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Introduction: Research is a critical component of academic medicine that may or may not be prioritized in centers with high clinical volumes. The benefits of research expansion go beyond notoriety and industry partnerships, expanding into resident training and preparation of the next generation of physician-scientists. Improving a division or department's research portfolio requires a commitment to reorganizing structure, personnel, resources, and a dedication to innovative funding models. To improve research productivity and quality, our group placed several initiatives into motion beginning in August 2017 that we have outlined and evaluated in the present study. Some of these initiatives included restructuring leadership, resourcing both bench and clinical outcomes research, providing initial funding directly from clinical profits and rewarding research fiscally., Methods: Reviews of hiring records, publications, grant allocations, and interviews with key personnel were used to generate a road map of initiatives. Average impact factor was calculated by averaging journal impact factors for all publications from the department each year, excluding any publications with greater than 5 times the raw average, and creating a corrected average that more accurately represented the work. Student t tests were used to compare mean number of publications and impact factors from 2010 to 2017 to those from 2018 to 2022., Results: Prior to restructuring (2010-2017), the department published an average of 9 articles annually, which increased to an average of 42 articles since that time (P < 0.01). Average impact increased from 0 in 2010 to 4.02 in 2022, with the number of publications in top 10 plastic surgery journals following a similar trajectory with 1 publication in 2010 and 31 in 2023. Following an initial $1 million investment to create an institutionally directed fund in 2018, the department leveraged its research to earn $3 million in endowments, $1.25 million in industry partnerships, $3.23 million in Department of Defense funding, and $1.65 million from a multi-institutional National Institutes of Health grant., Conclusion: Deliberate prioritization of research initiatives as noted above has led to remarkable growth in academic output., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A mathematical model-based parcellation of magnetic resonance diffusion tensor images (DTI) has been developed to quantify progressive changes in three types of tissues - grey (GM), white matter (WM), and damaged spinal cord tissue, along with behavioral assessments over a 6 month period following targeted spinal cord injuries (SCI) in monkeys. Sigmoid Gompertz function based fittings of DTI metrics provide early indicators that correlate with, and predict, recovery of hand grasping behavior. Our three tissue pool model provided unbiased, data-driven segmentation of spinal cord images and identified DTI metrics that can serve as reliable biomarkers of severity of spinal cord injuries and predictors of behavioral outcomes., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Peripheral nerve repair is limited by Wallerian degeneration coupled with the slow and inconsistent rates of nerve regrowth. In more proximal injuries, delayed nerve regeneration can cause debilitating muscle atrophy. Topical application of polyethylene glycol (PEG) during neurorrhaphy facilitates the fusion of severed axonal membranes, immediately restoring action potentials across the coaptation site. In preclinical animal models, PEG-fusion resulted in remarkable early functional recovery., Methods: This is the first randomized clinical trial comparing functional outcomes between PEG-fusion and standard neurorrhaphy. Participants with digital nerve transections were followed up at 2 weeks, 1 month, and 3 months postoperatively. The primary outcome was assessed using the Medical Research Council Classification (MRCC) rating for sensory recovery at each timepoint. Semmes-Weinstein monofilaments and static two-point discrimination determined MRCC ratings. Postoperative quality of life was measured using the Michigan Hand Questionnaire (MHQ)., Results: Forty-eight transected digital nerves (25 control, 23 PEG) across twenty-two patients were analyzed. PEG-fused nerves demonstrated significantly higher MRCC scores at 2 weeks (OR 16.95, 95% CI: 1.79 - 160.38, p = 0.008) and 1 month (OR 13.40, 95% CI: 1.64 - 109.77, p = 0.009). Participants in the PEG cohort also had significantly higher average MHQ scores at 2 weeks (Hodge's g 1.28, 95% CI: 0.23 - 2.30, p = 0.0163) and 1 month (Hodge's g 1.02, 95% CI: 0.04 - 1.99, p = 0.049). No participants had adverse events related to the study drug., Conclusion: PEG-fusion promotes early sensory recovery and improved patient well-being following peripheral nerve repair of digital nerves., (Copyright © 2024 by the American Society of Plastic Surgeons.)

In surgical procedures where the risk of accidental nerve damage is prevalent, surgeons commonly use electrical stimulation (ES) during intraoperative nerve monitoring (IONM) to assess a nerve's functional integrity. ES, however, is subject to off-target stimulation and stimulation artifacts disguising the true functionality of the specific target and complicating interpretation. Lacking a stimulation artifact and having a higher degree of spatial specificity, infrared neural stimulation (INS) has the potential to improve upon clinical ES for IONM. Here, we present a direct comparison between clinical ES and INS for IONM performance in an in vivo rat model. The sensitivity of INS surpasses that of ES in detecting partial forms of damage while maintaining a comparable specificity and sensitivity to more complete forms. Without loss in performance, INS is readily compatible with existing clinical nerve monitoring systems. These findings underscore the clinical potential of INS to improve IONM and surgical outcomes., (© 2023. The Author(s).)

Background: Lead exposures from legacy sources threaten children's health. Soil in Omaha, Nebraska, was contaminated by emissions from a lead smelter and refinery. The U.S. Environmental Protection Agency excavated and replaced contaminated soil at the Omaha Lead Superfund Site between 1999 and 2016., Objectives: The goal of this study was to assess the association of soil lead level (SLL) and soil remediation status with blood lead levels (BLLs) in children living near or on the site., Methods: We linked information on SLL at residential properties with children's BLLs and assigned remediation status to children's BLL measurements based on whether their measurements occurred during residence at remediated or unremediated properties. We examined the association of SLL and remediation status with elevated BLL (EBLL). We distinguished the roles of temporal trend and the intervention with time-by-intervention-status interaction contrasts. All analyses estimated odds ratios (ORs) with a generalized estimating equations approach to ensure robustness under the complex correlations among BLL measurements. All analyses controlled for relevant covariates including children's characteristics., Results: EBLL ( > 5 μ g / dL ) was associated with both residential SLL [e.g., OR = 2.00 ; 95% confidence interval (CI): 1.83, 2.19; > 400 - 800 vs. ≤ 200  ppm ] and neighborhood SLL [e.g., OR = 1.85 (95% CI: 1.62, 2.11; > 400 - 800 vs. ≤ 200  ppm )] before remediation but only with neighborhood SLL after remediation. The odds of EBLL were higher before remediation [OR 1.52 (95% CI: 1.34, 1.72)]. Similarly, EBLL was positively associated with preremediation status in our interaction analysis [interaction OR = 1.18 (95%CI: 1.02, 1.37)]., Discussion: Residential and neighborhood SLLs were important predictors of EBLLs in children residing near or on this Superfund site. Neighborhood SLL remained a strong predictor following remediation. Our data analyses showed the benefit of soil remediation. Results from the interaction analyses should be interpreted cautiously due to imperfect correspondence of remediation times between remediation and comparison groups. https://doi.org/10.1289/EHP8657.

Fifteen years following the approval of the first human papillomavirus (HPV) vaccine, cervical cancer continues to be a significant source of morbidity and mortality among women in low-resource settings. It is the second-leading cause of cancer-related deaths in women globally and the leading cause of cancer-related deaths in Sub-Saharan Africa. Vaccine delivery and programmatic costs may hinder the distribution of HPV vaccines in low-resource settings, and ultimately influence access to HPV vaccines. While reviews have been conducted on the cost-effectiveness of HPV vaccines, little is known about the cost and effectiveness of vaccination strategies. The purpose of this systematic review was to synthesize evidence on the cost and cost-effectiveness of vaccination strategies utilized to increase access to HPV vaccines. Search queries were created for CINAHL Plus, Embase, and PubMed. Our search strategy focused on articles that contained information on HPV vaccine uptake/reach, HPV vaccination costs, or the cost-effectiveness of HPV vaccination programs. We retrieved 773 articles from the databases, assessed 251 full-texts, and included 15 articles in our final synthesis. Countries without national HPV vaccination programs aimed to identify and adopt sustainable strategies to make HPV vaccines available to adolescents through demonstration programs. In contrast, countries with national vaccination programs focused on identifying cost-effective interventions to increase vaccination rates to meet nationally recommended standards. There is a dire need for HPV vaccination programs and intervention studies tailored to settings in low- and middle-income countries to increase access to HPV vaccines. Future studies should also evaluate the cost-effectiveness of implemented strategies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Purpose: Biomaterials used to restore digital nerve continuity after injury associated with a defect may influence ultimate outcomes. An evaluation of matched cohorts undergoing digital nerve gap reconstruction was conducted to compare processed nerve allograft (PNA) and conduits. Based on scientific evidence and historical controls, we hypothesized that outcomes of PNA would be better than for conduit reconstruction., Methods: We identified matched cohorts based on patient characteristics, medical history, mechanism of injury, and time to repair for digital nerve injuries with gaps up to 25 mm. Data were stratified into 2 gap length groups: short gaps of 14 mm or less and long gaps of 15 to 25 mm. Meaningful sensory recovery was defined as a Medical Research Council scale of S3 or greater. Comparisons of meaningful recovery were made by repair method between and across the gap length groups., Results: Eight institutions contributed matched data sets for 110 subjects with 162 injuries. Outcomes data were available in 113 PNA and 49 conduit repairs. Meaningful recovery was reported in 61% of the conduit group, compared with 88% in the PNA group. In the group with a 14-mm or less gap, conduit and PNA outcomes were 67% and 92% meaningful recovery, respectively. In the 15- to 25-mm gap length group, conduit and PNA outcomes were 45% and 85% meaningful recovery, respectively. There were no reported adverse events in either treatment group., Conclusions: Outcomes of digital nerve reconstruction in this study using PNA were consistent and significantly better than those of conduits across all groups. As gap lengths increased, the proportion of patients in the conduit group with meaningful recovery decreased. This study supports the use of PNA for nerve gap reconstruction in digital nerve reconstructions up to 25 mm., Type of Study/level of Evidence: Therapeutic III., (Copyright © 2020 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Introduction: Advanced age alters many physiological processes in the body, including both innate and adaptive immune responses, affecting burn wound healing. Previous findings in our lab led us to look more closely at eosinophil infiltration of burn tissues. We hypothesize that burn wounds within the older population present with an increased population of eosinophils than those in the younger population., Methods: A pilot study was performed utilizing samples collected from male and female patients 30-years-old and younger and 65-years-old and older. Samples were collected at day (PBD) 2-6 after burn. Deep partial-thickness burn tissues were collected during surgery, formalin-fixed paraffin embedded (FFPE), and assessed by H&E to confirm deep partial-thickness injury. Immunohistochemistry (IHC) was then performed for Major Basic Protein (MBP) to identify eosinophils. Eosinophils/mm burn were calculated. Welch's Test was used to determine statistical significance of eosinophil measurements between young and old groups., Results: Thirteen samples, were divided into two groups, Young (n=10) and Old (n=3). The mean and median age for Young was 23yo (Max 30yo; Min. 17yo). The mean age was 81yo and the median 84yo for the Old (Max. 93yo; Min. 67yo). Other demographics included race. It was found that the Young and Old groups had a mean of 0.171 Eos/mm and 0.910 Eos/mm, respectively, which was statistically significant (p=0.017)., Conclusion: Older patients do present with increased eosinophil infiltration in the early stages of burn wound healing within our small sample set. Increased sample numbers will be required to confirm this discovery., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Treatment for mandibular fractures is commonly performed via open reduction fixation with mini titanium or resorbable plates and screws. The investigators hypothesized differences in maximum mechanical stress forces and deflection with each plating material; however, it was proposed that the experimental forces withstood by the resorbable system would be enough to withstand normal forces produced during mastication. The sample was composed of fresh cadaver mandibles that were harvested, fractured, and fixated with plates and screws. The predictor variable was fracture fixation and included a titanium plating or resorbable poly-L-lactide plating system. The primary outcome measure was maximum load withstood before plating failure measured in Newtons (N). Descriptive and bivariate statistics were computed, P value was set at .05. The sample was composed of six mandibles with and grouped by type of fixation modality, Titanium (T) (n = 3) and Resorbable (n = 3). There was a statistically significant correlation between the T group and increased maximum load (N) before failure as compared to the R group, (P = 0.023). The results suggest that fracture fixation with titanium plates and screws can withstand greater maximum forces before failure; however, the resorbable plating system withstood forces similar to/or greater than the maximum forces produced during normal mastication., (© 2020 Published by Elsevier Ltd.)

Polyethylene glycol (PEG) is a cell membrane fusogen (de StGroth et al., 1980; Hoehn et al., 1978 [2]; Pontecorvo et al., 1975 [3]). In clinical application PEG allows some axonal fusion in peripheral nerve repairs, resulting in retention of some mobility and sensation during the regeneration process and reducing muscular atrophy. Several manuscripts exist concerning in vivo models of PEG fusion, while there is a distinct lack of in vitro studies. This study optimizes an experimental in vitro PEG fusion procedure in B35 rat neuroblastoma cells, through alteration of PEG and dimethyl sulfoxide (DMSO) concentrations and utilizes flow cytometry for assessment. The optimized procedure was then tested on B104-1-1 cells, a mouse neuroblastoma line expressing P2X7R, to validate our in vitro procedure/model against previous in vivo testing of P2X7R modulators, Brilliant Blue FCF (FCF) and bzATP. In brief, two cell populations were differentially stained, mixed, pre-treated (if applicable) and PEG-fused. Initial optimization generated the highest fusion rates with 70% PEG + 0% DMSO. Subsequent testing of the model with FCF and bzATP proved that assessment over time is required when evaluating potential modulators of PEG fusion. Our conclusion, at 72 h post PEG fusion, is that the optimized procedure is suitable for initial candidate testing of modulators of PEG fusion. In vitro experiments with FCF and bzATP corroborated previous in vivo findings and confirmed that DMSO is not required to aid PEG fusion in the in vitro model. The development of this cellular based in vitro model will be invaluable as a substitute for initial assessment of chemical modulators of PEG fusion., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

On March 24 and 25, 2017 researchers and clinicians from around the world met at Temple University in Philadelphia to discuss the current knowledge of Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human disease. The conference was held because of shared concern that MAP is a zoonotic bacterium that poses a threat not only to animal health but also human health. In order to further study this problem, the conferees discussed ways to improve MAP diagnostic tests and discussed potential future anti-MAP clinical trials. The conference proceedings may be viewed on the www.Humanpara.org website. A summary of the salient work in this field is followed by recommendations from a majority of the conferees.

Processed nerve allografts (PNAs) have been demonstrated to have improved clinical results compared with hollow conduits for reconstruction of digital nerve gaps less than 25 mm; however, the use of PNAs for longer gaps warrants further clinical investigation. Long nerve gaps have been traditionally hard to study because of low incidence. The advent of the RANGER registry, a large, institutional review board-approved, active database for PNA (Avance Nerve Graft; AxoGen, Inc, Alachua, FL) has allowed evaluation of lower incidence subsets. The RANGER database was queried for digital nerve repairs of 25 mm or greater. Demographics, injury, treatment, and functional outcomes were recorded on standardized forms. Patients younger than 18 and those lacking quantitative follow-up data were excluded. Recovery was graded according to the Medical Research Council Classification for sensory function, with meaningful recovery defined as S3 or greater level. Fifty digital nerve injuries in 28 subjects were included. There were 22 male and 6 female subjects, and the mean age was 45. Three patients gave a previous history of diabetes, and there were 6 active smokers. The most commonly reported mechanisms of injury were saw injuries (n = 13), crushing injuries (n = 9), resection of neuroma (n = 9), amputation/avulsions (n = 8), sharp lacerations (n = 7), and blast/gunshots (n = 4). The average gap length was 35 ± 8 mm (range, 25-50 mm). Recovery to the S3 or greater level was reported in 86% of repairs. Static 2-point discrimination (s2PD) and Semmes-Weinstein monofilament (SWF) were the most common completed assessments. Mean s2PD in 24 repairs reporting 2PD data was 9 ± 4 mm. For the 38 repairs with SWF data, protective sensation was reported in 33 repairs, deep pressure in 2, and no recovery in 3. These data compared favorably with historical data for nerve autograft repairs, with reported levels of meaningful recovery of 60% to 88%. There were no reported adverse effects. Processed nerve allograft can be used to reconstruct long gap nerve defects in the hand with consistently high rates of meaningful recovery. Results for PNA repairs of digital nerve injuries with gaps longer than 25 mm compare favorably with historical reports for nerve autograft repair but without donor site morbidity.

Traumatic injuries to PNS and CNS axons are not uncommon. Restoration of lost behaviors following severance of mammalian peripheral nerve axons (PNAs) relies on regeneration by slow outgrowths and is typically poor or nonexistent when after ablation or injuries close to the soma. Behavioral recovery after severing spinal tract axons (STAs) is poor because STAs do not naturally regenerate. Current techniques to enhance PNA and/or STA regeneration have had limited success and do not prevent the onset of Wallerian degeneration of severed distal segments. This Review describes the use of a recently developed polyethylene glycol (PEG) fusion technology combining concepts from biochemical engineering, cell biology, and clinical microsurgery. Within minutes after microsuturing carefully trimmed cut ends and applying a well-specified sequence of solutions, PEG-fused axons exhibit morphological continuity (assessed by intra-axonal dye diffusion) and electrophysiological continuity (assessed by conduction of action potentials) across the lesion site. Wallerian degeneration of PEG-fused PNAs is greatly reduced as measured by counts of sensory and/or motor axons and maintenance of axonal diameters and neuromuscular synapses. After PEG-fusion repair, cut-severed, crush-severed, or ablated PNAs or crush-severed STAs rapidly (within days to weeks), more completely, and permanently restore PNA- or STA-mediated behaviors compared with nontreated or conventionally treated animals. PEG-fusion success is enhanced or decreased by applying antioxidants or oxidants, trimming cut ends or stretching axons, and exposure to Ca(2+) -free or Ca(2+) -containing solutions, respectively. PEG-fusion technology employs surgical techniques and chemicals already used by clinicians and has the potential to produce a paradigm shift in the treatment of traumatic injuries to PNAs and STAs., (© 2015 Wiley Periodicals, Inc.)

Restoration of neuronal functions by outgrowths regenerating at ∼1 mm/day from the proximal stumps of severed peripheral nerves takes many weeks or months, if it occurs at all, especially after ablation of nerve segments. Distal segments of severed axons typically degenerate in 1-3 days. This study shows that Wallerian degeneration can be prevented or retarded, and lost behavioral function can be restored, following ablation of 0.5-1-cm segments of rat sciatic nerves in host animals. This is achieved by using 0.8-1.1-cm microsutured donor allografts treated with bioengineered solutions varying in ionic and polyethylene glycol (PEG) concentrations (modified PEG-fusion procedure), being careful not to stretch any portion of donor or host sciatic nerves. The data show that PEG fusion permanently restores axonal continuity within minutes, as initially assessed by action potential conduction and intracellular diffusion of dye. Behavioral functions mediated by the sciatic nerve are largely restored within 2-4 weeks, as measured by the sciatic functional index. Increased restoration of sciatic behavioral functions after ablating 0.5-1-cm segments is associated with greater numbers of viable myelinated axons within and distal to PEG-fused allografts. Many such viable myelinated axons are almost certainly spared from Wallerian degeneration by PEG fusion. PEG fusion of donor allografts may produce a paradigm shift in the treatment of peripheral nerve injuries., (© 2014 Wiley Periodicals, Inc.)