visceral content within the herniation, amniotic fluid index, defect size, and abdominal circumference (AC). Ultrasound variables were correlated with full enteral feeding and the diagnosis of a complex gastroschisis. RESULTS: Bivariate analysis demonstrated an increased time to full enteral feeds with increasing number of surgeries, EAID, and IAID. Additionally, there was a significant relationship between IAID and AC percentile with the diagnosis of complex gastroschisis. On multivariate analysis, only IAID was significant and increasing diameter had a 2.82 (95% CI 1.02-7.78) higher odds of a longer time to full enteral feeds and a 1.2 (95% CI 1.05-1.36) greater odds of the diagnosis of a complex gastroschisis. CONCLUSIONS: Based on these findings, IAID is associated with a longer time to full enteral feeding and the diagnosis of complex gastroschisis.

Body contouring in adolescents after bariatric surgery.

BACKGROUND: Bariatric surgery leads to sustained weight loss and resolution of obesity-associated co-morbidities in severely obese adolescents. However, one consequence of massive weight loss is excess skin and soft tissue. Many details regarding the timing, outcomes, and barriers associated with body contouring surgery (BCS) in youth who have undergone bariatric surgery are unknown. OBJECTIVES: Describe the incidence and effect of BCS following bariatric surgery among adolescents. SETTING: University Hospitals. METHODS: Teen-Longitudinal Assessment of Bariatric Surgery is a prospective multi-institutional study of 242 adolescents who underwent bariatric surgery from 2007 to 2012. Utilization of BCS was analyzed in this population with comparison of anthropometrics and excess skin-related symptoms between those who did and those who did not undergo BCS. RESULTS: Among the 198 study participants with BCS data available, 25 (12.6%) underwent 41 body contouring procedures after bariatric surgery. The most common BCS was panniculectomy (n = 23). Presence of pannus-related symptoms at baseline and the magnitude of weight loss within the first year after bariatric surgery were independently associated with subsequent panniculectomy (P = .04 and P = .03, respectively). All adolescents who underwent panniculectomy experienced resolution of pannus-related symptoms. At 5 years after bariatric surgery, 74% of those who did not undergo panniculectomy reported an interest in the procedure, and 58% indicated that cost/insurance coverage was the barrier to obtaining BCS. CONCLUSION: Few adolescents who underwent bariatric surgery later underwent BCS procedures. Panniculectomy effectively treated pannus-related symptoms. Disparities in access to surgical care for adolescents who desire BCS warrants further investigation.

Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy.

BACKGROUND: Stem cell therapy is the next generation a well-established technique. Cell therapy with mesenchymal stem cells (MSC) has been demonstrated to enhance wound healing in diabetic mice, at least partly due to improved growth factor production. However, it is unclear whether MSC can biomechanically affect wound closure. Utilizing the well-established cell-populated collagen gel contraction model we investigated the interactions between MSC and the extracellular matrix. METHODS: Murine fetal liver-derived Mesenchymal Stem Cells (MSCs) or fetal Dermal Fibroblasts (DFs) were cultured in cell-populated collagen gels (CPCGs). The effect of cell density, conditioned media, growth factors (TGF-B1, FGF, PDGF-BB), cytoskeletal disruptors (colchicine, cytochalasin-D), and relative hypoxia on gel contraction were evaluated. Finally, we also measured the expression of integrin receptors and some growth factors by MSCs within the contracting gels. RESULTS: Our results show that at different densities, MSCs induced a higher gel contraction compared to DFs. Higher cell density resulted in faster and more complete contraction of CPCGs. Cytoskeletal inhibitors either inhibited or prevented MSC-mediated contraction in a dose dependent fashion. Growth factors, conditioned media from both MSC and DF, and hypoxia all influenced CPCG contraction. DISCUSSION: The results suggest that MSCs are capable of directly contributing to wound closure through matrix contraction, and they are more effective than DF. In addition, this study demonstrates the importance of how other factors such as cell concentration, cytokines, and oxygen tension can provide potential modulation of therapies to correct wound healing impairments.

MOMS Plus: Single-Institution Review of Outcomes for Extended BMI Criteria for Open Fetal Repair of Myelomeningocele.

BACKGROUND: In utero repair has become an accepted therapy to decrease the rate of ventriculoperitoneal shunting and improve neurologic function in select cases of myelomeningocele. The Management of Myelomeningocele Study (MOMS) trial excluded patients with a BMI >35 due to concerns for increased maternal complications and preterm delivery, limiting the population that may benefit from this intervention. OBJECTIVES: The aim of this study was to evaluate outcomes associated with extending the maternal BMI criteria to 40 in open fetal repair of myelomeningocele. METHOD: Retrospective review of fetal closure of myelomeningocele at a quaternary referral center between 2013 and 2016 with maternal BMI ranging from 35 to 40. RESULTS: Eleven patients with a BMI >35 were identified. The average BMI was 37. The average maternal age at the time of evaluation was 27 years. The average gestational age at fetal surgery was 24 weeks. Gestational age at birth was an average of 32 weeks. There was one perinatal death immediately following the fetal intervention. The shunt rate at 1 year was 45% (5/11 patients). CONCLUSIONS: In this single-institution review of expanded BMI criteria for fetal repair of myelomeningocele, we did not observe any adverse maternal outcomes associated with maternal obesity; however, the gestational age at delivery was 2 weeks earlier compared to the MOMS trial.

Change in gastrointestinal symptoms over the first 5 years after bariatric surgery in a multicenter cohort of adolescents.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are effective for weight loss in adolescents with severe obesity. However, little is known about adverse gastrointestinal symptoms (GIS) following these operations in adolescents. The objective was to examine GIS over 5 years after surgery and differences by surgery type. METHODS: We prospectively studied 228 adolescents (161 RYGB, 67 VSG) undergoing bariatric surgery. Gastrointestinal symptoms were assessed before surgery, at 6-months, and yearly to 5 years after surgery. Symptom severity was dichotomized for analysis. Analysis of post-surgery symptoms involved linear models adjusting for baseline symptoms, BMI, early post-operative complication, sex, and race. RESULTS: Participants at surgery were 17 ±â€¯1.6 years with preoperative BMI 53 ±â€¯9.4 kg/m2. From 6 months to 5 years, gastroesophageal reflux symptoms (GERS), nausea, bloating, and diarrhea increased. Crude prevalence rates of GERS increased from 4% (1% RYGB, 11% VSG) at 6-months post-surgery to 14% (10% RYGB, 26% VSG) at 5-years. In adjusted analyses, the VSG group experienced 4-fold (4.85 95% CI 2.63, 8.91, p < 0.0001) greater odds of GERS compared to RYGB. CONCLUSIONS: Adolescents who underwent VSG experienced greater risk of GERS compared to those undergoing RYGB. Adolescents undergoing VSG should be counseled preoperatively about GERS and objectively monitored postoperatively for gastroesophageal reflux when indicated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT00474318, https://clinicaltrials.gov/ct2/show/NCT00474318?term=Teen-LABS&rank=1. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level II.

Pilot Prehabilitation Program for Patients With Esophageal Cancer During Neoadjuvant Therapy and Surgery.

BACKGROUND: Locally advanced esophageal cancer is often treated with neoadjuvant therapy followed by surgery. Many patients present with or experience clinical deconditioning during neoadjuvant therapy. Prehabilitation programs in other areas of surgery have demonstrated improved postoperative outcomes. The aims of this study were to evaluate the feasibility of a pilot prehabilitation program and determine preliminary effects on surgical and cancer-related outcomes. METHODS: A retrospective review of patients treated at a single institution with resectable esophageal cancer was performed (n = 22). Patients in the prehabilitation group received protocol-structured intervention in several clinical domains including nutrition, psychosocial support, and physical exercise. RESULTS: Clinical stage and comorbidities were well matched between groups. The structured prehabilitation program was feasible and well received by participants. Fewer patients required admission during neoadjuvant therapy in the prehabilitation group (27.3% versus 54.5%). Percentage weight loss during treatment was 3.0% in the prehabilitation group versus 4.3% in the control group. Compared with the control group, the prehabilitation group demonstrated 0.0% versus 18.2% 30-d postoperative readmission rate and 18.2% versus 27.3% 90-d postoperative readmission rate. There were no statistically significant differences between groups in regard to complications or mortality. CONCLUSIONS: The pilot prehabilitation program demonstrated feasibility of implementing a structured program for patients receiving neoadjuvant therapy for esophageal cancer. Although the small population limits evaluation of statistical significance, trends in the data suggest a potential benefit of the prehabilitation program on neoadjuvant hospital admission rates, postsurgical readmission rates, and nutritional status.

Differential Expression of Transforming Growth Factor-ß1 Is Associated With Fetal Regeneration After Myocardial Infarction.

BACKGROUND: Global extracellular matrix (ECM)-related gene expression is decreased after myocardial infarction (MI) in fetal sheep when compared with adult sheep. Transforming growth factor (TGF)-ß1 is a key regulator of ECM; therefore we hypothesize that TGF-ß1 is differentially expressed in adult and fetal infarcts after MI. METHODS: Adult and fetal sheep underwent MI via ligation of the left anterior descending coronary artery. Expression of TGF-ß1 and ECM-related genes was evaluated by ovine-specific microarray and quantitative polymerase chain reaction. Fibroblasts from the left ventricle of adult and fetal hearts were treated with TGF-ß1 or a TGF-ß1 receptor inhibitor (LY36497) to evaluate the effect of TGF-ß1 on ECM-related genes. RESULTS: Col1a1, col3a1, and MMP9 expression were increased in adult infarcts 3 and 30 days after MI but were upregulated in fetal infarcts only 3 days after MI. Three days after MI elastin expression was increased in adult infarcts. Despite upregulation in adult infarcts both 3 and 30 days after MI, TGF-ß1 was not upregulated in fetal infarcts at any time point. Inhibition of the TGF-ß1 receptor in adult cardiac fibroblasts decreased expression of col1a1, col3a1, MMP9, elastin, and TIMP1, whereas treatment of fetal cardiac fibroblasts with TGF-ß1 increased expression of these genes. CONCLUSIONS: TGF-ß1 is increased in adult infarcts compared with regenerative, fetal infarcts after MI. Although treatment of fetal cardiac fibroblasts with TGF-ß1 conveys an adult phenotype, inhibition of TGF-ß1 conveys a fetal phenotype to adult cardiac fibroblasts. Decreasing TGF-ß1 after MI may facilitate myocardial regeneration by "fetalizing" the otherwise fibrotic, adult response to MI.

Use of Cerium Oxide Nanoparticles Conjugated with MicroRNA-146a to Correct the Diabetic Wound Healing Impairment.

BACKGROUND: Diabetic wounds have become one of the most challenging public health issues of the 21st century, yet there is no effective treatment available. We have previously shown that the diabetic wound healing impairment is associated with increased inflammation and decreased expression of the regulatory microRNA miR-146a. We have conjugated miR-146a to cerium oxide nanoparticles (CNP-miR146a) to target reactive oxygen species (ROS) and inflammation. This study aimed to evaluate the consequences of CNP-miR146a treatment of diabetic wounds. STUDY DESIGN: Eight-millimeter wounds were created on the dorsal skin of Db/Db mice and treated with PBS or differing concentrations of CNP-mir146a (1; 10; 100; or 1,000 ng) at the time of wounding. Rate of wound closure was measured until the wounds were fully healed. At 4 weeks post-healing, a dumbbell-shaped skin sample was collected, with the healed wound in the center, and an Instron 5942 testing unit was used to measure the maximum load and modulus. RESULTS: Our data showed that diabetic wounds treated with PBS or 1 ng CNP-miR146a took 18 days to heal. Treatment with 10, 100, or 1,000 ng of CNP+miR-146a effectively enhanced healing, and wounds were fully closed at day 14 post-wounding. The healed skin from the CNP-miR146a-treated group showed a trend of improved biomechanical properties (increased maximum load and modulus), however it did not reach significance. CONCLUSIONS: We found that a 100-ng dose of CNP-miR146a improved diabetic wound healing and did not impair the biomechanical properties of the skin post-healing. This nanotechnology-based therapy is promising, and future studies are warranted to transfer this therapy to clinical application.

A Single Surgeon Laparoscopic Duodenoduodenostomy Case Series for Congenital Duodenal Obstruction in an Academic Setting.

Introduction: Laparoscopic duodenoduodenostomy can be performed to repair congenital duodenal obstructions from atresia or duodenal web. There are only a few published case series in the literature. We are reporting on a single surgeon's experience with the operation and discuss the technical aspects of the operation. Material and Methods: A retrospective chart review was performed using the electronic medical record identifying all patients who underwent laparoscopic duodenoduodenostomy or duodenojejunostomy at two institutions by a singular surgeon. Results: Fifteen patients were identified as having undergone laparoscopic duodenoduodenostomy from 2010 until 2017. The weight at the time of the operation ranged from 1.5 to 8.7 kg (median 2.5 kg). The age ranged from 0 days to 15 months (median 3 days). Operative time (including other procedures) ranged from 2 hours 10 minutes to 3 hours 45 minutes with a median of 2 hours 55 minutes. One case was converted to open due to poor visualization. One patient developed a stricture that required open anastomotic revision 4 weeks after the initial surgery. In 1 patient, an enterotomy in the first portion of the duodenum was created from a retraction stitch-this was immediately recognized and repaired by primary laparoscopic closure. One patient had a small anastomotic leak that was treated with antibiotics. There were no mortalities and no intraoperative blood loss requiring transfusion. Conclusion: Laparoscopic duodenoduodenostomy is an operation that can be performed with excellent outcomes following simple steps that are easily taught in a teaching setting.