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Background:. Training local surgeons and building local surgical capacity is critical to closing the gap in unmet surgical burden in low- and middle-income country (LMIC) settings. We propose a conceptual framework to quantify the impact of a single surgeon’s training across multiple generations of trainees. Methods:. A literature review was conducted to identify existing models for quantifying the impact of training. A model to estimate the attributable impact of surgical training was devised, based on a surgeon’s attributable impact on a trainee and the lifetime number of cases trainees would perform. A quantitative survey was sent to high-income country and LMIC-based surgeons to determine the model’s inputs across eight index procedures in reconstructive plastic surgery. Results:. We found no existing models for quantifying the multigenerational impact of training in surgery, medicine, or nonmedical fields. Twenty-eight US-based academic plastic surgeons and 19 LMIC-based surgeons representing 10 countries provided responses. The lifetime impact of multigenerational surgical training ranged from 4100 attributable cases (skin graft) to 51,900 attributable cases (cleft lip repair) in high-income countries and from 18,200 attributable cases (carpal tunnel release) to 134,300 attributable cases (cleft lip repair) in LMICs. Conclusions:. There is a sizeable impact in the first generation of training, and this impact is even greater in the second generation of training, highlighting the importance of a “multiplier effect,” particularly in LMIC settings. Given the paucity of surgeons, this multiplier effect is critical in closing the surgical gap, as efforts are underway to train new cohorts of reconstructive plastic surgeons.

Abstract Daptomycin is a cyclic lipodepsipeptide antibiotic reserved for the treatment of serious infections by multidrug-resistant Gram-positive pathogens. Its mode of action is considered to be multifaceted, encompassing the targeting and depolarization of bacterial cell membranes, alongside the inhibition of cell wall biosynthesis. To characterize the daptomycin mode of action, 15N cross-polarization at magic-angle spinning NMR measurements were performed on intact whole cells of Staphylococcus aureus grown in the presence of a sub-inhibitory concentration of daptomycin in a chemically defined media containing l-[ϵ-15N]Lys. Daptomycin-treated cells showed a reduction in the lysyl-ε-amide intensity that was consistent with cell wall thinning. However, the reduced lysyl-ε-amine intensity at 10 ppm indicated that the daptomycin-treated cells did not accumulate in Park’s nucleotide, the cytoplasmic peptidoglycan (PG) precursor. Consequently, daptomycin did not inhibit the transglycosylation step of PG biosynthesis. To further elucidate the daptomycin mode of action, the PG composition of daptomycin-susceptible Enterococcus faecalis grown in the presence of daptomycin was analyzed using liquid chromatography-mass spectrometry. Sixty-nine muropeptide ions correspond to PG with varying degrees of modifications including crosslinking, acetylation, alanylation, and 1,6-anhydrous ring formation at MurNAc were quantified. Analysis showed that the cell walls of daptomycin-treated E. faecalis had a significant reduction in PG crosslinking which was accompanied by an increase in lytic transglycosylase activities and a decrease in PG-stem modifications by the carboxypeptidases. The changes in PG composition suggest that daptomycin inhibits cell wall biosynthesis by impeding the incorporation of nascent PG into the cell walls by transpeptidases and maturation by carboxypeptidases. As a result, the newly formed cell walls become highly susceptible to degradation by the autolysins, resulting in thinning of the cell wall.

Outcomes after repair of chronic rotator cuff injuries remain suboptimal. Type-1 collagen-rich tendon hydrogel was previously reported to improve healing in a rat chronic rotator cuff injury model. Stem cell seeding of the tendon hydrogel improved bone quality in the same model. This study aimed to examine whether there was a synergistic and dose-dependent effect of platelet-rich plasma (PRP) on tendon–bone interface healing by combining PRP with stem cell–seeded tendon hydrogel. Human cadaveric tendons were processed into a hydrogel. PRP was prepared at two different platelet concentrations: an initial concentration (initial PRP group) and a higher concentration (concentrated PRP group). Tendon hydrogel was mixed with adipose-derived stem cells and one of the platelet concentrations. Methylcellulose, as opposed to saline, was used as a negative control due to comparable viscosity. The supraspinatus tendon was detached bilaterally in 33 Sprague-Dawley rats (66 shoulders). Eight weeks later, each detached tendon was repaired, and a hydrogel mixture or control was injected at the repair site. Eight weeks after repair, shoulder samples were harvested and assigned for biomechanical testing (n = 42 shoulders) or a combination of bone morphological and histological assessment (n = 24 shoulders). Biomechanical testing showed significantly higher failure load and stiffness in the concentrated PRP group than in control. Yield load in the initial and concentrated PRP groups were significantly higher than that in the control. There were no statistically significant differences between the initial and concentrated PRP groups. The addition of the highly concentrated PRP to stem cells–seeded tendon hydrogel improved healing biomechanically after chronic rotator cuff injury in rats compared to control. However, synergistic and dose-dependent effects were not seen.

Ankle arthroscopy and the Brostrom procedure are common interventions for ankle instability, but they do carry a risk of vascular injury resulting in a pseudoaneurysm. We present a rare case of anterior tibial artery pseudoaneurysm after ankle arthroscopy and Brostrom procedure treated with direct thrombin injection. A 40-year-old male patient presented with progressive left anterior ankle pain and swelling 5 months after a left ankle arthroscopy and Brostrom procedure. MRI and ultrasound imaging was consistent with anterior tibial artery pseudoaneurysm. He was referred to interventional radiology for treatment. His pseudoaneurysm was successfully treated with an ultrasound guided direct thrombin injection. Several potential treatments are available for treatment of pseudoaneurysms. This includes surgical intervention, endovascular treatment, external compression, and direct thrombin injection. All of these treatment options have been explored in literature. Of these possible treatments, direct thrombin injection has the best combination of efficacy, complication rate, and recurrence rate, which makes it the preferred treatment for a pseudoaneurysm.

Objective:. The objective of this study was to quantify the cost-effectiveness and economic value of a reconstructive surgery visiting educator trip program in a resource-constrained setting. Background:. Reconstructive surgical capacity remains inadequate in low- and middle-income countries, resulting in chronic disability and a significant economic toll. Education and training of the local surgical workforce to sustainably expand capacity have been increasingly encouraged, but economic analyses of these interventions are lacking. Methods:. Data were analyzed from 12 visiting educator trips and independently-performed surgical procedures at 3 Vietnamese hospitals between 2014 and 2019. A cost-effectiveness analysis was performed using standardized methodology and thresholds to determine cost-effectiveness. Sensitivity analyses were performed with disability weights, discounting, and costs from different perspectives. Economic benefit was estimated using both the human capital method and the value of a statistical life method, and a benefit-cost ratio was computed. Results:. In the base case analysis, the visiting educator program was very cost-effective at $581 per disability-adjusted life year (DALY) averted. Economic benefit was between $21·6 million and $29·3 million, corresponding to a 12- to 16-fold return on investment. Furthermore, when considering only costs to the organization, the cost decreased to $61 per DALY averted, with a 113- to 153-fold return on investment for the organization. Conclusions:. Visiting educator programs, which build local reconstructive surgical capacity in limited-resource environments, can be very cost-effective with significant economic benefit and return on investment. These findings may help guide organizations, donors, and policymakers in resource allocation in global surgery.

Radiation-induced sarcomas are a known, rare, complication from prior therapeutic radiation therapy. Radiation-induced sarcomas have been reported to have poor associated prognoses with increased morbidity and mortality when compared to primary sarcomas. In this case report, we discuss a 27-year-old female who presented at the age of 17 during pregnancy with an inability to bear weight and was subsequently diagnosed with Ewing's sarcoma of her femur. Adequate response to treatment was obtained with the initial treatment and the patient represented with acute, severe pain of her femur at the site of prior Ewing's. Extensive workup demonstrated radiation-induced osteosarcoma at the site of her prior Ewing's sarcoma in the radiation field. Multidisciplinary teams including orthopedics, pathology, medical oncology, and radiology are vital for appropriate and efficacious diagnosis of radiation-induced sarcomas. Despite the rarity of radiation-induced sarcoma, the ability to recognize and diagnose recurrent sarcoma is important for radiologists, particularly considering the associated poor prognosis. Early diagnosis and aggressive multidisciplinary treatment is crucial to improving patient morbidity and mortality. In this case, the diagnosis of radiation-induced osteosarcoma allowed expedited workup and initial aggressive, lifesaving treatment for our patient. Keywords: Radiation, Induced, Sarcoma, Ewing's, Osteosarcoma, Radiology

Summary: Early detection of limb ischemia, strokes, and heart attacks may be enabled via long-term monitoring of arterial health. Early stenosis, decreased blood flow, and clots are common after surgical vascular bypass or plaque removal from a diseased vessel and can lead to the above diseases. Continuous arterial monitoring for the early diagnosis of such complications is possible by implanting a sensor during surgery that is wirelessly monitored by patients after surgery. Here, we report the design of a wireless capacitive sensor wrapped around the artery during surgery for continuous post-operative monitoring of arterial health. The sensor responds to diverse artery sizes and extents of occlusion in vitro to at least 20 cm upstream and downstream of the sensor. It demonstrated strong capability to monitor progression of arterial occlusion in human cadaver and small animal models. This technology is promising for wireless monitoring of arterial health for pre-symptomatic disease detection and prevention.

Background:. The purpose of this study was to determine the feasibility of using mouse models for translational study of flexor tendon repair and reconstruction. Methods:. Quantitative data detailing the gross anatomy, biomechanical characteristics, and microscopic structure of the deep digit flexor tendon (DDF) of the mouse hindpaw were obtained. Histological characterization of the DDF and the anatomy of the digit in the mouse hindpaw are detailed. Biomechanical testing determined the load-to-failure, stress, elastic modulus, and the site of tendon failure. Results:. In gross anatomy, the origins and insertions of the mouse deep digit flexor tendon are similar to those of the human digit, surrounded by a synovial sheath that is only 1- to 2-cells thick. A neurovascular network runs on each side of the digit outside the synovial sheath, but does not clearly penetrate it. The thickness of the DDF is 0.14 ± 0.03 mm and the width is 0.3 ± 0.03 mm. The thickness of the DDF is less than that of 9-0 nylon needle. The mean failure force of the deep flexor tendon was 2.79 ± 0.53N. Conclusions:. The gross anatomy of the mouse hindpaw digit is similar to that of the human digit except for key differences seen in the synovial sheath and vascular supply. The dimensions of the mouse DDF make it challenging to create a clinically translatable repair model using currently available surgical techniques. Despite the similarities between the human and mouse anatomy, and the powerful basic science tools available in murine models, mice are an unreliable model for assessing flexor tendon injury and repair.

Background:. Our laboratory has previously developed a novel collagen-rich hydrogel (cHG), which significantly increases the speed of wound healing in diabetic rats. Methods:. In this study, we examine the in vitro survival and migration of fibroblasts, endothelial cells, and adipose-derived stem cells in a novel cHG. Furthermore, we test the ability of adipose-derived stem cell–seeded cHG to support cell survival and accelerate healing in vivo. Results:. In vitro, cell survival within the cHG was retained for 25 days. We were unable to detect cellular migration into, out of, or through cHG. In the in vivo model, bioluminescence of stem cells seeded within the cHG in diabetic rat wounds was detected until day 10. Rate of wound closure was higher for cHG plus adipose-derived stem cells versus control from day 2 until day 16 and significant on days 6, 8, and 12 (P < 0.05). This significant difference was also observed on day 16 by histology (P ≤ 0.05). Conclusions:. We conclude that cHG is a good candidate for delivering adipose-derived stem cells, endothelial cells, and fibroblasts to wounds. Future studies will determine whether the delivery of combinations of different cell lines in cHG further enhances wound healing.

Abstract Mycobacteria possess a multi-layered cell wall that requires extensive remodelling during cell division. We investigated the role of an amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase, a peptidoglycan remodelling enzyme implicated in cell division. We demonstrated that deletion of MSMEG_6281 (Ami1) in Mycobacterium smegmatis resulted in the formation of cellular chains, illustrative of cells that were unable to complete division. Suprisingly, viability in the Δami1 mutant was maintained through atypical lateral branching, the products of which proceeded to form viable daughter cells. We showed that these lateral buds resulted from mislocalization of DivIVA, a major determinant in facilitating polar elongation in mycobacterial cells. Failure of Δami1 mutant cells to separate also led to dysregulation of FtsZ ring bundling. Loss of Ami1 resulted in defects in septal peptidoglycan turnover with release of excess cell wall material from the septum or newly born cell poles. We noted signficant accumulation of 3-3 crosslinked muropeptides in the Δami1 mutant. We further demonstrated that deletion of ami1 leads to increased cell wall permeability and enhanced susceptiblity to cell wall targeting antibiotics. Collectively, these data provide novel insight on cell division in actinobacteria and highlights a new class of potential drug targets for mycobacterial diseases.

Summary:. Hand surgeons refer to deep lacerations of the volar distal forearm as “spaghetti wrists.” Given that multiple tendons, vessels, and nerves often require repair, this injury may be intimidating. We review management of spaghetti wrists and summarize with 10 simplifying tips.

Background:. In Nepal, burn trauma causes more than 55,000 injuries each year. Burn-related mortality is high in Nepal, in part due to lack of allograft, leading to high infection rates. To address this challenge, our collaboration between Kirtipur Hospital, America Nepal Medical Foundation, Stanford University, and ReSurge International established Nepal’s first skin bank. Methods:. We identified 3 major tasks to create a sustainable skin banking program: 1) identify and acquire the equipment and personnel needed to collect, process, store, and graft cadaveric skin for burn injuries; 2) develop safe donation protocols and documentation tools that remain feasible for low-resource settings; and 3) develop a long-term awareness program to educate the Nepali people on skin donation, a previously foreign concept. Results:. Kirtipur Hospital acquired the necessary equipment and materials for the skin bank through a combination of local and international fundraising efforts. Existing U.S. skin banking protocols were adapted for the Nepali setting and piloted on potential patients, donors, and physicians. For the first time in the hospital’s history, patients with > 40% total body surface area burns were successfully treated with extensive allografts. Conclusions:. It is feasible to create a skin bank in a country with no tradition of allograft skin use. Long-term sustainability now depends on spreading awareness and education in the Kathmandu Valley to overcome religious and cultural barriers that have hindered donor recruitment. Our low-cost and high-impact skin bank provides a model to expand this system to other hospitals both within Nepal and beyond.

Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design.

To obtain an insight to high humidity-caused friction modulation in brake pad-rotor interface, the adhesion phenomenon due to a liquid bridge is simulated using an advanced particle method by varying the shearing speed of the interface. The method, called generalized interpolation material point for fluid-solid interactions (GIMP-FSI), was recently developed from the material point method (MPM) for fluid-solid interactions at small scales where surface tension dominates, thus suitable for studying the partially wet brake friction due to high humidity at a scale of 10 m. Dynamic capillary effects due to surface tension and contact angles are simulated. Adhesion forces calculated by GIMP-FSI are consistent with those from the existing approximate meniscus models. Moreover, the numerical results show that capillary effects induce modulations of adhesion as slip speed changes. In particular, the adhesion modulation could be above 30% at low speed. This finding provides insights into how the high humidity-caused friction could cause modulations of brake, which are unable to be achieved by conventional models. Therefore, the numerical analysis helps to elucidate the complex friction mechanisms associated with brakes that are exposed to high humidity environments.

Retinal long-chain PUFAs (LC-PUFAs, C12-C22) play important roles in normal human retinal function and visual development, and some epidemiological studies of LC-PUFA intake suggest a protective role against the incidence of advanced age-related macular degeneration (AMD). On the other hand, retinal very long-chain PUFAs (VLC-PUFAs, Cn>22) have received much less attention since their identification decades ago, due to their minor abundance and more difficult assays, but recent discoveries that defects in VLC-PUFA synthetic enzymes are associated with rare forms of inherited macular degenerations have refocused attention on their potential roles in retinal health and disease. We thus developed improved GC-MS methods to detect LC-PUFAs and VLC-PUFAs, and we then applied them to the study of their changes in ocular aging and AMD. With ocular aging, some VLC-PUFAs in retina and retinal pigment epithelium (RPE)/choroid peaked in middle age. Compared with age-matched normal donors, docosahexaenoic acid, adrenic acid, and some VLC-PUFAs in AMD retina and RPE/choroid were significantly decreased, whereas the ratio of n-6/n-3 PUFAs was significantly increased. All these findings suggest that deficiency of LC-PUFAs and VLC-PUFAs, and/or an imbalance of n-6/n-3 PUFAs, may be involved in AMD pathology.

This study introduces a novel modular soft actuator designed for an anthropomorphic robotic finger that addresses the need for adaptive behavior and precise joint-angle control. The key innovation is its modular design, which enables independent pressure regulation in each air chamber, thus achieving superior precision compared to traditional PneuNets soft actuators. A rigid skeleton is integrated to enhance force transmission and measurement capabilities and thus ensure effective force handling and transmission within each module. The versatility of the actuator is demonstrated through its adaptability in various scenarios, and its features include adaptive positional control achieved by modulating the inflation in each air chamber. This research includes kinematic and kinetostatic analyses to ensure precise control of joint angles and forces at the finger’s endpoint. Experimental results confirm the actuator’s excellent performance and adaptability, providing valuable insights for advancing soft-actuator technology. The findings suggest significant potential for this actuator in diverse applications, emphasizing its role in the future development of precise and adaptable robotic systems.