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Tumor-homing neural stem cell (NSC) therapy is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tumor-homing NSC therapy therapies that maintain durable tumor suppression remains a challenge. Herein, we report a synergistic combination regimen where the novel small molecule TR-107 augments NSC-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy (hiNeuroS-TRAIL) in models of the incurable brain cancer glioblastoma (GBM) in vitro . We report that the combination of hiNeuroS-TRAIL and TR-107 synergistically upregulated caspase markers and restored sensitivity to the intrinsic apoptotic pathway by significantly downregulating inhibitory pathways associated with chemoresistance and radioresistance in the TRAIL-resistant LN229 cell line. This combination also showed robust tumor suppression and enhanced survival of mice bearing human xenografts of both solid and invasive GBMs. These findings elucidate a novel combination regimen and suggest that the combination of these clinically relevant agents may represent a new therapeutic option with increased efficacy for patients with GBM., Competing Interests: S.D.H. has ownership interest as the CSO of Falcon Therapeutics., (© 2024 The Authors. Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.)

Objectives: Burnout is common among junior faculty. Professional development has been proposed as a method to improve engagement and reduce burnout among academic physicians. The Penn State College of Medicine Junior Faculty Development Program (JFDP) is a well-established, interdisciplinary program. However, an increase in burnout was noted among participants during the program. The authors sought to quantify the change in burnout seen among JFDP participants across 3 cohorts, and to explore sources of well-being and burnout among participants., Methods: Through a sequential explanatory mixed methods approach, participants in the 2018/19, 2019/20, and 2020/21 cohorts took a survey assessing burnout (Copenhagen Burnout Inventory), quality of life (QoL), job satisfaction, and work-home conflict at the start and end of the course. Descriptive statistics were generated as well as Pearson χ 2 test/Fisher exact test for categorical variables and Wilcoxon rank sum tests for continuous variables for group comparisons. To better understand the outcome, past participants were invited to interviews regarding their experience of burnout during the course. Inductive thematic analysis (kappa = 0.86) was used to derive themes., Results: Start- and end-of-course surveys were completed by 84 and 75 participants, respectively (response rates: 95.5% and 85.2%). Burnout associated with patient/learner/client/colleague increased ( P  = .005) and QoL decreased ( P  = .02) at the end compared with the start. Nonsignificant trends toward worsening in other burnout categories, work-home conflict, and job satisfaction were also observed. Nineteen interviews yielded themes related to risks and protective factors for burnout including competing demands, benefits of networking, professional growth, and challenges related to diverse faculty roles., Conclusion: Junior Faculty Development Program participants demonstrated worsening of burnout and QoL during the program while benefiting from opportunities including skill building and networking. The impact of Junior Faculty Development Programs on the well-being of participants should be considered as an element of their design, evaluation, and refinement over time., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Hydrogels are a class of biomaterials widely implemented in medical applications due to their biocompatibility and biodegradability. Despite the many successes of hydrogel-based delivery systems, there remain challenges to hydrogel drug delivery such as a burst release at the time of administration, a limited ability to encapsulate certain types of drugs (i.e., hydrophobic drugs, proteins, antibodies, and nucleic acids), and poor tunability of geometry and shape for controlled drug release. This review discusses two main important advances in hydrogel fabrication for precision drug release: first, the incorporation of nanocarriers to diversify their drug loading capability, and second, the design of hydrogels using 3D printing to precisely control drug dosing and release kinetics via high-resolution structures and geometries. We also outline ongoing challenges and discuss opportunities to further optimize drug release from hydrogels for personalized medicine. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies., (© 2021 Wiley Periodicals LLC.)

Induced neural stem cells (iNSCs) have emerged as a promising therapeutic platform for glioblastoma (GBM). iNSCs have the innate ability to home to tumor foci, making them ideal carriers for antitumor payloads. However, the in vivo persistence of iNSCs limits their therapeutic potential. We hypothesized that by encapsulating iNSCs in the FDA-approved, hemostatic matrix FLOSEAL®, we could increase their persistence and, as a result, therapeutic durability. Encapsulated iNSCs persisted for 95 days, whereas iNSCs injected into the brain parenchyma persisted only 2 weeks in mice. Two orthotopic GBM tumor models were used to test the efficacy of encapsulated iNSCs. In the GBM8 tumor model, mice that received therapeutic iNSCs encapsulated in FLOSEAL® survived 30 to 60 days longer than mice that received nonencapsulated cells. However, the U87 tumor model showed no significant differences in survival between these two groups, likely due to the more solid and dense nature of the tumor. Interestingly, the interaction of iNSCs with FLOSEAL® appears to downregulate some markers of proliferation, anti-apoptosis, migration, and therapy which could also play a role in treatment efficacy and durability. Our results demonstrate that while FLOSEAL® significantly improves iNSC persistence, this alone is insufficient to enhance therapeutic durability., Competing Interests: Shawn D. Hingtgen has an ownership interest in Falcon Therapeutics, Inc., which has licensed aspects of iNSC technology from the University of North Carolina at Chapel Hill. Hunter N. Bomba, Abigail Carey‐Ewend, Kevin T. Sheets, Alain Valdivia, Morgan Goetz, Ingrid A. Findlay, Lauren E. Kass, and Simon Khagi have no competing interests to disclose., (© 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

The objective of this study is to understand patients' perspectives about system-based barriers that may influence decision-making regarding following discharge instructions. In this qualitative study, subjects were interviewed by phone 1-4 weeks following being discharged to home from the emergency department (ED). We used a semi-structured interview guide to ask a series of open-ended questions about subjects' recent ED visit and subsequent course, including discharge instructions, whether or not they complied with those instructions, and reasoning behind their decisions to follow-up or not. All interviews were recorded and transcribed to identify themes among the transcripts, which were analyzed to identify barriers to compliance. While the majority of those interviewed expressed no specific concerns or challenges, four system-based themes did emerge regarding patient attitudes toward and experiences with discharge instructions. They were: (1) failure to ensure clarity about diagnosis at the time of discharge from the ED, (2) failure to identify patients' feelings of hopelessness regarding the utility of follow-up, (3) difficulty in scheduling follow-up appointments, and (4) the importance of a clear discharge process. This study finds several system-based barriers might influence compliance. The four identified themes suggest a recurring cycle of visiting the ED, being discharged to primary care or specialists, and ultimately returning to the ED. We propose that systems-based interventions may help to break this cycle.

Objectives: The objectives were 1) to design systems ethnography roles for first-year medical students that could enhance student learning with regard to healthcare systems, ethnography, and systems thinking and 2) to describe strategies for other education programs seeking to implement systems ethnography roles in clinical settings., Methods: Fourteen medical students were educated about ethnography and systems thinking and linked with patients in the emergency department (ED) for 12 to 15 hours to observe patient experiences and clinical processes. Students submitted written assignments, participated in a debriefing exercise with ED and medical education leadership, and completed an electronic survey regarding educational benefits and perceived clinical value conferred to the ED using 5-point Likert-scale questions. Qualitative methods were used to analyze both students' assignments and notes taken during the debriefing session, including small-group report-outs and discussions, and to identify vulnerabilities in the patient experience., Results: Students identified one overarching theme of the patient experience-prolonged waiting in close proximity to the fast-paced, hectic "world" of the ED. Four key categories of systems vulnerabilities were identified through student observations: 1) patient experience; 2) communication and collaboration; 3) processes, physical space, and resources; and 4) professionalism. Students reported improved appreciation for challenges experienced by patients (3.92/5), importance of communication between providers and patients (3.92/5), and improved understanding of the patient experience while receiving care (3.77/5)., Conclusions: These results demonstrate how innovative systems ethnography experiences for medical students can provide unique educational opportunities while at the same time adding value by highlighting shortcomings in the care environment that can be used for system improvement.

Single breath counting (SBC) is the measurement of how far an individual can count in cadence with a metronome set at 2 beats per second in a normal speaking voice following a maximal effort inhalation. Previous work has demonstrated that it correlates well with standard measures of pulmonary function. The objective of this study is to derive a "normogram" of healthy children showing the expected SBC value as a function of easily measured physiologic parameters (age, gender, height, and weight). This was a prospective observational study of a convenience sample of healthy children presenting for well-child checks or non-respiratory complaints at a large tertiary care center. Correlation was determined by the Pearson's product correlation coefficient (r) and r (2) determined as a measure of shared variance. Multiple regression analysis was performed on demographic data to determine a best linear fit with calculation of the coefficient of determination (R (2)). A total of 105 children served as the basis for analysis; 54 (51.4 %) were male and average age was 9.7 (median 10, range 3-15) years. For both males and females, height correlated most strongly with SBC score (r = 0.730 and 0.725, respectively). In both genders, height alone accounted for more than 50 % of the observed variance in the results (r (2) = 0.533 and 0.526, respectively). Breath counting, an easy to perform test that appears to correlate well with standard measures of pulmonary function and shows promise for measuring asthma severity in children. We present an equation for predicting normal results (a "normogram").

A prospective, consecutive study was performed to determine if medical student supervision in the emergency department (ED) changes patient throughput time (ie, the time from triage to discharge). The mean patient throughput time on days when medical students were present in the ED (group 1) was compared to the mean patient throughput time on days when medical students were absent from the ED (group 2). Throughput time was measured in minutes. The mean throughput times of the two groups were compared by the two tailed t test (P < .05). The study had a power of 90% (beta = .10) to detect a throughput time difference of 20 minutes. The two groups were also compared for mean daily acuity (as gauged by mean daily number of patient admissions) and mean daily patient census. The differences in mean daily throughput times (group 1, 145.2 min v group II, 150.6 min; P = .40), mean daily census (group 1, 28.1 patients v group 2, 28.1 patients; P = .75), and mean daily admissions (group 1, 10.4 patients v group 2, 10.7 patients; P = .74) were all insignificant. Precepting medical students in this ED did not significantly change patient throughput times.

Society has a right to expect that all physicians possess basic knowledge of emergency care and the skills to manage acute problems. Competency in the care of acutely ill and injured patients is one of the fundamental exit goals of most medical schools as mandated by the Liaison Committee on Medical Education. Several groups have called for strengthening the general components of undergraduate medical education, and surveys during the early years of the development of the field of emergency medicine (EM) showed that only a small percentage of schools required significant education in EM. This paper defines the goals and objectives of undergraduate EM education in order to help guide the development of curricular offerings as the role of EM in undergraduate medical school education increases. This paper was developed by the SAEM Education Committee and presents this committee's beliefs on what all graduating medical students should know about assessment and treatment of acutely sick and injured patients. It also suggests methods by which acquisition of this information can occur in medical school education.

A 65-year-old man presented with an episode of loss of consciousness associated with a fever and headache. His history was significant for 1 year of short-term memory loss. Computed tomographic scanning showed a third ventricular mass that was ultimately resected and pathologically confirmed as a colloid cyst. The patient's postoperative course was complicated by a dense left hemiparesis. A brief discussion of colloid cysts of the third ventricle is presented.

Objective: To compare the changes in hematocrit (Hct) between phlebotomized and nonphlebotomized individuals given IV crystalloid., Methods: A prospective, crossover volunteer study was performed comparing Hct changes immediately and 30 minutes after IV crystalloid bolus in 20 healthy adults with and without prebolus phlebotomy. In the control portion, volunteers were given a 15-mL/kg bolus of normal saline over 30 minutes with Hct determination before (H1), immediately after (H2), and 30 minutes after (H3) crystalloid infusion. At least 7 days later, the same subjects were phlebotomized 1 unit of blood and then administered a 15-mL/kg IV bolus of normal saline 30 minutes later. Hcts were obtained before (H4) and 30 minutes after (H5) phlebotomy (immediately prior to crystalloid infusion). Hcts were also obtained immediately after (H6) and 30 minutes after (H7) crystalloid infusion. A post-hoc test performance analysis was then performed to determine the Hct drop thresholds that would yield the maximal sensitivity and specificity for 500 mL of blood loss (via phlebotomy) in this population., Results: The Hct (%) drops in the nonphlebotomized individuals receiving IV fluids averaged 4.5 +/- 1.3 immediately and 3.2 +/- 1.3 30 minutes after infusion. These drops were different (p < 0.05) from the Hct drop in individuals receiving IV fluids after phlebotomy, which averaged 6.6 +/- 1.5 and 5.7 +/- 1.1, respectively. Post-hoc analysis revealed that Hct drops of 5.4 immediately, or 4.3 at 30 minutes after infusion, had a sensitivity of > 90% and a specificity of 75% for identification of patients in the phlebotomy group., Conclusions: The practice of measuring serial Hcts may be helpful to identify trauma patients with occult blood loss. A prospective clinical trial is needed to validate these Hct drop thresholds (immediate and 30 minutes postinfusion) in crystalloid-resuscitated trauma patients.

Isolated fallopian tube torsion is a rare entity that most frequently occurs during the menstruating years, but has also been reported in premenopausal and postmenopausal women. Diagnosis of this condition is often delayed because of the rarity of its occurrence and prolonged investigations to rule out more common causes of acute abdominal pain. A case of a 13-year-old girl with isolated left fallopian tube torsion is presented. A high index of suspicion must be maintained for adnexal torsion in women with abdominal pain so that an attempt can be made to salvage the adnexal structures.

To evaluate the recently published Utstein algorithm (Ann Emerg Med 1991;20:861), the authors conducted a retrospective review of all advanced life support (ALS) trip sheets and hospital records of patients with prehospital cardiac arrests between January 1988 and December 1989. Telephone follow-up was used to determine 1-year survival rates. Of 713 arrests in the 24-month study period, 601 were of presumed cardiac etiology. Approximately 599 of these charts were available for analysis. One hundred ninety-three (32.2%) of these had return of spontaneous circulation (ROSC), 36 (6.0%) survived to hospital discharge, and 24 were alive at 1-year follow-up (4.0% of total or 67% of survivors to discharge). The Utstein style was found to be a useful algorithmic format for reporting prehospital cardiac arrest data in a manner that should allow direct comparison between emergency medical service (EMS) systems. Existing prehospital record-keeping practices (trip sheets) are easily adapted to this style of data collection, although certain data for the template (eg, resuscitations not attempted and alive at 1-year) are more difficult to ascertain. Additionally, the authors report their own experience during a 2-year period, including data that suggest that the majority of patients with cardiac arrest who survive to hospital discharge are still alive at 1 year.