Loss of developmentally derived Irf8+ macrophages promotes hyperinnervation and arrhythmia in the adult zebrafish heart.

Recent developments in cardiac macrophage biology have broadened our understanding of the critical functions of macrophages in the heart. As a result, there is further interest in understanding the independent contributions of distinct subsets of macrophage to cardiac development and function. Here, we demonstrate that genetic loss of interferon regulatory factor 8 (Irf8)-positive embryonic-derived macrophages significantly disrupts cardiac conduction, chamber function, and innervation in adult zebrafish. At 4 months post-fertilization (mpf), homozygous irf8st96/st96 mutants have significantly shortened atrial action potential duration and significant differential expression of genes involved in cardiac contraction. Functional in vivo assessments via electro- and echocardiograms at 12 mpf reveal that irf8 mutants are arrhythmogenic and exhibit diastolic dysfunction and ventricular stiffening. To identify the molecular drivers of the functional disturbances in irf8 null zebrafish, we perform single cell RNA sequencing and immunohistochemistry, which reveal increased leukocyte infiltration, epicardial activation, mesenchymal gene expression, and fibrosis. Irf8 null hearts are also hyperinnervated and have aberrant axonal patterning, a phenotype not previously assessed in the context of cardiac macrophage loss. Gene ontology analysis supports a novel role for activated epicardial-derived cells (EPDCs) in promoting neurogenesis and neuronal remodeling in vivo. Together, these data uncover significant cardiac abnormalities following embryonic macrophage loss and expand our knowledge of critical macrophage functions in heart physiology and governing homeostatic heart health.

Metabolomic changes following GenX and PFBS exposure in developing zebrafish.

Short chain per- and polyfluoroalkyl substances (PFAS), including hexafluoropropylene oxide dimer acid (GenX) and perfluorobutane sulfonate (PFBS), are replacement chemicals for environmentally persistent, long-chain PFAS. Although GenX and PFBS have been detected in surface and ground water worldwide, few studies provide information on the metabolic alterations or risks associated with their exposures. In this study, larval zebrafish were used to investigate the toxicity of early-life exposure to GenX or PFBS. Zebrafish were chronically exposed from 4 h post-fertilization (hpf) to 6 days post-fertilization (dpf) to 150 µM GenX or 95.0 µM PFBS. Ultra-high-performance liquid chromatography paired with high-resolution mass spectrometry was used to quantify uptake of GenX and PFBS into zebrafish larvae and perform targeted and untargeted metabolomics. Our results indicate that PFBS was 20.4 % more readily absorbed into the zebrafish larvae compared to GenX. Additionally, PFBS exposure significantly altered 13 targeted metabolites and 21 metabolic pathways, while GenX exposure significantly altered 1 targeted metabolite and 17 metabolic pathways. Exposure to GenX, and to an even greater extent PFBS, resulted in a number of altered metabolic pathways in the amino acid metabolism, with other significant alterations in the carbohydrate, lipid, cofactors and vitamins, nucleotide, and xenobiotics metabolisms. Our results indicate that GenX and PFBS impact the zebrafish metabolome, with implications of global metabolic dysregulation, particularly in metabolic pathways relating to growth and development.

Burn and Trauma Burden and Screening for Interpersonal Violence During the COVID-19 Pandemic.

INTRODUCTION: Nationwide shelter-in-place (SIP) orders during the pandemic have had long-lasting effects, including increased rates of domestic violence and interpersonal violence. Screening for violence varies by institution, which tool is used, and when. Given increases in burn and trauma admissions over the course of the pandemic, we sought to examine trends at our institution during this time period to better guide care and anticipate system-level effects. METHODS: We performed a retrospective cohort study of pediatric burn and adult burn and trauma patients at our level 1 trauma/burn center between March-May 2019 and March-May 2020. Home safety screening was performed by nursing staff using a 1-part screening questionnaire. Patients presenting before March 15, 2020, were defined as "pre-SIP; " between March 16-May 19, 2020, were "during SIP; " and those after May 19, 2020, were designated as "post-SIP." Descriptive and chi-square statistics were used. Demographic, injury patterns, and screening information were collected. RESULTS: Blunt trauma comprised 60% of injuries, followed by burns (30%) then penetrating injury (7%). Over the entire time period analyzed, 1822 patients had documented home safety screening; ∼2% of patients screened reported a safety concern pre-SIP, compared to 3% of patients during SIP. There were higher rates of burns and penetrating injury during SIP compared to other periods (P ≤ 0.0001). Home safety screening rates were 94%-95% pre- and during SIP, but dropped to 85% post-SIP (P < 0.0001). Home safety concerns were reported almost 2% of the time pre-SIP and 3% during SIP (P = 0.016). CONCLUSIONS: We noted an increase in trauma and burns during and after SIP orders, consistent with the experiences of other institutions. Implementation of a nurse-driven screening process demonstrated high compliance with appropriate referrals. The burden of burn and traumatic injury remains significant, highlighting a need for continued psychosocial screening and the provision of psychosocial support resources in the acute trauma setting.

Evaluation of Neural Regulation and Microglial Responses to Brain Injury in Larval Zebrafish Exposed to Perfluorooctane Sulfonate.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are biopersistent, global pollutants. Although some in vitro and epidemiological studies have explored the neurotoxic potential of perfluorooctane sulfonate (PFOS), a prevalent PFAS congener, it is unknown how developmental PFOS exposure affects neuronal signaling, microglia development, and microglial-neuron communication. OBJECTIVES: We sought to determine the extent to which PFOS exposure disrupts brain health, neuronal activity, and microglia-neuron communication during development. In addition, although PFOS impairs humoral immunity, its impact on innate immune cells, including resident microglia, is unclear. As such, we investigated whether microglia are cellular targets of PFOS, and, if so, whether disrupted microglial development or function could contribute to or is influenced by PFOS-induced neural dysfunction. METHODS: Zebrafish were chronically exposed to either a control solution [0.1% dimethyl sulfoxide (DMSO)], 7µM PFOS, 14µM PFOS, 28µM PFOS, or 64µM perfluorooctanoic acid (PFOA). We used in vivo imaging and gene expression analysis to assess microglial populations in the developing brain and to determine shifts in the microglia state. We functionally challenged microglia state using a brain injury model and, to assess the neuronal signaling environment, performed functional neuroimaging experiments using the photoconvertible calcium indicator calcium-modulated photoactivatable ratiometric integrator (CaMPARI). These studies were paired with optogenetic manipulations of neurons and microglia, an untargeted metabolome-wide association study (MWAS), and behavioral assays. RESULTS: Developmental PFOS exposure resulted in a shift away from the homeostatic microglia state, as determined by functional and morphological differences in exposed larvae, as well as up-regulation of the microglia activation gene p2ry12. PFOS-induced effects on microglia state exacerbated microglia responses to brain injury in the absence of increased cell death or inflammation. PFOS exposure also heightened neural activity, and optogenetic silencing of neurons or microglia independently was sufficient to normalize microglial responses to injury. An untargeted MWAS of larval brains revealed PFOS-exposed larvae had neurochemical signatures of excitatory-inhibitory imbalance. Behaviorally, PFOS-exposed larvae also exhibited anxiety-like thigmotaxis. To test whether the neuronal and microglial phenotypes were specific to PFOS, we exposed embryos to PFOA, a known immunotoxic PFAS. PFOA did not alter thigmotaxis, neuronal activity, or microglial responses, further supporting a role for neuronal activity as a critical modifier of microglial function following PFOS exposure. DISCUSSION: Together, this study provides, to our knowledge, the first detailed account of the effects of PFOS exposure on neural cell types in the developing brain in vivo and adds neuronal hyperactivity as an important end point to assess when studying the impact of toxicant exposures on microglia function. https://doi.org/10.1289/EHP12861.

Handoffs and the challenges to implementing teamwork training in the perioperative environment.

Perioperative handoffs are high-risk events for miscommunications and poor care coordination, which cause patient harm. Extensive research and several interventions have sought to overcome the challenges to perioperative handoff quality and safety, but few efforts have focused on teamwork training. Evidence shows that team training decreases surgical morbidity and mortality, and there remains a significant opportunity to implement teamwork training in the perioperative environment. Current perioperative handoff interventions face significant difficulty with adherence which raises concerns about the sustainability of their impact. In this perspective article, we explain why teamwork is critical to safe and reliable perioperative handoffs and discuss implementation challenges to the five core components of teamwork training programs in the perioperative environment. We outline evidence-based best practices imperative for training success and acknowledge the obstacles to implementing those best practices. Explicitly identifying and discussing these obstacles is critical to designing and implementing teamwork training programs fit for the perioperative environment. Teamwork training will equip providers with the foundational teamwork competencies needed to effectively participate in handoffs and utilize handoff interventions. This will improve team effectiveness, adherence to current perioperative handoff interventions, and ultimately, patient safety.

Team FIRST framework: Identifying core teamwork competencies critical to interprofessional healthcare curricula.

Interprofessional healthcare team function is critical to the effective delivery of patient care. Team members must possess teamwork competencies, as team function impacts patient, staff, team, and healthcare organizational outcomes. There is evidence that team training is beneficial; however, consensus on the optimal training content, methods, and evaluation is lacking. This manuscript will focus on training content. Team science and training research indicates that an effective team training program must be founded upon teamwork competencies. The Team FIRST framework asserts there are 10 teamwork competencies essential for healthcare providers: recognizing criticality of teamwork, creating a psychologically safe environment, structured communication, closed-loop communication, asking clarifying questions, sharing unique information, optimizing team mental models, mutual trust, mutual performance monitoring, and reflection/debriefing. The Team FIRST framework was conceptualized to instill these evidence-based teamwork competencies in healthcare professionals to improve interprofessional collaboration. This framework is founded in validated team science research and serves future efforts to develop and pilot educational strategies that educate healthcare workers on these competencies.

Outpatient Telemedicine Program in Vascular Surgery Reduces Patient Travel Time, Cost, and Environmental Pollutant Emissions.

BACKGROUND: We analyze the impact of outpatient telemedicine services on the travel burden of vascular surgery patients with regard to distance, time, and cost, as well as the emission of environmental pollutants. METHODS: Retrospective analysis was used to compare the patient travel expenditure and environmental impact associated with telemedicine encounters versus hypothetical in-person traditional consultations for all outpatient virtual care encounters with vascular surgery patients from October 2015 to October 2017. The primary outcomes measured were travel distance saved, travel time saved, travel costs saved, reduction in fuel consumption, and reduction in environmental pollutant emission. RESULTS: Over a two-year period, 146 outpatient telemedicine encounters were conducted among 87 unique patients (61 females, 26 males; mean age, 60 ± 13 years). The average one-way distance saved by the utilization of telemedicine services was 15.6 ± 6.3 miles, with an average roundtrip savings of 31.2 miles. The average one-way travel time saved was 19.5 ± 9.2 minutes, with an average roundtrip savings of 39 minutes. By using telemedicine services, these vascular surgery patients saved an average of $4.26 in gas and parking costs at each telemedicine encounter. The total reduction in passenger vehicle emission of environmental pollutants, including carbon dioxide, carbon monoxide, nitric oxides, and volatile organic compounds was 1632 kg, 42,867 g, 3160 g, and 4715 g, respectively, with a total of 194 gallons of gas saved from driving. CONCLUSIONS: Utilization of telemedicine services reduces the travel distance, time, and costs for vascular surgery patients. Outpatient telemedicine programs may also provide environmental benefit through the reduction of greenhouse gas and pollutant emissions.