10 research outputs found

    An Extended View of the Temporal Dynamics of Caspase Activity During the Extrinsic Pathway of Apoptosis in Jurkat T-Lymphocytes

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    Apoptosis, a process in which a cell systematically triggers its own death in response to DNA damage or external stimuli, is widely utilized in the body to maintain a homeostatic quantity of cells. Malfunctions in this process can result in numerous consequences, particularly tumor development. For a cell to undergo apoptosis, there are two major pathways, dependent upon the method of induction: the extrinsic and intrinsic pathways. The goal of this research is to elucidate the temporal dynamics of apoptosis in Jurkat T-lymphocytes with respect to caspase activity in the extrinsically-activated pathway, using fluorescence microscopy. Microfluidic devices were fabricated from polydimethylsiloxane (PDMS) and contained an antibody-coated channel. The devices were used for cellular capture of the lymphocytes to trap and observe cells in a controlled, sustainable- environment for a given duration. The antibody coated in the channel, anti-CD95, induces apoptosis through Fas receptor binding. The result of the antibody binding is the activation of a caspase enzyme, creating a destructive caspase cascade. General caspase activation was visualized over a 9-hour period with the fluorogenic caspase probe L-bisaspartic acid Rhodamine 110 (D2R). Derivatives of the fluorogenic probe containing sequences to specific caspases were used to monitor the first and last caspases to be activated in the apoptotic pathway. The derivative (IETD)2R was used to monitor the primary initiator caspase activation (caspase-8) and the (DEVD)2R for executioner caspase activation (caspase-3). The overall average caspase activity began 2.4 ± 0.6 hours post-induction and lasted 360 ± 60 minutes, caspase-8 activity was shown to start 1.8 ± 0.8 hours after induction and remain active for 120 ± 40 minutes, and caspase-3 activity started 5.2 ± 1.0 hours after induction, lasting 130 ± 60 minutes. Timing of caspase activation is an important field of study as it could be helpful in designing apoptosis-targeted therapies

    The Temporal Dynamics of Caspase-3 Activation in the Extrinsic Process of Apoptosis

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    Apoptosis is a process of cell death that occurs within the body. Caspases are a family of enzymes which activate each other to degrade cellular proteins leading to the death of the cell. The steps of apoptosis are well known, however the timing of caspase activity within the cell is not. The purpose of this research is to understand the temporal dynamics of the caspase-3 activation in the extrinsic pathway of apoptosis. Cells are examined by fluorescence microscopy using an affinity microfluidic device and a fluorogenic caspase probe derived from Rhodamine 110. Fluorescence is monitored over a period of 6 hours, indicating the level of caspase activity within the cell. This procedure is conducted for caspase-3 using a DEVD2R probe. Caspase-3 activity was shown to start 5.3 hours post-induction lasting 20-40 minutes. Understanding the timing of caspase activation could be helpful in designing apoptosis-targeted therapies

    Complications associated with Dermabond® during head and neck surgery: MAUDE and literature review.

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    INTRODUCTION: Dermabond® is a liquid surgical sealant containing 2-octyl-cyanoacrylate that has been widely used during head and neck surgeries. This study aims to provide a summary of adverse events related to Dermabond® in head and neck procedures as reported in the MAUDE database, and to report a complete overview of all documented adverse events related to Dermabond® use in current literature. METHODS: The US Food and Drug Administration\u27s Manufacturer and User Facility Device Experience (MAUDE) database was queried for reports of adverse events related to Dermabond® use from January 1, 2010, to February 1, 2020. Data were extracted from reports pertaining to head and neck procedures. In addition, literature review was performed from January 1970 to January 2021. Various adverse events related to Dermabond® were included in the study. RESULTS: We identified 32 adverse events, from which 29 (90.6%) were patient-related events and 3 (9.4%) were operator-related events. Of the patient-related events, contact dermatitis (CD) (20 [69.0%]) was the most common, followed by wound dehiscence (4 [13.8%]). All of the operator-related events were from inadvertent cut injury (3 [100%]). Following the literature review, adverse events of Dermabond® were categorized into CD, wound dehiscence, infection, and cut injury. CONCLUSION: Dermabond® demonstrated utility in various surgical procedures including head and neck surgeries but are associated with risks. This study identified adverse events associated with Dermabond®. Further studies are needed to establish the causation of contact dermatitis in certain populations

    Disasters on campus: A cross-sectional survey of college EMS systems\u27 preparedness to respond to mass casualty incidents

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    OBJECTIVE: The objective of this study was to assess the training and readiness levels of Collegiate Emergency Medical Service (EMS) providers to respond to mass casualty incidents (MCIs). METHODS: An anonymous cross-sectional survey of Collegiate EMS providers was performed. PARTICIPANTS: Participants were US-based EMS providers affiliated with the National Collegiate Emergency Medical Services Foundation. OUTCOME MEASURES: The main outcome measures were levels of EMS experience and MCI training, subjective readiness levels for responding to various MCI scenarios, and analyzing the effect of the COVID-19 pandemic on MCI response capabilities. RESULTS: Respondents had a median age of 21 years (interquartile range IQR 20, 22), with 86 percent (n = 96/112) being trained to the Emergency Medical Technician-Basic level. Providers reported participating in an average of 1.6 MCI trainings over the last four years (IQR, 1.0, 2.2). Subjective MCI response readiness levels were highest with active assailant attacks followed by large event evacuations, natural disasters, hazardous material (HAZMAT) incidents, targeted automobile ramming attacks, explosions, and finally bioweapons release. Disparate to this, only 18 percent of participants reported training in the fundamentals of tactical and disaster medicine. With respect to the effect of the COVID-19 pandemic on MCI readiness, 27 percent of respondents reported being less prepared, and there was a statistically significant decrease in subjective readiness to respond to HAZMAT incidents. CONCLUSION: Given low rates of MCI training but high rates of self-assessed MCI preparedness, respondents may overestimate their readiness to adequately respond to the complexity of a real-world MCI. More objective assessment measures are needed to evaluate provider preparedness

    Firearms-related injury and sex: a comparative National Trauma Database (NTDB) Study

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    Background Existing study findings on firearms-related injury patterns are largely skewed towards males, who comprise the majority of this injury population. Given the paucity of existing data for females with these injuries, we aimed to elucidate the demographics, injury patterns, and outcomes of firearms-related injury in females compared with males in the USA.Materials and methods A 7-year (2013–2019) retrospective review of the National Trauma Database was conducted to identify all adult patients who suffered firearms-related injuries. Patients who were males were matched (1:1, caliper 0.2) to patients who were females by demographics, comorbidities, injury patterns and severity, and payment method, to compare differences in mortality and several other post-injury outcomes.Results There were 196 696 patients admitted after firearms-related injury during the study period. Of these patients, 23 379 (11.9%) were females, 23 378 of whom were successfully matched to a male counterpart. After matching, females had a lower rate of in-hospital mortality (18.6% vs. 20.0%, p<0.001), deep vein thrombosis (1.2% vs. 1.5%, p=0.014), and had a lower incidence of drug or alcohol withdrawal syndrome (0.2% vs. 0.5%, p<0.001) compared with males.Conclusion Female victims of firearms-related injuries experience lower rates of mortality and complications compared with males. Further studies are needed to elucidate the cause of these differences.Level of evidence Level III

    The Effects of Attention Deficit Hyperactivity Disorder and Other Psychiatric Comorbidities to Outcomes in Trauma Patients

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    BACKGROUND: Psychiatric illnesses affect outcomes in trauma. Studies have examined the relationship between depression, schizophrenia, post-traumatic stress disorder, and other mental disorders with trauma, yet few have examined attention-deficit-hyperactivity disorder (ADHD). Attention-deficit-hyperactivity disorder has been suggested to increase the risk of injury, but severity and outcomes of the injury are not frequently studied. The relationship of additional psychiatric disorders in patients with ADHD to traumatic injury was also examined in this study. METHODS: A 5-year retrospective analysis was performed using the trauma registry of an urban ACS verified level 1 trauma center. Patients with ADHD were separated into ADHD Only and ADHD+ (having additional psychiatric comorbidities) and compared to a matched population of non-ADHD patients and patients with non-ADHD psychiatric disorders to analyze their demographics and outcomes. Descriptive statistics were used to analyze the data as appropriate. RESULTS: Seventy-three patients with ADHD were identified, with over half having additional psychiatric comorbidities (58.9%). The majority of ADHD patients were White (54.8%) vs Black (61.6%) at admission. At admission non-ADHD patients had significantly fewer psychiatric comorbidities (11%) compared to ADHD patients (58.9%). ADHD with psychiatric comorbidities patients had significantly higher ISS and longer hospital LOS. However, GCS and ICU LOS were not different between the two groups. CONCLUSIONS: Patients with ADHD were significantly more likely to have psychiatric comorbidities and experience worse outcomes compared to patients without ADHD

    Cricothyrotomy Online: Quality Assessment of Educational Videos on YouTube

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    BACKGROUND: Medical learners may use YouTube® videos to prepare for procedures. Videos are convenient and readily available, but without any uploading standards, their accuracy and quality for education are uncertain. We assessed the quality of emergency cricothyrotomy videos on YouTube through an expert panel of surgeons with objective quality metrics. METHODS: A YouTube® search for emergency cricothyrotomy was performed and results were filtered to remove animations and lectures. The 4 most-viewed videos were sent to a panel of trauma surgeons for evaluation. An educational quality (EQ) score was generated for each video based on its ability to explain the procedure indications, orient the viewer to the patient, provide accurate narration, provide clear views of procedure, identify relevant instrumentation and anatomy, and explain critical maneuvers. Reviewers were also asked if safety concerns were present and encouraged to give feedback in a free-response field. RESULTS: Four surgical attendings completed the survey. The median EQ score was 6 on a 7-point scale (95% CI [6, 6]). All but one of the individual parameters had a median EQ score of 6 (95% CI: indications [3, 7], orientation [5, 7], narration [6, 7], clarity [6, 7], instruments [6, 7], anatomy [6, 6], critical maneuvers [5, 6]). Safety received a lower EQ score (5.5, 95% CI [2, 6]). CONCLUSIONS: The most-viewed cricothyrotomy videos were rated positively by surgical attendings. Still, it is necessary to know if medical learners can distinguish high from low quality videos. If not, this suggests a need for surgical societies to create high-quality videos that can be reliably and efficiently accessed on YouTube®

    A multicenter, citywide report on recurrent violent injury

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    INTRODUCTION: The incidence of and risk factors for recurrent violent trauma are not well known. This information is needed to focus violence prevention efforts on at-risk cohorts. The purpose of this study was to determine the incidence of and risk factors for recurrence following violent injury in a large urban setting. We hypothesize that the overall incidence of recurrent violent injury is low but there are specific at-risk cohorts. METHODS: A retrospective, citywide study of patients who sustained blunt assault or penetrating trauma from 2013 to 2019 was performed. Patients were tracked across all trauma centers using their name and date of birth. The primary outcome was incidence of recurrent violent injury, which was calculated by dividing the number of readmitted patients by the number who survived previous admissions due to penetrating trauma or blunt assault. Associations between readmission and injury severity score, abbreviated injury score, age, sex, hospital, mechanism of injury (MOI), and disposition were determined. Kaplan-Meier curves were plotted to determine the incidence of recurrent injury over time. A multivariable Cox proportional hazard model was used to examine the relationships between characteristics at first admission and time-to-readmission. RESULTS: The recurrent injury rate was 836 patients (6.33%) out of 13,211 injured patients. Male, age 14-45 years old, discharge to jail or left against medical advice, and moderate/severe head injury were associated with re-injury. There was no association between recurrence and mechanism of injury or overall injury severity. Discharge to home was associated with a lower re-injury rate. CONCLUSION: The low recurrent injury rate despite high injury prevalence suggests injury prevention efforts should target this demographic and their non-injured peers

    Exposure to a Virtual Reality Mass-Casualty Simulation Elicits a Differential Sympathetic Response in Medical Trainees and Attending Physicians

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    BACKGROUND: Previous studies have demonstrated the use of virtual reality (VR) in mass-casualty incident (MCI) simulation; however, it is uncertain if VR simulations can be a substitute for in-person disaster training. Demonstrating that VR MCI scenarios can elicit the same desired stress response achieved in live-action exercises is a first step in showing non-inferiority. The primary objective of this study was to measure changes in sympathetic nervous system (SNS) response via a decrease in heart rate variability (HRV) in subjects participating in a VR MCI scenario. METHODS: An MCI simulation was filmed with a 360º camera and shown to participants on a VR headset while simultaneously recording electrocardiography (EKG) and HRV activity. Baseline HRV was measured during a calm VR scenario immediately prior to exposure to the MCI scenarios, and SNS activation was captured as a decrease in HRV compared to baseline. Cognitive stress was measured using a validated questionnaire. Wilcoxon matched pairs signed rank analysis, Welch\u27s t-test, and multivariate logistic regression were performed with statistical significance established at P \u3c.05. RESULTS: Thirty-five subjects were enrolled: eight attending physicians (two surgeons, six Emergency Medicine [EM] specialists); 13 residents (five Surgery, eight EM); and 14 medical students (six pre-clinical, eight clinical-year students). Sympathetic nervous system activation was observed in all groups during the MCI compared to baseline (P \u3c.0001) and occurred independent of age, sex, years of experience, or prior MCI response experience. Overall, 23/35 subjects (65.7%) reported increased cognitive stress in the MCI (11/14 medical students, 9/13 residents, and 3/8 attendings). Resident and attending physicians had higher odds of discordance between SNS activation and cognitive stress compared to medical students (OR = 8.297; 95% CI, 1.408-64.60; P = .030). CONCLUSIONS: Live-actor VR MCI simulation elicited a strong sympathetic response across all groups. Thus, VR MCI training has the potential to guide acquisition of confidence in disaster response

    Measures of crowding in the emergency department: A systematic review.

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    OBJECTIVES: Despite consensus regarding the conceptual foundation of crowding, and increasing research on factors and outcomes associated with crowding, there is no criterion standard measure of crowding. The objective was to conduct a systematic review of crowding measures and compare them in conceptual foundation and validity. METHODS: This was a systematic, comprehensive review of four medical and health care citation databases to identify studies related to crowding in the emergency department (ED). Publications that describe the theory, development, implementation, evaluation, or any other aspect of a \u27crowding measurement/definition\u27 instrument (qualitative or quantitative) were included. A measurement/definition instrument is anything that assigns a value to the phenomenon of crowding in the ED. Data collected from papers meeting inclusion criteria were: study design, objective, crowding measure, and evidence of validity. All measures were categorized into five measure types (clinician opinion, input factors, throughput factors, output factors, and multidimensional scales). All measures were then indexed to six validation criteria (clinician opinion, ambulance diversion, left without being seen (LWBS), times to care, forecasting or predictions of future crowding, and other). RESULTS: There were 2,660 papers identified by databases; 46 of these papers met inclusion criteria, were original research studies, and were abstracted by reviewers. A total of 71 unique crowding measures were identified. The least commonly used type of crowding measure was clinician opinion, and the most commonly used were numerical counts (number or percentage) of patients and process times associated with patient care. Many measures had moderate to good correlation with validation criteria. CONCLUSIONS: Time intervals and patient counts are emerging as the most promising tools for measuring flow and nonflow (i.e., crowding), respectively. Standardized definitions of time intervals (flow) and numerical counts (nonflow) will assist with validation of these metrics across multiple sites and clarify which options emerge as the metrics of choice in this crowded field of measure
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