Performance Differences in Elite National Basketball Association and Women's National Basketball Association Players Based Upon Whether the Dominant or Non-dominant Achilles Tendon Was Ruptured.

Background National Basketball Association (NBA) and Women's National Basketball Association (WNBA) players with Achilles tendon ruptures have previously been noted to have a significant decline in performance post-injury. There has been recent anecdotal evidence that elite players with dominant Achilles tendon ruptures may be able to return at a higher level of play post-rupture. Objective This study aimed to evaluate for any differences in performance in higher-performing NBA and WNBA players with dominant versus non-dominant Achilles tendon ruptures pre- and post-injury. Methods This study was conducted at the University of Pennsylvania, Department of Physical Medicine and Rehabilitation. NBA and WNBA players with an Achilles tendon rupture from 1990 to 2020 were identified. Only elite players, indicated by an average player efficiency rating (PER) of >15 in either of the three seasons pre/post-injury, were included. The average PER, offensive rating, defensive rating, and usage percentage were compared in the three seasons pre- and post-injury. Results Eighteen players met the inclusion criteria, and nine each were classified as dominant and non-dominant Achilles tendon ruptures based on their primary shooting hand. There was no significant difference between the dominant and non-dominant rupture groups in any outcomes pre-injury, including age. The non-dominant cohort had a significant decline in PER (20.04 vs. 14.16; p < 0.001) and offensive rating (110.33 vs. 101.56; p = 0.004) post-injury. There was no significant difference observed post-injury in defensive rating or usage percentage. The dominant cohort had no significant difference in any outcomes post-injury, returning to the same level of play as pre-injury. Despite no difference existing between the groups at baseline, the dominant group performed significantly better post-rupture with regard to PER (19.56 vs. 14.16; p < 0.001) and offensive rating (114.00 vs. 101.56; p < 0.001) versus the non-dominant group. Conclusion Elite NBA and WNBA players with dominant Achilles tendon ruptures had no change in performance post-injury, returning to the same level of production as pre-injury. Post-rupture, they demonstrated notably superior outcomes versus the non-dominant group with regard to PER and offensive rating. The non-dominant rupture group experienced the same decline in PER and offensive rating post-injury observed in previous studies. The data indicate that elite NBA and WNBA players with a dominant Achilles tendon rupture have a much more favorable recovery post-injury and are able to return to the same level of performance.

Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol.

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.

Tnfaip8 and Tipe2 Gene Deletion Ameliorates Immediate Proteoglycan Loss and Inflammatory Responses in the Injured Mouse Intervertebral Disc.

OBJECTIVE: TNFAIP8 and TIPE2 belong to TNFa-induced protein 8 (TNFAIP8/TIPE) family. They control apoptosis and direct leukocyte migration. Nucleus pulposus (NP) cell loss is a hallmark of intervertebral disc (IVD) degeneration in response to injury, and inflammation may cause pain. Here, we examined the effects of TNFAIP8/TIPE2 deficiency on the IVDs in mice with these genes deleted. DESIGN: Tail IVDs in Tnfaip8 or Tipe2 single and double knockout mice (Tnfaip8-/-, Tipe2-/-, and Tnfaip8/Tipe2 dko), and wild type (WT) controls were injured. The spine motion segments were stained with Safranin O to reveal proteoglycans. Macrophages were identified by immunostaining, and selected inflammatory marker and collagen gene expression was examined by Real Time PCR. RESULTS: The injured tail IVDs of Tnfaip-/-, Tipe2-/-, and Tnfaip8/Tipe2 dko mice all displayed higher levels of proteoglycans than WT controls. Fewer macrophages were found in the injured IVDs of Tipe2-/- and Tnfaip8/Tipe2 dko mice than WT. Il6, Adam8 and Col1 gene expression was downregulated in the injured IVDs of Tnfip8/Tipe2 dko mice. CONCLUSIONS: TNFAIP8 and TIPE2 loss of function ameliorated proteoglycan loss and inflammation in the injured IVDs. They may serve as molecular targets to preserve disc structure and reduce inflammation.

Trends in Point of Care Ultrasound Familiarity Among Undergraduate Medical Clerkship Educators.

OBJECTIVES: Despite growing use of point of care ultrasound (POCUS), there remains a paucity of data about familiarity with POCUS among educators who dictate curricular content in undergraduate medical education. This paper aims to longitudinally characterize the level of comfort and frequency of POCUS use among faculty involved in undergraduate clerkship education. METHODS: A web-based cross-sectional survey assessing comfort, frequency of use, and awareness of indications for POCUS among faculty involved in Internal Medicine, Family Medicine, and Surgery undergraduate clerkship education in a single urban academic medical center in 2016 and again in 2022. RESULTS: A total of 45 responses from 2016 and 30 responses from 2022 are included. The percentage of faculty "not comfortable" with performing POCUS decreased from 78% to 46%, although the overall change in comfort was not statistically significant. Comfort interpreting POCUS images, frequency of POCUS use, and familiarity with the clinical applications of POCUS all improved. Faculty identified multiple barriers to more frequent POCUS use. CONCLUSIONS: Over a six-year period at one urban, academic medical center, comfort with POCUS and frequency of use have increased slightly but remain low among core faculty responsible for clerkship education. There are still large gaps in knowledge and very few faculty regularly use POCUS, which can be attributed to multiple different barriers.

Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass.

OBJECTIVES: Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. DESIGN: Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. SETTING: This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. PATIENTS: One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index ( r = -0.225; ß = -0.037; p = 0.001 and proportion of perfused vessels: r = -0.17; ß = -0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O 2 /s/10 6 cells; p = 0.002). CONCLUSIONS: Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested.

The Effect of Kyphoplasty on Opioid Use in Patients With Vertebral Compression Fractures.

Objective The primary objective of this study was to assess opioid use in the 90 days following kyphoplasty (KP) compared to the period between compression fracture and KP. Methods All patients aged 50-85 who underwent KP following a newly diagnosed vertebral compression fracture (VCF) at a large, urban academic medical center between January 1st, 2015, and January 1st, 2023, were screened for inclusion. Patients were excluded if they had an opioid prescription in the month prior to the compression fracture, had a history of malignancy, or underwent concomitant or other surgical procedures in the 90 days following KP. Opioid measures, including the prescribed amount of morphine milliequivalents (MME) per day, number of opioid days, and total MME (MME per day x number of opioid days), in addition to numerical rating scale (NRS) pain scores, were analyzed pre- and post-KP. Results A total of 27 patients met the eligibility criteria, with a mean age of 69.7 and 59.2% being female. Sixteen patients (59%) had received an opioid prescription between compression fracture and KP (opioid group). The median differences pre- and post-KP in prescribed MMEs per day, number of opioid days, and total MMEs were 17.7 (p=.0009), 11.0 (p=.0004), and 232.5 (p<.0001), respectively. There was a significant difference in NRS pain scores in both the opioid group (6.25, p<.0001) and the non-opioid group (4.36, p<.0001) pre- and post-KP. Conclusion Our findings suggest that KP may be associated with a reduction in both opioid use and pain scores in opioid-naïve patients with VCFs. Larger studies that directly compare KP to conservative management are needed to fully assess the impact of KP on opioid and pain outcome measures.

First-Year Medical Students' Perceptions of Stigma Toward People With Opioid Use Disorder Before and After an Educational Intervention.

BACKGROUND: Stigma among medical trainees toward people with opioid use disorder (OUD) compounds the problems associated with opioid addiction. People with OUD who experience overt and implicit stigma from healthcare providers are less likely to seek and receive treatment, further restricting their access to already limited resources. The objective of our study was to assess an educational strategy to mitigate stigma toward people with OUD among first-year medical students. METHODS: This study assessed perceptions of stigma toward people with OUD among first-year medical students using an adaptation of a brief, validated opioid stigma scale before and after an educational intervention. The intervention consisted primarily of a recorded panel in which people with a history of OUD shared their experiences with stigma followed by small group discussions. RESULTS: After the educational intervention, students were more likely to respond that (1) they believed most people held negative beliefs about people with OUD and (2) they personally disagreed with negative statements about people with OUD. CONCLUSIONS: Educational interventions addressing stigma toward people with OUD are potentially effective and should be integrated into medical curricula. Such interventions are a crucial part of the effort to improve the medical care of people with OUD.

Outcomes for a Heat Illness Prevention Program in Outdoor Workers: A 9-Year Overview.

OBJECTIVE: To describe the outcomes effect of removing the medical surveillance component from a heat illness prevention program (HIPP) for outdoor workers from a Central Texas municipality. METHODS: Heat-related illness (HRI) frequency and workers' compensation (WC) cost were assessed retrospectively in a cohort of 329 workers from 2011-2019. During 2011-2017, the HIPP included training, acclimatization, and medical surveillance. In 2018-2019, a modified (mHIPP) was implemented that included training and acclimatization, but without medical surveillance. RESULTS: The HRI rate during HIPP averaged 19.5 per 1000 workers during the first 4 years, dropped to 1.01 per 1,000 workers over the next 3 years, (2015-2017), and increased during mHIPP, to 7.6 per 1,000 workers. DISCUSSION: Although the case increase during the mHIPP was small, medical surveillance may be an important component in lowering workforce HRI.

Investigation of Cerebral Mitochondrial Injury in a Porcine Survivor Model of Carbon Monoxide Poisoning.

INTRODUCTION: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV). One of the glaring gaps is the lack of rigorous experimental models that may recapitulate survivors of acute CO poisoning in the early phase. The primary objective of this preliminary study is to use our advanced swine platform of acute CO poisoning to develop a clinically relevant survivor model to perform behavioral assessment and MRI imaging that will allow future development of biomarkers and therapeutics. METHODS: Four swine (10 kg) were divided into two groups: control (n = 2) and CO (n = 2). The CO group received CO at 2000 ppm for over 120 min followed by 30 min of re-oxygenation at room air for one swine and 150 min followed by 30 min of re-oxygenation for another swine. The two swine in the sham group received room air for 150 min. Cerebral microdialysis was performed to obtain semi real-time measurements of cerebral metabolic status. Following exposures, all surviving animals were observed for a 24-h period with neurobehavioral assessment and imaging. At the end of the 24-h period, fresh brain tissue (cortical and hippocampal) was immediately harvested to measure mitochondrial respiration. RESULTS: While a preliminary ongoing study, animals in the CO group showed alterations in cerebral metabolism and cellular function in the acute exposure phase with possible sustained mitochondrial changes 24 h after the CO exposure ended. CONCLUSIONS: This preliminary research further establishes a large animal swine model investigating survivors of CO poisoning to measure translational metrics relevant to clinical medicine that includes a basic neurobehavioral assessment and post exposure cellular measures.

Quantifying interaction with robotic toys in pre-term and full-term infants.

Infants born pre-term are at an increased risk for developmental, behavioral, and motor delay and subsequent disability. When these problems are detected early, clinical intervention can be effective at improving functional outcomes. Current methods of early clinical assessment are resource intensive, require extensive training, and do not always capture infants' behavior in natural play environments. We developed the Play and Neuro Development Assessment (PANDA) Gym, an affordable, mechatronic, sensor-based play environment that can be used outside clinical settings to capture infant visual and motor behavior. Using a set of classification codes developed from the literature, we analyzed videos from 24 pre-term and full-term infants as they played with each of three robotic toys designed to elicit different types of interactions-a lion, an orangutan, and an elephant. We manually coded for frequency and duration of toy interactions such as kicking, grasping, touching, and gazing. Pre-term infants gazed at the toys with similar frequency as full-term infants, but infants born full-term physically engaged more frequently and for longer durations with the robotic toys than infants born pre-term. While we showed we could detect differences between full-term and pre-term infants, further work is needed to determine whether differences seen were primarily due to age, developmental delays, or a combination.

The association between specific narrative elements and patient perspectives on acute pain treatment.

BACKGROUND: Narratives are effective tools for communicating with patients about opioid prescribing for acute pain and improving patient satisfaction with pain management. It remains unclear, however, whether specific narrative elements may be particularly effective at influencing patient perspectives. METHODS: This study was a secondary analysis of data collected for Life STORRIED, a multicenter RCT. Participants included 433 patients between 18 and 70 years-old presenting to the emergency department (ED) with renal colic or musculoskeletal back pain. Participants were instructed to view one or more narrative videos during their ED visit in which a patient storyteller discussed their experiences with opioids. We examined associations between exposure to individual narrative features and patients' 1) preference for opioids, 2) recall of opioid-related risks and 3) perspectives about the care they received. RESULTS: Participants were more likely to watch videos featuring storytellers who shared their race or gender. We found that participants who watched videos that contained specific narrative elements, for example mention of prescribed opioids, were more likely to recall having received information about pain treatment options on the day after discharge (86.3% versus 72.9%, p = 0.02). Participants who watched a video that discussed family history of addiction reported more participation in their treatment decision than those who did not (7.6 versus 6.8 on a ten-point scale, p = 0.04). CONCLUSIONS: Participants preferentially view narratives featuring storytellers who share their race or gender. Narrative elements were not meaningfully associated with patient-centered outcomes. These findings have implications for the design of narrative communication tools.

Development of a novel observed structured clinical exam to assess clinical ultrasound proficiency in undergraduate medical education.

OBJECTIVES: A pilot study was performed to develop and test an observed structured clinical exam (OSCE) for clinical ultrasound in second-year medical students. The goal was to assess a longitudinal clinical ultrasound curriculum for medical students and to help determine readiness to perform ultrasound during clinical clerkships. METHODS: The OSCE contained 40 tasks over 30 min in a one-to-one examiner to examinee environment using standardized patients covering cardiac, pulmonary, and inferior vena cava (IVC) ultrasound exams along with 6 critical diagnoses. Examinees were assessed using a binary checklist approach. A two-way ANOVA analysis was performed to determine if there were differences between the day and session the OSCE was administered. Results are presented as mean ± standard deviation. RESULTS: One hundred fifty-two students were tested with an overall mean score of 64.9 ± 17.6%. Scores between the cardiac, IVC, and lung sections varied-67.8% ± 18.8%, 62.4% ± 26.2%, and 57.1% ± 20.6%, respectively. One hundred twenty-six (82.9%) answered at least one critical diagnosis incorrectly. Students in the late session performed better than the early session (1: 60% vs 2: 69%, p = .001). CONCLUSIONS: Students performed better in later sessions. Additionally, the number of questions left blank at the end of the exam suggests that the length of the OSCE should be evaluated. Incorporating critical diagnoses was challenging for examinees. The proposed OSCE is a valuable assessment tool that could be adapted to assess student's readiness to use clinical ultrasound prior to clerkships.

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

INTRODUCTION: Microcirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. METHODS: Adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. RESULTS: Of 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). CONCLUSIONS: Poor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Perceptions of the Availability of Personal Protective Equipment and Its Association With Burnout Among US Healthcare Personnel During the SARS-CoV-2 Pandemic, 2020-2021.

OBJECTIVE: The aim of the study is to explore associations among personal protective equipment (PPE) availability, workplace environment, and burnout among US healthcare personnel during the COVID-19 pandemic. METHODS: The study used an online healthcare provider (HCP) survey (December 2020-February 2021) regarding PPE confidence, availability, burnout, and workplace environment. RESULTS: Lack of appropriate PPE was reported by 27% of 799 US HCP surveyed. Burnout, reported by 77% of HCP, was more likely among females, those with fewer years of professional experience, and those with a higher desire to quit, and less likely for those who perceived PPE was adequate or their employer took all steps to minimize workplace risks. CONCLUSIONS: This study suggests that lack of adequate PPE can lead to HCP burnout, which may result in employees quitting. A pandemic preparedness plan that includes adequate PPE is essential for HCP well-being, patient health, and employer fiscal health.

COVID-19 vaccine uptake before and after a vaccine mandate at a major academic hospital: Trends by race/ethnicity and level of patient contact.

OBJECTIVES: To assess vaccine coverage rates before and after implementation of a COVID-19 vaccine mandate among Health care Personnel (HCP) and demographic characteristics associated with vaccine uptake Design, Setting, and Participants: Cohort study conducted among 10,889 hospital employees followed from Dec 16, 2020 - October 31, 2021, at a large academic hospital in Philadelphia. MAIN OUTCOME AND MEASURES: Time to COVID-19 vaccination and vaccine series completion rates before and after implementation of a COVID-19 vaccine mandate based on age, gender, race/ethnicity, and level of patient contact/occupational group. RESULTS: The vaccination series completion rate was 86.0% prior to mandate announcement, and increased to 98.7% after mandate implementation. Rates before mandate announcement were highest among Asians (96.2%), Whites (94.0%), males (89.7%), employees ≥ 65 years of age (95.2%), and employees with direct patient care (physicians, 99.0%, and nurses, 93.3%). Hospital educational initiatives (including Town Halls and discussions with Black and Hispanic employees with the lowest vaccination rates) appeared to improve uptake. The largest increase in series completion after mandate announcement occurred among Blacks, those of other/multiracial backgrounds, and Hispanics (35.6%, 22.4%, and 10.8%, respectively) as well as those with some or no direct patient contact (24.5% and 18.3%, respectively). Medical or religious exemptions were approved for 64 (<0.6%) employees and 38 (<0.4%) left their positions (8 voluntary, 30 involuntary) specifically due to the COVID-19 vaccine mandate. No clinically meaningful differences by age, gender, or race/ethnicity for those who were vaccinated under the mandate versus those who left their positions were noted. CONCLUSIONS AND RELEVANCE: These results suggest that while mandates may be challenging to institutions and enforcement unpopular, they play an important role in reducing hesitancy and securing high vaccination rates among HCP, a group at high risk of COVID-19 given their employment and who can be a source of disease transmission to patients.

Cell-Free DNA as a Biomarker in a Rodent Model of Chlorpyrifos Poisoning Causing Mitochondrial Dysfunction.

INTRODUCTION: Organophosphates (OPs) are a major public health problem worldwide due to ease of access and high toxicity lacking effective biomarkers and treatment. Cholinergic agents such as OPs and carbamates are responsible for many pesticide-related deaths. While the inhibition of AChE is thought to be the main mechanism of injury, there are other important pathways that contribute to the overall toxicity of OPs such as mitochondrial dysfunction. An existing gap in OP poisoning are biomarkers to gauge severity and prognosis. Cell-free DNA (cfDNA) are novel biomarkers that have gained increased attention as a sensitive biomarker of disease with novel use in acute poisoning. This study investigates alterations in cerebral mitochondrial function in a rodent model of chlorpyrifos poisoning with the use of cfDNA as a potential biomarker. METHODS: Twenty rodents were divided into two groups: Control (n = 10) and Chlorpyrifos (n = 10). Chlorpyrifos was administered through the venous femoral line with a Harvard Apparatus 11 Elite Syringe pump (Holliston, MA, USA) at 2 mg/kg. Animals were randomized to receive chlorpyrifos versus the vehicle (10% DMSO) for 60 min which would realistically present an acute exposure with continued absorption. At the end of the exposure (60 min), isolated mitochondria were measured for mitochondrial respiration along with measures of acetylcholinesterase activity, cfDNA, cytokines and western blot. RESULTS: The Chlorpyrifos group showed a significant decrease in heart rate but no change in the blood pressure. There was a significant increase in bulk cfDNA concentrations and overall decrease in mitochondrial respiration from brain tissue obtained from animals in the Chlorpyrifos group when compared to the Control group with no difference in acetylcholinesterase activity. In addition, there was a significant increase in both IL-2 and IL-12 in the Chlorpyrifos group. CONCLUSIONS: In our study, we found that the total cfDNA concentration may serve as a more accurate biomarker of OP exposure compared to acetylcholinesterase activity. In addition, there was an overall decrease in cerebral mitochondrial function in the Chlorpyrifos group when compared to the Control group.

Tnfa , Il6 , Cxcl1 , and Adam8 Genes Are the Early Markers After Mouse Tail Intervertebral Disc Injury.

OBJECTIVES: The early molecular events after intervertebral disc injury remain unclear. In this study, we aimed to compare inflammatory markers from 1 day to 4 wks after injury to have a comprehensive understanding of the intervertebral disc response to injury. DESIGN: Mouse tail intervertebral disc injury was induced by a needle puncture. Inflammatory marker gene expression and morphological changes were recorded at 1 day, 1 wk, and 4 wks after injury. RESULTS: Tnfa , Il6 , and Cxcl1 gene expression peaked at day 1 post-needle puncture of the mouse intervertebral disc, Adam8 gene expression peaked at 1-wk time point, while Tipe2 gene expression was upregulated at week 4 postinjury. F4/80 positive cells, likely to be macrophages, are present as early as day 1 in the injured intervertebral discs and consistently present at week 4 postinjury. Loss of Safranin O staining and increased histological scores of the injured intervertebral discs are consistent with progressive degeneration after injury. CONCLUSIONS: Inflammatory cytokines including Tnfa precede Tipe2 , suggesting that Tipe2 is likely induced by Tnfa . Upregulation of Adam8 and Cxcl1 gene expression persisted at week 4, suggesting that they play a role in the transition to chronic phase of intervertebral disc degeneration.

Best Practices for Implementation of an Employee Health COVID-19 Vaccine Clinic-A Model for Future Pandemic Preparedness.

OBJECTIVES: The aims of the study are to determine best practices from two large-scale, academic medical centers' employee coronavirus 2019 (COVID-19) vaccination clinics and to apply them to create scalable modules for rapid administration of 10,000 vaccinations. METHODS: The weekly number of COVID-19 vaccine doses administered was captured. Processes were compared to determine best practices, which informed the scalable financial model. RESULTS: Within the first 3 months, more than 60,000 COVID-19 vaccine doses were administered, and 70% of employees were fully vaccinated in 4 months with more than 95% by the vaccine mandate deadline. The estimated cost of delivering one dose was $29.95 ($299,505/10,000) compared with $35-$39 per dose when delivered by an on-site retail pharmacy. CONCLUSIONS: Successful, safe, and rapid delivery of more than 60,000 COVID-19 vaccine doses in 3 months is practical and scalable. Learnings go beyond COVID-19 and can be applied to future outbreaks/pandemics.

Personalized risk communication and opioid prescribing in association with nonprescribed opioid use: A secondary analysis of a randomized controlled trial.

BACKGROUND: To determine the impact of personalized risk communication and opioid prescribing on nonprescribed opioid use, we conducted a secondary analysis of randomized controlled trial participants followed prospectively for 90 days after an emergency department (ED) visit for acute back or kidney stone pain. METHODS: A total of 1301 individuals were randomized during an encounter at four academic EDs into a probabilistic risk tool (PRT) arm, a narrative-enhanced PRT arm, or a general risk information arm (control). In this secondary analysis, both risk tool arms were combined and compared with the control arm. We used logistic regressions to determine associations between receiving personalized risk information, receiving an opioid prescription in the ED, and nonprescribed opioid use in general and by race. RESULTS: Complete follow-up data were available for 851 participants; 23.3% (n = 198) were prescribed opioids (34.2% of White vs. 11.6% of Black participants, p < 0.001). Fifty-six (6.6%) participants used nonprescribed opioids. Participants in the personalized risk communication arms had lower nonprescribed opioid use odds (adjusted odds ratio [aOR] 0.58, 95% confidence interval [CI] 0.4-0.83). Black versus White participants had greater nonprescribed opioid use odds (aOR 3.47, 95% CI 2.05-5.87, p < 0.001). Black participants who were prescribed opioids had a lower marginal probability of using nonprescribed opioids versus those who were not (0.06, 95% CI 0.04-0.08, p < 0.001 vs. 0.10, 95% CI 0.08-0.11, p < 0.001). The absolute risk difference in nonprescribed opioid use for Black and White participants, respectively, in the risk communication versus the control arm, was 9.7% and 0.1% (relative risk ratio 0.43 vs. 0.95). CONCLUSIONS: Among Black but not White participants, personalized opioid risk communication and opioid prescribing were associated with lower odds of nonprescribed opioid use. Our findings suggest that racial disparities in opioid prescribing-which have been previously described within the context of this trial-may paradoxically increase nonprescribed opioid use. Personalized risk communication may effectively reduce nonprescribed opioid use, and future research should be designed specifically to explore this possibility in a larger cohort.