Vascularized Composite Allograft Versus Prosthetic for Reconstruction After Facial and Hand Trauma: Comparing Cost, Complications, and Long-term Outcome.

ABSTRACT: In the past decade, vascularized composite allotransplantation (VCA) has become clinical reality for reconstruction after face and hand trauma. It offers patients the unique opportunity to regain form and function in a way that had only been achieved with traditional reconstruction or with the use of prostheses. On the other hand, prostheses for facial and hand reconstruction have continued to evolve over the years and, in many cases, represent the primary option for patients after hand and face trauma. We compared the cost, associated complications, and long-term outcomes of VCA with prostheses for reconstruction of the face and hand/upper extremity. Ultimately, VCA and prostheses represent 2 different reconstructive options with distinct benefit profiles and associated limitations and should ideally not be perceived as competing choices. Our work adds a valuable component to the general framework guiding the decision to offer VCA or prostheses for reconstruction after face and upper extremity trauma.

Incidence of Frontal Sinus Fractures: A Single-Institution 12-year Experience.

Frontal sinus fractures' reported incidence has varied widely in the United States. Although the past couple of decades have demonstrated an overall decrease among patients with facial fractures, the overall incidence of frontal sinus fractures remains unclear. We report our experience at a level 1 trauma center in the northeast region of the United States and analyze patients who have presented to our Emergency Department with facial fractures in a 12-year period, from 2011 to 2022. Our data show that 1.5% of all facial fracture patients had a frontal sinus fracture. Of those patients, 50% were victims of assault, 25% were involved in a motor vehicle accident, 12.5% were involved in a bicycle accident, and 12.5% were involved in a pedestrian struck by a vehicle. Overall, our data corroborate the decreasing national trend in frontal sinus fracture incidence and set the stage for further studies looking at the contributing factors for the observed decline.

Novel Strategies in Transplantation: Genetic Engineering and Vascularized Composite Allotransplantation.

INTRODUCTION: Despite the clinical success in vascularized composite allotransplantation (VCA), systemic immunosuppression remains necessary to prevent allograft rejection. Even with potent immunosuppressive regimens (tacrolimus, mycophenolate mofetil, and steroids), most patients experience several rejection episodes, often within the same year. The risk of systemic side effects must constantly be weighed against the risk of under-immunosuppression and, thus, acute and chronic rejection. In this context, genomic editing has emerged as a potential tool to minimize the need for toxic immunosuppressive regimens and has gained attention in the fields of solid organ transplantation and xenotransplantation. This strategy may also be relevant for the future of VCA. METHODS: We discuss the topic of genetic engineering and review recent developments in this field that justify investigating tools such as clustered regularly interspaced short palindromic repeats/Cas9 in the context of VCA. RESULTS: We propose specific strategies for VCA based on the most recent gene expression data. This includes the well-known strategy of tolerance induction. Specifically, targeting the interaction between antigen-presenting cells and recipient-derived T cells by CD40 knockout may be effective. The novelty for VCA is a discovery that donor-derived T lymphocytes may play a special role in allograft rejection of facial transplants. We suggest targeting these cells prior to transplantation (e.g., by ex vivo perfusion of the transplant) by knocking out genes necessary for the long-term persistence of donor-derived immune cells in the allograft. CONCLUSION: Despite the demonstrated feasibility of VCA in recent years, continued improvements to immunomodulatory strategies using tools like clustered regularly interspaced short palindromic repeats/Cas9 could lead to the development of approaches that mitigate the limitations associated with rejection of this life-giving procedure.

RNA SHAPE chemistry with aromatic acylating reagents.

As chemical methods for RNA secondary structure determination, SHAPE chemistry (selective 2'-hydroxyl acylation analyzed by primer extension) has been developed to specifically target flexible nucleotides (often unpaired nucleotides) independently to their purine or pyrimidine nature. In order to improve the specificity of acylating reagents towards unpaired nucleotides, we have explored the reactivity of symmetric anhydrides, acyl fluorides, active esters like succinimidyl ester and cyanomethyl esters for 2'-O-acylation reaction. Among the tested compounds, only the acyl fluoride 4 showed a low reactivity (compared to NMIA). However, this study is the first to show that nucleophilic catalysts like DMAP greatly improved the selective 2'-hydroxyl acylation by symmetric anhydrides, acyl fluorides and succinimidyl ester, with the 2-fluorobenzoic anhydride 5 being the most reactive.

Skipped sentinel lymph node basin in a patient with forearm cutaneous melanoma: A case report.

Sentinel lymph node biopsy is an important tool in the management of malignant melanoma, particularly in predicting micrometastasis to regional lymph nodes. Cases of secondary drainage to lymph nodes outside of conventional nodal basins and overall unusual lymph node localization have been reported. The present study reports a unique case of a 'skipped sentinel lymph node basin' pattern in a patient with a right forearm malignant melanoma. Lymphatic mapping using cutaneous lymphoscintigraphy revealed localization at the right supraclavicular lymph node, bypassing right axilla localization despite no prior axillary dissection or previous surgery or radiation. This unique pattern outlined in the present report adds to our understanding of disease localization and unique presentations.

From permeation to pore nucleation in smectic stacks.

The last stage of the spreading of a stratified droplet in the odd wetting case is the evolution from a trilayer to a monolayer, that is, vanishing of the last bilayer in the stack. We studied it in the case of 8CB smectic liquid crystal on a hydrophilic surface. Receding of the last bilayer is accompanied by formation of pores in it, which appear in the outer part of it. From analysis of real-time experimental observations of this phenomenon, we demonstrate that the dislocation loops which border these pores are not located at the same height in the trilayer stack as the dislocation lines that border the bilayer. Also, careful analysis of our results using a recently developed theoretical approach of smectic liquid nanodrop spreading strongly suggests that pore nucleation is triggered by differences in chemical potential between adjacent layers, which contrasts with the classical scheme where it is attributed to lateral tension along the layers.

Regulatory T Cells: Liquid and Living Precision Medicine for the Future of VCA.

Transplant rejection remains a challenge especially in the field of vascularized composite allotransplantation (VCA). To blunt the alloreactive immune response' stable levels of maintenance immunosupression are required. However' the need for lifelong immunosuppression poses the risk of severe side effects, such as increased risk of infection, metabolic complications, and malignancies. To balance therapeutic efficacy and medication side effects, immunotolerance promoting immune cells (especially regulatory T cells [Treg]) have become of great scientific interest. This approach leverages immune system mechanisms that usually ensure immunotolerance toward self-antigens and prevent autoimmunopathies. Treg can be bioengineered to express a chimeric antigen receptor or a T-cell receptor. Such bioengineered Treg can target specific antigens and thereby reduce unwanted off-target effects. Treg have demonstrated beneficial clinical effects in solid organ transplantation and promising in vivo data in VCAs. In this review, we summarize the functional, phenotypic, and immunometabolic characteristics of Treg and outline recent advancements and current developments regarding Treg in the field of VCA and solid organ transplantation.

Sliding velocity dependence of adhesion in a nanometer-sized contact.

The influence of sliding velocity on the adhesion force in a nanometer-sized contact was investigated with a novel atomic force microscope experimental setup that allows measuring adhesion forces while the probe is sliding at continuous and constant velocities. For hydrophobic surfaces, the adhesion forces (mainly van der Waals forces) remain constant, whereas for hydrophilic surfaces, adhesion forces (mainly capillary forces) decrease linearly with a logarithmic increase of the sliding velocity. The experimental data are well explained by a model based on a thermally activated growth process of a capillary meniscus.

Mechanism of lipid nanodrop spreading in a case of asymmetric wetting.

Using the surface enhanced ellipsometric contrast microscopy, we follow the last stage of the spreading of egg phosphatidylcholine nanodroplets on a hydrophilic substrate in a humid atmosphere, focusing on the vanishing trilayer in terraced droplets reduced to coexisting monolayer and trilayer. We find that the line interface between them exhibits two coexisting states, one mobile and one fixed. From there, it is possible to elucidate the internal structure and the spreading mechanism of the stratified liquid in a case of asymmetric wetting, i.e., where the lipid film is made of an odd number of leaflets.

Nature of Dynamic Friction in a Humid Hydrophobic Nanocontact.

The physics of dynamic friction on water molecule contaminated surfaces is still poorly understood. In line with the growing interest in hydrophobic contact for industrial applications, this paper focuses on friction mechanisms in such interfaces. As a commonly used material, contact with graphite is considered in a twin-fold approach based on experimental investigations using the circular mode atomic force microscopy technique combined with molecular dynamic simulations. We demonstrate that an intuitive paradigm, which asserts that water molecules are squeezed out of a hydrophobic contact, should be refined. As a consequence, we introduce a mechanism considering a droplet produced within the sliding nanocontact by the accumulation of water adsorbed on the substrate. Then we show that a full slip regime of the droplet sliding on the hydrophobic substrate explains the experimental tribological behavior.

Roux-en-Y Gastric Bypass Surgery Has Early Differential Effects on Bile Acids and the Levels of Complement Component 3 and Acylation-Stimulating Protein.

BACKGROUND: Bile acids have been implicated in the mechanism by which Roux-en-Y gastric bypass (RYGB) can induce remission of type 2 diabetes (T2D). Our goal was to identify circulating proteins whose levels changed after RYGB when dysglycemic parameters normalized. MATERIALS AND METHODS: This was a retrospective study of 26 participants who underwent RYGB. Blood proteins were identified using two-dimensional electrophoresis and mass spectroscopy. Complement proteins were measured using immunoassays and bile acids measured using ultra-high-performance liquid chromatography and mass spectroscopy. RESULTS: A total of 7/452 blood proteins were found to change 2 days after RYGB. Complement component 3 (C3) was selected because of its regulation by bile acids and the glucoregulatory function of its proteolytically processed product C3adesArg or acylation-stimulating protein (ASP). The median (inter-quartile range/IQR) C3 level was 47.4 (34.5, 65.9) mg/dL before surgery decreasing to 40.9 (13.4, 64.1) mg/dL within 2 days after surgery (p = 0.0292). The median (IQR) ASP level increased from 2.8 (0.9, 7.3) nM before surgery to 8.0 (5.3, 14.1) nM within 2 days after surgery (p = 0.0016). ASP levels increased in 14/17 (82%) with T2D remission and in 6/6 with normoglycemia but decreased in 3/3 with persistent T2D. Of ten bile acids measured, the levels of ursodeoxycholic acid (UDCA) were significantly decreased after RYGB and the levels of taurodeoxycholic acid (TDCA) were significantly decreased with T2D remission. CONCLUSIONS: These data further support an association of C3 with glucose metabolism and implicate bile acids and ASP in the early remittive effects of RYGB on T2D.

Quantitative spreading kinetics of a three molecular layer liquid patch.

The late stage kinetics of the spreading of a smectic nanodrop on a solid surface was investigated by direct and real time imaging of a three molecular layer patch using the SEEC microscopy. Experimental data do not conform to the only available theory, which covers only weakly stratified liquids. A new model is proposed, in remarkable agreement with experiments, in which the spreading mechanism appears to be a quasi-static process ruled by solid/liquid interactions, 2D Laplace pressure, and separate edge and surface permeation coefficients.

Restoring the Severed Breast and Chest following Seat Belt Trauma.

In this article, we presented 2 cases of rare clinical presentation of 3-point lap-diagonal seat belt injuries and provided a brief overview of the spectrum of the associated deformity and morbidity. Both of our patients presented in a delayed fashion during the subacute period at 12 and 4 months, respectively, following their traumatic seat belt injuries, which improved with surgical intervention. Ideally, these injuries should be repaired during the subacute period once any life-threatening injuries have been addressed, because seat belt-restraint injuries may otherwise lead to chronic pain, functional loss, and physical deformity.

Ethnic and Gender Diversity Comparison between Surgical Patients and Caring Surgeons.

BACKGROUND: Diversity within the medical workforce remains a topic of discussion in academia, particularly when it comes to the underrepresentation of certain ethnic groups and gender in the surgical specialties. In this article, we look at how the gender and ethnicity of surgeons at a large academic institution in a rural setting compare with those of the population it serves. METHODS: We looked at demographic data from 2008 to 2018 and compared population trends among surgeons and patients. RESULTS: We found that while whites represent the large majority in both the surgeon and patient populations, absolute number and percentage of whites in the patient population seem to be trending downward from 2008 to 2018, but trending upward among surgeons (attendings and residents). In addition, we found that while Asians make up only 1% of the patient population, they represent the second largest group (17%) among surgeons, with more than twice the proportion percentage of the second largest group within the patient population, composed of Hispanics (6%). Finally, we found a significant gender difference between the 2 populations with almost two-thirds of the surgeons being men, compared with the nearly even split of men and women within the patient population. CONCLUSIONS: Ultimately, understanding how gender and ethnic diversity in the surgical workforce compares with that of the patient population being served may aid in designing training programs to address cultural competency and awareness as well as in impacting administrative decisions and hiring.

Bile acids upregulate BRCA1 and downregulate estrogen receptor 1 gene expression in ovarian cancer cells.

Two major risk factors for ovarian cancer include loss-of-function mutations in the BRCA1 (breast cancer 1, early onset) gene and aspects of estrogen metabolism. Modulation of the levels of the normal BRCA1 allele and estrogen receptor expression may therefore be a preventive strategy. Consensus binding motifs for the bile acid-responsive transcription factor farnesoid X receptor were identified in the BRCA1 and estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) genes, supported by chromatin immunoprecipitation sequencing data. Two major bile acids, deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA), resulted in a greater than four-fold induction of BRCA1 transcript levels at 10 µmol/l and a greater than six-fold induction at 50 µmol/l relative to untreated control OVCAR3 ovarian cancer cells. Conversely, CDCA and DCA at 10 µmol/l resulted in about a 75% decrease in ESR1 expression in response to 10 µmol/l CDCA and DCA and close to 90% reduction with 50 µmol/l CDCA and DCA. Bile acids had no effects on ESR2 gene transcript levels. The inverse regulation of BRCA1 and ESR1 gene expression in response to physiological levels of bile acids could have important implications for disease penetrance and chemoprevention strategies in carriers of BRCA1 mutations.

Exploring wear at the nanoscale with circular mode atomic force microscopy.

The development of atomic force microscopy (AFM) has allowed wear mechanisms to be investigated at the nanometer scale by means of a single asperity contact generated by an AFM tip and an interacting surface. However, the low wear rate at the nanoscale and the thermal drift require fastidious quantitative measurements of the wear volume for determining wear laws. In this paper, we describe a new, effective, experimental methodology based on circular mode AFM, which generates high frequency, circular displacements of the contact. Under such conditions, the wear rate is significant and the drift of the piezoelectric actuator is limited. As a result, well-defined wear tracks are generated and an accurate computation of the wear volume is possible. Finally, we describe the advantages of this method and we report a relevant application example addressing a Cu/Al2O3 nanocomposite material used in industrial applications.

Genetics of Bariatric Surgery Outcomes.

Outcomes after bariatric surgery can vary widely and seem to have a significant genetic component. Only a small number of candidate gene and genome-wide association studies have analyzed bariatric surgery outcomes. The role of bile acids in mediating the beneficial effects of bariatric surgery implicate genes regulated by the farnesoid X receptor transcription factor.

Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery.

Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D) mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs) as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR) transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

Circular mode: a new scanning probe microscopy method for investigating surface properties at constant and continuous scanning velocities.

In this paper, we introduce a novel scanning probe microscopy mode, called the circular mode, which offers expanded capabilities for surface investigations especially for measuring physical properties that require high scanning velocities and/or continuous displacement with no rest periods. To achieve these specific conditions, we have implemented a circular horizontal displacement of the probe relative to the sample plane. Thus the relative probe displacement follows a circular path rather than the conventional back and forth linear one. The circular mode offers advantages such as high and constant scanning velocities, the possibility to be combined with other classical operating modes, and a simpler calibration method of the actuators generating the relative displacement. As application examples of this mode, we report its ability to (1) investigate the influence of scanning velocity on adhesion forces, (2) measure easily and instantly the friction coefficient, and (3) generate wear tracks very rapidly for tribological investigations.

In situ determination of the thermodynamic surface properties of chemically modified surfaces on a local scale: an attempt with the atomic force microscope.

We have monitored deflection-distance curves with an atomic force microscope (AFM) in contact mode, with a silicon nitride tip, on chemically modified silicon wafers, in the air. The wafers were modified on their surface by grafting self-assembled monolayers (SAMs) of different functional groups such as methyl, ester, amine, or methyl fluoride. A chemically modified surface with a functionalized hydroxyl group was also considered. Qualitative analysis allowed us to compare adhesive forces versus chemical features and surface energy. The systematic calibration procedure of the AFM measurements was performed to produce quantitative data. Our results show that the experimentally determined adhesive force or thermodynamic work of adhesion increases linearly with the total surface energy determined with contact angles measured with different liquids. The influence of capillary condensation of atmospheric water vapor at the tip-sample interface on the measured forces is discussed. Quantitative assessment values were used to determine in situ the SAM-tip thermodynamic work of adhesion on a local scale, which have been found to be in good agreement with quoted values. Finally, the determination of the surface energy of the silicon wafer deduced from the thermodynamic work of adhesion is also proposed and compared with the theoretical value.