Perceptions of Competition-Based Learning After a Brief Experience at a National Surgical Meeting.

BACKGROUND: Competition-based learning (CBL) facilitates learning through competitions. At the 2022 & 2023 Annual SAGES meetings, we evaluated a CBL experience (TOP GUN Shootout) developed from a modified version of the previously validated TOP GUN Laparoscopic Skills and Suturing Program. The project sought to evaluate the TOP GUN Shootout's (TGS) ability to enhance participant engagement in pursuit of laparoscopic surgical skills. METHODS: Participants competed in the TGS. Their scores (time and errors) were recorded for: Fundamentals of Laparoscopic Surgery Peg Pass, Cup Drop Task, and Intracorporeal Suturing. All participants completed a 10-question satisfaction survey on a 7-point Likert scale, with questions assessing 3 domains: (1) capability/confidence in MIS skill performance prior to the competition; (2) applicability and satisfaction with TGS's capacity to develop MIS skills; and (3) interest in seeking additional MIS training and appropriateness of CBL in MIS training. Descriptive statistics were used to evaluate these areas. RESULTS: Overall, 121 participants completed the TGS, of whom 84 (69%) completed the satisfaction survey. The average age was 32.9 years, 67% were males. On average (+/- SD), participant satisfaction was 5.04 (+/- 2.08) for Domain 1, 6.20 (+/- 1.28) for Domain 2, and 6.58 (+/- .95) for Domain 3. CONCLUSION: Participants described an overall lack of confidence in their MIS skills prior to the 2022-2023 Annual SAGES conference. Participants felt that this brief CBL experience, aided in the development of their MIS skills. Furthermore, this brief CBL experience may inspire learners to seek out further training of their MIS skills.

Context-specific synthetic T cell promoters from assembled transcriptional elements.

Genetic engineering of human lymphocytes for therapeutic applications is constrained by a lack of transgene transcriptional control, resulting in a compromised therapeutic index. Incomplete understanding of transcriptional logic limits the rational design of contextually responsive genetic modules1. Here, we juxtaposed rationally curated transcriptional response element (TRE) oligonucleotides by random concatemerization to generate a library from which we selected context-specific inducible synthetic promoters (iSynPros). Through functional selection, we screened an iSynPro library for "IF-THEN" logic-gated transcriptional responses in human CD8+ T cells expressing a 4-1BB second generation chimeric antigen receptor (CAR). iSynPros exhibiting stringent off-states in quiescent T cells and CAR activation-dependent transcriptional responsiveness were cloned and subjected to TRE composition and pattern analysis, as well as performance in regulating candidate antitumor potency enhancement modules. These data reveal synthetic TRE grammar can mediate logic-gated transgene transcription in human T cells that, when applied to CAR T cell engineering, enhance potency and improve therapeutic indices.

The evolution of surgical virtual education and telementoring: One surgeon's journey.

The first era of the global proliferation of surgical advancements involved surgical infection rate and technique breakthroughs by Lister, Halsted, and others. This was propagated by letters, academic papers, and international visits. While success was achieved, it was at a suboptimal pace. In the current era of minimally invasive surgical approaches, these methods are inadequate. This paper chronicles the development and application of virtual learning and telementoring as force multipliers to speed procedural adoption and proliferation.

Rationally Designed Transgene-Encoded Cell-Surface Polypeptide Tag for Multiplexed Programming of CAR T-cell Synthetic Outputs.

Synthetic immunology, as exemplified by chimeric antigen receptor (CAR) T-cell immunotherapy, has transformed the treatment of relapsed/refractory B cell-lineage malignancies. However, there are substantial barriers-including limited tumor homing, lack of retention of function within a suppressive tumor microenvironment, and antigen heterogeneity/escape-to using this technology to effectively treat solid tumors. A multiplexed engineering approach is needed to equip effector T cells with synthetic countermeasures to overcome these barriers. This, in turn, necessitates combinatorial use of lentiviruses because of the limited payload size of current lentiviral vectors. Accordingly, there is a need for cell-surface human molecular constructs that mark multi-vector cotransduced T cells, to enable their purification ex vivo and their tracking in vivo. To this end, we engineered a cell surface-localizing polypeptide tag based on human HER2, designated HER2t, that was truncated in its extracellular and intracellular domains to eliminate ligand binding and signaling, respectively, and retained the membrane-proximal binding epitope of the HER2-specific mAb trastuzumab. We linked HER2t to CAR coexpression in lentivirally transduced T cells and showed that co-transduction with a second lentivirus expressing our previously described EGFRt tag linked to a second CAR efficiently generated bispecific dual-CAR T cells. Using the same approach, we generated T cells expressing a CAR and a second module, a chimeric cytokine receptor. The HER2txEGFRt multiplexing strategy is now being deployed for the manufacture of CD19xCD22 bispecific CAR T-cell products for the treatment of acute lymphoblastic leukemia (NCT03330691).

Patient and Provider Cocreation of Mobile Texting Apps to Support Behavioral Health: Usability Study.

BACKGROUND: Mobile technologies hold potential for improving the quality of care and engagement of patients. However, there are considerable challenges in ensuring that technologies are relevant, useful, and engaging. While end users such as patients and providers are increasingly involved in the design of health technologies, there are limited examples of their involvement in directly creating technologies for their personal use. OBJECTIVE: We aim to evaluate the feasibility and acceptability of patients and providers creating mobile texting apps to support treatment goals. METHODS: In an 11-month usability study, we enrolled 4 providers and 28 patients in an intensive outpatient program for obsessive-compulsive disorder. Patients and providers created their own mobile texting apps using a visual app development platform. A subsample of 10 patients and 4 providers completed a usability measure. RESULTS: Participants created a total of 360 unique mobile text messages (1787 total messages sent). There were 4 types of messages identified, including personalized reminders, clinical exposures, interactive prompts, and encouraging/informational messages. A total of 9 out of 10 (90%) patients agreed that the messages were relevant to their recovery, and 8 out of 10 (80%) agreed that the messages were effective at helping complete treatment plans. CONCLUSIONS: Enabling patients and providers to cocreate apps for their own use by using a visual application platform is feasible and holds potential for increasing the relevance, sustainability, and effectiveness of digital health technologies.

Medical Applications of Drones for Disaster Relief: A Review of the Literature.

INTRODUCTION: Rapid progress has been made with unmanned aerial systems (UAS), which are now used in a wide variety of different fields, including media, agriculture, wildlife, and infrastructure. However, the application of UAS for medical purposes, and in particular disaster relief efforts, has been slower to develop. This paper will review and present pertinent studies in the literature. METHODOLOGY: Studies related to drones and medical applications for disaster relief were identified as part of a larger search regarding the civilian application of drones. A search for civilian drone applications was performed in the EBSCO (Elton B. Stephens Company) database. Non-civilian applications as well as redundant sources were excluded. RESULTS: The search identified 711 sources pertaining to civilian drone applications. Of these, 117 involved drone applications in disaster relief, and 28 articles specifically addressed medical uses. CONCLUSION: Drones can be useful during immediate and non-immediate medical disaster relief efforts. They can provide an instant telecommunications infrastructure, assist in telemedicine-enabled clinical services, perform equipment/drug/patient delivery, enhance search and rescue efforts, assess damage and map disaster zones. Rapid processing of permission for emergency operations, promotion of industry expansion, public awareness, and public participation must be emphasized for these to become routine applications. There is a major concern about the organizational umbrella that would promote this initiative. Creation of an organization such as a Drone Civil Air Patrol Wing (DCAPW) could improve our ability to provide post-disaster healthcare delivery services.

Surgical and Medical Applications of Drones: A Comprehensive Review.

BACKGROUND: Drones have the ability to gather real time data cost effectively, to deliver payloads and have initiated the rapid evolution of many industrial, commercial, and recreational applications. Unfortunately, there has been a slower expansion in the field of medicine. This article provides a comprehensive review of current and future drone applications in medicine, in hopes of empowering and inspiring more aggressive investigation. DATABASE: A literature search was performed by EBSCO (Elton B. Stephens Company) Discovery Service, searching the phrases "drones," "UAV," "unmanned aerial vehicles," "UAS," and "unmanned aerial systems." A second search was used to identify sources that contained "drone" in the subject or title and "medicine" in any of the text, yielding 60,260 results. After screening for irrelevant material, 1296 sources remained applicable. Major themes and number of sources were as follows: 116 public health and medical surveillance, 8 telemedicine, and 78 medical transport systems. CONCLUSION: Drones are used for surveillance of disaster sites and areas with biological hazards, as well as in epidemiology for research and tracking disease spread. Telecommunication drones are being used for diagnosis and treatment, perioperative evaluation, and telementoring in remote areas. Drones have the potential to be reliable medical delivery platforms for microbiological and laboratory samples, pharmaceuticals, vaccines, emergency medical equipment, and patient transport. Government agencies have placed drone use on the national agenda. The next steps include aggressive research initiatives in the areas of safety, industry expansion, increased public awareness, and participation.

SAGES Mini Med School: inspiring high school students through exposure to the field of surgery.

OBJECTIVE: The SAGES Mini Med School (SMMS) was designed to expose high school students to the field of surgery through mentoring, knowledge transfer, and hands-on experience with simulation. The objective of this paper is to profile the evolutionary development, performance metrics, and satisfaction queries of this innovative effort. METHODS: Sixty-one high school students, grades 9-12, took part in the (SMMS) program during the 2015 SAGES Annual Congress. The students completed a surgical skills lab session where they attempted tasks associated with the development of open surgical and laparoscopic skills. The lab included a warm-up with the validated Super Monkey Ball video game, Top Gun Pea Drop task, FLS Peg Transfer task, open knot tying station, and open instrument tie station. RESULTS: The following are the results of the surgical skills lab. For the Super Monkey Ball task, 60 students participated with an average score of 73.0 s (SD = 53.9; range 59.1-87.0; median = 74). Sixty students participated in the Surgeons Knot and Pea Drop tasks with average times of 26.6 s (SD = 19.3; range 21.7-31.6; median = 21.0) and 113.8 s (SD = 65.9; range 96.6-131.0; median = 101.0), respectively. Sixty students participated in the Instrument Tie and 56 students participated in the Peg Transfer stations with average times of 51.7 s (SD = 34.5; range 42.8-60.6; median = 39.5) and 173.1 s (SD = 25.0; range 166.4-179.8; median = 180.0), respectively. 51 (83.6%) agreed that the Mini Med School made them more likely to consider a career in medicine. When asked if the program made them more likely to consider a career in surgery 42 (68.8%) agreed. All 61 respondents (100%) said that they would recommend the program to others. CONCLUSIONS: The SMMS program showed that the students had an excellent aptitude for the performance of validated surgical subtasks with high satisfaction, and increased consideration of a career in medicine/surgery. Long-term studies are needed to evaluate the impact on workforce recruitment.

Intact piRNA pathway prevents L1 mobilization in male meiosis.

The PIWI-interacting RNA (piRNA) pathway is essential for retrotransposon silencing. In piRNA-deficient mice, L1-overexpressing male germ cells exhibit excessive DNA damage and meiotic defects. It remains unknown whether L1 expression simply highlights piRNA deficiency or actually drives the germ-cell demise. Specifically, the sheer abundance of genomic L1 copies prevents reliable quantification of new insertions. Here, we developed a codon-optimized L1 transgene that is controlled by an endogenous mouse L1 promoter. Importantly, DNA methylation dynamics of a single-copy transgene were indistinguishable from those of endogenous L1s. Analysis of Mov10l1-/- testes established that de novo methylation of the L1 transgene required the intact piRNA pathway. Consistent with loss of DNA methylation and programmed reduction of H3K9me2 at meiotic onset, the transgene showed 1,400-fold increase in RNA expression and consequently 70-fold increase in retrotransposition in postnatal day 14 Mov10l1-/- germ cells compared with the wild-type. Analysis of adult Mov10l1-/- germ-cell fractions indicated a stage-specific increase of retrotransposition in the early meiotic prophase. However, extrapolation of the transgene data to endogenous L1s suggests that it is unlikely insertional mutagenesis alone accounts for the Mov10l1-/- phenotype. Indeed, pharmacological inhibition of reverse transcription did not rescue the meiotic defect. Cumulatively, these results establish the occurrence of productive L1 mobilization in the absence of an intact piRNA pathway but leave open the possibility of processes preceding L1 integration in triggering meiotic checkpoints and germ-cell death. Additionally, our data suggest that many heritable L1 insertions originate from individuals with partially compromised piRNA defense.

Performance of High School Students in a Laparoscopic Training Program.

BACKGROUND AND OBJECTIVES: We hypothesized that high school students can be subjected to the same laparoscopic surgical training curriculum used by surgeons and successfully complete it. The goal of this study was to evaluate the appropriateness of early training in minimally invasive surgical techniques. METHODS: Thirteen high school students, ages 15-18, participated in the validated Top Gun Surgeon Laparoscopic Skills and Suturing program. The students performed 3 preparatory drills 10 times each. The students' scores were then compared to a database of 393 surgeons. Performance graphs were prepared to allow comparison of skills acquisition between the 2 training groups. RESULTS: All 13 students successfully completed the tasks. The Students' performance (expressed as time/percentile range/average percentile) for each task were as follows: rope pass 101.8 seconds/3.8-47.1/11.8; bean drop 149.5 seconds/18.7-96.0/59.4; triangle transfer 303.2 seconds/1.3-16.0/5.8. The students started each drill with slower times, but their average improvement (decreased time to complete tasks) was more rapid than that of the surgeons between the first and second trials for each drill (-83 seconds vs -25 seconds, -120 seconds vs -53 seconds, -100 seconds vs -60 seconds). Average student times compared to average surgeon times during the last trials measured were not significantly different in the triangle transfer and rope pass drills (P = .40 and .18, respectively). Students' times were significantly faster than surgeons' in the last measured trial of the bean drop (P = .039). CONCLUSIONS: Despite the small sample size, this investigation suggests that high school students can successfully complete skill-building programs in minimally invasive surgery. Further study is needed to evaluate the appropriateness of starting surgical training of future residents at an earlier stage of their careers.

Design and Development of a Novel Distance Learning Telementoring System Using Off-the-Shelf Materials and Software.

OBJECTIVE: To design and develop a distance learning (DL) system for the transference of laparoscopic surgery knowledge and skill constructed from off-the-shelf materials and commercially available software. INTRODUCTION: Minimally invasive surgery offers significant benefits over traditional surgical procedures, but adoption rates for many procedures are low. Skill and confidence deficits are two of the culprits. DL combined with simulation training and telementoring may address these issues with scale. MATERIALS AND METHODS: The system must be built to meet the instruction requirements of a proven laparoscopic skills course (Top Gun). Thus, the rapid sharing of multimedia educational materials, secure two-way audio/visual communications, and annotation and recording capabilities are requirements for success. These requirements are more in line with telementoring missions than standard distance learning efforts. RESULTS: A DL system with telementor, classroom, and laboratory stations was created. The telementor station consists of a desktop computer and headset with microphone. For the classroom station, a laptop is connected to a digital projector that displays the remote instructor and content. A tripod-mounted webcam provides classroom visualization and a Bluetooth® wireless speaker establishes audio. For the laboratory station, a laptop with universal serial bus (USB) expander is combined with a tabletop laparoscopic skills trainer, a headset with microphone, two webcams and a Bluetooth® speaker. The cameras are mounted on a standard tripod and an adjustable gooseneck camera mount clamp to provide an internal and external view of the training area. Internet meeting software provides audio/visual communications including transmission of educational materials. CONCLUSION: A DL system was created using off-the-shelf materials and commercially available software. It will allow investigations to evaluate the effectiveness of laparoscopic surgery knowledge and skill transfer utilizing DL techniques.

Impact of Super Monkey Ball and Underground video games on basic and advanced laparoscopic skill training.

OBJECTIVE: This abstract profiles the comparison of correlations between previously validated Super Monkey Ball (SMB) and recently introduced Underground (U) video game on the Nintendo Wii U to multiple validated tasks used for developing basic and advanced laparoscopic skills. METHODS: Sixty-eight participants, 53 residents and 15 attending surgeons, performed the Top Gun Pea Drop, FLS Peg Pass, intracorporeal suturing, and two video games (SMB and U). SMB is an over-the-counter game, and U was formulated for laparoscopic skill training. RESULTS: Spearman's rank correlations were performed looking at performance comparing the three validated laparoscopic training tasks, and SMB/U. The SMB score had a moderate correlation with intracorporeal suturing (ρ = 0.39, p < 0.01), and the final score involving all three tasks (ρ = 0.39, p < 0.01), but low correlations with Pea Drop Drill and FLS Peg Transfer (ρ = 0.11, 0.18, p < 0.01). The U score had a small correlation with intracorporeal suturing and final score (ρ = 0.09, 0.13, p < 0.01). However, there were correlations between U score and Pea Drop Drill, and FLS Peg Transfer (ρ = 0.24, 0.27, p < 0.01, respectively). CONCLUSION: In this study, SMB had a very significant correlation with intracorporeal suturing. U demonstrated more of a correlation with basic skills. At this point, our conclusion would be that both are effective for laparoscopic skill training, and they should be used in tandem rather than alone.

Retrotransposition creates sloping shores: a graded influence of hypomethylated CpG islands on flanking CpG sites.

Long interspersed elements (LINEs), through both self-mobilization and trans-mobilization of short interspersed elements and processed pseudogenes, have made an indelible impact on the structure and function of the human genome. One consequence is the creation of new CpG islands (CGIs). In fact, more than half of all CGIs in the genome are associated with repetitive DNA, three-quarters of which are derived from retrotransposons. However, little is known about the epigenetic impact of newly inserted CGIs. We utilized a transgenic LINE-1 mouse model and tracked DNA methylation dynamics of individual germline insertions during mouse development. The retrotransposed GFP marker sequence, a strong CGI, is hypomethylated in male germ cells but hypermethylated in somatic tissues, regardless of genomic location. The GFP marker is similarly methylated when delivered into the genome via the Sleeping Beauty DNA transposon, suggesting that the observed methylation pattern may be independent of the mode of insertion. Comparative analyses between insertion- and non-insertion-containing alleles further reveal a graded influence of the retrotransposed CGI on flanking CpG sites, a phenomenon that we described as "sloping shores." Computational analyses of human and mouse methylomic data at single-base resolution confirm that sloping shores are universal for hypomethylated CGIs in sperm and somatic tissues. Additionally, the slope of a hypomethylated CGI can be affected by closely positioned CGI neighbors. Finally, by tracing sloping shore dynamics through embryonic and germ cell reprogramming, we found evidence of bookmarking, a mechanism that likely determines which CGIs will be eventually hyper- or hypomethylated.

LINE-1-derived poly(A) microsatellites undergo rapid shortening and create somatic and germline mosaicism in mice.

Interspersed and tandem repeat sequences comprise the bulk of mammalian genomes. Interspersed repeats result from successive replication by transposable elements, such as Alu and long interspersed element type 1 (L1). Microsatellites are tandem repeats of 1-6 base pairs, among which poly(A) microsatellites are the most abundant in the human genome. The rise and fall of a microsatellite has been depicted as a life cycle. Previous studies have demonstrated that Alu and L1 insertions are a major source of A-rich microsatellites owing to the concurrent formation of a poly(A) DNA tract at the 3'-end of each insertion. The fate of such poly(A) tracts has been studied by surveying the length distribution of genomic resident Alu and L1 insertions. However, these cross-sectional studies provide no information about the tempo of mutation immediately after birth. In this study, de novo L1 insertions were created using a transgenic L1 mouse model and traced through generations to investigate the early life of poly(A) microsatellites. High frequencies of intra-individual and intergenerational shortening were observed for long poly(A) tracts, creating somatic and germline mosaicism at the insertion site, whereas little variation was observed for short poly(A) alleles. As poly(A) microsatellites are the major intrinsic signal for nucleosome positioning, their remarkable abundance and variability make them a significant source of epigenetic variation. Thus, the birth of poly(A) microsatellites from retrotransposons and the subsequent rapid and variable shortening represent a new way with which retrotransposons can modify the genetic and epigenetic architecture of our genome.

The effect of video game "warm-up" on performance of laparoscopic surgery tasks.

BACKGROUND: Performing laparoscopic procedures requires special training and has been documented as a significant source of surgical errors. "Warming up" before performing a task has been shown to enhance performance. This study investigates whether surgeons benefit from "warming up" using select video games immediately before performing laparoscopic partial tasks and clinical tasks. METHODS: This study included 303 surgeons (249 men and 54 women). Participants were split into a control (n=180) and an experimental group (n=123). The experimental group played 3 previously validated video games for 6 minutes before task sessions. The Cobra Rope partial task and suturing exercises were performed immediately after the warm-up sessions. RESULTS: Surgeons who played video games prior to the Cobra Rope drill were significantly faster on their first attempt and across all 10 trials. The experimental and control groups were significantly different in their total suturing scores (t=2.28, df=288, P<.05). The overall Top Gun score showed that the experimental group performed marginally better overall. CONCLUSION: This study demonstrates that subjects completing "warming-up" sessions with select video games prior to performing laparoscopic partial and clinical tasks (intracorporeal suturing) were faster and had fewer errors than participants not engaging in "warm-up." More study is needed to determine whether this translates into superior procedural execution in the clinical setting.

A traumatic abdominal wall hernia repair: a laparoscopic approach.

BACKGROUND: Traumatic abdominal wall hernias from blunt trauma usually occur as a consequence of motor vehicle collisions where the force is tangential, sudden, and severe. Although rare, these hernias can go undetected due to preservation of the skin overlying the hernia defect. Open repairs can be challenging and unsuccessful due to avulsion of muscle directly from the iliac crest, with or without bone loss. A laparoscopic approach to traumatic abdominal wall hernia can aid in the delineation of the hernia and allow for a safe and effective repair. CASE DESCRIPTION: A 36-year-old female was admitted to our Level 1 trauma center with a traumatic abdominal wall hernia located in the right flank near the iliac crest after being involved in a high-impact motor vehicle collision. Computed tomography and magnetic resonance imaging of the abdomen revealed the presence of an abdominal wall defect that was unapparent on physical examination. The traumatic abdominal wall hernia in the right flank was successfully repaired laparoscopically. One-year follow-up has shown no sign of recurrence. DISCUSSION: A traumatic abdominal wall hernia rarely presents following blunt trauma, but should be suspected following a high-impact motor vehicle collision. Frequently, repair is complicated by the need to have fixation of mesh to bony landmarks (eg, iliac crest). In spite of this challenge, the laparoscopic approach with tension-free mesh repair of a traumatic abdominal wall hernia can be accomplished successfully using an approach similar to that taken for laparoscopic inguinal hernia repair.

L1 expression and regulation in humans and rodents.

Long interspersed elements type 1 (LINE-1s, or L1s) have impacted mammalian genomes at multiple levels. L1 transcription is mainly controlled by its 5' untranslated region (5'UTR), which differs significantly among active human and rodent L1 families. In this review, L1 expression and its regulation are examined in the context of human and rodent development. First, endogenous L1 expression patterns in three different species-human, rat, and mouse-are compared and contrasted. A detailed account of relevant experimental evidence is presented according to the source material, such as cell lines, tumors, and normal somatic and germline tissues from different developmental stages. Second, factors involved in the regulation of L1 expression at both transcriptional and posttranscriptional levels are discussed. These include transcription factors, DNA methylation, PIWI-interacting RNAs (piRNAs), RNA interference (RNAi), and posttranscriptional host factors. Similarities and differences between human and rodent L1s are highlighted. Third, recent findings from transgenic mouse models of L1 are summarized and contrasted with those from endogenous L1 studies. Finally, the challenges and opportunities for L1 mouse models are discussed.

Presentation and minimally invasive treatment of a type IV giant paraesophageal hernia.

Paraesophageal hernias (PEHs) result from a defect of the diaphragmatic hiatus with a gradual enlargement of the hiatal opening, allowing abdominal contents to shift into the mediastinum. PEHs are often confused with sliding hiatal hernias; however, it is paramount that physicians understand the subtle presentation differences in the types of diaphragmatic incompetence, as treatment may vary greatly. The type IV giant PEH is a dangerous variant that, once recognized, usually requires surgical intervention. In recent years, the laparoscopic approach has been associated with decreases in morbidity, hospital stay, and time off work, as well as increased quality of life. This case involves the proper workup and minimally invasive treatment of a 56-year-old black female who presented with a symptomatic giant PEH with colon, stomach, and duodenum displacement into the chest.