Search

Purpose Service learning consists of service activities that respond to community-identified concerns, active learning about the population being served, and self-reflecting on the experience. The Service Learning Program (SLP) is a novel, student-led, longitudinal volunteering experience designed to address social determinants of health (SDOH) education in the undergraduate medical school curriculum. In this program, medical students complete requirements in three domains of service, education, and self-reflection over the span of one academic year. Methods and materials Participating students are sent surveys prior to and after a year of participation in SLP, which are aimed to measure changes in their perceived knowledge, attitudes, and skills in multiple domains related to service learning and social determinants of health. Results Over the course of the 2019-2020 year, 110 students who participated in SLP responded to both pre- and post-surveys. These students reported significant improvements in their confidence in various knowledge and skills related to SDOH, such as identifying vulnerable populations and assessing community needs. They also were more likely to report that learning about social determinants of health was 'very important' after participating the program. Conclusions Medical students participating in a longitudinal service learning program focused on SDOH can acquire knowledge and skills that will empower them to understand, advocate, and care for underserved populations as future physicians. This program provides a model for integrating service learning into undergraduate medical education.

NASA's Human Research Program's (HRP) Exploration Medical Capability (ExMC) Element adopted Systems Engineering (SE) principles and Model Based Systems Engineering (MBSE) tools to capture the system functions, system architecture, requirements, interfaces, and clinical capabilities for a future exploration medical system. There are many different stakeholders who may use the information in the model: systems engineers, clinicians (physicians, nurses, and pharmacists), scientists, and program managers. Many of these individuals do not have access to MBSE modeling tools or have never used these tools. Many of these individuals (clinicians, scientists, even program managers) may have no experience with SE in general let alone interpreting a systems model. The challenge faced by ExMC was how to present the content in the model to non-modelers in a way they could understand with limited to no training in MBSE or the Systems Modeling Language (SysML) without using the modeling tool. Therefore, from the model, ExMC created an HTML report that is accessible to anyone with a browser. When creating the HTML report, the ExMC SE team talked to stakeholders and received their feedback on what content they wanted and how to display this content. Factoring in feedback, the report arranges the content in a way that not only directs readers through the SE process taken to derive the requirements, but also helps them to understand the fundamental steps in an SE approach. The report includes links to source information (i.e., NASA documentation that describes levels of care) and other SE deliverables (e.g., Concept of Operations). These links were provided to aid in the understanding of how the team created this content through a methodical SE approach. This paper outlines the process used to develop the model, the data chosen to share with stakeholders, many of the model elements used in the report, the review process stakeholders followed, the comments received from the stakeholders, and the lessons ExMC learned through producing this HTML report.

Social media is an underutilized method for the surveillance of the patient perspective regarding their pharmacologic therapies. The purpose of this study was to investigate the nature of content posted on the social media platform Instagram with respect to the systemic acne medication isotretinoin. The search term "#accutane" was queried into Instagram to generate all public posts using this hashtag between February 1 and May 31, 2018. Four independent investigators then scrutinized posts for eligibility. Our inclusion criteria were posts written in English, accessible by URL, primarily focused on isotretinoin, and posted by users of the medication. Data regarding multiple variables (tone of post, reason for positive or negative elements, posting of a face or other body part, mention of side effects, etc.) from each individual post was then entered into a Microsoft Excel template. Of 7,661 posts, 3,082 were eligible. Among posts that contained negative tone (n=1312), this element was more commonly due to the presence of side effects (65%) than lack of improvement in skin appearance (33%). Overall, 1,263 posters (41%) mentioned adverse effects of oral isotretinoin, most commonly dry facial skin (17%), dry/cracked lips (16%), or arthralgias/myalgias (8%). Neuropsychiatric side effects were also documented, with users reporting fatigue (4%), mood changes (3%), and headache (2%). In conclusion, reported side effects of oral isotretinoin on Instagram closely tracked its known side effects in frequency. Social media may be a valuable tool to surveil the general pattern and burden of adverse effects for patients undergoing treatment of dermatologic conditions.

The coronavirus (COVID-19) pandemic temporarily suspended medical student involvement in clinical rotations, resulting in the need to develop virtual clinical experiences. The cancellation of clinical ophthalmology electives and away rotations reduces opportunities for exposure to the field, to network with faculty, conduct research, and prepare for residency applications. We review the literature and discuss the impact and consequences of COVID-19 on undergraduate medical education with an emphasis on ophthalmic undergraduate medical education. We also discuss innovative learning modalities used from medical schools around the world during the COVID-19 pandemic such as virtual didactics, online cases, and telehealth. Finally, we describe a novel, virtual neuro-ophthalmology elective created to educate medical students on neuro-ophthalmology foundational principles, provide research and presentation opportunities, and build relationships with faculty members. These innovative approaches represent a step forward in further improving medical education in ophthalmology during COVID-19 pandemic and beyond.

Background: While reconstruction of the medial patellofemoral ligament (MPFL) is one of the most frequently performed surgical procedures in skeletally immature patients with patellar instability, there is an inherent risk to the distal femoral physis during femoral tunnel placement Methods: This case report describes a distal femoral valgus deformity caused by partial lateral physeal growth arrest after MPFL reconstruction. Results: The acquired distal femoral valgus deformity was successfully treated with a distal femoral varus-producing osteotomy. Conclusion: This case highlights the importance of understanding the distal femoral anatomy and avoiding areas where the physis may be violated.

Introduction: We have previously established a tissue scale mathematical model with 5 coupled, ordinary differential equations (ODEs) describing the longitudinal relationship of vasculature, hypoxia, necrosis, immune infiltration, and tumor growth in a preclinical model of human epidermal growth factor receptor 2 positive (HER2+) breast cancer undergoing trastuzumab treatment. The purpose of this study is to expand this model to multiple scales (tissue and cellular) and to explicitly include the effects of combination trastuzumab-paclitaxel therapy as measured by time-resolved microscopy of in vitro HER2+ breast cancer cells. This requires interlacing experimental data and additional ODEs at the cellular scale to incorporate drug dynamics within the tissue scale model for overall tumor growth. An integrated multi-scale mathematical-experimental approachbridging in vivo and in vitro experimental data has potential to elucidate the optimal strategies for combination therapy for HER2+ breast cancer. Experimental: In vitro data was collected to longitudinally evaluate BT474 HER2+ human cancer cells growth when treated with trastuzumab (25-50 ug/ml) and/or paclitaxel (10-250 nmol/L) measured by time-resolved microscopy. Changes in confluence before and after treatment are recorded every 3 hours over the course of 7 days. Ongoing studies are quantifying the change in confluence for these cells with alternating dosing and timing of the two therapies. Modeling: Thein vivo, tissue-scale model parameters were calibrated using mean and 95% confidence intervals of tumor volume from caliper measurements, vasculature and hypoxia from imaging data, and necrosis from histology. The in vitro scale of the model is calibrated with confluence data for controls to define intervals for growth rates and carrying capacities. Experimental results for single drug applications are used to estimate cell death, and data from combinations of both the targeted anti-HER2 therapy and cytotoxic therapies provide estimates of synergistic drug effects. After calibration of parameters, the two scales of the model are coupled via the tumor volume and vasculature components to simulate the effects of combination therapy in vivo. Results and Discussion: The confluence data shows that trastuzumab dosing in combination with paclitaxel results in the greatest reduction in tumor cells than either drug alone (p < 0.05), and there are distinct differences in alternating the order and timing of these drugs. Further, preliminary results show that the model's in vitro scale equations can be calibrated with the available longitudinal data. As dosing of combination therapy in vitro provides the opportunity to quantify the effects of combination therapy that would not be feasible to collect in an in vivo setting, our aim is to generate experimentally testable predictions for improved combination therapy in vivo with our multiscale model. This is an important step for future clinical translation to provide temporal guidance of standard-of-care, combination therapies, potentially leading to significantly improved anticancer response in HER2+ breast cancer. We acknowledge the support of NCI U01CA174706, NCI R01CA186193, CPRIT RR160005, and ACS RSG-18-006-01-CCE. Citation Format: Jarrett AM, Shah A, Bloom MJ, Yankeelov TE, Sorace AG. A multi-scale mathematical model of combination targeted and cytotoxic therapy to evaluate treatment response in HER2+ breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-33.

The goal of this study is to experimentally and computationally investigate combination trastuzumab-paclitaxel therapies and identify potential synergistic effects due to sequencing of the therapies with in vitro imaging and mathematical modeling. Longitudinal alterations in cell confluence are reported for an in vitro model of BT474 HER2+ breast cancer cells following various dosages and timings of paclitaxel and trastuzumab combination regimens. Results of combination drug regimens are evaluated for drug interaction relationships based on order, timing, and quantity of dose of the drugs. Altering the order of treatments, with the same total therapeutic dose, provided significant changes in overall cell confluence (p in vitro data to simulate the tumor cell response to the individual therapies. A collective model merging the two individual drug response models was designed to investigate the potential mechanisms of synergy for paclitaxel-trastuzumab combinations. This collective model shows increased synergy for regimens where trastuzumab is administered prior to paclitaxel and suggests trastuzumab accelerates the cytotoxic effects of paclitaxel. The synergy derived from the model is found to be in agreement with the combination index, where both indicate a spectrum of additive and synergistic interactions between the two drugs dependent on their dose order. The combined in vitro results and development of a mathematical model of drug synergy has potential to evaluate and improve standard-of-care combination therapies in cancer.

Purpose: Optimization of drug synergy has potential to improve efficacy of combination treatments. Breast cancer that overexpresses the human epidermal growth factor receptor (HER2) has a higher chance of metastasis and recurrence compared to HER2- patients. Standard-of-care treatment typically includes chemotherapy (i.e., paclitaxel, doxorubicin) followed by or in combination with targeted antibody treatments (i.e., trastuzumab, pertuzumab). The purpose of this study is to investigate, the timing, order, and dosage of standard-of-care combination therapies and how they affect the overall efficacy of treatment in HER2+ breast cancer in vitro and in vivo. Experimental Procedure: BT474, HER2+ breast cancer cells were longitudinally evaluated with time resolved microscopy to measure changes in cell confluence (Incucyte). Cells were treated with combinations of trastuzumab (10-50 ug/ml) and paclitaxel (10-150 nmol/L) with alternating sequencing and timing (24, 48 hrs) of the therapies (N=8 replicates per combination). Cellular confluence was measured over 4 days and normalized percent changes were calculated. BT474 tumor-bearing mice (N=42) were treated singularly or in combination with alternating sequencing of trastuzumab (10 mg/kg) and doxorubicin (1.5 mg/kg). Tumors were evaluated for changes in tumor size and survival. An unpaired t-test was used for statistical comparisons for in vitro and in vivo studies. Assessment of cellular and tumor microenvironment influences on drug synergy are ongoing. Results: Experimental outcomes indicate that alternating order and dose play a crucial role in the anticancer efficacy and synergistic drug effects. Trastuzumab (25 ug/ml) dosing prior to paclitaxel (50 nmol) significantly decreased cell confluence compared to the same total therapeutic dose where paclitaxel was introduced first in vitro (p < 0.001). Similarly, trastuzumab dosing in vivo prior to a one dose of chemotherapy achieves the same tumor response as a two doses of chemotherapy administered simultaneously with trastuzumab (p < 0.001). Discussion and Conclusions: Sequencing of targeted and chemotherapies altered treatment response both in vivo and in vitro, resulting in differences in overall cancer cell death. In vitro longitudinal imaging can provide numerous combinations of treatments can be tested to ultimately find optimal treatments to test in vivo. Recent evidence also shows that targeted anti-HER2 therapy can alter vascularity, oxygenation, and immune cell infiltration in HER2+ breast cancer tumors; therefore, further investigations in the temporal effects of the tumor microenvironment are warranted. Improved temporal windows of anticancer effects for standard-of-care combination therapies could improve breast cancer treatment regimens and potentially minimize toxic side effects. Funding was provided by CPRIT RR160005 and ACS-RSG-18-006-01-CCE. Citation Format: Alay Shah, Angela Jarrett, Anum Syed, Thomas Yankeelov, Anna Sorace. Trastuzumab sensitizes HER2+ breast cancer to increase efficacy of chemotherapy in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 296.

A highly sensitive, selective and high-throughput liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for simultaneous quantification of sulfamethoxazole (SMZ) and trimethoprim (TMP) has been developed and validated using imipramine as an internal standard. The analytes were extracted from 50 µL human plasma using solid phase extraction (SPE) and separated on Thermo Hypersil Gold C18 (50 mm × 4.6 mm, 5 μm) column under isocratic conditions in a run time of 2.5 min. Detection was carried out by tandem mass spectrometer, interfaced with electro spray ionization and operating in positive ionization mode. The calibration curves were linear over the concentration range of 0.88–80 µg/mL for SMZ and 0.03–30 µg/mL for TMP. The intra- and inter-day accuracy and precision (% CV) evaluated at four quality control levels were within 93.5–105.0% and 1.3–7.2% respectively. The absolute recovery was greater than 81% for both the analytes at two concentration levels. Stability of SMZ and TMP was assessed under different storage conditions. The validated method was successfully applied for a bioavailability study in 12 healthy volunteers after oral administration of 800 mg of SMZ and 160 mg of TMP succinate tablet formulations under fasting condition.