Regulation of vascular endothelial integrity by mesenchymal stem cell extracellular vesicles after hemorrhagic shock and trauma.

BACKGROUND: Patients with hemorrhagic shock and trauma (HS/T) are vulnerable to the endotheliopathy of trauma (EOT), characterized by vascular barrier dysfunction, inflammation, and coagulopathy. Cellular therapies such as mesenchymal stem cells (MSCs) and MSC extracellular vesicles (EVs) have been proposed as potential therapies targeting the EOT. In this study we investigated the effects of MSCs and MSC EVs on endothelial and epithelial barrier integrity in vitro and in vivo in a mouse model of HS/T. This study addresses the systemic effects of HS/T on multiorgan EOT. METHODS: In vitro, pulmonary endothelial cell (PEC) and Caco-2 intestinal epithelial cell monolayers were treated with control media, MSC conditioned media (CM), or MSC EVs in varying doses and subjected to a thrombin or hydrogen peroxide (H2O2) challenge, respectively. Monolayer permeability was evaluated with a cell impedance assay, and intercellular junction integrity was evaluated with immunofluorescent staining. In vivo, a mouse model of HS/T was used to evaluate the effects of lactated Ringer's (LR), MSCs, and MSC EVs on endothelial and epithelial intercellular junctions in the lung and small intestine as well as on plasma inflammatory biomarkers. RESULTS: MSC EVs and MSC CM attenuated permeability and preserved intercellular junctions of the PEC monolayer in vitro, whereas only MSC CM was protective of the Caco-2 epithelial monolayer. In vivo, both MSC EVs and MSCs mitigated the loss of endothelial adherens junctions in the lung and small intestine, though only MSCs had a protective effect on epithelial tight junctions in the lung. Several plasma biomarkers including MMP8 and VEGF were elevated in LR- and EV-treated but not MSC-treated mice. CONCLUSIONS: In conclusion, MSC EVs could be a potential cell-free therapy targeting endotheliopathy after HS/T via preservation of the vascular endothelial barrier in multiple organs early after injury. Further research is needed to better understand the immunomodulatory effects of these products following HS/T and to move toward translating these therapies into clinical studies.

In Situ Enhancement and Isotopic Labeling of Biogenic Coalbed Methane.

Subsurface microbial (biogenic) methane production is an important part of the global carbon cycle that has resulted in natural gas accumulations in many coal beds worldwide. Laboratory studies suggest that complex carbon-containing nutrients (e.g., yeast or algae extract) can stimulate methane production, yet the effectiveness of these nutrients within coal beds is unknown. Here, we use downhole monitoring methods in combination with deuterated water (D2O) and a 200-liter injection of 0.1% yeast extract (YE) to stimulate and isotopically label newly generated methane. A total dissolved gas pressure sensor enabled real-time gas measurements (641 days preinjection and for 478 days postinjection). Downhole samples, collected with subsurface environmental samplers, indicate that methane increased 132% above preinjection levels based on isotopic labeling from D2O, 108% based on pressure readings, and 183% based on methane measurements 266 days postinjection. Demonstrating that YE enhances biogenic coalbed methane production in situ using multiple novel measurement methods has immediate implications for other field-scale biogenic methane investigations, including in situ methods to detect and track microbial activities related to the methanogenic turnover of recalcitrant carbon in the subsurface.

Temporal mapping of the closure of the anterior fontanelle and contiguous sutures using computed tomography, in silico models of modern infants.

The aim of this study is to quantify and statistically model the age-related decline in the fibrous connective tissue interface of the anterior fontanelle in modern Australian infants, using three-dimensional, semi-automated computed-assisted design protocols. Non-linear regression with variance models, using power functions, combined with quantile regression of the 5th and 95th population percentiles, were utilised to assess absolute anterior fontanelle surface area (AFSA) as a function of age, using multi-slice cranial computed tomography scans obtained from 256 infants aged < 30 months (males: n = 126, females: n = 109) from Brisbane children's hospitals. Normalised AFSA (NFSA), standardised for variation in cephalic size, followed a progressive decline from birth, the greatest velocity change occurring between the 3-6 and 6-9 month cohorts. Growth of the neurocranium is the most significant within the first 8 months postpartum, with a mean increase of 19.03 mm in maximum cranial length and 10.04 mm in breadth. Directionality of fontanelle closure, quantified using spline curves refutes fundamental assumptions that the anterior fontanelle is consistent with a quadrilateral, and contiguous sutures exhibit constant velocity of closure. The present study provides normative values for fontanelle size and diameters as well as new predictive non-linear models for age substantiation, screening of developmental abnormalities and indicators of suspected child maltreatment in modern infants aged birth to 30 months.

Invasive Aspergillus Laryngotracheobronchitis in an Adult with Primary CNS Lymphoma.

Invasive aspergillosis can be difficult to diagnose, and early recognition and initiation of therapy is imperative for improving patient outcomes. A case of invasive Aspergillus laryngotracheobronchitis is presented here with a review of the relevant literature. A 58-year-old male undergoing treatment for CNS lymphoma presented with neutropenic sepsis and acute respiratory distress requiring intubation. Following extubation, he reported persistent hoarseness for 1-month duration and he was found to have pseudomembranous plaques and ulcers of the larynx, trachea, and right mainstem bronchus consistent with Aspergillus laryngotracheobronchitis. Invasive Aspergillus laryngotracheobronchitis should be considered in immunocompromised patients presenting with persistent hoarseness.

Handoffs and transitions in critical care (HATRICC): protocol for a mixed methods study of operating room to intensive care unit handoffs.

BACKGROUND: Operating room to intensive care unit handoffs are high-risk events for critically ill patients. Studies in selected patient populations show that standardizing operating room to intensive care unit handoffs improves information exchange and decreases errors. To adapt these findings to mixed surgical populations, we propose to study the implementation of a standardized operating room to intensive care unit handoff process in two intensive care units currently without an existing standard process. METHODS/DESIGN: The Handoffs and Transitions in Critical Care (HATRICC) study is a hybrid effectiveness- implementation trial of operating room to intensive care unit handoffs. We will use mixed methods to conduct a needs assessment of the current handoff process, adapt published handoff processes, and implement a new standardized handoff process in two academic intensive care units. Needs assessment: We will use non-participant observation to observe the current handoff process. Focus groups, interviews, and surveys of clinicians will elicit participants' impressions about the current process. Adaptation and implementation: We will adapt published standardized handoff processes using the needs assessment findings. We will use small group simulation to test the new process' feasibility. After simulation, we will incorporate the new handoff process into the clinical work of all providers in the study units. EVALUATION: Using the same methods employed in the needs assessment phase, we will evaluate use of the new handoff process. DATA ANALYSIS: The primary effectiveness outcome is the number of information omissions per handoff episode as compared to the pre-intervention period. Additional intervention outcomes include patient intensive care unit length of stay and intensive care unit mortality. The primary implementation outcome is acceptability of the new process. Additional implementation outcomes include feasibility, fidelity and sustainability. DISCUSSION: The HATRICC study will examine the effectiveness and implementation of a standardized operating room to intensive care unit handoff process. Findings from this study have the potential to improve healthcare communication and outcomes for critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02267174. Date of registration October 16, 2014.

Tooth size discrepancies in Class II division 1 and Class III malocclusion requiring surgical-orthodontic or orthodontic treatment.

OBJECTIVE: To compare mean anterior (AR) and mean overall (OR) tooth size ratios, prevalence of clinically significant tooth size discrepancies (TSDs) and correlation between AR and OR in subjects with Class II division 1 and Class III malocclusion treated by surgical-orthodontic or orthodontic means. DESIGN: Retrospective, cross-sectional. SETTING: State-funded and private clinics. PARTICIPANTS: From pre-treatment cohorts of 770 surgical and 610 non-surgical subjects, Class II division 1 and Class III malocclusion groups were identified with 60 surgical and 60 non-surgical subjects, comprising 30 males and 30 females, in each. METHODS: AR and OR were calculated by landmarking digital models. Differences in AR and OR and their relationship were analysed using two-way analysis of variance (ANOVA) and a correlation coefficient, respectively. The proportions of the surgical and non-surgical groups with a TSD were assessed using logistic regression. Intra-examiner reproducibility involved re-landmarking 30 randomly selected image sets and differences in ARs and ORs were compared using a paired t-test. Random error was assessed using the intraclass correlation coefficient (ICC). Analyses were performed using SAS (SAS Institute Inc., Cary, NC, USA) at the 5% level of significance. RESULTS: There were no statistically significant differences associated with the measurement of either the mean AR (P = 0·913) or the mean OR (P = 0·874). ICC values were very high (AR = 0·95; OR = 0·90). Differences existed between both Class II and Class III surgical (AR: P<0·001; OR: P<0·001) and non-surgical groups (AR: P = 0·012; OR: P = 0·003). The AR and OR relationship was strong (correlation coefficient = 0·72). The highest percentage of clinically significant TSDs was seen in the AR of both Class II and Class III surgical groups (23·3%). CONCLUSIONS: In the cohort examined: AR and OR differed significantly for malocclusion groups. The prevalence of clinically significant TSDs did not differ significantly between surgical and non-surgical groups although the highest percentage of clinically significant TSDs was recorded for AR in Class II and Class III surgical cases. AR and OR were closely related.

Regulation of Vascular Endothelial Integrity by Mesenchymal Stem Cell Extracellular Vesicles after Hemorrhagic Shock and Trauma.

BACKGROUND: Patients with hemorrhagic shock and trauma (HS/T) are vulnerable to the endotheliopathy of trauma (EOT), characterized by vascular barrier dysfunction, inflammation, and coagulopathy. Cellular therapies such as mesenchymal stem cells (MSCs) and MSC extracellular vesicles (EVs) have been proposed as potential therapies targeting the EOT. In this study we investigated the effects of MSCs and MSC EVs on endothelial and epithelial barrier integrity in vitro and in vivo in a mouse model of HS/T. This study addresses systemic effects of HS/T on multiorgan EOT in HS/T model. METHODS: In vitro, pulmonary endothelial cell (PEC) and Caco-2 intestinal epithelial cell monolayers were treated with control media, MSC conditioned media (CM), or MSC EVs in varying doses and subjected to a thrombin or hydrogen peroxide (H2O2) challenge, respectively. Monolayer permeability was evaluated with a cell impedance assay, and intercellular junction integrity was evaluated with immunofluorescent staining. In vivo, a mouse model of HS/T was used to evaluate the effects of lactated Ringer's (LR), MSCs, and MSC EVs on endothelial and epithelial intercellular junctions in the lung and small intestine as well as on plasma inflammatory biomarkers. RESULTS: MSC EVs and MSC CM attenuated permeability and preserved intercellular junctions of the PEC monolayer in vitro, whereas only MSC CM was protective of the Caco-2 epithelial monolayer. In vivo, both MSC EVs and MSCs mitigated the loss of endothelial adherens junctions in the lung and small intestine, though only MSCs had a protective effect on epithelial tight junctions in the lung. Several plasma biomarkers including MMP8 and VEGF were elevated in LR- and EV-treated but not MSC-treated mice. CONCLUSIONS: In conclusion, MSC EVs could be a potential cell-free therapy targeting endotheliopathy after HS/T via preservation of the vascular endothelial barrier in multiple organs early after injury. Further research is needed to better understand the immunomodulatory effects of these products following HS/T and to move toward translating these therapies into clinical studies.

Impact of Social Vulnerability on Long-Term Growth Outcomes in Sutureless Versus Sutured Repair of Gastroschisis.

INTRODUCTION: The purpose of this study is to describe the long-term growth and nutrition outcomes of sutureless versus sutured gastroschisis repair. We hypothesized that weight z-score at 1 year would be affected by social determinants of health measured by the U.S. Centers for Disease Control Social Vulnerability Index (SVI). MATERIALS AND METHODS: We conducted a single-center retrospective review of patients who underwent gastroschisis repair (n = 97) from 2007 to 2018. Growth z-scores collected through 5 years of age and long-term clinical outcomes were compared based on the closure method and the type of gastroschisis (simple vs. complicated). Multiple regression analysis was performed to identify the impact of SVI themes and other covariates on weight for age z-score at 1 year. RESULTS: In total, 46 patients underwent sutureless repair and 51 underwent sutured repair with median follow-up duration of 2.5 and 1.9 years, respectively. Weight and length z-scores decreased after birth but normalized within the first year of life. Growth and long-term clinical outcomes were similar regardless of the closure method, while patients with complicated gastroschisis had higher rates of hospitalizations, small bowel obstructions, and additional abdominal surgeries. Using multiple regression, both low discharge weight and high SVI in the "minority status and language" theme were associated with lower weight for age z-scores at 1 year (p = 0.003 and p = 0.03). CONCLUSION: Sutureless and sutured gastroschisis repairs result in similar growth and long-term outcomes. Patients living in areas with greater social vulnerability may be at increased risk of poor weight gain. Patients should be followed at least through their first year to ensure appropriate growth.

Superlensing enables radio communication and imaging underwater.

Wireless radio communications provide a backbone to our technological civilization. However, radio communications are widely believed to be impossible in many situations where radios are surrounded by conductive media, such as underwater or underground, thus making ocean exploration difficult and creating well-known mine safety problems. In addition, since most imaging techniques rely on electromagnetic waves, the difficulty of electromagnetic wave propagation through biological tissues, which are mostly made of water, also severely limits bioimaging. Here we show that contrary to common beliefs, radio signals may be efficiently propagated through water over useful distances. Both radio communication and radio imaging through water may be enabled by superlensing of surface electromagnetic waves propagating along the water surface. We have demonstrated underwater radio communication over distances of several hundred skin depth in the MHz frequency range, which would require sensitivity below 10-100 W in a conventional radio communication channel. We also demonstrated subwavelength super-resolution radio imaging in the GHz range by using water surface as a superlens. Our results indicate new ways to perform bioimaging, as well as marine life safe techniques of wireless radio communication and imaging underwater, which are essential for ocean and seafloor exploration. We also anticipate that the developed techniques will provide invaluable means of studying the extraterrestrial water worlds, such as potentially inhabitable Jovian moons.

Histone deacetylase-6 modulates the effects of 4°C platelets on vascular endothelial permeability.

Platelets (PLTs) stored at 4°C exhibit equivalent or superior hemostatic function compared with 22°C PLTs, but have shorter circulation times and a decreased ability to modulate vascular permeability. These differences may be due to morphological changes and storage-induced activation. Using a proteomics-based approach, we found that 4°C-stored PLTs express decreased α-tubulin, a key PLT structural protein. PLT activation is characterized by α-tubulin deacetylation, which is regulated by histone deacetylase-6 (HDAC-6). We hypothesized that inhibition of HDAC-6 in stored PLTs will improve their ability to regulate vascular permeability through reduced activation and α-tubulin deacetylation. In an in vivo model of vascular permeability, treatment of 4°C PLTs with the HDAC-6 inhibitor tubacin enhanced the vasculoprotective properties of untreated 4°C PLTs. 4°C PLT circulation, however, was unchanged by tubacin treatment, suggesting that circulation time may not be a critical factor in determining the vasculoprotective effects of PLTs. Assessing the factor content of stored PLTs revealed that angiopoietin-1 (Ang-1) increased in 4°C PLTs over time, which was further enhanced by tubacin treatment. In addition, angiopoietin-2, an inducer of vascular leak and antagonist of Ang-1, inhibited PLT barrier protection, suggesting involvement of the Tie-2 pathway. This study demonstrates that HDAC-6 inhibition with tubacin attenuates the diminished vasculo-protective properties of 4°C PLTs, and these properties may be independent of PLT circulation time.

Targeting repair of the vascular endothelium and glycocalyx after traumatic injury with plasma and platelet resuscitation.

Severely injured patients with hemorrhagic shock can develop endothelial dysfunction, systemic inflammation, and coagulation disturbances collectively known as the endotheliopathy of trauma (EOT). Shedding of the endothelial glycocalyx occurs early after injury, contributes to breakdown of the vascular barrier, and plays a critical role in the pathogenesis of multiple organ dysfunction, leading to poor outcomes in trauma patients. In this review we discuss (i) the pathophysiology of endothelial glycocalyx and vascular barrier breakdown following hemorrhagic shock and trauma, and (ii) the role of plasma and platelet transfusion in maintaining the glycocalyx and vascular endothelial integrity.

RECOVERY OF ENDOTHELIOPATHY AT 24 HOURS IN AN ESTABLISHED MOUSE MODEL OF HEMORRHAGIC SHOCK AND TRAUMA.

ABSTRACT: Introduction: The endotheliopathy of trauma develops early after injury and consists of increased vascular permeability, inflammation, and dysfunctional coagulation. Persistence of these abnormalities ultimately leads to multiorgan failure. We hypothesized that extending an established 3-hour acute mouse model of hemorrhagic shock and trauma (HS/T) to a 24-hour survival model would allow for evaluation of persistent endotheliopathy and organ injury after HS/T. Methods: Adult male C57BL/6J mice underwent laparotomy, femoral artery cannulation, and blood withdrawal to induce HS to a MAP of 35 mm Hg for 90 minutes. Mice were resuscitated with either lactated Ringer's (LR) or fresh frozen plasma (FFP). Vascular permeability in the lung and gut was assessed by measuring extravasation of a fluorescent dextran dye. Lungs were evaluated for histopathologic injury, and immunofluorescent staining was used to evaluate intercellular junction integrity. Pulmonary inflammatory gene expression was evaluated using NanoString (Seattle, WA). All endpoints were evaluated at both 3 and 24 hours after initiation of shock. Results: Lactated Ringer's- and FFP-treated mice had an equal mortality rate of 17% in the 24-hour model. Lactated Ringer's-treated mice demonstrated increased vascular permeability in the lung and gut at 3 hours compared with sham mice (lung, P < 0.01; gut, P < 0.001), which was mitigated by FFP treatment (lung, P < 0.05; gut, P < 0.001). Twenty-four hours after shock, however, there were no differences in vascular permeability between groups. Similarly, although at 3 hours, the lungs of LR-treated mice demonstrated significant histopathologic injury, loss of tight and adherens junctions, and a pro-inflammatory gene expression profile at 3 hours, these endpoints in LR mice were similar to sham mice by 24 hours. Conclusions: In an established mouse model of HS/T, endotheliopathy and lung injury are evident at 3 hours but recover by 24 hours. Polytrauma models or larger animal models allowing for more severe injury coupled with supportive care are likely necessary to evaluate endotheliopathy and organ injury outside of the acute period.

Lyophilized plasma resuscitation downregulates inflammatory gene expression in a mouse model of sepsis.

BACKGROUND: Plasma resuscitation may improve outcomes by targeting endotheliopathy induced by severe sepsis or septic shock. Given the logistical constraints of using fresh frozen plasma in military settings or areas with prolonged prehospital care, dried products such as lyophilized plasma (LP) have been developed. We hypothesized that resuscitation with LP would decrease lung injury, inflammation, and mortality in a mouse sepsis model. METHODS: Adult male C57BL/6J mice received an intraperitoneal injection of cecal slurry. Twenty-two hours later, the mice were anesthetized, the femoral artery was cannulated, and the mice were randomized to receive resuscitation with LP (10 mL/kg) or lactated Ringer's (LR; 30 mL/kg) for 1 hour. At 48-hours post-cecal slurry injection, bronchoalveolar lavage fluid was collected, the lungs were harvested, and plasma was obtained. Mortality and bronchoalveolar lavage total protein concentration (as an indicator of permeability) were compared between groups. The lungs were analyzed for histopathology and inflammatory gene expression using NanoString, and the plasma was analyzed for biomarkers of inflammation and endothelial function. RESULTS: There was no significant difference in short-term mortality between LR and LP mice, 38% versus 47%, respectively ( p = 0.62). Bronchoalveolar lavage protein levels were similar among mice resuscitated with LR or LP, and there was a lack of significant histopathologic lung injury in all groups. However, LP resuscitation resulted in downregulation of pulmonary inflammatory genes, including signaling pathways such as Janus kinase-signal transducer and activator of transcription and nuclear factor κB, and a circulating inflammatory biomarker profile similar to sham animals. CONCLUSION: Resuscitation with LP did not improve mortality or reduce permeability or injury in this model compared with LR. However, LP downregulated pulmonary inflammatory gene signaling and may also reduce circulating biomarkers of inflammation. Future studies should evaluate LP resuscitation in combination with antibiotics and other therapeutics to determine whether the anti-inflammatory effects of LP may improve outcomes in sepsis.

Mesenchymal stem cell extracellular vesicles mitigate vascular permeability and injury in the small intestine and lung in a mouse model of hemorrhagic shock and trauma.

BACKGROUND: Hemorrhagic shock and trauma (HS/T)-induced gut injury may play a critical role in the development of multi-organ failure. Novel therapies that target gut injury and vascular permeability early after HS/T could have substantial impacts on trauma patients. In this study, we investigate the therapeutic potential of human mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC EVs) in vivo in HS/T in mice and in vitro in Caco-2 human intestinal epithelial cells. METHODS: In vivo, using a mouse model of HS/T, vascular permeability to a 10-kDa dextran dye and histopathologic injury in the small intestine and lungs were measured among mice. Groups were (1) sham, (2) HS/T + lactated Ringer's (LR), (3) HS/T + MSCs, and (4) HS/T + MSC EVs. In vitro, Caco-2 cell monolayer integrity was evaluated by an epithelial cell impedance assay. Caco-2 cells were pretreated with control media, MSC conditioned media (CM), or MSC EVs, then challenged with hydrogen peroxide (H2O2). RESULTS: In vivo, both MSCs and MSC EVs significantly reduced vascular permeability in the small intestine (fluorescence units: sham, 456 ± 88; LR, 1067 ± 295; MSC, 765 ± 258; MSC EV, 715 ± 200) and lung (sham, 297 ± 155; LR, 791 ± 331; MSC, 331 ± 172; MSC EV, 303 ± 88). Histopathologic injury in the small intestine and lung was also attenuated by MSCs and MSC EVs. In vitro, MSC CM but not MSC EVs attenuated the increased permeability among Caco-2 cell monolayers challenged with H2O2. CONCLUSION: Mesenchymal stem cell EVs recapitulate the effects of MSCs in reducing vascular permeability and injury in the small intestine and lungs in vivo, suggesting MSC EVs may be a potential cell-free therapy targeting multi-organ dysfunction in HS/T. This is the first study to demonstrate that MSC EVs improve both gut and lung injury in an animal model of HS/T.

Outcomes of Early Versus Late Tracheostomy in Patients With COVID-19: A Multinational Cohort Study.

Timing of tracheostomy in patients with COVID-19 has attracted substantial attention. Initial guidelines recommended delaying or avoiding tracheostomy due to the potential for particle aerosolization and theoretical risk to providers. However, early tracheostomy could improve patient outcomes and alleviate resource shortages. This study compares outcomes in a diverse population of hospitalized COVID-19 patients who underwent tracheostomy either "early" (within 14 d of intubation) or "late" (more than 14 d after intubation). DESIGN: International multi-institute retrospective cohort study. SETTING: Thirteen hospitals in Bolivia, Brazil, Spain, and the United States. PATIENTS: Hospitalized patients with COVID-19 undergoing early or late tracheostomy between March 1, 2020, and March 31, 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 549 patients from 13 hospitals in four countries were included in the final analysis. Multivariable regression analysis showed that early tracheostomy was associated with a 12-day decrease in time on mechanical ventilation (95% CI, -16 to -8; p < 0.001). Further, ICU and hospital lengths of stay in patients undergoing early tracheostomy were 15 days (95% CI, -23 to -9 d; p < 0.001) and 22 days (95% CI, -31 to -12 d) shorter, respectively. In contrast, early tracheostomy patients experienced lower risk-adjusted survival at 30-day post-admission (hazard ratio, 3.0; 95% CI, 1.8-5.2). Differences in 90-day post-admission survival were not identified. CONCLUSIONS: COVID-19 patients undergoing tracheostomy within 14 days of intubation have reduced ventilator dependence as well as reduced lengths of stay. However, early tracheostomy patients experienced lower 30-day survival. Future efforts should identify patients most likely to benefit from early tracheostomy while accounting for location-specific capacity.

Cryoprecipitate attenuates the endotheliopathy of trauma in mice subjected to hemorrhagic shock and trauma.

BACKGROUND: Plasma has been shown to mitigate the endotheliopathy of trauma. Protection of the endothelium may be due in part to fibrinogen and other plasma-derived proteins found in cryoprecipitate; however, the exact mechanisms remain unknown. Clinical trials are underway investigating early cryoprecipitate administration in trauma. In this study, we hypothesize that cryoprecipitate will inhibit endothelial cell (EC) permeability in vitro and will replicate the ability of plasma to attenuate pulmonary vascular permeability and inflammation induced by hemorrhagic shock and trauma (HS/T) in mice. METHODS: In vitro, barrier permeability of ECs subjected to thrombin challenge was measured by transendothelial electrical resistance. In vivo, using an established mouse model of HS/T, we compared pulmonary vascular permeability among mice resuscitated with (1) lactated Ringer's solution (LR), (2) fresh frozen plasma (FFP), or (3) cryoprecipitate. Lung tissue from the mice in all groups was analyzed for markers of vascular integrity, inflammation, and inflammatory gene expression via NanoString messenger RNA quantification. RESULTS: Cryoprecipitate attenuates EC permeability and EC junctional compromise induced by thrombin in vitro in a dose-dependent fashion. In vivo, resuscitation of HS/T mice with either FFP or cryoprecipitate attenuates pulmonary vascular permeability (sham, 297 ± 155; LR, 848 ± 331; FFP, 379 ± 275; cryoprecipitate, 405 ± 207; p < 0.01, sham vs. LR; p < 0.01, LR vs. FFP; and p < 0.05, LR vs. cryoprecipitate). Lungs from cryoprecipitate- and FFP-treated mice demonstrate decreased lung injury, decreased infiltration of neutrophils and activation of macrophages, and preserved pericyte-endothelial interaction compared with LR-treated mice. Gene analysis of lung tissue from cryoprecipitate- and FFP-treated mice demonstrates decreased inflammatory gene expression, in particular, IL-1ß and NLRP3, compared with LR-treated mice. CONCLUSION: Our data suggest that cryoprecipitate attenuates the endotheliopathy of trauma in HS/T similar to FFP. Further investigation is warranted on active components and their mechanisms of action.

All Hands on Deck: Local Public Health Agencies Leveraging the Incident Command System During Crises.

The COVID-19 pandemic has stretched limited public health resources beyond measures, particularly at the local level. What started as an interesting report of pneumonia of unknown etiology in late December 2019 in Wuhan, China, bloomed into an international crisis by mid-January 2020. However, it was not until late January, when the first case was reported in the United States, that a new reality took shape for US public health agencies. After all, severe acute respiratory syndrome never made it to this country, and the only 2 cases of Middle East respiratory syndrome here were imported and never spread. Local public health agencies are notoriously short-staffed and underfunded. Therefore, when a crisis looms, personnel from a multitude of areas within the agencies are called upon to help out. Under its innovative and forward-thinking leadership, the St. Louis County Department of Health internally implemented the Incident Command System, a component of the National Incident Management System. While reassignment of individuals to new responsibilities under a new and temporary reporting structure did not always go perfectly, Incident Command System kept its promise to be adaptable to a fast-evolving situation, to clearly outline needed areas of responsibility, and to provide scaffolding that kept the Department of Health functional in chaotic times. It was able to be implemented quickly within hours of the first confirmed COVID-19 case in St. Louis County and enhanced the quality and timeliness of the public health response. This experience is being shared to provide a model of how organizations with limited personnel can use the Incident Command System to reorganize and meet unexpected challenges with increased success.

Bayesian modeling predicts age and sex are not required for accurate stature estimation from femoral length.

Despite the recognized flaws in applying traditional stature estimation equations such as those of Trotter and Gleser (1952) [5] to a contemporary population, there are currently no available alternatives for stature estimation in Australia that address these limitations. Post mortem computed tomography (PMCT) DICOM scans of the left and right femora were acquired from 76 Australian deceased individuals aged 17-76 years for metric analysis. Femoral bicondylar length, femoral epicondylar breadth and anterior-posterior (AP) diameter, medial-lateral (ML) diameter, circumference and cortical area at the femoral midshaft were measured on three-dimensional (3D) models to build statistical models for estimating stature. In addition, Australian individuals aged 16-63 years (n=111) were measured in standing and supine positions to aid in the adjustment of supine stature of deceased individuals utilized in this study to standing stature. The results of this preliminary evaluation strongly indicate that the optimal model for estimating stature includes bicondylar femoral length and epicondylar breadth, that the effect of sex as an independent variable is very low, and there is limited practical benefit in including age in the estimation of stature. Our study indicates that the Australian population sampled represents a small yet significant shift in stature from the original Trotter and Gleser sample. Additionally, in the case of fragmentary remains, it was found that epicondylar breadth and AP diameter had the highest probability of accurate stature estimation in the absence of bicondylar femoral length. As stature forms a significant component of a biological profile and therefore aids in the personal identification of human remains, it is important that forensic anthropologists utilize the most accurate methodologies available. Stature estimation of Australian individuals is therefore achieved with higher accuracy through utilizing the femoral equations proposed in this study.