A Comparison of 2 Cage Sizes in Biportal Endoscopic Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: This study compared the fusion and subsidence rate and clinical outcomes when using different-sized static PEEK cages in BE-TLIF. SUMMARY OF BACKGROUND DATA: Biportal endoscopic techniques for transforaminal lumbar interbody fusion (BE-TLIF) have been shown to have similar clinical and fusion outcomes with faster clinical recovery in comparison to tubular surgery. Subsidence of the interbody, however, could be a complication. METHODS: Patients who underwent 1 or 2 level BE-TLIF for degenerative and isthmic spondylolisthesis between January 2019 and January 2022 were included. A 32×10 mm cage (group A) and a 40×15 mm cage (group B) were compared. The visual analog scale (VAS) for back and leg symptoms, and Oswestry disability index (ODI) were collected. Plain radiographs and computed tomography assessed fusion and subsidence at a minimum of 12 months. RESULTS: Of the 69 enrolled patients, 39 group A patients (51 levels) and 30 group B patients (32 levels) were compared. The operation time per level was 123 ± 15.8 and 138 ± 10.5 minutes per fusion level in groups A and B, respectively (P < 0.05). ODI improved from 64.8 ± 6.2 to 15.7 ± 7.1 in group A and from 65.3 ± 5.6 to 15.1 ± 6.3 in group B at the final follow-up (P < 0.05). VAS leg and back score improvement between the groups did not differ; however, the 3-month postoperative VAS back improvement was significantly higher in group B. The final fusion rate at the final follow-up did not significantly differ; however, the fusion ratio at 1 year was higher in group B (P < 0.05). Subsidence occurred in 5 cases (9.8%) in group A and none in group B (P < 0.05). CONCLUSION: BE-TLIF using a larger cage can be performed safely with similar patient-reported outcome measures with a faster fusion rate with less subsidence risk. LEVEL OF STUDY: III.

Highly Sensitive and Wide-Range Detection of Thiabendazole via Surface-Enhanced Raman Scattering Using Bimetallic Nanoparticle-Functionalized Nanopillars.

Thiabendazole (TBZ) is a benzimidazole; owing to its potent antimicrobial properties, TBZ is extensively employed in agriculture as a fungicide and pesticide. However, TBZ poses environmental risks, and excessive exposure to TBZ through various leakage pathways can cause adverse effects in humans. Therefore, a method must be developed for early and sensitive detection of TBZ over a range of concentrations, considering both human and environmental perspectives. In this study, we used silver nanopillar structures (SNPis) and Au@Ag bimetallic nanoparticles (BNPs) to fabricate a BNP@SNPi substrate. This substrate exhibited a broad reaction surface with significantly enhanced surface-enhanced Raman scattering hotspots, demonstrating excellent Raman performance, along with high reproducibility, sensitivity, and selectivity for TBZ detection. Ultimately, the BNP@SNPi substrate successfully detected TBZ across a wide concentration range in samples of tap water, drinking water, juice, and human serum, with respective limits of detection of 146.5, 245.5, 195.6, and 219.4 pM. This study highlights BNP@SNPi as a promising sensor platform for TBZ detection in diverse environments and contributes to environmental monitoring and bioanalytical studies.

Brain-Derived Neurotrophic Factor (BDNF) Enhances Osteogenesis and May Improve Bone Microarchitecture in an Ovariectomized Rat Model.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has gained attention as a therapeutic agent due to its potential biological activities, including osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of BDNF have not been fully understood. This study aimed to investigate the action of BDNF on the osteoblast differentiation in bone marrow stromal cells, and its influence on signaling pathways. In addition, to evaluate the clinical efficacy, an in vivo animal study was performed. METHODS: Preosteoblast cells (MC3T3-E1), bone marrow-derived stromal cells (ST2), and a direct 2D co-culture system were treated with BDNF. The effect of BDNF on cell proliferation was determined using the CCK-8 assay. Osteoblast differentiation was assessed based on alkaline phosphatase (ALP) activity and staining and the protein expression of multiple osteoblast markers. Calcium accumulation was examined by Alizarin red S staining. For the animal study, we used ovariectomized Sprague-Dawley rats and divided them into BDNF and normal saline injection groups. MicroCT, hematoxylin and eosin (H&E), and tartrate-resistant acid phosphatase (TRAP) stain were performed for analysis. RESULTS: BDNF significantly increased ALP activity, calcium deposition, and the expression of osteoblast differentiation-related proteins, such as ALP, osteopontin, etc., in both ST-2 and the MC3T3-E1 and ST-2 co-culture systems. Moreover, the effect of BDNF on osteogenic differentiation was diminished by blocking tropomyosin receptor kinase B, as well as inhibiting c-Jun N-terminal kinase and p38 MAPK signals. Although the animal study results including bone density and histology showed increased osteoblastic and decreased osteoclastic activity, only a portion of parameters reached statistical significance. CONCLUSIONS: Our study results showed that BDNF affects osteoblast differentiation through TrkB receptor, and JNK and p38 MAPK signal pathways. Although not statistically significant, the trend of such effects was observed in the animal experiment.

Improving Skin Paddle Reliability and Muscle Gliding in Free Functional Gracilis Transfers.

Free functional muscle transfer is an attractive option within reconstructive surgery when seeking to restore critical muscle function. The gracilis muscle has long been utilized for this purpose due to its expendability and consistent anatomy. Historically, survival of the skin overlying the distal one-third of the myocutaneous gracilis flap has been unpredictable. To address this, the myofasciocutaneous technique was developed, with prior studies demonstrating improved distal skin paddle viability with this approach; however, the mechanism is poorly defined. This study aimed to understand what factors contribute to survival benefit in myofasciocutaneous gracilis flaps. Using cadaveric dissections followed by latex dye injections, we discuss the creation of a deep fascial sheath that contains a rich vascular network and permits adhesion-free excursion at the recipient site. This study advances our understanding of the myofasciocutaneous gracilis flap and provides wider clinical applicability in free functional muscle transfer.

Tranexamic Acid Can Reduce Early Tendon Adhesions After Rotator Cuff Repair and Is Not Detrimental to Tendon-Bone Healing: A Comparative Animal Model Study.

PURPOSE: To determine the effects of topical tranexamic acid (TXA) administration on tendon adhesions, shoulder range of motion (ROM), and tendon healing in an acute rotator cuff repair rat model. METHODS: A total of 20 Sprague Dawley rats were used. Tendon adhesion, ROM, and biomechanical and histological analysis of tendon-bone healing was conducted at 3 and 6 weeks after surgery. The rats underwent rotator cuff repair surgery on both shoulders and were administered TXA via subacromial injections. The tendon adhesion was evaluated macroscopically and histologically. Biomechanical tendon healing was measured using a universal testing machine, and histological analysis was quantified by H&E, Masson's trichrome, and picrosirius red staining. RESULTS: At 3 weeks after surgery, the adhesion score was significantly lower in the TXA group (2.10 ± 0.32) than in the control group (2.70 ± 0.48) (P = .005), but there was no significant difference between the 2 groups at 6 weeks. Regarding ROM, compared with the control group, the TXA group showed significantly higher external rotation (36.35° ± 4.52° vs 28.42° ± 4.66°, P < .001) and internal rotation (45.35° ± 9.36° vs 38.94° ± 5.23°, P = .013) 3 weeks after surgery. However, at 6 weeks, there were no significant differences in external and internal rotation between the 2 groups. In the biomechanical analysis, no significant differences in gross examination (3 weeks, P = .175, 6 weeks, P = .295), load to failure (3 weeks, P = .117, 6 weeks, P = .295), or ultimate stress (3 weeks, P = .602, 6 weeks, P = .917) were noted between the 2 groups 3 and 6 weeks after surgery. In the histological analysis of tendon healing, no significant differences in the total score (3 weeks, P = .323, 6 weeks, P = .572) were found between the 2 groups 3 and 6 weeks after surgery. CONCLUSIONS: Topical TXA administration showed a beneficial effect in reducing tendon adhesions and improving ROM 3 weeks postoperatively and had no effect at 6 weeks. This suggests that additional intervention with TXA may be useful in achieving long-term improvement in shoulder stiffness. Additionally, TXA may increase tissue ground substance accumulation in the late postoperative period but does not adversely affect tendon-bone interface healing. CLINICAL RELEVANCE: The use of TXA after rotator cuff repair has no effect on tendon-bone interface healing in clinical practice and can improve shoulder stiffness in the early postoperative period. Additional research on the long-term effects is needed.

Monolithic 3D integration of 2D materials-based electronics towards ultimate edge computing solutions.

Three-dimensional (3D) hetero-integration technology is poised to revolutionize the field of electronics by stacking functional layers vertically, thereby creating novel 3D circuity architectures with high integration density and unparalleled multifunctionality. However, the conventional 3D integration technique involves complex wafer processing and intricate interlayer wiring. Here we demonstrate monolithic 3D integration of two-dimensional, material-based artificial intelligence (AI)-processing hardware with ultimate integrability and multifunctionality. A total of six layers of transistor and memristor arrays were vertically integrated into a 3D nanosystem to perform AI tasks, by peeling and stacking of AI processing layers made from bottom-up synthesized two-dimensional materials. This fully monolithic-3D-integrated AI system substantially reduces processing time, voltage drops, latency and footprint due to its densely packed AI processing layers with dense interlayer connectivity. The successful demonstration of this monolithic-3D-integrated AI system will not only provide a material-level solution for hetero-integration of electronics, but also pave the way for unprecedented multifunctional computing hardware with ultimate parallelism.

Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells.

Infections in early life can elicit substantially different immune responses and pathogenesis than infections in adulthood. Here, we investigate the consequences of murine cytomegalovirus infection in newborn mice on NK cells. We show that infection severely compromised NK cell maturation and functionality in newborns. This effect was not due to compromised virus control. Inflammatory responses to infection dysregulated the expression of major transcription factors governing NK cell fate, such as Eomes, resulting in impaired NK cell function. Most prominently, NK cells from perinatally infected mice have a diminished ability to produce IFN-γ due to the downregulation of long non-coding RNA Ifng-as1 expression. Moreover, the bone marrow's capacity to efficiently generate new NK cells is reduced, explaining the prolonged negative effects of perinatal infection on NK cells. This study demonstrates that viral infections in early life can profoundly impact NK cell biology, including long-lasting impairment in NK cell functionality.

Anatomical Consideration for Anterior Approach of Cervicothoracic Junction: A Computed Tomography Image Analysis.

Background: In the cervicothoracic junction (CTJ), there is limited working space to perform the posterior-only approach. Therefore, a combined anterior approach is required in some cases. However, the great vessels and sternum obstruct the anterior corridor and make the anterior approach difficult. We analyzed relevant anatomical structures encountered during the anterior approach in the CTJ and evaluated the feasibility of previously reported surgical corridors. Methods: We retrospectively examined 49 patients who underwent neck computed tomography angiography between January 2015 and May 2020. Using the coronal images, we measured the intercarotid artery angle (ICAA), intercarotid artery distance (ICAD), shape of the brachiocephalic trunk (BCT), and position of the BCT base. We then measured the most cranial level requiring manubriotomy for the anterior approach (ML), the most caudal level accessible through the superior corridor (SC), and the most caudal level through the inferior corridor (IC) according to the surgeon's line of sight using the sagittal axis image. Results: The mean ICAA and ICAD were 50.83° ± 15.23° and 33.38 ± 12.11 mm, respectively. Notably, BCT shape was of the convex type in most cases (42.9%), followed by the straight type (36.7%). In addition, the base of BCT was most commonly located inside the body (49%). Moreover, ICAA and ICAD were significantly greater in men. Although men mostly had the BCT base inside the body (64.3%), female mostly had it on the edge of the body (47.6%). Notably, ML showed the highest frequency (16.3%) in the T1 lower and upper bodies. Furthermore, through SC and IC, it was possible to approach the T4 lower body and T6 midbody, respectively. SC showed the highest frequency (16.3%) in the T3 lower body, and IC showed the highest frequency (20.4%) in the T5 midbody. Conclusions: ICAA and ICAD were larger and higher in men. BCT was convex and located inside the body in most cases. The accessible level of ML, SC, and IC were T1, T3, and T5, respectively. For the anterior approach in the CTJ, preoperative vascular and accessible level analysis of corridors is essential to decide on the appropriate corridor and reduce complications.

Technical Feasibility and Early Clinical Outcome of Biportal Endoscopic Transforaminal Lumbar Interbody Fusion Using Larger Cage.

BACKGROUND: Transforaminal lumbar interbody fusion with biportal endoscopic guidance (BE-TLIF) has been previously reported with promising clinical results. However, complications such as delayed union or subsidence occurred as with open surgery. We assumed using larger cages would result in less occurrence of such complications. We aimed to analyze the clinical outcome and technical feasibility of BE-TLIF using larger cages, initially designed for oblique lumbar interbody fusion. METHODS: We enrolled cases that underwent single-level BE-TLIF between January 2021 and January 2022. Polyetheretherketone cages that were larger than the conventional size were used. Diagnoses were degenerative spondylolisthesis or isthmic spondylolisthesis. Visual analog scale scores of the back and leg and Oswestry Disability Index were collected perioperatively. Modified Macnab criteria were used to evaluate the patients at the final follow-up. Radiologic outcome of interbody fusion rate and perioperative complications were analyzed. RESULTS: A total of 35 cases were included in this study. The mean age was 67.5 ± 8.4 and consisted of 13 male patients, and the mean follow-up duration was 18.3 ± 3.7 months. The majority (32/35, 91.3%) of the index level was located within the lower lumbar region, L4-S1. Oswestry Disability Index scores improved from 65.4 ± 5.4 preoperatively to 15.4 ± 6.1 at the final follow-up (P < 0.001). Visual analog scale scores of the leg decreased from 7.9 ± 1.5 to 1.7 ± 1.5 at the final follow-up (P < 0.001). Per the modified Macnab criteria on the final follow-up, 94% of the patients reported good/excellent. Most (94.2%) of the patients showed fusion grade I and II at the 1-year follow-up. No patient showed subsidence or other postoperative complication. CONCLUSIONS: BE-TLIF using a larger cage was safely performed without risk of subsidence during the 1-year follow-up. A cage with a larger footprint may be advantageous in BE-TLIF in the aspect of interbody fusion and subsidence.

The Philadelphia Shriners Hospital Approach to Brachial Plexus Birth Injury.

The care of children with brachial plexus birth injuries (BPBI) is a complex multidisciplinary endeavor. At the Shriners Hospital for Children in Philadelphia, we have sought to elevate the quality of care delivered to patients through outcomes research and collaboration with colleagues around the world. Our approach to the management of this challenging pathology has evolved time and again. Here, we describe our current approach to patient assessment and operative management in patients with BPBI and its many sequelae.

Management of Brachial Plexus Birth Palsies: The Stanford Experience.

The start of Stanford's brachial plexus birth palsy (BPBP) experience dates back to 1983, when Dr. Vincent Rod Hentz visited Dr. Alain Gilbert on sabbatical. Since then, our principles of care for patients with BPBP have evolved based on our group's longitudinal experience caring for children with the entire spectrum of sequelae that arise in children with BPBP. We base our clinical decision making on frequent serial examinations and use intraoperative evoked potentials to guide surgical decisions. Here, we discuss our current principles on surgical indications, timing of surgery, and preferred techniques for secondary surgery in patients with BPBP.

Surgical outcome of locked facet in distractive flexion injury of the subaxial cervical spine: Single institution retrospective study.

The optimal surgical treatment for patients suffering from distractive flexion injury of the subaxial cervical spine with a locked facet (LF) is unknown. Closed reduction via an anterior or posterior approach is a treatment option for LF. We examined the surgical outcomes of patients treated for locked facet distractive flexion injury (LF-DFI) in this case series, with a particular emphasis on the surgical approach and reduction maneuver. We retrospectively analyzed the patients with distractive flexion injury of the subaxial cervical spine who underwent surgery at our hospital between November 2006 and April 2021. Patients who did not have facet subluxation or dislocation or those who achieved LF reduction prior to skin incision were excluded from this study. The patients were divided into 2 groups based on their initial approach, anterior or posterior approach. Perioperative clinical outcomes, including the American Spinal Cord Injury Association scale score, radiological changes, and complications were analyzed. This study enrolled 12 patients with LF-DFI. Four and 8 patients underwent the anterior and posterior approaches, respectively. The LF was reduced using an anterior approach with traction between the vertebral bodies in the anterior approach group and using a posterior approach with partial facetectomy in the posterior approach group. The preoperative American Spinal Cord Injury Association scale scores were as follows: A, 1 patient; B, 1 patient; C, 3 patients; D, 4 patients; and E, 3 patients. Nine patients showed no neurologic deterioration after surgery, whereas 2 had an aggravated neurologic status. Postoperatively, patients who underwent posterior open reduction did not exhibit worsened neurologic symptoms, whereas 2 patients who underwent the anterior approach showed worsened neurologic symptoms. At the final follow-up, all patients achieved radiological fusion, and no complications other than neurologic deterioration were identified. In terms of worsening postoperative neurologic status, a posterior approach using partial facetectomy for LF reduction is considered a safer surgical technique than an anterior approach. To avoid iatrogenic intraoperative cord injury, we recommend posterior approach in patients with LF-DFI.

Direct Visualization of Subnanometer Variations in the Excitonic Spectra of 2D/3D Semiconductor/Metal Heterostructures.

The integration of metallic contacts with two-dimensional (2D) semiconductors is routinely required for the fabrication of nanoscale devices. However, nanometer-scale variations in the 2D/metal interface can drastically alter the local optoelectronic properties. Here, we map local excitonic changes of the 2D semiconductor MoS2 in contact with Au. We utilize a suspended and epitaxially grown 2D/metal platform that allows correlated electron energy-loss spectroscopy (EELS) and angle resolved photoelectron spectroscopy (nanoARPES) mapping. Spatial localization of MoS2 excitons uncovers an additional EELS peak related to the MoS2/Au interface. NanoARPES measurements indicate that Au-S hybridization decreases substantially with distance from the 2D/metal interface, suggesting that the observed EELS peak arises due to dielectric screening of the excitonic Coulomb interaction. Our results suggest that increasing the van der Waals distance could optimize excitonic spectra of mixed-dimensional 2D/3D interfaces and highlight opportunities for Coulomb engineering of exciton energies by the local dielectric environment or moiré engineering.

COMPARISON OF SURGEON MUSCULAR PROPERTIES BETWEEN STANDARD OPERATING MICROSCOPE AND DIGITALLY ASSISTED VITREORETINAL SURGERY SYSTEMS.

PURPOSE: To quantitatively analyze surgical ergonomics between standard operating microscope (SOM) and digitally assisted vitreoretinal surgery (DAVS) systems. METHODS: The surgeon conducted procedures on 110 patients; 52 patients underwent a combined phacoemulsification and pars plana vitrectomy (Phaco-PPV group, 24 using SOM and 28 using DAVS), and 58 patients underwent phacoemulsification (Phaco group, 30 using SOM and 28 using DAVS). The surgeon's muscle tone and stiffness in the sternocleidomastoid and the two positions of the upper trapezius (UT), which are 2-cm intervals along the UT muscle fibers, UT1 and UT2, were measured at preoperative, intraoperative, and postoperative time points. RESULTS: In the Phaco-PPV group using the SOM, intraoperative muscle tone and stiffness were higher than preoperative and postoperative values in the sternocleidomastoid ( P < 0.001, respectively), UT1 ( P < 0.001, respectively), and UT2 ( P < 0.001 and P < 0.01, respectively). In the Phaco group using the SOM, intraoperative muscle tone and stiffness were higher than pre- and postoperative values in the sternocleidomastoid ( P < 0.001, respectively) and UT1 ( P < 0.001 and P < 0.01, respectively). By contrast, when the surgeon used the DAVS, there were no differences in muscle properties at any measurement site or during any time point in the Phaco-PPV and Phaco groups ( P > 0.05). CONCLUSION: This study provides quantitative measurement of retina surgeon ergonomics, suggesting that compared with a SOM, the DAVS can reduce intraoperative muscle fatigue.

The Feasibility of Cross-Linguistic Speech Evaluation in the Care of International Cleft Palate Patients.

ABSTRACT: Many patients with cleft palate in developing countries never receive postoperative speech assessment or therapy. The use of audiovisual recordings could improve access to post-repair speech care. The present study evaluated whether English-speaking speech-language pathologists (SLPs) could assess cleft palate patients speaking an unfamiliar language (Tamil) using recorded media. Recordings obtained from Tamil-speaking participants were rated by 1 Tamil-speaking SLP and 3 English-speaking SLPs. Ratings were analyzed for inter-rater reliability and scored for percent correct. Accuracy of the English SLPs was compared with independent t tests and Analysis of Variance. Sixteen participants (mean age 14.5 years, standard deviation [SD] 7.4 years; mean age of surgery of 2.7 years, SD 3.7 years; time since surgery: 10.8 years, SD 5.7 years) were evaluated. Across the 4 SLPs, 5 speech elements were found to have moderate agreement, and the mean kappa was 0.145 (slight agreement). Amongst the English-speaking SLPs, 10 speech elements were found to have substantial or moderate agreement, and the mean kappa was 0.333 (fair agreement). Speech measures with the highest inter-rater reliability were hypernasality and consonant production errors. The average percent correct of the English SLPs was 60.7% (SD 20.2%). English SLPs were more accurate if the participant was female, under eighteen, bilingual, or had speech therapy. The results demonstrate that English SLPs without training in a specific language (Tamil) have limited potential to assess speech elements accurately. This research could guide training interventions to augment the ability of SLPs to conduct cross-linguistic evaluations and improve international cleft care by global health teams.

Bicortical Laminar Screws for Posterior Fixation of Subaxial Cervical Spine: A Radiologic Analysis With Computed Tomography Images.

STUDY DESIGN: Retrospective radiological analysis. OBJECTIVES: Translaminar screw (TLS) placement is one of the fixation techniques in the subaxial cervical spine. However, it can be difficult to use in small diameter of the lamina. This study proposed a novel bicortical laminar screw (BLS) and analyzed the related parameters using computed tomography (CT). METHODS: Cervical CT images taken at our institution from January 2013 to March 2017 were used for measurement. On the axial images, the maximum screw length (MSL) and trajectory angle (TA) of BLS and TLS were measured, together with the distance from the midline (DM) to the BLS entry point and the lamina width (LW). On the parasagittal images, the height of the lamina (LH) was measured. RESULTS: MSL of BLS and TLS were 21.00 and 20.97 mm, 19.02 and 20.91 mm, 18.45 and 21.01 mm, and 20.00 and 21.01 mm in C3, C4, C5, and C6, respectively. TA of the BLS and TLS were 21.24° and 34.90°, 19.05° and 34.22°, 18.65° and 33.61°, and 18.30° and 34.51° at C3, C4, C5, and C6, respectively. DM were 6.44, 5.77, 5.68, and 6.03 at C3, C4, C5, and C6, respectively. LW and LH were 3.52 and 12.44 mm, 2.87 and 12.49 mm, 2.76 and 12.42 mm, and 3.18 and 13.30 mm at C3, C4, C5, and C6, respectively. CONCLUSION: We suggest that BLS fixation is a feasible alternative option for posterior fixation to the lamina of the subaxial cervical spine. It may be especially useful when pedicle screw, lateral mass screw, and TLS are not appropriate.

Ultrasound Diagnosis of Prenatal Cleft Lip: How Does Its Accuracy Affect the Family?

ABSTRACT: Factors impacting the accuracy of ultrasound (US) diagnosis of cleft lip (CL) and its subsequent effect on parents are not well understood. Our objectives were to evaluate how the type of CL (complete versus incomplete) and associated cleft palate affect the accuracy of CL's prenatal diagnosis and to evaluate differences between parents' perception of prenatal US in cases of true-positive versus false-negative results. The authors performed a retrospective review of all patients who underwent repair for nonsyndromic CL following prenatal US. Patients were stratified by type of CL and associated cleft palate. Parents were called to determine if their child's CL was diagnosed via US and their perception of the results. Forty-seven children with complete and 40 with incomplete CL responded to phone calls. The presence of a complete CL (P = 0.001) and an associated cleft palate (P = 0.014) were independently associated with an increased likelihood of prenatal diagnosis. Parents who received a true-positive prenatal diagnosis of CL were more satisfied than those who received a false-negative diagnosis (P = 0.0063). True-positives perceived knowing of their child's diagnosis in advance to be more helpful than false-negatives believed it would have been. These results afford an improved context to interpret US studies and help physicians provide more informed prenatal counseling.

Rethinking Global Health Education in Plastic Surgery Residency.

Surgical disease is now among the most common, preventable, and growing contributors to the global burden of disease. The attitudes of trainees toward global surgery and the viability of a global surgery as an academic track have blossomed. More optimized experiences within residency education are necessary, however, to prepare the next generation of global surgeons. The field of plastic surgery is thus at an important crossroads in the effort to incorporate global surgery into training programs in a uniform fashion across the country. The recent American Council of Academic Plastic Surgeons meeting in February 2020 was dedicated to identifying strategies that will enhance the adoption of global surgery practices within plastic surgery. In this article, we discuss the principles, themes, and ideas that emerged from this session, and further develop concrete initiatives believed to be potentially fruitful. Some have been discussed in other surgical disciplines or presented in isolation to the plastic surgery community, but never as a cohesive set of recommendations that take into account the background and shortfalls of the current model for global health education in the 21st century. We then introduce five recommendations to optimize learner education: (1) clarification of learner expectations and roles; (2) domestic teaching for optimization of field experiences; (3) expansion of longitudinal, formal rotations; (4) strengthening of the role of research; and (5) integration of program financing.

Post-Traumatic Epilepsy in Zebrafish Is Drug-Resistant and Impairs Cognitive Function.

Post-traumatic epilepsy (PTE) is acquired epilepsy after traumatic brain injury (TBI). Despite the availability of more than 20 antiseizure medications (ASMs), there is no way at present to prevent epileptogenesis in TBI survivors, and many cases of PTE become drug-resistant. Importantly, the adverse effects of ASMs can significantly affect patients' quality of life. Mammalian models are commonly used for studying refractory PTE, but are expensive and laborious. Zebrafish models have become popular for studying epilepsy, but most focus on larvae, and there have been no reports to date of pharmacological screening in an adult zebrafish model of acquired epilepsy. Valid animal models are critical for understanding PTE and for developing novel therapeutics. The aim of the present study was to characterize the cognitive impairments of a zebrafish model of TBI that leads to the development of PTE. Using combined behavioral and electrophysiological approaches, we also characterized the pharmacological effects of the most commonly used ASMs to manage PTE (valproate, carbamazepine, and phenytoin). Zebrafish with PTE exhibited impairments in learning and memory, difficulty in decision making, and reduced social preference. Valproate and carbamazepine had a limited protective effect against behavioral seizures, and all three drugs failed to significantly reduce electrographical seizures. The negative impacts of TBI and ASMs in zebrafish parallel those observed in other animals, making the zebrafish model of PTE a promising high-throughput model of refractory and drug-resistant epilepsy.

HIF1α is required for NK cell metabolic adaptation during virus infection.

Natural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1α-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1αKO NK cells; however, their numbers were significantly reduced. Loss of HIF1α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1α-deficient NK cells showed increased expression of the pro-apoptotic protein Bim and glucose metabolism was impaired during cytokine stimulation in vitro. Similarly, during MCMV infection HIF1α-deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF1α-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response.